System and method for cardiac treatment

Abstract

A method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient. The method may include ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure, and ablating a greater splanchnic nerve to reduce stressed blood volume with exertion. The method may include ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure and at least one of: ablating pulmonary artery nerves of the patient to reduce cardiac sympathetic activity; and ablating pulmonary vein nerves of the patient to reduce arrhythmias.

Description

Attorney Docket No. A0012938W001SYSTEM AND METHOD FOR CARDIAC TREATMENTFIELD

[0001] The present disclosure generally relates to a method and system of treating coronary microvascular disease and reducing heart failure with preserved ejection.BACKGROUND

[0002] Heart failure (HF) is a complex disease state broadly defined by an inability of the heart to pump sufficiently to cope with its venous return and / or to deliver sufficient output to meet the metabolic demands of the body. Heart failure is an increasingly common, life-threatening cardiovascular disorder, characterized by marked disability, frequent hospitalization and high mortality. HF is increasingly prevalent in older individuals (up to 10% of the population) and it has become the most common cause for hospitalization in people >65 yrs. HF is a leading cause or contributor to hospitalization and therefore is emerging as a substantial contributor to healthcare spending. The particular clinical manifestations of HF are determined by the underlying cause of the heart failure.

[0003] The term heart failure (HF) refers broadly to a pathophysiologic disorder in which cardiac performance is incapable of delivering sufficient blood to meet metabolic demand (e.g. during physical activity or in severe cases at rest), or to accommodate venous return. A range of further sub-classifications and / or structure of the heart, can then be applied, based on the symptoms exhibited by the patient. Exemplary classifications of heart failure by symptoms or objective assessments are provided by the New York Heart Association (classes LIV, classes A-D)). Heart failure can also be defined by ejection fraction. Generally, patients exhibiting an ejection fraction of less than or equal to 0.35 are classified as having heart failure with reduced ejection fraction (HFrEF) while an ejection fraction above 0.35 is considered to be heart failure with preserved ejection fraction (HFpEF).

[0004] Congestive heart failure symptoms are indicative of congestive heart failure. Exemplary congestive heart failure symptoms include reduced cardiac output leading to easy fatigue and organ dysfunction (e.g. renal), and to symptoms related to congestion either in the lungs (causing breathlessness) or peripherally (leading to swelling of the lower limbs and abdomen).

[0005] A possible correlation has been identified between sedentary lifestyle and risk of ventricular arrhythmias based on a comparison of occurrences of ventricular arrhythmiasAttorney Docket No. A0012938W001 in healthy active vs. sedentary men, and men with previous myocardial infarction. One result of a sedentary lifestyle is that the size of the chambers of the heart may decrease, which often occurs as a result of increased muscle thickness. Accordingly, the greatest number and highest grades of ventricular arrhythmias during exercise were found in healthy sedentary men.

[0006] Nearly half of all patients with heart failure have a normal ejection fraction (EF), commonly referred to as heart failure with preserved ejection fraction (HFpEF). Further, a large subset of HFpEF population has underlying microvascular disease (MVD) with hypertension and inflammation at foundation. In congestive heart failure patients with HFpEF the amount of blood pumped from the heart's left ventricle with each beat (ejection fraction) is greater than 50%. Some invasive studies demonstrate the prevalence of MVD in HFpEF is consistently high, ranging between 70 - 85% depending on the diagnostic thresholds used, such as CFR <2 to < 2.5, IMR >23 to >25.

[0007] HFpEF is also commonly known as diastolic heart failure or diastolic dysfunction, as the deficit in function frequently relates to changes occurring during diastole and filling of the ventricles. Approximately half of people with heart failure have HFpEF, while the remainder display a reduction in ejection fraction, or heart failure with reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, likely because of the increasing prevalence of common risk factors, including older age, hypertension, metabolic syndrome, renal dysfunction and obesity. HFpEF is characterized by abnormal diastolic function, which manifests as an increase in the stiffness of the heart's left ventricle, a decrease in left ventricular relaxation when filling with blood before the next beat, and decreased chamber volume, which often occurs as a result of increased muscle thickness. There is an increased risk for atrial fibrillation and pulmonary hypertension for patient's experiencing HFpEF.

[0008] Changes from MVD can mediate thickening and stiffening of the left ventricle (LV) wall, or concentric remodeling, which are characteristic of HFpEF. In patients with hypertension or aortic stenosis, these remodeling processes are believed to be partly induced by a state of LV pressure overload. Specifically, wall stress increases to maintain ejection performance under an elevated load that the heart pumps against during systole (e.g., afterload). In this context, concentric remodeling occurs to minimize the changes in wall stress, as predicted by the law of Laplace.

