Post ablation autonomic nervous system neuromodulation treatment

Abstract

The invention discloses a method for post ablation treatment of a subject diagnosed with atrial arrhythmia, including: diagnosing a subject with atrial arrhythmia; performing an ablation procedure in a heart of the subject following the diagnosing; delivering a stimulation treatment following the ablation, where the stimulation is delivered with parameter values suitable for affecting occurrence of atrial arrhythmia and / or at least one symptom thereof in the subject following the ablation.

Description

[0001] POST ABLATION AUTONOMIC NERVOUS SYSTEM NEUROMODULATION

[0002] TREATMENT

[0003] RELATED APPLICATION / S

[0004] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 649,553 filed on May 20, 2024, the contents of which are incorporated herein by reference in their entirety.

[0005] FIELD AND BACKGROUND OF THE INVENTION

[0006] The present invention, in some embodiments thereof, relates to delivery of stimulation to a subject, and more particularly, but not exclusively, to delivery of median vagal nerve stimulation (mVNS) to the subject.

[0007] International Patent Application Publication number WO2022153321A1 describes “a system comprising a control module; a neuro- stimulation unit operationally controlled by the control module and configured to generate an electrical stimulation signal at a frequency of between 40-50 Hz; and at least two electrodes configured to be positioned in simultaneous dermal contact with an inner surface of the wrist of a subject, proximately to a median nerve of the subject, wherein each of the at least two electrodes is connected to the neuro-stimulation unit for delivering the generated electrical stimulation signal from the neuro-stimulation unit to the subject, wherein the electrical stimulation signal is configured to apply a neuromodulation treatment to the subject, to reduce occurrences of an arrhythmia-related condition in the subject” (Abstract).

[0008] International Patent Application Publication number W02017051408A1 describes “disclosed herein are portable and integrated modules and devices for non-intrusive neuromodulation and monitoring of heart function, and methods of operation thereof. The modules and devices include a monitoring unit, an electrical stimulation inducing unit, and three electrodes, such that one of the electrodes is dual-function, being controllably utilized for neuromodulation or for monitoring of heart function”.

[0009] International Patent Application Publication number WO2016128985A1 describes “the present invention discloses neuro-stimulation systems and methods for affecting cardiovascular function, particularly for improving heart rate variability and treating arrhythmia”. Yin J, et al. J Cardiovasc Electrophysiol. 2019, describes “objective: Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during followup. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice. Methods and results: Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5 / 40 [12.5%] vs 15 / 45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-a, IE-6, CRP, TGF-pi, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008. Conclusion: Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors” (Abstract).

[0010] SUMMARY OF THE INVENTION

[0011] Some examples of some embodiments of the invention are listed below (it should be noted that one or more features of an example may be used in combination with one or more features of another example):

[0012] Example 1. A method for post ablation treatment of a subject diagnosed with atrial arrhythmia, comprising: diagnosing a subject with atrial arrhythmia; performing an ablation procedure in a heart of said subject following said diagnosing; delivering a stimulation treatment following said ablation, wherein said stimulation is delivered with parameter values suitable for affecting occurrence of atrial arrhythmia and / or at least one symptom thereof in said subject following said ablation.

[0013] Example 2. A method according to example 1, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for attenuating occurrence and / or severity of said at least one symptom of said atrial arrhythmia.

[0014] Example 3. A method according to example 1 or example 2, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for eliminating appearance of said atrial arrhythmia and / or symptoms thereof in said subject following said ablation.

[0015] Example 4. A method according to any one of the previous examples, wherein said stimulation treatment is delivered during a blanking period of said ablation.

[0016] Example 5. A method according to any one of the previous examples, comprising determining an efficiency of said ablation during and / or at an end of said blanking period, wherein said determining an efficiency comprises determining intensity and / or occurrence of at least one arrhythmia symptom during said blanking period.

[0017] Example 6. A method according to any one of the previous examples, comprising modifying at least one parameter of said stimulation or stopping said delivering if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

[0018] Example 7. A method according to any one of the previous examples, comprising determining to repeat said performing of said ablation if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

[0019] Example 8. A method according to any one of the previous examples, wherein said at least one symptom comprises at least one of, heart palpitations, skipping heart beats, rushing heart beats, fatigue, shortness of breath, dizziness, lightheadedness, chest pain, chest discomfort, weakness and / or fainting or near fainting.

[0020] Example 9. A method according to any one of the previous examples, comprises collecting prior to said ablation, information on one or more occurrences of at least one symptom of said atrial arrhythmia in said subject, and setting at least one parameter of said stimulation treatment based on said collected information.

[0021] Example 10. A method according to any one of the previous examples, comprising setting at least one parameter of said stimulation treatment based on at least one parameter of said ablation procedure, wherein said at least one parameter comprises at least one of, ablation procedure completion time, ablation target, ablation parameters, ablation outcomes and / or complications during the ablation procedure.

[0022] Example 11. A method according to any one of the previous examples, wherein said at least one parameter of said stimulation treatment comprises timing for initiation of said stimulation treatment, frequency of stimulation sessions in which an electric field is actively delivered to said subject, interval between said stimulation sessions, time of day in which said electric field is delivered to the subject body, intensity of said electric field, frequency of said electric field, pulse width of said electric field, number of pulses of said electric field delivered to the subject in at least one stimulation session and / or duration of each pulse in said at least one stimulation session. Example 12. A method according to any one of the previous examples, wherein said delivering said stimulation treatment comprises delivering of an electric field to a median nerve and / or to an ulnar nerve of said subject with parameter values selected to attenuate or eliminate occurrence of said arrhythmia or said at least one symptom thereof.

[0023] Example 13. A method according to any one of the previous examples, wherein said delivering comprises delivering said electric field with a frequency between 30Hz and 60Hz.

[0024] Example 14. A method according to any one of the previous examples, wherein said delivering comprises delivering low frequency median vagal nerve stimulation (mVNS) and high frequency mVNS to said subject, wherein delivering of said low frequency mVNS comprises delivering of an electric field with a frequency between 1Hz and 20Hz, and wherein delivering of said high frequency mVNS comprises delivering an electric field with a frequency between 30Hz and 60Hz.

[0025] Example 15. A method according to any one of the previous examples, wherein said high frequency mVNS is delivered after delivery of said low frequency mVNS.

[0026] Example 16. A method according to any one of the previous examples, wherein said low frequency mVNS is delivered for a time period of up to 8 weeks following said ablation.

[0027] Example 17. A method according to any one of the previous examples, wherein said delivering comprises delivering said low frequency mVNS and said high frequency mVNS intermittently.

[0028] Example 18. A method according to any one of the previous examples, comprising monitoring a state of said subject following said performing.

[0029] Example 19. A method according to any one of the previous examples, wherein said monitoring is performed according to a predetermined scheduled, intermittently or continuously.

[0030] Example 20. A method according to any one of the previous examples, wherein said monitoring comprises measuring at least one physiological parameter from a body of said subject, and / or receiving input from said subject or from a caregiver of said subject.

[0031] Example 21. A method according to any one of the previous examples, wherein said at least one physiological parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, pulse oximetry, VO2 max, motion, indications of heart health, and / or Electrocardiogram (ECG) measurements.

[0032] Example 22. A method according to any one of the previous examples, wherein said input comprises information about at least one of, occurrence and / or intensity of at least one symptom of said atrial arrhythmia and / or information on a prodromal symptom of said atrial arrhythmia. Example 23. A method according to any one of the previous examples, comprising detecting early recurrence of atrial arrhythmia after said ablation based on results of said monitoring.

[0033] Example 24. A method according to any one of the previous examples, comprising modifying values of at least one parameter of said stimulation treatment based on results of said monitoring.

[0034] Example 25. A method according to any one of the previous examples, wherein said at least one parameter comprises at least one of, treatment duration, electric field pulse duration, electric field frequency, intermittency and / or intensity of said electric field delivered to said subject during said stimulation treatment.

[0035] Example 26. A method according to any one of the previous examples, comprising determining an arrhythmia state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia state comprises determining a change in a severity of said arrhythmia.

[0036] Example 27. A method according to any one of the previous examples, comprising determining an arrhythmia symptom state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia symptom state comprises determining a change in occurrence and / or intensity of a least one symptom of said atrial arrhythmia.

[0037] Example 28. A method according to any one of the previous examples, comprising determining efficiency of said ablation in said subject following said delivering based on results of said monitoring, and wherein said determining efficiency comprises determining said efficiency based on detecting early occurrence and / or severity of a least one symptom or findings from a measurement of said atrial arrhythmia following said performing of said ablation.

[0038] Example 29. A method according to any one of the previous examples, comprising deciding to repeat said performing of said ablation, and / or to provide a drug treatment to said subject and / or to continue with delivery of said stimulation treatment to said subject, if said determined efficiency is lower than a target efficiency.

[0039] Example 30. A method according to any one of the previous examples, comprising delivering said stimulation treatment to said subject prior to and / or during said ablation.

[0040] Example 31. A method according to any one of the previous examples, wherein said stimulation treatment is delivered to said subject following said ablation based on a responsiveness of said subject to said stimulation treatment delivered prior to said ablation.

[0041] Example 32. A method according to any one of the previous examples, wherein said atrial arrhythmia comprises atrial fibrillation, supraventricular tachycardia (SVT), Atrial flutter, Sinus tachycardia, premature atrial contractions (PACs), atrial tachycardia (AT), and Multifocal atrial tachycardia (MAT). Example 33. A method according to any one of the previous examples, wherein said delivering said stimulation comprises delivering median vagal nerve stimulation (mVNS) to a median and / or an ulnar nerve located in or near a wrist region of an arm of said subject.

[0042] Example 34. A method for affecting a post ablation blanking period in a subject, comprising: performing an ablation in a heart of a subject suffering from at least one arrhythmia symptom; estimating a blanking period following said ablation; delivering median vagal nerve stimulation (mVNS) treatment following said ablation, wherein said median nerve stimulation is delivered with parameter values suitable for attenuating atrial arrhythmia and / or for augmenting a balance of an autonomic nervous system in said subject following said ablation; shortening said estimated blanking period based on a responsiveness of said subject to said delivered mVNS.

[0043] Example 35. A method according to example 34, wherein said stimulation treatment is delivered during a blanking period of said ablation.

[0044] Example 36. A method according to any one of examples 34 or 35, wherein said delivering comprises delivering low frequency mVNS and high frequency mVNS to said subject, wherein delivering of said low frequency mVNS comprises delivering of an electric field with a frequency between 1Hz and 20Hz, and wherein delivering of said high frequency mVNS comprises delivering an electric field with a frequency between 30Hz and 60Hz.

[0045] Example 37. A method for reducing inflammation in a subject, comprising: diagnosing a subject with arrhythmia; performing an ablation procedure in a heart of said subject following said diagnosing; delivering low frequency median vagal nerve stimulation (mVNS) treatment to said subject prior to and / or following said ablation, wherein said delivering comprises delivering an electric field with a frequency between 1 Hz and 20 Hz to a median nerve and / or to an ulnar nerve of said subject.

[0046] Example 38. A method according to example 37, wherein said electric field is delivered to said subject with parameter values selected to reduce or prevent inflammation in said subject.

[0047] Example 39. A method according to any one of examples 37 or 38, wherein said delivering comprises delivering said mVNS treatment during a blanking period of said ablation procedure.

[0048] Example 40. A method according to any one of the previous examples, wherein said delivering comprises initiating said delivering of said mVNS treatment up to 2 weeks after said performing of said ablation procedure. Example 41. A method according to any one of the previous examples, wherein said delivering comprises initiating said delivering of said mVNS treatment up to 2 weeks after said performing of said ablation procedure.

[0049] Example 42. A method according to any one of the previous examples, wherein delivering said mVNS treatment prior to said performing of said ablation procedure comprises delivering said mVNS treatment at least 48 hours prior to said performing of said ablation procedure.

[0050] Example 43. A system for delivery of mVNS treatment comprising: a stimulation device, comprising: at least two electrodes; a housing shaped and sized to position said at least two electrodes near a median nerve or an ulnar nerve of a subject; a pulse generator configured to generate an electric field and to deliver said electric field via said at least two electrodes to a subject body; a memory, wherein said memory stores values of parameters of said electric field selected, wherein values of at least one parameter of said parameters is determined according to an ablation procedure performed or scheduled to be performed in said subject; a control circuitry configured to signal said pulse generator to generate said electric field according to parameters values stored in said memory and to deliver said electric field via said at least two electrodes to said median nerve and / or to said ulnar nerve.

[0051] Example 44. A system according to example 43, wherein said values of said parameters are selected to reduce occurrence of arrhythmia in said subject and / or to affect an autonomous nervous system of said subject, by said generated electric field.

[0052] Example 45. A system according to example 43 or example 44, wherein said values of said are selected to reduce sympathetic overdrive and parasympathetic or vagal overdrive in said subject, by said generated electric field.

[0053] Example 46. A system according to any one of the previous examples, wherein said parameters comprise frequency of said electric field, wherein said control circuitry is configured to signal said pulse generator to generate said electric field with frequency between 1 Hz and 20Hz, and / or with frequency between 30 Hz and 60 Hz.

[0054] Example 47. A system according to any one of the previous examples, wherein said at least one parameter comprises time before or after said ablation procedure for initiating the generation and delivery of said electric field to said subject. Example 48. A system according to any one of the previous examples, wherein said at least one parameter comprises frequency, intensity, pulse width, duration of said electric field delivery, and / or number of pulses of said electric field delivered to said subject.

[0055] Example 49. A system according to any one of the previous examples, wherein said memory stores information about said ablation procedure comprising, an estimated duration of a blanking period of said ablation procedure, a date of said ablation procedure, a target of said ablation procedure, measurements performed during said ablation procedure, and / or input received during the ablation procedure, and wherein values of said at least one parameter are determined according to said stored information about said ablation procedure.

[0056] Example 50. A system according to any one of the previous examples, comprising: at least one remote device in communication with said stimulation device, wherein said remote device comprises: a memory which stores information about said ablation procedure comprising, an estimated duration of a blanking period of said ablation procedure, a date of said ablation procedure, a target of said ablation procedure, measurements performed during said ablation procedure, and / or input received during the ablation procedure; a communication circuitry in communication with said stimulation device; a control circuitry configured to generate and deliver to said stimulation device programming information of said at least one parameter, wherein said programming information is generated based on said information stored in the information of said remote device.

[0057] Example 51. A system according to any one of the previous examples, wherein said memory stores a blanking period related indication which includes information about a starting time of a blanking period following said ablation procedure, a duration of said blanking period, an ending time of said blanking period and / or timing for assessment of a subject state during and / or following the blanking period, wherein said stimulation device further comprises at least one detector configured to record at least one signal from said subject body, and wherein said control circuitry measures at least one physiological parameter based on said at least one recorded signal and according to said blanking period related indication.

[0058] Example 52. A system according to any one of the previous examples, wherein said at least one physiological parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, pulse oximetry, VO2 max, motion, indications of heart health, and / or Electrocardiogram (ECG) measurements. Example 53. A system according to any one of the previous examples, wherein said control circuitry is configured to detect arrhythmia in said subject during said blanking period based on said measurements of said at least one physiological parameter.

[0059] Example 54. A system according to any one of the previous examples, wherein said stimulation device comprises a user interface configured to generate a human detectable indication, and wherein said control circuitry is configured to determine an efficiency or success of said ablation procedure performed in said subject based on said measurements of said at least one physiological parameter and / or said detected arrhythmia, and signal said user interface to generate said human detectable indication with information about the efficiency or success of said ablation procedure.

[0060] Example 55. A system according to any one of the previous examples, comprising: a remote device in communication with said stimulation device, wherein said remote device comprises: a communication circuitry configured to receive signals from said stimulation device; a memory, wherein said memory stores measurements of said at least one physiological parameter or indications thereof, performed by the stimulation device and received from said stimulation device using said communication circuitry, and / or input information received from said subject regarding at least one symptom of an arrhythmia; a control circuitry configured to determine an efficiency or success of said ablation procedure performed in said subject based on said measurements of said at least one physiological parameter or indications thereof, and / or based on said input information stored in said memory, to generate at least one indication according to said determined efficiency or success of said ablation procedure, and to deliver said at least one indication using said communication circuitry to at least one of, a monitoring center, a health maintenance organization, a cardiologist and / or to an expert monitoring a state of said subject following said ablation procedure.

[0061] Example 56. A system according to any one of the previous examples, wherein if said delivered at least one indication indicates that said ablation procedure was not efficient, said delivered at least one indication further comprises a suggestion to repeat said ablation procedure.

[0062] Example 57. A system according to any one of the previous examples, wherein if said delivered at least one indication indicates that said ablation procedure was not efficient, said delivered at least one indication further comprises a suggestion to initiate delivery of a drug treatment to said subject, to modify a drug treatment provided to said subject or to stop a drug treatment already provided to said subject. Example 101. A system for performing a method for post ablation treatment of a subject diagnosed with atrial arrhythmia, comprising: a. a stimulation device, as described herein; b. circuitry comprising instructions for delivering a stimulation treatment following said ablation, wherein said stimulation is delivered with parameter values suitable for affecting occurrence of atrial arrhythmia and / or at least one symptom thereof in said subject following said ablation.

[0063] Example 102. The system according to example 101, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for attenuating occurrence and / or severity of said at least one symptom of said atrial arrhythmia.

[0064] Example 103. The system according to example 101 or Example 102, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for eliminating appearance of said atrial arrhythmia and / or symptoms thereof in said subject following said ablation.