[0009] In healthy vessels, coronary blood flow and myocardial perfusion are regulated by coronary arteriolar tone. Coronary blood flow remains constant over a wideAttorney Docket No. A0012938W001 range of coronary perfusion pressures through dynamic changes in resistance vessel tone. These dynamic changes result from a series of partially redundant mechanisms, including adrenergic stimuli, changes in local oxygen tension, and the response to changes in transmural pressure. Such redundant control of coronary blood flow helps to mitigate myocardial ischemia during the development and progression of epicardial atherosclerosis. Because myocardial oxygen extraction is near-maximal at rest, myocardial oxygen delivery is almost completely dependent on coronary blood flow. Consequently, an increase in myocardial oxygen demand must be matched by a proportional increase in coronary blood flow to prevent myocardial ischemia. Coronary microvascular disease (CMD) attenuates coronary flow augmentation in response to stress and, if severe enough to lead to demand-supply mismatch, may lead to subclinical or clinical myocardial ischemia. With the development of CVD risk factors and atherosclerosis, the vascular endothelium becomes dysfunctional and the vasodilator response to pharmacological and physiological interventions is attenuated, resulting in blunted coronary blood flow augmentation or vasoconstriction with frank reduction in blood flow. There is evidence that more than one-half of atherosclerotic coronary arteries without focally obstructive stenoses display a significant longitudinal pressure gradient affecting coronary blood flow and myocardial perfusion, which can contribute to myocardial ischemia and symptoms. This may help to explain the discrepancy between ischemic symptoms and the low frequency of obstructive coronary artery disease (CAD) in large registries of invasive coronary angiography and recent diagnostic clinical trials with cardiac computed tomography angiography as provided in Viviany R. Taqueti, Marcelo F. Di Carli, Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the- Art Review, Journal of the American College of Cardiology, Volume 72, Issue 21, 2018, Pages 2625-2641, ISSN 0735-1097. Second, recognition that symptoms in patients with nonobstructive CAD may be related to CMD offers an opportunity for directing additional investigations to improving diagnosis and management. Viviany R. Taqueti, Marcelo F. Di Carli, Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review, Journal of the American College of Cardiology, Volume 72, Issue 21, 2018, Pages 2625-2641, ISSN 0735-1097.

[0010] Obesity, especially visceral obesity, is associated with microvascular disease MVD, including impairments in functional capillary density, endothelium-dependent vasodilation, vasomotion, and insulin-induced microvascular dilation and recruitment. An important consequence of MVD in obesity is that it contributes to impairment of insulin-Attorney Docket No. A0012938W001 mediated glucose disposal. Experimental evidence indicates that obesity shifts this balance toward less vasodilation, or even vasoconstriction, through adverse changes in adipokines, such as adiponectin, free fatty acids, and tumor necrosis factor-a. These changes impair insulin signal transduction in endothelial cells, resulting in less nitric oxide synthesis.

[0011] A second consequence of MVD in obesity is an increase in peripheral resistance and, other things being equal, blood pressure. Hypertension is characterized by multiple abnormalities of microvascular structure and function in many organs, such as reduced density (rarefaction) of arterioles, capillaries, and venules; enhanced constriction and reduced dilation of arterioles, including reduced endothelium-dependent vasodilation induced by insulin and other mediators; decreased arteriolar diameter; and increased wall-to-lumen ratio of small arteries (remodeling). Hypertension undoubtedly causes MVD, but, as reviewed elsewhere, MVD is currently thought to be both cause and consequence of high blood pressure.

[0012] Traditionally, CMD pathophysiology was thought to be a combination of microvascular architectural changes and endothelial dysfunction. Microvascular architectural changes include microvascular obstruction, with luminal narrowing of the arterioles and capillaries, and capillary rarefaction. Alternatively, or concurrently, endothelial or vascular smooth muscle (VSM) dysfunction may lead to an attenuated vasodilatory response or a pathological vasoconstrictive response to stimuli, leading to a blunted augmentation of, or reduction of, coronary blood flow (CBF) in response to stress. This can lead to a supplydemand mismatch in CBF, therefore leading to ischaemia and symptoms of angina. Patients with structural CMD appear to have more established cardiovascular risk factors, including poorly controlled hypertension, type 2 diabetes mellitus (T2DM) and a higher prevalence of exercise-induced hypertension as provided in Weerts, J.; Mourmans, S.G.J.; Barandiaran Aizpurua, A.; Schroen, B.L.M.; Knackstedt, C.; Eringa, E.; Houben, A.J.H.M.; van Empel, V.P.M. The Role of Systemic Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction. Biomolecules 2022, 72, 278.SUMMARY

[0013] The techniques of this disclosure generally relate to the techniques of this disclosure generally relate to systems and methods of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies (e.g., HFpEF) and promoting cardiac remodeling of left ventricular hypertrophy in the patient.Attorney Docket No. A0012938W001

[0014] In one aspect, the present disclosure provides a method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient. The method includes ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure, and ablating a greater splanchnic nerve to reduce stressed blood volume with exertion.

[0015] In another aspect, the disclosure provides an alternative method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient. The alternative method includes ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure and at least one of: ablating pulmonary artery nerves of the patient to reduce cardiac sympathetic activity; and ablating pulmonary veins of the patient to reduce arrhythmias.

[0016] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG. 1 is a schematic diagram of a first embodiment of a cardiac therapy system of the present disclosure;

[0018] FIG. 2 is an illustration of a renal denervation system of the cardiac therapy system;

[0019] FIG. 3 is an illustration of a greater splanchnic nerve ablation system of the cardiac therapy system;

[0020] FIG. 4 is a schematic diagram that illustrates a method of cardiac therapy of the present disclosure;

[0021] FIG. 5 is a schematic diagram that illustrates a method of delivering renal denervation;

[0022] FIG. 6 is a schematic diagram that illustrates a method of greater splanchnic nerve ablation;Attorney Docket No. A0012938W001

[0023] FIG. 7 is a schematic diagram that illustrates a second embodiment of a cardiac therapy system of the present disclosure;

[0024] FIG. 8 is a schematic diagram that illustrates a second embodiment of a method of cardiac therapy; and

[0025] FIG. 9 is an illustration of a patient after using a pulmonary artery denervation system of the present disclosure.

[0026] Corresponding parts are given corresponding reference numbers throughout the drawings.DETAILED DESCRIPTION

[0027] The present disclosure provides system and methods for treating microvascular dysfunction. Treatment includes dampening an autonomic response dysfunction in a patient and by combining therapies to produce a synergetic effect.

[0028] Referring to FIG. 1, a schematic diagram of an exemplary cardiac therapy system that may be used to deliver a cardiac therapy to a patient according to the present disclosure is indicated at reference number 10. The system 10 is generally used to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies (e.g., HFpEF) and promoting cardiac remodeling of left ventricular hypertrophy in the patient.

[0029] Referring to FIG. 1, a schematic diagram of an exemplary cardiac therapy system that may be used to deliver a cardiac therapy to a patient according to the present disclosure is indicated at reference number 10. The system 10 is generally used to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies (e.g., HFpEF) and promoting cardiac remodeling of left ventricular hypertrophy in the patient.

[0030] The system 10 includes a renal denervation system, generally indicated at reference number 12 and a greater splanchnic nerve (GSN) ablation system 14. Using the combination of the renal denervation system 12 and the GSN ablation system 14, the system 10 provides a synergetic therapeutic effect to lower the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies (e.g., HFpEF) and promote cardiac remodeling of left ventricular hypertrophy in the patient.

[0031] The renal denervation system 12 is configured to ablate renal nerves (e.g., nerves of a renal artery) to reduce sympathetic afferent and efferent activity to the kidney, which decreases blood pressure in the patient. For example, the system 12 may be configuredAttorney Docket No. A0012938W001 to ablate neural fibers surrounding or in proximity to the renal artery, such as at least partially denervating the kidney(s) innervated by the renal neural fibers. For example, neural fibers of sympathetic nerves are typically between 1 to 10 mm away from the wall of the renal artery and can be ablated using the renal denervation system 12.