[0065] Example 104. The system according to any one of examples 101-103, wherein said stimulation treatment is delivered during a blanking period of said ablation.

[0066] Examples 105. The system according to any one of examples 101-104, comprising determining an efficiency of said ablation during and / or at an end of said blanking period, wherein said determining an efficiency comprises determining intensity and / or occurrence of at least one arrhythmia symptom during said blanking period.

[0067] Example 106. The system according to any one of examples 101-105, comprising modifying at least one parameter of said stimulation or stopping said delivering if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

[0068] Example 107. The system according to any one of examples 101-106, comprising determining to repeat said performing of said ablation if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

[0069] Example 108. The system according to any one of examples 101-107, wherein said at least one symptom comprises at least one of, heart palpitations, skipping heart beats, rushing heart beats, fatigue, shortness of breath, dizziness, lightheadedness, chest pain, chest discomfort, weakness and / or fainting or near fainting.

[0070] Example 109. The system according to any one of examples 101-108, further comprising collecting, prior to said ablation, information on one or more occurrences of at least one symptom of said atrial arrhythmia in said subject, and further comprising setting at least one parameter of said stimulation treatment based on said collected information.

[0071] Example 110. The system according to any one of examples 101-109, wherein said at least one parameter of said stimulation treatment comprises timing for initiation of said stimulation treatment, frequency of stimulation sessions in which an electric field is actively delivered to said subject, interval between said stimulation sessions, time of day in which said electric field is delivered to the subject body, intensity of said electric field, frequency of said electric field, pulse width of said electric field, number of pulses of said electric field delivered to the subject in at least one stimulation session, and / or duration of each pulse in said at least one stimulation session.

[0072] Example 111. The system according to any one of examples 101-110, further comprising setting at least one parameter of said stimulation treatment based on at least one parameter of said ablation procedure, wherein said at least one parameter comprises at least one of, ablation procedure completion time, ablation target, ablation parameters, ablation outcomes and / or complications during the ablation procedure.

[0073] Example 112. The system according to any one of examples 101-111, wherein said at least one parameter of said stimulation treatment comprises timing for initiation of said stimulation treatment, frequency of stimulation sessions in which an electric field is actively delivered to said subject, interval between said stimulation sessions, time of day in which said electric field is delivered to the subject body, intensity of said electric field, frequency of said electric field, pulse width of said electric field, number of pulses of said electric field delivered to the subject in at least one stimulation session, and / or duration of each pulse in said at least one stimulation session.

[0074] Example 113. The system according to any one of examples 101-112, wherein said delivering said stimulation treatment comprises delivering of an electric field to a median nerve and / or to an ulnar nerve of said subject with parameter values selected to attenuate or eliminate occurrence of said arrhythmia or said at least one symptom thereof.

[0075] Example 114. The system according to any one of examples 101-113, wherein said delivering comprises one or more of: a. delivering said electric field with a frequency between 30Hz and 60Hz; b. delivering low frequency median vagal nerve stimulation (mVNS) and high frequency mVNS to said subject, wherein delivering of said low frequency mVNS comprises delivering of an electric field with a frequency between 1Hz and 20Hz, and wherein delivering of said high frequency mVNS comprises delivering an electric field with a frequency between 30Hz and 60Hz.

[0076] Example 115. The system according to any one of examples 101-114, wherein said high frequency mVNS is delivered after delivery of said low frequency mVNS.

[0077] Example 116. The system according to any one of examples 101-115, wherein said low frequency mVNS is delivered for a time period of up to 8 weeks following said ablation.

[0078] Example 117. The system according to any one of examples 101-116, wherein said delivering comprises delivering said low frequency mVNS and said high frequency mVNS intermittently.

[0079] Example 118. The system according to any one of examples 101-117, further comprising monitoring a state of said subject following said performing.

[0080] Example 119. The system according to any one of examples 101-118, wherein said monitoring is performed according to a predetermined scheduled, intermittently or continuously.

[0081] Example 120. The system according to any one of examples 101-119, wherein said monitoring comprises measuring at least one physiological parameter from a body of said subject, and / or receiving input from said subject or from a caregiver of said subject.

[0082] Example 121. The system according to any one of examples 101-120, wherein said at least one physiological parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, pulse oximetry, VO2 max, motion, indications of heart health, and / or Electrocardiogram (ECG) measurements.

[0083] Example 122. The system according to any one of examples 101-1121, wherein said input comprises information about at least one of, occurrence and / or intensity of at least one symptom of said atrial arrhythmia and / or information on a prodromal symptom of said atrial arrhythmia.

[0084] Example 123. The system according to any one of examples 101-122, further comprising detecting early recurrence of atrial arrhythmia after said ablation based on results of said monitoring.

[0085] Example 124. The system according to any one of examples 101-123, further comprising modifying values of at least one parameter of said stimulation treatment based on results of said monitoring.

[0086] Example 125. The system according to any one of examples 101-124, wherein said at least one parameter comprises at least one of, treatment duration, electric field pulse duration, electric field frequency, intermittency and / or intensity of said electric field delivered to said subject during said stimulation treatment.

[0087] Example 126. The system according to any one of examples 101-125, further comprising determining an arrhythmia state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia state comprises determining a change in a severity of said arrhythmia.

[0088] Example 127. The system according to any one of examples 101-126, further comprising determining an arrhythmia symptom state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia symptom state comprises determining a change in occurrence and / or intensity of a least one symptom of said atrial arrhythmia.

[0089] Example 128. The system according to any one of examples 101-127, further comprising determining efficiency of said ablation in said subject following said delivering based on results of said monitoring, and wherein said determining efficiency comprises determining said efficiency based on detecting early occurrence and / or severity of a least one symptom or findings from a measurement of said atrial arrhythmia following said performing of said ablation.

[0090] Example 129. The system according to any one of examples 101-128, comprising deciding to repeat said performing of said ablation, and / or to provide a drug treatment to said subject and / or to continue with delivery of said stimulation treatment to said subject, if said determined efficiency is lower than a target efficiency.

[0091] Example 130. The system according to any one of examples 101-129, further comprising delivering said stimulation treatment to said subject prior to and / or during said ablation.

[0092] Example 131. The system according to any one of examples 101-130, wherein said stimulation treatment is delivered to said subject following said ablation based on a responsiveness of said subject to said stimulation treatment delivered prior to said ablation.

[0093] Example 132. The system according to any one of examples 101-131, wherein said atrial arrhythmia comprises atrial fibrillation, supraventricular tachycardia (SVT), Atrial flutter, Sinus tachycardia, premature atrial contractions (PACs), atrial tachycardia (AT), and Multifocal atrial tachycardia (MAT).

[0094] Example 133. The system according to any one of examples 101-132, wherein said delivering said stimulation comprises delivering median vagal nerve stimulation (mVNS) to a median and / or an ulnar nerve located in or near a wrist region of an arm of said subject.

[0095] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. As will be appreciated by one skilled in the art, some embodiments of the present invention may be embodied as a system, method or computer program product. Accordingly, some embodiments of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, some embodiments of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon. Implementation of the method and / or system of some embodiments of the invention can involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of some embodiments of the method and / or system of the invention, several selected tasks could be implemented by hardware, by software or by firmware and / or by a combination thereof, e.g., using an operating system.

[0096] For example, hardware for performing selected tasks according to some embodiments of the invention could be implemented as a chip or a circuit. As software, selected tasks according to some embodiments of the invention could be implemented as a plurality of software instructions being executed by a computer using any suitable operating system. In an exemplary embodiment of the invention, one or more tasks according to some exemplary embodiments of method and / or system as described herein are performed by a data processor, such as a computing platform for executing a plurality of instructions. Optionally, the data processor includes a volatile memory for storing instructions and / or data and / or a non-volatile storage, for example, a magnetic hard-disk and / or removable media, for storing instructions and / or data. Optionally, a network connection is provided as well. A display and / or a user input device such as a keyboard or mouse are optionally provided as well.

[0097] Any combination of one or more computer readable medium(s) may be utilized for some embodiments of the invention. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0098] A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0099] Program code embodied on a computer readable medium and / or data used thereby may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0100] Computer program code for carrying out operations for some embodiments of the present invention may be written in any combination of one or more programming languages, including an object-oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).

[0101] Some embodiments of the present invention may be described below with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general- purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0102] These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function / act specified in the flowchart and / or block diagram block or blocks.

[0103] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0104] Some of the methods described herein are generally designed only for use by a computer, and may not be feasible or practical for performing purely manually, by a human expert. A human expert who wanted to manually perform similar tasks, such as delivering of median nerve stimulation and / or measuring physiological parameters from a subject, might be expected to use completely different methods, e.g., making use of expert knowledge and / or the pattern recognition capabilities of the human brain, which would be vastly more efficient than manually going through the steps of the methods described herein.

[0105] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0106] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0107] In the drawings:

[0108] Figure 1 is a general flow chart of a process for delivering median vagal nerve stimulation following an ablation procedure, according to some exemplary embodiments of the invention;

[0109] Figure 2 is a schematic illustration showing neuro pathways by which median nerve stimulation affects heart activity, according to some exemplary embodiments of the invention; Figures 3a-3c are schematic illustrations showing an effect of median nerve stimulation on the post-ablation blanking period, according to some exemplary embodiments of the invention;

[0110] Figure 4 is a block diagram of a system for delivery of stimulation and / or measurements, according to some exemplary embodiments of the invention;

[0111] Figure 5 is a flow chart of activities performed by the system, according to some exemplary embodiments of the invention;

[0112] Figure 6 is a flow chart of a process for augmenting autonomic nervous system balance by delivery of median nerve stimulation, according to some exemplary embodiments of the invention;

[0113] Figure 7 is a detailed flow chart of a process for affecting a post-ablation blanking period, according to some exemplary embodiments of the invention;

[0114] Figures 8a and 8b are flow charts showing a journey of a patient diagnosed with atrial fibrillation (AF) or suffering from at least one symptom of AF, according to some exemplary embodiments of the invention;

[0115] Figure 9a is a detailed block diagram of a device for delivery of median nerve stimulation, according to some exemplary embodiments of the invention;

[0116] Figure 9b is a schematic illustration showing communication of the device with external, and optionally remote, devices, according to some exemplary embodiments of the invention;

[0117] Figure 9c is a schematic illustration showing positioning of the device next to a median nerve during stimulation, according to some exemplary embodiments of the invention;

[0118] Figure 9d is a graph showing a stimulation signal, according to some exemplary embodiments of the invention; and

[0119] Figures 10a- 10b are images of exemplary ECGs taken before and after neuromodulation sessions, according to some exemplary embodiments of the invention.

[0120] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0121] The present invention, in some embodiments thereof, relates to delivery of stimulation to a subject, and more particularly, but not exclusively, to delivery of median vagal nerve stimulation (mVNS) to the subject.

[0122] A broad aspect of some embodiments of the invention relates to delivery of a stimulation, optionally in a form of an electric field, to a nerve of a subject following a cardiac ablation procedure performed in the subject. In some embodiments, the stimulation is delivered with parameter values suitable for affecting the autonomous nervous system in a way that reduces or eliminates occurrence and recurrence of arrhythmias, for example atrial arrhythmias or ventricle arrhythmias, following the ablation procedure. In some embodiments, the stimulation parameters, for example the electric field parameters, are suitable for generating a Vagus response in the subject after delivery of the electric field. In some embodiments, the stimulation is delivered to at least one median nerve and / or to at least one ulnar nerve of the subject.

[0123] According to some embodiments, the stimulation is delivered to the nerve during a blanking period following the ablation procedure, and optionally after the blanking period is completed. In some embodiments, the stimulation is delivered according to a stimulation treatment protocol. Alternatively or additionally, the stimulation is delivered in response to measurements of at least one physiological parameter and / or in response to receiving input information about at least one symptom in the subject.

[0124] According to some embodiments, the stimulation is initiated at least 10 minutes after completion of the ablation procedure, for example at least 1 hour, at least 2 hours, at least 6 hours, at least 6 hours, at least 24 hours, at least 48 hours, at least 1 week, at least two weeks after completion of the ablation procedure, or any intermediate, shorter or longer time period after completion of the ablation procedure.

[0125] According to some embodiments, one or more parameters of the median nerve stimulation, for example intensity, duration, wave form and / or frequency is determined based on the measurements of the at least one physiological parameter and / or based on the received input information about the at least one symptom. In some embodiments, the at least one physiological parameter is measured and / or the input information is received prior to the ablation procedure and / or following the ablation procedure. In some embodiments, the at least one physiological parameter is measured and / or the input information is received, by a stimulation device or by a stimulation system that includes a stimulation device coupled to the subject and one or more remote devices that are in communication with the stimulation device. In some embodiments, the one or more remote devices are used for measuring at least one physiological parameter and / or for receiving the input information. Additionally or optionally, the one or more remote devices are used for processing of the measured at least one physiological parameter and / or processing of the received input information.

[0126] According to some embodiments, the stimulation delivered to the subject after completion of the ablation procedure comprises high frequency stimulation, for example mVNS stimulation in which an electric field with a frequency between about 30 Hz and about 60 Hz, with a frequency between about 30 Hz and 50 Hz, with a frequency between 30 Hz and 40 Hz, or any intermediate, smaller or larger rang of frequency values us delivered to the subject. According to some embodiments, one or more parameter values of the electric field are determined based on information collected during the ablation procedure, for example, measurements performed during the ablation procedure, ablation duration, number of ablated sites, Isolated Pulmonary Veins (PVI) lesion set and parameters ,type of energy delivered during the ablation, amount of energy delivered during the ablation, ablation date, ablation target tissue, ablation success as determined during the procedure (Entrance Block, Exit Block, Non- inducibility) or right after the procedure is completed while the subject is still in the medical facility, events that occurred during the ablation procedure, ablation complications, contact force sensing, impedance monitoring, ECG, comments from an expert performing the ablation or the medical team participating in the ablation procedure. In some embodiments, a stimulation protocol is generated, and / or a stimulation device is programmed based on the information collected during the ablation procedure.

[0127] According to some exemplary embodiments, one or more parameter values of the electric field and / or at least one stimulation protocol are modified based on measurements and / or results of assessment performed during the blanking period, for example at about 1 month, at about 2 months, at about 3 months, at about 6 months, at about 1 year, at about 2 years, or any intermediate, shorter or longer time duration following the ablation procedure.

[0128] Potential advantages of reducing or eliminating recurrence of arrhythmias and related symptoms following an ablation procedure, for example during the blanking period, may be reducing a risk of ablation failure during and optionally following the ablation procedure that may lead to ablation redo, and improving a quality of life (QOL) of the subject. An additional potential advantage of reducing or eliminating early recurrence of arrhythmias, and related symptoms during a blanking period may be reducing or eliminating of late recurrence of arrhythmias, and related symptoms, after the blanking period, thereby achieving long term ablation success.

[0129] An aspect of some embodiments of the invention related to delivery of stimulation to a subject with parameter values suitable for attenuating inflammation of the subject, at a selected time period prior to a scheduled cardiac ablation procedure in the subject and / or at a selected time period after completion of a cardiac ablation procedure in the subject. In some embodiments, the subject is diagnosed with arrhythmia, for example an atrial arrhythmia, and the ablation procedure is configured to reduce or eliminate occurrence of the arrhythmia or at least one symptom of the arrhythmia in the subject. In some embodiments, the stimulation comprises a low frequency mVNS delivered to a median nerve and / or an ulnar nerve of the subject, with a frequency between about 1 Hz and about 20 Hz, for example with a frequency between about 1 Hz and about 10 Hz, between about 5 Hz and about 15 Hz, between about 10 Hz and about 20

[0130] Hz, or any intermediate, smaller or larger frequency value.

[0131] According to some embodiments, the low frequency mVNS is delivered with parameter values selected to reduce in at least 10%, in at least 20%, in at least 50%, in at least 70%, in at least 80%, in at least 90%, or any intermediate, smaller or larger percentage value, measurements of at least one biomarker indicating inflammation in the subject. In some embodiments, the at least one biomarker comprises at least one of, tumor Necrosis Factor Alpha (TNF-a), Interleukin 6 (IL-6), C-Reactive Protein (CRP), Transforming Growth Factor Beta 1 (TGF-pi), Matrix Metallopeptidase 2 (MMP2), Heart Rate Variability (HRV), standard deviation of R-R intervals (SDNN) power in the high frequency band of HRV (HF-HRV), power in the low frequency band of HRV (LF-HRV), the ratio of LF to HF power (LF / HF ratio), square root of the mean squared differences of successive NN intervals.

[0132] According to some embodiments, value of at least one parameter of the low frequency mVNS, for example frequency, duration, pulse length, and / or intensity, is modified in response to the measurements of the at least one inflammation biomarker.

[0133] According to some embodiments, the low frequency mVNS is delivered before or after, delivery a high frequency mVNS, which is delivered as an electric field with a frequency between about 30 Hz and about 60 Hz, with a frequency between about 30 Hz and 50 Hz, with a frequency between 30 Hz and 40 Hz, or any intermediate, smaller or larger rang of frequency values us delivered to the subject. Optionally, the high frequency mVNS and the low frequency mVNS are delivered intermittently, before and / or after the ablation procedure. Optionally, a ratio and / or intermittency between the high frequency mVNS and the low frequency mVNS is modified based on at least one of, measurements of the at least one inflammation biomarker, measurements of at least one physiological parameter performed before and / or after the ablation procedure, and / or input information received regarding an occurrence of at least one arrhythmia symptom.

[0134] According to some embodiments, the low frequency mVNS is delivered during a blanking period following an ablation procedure. In some embodiments, the low frequency mVNS is delivered for a time period of up to 12 weeks following an ablation procedure, for example up to 10 weeks, up to 8 weeks, up to 4 weeks, up to 2 weeks, or any intermediate, shorter or longer time period following an ablation procedure.

[0135] An aspect of some embodiments of the invention relates to affecting a post- ablation blanking period by delivering an electric field to at least one nerve of a subject, for example a nerve affecting the autonomic nervous system and Vagus-stellate axis. In some embodiments, the at least one nerve comprises a median nerve or an ulnar nerve of a subject. In some embodiments, the delivery of the electric field shortens the post-ablation blanking period. In some embodiments, shortening of the blanking period allows, for example, early determining of an efficiency of the ablation procedure, for example after less than 3 months from completing the ablation procedure. In some embodiments, the delivered electric field is delivered following an ablation procedure performed in a patient diagnosed with arrhythmia, for example atrial tachyarrhythmias (ATs). In some embodiments, the arrhythmia comprises Atrial Fibrillation (AF), Atrial tachycardia (AT), Atrial flutter (AFL), Supraventricular tachycardia (SVT|), Premature Atrial Contractions (PACs), Premature ventricular contractions (PVC).

[0136] As used herein, ablation of heart tissue or cardiac ablation means destruction of tissue in the heart by delivering energy, for example cold (Cryo-ablation) or heat (for example via Radio Frequency - RF ablation) or electrical (for example pulsed field ablation) to the tissue, optionally leading to formation of scar tissue. This scar tissue helps disrupt or block abnormal electrical signals causing the arrhythmia.

[0137] According to some embodiments, the electric field is delivered during a post-ablation blanking period, for example a specific timeframe following the ablation procedure during which any recurrence of atrial fibrillation (AF), atrial flutter (AFL), or other atrial tachyarrhythmias (ATs) is not considered a treatment failure or indicative of long-term recurrence. This period may allow for the healing and stabilization of the ablated tissue and / or the optimization of antiarrhythmic medications, optionally making it difficult to distinguish between transient arrhythmias and true procedural failures. This period allows, for example, for a more accurate assessment of long-term procedural success and optimizes patient management strategies.

[0138] According to some embodiments, the electric field is delivered to the median nerve, optionally immediately after ablation, during a blanking period, for example a time period of up to 6 months, for example up to 5 months, up to 4 months, up to 3 months, up to 2 months, or any intermediate, shorter or longer time period following the ablation procedure, optionally when the subject is outside a medical facility. In some embodiments, the delivered electric field reduced the number of arrhythmia episode recurrences and related symptom episodes, which are episodes in which the subject feels or senses symptoms of the arrhythmia, following the ablation, for example during the blanking period.

[0139] According to some embodiments, the delivered electric field shortens the post ablation blanking period by reducing occurrence or eliminating transient arrhythmias following the ablation procedure, thereby allowing to determine the efficiency of the ablation procedure in a time period shorter than 2 months, for example in a time period shorter than 1 months, shorter than 1 month or any intermediate, shorter or longer time period following the ablation procedure.

[0140] An aspect of some embodiments of the invention relates to reducing occurrence of arrhythmia and / or related symptoms following an ablation procedure. In some embodiments, the arrhythmia and / or related symptoms are reduced by delivering an electric field to a median nerve, at a time period following the ablation procedure. In some embodiments, stimulation of the median nerve by the electric field produces a sympatho-inhibitory effect, which results in decreased cardiac sympathetic drive and / or inflammation that triggers atrial arrhythmias and AF. In some embodiments, the reducing of arrhythmia and related symptoms occurrence, allows for example to more accurately identify a real ablation failure vs procedural induced early recurrences seeming like failure of the ablation procedure.

[0141] According to some embodiments, the electric field is delivered, for example intermittently, to the median nerve during a blanking period following an ablation procedure. In some embodiments, the delivered electric field reduced the number of arrhythmia occurrences and / or related symptom episodes, which are episodes in which the subject feels or senses symptoms of the arrhythmia, following the ablation, for example during the blanking period. Alternatively or additionally, the delivered electric field lowers arrhythmia occurrences detected by an external device and / or related symptoms severity following the ablation procedure.

[0142] An aspect of some embodiments of the invention relates to augmenting autonomic nervous system balance by delivery of stimulation, for example median vagal nerve stimulation (mVNS) with different frequencies, optionally following an ablation procedure. In some embodiments, low frequency mVNS is delivered to a subject following ablation, for example to reduce inflammation of heart tissue caused by the ablation process. In some embodiments, delivery of low frequency mVNS comprises delivery of an electric field with frequency between about 1 Hz and about 20 Hz, for example with frequency between 1 Hz and 10 Hz, with frequency between 5 Hz and 15Hz, with frequency between 10 Hz and 20 Hz or any intermediate, smaller or larger frequency. In some embodiments, high frequency stimulation is delivered, for example to reduce occurrence of arrhythmia or related symptoms. In some embodiments, delivery of high frequency stimulation, for example mVNS, comprises delivery of an electric field with frequency between about 30 Hz and about 50 Hz, for example with frequency between 40 Hz and 45 Hz, with frequency between 42 Hz and 50 Hz, with frequency between 45 Hz and 50Hz, or any intermediate, smaller or larger frequency.

[0143] In some embodiments, the low frequency mVNS is followed by delivery of high frequency mVNS, for example to reduce occurrence of arrhythmia or related symptoms. In some embodiments, the low frequency mVNS and the high frequency mVNS are delivered during a blanking period of the ablation procedure.

[0144] According to some embodiments, the low frequency mVNS is delivered optionally immediately, after ablation for a time period of up to 2 weeks after the ablation, for example for a time period of up to 10 days following the ablation, for a time period of up to 7 days following the ablation, or any intermediate, shorter or longer time period following the ablation. In some embodiments, frequency and / or duration of the low frequency mVNS is determined based on measurements of at least one inflammation or an autonomic nervous system marker, for example heart rate variability (HRV). Optionally, the frequency and / or the duration are adjusted during the delivery of the mVNS to the subject.

[0145] In some embodiments, the high frequency mVNS is delivered up to 90 days after completing the delivery of the low frequency mVNS to the subject. Alternatively, the low frequency mVNS and the high frequency mVNS are delivered intermittently to the subject following the ablation, optionally during the blanking period.

[0146] Optionally, the high frequency stimulation is additionally delivered after the blanking period, for example up to 1 years following the ablation procedure.

[0147] According to some embodiments, delivery of low frequency mVNS and high frequency mVNS is optionally used to attenuate cardiac remodeling following an ablation procedure. In some embodiments, the delivery of the low frequency mVNS attenuates structural and / or pathological remodeling of the heart caused by inflammation. Additionally, the high frequency mVNS attenuates structural and / or pathological remodeling of the heart caused by arrhythmia recurrence, for example AF, AFL (flutter) recurrence and other atrial arrhythmias such as PAC's AT' SVT.

[0148] According to some exemplary embodiments, as mentioned above, high frequency stimulation and low frequency stimulation are delivered intermittently, during one or more neuromodulation sessions. Optionally, when detecting an inflammation process, a stimulation protocol is adjusted or replaced with a protocol for low frequency stimulation. In some embodiments, the inflammation process is detected by detecting at least one of, abrupt changes in HRV, and / or inflammation markers.

[0149] Optionally, delivery of low frequency mVNS and high frequency mVNS prevents atrial arrhythmia occurrences following an ablation procedure, by promoting faster healing of the heart tissue, and / or by stabilizing the heart in a new functional state.

[0150] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0151] Exemplary general process for stimulation delivery following ablation

[0152] Catheter ablation of atrial fibrillation is a common procedure performed by experts, for example by cardiac electrophysiologists, now estimated to exceed 500,000 procedures annually worldwide. Despite significant advances in the field of catheter ablation of AF, there remains a high rate of clinical recurrences of symptomatic atrial arrhythmias, typically -40% 1-year recurrence rate in most multicenter clinical trials. Atrial arrhythmias occurring during the early stages after ablation may contribute to the development of later phase ablation failure manifesting as higher AF recurrence rates in up to 18 months after the procedure.

[0153] According to some exemplary embodiments, Vagus nerve stimulation (VNS), for example median nerve stimulation that affects vagal tone, vagal nerve stimulation is delivered post ablation. In some embodiments, and without being bound by any theory, median nerve stimulation is a form of afferent peripheral nerve stimulation that affects the Nucleus Tractus Solitarii (NTS) region of the medulla in the brain resulting changes in autonomic (sympathetic / parasympathetic) balance. The stimulation is delivered post ablation, to reduce or eliminate clinical recurrences of symptomatic or non- symptomatic arrhythmias, for example symptomatic atrial arrhythmias, or optionally any symptom related to arrhythmia, following an ablation procedure. In some embodiments, the symptom comprises at least one of, Palpitations, fast heartbeat, slow heartbeat, chest pain, dizziness, lightheadedness, fainting or near-fainting, Shortness of breath, fatigue, weakness, sweating, anxiety, and confusion.

[0154] Reference is now made to fig. 1, depicting a general process for delivery of vagal stimulation, for example median vagal nerve stimulation, following an ablation procedure, according to some exemplary embodiments of the invention.

[0155] According to some exemplary embodiments, a subject is diagnosed with an arrhythmia, at block 102. In some embodiments, the arrhythmia is an atrial arrhythmia, for example, supraventricular tachycardia (SVT), Atrial fibrillation (AFib), Atrial flutter (AFE), Sinus tachycardia, Premature atrial contractions (PACs), and Multifocal atrial tachycardia (MAT). In some embodiments, SVT comprises Atrioventricular nodal reentrant tachycardia (AVNRT), Atrioventricular reentrant tachycardia (AVRT), and / or Wolff-Parkinson-White (WPW) syndrome. In some embodiments, AFib comprises paroxysmal AFib, persistent AFib, and / or long-standing persistent AFib. In some embodiments, during or following diagnosing at block

[0156] 102. an expert decided that the subject should undergo an ablation procedure.

[0157] According to some exemplary embodiments, stimulation is optionally delivered at block

[0158] 103. In some embodiments, the stimulation, for example median nerve stimulation is delivered with an electric field having low frequency, for example to prevent inflammation prior to the ablation procedure.

[0159] According to some exemplary embodiments, heart tissue of the subject is ablated, at block

[0160] 104. In some embodiments, during an ablation procedure, for example pulmonary vein isolation (PVI,) energy, for example cold (Cryoablation) or heat (radio frequency ablation) or electrical short pulses (pulsed field ablation) or any other type of ablation are delivered to one or more target regions of heart tissue. In some embodiments, an expert performing the ablation, for example an electrophysiologist cardiologist, determines the one or more target regions prior to the procedure. In some embodiments, the predetermined target region are regions that when ablated will disrupt or block generation and / or delivery of abnormal electrical signals causing the arrhythmia.

[0161] According to some exemplary embodiments, vagal nerve stimulation (VNS), for example median VNS (mVNS), is delivered to the subject following the ablation procedure, at block 106. In some embodiments, the mVNS stimulation is delivered by delivering an electric field between at least two electrodes from outside the subject body. Alternatively, at least one electrode of the at least two electrodes is at least partly implanted into the subject body, for example into a subject hand. In some embodiments, the at least two electrodes are placed in contact with a skin surface, optionally a skin surface of a subject hand.

[0162] According to some exemplary embodiments, the electric field is delivered by at least two electrodes contacting a skin surface of the subject forearm or wrist region, optionally at an anterior side of the subject forearm or wrist. In some embodiments, at least one electrode contacts an anterior side of the subject forearm or wrist, and at least one electrode contacts a posterior side of the subject forearm or wrist, during the delivery of the electric field. In some embodiments, the at least two electrodes are electrodes of a device, for example a wearable device, which is shaped and sized to surround and / or to be fastened to the subject forearm or wrist. In some embodiments, the device is the device described in WO2022153321A1, incorporating herein as a reference in its entirety.

[0163] According to some exemplary embodiments, the mVNS is delivered according to a treatment protocol, and is initiated at least 1 hour, at least 6 hours, at least 12 hours, at least 1 day, at least 2 days, or any intermediate, shorter or longer time period following the ablation procedure. In some embodiments, the mVNS is initiated during the ablation procedure, for example following tissue ablation when the subject is in the ablation treatment room. In some embodiments, the mVNS is delivered for a time period of at least 1 day, at least 1 week, at least 1 month, at least 3 months, at least 6 months, at least 10 months, at least 12 months, following the ablation procedure. Optionally, the mVNS is delivered during a blanking period following the ablation procedure, for example a predetermined blanking period determined prior, during and / or following the ablation procedure.

[0164] According to some exemplary embodiments, ablation efficiency is determined at block 108. In some embodiments, the ablation efficiency is determined based on the re-occurrence of one or more measurements or symptoms related to the arrhythmia after performing the ablation. In some embodiments, the one or more arrhythmia occurrences or symptoms are measured by the monitoring functions of the device delivering the mVNS. Alternatively or additionally, the one or more arrhythmia occurrences or symptoms are measured by at least one different device or by at least one detector, for example a sensor in communication with the mVNS device. Alternatively or additionally, the one or more symptoms is reported by the subject.

[0165] According to some exemplary embodiments, ablation efficiency is determined at an end of a blanking period, for example at an end of a predetermined blanking period. Alternatively, the ablation efficiency is determined during or at an end of a time period in which the delivered mVNS stimulation successfully attenuated or eliminated transient arrhythmias or episodes of irregular heartbeats, or other arrhythmia symptoms following the ablation.

[0166] According to some exemplary embodiments, the ablation efficiency is determined by determining a relation between a occurrences number and / or intensity of measured occurrences of arrhythmia or related symptoms occurred prior to the ablation and the number and / or intensity of measured occurrences of arrhythmia or related symptoms occurred following the ablation. In some embodiments, determining ablation efficiency comprises determining if the ablation was successful or the ablation procedure needs to be repeated (ablation redo).

[0167] According to some exemplary embodiments, an arrhythmia state following ablation is determined at block 110. In some embodiments, determining of an arrhythmia state comprises determining if the arrhythmia became worst, remained the same or became better, following the ablation procedure. Optionally, determining an arrhythmia state comprises determining a change in a characteristic of the arrhythmia diagnosed at block 102, following the ablation procedure.

[0168] According to some exemplary embodiments, the arrhythmia state is determined based on measurements of at least one physiological or clinical parameter, for example heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, and / or indications of heart health. Optionally, the measurements comprise Electrocardiogram (ECG) measurements. In some embodiments, the measurements are performed by the device delivering the mVNS or by at least one detector in communication with the mVNS device. Alternatively, the measurements are performed by at least one different device. In some embodiments, measurements are performed during delivery of an electric field to the subject, for example using at least one detector of the stimulation device. Alternatively or additionally, the measurements are performed by at least one detector of a remote or an additional device, for example a device that is in communication with the stimulation device, or a device that is in communication with a system which includes the stimulation device, for example a smartwatch, a smart ring, a smart bracelet, or any other wearable device.

[0169] According to some exemplary embodiments, an arrhythmia symptoms state following ablation is determined at block 112. In some embodiments, determining a state of arrhythmia occurrences or symptoms comprises determining if an intensity of the symptoms of the arrhythmia increased, remained the same or decreased following the ablation. Alternatively or additionally, determining a state of arrhythmia symptoms comprises determining if the number of events in which a subject sensed arrhythmia symptoms increased, decreased or remained the same. In some embodiments, the state of arrhythmia symptoms is determined based on measurements for example as described at block 110 and / or based on input received from the subject. In some embodiments, the input is received from the subject using an application software stored in a personal, optionally mobile, device, for example a smartphone, of the subject, and / or using a personal assistant device.

[0170] Exemplary effect of stimulation on heart tissue and heart activity

[0171] Reference is now made to fig. 2, depicting an effect of VNS, for example mVNS on heart tissue and activity, according to some exemplary embodiments of the invention.

[0172] According to some exemplary embodiments, a device, for example a stimulation device 202 is configured to deliver an electric field 204 to nerve, for example a median nerve 206, or branches thereof. In some embodiments, the electric field 204 is delivered via at least two electrodes 208 and 210 of the device 202. In some embodiments, the electric field 204 is delivered between the two electrodes 208 and 210 to the nerve 206. In some embodiments, the electric field is delivered transcutaneously through the skin surface to the nerve 206.

[0173] According to some exemplary embodiments, the delivered electric field 204 affects one or more regions of the nervous system 212 that control sympathetic and / or parasympathetic activity of the heart 214. In some embodiments, the one or more nervous system targets comprise brain targets, for example a Hypothalamus brain region, and a NTS brain region. In some embodiments, the one or more nervous system targets include targets outside the brain, for example the stellate ganglion, and the Ganglionated plexi (GP) of the heart. In some embodiments, the one or more nervous system regions control activity of the heart 214 via sympathetic fibers 216 and parasympathetic fibers 218 interconnecting the one or more brain regions and tissue of the heart 214. Additionally, the one or more regions of the nervous system modulate inflammation, for example inflammation of heart tissue via the parasympathetic fibers.

[0174] According to some exemplary embodiments, sympathetic and parasympathetic activation of the heart 214 is determined based on at least one parameter of the delivered electric field, for example frequency. In some embodiments, delivery of an electric field with low frequency, for example with a frequency between about 1 Hz and about 20 Hz, reduces inflammation and increase parasympathetic (Vagal) activity and / or reduces sympathetic activity. In some embodiments, delivery of an electric field with high frequency, for example with a frequency between about 30 Hz and about 40Hz, reduces parasympathetic activity and / or induces mild sympathetic activity. In some embodiments, controlling sympathetic and parasympathetic activity of the heart allows, for example to affect inflammation processes of the heart tissue and / or to reduce sympathetic activity, for example sympathetic overdrive triggering atrial arrhythmias or parasympathetic overdrive triggering atrial arrhythmias.