[0032] Referring to FIG. 2, in one suitable example, the renal denervation system 12 includes a renal denervation catheter 18 and a renal denervation generator 20. The renal denervation generator delivers energy through the renal denervation catheter 18. The renal denervation catheter 18 is positioned in a renal artery of the patient. In a preferred embodiment, the renal denervation catheter 18 is a six French compatible catheter with a plurality of electrodes 22 spaced along the catheter and a .014 guidewire 24. In an embodiment, the renal denervation catheter 18 is delivered to a renal artery of the patient using a rapid exchange system with the guidewire 24. Once positioned in the renal artery, the guidewire 24 is retracted such that the renal denervation catheter 18 conforms to the patient's renal artery without occluding blood flow. A helical ablation pattern is then performed through the renal denervation catheter 18 with energy delivered to electrodes of the renal denervation catheter to ablate renal nerves or bundles. RF energy delivered from the electrodes is monitored by impedance and temperature measurements of the electrodes. After the energy is delivered and the helical ablation pattern is performed through the renal denervation catheter 18, the renal denervation catheter may be repositioned to a contralateral renal artery of the patient (e.g., right kidney). Once repositioned, the helical ablation pattern is performed in the contralateral renal artery with the renal denervation catheter 18, and energy is delivered through the renal denervation catheter by the renal denervation generator 20. A suitable renal denervation system is described in U.S. Serial No. 15 / 851,68, filed December 21, 2017, the entirety of which is hereby incorporated by reference.

[0033] The renal nerves or bundles may be ablated in other ways other than catheter radiofrequency ablation, as described above. For example, known system for renal denervation includes ultrasound renal denervation (e.g., high intensity focused ultrasound), cryoablation, microwave ablation, pharmaceutical denervation, among other possible method for ablating the renal nerves or bundles.

[0034] Referring to FIG. 3, the GSN ablation system 14 includes a greater splanchnic nerve (GSN) ablation catheter 26 configured to be positioned, for example, in an intercostal vein 28 the patient. An ablation pattern is performed through the GSN ablation catheter 26 with energy delivered to the greater splanchnic nerve ablation catheter to ablate nerve tissue. A suitable GSN ablation system including a GSN ablation catheter is shown and described inAttorney Docket No. A0012938W001U.S. Serial No. 16 / 318,447, filed July 31, 2017, the entirety of which is incorporated by reference herein. Other systems and methods for ablating the GSN to produce the therapeutic effects described herein are included within the scope of the present disclosure.

[0035] Ablation of a right-sided greater splanchnic nerve (GSN) of the patient can reduce excessive splanchnic vasoconstriction, potentially improving the handling of volume shifts in patients with heart failure with preserved ejection fraction (HFpEF), including HFpEF with MVD. Further, ablation of a right-sided GSN reduces pulmonary capillary wedge pressure (PCWP) and promotes an environment for cardiac remodeling, (e.g., inducing remodeling of hypertrophy of the left ventricle of the patient's heart). As twenty-five percent of a person's blood is stored in the person's liver and spleen, small increases in sympathetic tone can produce large fluid shifts. Through ablating one of the two greater splanchnic nerve of the patient, stressed blood volume with exertion is reduced. This reduces a volume of blood a heart needs to work with and reduced oxygen demand on affected myocardium. Combining the greater splanchnic nerve ablation system 14 with the renal denervation system 12 for afterload reduction, promotes a reversal of MVD and / or HFpEF (e.g., HFpEF with MVD) using myocardial remodeling.

[0036] As will be appreciated by one skilled in the art, aspects of the embodiments disclosed herein may be embodied as a system, method, computer program product or any combination thereof. For example, referring to FIG. 4, the cardiac therapy system 10 can be a method for re-remodeling hypertrophy and inducing anti-inflammatory reflex is generally indicated at reference number 50. The method 50 generally includes step 52 comprising ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure, and step 54 comprising ablating a greater splanchnic nerve to reduce stressed blood volume with exertion. Each of these steps 52, 54 may be performed simultaneously or consecutively or in any order suitable for treating MVD and / or reducing HFpEF, and in particular, for treating HFpEF with MVD.

[0037] In an embodiment, referring to FIG. 5, step 52 of delivering renal denervation includes step 58 of delivering renal denervation using the renal denervation catheter comprising using a rapid exchange system with the guidewire 24, step 60 of retracting the guidewire such that the renal denervation catheter conforms to the patient's renal artery, step 62 of performing a helical ablation pattern with the renal denervation catheter, and step 64 of delivering energy through the renal denervation catheter with the renal denervation generator. Further, step 52 of delivering renal denervation may include step 66 of monitoring the energy through impedance and temperature measurements of each electrodes 22 on the renalAttorney Docket No. A0012938W001 denervation catheter and step 68 of utilizing simplicity algorithms for delivering energy through the renal denervation catheter to lower blood pressure of the patient. Further, step 52 of delivering renal denervation may include step 70 of repositioning the renal denervation catheter a contralateral renal artery of the patient and preforming steps 58-70. In an embodiment, repositioning can be done after performing a helical ablation pattern or multiple iterations of performing a helical ablation pattern. In a preferred embodiment, multiple iterations of performing the helical ablation pattern of 60 seconds can be performed before repositioning. The step 52 may include other steps for ablating (e.g., denervation of) the renal sympathetic nerves.