[0175] According to some exemplary embodiments, the electric field 204 is delivered following ablation with parameter values suitable to control sympathetic and / or parasympathetic activity of the heart and to reduce inflammation affecting the heart tissue, thereby optionally allowing faster recovery of the heart after the ablation. Optionally the faster recovery of heart tissue shortens the blanking period following the ablation.

[0176] According to some exemplary embodiments, the delivered electric field 204 can control cardiac remodeling after the ablation, by modulating processes involved in cardiac remodeling by affecting the sympathetic and / or the parasympathetic nervous systems and / or optionally by affecting an intrinsic cardiac ganglionic plexi nervous system. In some embodiments, controlling cardiac remodeling comprises controlling changes, optionally attenuating changes, in at least one of, size, mass, geometry, and function of the heart and autonomic nervous system state following ablation.

[0177] Exemplary blanking period reduction

[0178] According to some exemplary embodiments, during an ablation procedure, one or more targeted areas in the heart suspected to be responsible for arrhythmias are destroyed using radiofrequency energy, cryotherapy, pulsed electrical field or other techniques. Following the ablation, the heart tissue undergoes a healing process, forming scar tissue where the ablation was performed. A blanking period following ablation refers to a specific timeframe during which an occurrence of cardiac arrhythmias is not considered indicative of treatment failure. In some embodiments, the blanking period ranges from about 1 to 20 weeks post ablation, for example from about 3 to 12 weeks post-ablation, from about 2 to 10 weeks post ablation, or any intermediate, shorter or longer time period. Optionally, the blanking period post ablation lasts or is defined as a time period of 8 weeks following an ablation procedure. Without being bound by any theory, one or more biological response that occurs following the ablation procedure, and optionally during the blanking period, may occur as part of a healing process and therefore is not necessarily indicative of treatment failure or a need for further intervention. In some embodiments, this biological response comprises at least one of, transient arrhythmias or episodes of irregular heartbeat.

[0179] According to some exemplary embodiments, delivery of VNS, for example mVNS allows for example to reduce or shorten the blanking period, thereby deciding sooner if a further intervention or a repeated ablation is needed.

[0180] Reference is now made to figs. 3A-3C depicting an effect of mVNS delivery on a postablation blanking period, according to some exemplary embodiments of the invention.

[0181] According to some exemplary embodiments, for example as shown in fig. 3A, during a pre-ablation time period 302, a subject experiences one or more episodes of arrhythmia occurrence or related symptoms, for example episodes 304 and 306. In some embodiments, an occurrence of the episodes is sporadic or persistent. In some embodiments, the intensity of symptoms varies between the episodes.

[0182] According to some exemplary embodiments, during the pre-ablation period a decision to perform an ablation procedure is taken, and ablation 308 is performed. In some embodiments, a blanking period 310 follows the ablation 308 and lasts between 1 week and 4 months. In some embodiments, during this time period, occurrence of arrhythmia symptoms events, for example events 312 and 314 is monitored. Additionally, intensity of the symptoms is also monitored. In some embodiments, a length of the blanking period is predetermined.

[0183] According to some exemplary embodiments, during the blanking period 310 there is an increase in symptoms occurrence and / or an increase in the intensity of the symptoms due to the ablation procedure, and the healing process of the tissue.

[0184] According to some exemplary embodiments, when the blanking period 310 ends, efficiency of the ablation procedure is determined. In some embodiments, the ablation efficiency is determined based on measurements performed during and / or following the blanking period 310. Alternatively or additionally, the ablation efficiency is determined based on input received from the subject, for example input with information about occurrence and / or intensity of symptoms following the ablation, for example during and / or following the blanking period. In some embodiments, determining ablation efficiency comprises determining if the ablation was successful in reducing or eliminating occurrence of atrial arrhythmias and / or related symptoms. Alternatively or additionally, determining ablation efficiency comprises determining if the ablation was successful in reducing atrial arrhythmias and or related symptoms intensity.

[0185] According to some exemplary embodiments, if the efficiency of the ablation procedure was lower than a target efficient, then the ablation is repeated.

[0186] According to some exemplary embodiments, for example as shown in fig. 3B, mVNS 316 is delivered during a blanking period 318. In some embodiments, the mVNS is delivered according to a stimulation protocol which comprises intermittent delivery of an electric field to the median vagal nerve. In some embodiments, as described with regard to fig. 3A, arrhythmia occurrence and symptoms are monitored during the blanking period. In some embodiments, delivery of the mVNS during the blanking period reduces or eliminated occurrence of atrial arrhythmias or arrhythmia related symptoms, for example occurrence of arrhythmia related symptom event 320. Alternatively, the mVNS delivery reduces an intensity of atrial arrhythmias and / or related symptoms during the blanking period.

[0187] According to some exemplary embodiments, reduction of atrial arrhythmia occurrence or related symptoms and / or arrhythmia occurrence and / or symptoms intensity by the mVNS, allows to increase success of the ablation procedure, by reducing or eliminating occurrence of symptoms generate by the ablation or by the healing process of the heart tissue following the ablation. In some embodiments, reduction of arrhythmia symptoms occurrence and / or symptoms intensity by the mVNS optionally increases an efficiency of the ablation performed in the subject and reduces the need for a repeated ablation. In some embodiments, the subject continues to receive the mVNS following the blanking period according to the protocol used during the blanking period or according to a new protocol. Alternatively, in case of early occurrence of arrhythmia, even when receiving mVNS treatment, an ablation procedure is repeated in the subject

[0188] According to some exemplary embodiments, the blanking period following the ablation prevents accurate determining if the ablation was successful because during this time period arrhythmia symptoms occur due to the ablation process, damage to the tissue and healing of the tissue. Therefore, the determining if an ablation process was successful is postponed to the end of the blanking period. In some embodiments, for example as shown in fig. 3C, the delivery of mVNS 322 shortens the blanking period 324 by promoting tissue healing and / or allowing heart tissue to reach a steady state following ablation. In some embodiments, delivery of mVNS 322 reduces or eliminates arrhythmia symptoms caused by the ablation process and therefore it helps to reduce or eliminate damage to the heart tissue caused by the arrhythmia occurrence or related symptoms and improve patient quality of life.

[0189] Exemplary system

[0190] According to some exemplary embodiments, a system for delivery of VNS, for example mVNS, comprises a device for delivery of the stimulation to a subject, optionally following ablation, and one or more additional devices in communication with the stimulation device. In some embodiments, the system is configured to control the stimulation device and to receive input from the stimulation device or from the one or more additional devices regarding the subject response to the stimulation. In some embodiments, the system is used to deliver indications regarding the stimulation process and / or the subject response to an expert, for example a cardiologist monitoring the subject state and / or a cardiologist who performed the ablation. Optionally, the system is used to deliver indications regarding the stimulation process and / or the subject response to a Health Maintenance Organization (HMO) or to a monitoring center, for example indications regarding a success of the ablation process in the subject. Alternatively or additionally, the system is configured to store stimulation parameters, measurements, input signals and / or any other type of data in a remote device of the system.

[0191] Reference is now made to fig. 4, depicting a system for delivery of VNS, for example mVNS, according to some exemplary embodiments of the invention.

[0192] According to some exemplary embodiments, system 402 comprises a device 404 configured to deliver VNS to a subject. In some embodiments, the device 404 comprises a housing 406 configured to be attached to a body of a subject, for example to a hand of the subject. In some embodiments, the housing is configured to be attached or fastened around a hand of a subject, for example around a wrist of the subject, optionally by at least one fastener.

[0193] According to some exemplary embodiments, the device 404 comprises at least two electrodes, for example electrodes 408. In some embodiments, the electrodes 408 are positioned in the housing to contact a tissue surface, for example skin surface of the subject. In some embodiments, the electrodes 408 penetrate at least partly through the housing, for example through a tissue contacting surface of the housing 406. Alternatively, the electrodes 408 are coupled to the tissue contacting surface. In some embodiments, the electrodes 408 are configured to deliver an electric field to the tissue, optionally transcutaneously or percutaneously, to a target region in the tissue. In some embodiments, the target tissue comprises a nerve for example a median nerve, or branches thereof.

[0194] According to some exemplary embodiments, the device 404 comprises a control circuitry 410 functionally coupled to memory 412. In some embodiments, memory stores one or more stimulation protocols and / or values of at least one parameter of an electric field to be delivered during the stimulation. In some embodiments, the at least one parameter comprises at least one of, frequency, intensity, wave form, duration, and / or pulse width of the electric field. Additionally or alternatively, the memory 412 comprises values of one or more parameters of a stimulation treatment, for example, maximal and / or minimal number of electric field pulses per second, per hour, per day, timing for delivery of the pulses, number of pulses in a single train of pulses, number of trains per hour or per day, and interval between trains. In some embodiments, the memory comprises values regarding the overall duration of the mVNS treatment.

[0195] According to some exemplary embodiments, the memory 412 stores measurements of at least one physiological parameter, optionally recorded or measured by the device, for example heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, temperature, pulse oximetry, motion, cardiac events, parameter indications of heart health, and / or Electrocardiogram (ECG) measurements.

[0196] According to some exemplary embodiments, a stimulation treatment comprises at least one, or two or more stimulation sessions separated by intervals. In some embodiments, the memory 412 stores a protocol of a stimulation treatment which includes number of stimulation sessions, interval between two consecutive stimulation sessions, duration of each stimulation session, and / or stimulation parameters. In some embodiments, the memory 412 stores measurement parameters which include type of measurement, measurement timing and / or measurement duration.

[0197] According to some exemplary embodiments, a duration of the overall stimulation treatment, number of stimulation sessions, frequency of stimulation sessions, duration of each stimulation session, stored in the memory 412 is determined according to a duration of a blanking period, according to the timing needed for determining an efficiency of the ablation and / or according to measurements performed by the device.

[0198] According to some exemplary embodiments, the device 402 comprises a pulse generator 414 functionally coupled to the control circuitry 410 and to the electrodes 408. In some embodiments, the pulse generator is configured to generate and deliver the electric field to the electrodes 408. In some embodiments, the pulse generator 414 is configured to generate the electric field according to the parameter values stored in the memory 412, optionally in response to a signal from the control circuitry 410. Alternatively or additionally, the pulse generator 414 generates the electric field according to parameter values received from a remote device 422, for example from an application software installed in the remote device.

[0199] According to some exemplary embodiments, the pulse generator 414 is configured to generate and deliver the electric field via one or more electrodes 408 to the subject body according to a predetermined schedule of a stimulation treatment protocol stored in the memory 412. Alternatively or additionally, the pulse generator 414 is configured to generate and deliver the electric field via one or more electrodes 408 to the subject body according to results of measurements performed by the device 404 or by a different device in communication with the device 404, with the communication device 420 or with the remote device 422. In some embodiments, the control circuitry 410 signals the pulse generator 414 to generate and deliver the electric field if the measurements indicate a current arrhythmia event, for example initiation of an arrhythmia event or an ongoing arrhythmia event. Optionally, the electric field is generated and delivered until the arrhythmia event stops, for example as indicated by results of repeated measurements. Optionally, the generation and delivery of the electric field continues after the arrhythmia event is stopped.

[0200] According to some exemplary embodiments, the device 404 comprises a user interface 416, configured to generate and deliver indications, for example human detectable indications. Additionally, the user interface 416 is configured to receive an input signal, for example from a subject programming or wearing the device 404. In some embodiments, the user interface comprises an audio signal generator and / or a visual signal generator.

[0201] According to some exemplary embodiments, the device 404 optionally comprises at least one detector 417 for example at least one sensor, for detecting at least one physiological or clinical parameter of the subject. In some embodiments, the at least one physiological or clinical parameter comprises heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, temperature, pulse oximetry, motion, cardiac events, parameter indications of heart health, and / or ECG measurements.

[0202] According to some exemplary embodiments, the device 404 comprises a communication circuitry 418 configured to deliver and / or receive signals from at least one different device. Optionally, the communication circuitry 418 is configured to receive signals from at least one external detector or at least one different device configured to measure the at least one physiological or clinical parameter.

[0203] According to some exemplary embodiments, the control circuitry 410 measures the at least one physiological or clinical parameter based on signals received from the at least one detector 417 and / or based on signals received from the communication circuitry 418, and optionally to deliver or to stop delivering of the electric field via the at least two electrodes to the tissue based on the received signals.

[0204] According to some exemplary embodiments, the device 404 using the control circuitry 410 is configured to deliver information, for example measurements of at least one physiological parameter or clinical parameter, log files, treatment current and intensity, leads on / off (patient touching the electrodes), and / or information about indications generated by the user interface 416, to a communication device 420, for example a portable communication device, via the communication circuitry 418. In some embodiments, the portable communication device comprises at least one of, a cellular device, a mobile device, a tablet, a personal assistance device, and a wearable device. In some embodiments, the device 404 delivers the information to a software application, for example a computer program, stored in a memory of the communication device 420. In some embodiments, the software application is part of the system 402.

[0205] According to some exemplary embodiments, the communication device 420 comprises a user interface configured to receive input from a subject and / or to deliver human detectable indication to the subject, optionally via a speaker and / or a display of the communication device 420. In some embodiments, the communication device 420 using the software application and at least one detector of the communication device 420 is configured to measure the physiological or clinical parameter. Additionally or alternatively, the communication device 420 using the software application is configured to receive input data from a user of the device 404, for example input data with information about occurrence of arrhythmia, arrhythmia related symptoms, arrhythmia triggers and / or about an intensity of the symptoms.

[0206] According to some exemplary embodiments, the communication device 420 is configured to communicate, for example to deliver and / or to receive signals, with at least one remote device. In some embodiments, the remote device comprises at least one of a computer, a server, a cloud storage, a different communication device and / or a database. In some embodiments, the remote device 422 receives information from the communication device 420, optionally via the software application. In some embodiments, the information comprises data delivered to the communication device from the stimulation device 404, data received from a user of the stimulation device 404. In some embodiments, the remote device 422 stores the received data, processes the received data and / or generates new data based on the processing results and / or based on the received data. In some embodiments, the new data comprises at least one of, suggestions to modify a treatment, for example the stimulation treatment, delivered to the subject using the stimulation device 404, suggestions to modify the mVNS stimulation protocol or parameter values thereof, indications regarding the progress of the mVNS treatment and / or indications regarding occurrence and / or intensity of arrhythmia symptoms.

[0207] According to some exemplary embodiments, the remote device 422 delivers indications and / or suggestions, for example indications and / or suggestions included in the new data to the communication device 420. Optionally, the communication device programs the device 404, optionally automatically, based on the indications received from the remote device 422. In some embodiments, programming of the device comprises providing treatment parameter values, and / or electric field parameter values to be used during stimulation. Alternatively or additionally, programming comprises starting a stimulation session or stopping a stimulation session. Alternatively, the communication device 420 delivers human detectable indications with suggestions to program the device 404 and / or suggestions to modify a treatment regimen delivered to the subject using a user interface of the communication device, and optionally via the software application.

[0208] According to some exemplary embodiments, the remote device 422 delivers indications and / or suggestions, for example indications and / or suggestions included in the new data to an expert 424, for example a cardiologist performing the ablation in the subject, and / or to a cardiologist 426 monitoring a state of the subject using the stimulation device 404. In some embodiments, the remote device optionally receives input from the expert 424 and / or from the cardiologist. In some embodiments, the input comprises at least one, instructions to the subject, modifications or suggestions to modify the stimulation treatment, and / or modifications or suggestions to modify at least one additional treatment delivered to the subject, for example a drug treatment. In some embodiments, the remote device 422 delivers the input from the expert 424 and / or from the cardiologist 426 to the subject using the communication device 420. In some embodiments, the remote device 422 processes the input received from the expert 424 and / or from the cardiologist 426, optionally with data stored in the remote device 422 and delivers the processing results to the communication device 420.

[0209] According to some exemplary embodiments, the remote device 422 delivers indications regarding the subject state, occurrence of arrhythmia and / or arrhythmia related symptoms and / or intensity of arrhythmia or related symptoms and / or measurements performed by the device 404, for example ECG measurements and / or log files of the device 404 and / or information about the stimulation delivered to the subject, to a health maintenance organization 428 (HMO) or to a monitoring center 430, for example a remote monitoring center (RMC) or a remote patient monitoring (RPM). In some embodiments, the HMO 428 and / or the monitoring center 430, stores the received data, process the received data and / or generate reports, suggestions, and / or observations based on the received data.

[0210] According to some exemplary embodiments, the system 402 comprises a software application, for example the software application installed in the communication device 420. In some embodiments, the expert 424, the cardiologist 426 and / or the HMO 428 communicate with the remote device 422 via the software application, which is optionally includes a web-based user interface.

[0211] According to some exemplary embodiments, the control circuitry 410 of the device is configured to measure at least one physiological parameter, based on at least one signal recorded by the at least one detector 418. In some embodiments, the control circuitry 410 is configured to detect an arrhythmia event based on the measurements. Additionally or optionally, the control circuitry is configured to determine efficiency, for example determine a success of an ablation procedure performed in the subject based on the detected arrhythmia and / or based on the measurements of the at least one physiological parameter. In some embodiments, the control circuitry is configured to generate an indication, for example a human detectable indication based on at least one of, the measurements of the at least one physiological parameter, the detection of the arrhythmia event and / or the determined efficiency or success of the ablation procedure.

[0212] According to some exemplary embodiments, optionally, the indication comprises information about the measurements, for example results of the measurements such as results of ECG measurements. Optionally or additionally, the indication comprises suggestions how to modify at least one treatment provided to the subject in view of the measurements, the detection of the arrhythmia event and / or the determined efficiency or success of the ablation procedure. Optionally, the indication is transmitted to a remote device, for example to a remote device of an expert 424, a cardiologist 426, an HMO 428 and / or a monitoring center, or an Independent Diagnostic Testing Facility (IDTF), optionally in a form of a text message or any electronic form of a message.

[0213] Alternatively or additionally, the remote device 422 is configured to receive information, for example measurements of the at least one physiological parameter and / or log files from the device 404, and store the information in a memory of the remote device 422. In some embodiments, the memory of the remote device 422 comprises input information received from a caregiver or from the subject with information about occurrence of at least one arrhythmia symptom. Additionally or optionally, the memory of the remote device 422 further comprises information about an ablation procedure performed din the subject. In some embodiments, the remote device 422 is configured to detect an arrhythmia event in the subject and / or to determine an efficiency or success of an ablation procedure performed in the subject, based on the information stored in the memory of the remote device 422.

[0214] According to some exemplary embodiments, the remote device 422 is configured to generate an indication regarding the detected arrhythmia event and / or the determined efficiency or success of the ablation procedure. In some embodiments, the remote device 422 is configured to program the device 404 based on the detected arrhythmia event and / or the determined efficiency or success of the ablation procedure, for example to program at least one parameter of a stimulation delivered by the device 404 and / or at least one parameter of measurements performed by the device 404, for example timing and / or type of measurements.

[0215] According to some exemplary embodiments, the remote device 422 is configured to generate an deliver a human detectable indication to the expert 424, to the cardiologist 426 to the HMO 429 and / or to the monitoring or to an Independent Diagnostic Testing Facility (IDTF) center 430, with information about at least one of, measurements and / / or input information stored in the memory of the remote device 422, the detection of the arrhythmia event and / or the determined efficiency or success of the ablation procedure. In some embodiments, the indication is delivered as a text message or as any type of an electronic message, for example as a short message (SMS). Optionally or additionally, the indication comprises suggestions how to modify at least one treatment provided to the subject in view of the measurements, the detection of the arrhythmia event and / or the determined efficiency or success of the ablation procedure.

[0216] Exemplary system activity

[0217] According to some exemplary embodiments, a system, for example system 402 shown in fig. 4, is used for delivery of stimulation, for example mVNS, to a subject following ablation performed in the subject. In some embodiments, the system receives signals indicating at least one of, subject state, stimulation delivery state, stimulation treatment state, state of the stimulation device, arrhythmia occurrence and / or intensity of symptoms. In some embodiments, the system can automatically modify the stimulation treatment delivered to the subject, for example by programming of the stimulation device, based on the received signals. Alternatively, the system can provide instructions or suggestions to modify the stimulation treatment. Alternatively or additionally, the system can provide instructions or suggestion to modify an overall treatment delivered to the subject, for example instructions to stop the stimulation treatment, instructions to schedule a visit with a cardiologist or an expert, instructions to modify, initiate or stop at least one additional treatment, for example a drug treatment, based on the received signals. According to some exemplary embodiments, the system receives signals, programs the stimulation device and / or delivers instructions or suggestion when the subject is outside a medical facility, for example when the subject is at home, optionally engaged in everyday activities. In some embodiments, the suggestions include suggestions with regard to a treatment delivered to the subject, and / or suggestions regarding lifestyle modifications. In some embodiments, the suggestions regarding lifestyle modifications are generated based on detected or self-reported triggers of AF.

[0218] Reference is now made to fig. 5 depicting activities performed by the system, according to some exemplary embodiments of the invention.

[0219] According to some exemplary embodiments, a system for example system 402 shown in fig. 4, optionally measures at least one physiological parameter prior to an ablation procedure, at block 502. Optionally, the at least one physiological parameter is an indicator of at least one arrhythmia symptom. In some embodiments, the system measures the at least one physiological parameter prior to a planned ablation procedure or prior to determining that a subject is in a need for an ablation procedure. In some embodiments, the system measures the at least one physiological parameter based on signals received from at least one detector, for example a sensor, associated with the system. In some embodiments, the at least one detector is a detector of a stimulation device, for example detector 417 of device 404. Alternatively or additionally, the at least one detector is a detector of a communication device, for example device 420. Alternatively, the at least one detector is a detector of a device in communication with the system, with the communication device, with a remote device 422, and / or with the stimulation device 404, for example a detector of a wearable device, a detector of a smart watch, and / or a detector of an activity monitoring device.

[0220] Optionally, the measuring of the physiological parameter is performed by the stimulation device 404. Optionally, the system 402 or the device 404 are in communication with at least one external monitoring device, that is configured to record signals and / or measure at least one physiological parameter, and / or receive input from a user. Optionally, the at least one external monitoring device is configured to transmit the recorded signals, the measured physiological parameter and / or the received input to any device of the system 402, for example for further processing

[0221] According to some exemplary embodiments, the system optionally receives pre-ablation information about arrhythmia events and or related symptoms, at block 504. In some embodiments, the system receives the information before performing an ablation in the subject. In some embodiments, the system receives the information from a subject who is a user of the stimulation device and receives the stimulation, from a caregiver of the subject, and / or from a cardiologist monitoring a state of the subject. In some embodiments, the information is received using a user interface of the device 404, a user interface of the communication device 420, or a user interface associated with the system, for example a user interface of the software application described in fig. 4.

[0222] According to some exemplary embodiments, the system receives ablation data at block 506. In some embodiments, the ablation data comprises at least one of, information about at least one ablated region, date of the ablation, measurements of cardiac conductivity, type of ablation, intensity of ablation, measurements performed during the ablation procedure, ablation duration, number of ablated sites, Isolated Pulmonary Veins (PVI), lesion set and parameters, type of energy delivered during the ablation, amount of energy delivered during the ablation, ablation target tissue, ablation success as determined during the procedure (Entrance Block, Exit Block, Non-inducibility) or right after the procedure is completed while the subject is still in the medical facility, events that occurred during the ablation procedure, ablation complications, contact force sensing, impedance monitoring, ECG, and / or duration of a predicted blanking period. In some embodiments, the system receives the ablation data using a user interface, for example as described at block 504.

[0223] According to some exemplary embodiments, the system receives information on the subject, at block 508. In some embodiments, the system receives information regarding a clinical and / or personal state of the subject. In some embodiments, the system receives information about at least one of, the everyday activities of the subject, family status, subject work, hobbies, daily and / or weekly time plans, sport activities, drug regime, an arrhythmia trigger map and / or medical history. Optionally, the system receives personal data about the subject from social media and / or other health apps. Optionally, the system receives medical and / or clinical data about the subject from one or more databases, for example one or more databases of a HMO, a medical organization, a monitoring center for example an IDTF, and / or a medical facility.

[0224] According to some exemplary embodiments, the system selects a stimulation protocol, at block 510. In some embodiments, the system selects the stimulation protocol based on the ablation data received at block 506 and / or based on the subject data received at block 508. In some embodiments, selecting a stimulation protocol comprises selecting a set of stimulation parameters comprising at least one of, values of one or more electric field parameters, timing of stimulation delivery, stimulation location, and / or stimulation target. In some embodiments, selecting a stimulation protocol comprises selecting a stimulation protocol out of a plurality of stimulation protocols stored in a memory associated with the system, for example in a memory of the stimulation device 404, in a memory of the communication device 420 and / or in a memory of the remote device 422.

[0225] Alternatively to the selection of a stimulation protocol at block 510, the system modifies an existing stimulation protocol stored in a memory, for example a memory circuit or a memory module, associated with the system.

[0226] Alternatively to the selection of a stimulation protocol at block 510, the system selects or determines values of at least one stimulation parameter.

[0227] Alternatively to the selection of a stimulation protocol at block 510, the system delivers one or more indications, for example human detectable indications, with suggestions for a stimulation protocol and / or for values of at least one stimulation parameter. In some embodiments, the indications are delivered using a user interface, for example a display or a speaker, of the stimulation device 404, a user interface of the communication device 420, and / or a user interface of the software application, which is optionally an internet web-based user interface.

[0228] According to some exemplary embodiments, the system delivers stimulation, for example mVNS, at block 512. In some embodiments, the system delivers the stimulation using the stimulation device 404, according to a stimulation protocol and / or according to predetermined stimulation parameter values. In some embodiments, delivery of stimulation comprises delivery of an electric field to a tissue of a hand of the subject optionally comprising a median nerve or at least one branch thereof. Alternatively or additionally, the system delivers the stimulation to a tragus nerve, to a peroneal nerve, to a nerve of the neck, for example a direct vagal stimulation

[0229] According to some exemplary embodiments, the stimulation is delivered to the subject intermittently within a pre-determined time period. Optionally or additionally, the stimulation is delivered when the subject is asleep.

[0230] According to some exemplary embodiments, the stimulation is delivered during an ablation blanking period. In some embodiments, the stimulation is initiated following the ablation procedure, optionally when the subject is still in an operating room or in a medical facility. Optionally, the stimulation continues after the blanking period ends.

[0231] According to some exemplary embodiments, at least one physiological parameter is measured, at block 513. In some embodiments, the at least one physiological parameter comprises heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, and / or ECG. In some embodiments, the at least one physiological parameter is an indicator of cardiac events, and / or indicator of heart health. According to some exemplary embodiments, at least one arrhythmia symptom, state and / or parameter is monitored, at block 514. In some embodiments, the at least one arrhythmia symptom, state and / or parameter is monitored following the ablation procedure and during the delivery of the stimulation treatment, for example between delivery of active stimulation and / or during delivery of active stimulation. In some embodiments, the at least one arrhythmia symptom, state and / or parameter is monitored during the blanking period. In some embodiments, monitoring the at least one symptom, state and / or parameter is based on the measurements performed at block 513. Alternatively or additionally, the monitoring is based receiving input from the subject or from a caregiver of the subject, about the symptom. In some embodiments, monitoring the at least one symptom, state and / or parameter comprises monitoring an occurrence of the symptom, a frequency of the symptom occurrence and / or an intensity of the symptom. In some embodiments, monitoring is performed by the stimulation device 404, by the communication device 420 and / or by the remote device 422.

[0232] According to some exemplary embodiments, the system generates, for example calculates, a score indicating ablation efficiency, at block 516. In some embodiments, the score is generated based on the results of the symptom monitoring performed at block 514. In some embodiments, the score is generated by determining a relation, for example comparing, measurements and / or input regarding an occurrence of the at least one symptom following the ablation procedure, optionally during the blanking period, and at least one indication, for example a reference value, stored in a memory of the system. Optionally the at least one indication comprises previous measurements and / or previous input regarding the at least one symptom, for example information received at blocks 502 and / or 504.

[0233] According to some exemplary embodiments, the system determines ablation efficiency at block 518. In some embodiments, the system determines ablation efficiency based on the score generated at block 516. In some embodiments, the system determines ablation efficiency, for example by determining a relation between the score generated at block 516 and at least one reference value or indication thereof, indicating a desired, for example, a target efficiency.

[0234] According to some exemplary embodiments, if the score generated at block 516 is higher or equal to the at least one reference value, the system determines that the ablation was efficient. Optionally, in case the ablation is efficient, there is no need to repeat the ablation process.

[0235] According to some exemplary embodiments, if the score generated at block 516 is lower than the at least one reference value, the system determines that the ablation was not efficient. Optionally, in case the ablation is not efficient, there is a need to repeat the ablation procedure, also termed herein as ablation redo. According to some exemplary embodiments, the system generates an indication at block 520. In some embodiments, the system generates an indication, for example a human detectable indication, with the results of the efficiency determining and optionally with the score generated at block 516. In some embodiments, the generated indication comprises instructions or suggestions.

[0236] According to some exemplary embodiments, in case the ablation is efficient, the indication comprises instructions or suggestions to stop an anti- arrhythmia treatment, for example a stimulation and / or a drug treatment given to the subject. In some embodiments, if the ablation is not efficient the indication comprises instructions or suggestions to at least one of, repeat an ablation procedure, and / or initiate or continue with a drug treatment.

[0237] According to some exemplary embodiments, the generated indication is delivered to at least one of, an expert performing the ablation, a cardiologist and / or an HMO, for example as described in fig. 4.

[0238] Exemplary augmenting autonomic balance

[0239] According to some exemplary embodiments, autonomic imbalance plays a role in initiating and / or maintenance of an arrhythmia, for example atrial fibrillation (AF). In some embodiments, delivery of low frequency mVNS and high frequency mVNS, allows for example to augment autonomic imbalance following an ablation procedure by optionally reducing tissue inflammation and attenuating arrhythmia recurrence.

[0240] Reference is now made to fig. 6, depicting a process for augmenting autonomic balance, according to some exemplary embodiments of the invention.

[0241] According to some exemplary embodiments, ablation is performed in a subject, at block 650. In some embodiments, the subject is a patient diagnosed with arrhythmia and / or suffers from at least one arrhythmia symptom. In some embodiments, the ablation is performed as described, for example, at blocks 102 of fig. 1, and at block 714 of fig. 7.

[0242] According to some exemplary embodiments, the subject is selected for post-ablation median nerve stimulation, at block 652. In some embodiments, a subject undergoing AF ablation for paroxysmal or persistent AF is selected at block 652. In some embodiments, men and women ages >18 years are selected at block 652.

[0243] According to some exemplary embodiments, a stimulation device is programmed, at block 654. In some embodiments, parameters of the stimulation treatment are programmed into the stimulation device at block 654. In some embodiments, programing stimulation comprises determining values of stimulation parameters, for example values of an electric field delivered to the subject during stimulation. In some embodiments, the programming is performed according to the selected subject, for example according to a clinical state of the subject and other subject characteristics, for example as described at block 708. In some embodiments, the programming is performed according to a predetermined plan for augmenting autonomic balance of the heart.

[0244] According to some exemplary embodiments, programming the stimulation device comprises programming the stimulation device with at least two sets of stimulation parameters, at least one first set of stimulation parameters for delivering of low frequency stimulation, for example mVNS, and at least one second set of stimulation parameters for delivery of high frequency stimulation, for example mVNS. In some embodiments, the first set of stimulation parameter comprises a frequency value of an electric field between about 1Hz and about 20Hz, for example between 1Hz and 8Hz, between 2Hz and 10Hz, between 7Hz and 15Hz, between 10 Hz and 20 Hz or any intermediate, smaller or larger frequency value. In some embodiments, the second set of stimulation parameter comprises a frequency value of an electric field between 30Hz and 60Hz, for example between 30Hz and 40Hz, between 35Hz and 45Hz, between 40Hz and 50Hz, between 45Hz and 60Hz, or any intermediate, smaller or larger frequency value.

[0245] According to some exemplary embodiments, low frequency mVNS is delivered to the median vagal nerve, at block 656. In some embodiments, the device delivers the low frequency mVNS using the first set of stimulation parameters. In some embodiments, the low frequency mVNS is delivered for a time period of up to 48 hours after completion of the ablation, for example for a time period of up to 4 days, at up to 1 week, up to 1 month, after completion of the ablation. Optionally, the low frequency mVNS is delivered prior to performing ablation at block 650, for example to prevent or reduce inflammation in the body prior to the ablation procedure

[0246] According to some exemplary embodiments, inflammation is optionally determined at block 658. In some embodiments, the inflammation is determined based on measurements of one or more inflammation markers, for example TNF-a, IL-6, CRP, TGF-pi, MMP2. Alternatively or additionally, inflammation is determined based on measurements of at least one physiological parameter which indicates inflammation or is correlated with an inflammation response, for example HRV, standard deviation of R-R intervals (SDNN) power in the high frequency band of HRV (HF-HRV), power in the low frequency band of HRV (LF-HRV), the ratio of LF to HF power (LF / HF ratio), square root of the mean squared differences of successive NN intervals.

[0247] In some embodiments, determining of inflammation comprises determining a level of inflammation. In some embodiments, measurements of the one or more inflammation markers and determining of inflammation is performed in a timed relation with the delivery of the low frequency mVNS, for example before, during and / or following the delivery of the low frequency mVNS. In some embodiments, values of one or more parameters of the low frequency mVNS is determined or adjusted based on the determining results. For example, if inflammation is still evident after a pre-determined time period for delivery of the low frequency mVNS, the delivery period is prolonged. Alternatively, if inflammation is reduced then delivery of the low frequency mVNS is stopped.

[0248] According to some exemplary embodiments, high frequency mVNS is delivered to the median vagal nerve, at block 660. In some embodiments, the high frequency mVNS is delivered using the at least one second set of stimulation parameters. In some embodiments, the high frequency mVNS is delivered after the delivery of the low frequency mVNS, or intermittently with the delivery of the low frequency mVNS. In some embodiments, the high frequency mVNS is delivered during a time period of at least two weeks, for example at least 1 month, at least 2 months, or any intermediate, shorter or longer time period. Optionally, the high frequency mVNS is delivered until an end of a blanking period. Optionally, the high frequency mVNS is additionally delivered after the blanking period.

[0249] According to some exemplary embodiments, a state of the arrhythmia is optionally determined at block 662. In some embodiments, the state of the arrhythmia is determined based on measurements of at least one physiological or clinical parameter indicating recurrence of the arrhythmia, for example occurrence of at least one arrhythmia symptom following the ablation. In some embodiments, the state of the arrhythmia is determined in a time relation with the delivery of the high frequency mVNS, for example before, during and / or after the delivery of the high frequency mVNS. Optionally, at least one parameter of the delivery of the high frequency mVNS is determined or adjusted based on the determining results. For example, if a recurrence of arrhythmia is detected, at least one of, a frequency, wave form, intensity, timing and / or duration of the high frequency mVNS is modified. In some embodiments, the arrhythmia state is determined based on measurements performed by the device 404 or the system 402, shown in fig. 4 and / or based on input received by the device or the system 402, for example input regarding an occurrence of at least one arrhythmia symptom.

[0250] Exemplary detailed process for determining ablation efficiency

[0251] According to some exemplary embodiments, ablation efficiency is determined after delivery of a stimulation treatment to a subject, following an ablation procedure performed in the subject. In some embodiments, determining efficiency of the ablation procedure allows, for example, to decide and select a treatment regime. In some embodiments, the treatment regime may include re-performing of the ablation procedure. Alternatively, the treatment regime may include a drug treatment and / or a VNS, for example a mVNS treatment. Alternatively, for example if the ablation was efficient, there is no need for an anti- arrhythmic treatment for the subject.

[0252] According to some exemplary embodiments, the system, for example system 402 is used as a decision guiding system, optionally assisting a cardiologist to select a treatment, for example an anti- arrhythmic treatment for the subject, following an ablation procedure and / or following a blanking period of the ablation.

[0253] Reference is now made to fig. 7 depicting a general process for determining an ablation efficiency and for determining of a suitable treatment following an ablation and / or a blanking period, according to some exemplary embodiments of the invention.

[0254] According to some exemplary embodiments, a subject is optionally provided with a stimulation device, at block 702. In some embodiments, the device is the stimulation device 404. In some embodiments, the subject is diagnosed with arrhythmia, for example atrial arrhythmia. In some embodiments, the subject receives the device after experiencing at least one arrhythmia occurrence or related symptom. In some embodiments, the subject receives the device at a medical facility, for example a clinic or a hospital.

[0255] According to some exemplary embodiments, the subject receives the device in order to initiate a stimulation protocol. Additionally, the subject receives the device for measuring one or more physiological and / or clinical parameters during a stimulation treatment, for example during or between stimulation sessions in which an electric field is delivered to the subject body, for example for affecting a Vagus nerve, optionally a median vagal nerve.

[0256] According to some exemplary embodiments, data is optionally received from the device, at block 704. In some embodiments, receiving the data from the device means receiving data from the system, for example system 402. In some embodiments, the data is received by an expert, for example a cardiologist. In some embodiments, the received data includes at least one of, measurements of at least one physiological parameter indicating an arrhythmia occurrence or related symptom and / or a state of the subject heart, input from the subject regarding at least one arrhythmia occurrence or related symptom, information about delivery of stimulation, for example in the form of an electric field, and / or activity of the stimulation device.

[0257] According to some exemplary embodiments, the cardiologist optionally determines responsiveness of the subject to the stimulation, at block 706. In some embodiments, the cardiologist determines responsiveness of the subject to the stimulation based on the data received at block 706. In some embodiments, determining a responsiveness comprises determining whether the subject body, for example the subject heart, responded to the stimulation, for example by reducing occurrence of at least one arrhythmia or related symptom or intensity thereof, during a period in which stimulation is delivered intermittently to the median Vagus nerve. Alternatively or additionally, determining a responsiveness of the subject to the stimulation comprises determining if there was a target change, for example a desired change, in at least one physiological parameter in response to the stimulation, for example determining if there was a target change in heart rate, heart rate variability, and / or ECG signal in response to the stimulation.

[0258] According to some exemplary embodiments, if the responsiveness of the subject is not a target responsiveness or is lower than a target responsiveness, then stimulation treatment is stopped. Alternatively, a stimulation protocol or at least one parameter of the stimulation is modified, optionally at least one parameter of the delivered electric field is modified, for example frequency, wave form, intensity and / or duration.

[0259] According to some exemplary embodiments, the determining responsiveness of the subject to the stimulation is optionally performed in order to determine whether a stimulation treatment can be performed in a subject following a future ablation procedure.

[0260] According to some exemplary embodiments, the cardiologist characterizes a subject state, at block 708. In some embodiments, the characterization comprises determining occurrence frequency and / or intensity of at least one arrhythmia occurrence or related symptom in the subject. Additionally, the characterization comprises characterizing an arrhythmia in the subject, for example identifying origin of the arrhythmia in the subject heart and / or electrical conduction pathways involved in the arrhythmia. Additionally, the characterization comprises determining responsiveness of the subject arrhythmia to at least one treatment, for example a drug treatment and / or a mVNS treatment. In some embodiments, determining responsiveness of the subject arrhythmia to the at least one treatment comprises determining an effect of the at least one treatment on occurrence of at least one arrhythmia symptom and / or an intensity of the at least one symptom.

[0261] According to some exemplary embodiments, characterizing a subject comprises receiving, information on the subject current and / or past clinical state, and / or information on a regime of at least one drug provided to the subject.

[0262] According to some exemplary embodiments, the cardiologist decides to perform ablation in the subject, at block 710. In some embodiments, the decision to perform ablation is based on the characterization of the subject performed at block 708. Alternatively or additionally, the cardiologist decides to perform an ablation procedure in the subject if an at least one arrhythmia symptom occurs too frequent and / or the intensity of the at least one arrhythmia symptom is higher than a tolerable intensity. Alternatively or additionally, the cardiologist decides to perform the ablation procedure if at least one ablation target is identified and reachable by an ablation catheter.

[0263] According to some exemplary embodiments, optionally a blanking period is estimated at block 712. In some embodiments, the blanking period is estimated at block 712. In some embodiments, the blanking period is estimated based on the planned ablation, for example based on the selected ablation target. Additionally or alternatively, the blanking period is estimated based on the subject state characterization performed at block 708, for example based on at least one of, subject health, medical history, drug regime, arrhythmia symptoms occurrence and / or arrhythmia symptom intensity. Additionally or optionally, the blanking period is estimated based on the responsiveness of the subject to the stimulation. Optionally, the blanking period is estimated using on or more statistical algorithms, tables and / or lookup tables, associating the subject state and / or planned ablation information with a blanking period following the ablation. In some embodiments, the cardiologist estimates the blanking period duration, optionally based on information received from a stimulation and / or an assessment system, for example system 402 shown in fig. 4.

[0264] According to some exemplary embodiments, estimating a blanking period comprises estimating a blanking period to be between 1 week and 4 months, for example a blanking period duration between 1 week and 2 months, between 1 month and 4 months, between 3 weeks and 4 months, or any intermediate, shorter or longer blanking period duration. In some embodiments, if the subject is responsive to the stimulation, as optionally determined at block 706, then the blanking period duration is shorter than 8 weeks, for example shorter than 7 weeks, shorter than 5 weeks, shorter than 3 weeks, or any intermediate, shorter or longer time duration.

[0265] According to some exemplary embodiments, ablation is performed at block 714. In some embodiments, the ablation is performed by a cardiologist in a medical facility, for example a hospital or a clinic. In some embodiments, during the ablation procedure performed in an ablation or a catheterization room, at least one target in the subject heart is ablated. In some embodiments, the at least one ablation target comprises a tissue of the heart acting as an electrical activity source or a tissue of the heart used for conduction of electrical activity.

[0266] According to some exemplary embodiments, during the ablation procedure energy for example cold or heat or pulsed filed (PFA) is delivered to the at least one ablation target in a level that is sufficient to prevent functional activity of the tissue either as an electrical activity source and / or for conducting electrical signals in the heart. In some embodiments, the delivered energy forms a scar tissue at the at least one ablation target. According to some exemplary embodiments, the blanking period is optionally estimated after the ablation procedure. In some embodiments, the blanking period estimation is based on the ablation procedure performed in the subject, and is similar to the description of block 712. Alternatively, a blanking period estimated at block 712 is updated following the ablation procedure, and is based on the subject state following the ablation, and / or on the actual ablation procedure performed in the subject.

[0267] According to some exemplary embodiments, a stimulation device is provided to the subject at block 716. In some embodiments, the stimulation device is provided to the subject at the end of the ablation procedure while the subject is still in the medical facility. Alternatively, the stimulation device is provided to the subject at a clinic or at a medical facility, at least 24 hours, at least 48 hours, at least 96 hours, at least 1 week after the ablation procedure.

[0268] According to some exemplary embodiments, the device is programmed, at block 718. In some embodiments, the device is programmed following the ablation procedure by a person, for example a cardiologist performing the ablation. In some embodiments, programming the device comprises selecting stimulation parameter values, for example intensity values, frequency values, stimulation timing values, and / or stimulation duration values. Alternatively, the programming comprises selecting a stimulation protocol out of at least two stimulation protocols stored in a memory of the device or in a memory of a system, for example system 402 shown in fig. 4.

[0269] Optionally, programming the device comprises evoking at least one arrhythmia occurrence or related symptom and selecting stimulation parameter values that attenuate occurrence or related symptom intensity or stimulation parameter values that stop the symptom. Optionally, programming of the device comprises selecting stimulation parameter values that are suitable to attenuate and / or eliminate at least one arrhythmia symptom detected prior or during the ablation procedure.

[0270] Additionally, programming the device comprises programming measurements performed by the device during and / or following stimulation. In some embodiments, the measurements are measurements of at least one physiological or clinical parameter, optionally performed by at least one detector, for example detector 417 of device 404 shown in fig. 4. In some embodiments, programming measurements comprises programming measurements timing. In some embodiments, the at least one physiological or clinical parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, indications of heart health and / or ECG measurements. In some embodiments, the programming of measurements comprises programming of measurements performed by the system 402, using at least one detector associated with the system, for example at least one detector of the communication device and / or at least one detector of a device associated with the communication device 420 or with the remote device 422.

[0271] Optionally, programming measurements performed by the device or by the system, comprises setting a reminders schedule for a subject using the stimulation device to provide input data.

[0272] Optionally, the programming at block 718 comprises updating a previous programming of the device or of the system.

[0273] According to some exemplary embodiments, at least one indication regarding the initiation of a stimulation treatment or delivery of stimulation, is received from the device at block 719.

[0274] According to some exemplary embodiments, following the ablation procedure, data is optionally received from the device, at block 720. In some embodiments, the data comprises measurements of the at least one physiological or clinical parameter. Alternatively, the received data comprises one or more log files or any report of the activation of the device and / or of the stimulation. In some embodiments, the data is received by the system and is optionally delivered via a user interface of the system to a cardiologist, an expert, a healthcare provider, and / or to the subject using the device.

[0275] According to some exemplary embodiments, arrhythmia information, for example, arrhythmia state, parameter and / or occurrence or related symptoms information is received from intermittent monitoring at block 722. In some embodiments, symptoms information comprises information about at least one symptom, for example an arrhythmia symptom. In some embodiments, the symptom information comprises occurrence or early recurrence and / or intensity of at least one arrhythmia occurrence or related symptom occurring following the ablation procedure, optionally during the blanking period of the ablation process.

[0276] According to some exemplary embodiments, receiving symptoms information comprises receiving signals from at least one detector or a device measuring the at least one physiological or clinical parameter. Alternatively or additionally, receiving symptoms information comprises receiving at least one input signal from the subject regarding symptom occurrence or symptom intensity. In some embodiments, the at least one input signal is received from the subject using at least one user interface associated with the system.

[0277] According to some exemplary embodiments, a program of the stimulation device is optionally modified, at block 724. In some embodiments, the program is modified during the blanking period based on the symptoms information received at block 722 and / or based on the data received at block 720. In some embodiments, the information received includes information about an early recurrence of an arrhythmia event and / or a related symptom, optionally based on measurements of at least one physiological parameter. In some embodiments, modifying the device program comprises modifying at least one parameter of the stimulation and / or at least one parameter of measurements performed by the device. Alternatively, modifying the program comprises selecting a different stimulation protocol. In some embodiments, modifying the device program comprises modifying at least one parameter of the stimulation, for example to improve efficiency of the stimulation in attenuating intensity of at least one arrhythmia symptom and / or reducing or eliminating occurrence of the at least one arrhythmia symptom. In some embodiments, the program of the device is optionally modified during the ablation blanking period. In some embodiments, the program of the device is optionally modified by an expert, a cardiologist, a healthcare provider or the subject receiving the stimulation.

[0278] According to some exemplary embodiments, ablation efficiency is determined at block 726. In some embodiments, the ablation efficiency is determined based on symptoms information received at block 722 and / or the data received at block 720. In some embodiments, an expert, for example the cardiologist who performed the ablation or a cardiologist monitoring the subject state, determine ablation efficiency based on signals received from the system, for example signals received from the device 404, from the communication device 420 and / or signals received from the remote device 422. Optionally, the expert determines ablation efficiency based on a score calculated by the system, for example as described at block 516 of fig. 5.

[0279] According to some exemplary embodiments, determining ablation efficiency comprises determining if the ablation procedure was sufficient to eliminate occurrence of at least one arrhythmia symptom, or to reduce intensity of the at least one arrhythmia symptom to a tolerable level.

[0280] According to some exemplary embodiments, the expert decides to repeat the ablation procedure at block 728. In some embodiments, the expert decides to repeat the ablation procedure based on the determined efficiency of the ablation, for example when determining that the ablation performed at block 714 was not efficient. Optionally, the expert decides to repeat the ablation procedure based on at least one indication with suggestions received from the system.

[0281] According to some exemplary embodiments, the expert decides to proceed following the blanking period with stimulation only at block 730. In some embodiments, the expert decides to continue with stimulation only based on the determined efficiency of the ablation, for example when determining that the ablation performed at block 714 was efficient and there is a need for a maintenance treatment optionally by the stimulation to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Alternatively, the expert decides to continue with stimulation only when ablation was not efficient but simulation was sufficiently efficient to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Optionally, the expert decides to proceed with stimulation treatment based on at least one indication with suggestions received from the system.

[0282] According to some exemplary embodiments, the expert decides to proceed following the blanking period with stimulation and a drug treatment at block 732. In some embodiments, the expert decides to proceed with stimulation and a drug treatment based on the determined efficiency of the ablation, for example when determining that the ablation performed at block 714 was efficient and there is a need for a maintenance treatment optionally by the stimulation in combination with a drug treatment to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Alternatively, the expert decides to continue with stimulation and drug treatment when ablation was not efficient but simulation in combination with a drug treatment is expected to be sufficiently efficient to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Optionally, the expert decides to proceed with a combined treatment of both stimulation and drug administration based on at least one indication with suggestions received from the system.

[0283] According to some exemplary embodiments, the expert decides to proceed following the blanking period with a drug treatment at block 734. In some embodiments, the expert decides to proceed with a drug treatment based on the determined efficiency of the ablation, for example when determining that the ablation performed at block 714 was efficient and there is a need for a maintenance treatment optionally by administering at least one drug to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Alternatively, the expert decides to continue with a drug treatment when ablation was not efficient but a drug treatment is expected to be sufficiently efficient to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Optionally, the expert decides to proceed with a drug treatment based on at least one indication with suggestions received from the system.

[0284] According to some exemplary embodiments, the expert decides to proceed following the blanking period with no treatment at block 736. In some embodiments, the expert decides to proceed with no treatment based on the determined efficiency of the ablation, for example when determining that the ablation performed at block 714 was efficient and there is no need for any other treatment to reduce symptom intensity and / or to reduce or eliminate symptom occurrence. Optionally, the expert decides to proceed with no additional treatment based on at least one indication with suggestions received from the system. Exemplary atrial fibrillation (AF) patient journey

[0285] According to some exemplary embodiments, the stimulation treatment, for example the median vagal stimulation is delivered to a subject diagnosed with atrial arrhythmia, for example AF, or to a subject suffering from at least one symptom of AF. In some embodiments, symptoms of AF comprise at least one of, heart palpitations, fatigue, shortness of breath, dizziness, lightheadedness, chest pain, chest discomfort, weakness and / or fainting or near fainting. In some embodiments, the stimulation treatment is delivered to a subject diagnosed with AF or suffering from at least one AF symptom that underwent a heart ablation procedure. In some embodiments, the stimulation reduces occurrence of symptoms and / or intensities of symptoms by affecting at least one brain region controlling at least one sympathetic and / or para-sympathetic pathway from the at least one brain region to heart tissue.

[0286] Reference is now made to figs. 8A and 8B depicting an AF patient journey, according to some exemplary embodiments of the invention.

[0287] According to some exemplary embodiments, a subject / patient experiences at least one AF symptom, at block 802. In some embodiments, the subject senses the at least one AF symptom and is capable of reporting occurrence of the symptom.

[0288] Alternatively, measurements show AF, at block 804. In some embodiments, the measurements comprise ECG measurements. In some embodiments, the measurements show irregular or erratic heartbeats.

[0289] According to some exemplary embodiments, the subject undergoes validation of the AF, at block 806. In some embodiments, the validation comprises performing ECG and / or Holter monitor measurements. In some embodiments, the validation is performed at least partly in a medical facility, for example at a clinic or at a hospital.

[0290] According to some exemplary embodiments, the AF is diagnosed and classified, at block 808. In some embodiments, the AF is diagnosed and classified at block 808 based on the reports of the subject experiencing at least one AF symptom and / or based on the measurements performed during the validation at block 806. In some embodiments, the AF in the subject is classified into Paroxysmal AF, Persistent AF, long-standing persistent AF, or permanent AF, at block 808.

[0291] According to some exemplary embodiments, a risk of the subject to develop stroke is estimated at block 810. In some embodiments, the stroke risk is estimated using the CHA2DS2- VASc scoring system, or a variation of a CHAD-VAS scoring system. Alternatively or additionally, the stroke risk is estimated using at least one of, Echocardiogram, Transesophageal Echocardiography (TEE), D-Dimer Test, Holter Monitor / Event Recorder, Blood Test, CT, MRI, and / or a HAS-BLED scoring system.

[0292] According to some exemplary embodiments, if the risk of stroke is estimated to high, for example if a score of a risk exam is higher than a reference value, then an anticoagulants treatment is provided to the subject at block 814. In some embodiments, the anticoagulants treatment comprises Novel Oral Anticoagulants, also known as non-vitamin K antagonist oral anticoagulants, for example dabigatran, rivaroxaban, apixaban, and edoxaban. Alternatively, if the risk is low, for example if a score of a risk exam is lower than a reference value, then no anticoagulants are provided to the subject, at block 812.

[0293] According to some exemplary embodiments, assessment of heart structure and / or symptoms severity is performed at block 816. In some embodiments, the symptoms assessment is performed using at least one of, European Heart Rhythm Association (EHRA) scoring system, Atrial Fibrillation Effect on Quality of Life (AFEQT) Questionnaire, Atrial Fibrillation Severity Scale (AFSS), EuroQol (for example EuroQol-5D questionnaire), and / or Visual Analog Scale (VAS). Alternatively or additionally, heart structure assessment is performed using one or more imaging techniques, and / or measurements of heart activity. In some embodiments, the assessment performed at block 816 is similar to the subject state characterization described at block 708 of fig- 7.

[0294] According to some exemplary embodiments, a treatment is determined at block 818. In some embodiments, the treatment is determined based on the assessment performed at block 816. Alternatively or additionally, the treatment is determined based on at least one of, validation performed at block 806, AF diagnosis and classification performed at block 808 and / or estimation of a risk for stroke performed at block 810. Optionally, median- vagal nerve stimulation is delivered to the subject prior to the determining of the treatment, and, in some embodiments, the determining of the treatment is based on a responsiveness of the subject to the stimulation.

[0295] According to some exemplary embodiments, determining a treatment comprises determining if a subject will receive at least one antiarrhythmic drug or if the subject will be ablated.

[0296] According to some exemplary embodiments, an ablation procedure is performed at block 820. In some embodiments, during the ablation procedure energy is delivered to at least one target region in the heart forming scar tissue at the at least one target region. In some embodiments, the ablation causes inflammation and / or autonomic nervous system (ANS) imbalance, leading to occurrence of atrial arrhythmia or related symptoms. In some embodiments, a blanking period is a period after the ablation procedure where a cardiologist is unable to determine if arrhythmia symptoms subject experiences are due to failure of the ablation procedure or part of the healing process of the heart following the ablation procedure. In some embodiments, the blanking period lasts up to about 100 days, for example up to about 90 days, up to about 70 days, up to about 60 days, up to about 40 days, or any intermediate, shorter or longer time duration.

[0297] Optionally, the subject receives at least one drug, for example an antiarrhythmic drug following the ablation, at block 822.

[0298] According to some exemplary embodiments, the subject receives VNS, for example mVNS following the ablation procedure, at block 824. In some embodiments, the subject receives the mVNS during the blanking period. In some embodiments, the stimulation is delivered using the device 404 shown in fig. 4. In some embodiments, the stimulation is delivered with high frequency, for example with a low frequency electric field, optionally for treating inflammation following the ablation procedure. Alternatively or additionally, the stimulation is delivered with high frequency, for example as a low frequency electric field to treat the ANS imbalance.

[0299] According to some exemplary embodiments, the mVNS is delivered according to the characterization of the subject state prior to the ablation procedure, for example according to the assessment performed at block 816. In some embodiments, the mVNS is delivered according to measurements and / or assessment of symptoms, performed during the ablation procedure, for example at an end of the ablation procedure and optionally as part of a test where atrial arrhythmia is intentionally induced in order to check success of the ablation procedure to affect at least one specific target region in the heart.

[0300] According to some exemplary embodiments, heart activity and / or symptoms are monitored at block 826. In some embodiments, heart activity and / or symptoms are monitored during the blanking period of the ablation procedure. In some embodiments, heart activity and / or symptoms are monitored using measurements performed by the device, for example device 404 or by at least one detector associated or in communication with the system 402. In some embodiments, symptoms monitoring comprises receiving at least one input signal from the subject regarding sensing of at least one symptom. For example, an arrhythmia symptom.

[0301] According to some exemplary embodiments, the monitoring is performed during the delivery of the stimulation treatment, for example in between active delivery of the electric field to the subject. Optionally, stimulation is modified based on results of the monitoring, for example according to occurrence and / or intensity of at least one symptom detected during the blanking period.

[0302] According to some exemplary embodiments, assessment of the ablation procedure is performed at block 828. In some embodiments, the assessment is performed at an end of the ablation period. In some embodiments, the assessment is performed by measuring at least one physiological or clinical parameter indicating heart activity using a smartwatch, an activity tracking device, a consumer ECG, a 12 lead ECG, a Holter monitor, and / or an ECG patch. Alternatively or additionally, the assessment is performed based on indication of symptom measurements or an indication of a symptom sensed by the subject during the blanking period.

[0303] According to some exemplary embodiments, if the ablation was successful, then the subject optionally receives at least one anti-coagulation treatment, using at least one anticoagulation drug, at block. 830. In some embodiments, the anti-coagulation treatment is provided, for example, to reduce a risk for developing stroke. In some embodiments, the anticoagulation treatment is similar or is a variation of a treatment provided at block 814.

[0304] Additionally or alternatively, if the ablation was successful, the subject optionally receives a mVNS stimulation treatment at block 832. In some embodiments, the mVNS stimulation treatment is similar to the treatment delivered at block 824, or is a variation thereof. For example, values of one or more parameters of the stimulation treatment are modified according to a time period that passed from the ablation procedure and / or according to results of measurements of the at least one physiological or clinical parameter performed following the ablation procedure, and optionally performed continuously or intermittently following the ablation.

[0305] According to some exemplary embodiments, an ablation assessment is performed at least 1 week following the ablation procedure, for example at least about 2 weeks, at least about 4 weeks, at least about 6 weeks, at least about 8 weeks, at least about 3 months, at least about 5 months, at least about 6 months, at least about 10 months, at least about 12 months, or any intermediate, longer or shorter time period following the ablation procedure. In some embodiments, the ablation assessment is performed about 8 weeks, about 3 months, about 6 months and / or about 1 year following the ablation procedure. In some embodiments, the ablation assessment is performed at block 836 as describe at block 828.

[0306] According to some exemplary embodiments, if the assessment performed at block 836 indicates that the ablation is successful, then the subject optionally continuous to receive the anticoagulation treatment and / or the stimulation treatment. Alternatively, the subject receives no treatment. According to some exemplary embodiments, if the assessment performed at block 836 indicates that the ablation is not successful, then a repeated ablation procedure is optionally performed at block 838. Alternatively or additionally, a drug treatment is optionally initiated or modified at block 840. For example, a treatment with at least one antiarrhythmic drug is optionally initiated or modified at block 840. Alternatively or additionally, a stimulation treatment, for example a mVNS treatment is optionally initiated or modified at block 842.

[0307] According to some exemplary embodiments, if the assessment performed at block 828 indicates that the ablation is not successful, then a repeated ablation procedure is performed at block 844, with or without an anticoagulation treatment. Alternatively, mVNS stimulation is delivered to the subject at block 846. Alternatively or additionally, a drug treatment comprising at least one of, anticoagulant, antiarrhythmic drug, and / or rate control is delivered to the subject at block 848.

[0308] According to some exemplary embodiments, assessment of the subject state is performed at block 850. In some embodiments, the assessment is performed, for example as described at blocks 828 and / or 836.

[0309] According to some exemplary embodiments, if the assessment performed at block 850 indicates that the subject still experiences at least one arrhythmia symptom, then a repeated ablation procedure is optionally performed at block 838. Alternatively or additionally, a drug treatment is optionally initiated or modified at block 840. For example, a treatment with at least one antiarrhythmic drug is optionally initiated or modified at block 840. Alternatively or additionally, a stimulation treatment, for example a mVNS treatment is optionally initiated or modified at block 842.

[0310] Exemplary device

[0311] According to some exemplary embodiments, a device, for example device 402 shown in fig. 4, is a home-care, wearable, medical device. In some embodiments, the device is configured to deliver pre-scheduled, non-invasive, peripheral neuromodulation therapy in patients with atrial arrhythmia, for example AF and optionally paroxysmal AF. In some embodiments, the device is intended for use at home under a direction of a licensed medical professional and in conjunction to standard medical therapy by adult patients with AF, for example paroxysmal atrial fibrillation, to aid in the reduction of AF burden and symptoms. In some embodiments, the device is configured to record using at least one detector, store, and / or transmit at least one of the following physiological data: i) Heart Rate; ii) Electrocardiogram (ECG); and iii) Heart Rate Variability, and derivative parameters, for example oxygen saturation. In some embodiments, the device comprises a gyroscope and / or an accelerometer, configured to record at least one parameter related to movement of the subject, for example motion, activity and / or rest of the subject. In some embodiments, the device stores the recorded movement parameter in a memory of the device, and optionally transmits the recorded movement parameter to a remote device. In some embodiments, the measurements are performed by a system that includes the device, for example by at least one different device that includes at least one detector.

[0312] According to some exemplary embodiments, the device comprises a miniature ECG and Stimulation Unit (mESU) configured to deliver stimulation and to perform ECG measurements. Reference is now made to fig. 9A, depicting modules of the mESU unit, according to some exemplary embodiments of the invention.

[0313] According to some exemplary embodiments, the device is a wearable device composed of a packed electronic housing and a wrist band housing. In some embodiments, the packaged electronics (mESU) includes embedded software. In some embodiments, the wrist band housing includes a Thermoplastic polyurethane (TPU) band and a user interface module which consists of a LED indicator, a buzzer, an OLED screen and an on / off switch.

[0314] According to some exemplary embodiments, the mESU comprises a communication circuitry for wireless communication with at least one remote device, for example a smartwatch, a smart band, a smart ring, or any personal health monitoring device, optionally using wireless signals. In some embodiments, the mESU transmits information optionally including measurements performed by the mESU and / or log files to the remote device. Optionally, the mESU is activated, for example to perform one or more measurements and / or to deliver stimulation based on a signal received form the remote device. In some embodiments, the communication circuitry of the mESU comprises a Bluetooth module configured to generate and / or receive Bluetooth Low Energy (BLE) signals.

[0315] Additionally, the device is internally powered by at least one battery, for example a Li- Ion rechargeable battery where charging connectors are directed to the inner side of the device thus optionally preventing charging while the device is on the patient’s wrist.

[0316] According to some exemplary embodiments, the device 902 comprises at least on stimulation electrode 904 configured to deliver an electric field to a tissue. In some embodiments, the electrode 904 is an "internal" electrode (an electrode on an inner part of the bracelet / wrist band), configured to be in contact with a skin of a patient during a neurostimulation session. In some embodiments, the device 902 further includes at least one additional electrode, for example a dual function electrode 906. In some embodiments, electrode 906 is an "internal" electrode configured to be in contact with a skin of a patient during sessions which is used for stimulation during a stimulation session with the electrode 904 and / or for ECG acquisition during a monitoring session.

[0317] According to some exemplary embodiments, the device 902 further includes at least one ECG sensing electrode 908. In some embodiments, the electrode 908 is an "external' electrode (an electrode on the outer part of the bracelet / wrist band) that is used during ECG reading.

[0318] According to some exemplary embodiments, the device 902 comprises a stimulation unit, for example an electrical stimulation inducing unit 910. In some embodiments, the unit 910 comprises a voltage step up module 912. In some embodiments, the module 912 is a circuitry used for increasing neuromodulation signal intensity (voltage). In some embodiments, the parameters are determined according to treatment type and controlled by a control unit 914. In some embodiments, the unit 910 comprises a Polarity and Timing Switches module 916. In some embodiments, module 916 is a circuitry for inducing a bi-phasic signal with specific time constraints (pulse rate, pulse width, etc.). In some embodiments, the switches are also used to disconnect stimulation circuitry from both electrodes. In some embodiments, the unit 910 comprises a current measurements module 918 configured to measure current flow through the electrodes, for example electrodes 904 and 906, to the patient body.

[0319] According to some exemplary embodiments, the device 902 comprises an ECG acquisition unit 920. In some embodiments, the unit 920 comprises a voltage amplification module 922, which is circuitry configured to amplify the voltage difference measured between two parts of the human body used for ECG reading. In some embodiments, the unit 920 comprises at least one analog filter 924. In some embodiments, the filter 924 is a circuitry used for filtering the signal sampled from the body during ECG reading. In some embodiments, the unit 920 comprises an analog-digital converter circuitry 926, used for sampling the analog signal allowing further analysis in MCU.

[0320] According to some exemplary embodiments, the device 902 further includes a power management circuitry 928. In some embodiments, the circuitry 928 is configured to control and supply power to components of the device 902. In some embodiments, a switch connects a power source, for example at least one battery, to the circuitry 928.

[0321] According to some exemplary embodiments, the device 902 comprises a communication unit 930. In some embodiments, the unit 930 is configured to transmit and / or receive signals from at least one additional device. Optionally, the communication unit 930 is used for BLE (Bluetooth Low Energy) communication.

[0322] According to some exemplary embodiments, the device 902 comprises the control unit 914. In some embodiments, the unit 914 comprises a microcontroller, configured to at least one of, receive and transmit data, for reading an ECG sampled signal, for controlling the stimulus parameters, and for controlling and monitoring the user interface. Furthermore, in some embodiments, the control unit 914 monitors the device, for example the mESU internal status during operation.

[0323] According to some exemplary embodiments, the device 902 comprises a user interface 932. In some embodiments, the user interface 932 is configured to receive input and / or to generate and deliver at least one indication, for example a human detectable indication. In some embodiments, the user interface 932 comprises at least one light emitting diode (LED), at least one buzzer, and / or a display.

[0324] Reference is now made to fig. 9B, depicting communication of the device with at least one additional device, according to some exemplary embodiments of the invention.

[0325] According to some exemplary embodiments, in order to control the treatment delivered, and to store and / or analyze acquired data, the device 902 interacts with a mobile application 940 which, in turn, interacts with a cloud-based server application 942.

[0326] Reference is now made to fig. 9C depicting positioning of the device on a hand of a subject, optionally around a wrist of the subject, according to some exemplary embodiments of the invention.

[0327] According to some exemplary embodiments, a device, for example device 402 shown in fig. 4 or device 902 shown in fig. 9A comprises at least one flexible fastener 950, optionally shaped as a band or a bracelet, that is configured to position the device around an arm of a subject, optionally around a wrist, such that at least two electrodes, for example electrodes 952 and 954 contact a skin surface of the arm. In some embodiments, the at least two electrodes contact an underside of the arm, for example at a wrist region of the arm. In some embodiments, the electrodes are spaced apart and are positioned each on a different side of a nerve 956, for example a median vagal nerve. In some embodiments, an electric field generated by the device is delivered by the electrodes 952 and 954 and between the electrodes transcutaneously to a tissue of the arm, for example an underside of the hand comprising the nerve 956.

[0328] Reference is now made to fig. 9D, depicting a signal of an electric field generated by the device, according to some exemplary embodiments of the invention.

[0329] According to some exemplary embodiments, the stimulation comprises a delivery of an electric field having a low current through a patient arm. In some embodiments, the electric field has a current lower than 25 mA, for example lower than 20 mA, lower than 15 mA, lower than 10 mA, lower than 5 mA, or any intermediate, smaller or larger value. In some embodiments, the electric field is delivered as a bi-phasic pulse, for example pulse 960. Optionally pulse 960 is a symmetrical or asymmetrical bi-phasic waveform having an intensity between + / - 0-80V.

[0330] According to some exemplary embodiments, the electric field is delivered in a frequency between 0.5Hz and 100Hz, for example in a frequency between 0.5Hz and 20 Hz, in a frequency between 5Hz and 50Hz, in a frequency between 20Hz and 100Hz, or any intermediate, smaller or larger frequency or range of frequencies. Optionally, a frequency preset is between 40Hz and 50Hz, for example between 40Hz and 47Hz, between 43Hz and 47Hz, or any intermediate, smaller or larger frequency or range of frequencies. In some embodiments, the electric field is delivered with mixed, and optionally alternating frequencies.

[0331] According to some exemplary embodiments, the electric field is delivered with intermittency Ranges: On / Off 1-60 / 0-30 sec. In some embodiments, the electric field is delivered with an intermittency preset: On / Off 10 / 1 sec. In some embodiments, an intensity, for example an output voltage, of the electric field is between 0V and about 80V, for example between 0V and about 50V, between about 30V and about 80V, between about 20V and about 60V, or any intermediate, smaller or larger value or range of values. In some embodiments, the electric field is delivered with an output peak current lower than about 25 mA, for example lower than about 20 mA, lower than about 15 mA, lower than about 10 mA, lower than about 5 mA, or any intermediate, smaller or larger value. In some embodiments, the electric field is delivered with an active “on” pulse width 962 in a range between 50ps and 400ps, for example about 200ps, lOOps and 300ps, or any intermediate, smaller or larger pulse width.

[0332] As used herein with reference to quantity or value, the term “about” means “within ± 20 % of’.

[0333] The terms “comprises”, “comprising”, “includes”, “including”, “has”, “having” and their conjugates mean “including but not limited to”.

[0334] The term “consisting of’ means “including and limited to”.

[0335] The term “consisting essentially of’ means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0336] As used herein, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.

[0337] Throughout this application, embodiments of this invention may be presented with reference to a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as “from 1 to 6” should be considered to have specifically disclosed subranges such as “from 1 to 3”, “from 1 to 4”, “from 1 to 5”, “from 2 to 4”, “from 2 to 6”, “from 3 to 6”, etc.; as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0338] Whenever a numerical range is indicated herein (for example “10-15”, “10 to 15”, or any pair of numbers linked by these another such range indication), it is meant to include any number (fractional or integral) within the indicated range limits, including the range limits, unless the context clearly dictates otherwise. The phrases “range / ranging / ranges between” a first indicate number and a second indicate number and “range / ranging / ranges from” a first indicate number “to”, “up to”, “until” or “through” (or another such range-indicating term) a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numbers therebetween

[0339] Unless otherwise indicated, numbers used herein and any number ranges based thereon are approximations within the accuracy of reasonable measurement and rounding errors as understood by persons skilled in the art.

[0340] As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0341] As used herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

[0342] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements. Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

[0343] EXAMPLES

[0344] Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.

[0345] Randomized Controlled Trial (RTC) - Preliminary results

[0346] Purpose of the Study

[0347] The purpose of the RCT was to determine the effect of the system by delivering median / Vagus nerve neuromodulation (mVNS) on atrial arrhythmia recurrence, burden and related symptoms in patients undergoing catheter ablation for both paroxysmal and persistent Atrial Fibrillation (AF).

[0348] Study Design

[0349] Prospective, controlled, double-blind, randomized multi-site clinical trial enrolling 90 patients with a planned follow up period of 6 months. The first 15 patients were not randomized and received the active median / vagal stimulation only (open label).

[0350] Study conduct

[0351] The first 15 patients were enrolled in an open-label phase, received active neuromodulation only, and were not randomized. Treatment commenced immediately after ablation, and all patients received continuous monitoring via patch ECG recorders for the first month, and again at week 6 for an additional two weeks. Neuromodulation was performed daily for the first two weeks, then three times per week for the remainder of the six-month treatment period, with additional sessions triggered by symptoms or when detected by the system ECG monitoring from the device. Patients received training on how to use the system and continued standard-of-care medications, while arrhythmia-related symptoms were documented using a patient diary or app-based questionnaire.

[0352] Preliminary results from the Open Label Group (n=ll)

[0353] The following tables (table 1 and Table 2) shows the preliminary results of 11 patients from the 15 patients in the open label group, where: AF burden (% of time in AF) from continuous ECG patch monitoring mounted immediately after ablation for 12-30 days (n=l l, average 26 days) and again at week 6 after ablation for an average of 11 days (n=4).

[0354] Table 1

[0355] Table 2

[0356] Data from 11 patients (out of the 15) who received immediate post-ablation median / vagal nerve stimulation via the system / device, shows that none experienced atrial fibrillation (AF) episodes during the first month, as confirmed by continuous ECG monitoring. Furthermore, among the four patients (001, 002, 007 and 013) with available data extending into the second month, none exhibited AF recurrence.

[0357] These outcomes contrast with findings from the PUESED AF trial, which reported early recurrence of atrial tachyarrhythmias (ERAT) in 27.1% of patients with paroxysmal AF and 31.6% with persistent AF. Notably, 73% of these recurrences occurred within the first month post-procedure. Additionally, broader literature indicates that early AF recurrence rates within the first two months post-ablation can reach up to 42%.

[0358] In addition, acute reduction in cardiac ectopy in the form of premature beats were observed in 2 Min ECG’s taken immediately before (Figure 10A) Vs. immediately after (Figure 10B) neuromodulation sessions were also apparent in this post ablation population, as shown for example in Figures 10A and 10B.

[0359] Therefore, it has been shown that patients who received treatment did not experience AF episodes, in contrast to findings from studies and literature showing that AF recurrence rates in this population are -30%. Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A method for post ablation treatment of a subject diagnosed with atrial arrhythmia, comprising: a. diagnosing a subject with atrial arrhythmia; b. performing an ablation procedure in a heart of said subject following said diagnosing; c. delivering a stimulation treatment following said ablation, wherein said stimulation is delivered with parameter values suitable for affecting occurrence of atrial arrhythmia and / or at least one symptom thereof in said subject following said ablation.

2. The method according to claim 1, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for attenuating occurrence and / or severity of said at least one symptom of said atrial arrhythmia.

3. The method according to claim 1, wherein said delivering comprises delivering said stimulation treatment with parameter values suitable for eliminating appearance of said atrial arrhythmia and / or symptoms thereof in said subject following said ablation.

4. The method according to claim 1, wherein said stimulation treatment is delivered during a blanking period of said ablation.

5. The method according to claim 4, comprising determining an efficiency of said ablation during and / or at an end of said blanking period, wherein said determining an efficiency comprises determining intensity and / or occurrence of at least one arrhythmia symptom during said blanking period.

6. The method according to claim 5, comprising modifying at least one parameter of said stimulation or stopping said delivering if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

7. The method according to claim 6, comprising determining to repeat said performing of said ablation if said determining an efficiency indicates that said intensity and / or occurrence of said at least one arrhythmia symptom is higher than a predetermined value.

8. The method according to claim 1, wherein said at least one symptom comprises at least one of, heart palpitations, skipping heart beats, rushing heart beats, fatigue, shortness of breath, dizziness, lightheadedness, chest pain, chest discomfort, weakness and / or fainting or near fainting.

9. The method according to claim 1, further comprising collecting, prior to said ablation, information on one or more occurrences of at least one symptom of said atrial arrhythmia in said subject, and further comprising setting at least one parameter of said stimulation treatment based on said collected information.

10. The method according to claim 9, wherein said at least one parameter of said stimulation treatment comprises timing for initiation of said stimulation treatment, frequency of stimulation sessions in which an electric field is actively delivered to said subject, interval between said stimulation sessions, time of day in which said electric field is delivered to the subject body, intensity of said electric field, frequency of said electric field, pulse width of said electric field, number of pulses of said electric field delivered to the subject in at least one stimulation session, and / or duration of each pulse in said at least one stimulation session.

11. The method according to claim 1, further comprising setting at least one parameter of said stimulation treatment based on at least one parameter of said ablation procedure, wherein said at least one parameter comprises at least one of, ablation procedure completion time, ablation target, ablation parameters, ablation outcomes and / or complications during the ablation procedure.

12. The method according to claim 11, wherein said at least one parameter of said stimulation treatment comprises timing for initiation of said stimulation treatment, frequency of stimulation sessions in which an electric field is actively delivered to said subject, interval between said stimulation sessions, time of day in which said electric field is delivered to the subject body, intensity of said electric field, frequency of said electric field, pulse width of said electric field, number of pulses of said electric field delivered to the subject in at least one stimulation session, and / or duration of each pulse in said at least one stimulation session.

13. The method according to claim 1, wherein said delivering said stimulation treatment comprises delivering of an electric field to a median nerve and / or to an ulnar nerve of said subject with parameter values selected to attenuate or eliminate occurrence of said arrhythmia or said at least one symptom thereof.

14. The method according to claim 12, wherein said delivering comprises one or more of: a. delivering said electric field with a frequency between 30Hz and 60Hz; b. delivering low frequency median vagal nerve stimulation (mVNS) and high frequency mVNS to said subject, wherein delivering of said low frequency mVNS comprises delivering of an electric field with a frequency between 1Hz and 20Hz, and wherein delivering of said high frequency mVNS comprises delivering an electric field with a frequency between 30Hz and 60Hz.

15. The method according to claim 14, wherein said high frequency mVNS is delivered after delivery of said low frequency mVNS.

16. The method according to claim 14, wherein said low frequency mVNS is delivered for a time period of up to 8 weeks following said ablation.

17. The method according to claim 14, wherein said delivering comprises delivering said low frequency mVNS and said high frequency mVNS intermittently.

18. The method according to claim 1, further comprising monitoring a state of said subject following said performing.

19. The method according to claim 18, wherein said monitoring is performed according to a predetermined scheduled, intermittently or continuously.

20. The method according to claim 19, wherein said monitoring comprises measuring at least one physiological parameter from a body of said subject, and / or receiving input from said subject or from a caregiver of said subject.

21. The method according to claim 20, wherein said at least one physiological parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, pulse oximetry, VO2 max, motion, indications of heart health, and / or Electrocardiogram (ECG) measurements.

22. The method according to claim 20, wherein said input comprises information about at least one of, occurrence and / or intensity of at least one symptom of said atrial arrhythmia and / or information on a prodromal symptom of said atrial arrhythmia.

23. The method according to claim 18, further comprising detecting early recurrence of atrial arrhythmia after said ablation based on results of said monitoring.

24. The method according to claim 18, further comprising modifying values of at least one parameter of said stimulation treatment based on results of said monitoring.

25. The method according to claim 24, wherein said at least one parameter comprises at least one of, treatment duration, electric field pulse duration, electric field frequency, intermittency and / or intensity of said electric field delivered to said subject during said stimulation treatment.

26. The method according to claim 18, further comprising determining an arrhythmia state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia state comprises determining a change in a severity of said arrhythmia.

27. The method according to claim 18, further comprising determining an arrhythmia symptom state following said delivering based on results of said monitoring, and wherein said determining an arrhythmia symptom state comprises determining a change in occurrence and / or intensity of a least one symptom of said atrial arrhythmia.

28. The method according to claim 18, further comprising determining efficiency of said ablation in said subject following said delivering based on results of said monitoring, and wherein said determining efficiency comprises determining said efficiency based on detecting early occurrence and / or severity of a least one symptom or findings from a measurement of said atrial arrhythmia following said performing of said ablation.

29. The method according to claim 28, comprising deciding to repeat said performing of said ablation, and / or to provide a drug treatment to said subject and / or to continue with delivery of said stimulation treatment to said subject, if said determined efficiency is lower than a target efficiency.

30. The method according to claim 1, further comprising delivering said stimulation treatment to said subject prior to and / or during said ablation.

31. The method according to claim 30, wherein said stimulation treatment is delivered to said subject following said ablation based on a responsiveness of said subject to said stimulation treatment delivered prior to said ablation.

32. The method according to claim 1, wherein said atrial arrhythmia comprises atrial fibrillation, supraventricular tachycardia (SVT), Atrial flutter, Sinus tachycardia, premature atrial contractions (PACs), atrial tachycardia (AT), and Multifocal atrial tachycardia (MAT).

33. The method according to claim 1, wherein said delivering said stimulation comprises delivering median vagal nerve stimulation (mVNS) to a median and / or an ulnar nerve located in or near a wrist region of an arm of said subject.

34. A method for affecting a post ablation blanking period in a subject, comprising: a. performing an ablation in a heart of a subject suffering from at least one arrhythmia symptom; b. estimating a blanking period following said ablation; c. delivering median vagal nerve stimulation (mVNS) treatment following said ablation, wherein said median nerve stimulation is delivered with parameter values suitable for attenuating atrial arrhythmia and / or for augmenting a balance of an autonomic nervous system in said subject following said ablation; d. shortening said estimated blanking period based on a responsiveness of said subject to said delivered mVNS.

35. The method according to claim 34, wherein said stimulation treatment is delivered during a blanking period of said ablation.

36. The method according to claim 34, wherein said delivering comprises delivering low frequency mVNS and high frequency mVNS to said subject, wherein delivering of said low frequency mVNS comprises delivering of an electric field with a frequency between 1Hz and 20Hz, and wherein delivering of said high frequency mVNS comprises delivering an electric field with a frequency between 30Hz and 60Hz.

37. A method for reducing inflammation in a subject, comprising: a. diagnosing a subject with arrhythmia; b. performing an ablation procedure in a heart of said subject following said diagnosing; c. delivering low frequency median vagal nerve stimulation (mVNS) treatment to said subject prior to and / or following said ablation, wherein said delivering comprises delivering an electric field with a frequency between 1 Hz and 20 Hz to a median nerve and / or to an ulnar nerve of said subject.

38. The method according to claim 37, wherein said electric field is delivered to said subject with parameter values selected to reduce or prevent inflammation in said subject.

39. The method according to claim 37, wherein said delivering comprises delivering said mVNS treatment during a blanking period of said ablation procedure.

40. The method according to claim 37, wherein said delivering comprises initiating said delivering of said mVNS treatment up to 2 weeks after said performing of said ablation procedure.

41. The method according to claim 37, wherein said delivering comprises initiating said delivering of said mVNS treatment up to 2 weeks after said performing of said ablation procedure.

42. The method according to claim 37, wherein delivering said mVNS treatment prior to said performing of said ablation procedure comprises delivering said mVNS treatment at least 48 hours prior to said performing of said ablation procedure.

43. A system for delivery of mVNS treatment comprising: a stimulation device, comprising: a. at least two electrodes; b. a housing shaped and sized to position said at least two electrodes near a median nerve or an ulnar nerve of a subject; c. a pulse generator configured to generate an electric field and to deliver said electric field via said at least two electrodes to a subject body; d. a memory, wherein said memory stores values of parameters of said electric field selected, wherein values of at least one parameter of said parameters is determined according to an ablation procedure performed or scheduled to be performed in said subject; e. a control circuitry configured to signal said pulse generator to generate said electric field according to parameters values stored in said memory and to deliver said electric field via said at least two electrodes to said median nerve and / or to said ulnar nerve.

44. The system according to claim 43, wherein said values of said parameters are selected to reduce occurrence of arrhythmia in said subject and / or to affect an autonomous nervous system of said subject, by said generated electric field.

45. The system according to claim 44, wherein said values of said are selected to reduce sympathetic overdrive and parasympathetic or vagal overdrive in said subject, by said generated electric field.

46. The system according to claim 43, wherein said parameters comprise frequency of said electric field, wherein said control circuitry is configured to signal said pulse generator to generate said electric field with frequency between 1 Hz and 20Hz, and / or with frequency between 30 Hz and 60 Hz.

47. The system according to claim 43, wherein said at least one parameter comprises time before or after said ablation procedure for initiating the generation and delivery of said electric field to said subject.

48. The system according to claim 43, wherein said at least one parameter comprises frequency, intensity, pulse width, duration of said electric field delivery, and / or number of pulses of said electric field delivered to said subject.

49. The system according to claim 43, wherein said memory stores information about said ablation procedure comprising, an estimated duration of a blanking period of said ablation procedure, a date of said ablation procedure, a target of said ablation procedure, measurements performed during said ablation procedure, and / or input received during the ablation procedure, and wherein values of said at least one parameter are determined according to said stored information about said ablation procedure.

50. The system according to claim 43, further comprising: a. at least one remote device in communication with said stimulation device, wherein said remote device comprises: i. a memory which stores information about said ablation procedure comprising, an estimated duration of a blanking period of said ablation procedure, a date of said ablation procedure, a target of said ablation procedure, measurements performed during said ablation procedure, and / or input received during the ablation procedure; ii. a communication circuitry in communication with said stimulation device; iii. a control circuitry configured to generate and deliver to said stimulation device programming information of said at least one parameter, wherein said programming information is generated based on said information stored in the information of said remote device.

51. The system according to claim 43, wherein said memory stores a blanking period related indication which includes information about a starting time of a blanking period following said ablation procedure, a duration of said blanking period, an ending time of said blanking period and / or timing for assessment of a subject state during and / or following the blanking period, wherein said stimulation device further comprises at least one detector configured to record at least one signal from said subject body, and wherein said control circuitry measures at least one physiological parameter based on said at least one recorded signal and according to said blanking period related indication.

52. The system according to claim 51, wherein said at least one physiological parameter comprises at least one of, heart rate, heart rate variability (HRV), electrical activity, heart rhythm, electrical conduction, cardiac events, pulse oximetry, VO2 max, motion, indications of heart health, and / or Electrocardiogram (ECG) measurements.

53. The system according to claim 51, wherein said control circuitry is configured to detect arrhythmia in said subject during said blanking period based on said measurements of said at least one physiological parameter.

54. The system according to claim 53, wherein said stimulation device comprises a user interface configured to generate a human detectable indication, and wherein said control circuitry is configured to determine an efficiency or success of said ablation procedure performed in said subject based on said measurements of said at least one physiological parameter and / or said detected arrhythmia, and signal said user interface to generate said human detectable indication with information about the efficiency or success of said ablation procedure.

55. The system according to claim 51, comprising: a. a remote device in communication with said stimulation device, wherein said remote device comprises: i. a communication circuitry configured to receive signals from said stimulation device; ii. a memory, wherein said memory stores measurements of said at least one physiological parameter or indications thereof, performed by the stimulation device and received from said stimulation device using said communication circuitry, and / or input information received from said subject regarding at least one symptom of an arrhythmia; iii. a control circuitry configured to determine an efficiency or success of said ablation procedure performed in said subject based on said measurements of said at least one physiological parameter or indications thereof, and / or based on said input information stored in said memory, to generate at least one indication according to said determined efficiency or success of said ablation procedure, and to deliver said at least one indication using said communication circuitry to at least one of, a monitoring center, a health maintenance organization, a cardiologist and / or to an expert monitoring a state of said subject following said ablation procedure.

56. The system according to claim 55, wherein if said delivered at least one indication indicates that said ablation procedure was not efficient, said delivered at least one indication further comprises a suggestion to repeat said ablation procedure.

57. The system according to claim 55, wherein if said delivered at least one indication indicates that said ablation procedure was not efficient, said delivered at least one indication further comprises a suggestion to initiate delivery of a drug treatment to said subject, to modify a drug treatment provided to said subject or to stop a drug treatment already provided to said subject.

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