[0038] In an embodiment, referring to FIG. 6, step 54 of delivering greater splanchnic nerve ablation includes step 72 of delivering a greater splanchnic nerve ablation catheter into a distal section of an intercostal vein, step 74 of performing an ablation pattern with the greater splanchnic nerve ablation catheter, step 76 of delivering energy through the greater splanchnic nerve ablation catheter. The ablation energy used may be radiofrequency energy or other energy.

[0039] Referring to FIG. 7, a schematic diagram of another exemplary cardiac therapy system is generally indicated at reference number 110. The cardiac therapy system 110 may be used to dampen autonomic response dysfunction and by combining therapies there is a synergetic effect. The cardiac therapy system 110 is substantially similar to the cardiac therapy system 10. As such, like elements have been given like reference numbers plus 100. However, the cardiac therapy system 110 includes a pulmonary artery denervation (PADN) system generally indicated at reference number 115 in place of the greater splanchnic nerve ablation system 14 of the cardiac therapy system 10. Referring to FIG. 8, the cardiac therapy system 110 can be used to perform a method for dampening autonomic response dysfunction and by producing a synergetic effect in a patient, thereby treating MVD and / or reducing HFpEF, and in particular, treating HFpEF with MVD.

[0040] Referring to FIG. 7, the cardiac therapy system 110 includes a renal denervation system generally indicated at reference number 112, and the pulmonary artery denervation system generally indicated at reference number 115. The renal denervation system 112 lowers sympathetic nervous system (SNS) response to reduce afterload and inflammation in a patient similar to the renal denervation system 12 of the cardiac therapy system 10. The pulmonary artery denervation system reduces cardiac sympathetic activity, which leads to a lower pressure and reduction in preload.Attorney Docket No. A0012938W001

[0041] The pulmonary artery denervation (PADN) system 115 includes a pulmonary artery denervation (PADN) catheter and pulmonary artery denervation (PADN) generator. The PADN catheter is configured to deliver ablation energy from the PADN generator to the pulmonary artery nerves or pulmonary vein nerves. In one example, the energy delivered may be radiofrequency energy, although other types of energy suitable for ablating the pulmonary artery nerves may be used. While the greater PADN ablation system 14 focuses on reducing workload (oxygen demand) on the patient's left side heart, the pulmonary artery denervation system 115 focuses on reducing workload (oxygen demand) on the patient's right side heart to promote remodeling and reversal of MVD. A suitable pulmonary artery denervation system is shown and described in U.S. Serial No. 15 / 228,358, filed August 4, 2016, the entirety of which is hereby incorporated by reference herein.

[0042] Referring to FIG. 9, the pulmonary artery denervation system 115 reduces cardiac sympathetic activity, reduces Serum NE, ANG II, and increases RVOT ERP, resulting in an improvement of cardiac hemodynamics.

[0043] The invention may be further described by reference to the following numbered paragraphs:1. A method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the method comprising: ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and ablating a greater splanchnic nerve to reduce stressed blood volume with exertion.2. The method of cardiac treatment set forth in paragraph 1, wherein said ablating renal sympathetic nerves and said ablating a greater splanchnic nerve are performed simultaneously.3. The method of cardiac treatment set forth in paragraph 1, wherein said ablating renal sympathetic nerves and said ablating a greater splanchnic nerve are performed consecutively.4. The method of cardiac treatment set forth in any one of paragraphs 1 to 3, wherein said ablating renal sympathetic nerves comprises ablating the renal sympathetic nerves.Attorney Docket No. A0012938W0015. The method of cardiac treatment set forth in paragraph 4, wherein said ablating the renal sympathetic nerves is performed using an ablation catheter figured to be delivered into a renal artery of the patient.6. The method of cardiac treatment set forth in paragraph 5, wherein said ablation catheter is a radiofrequency ablation catheter.7. The method of cardiac treatment set forth in any one of paragraphs 1 to 6, wherein said ablating a greater splanchnic nerve comprises delivering a greater splanchnic nerve ablation catheter into a distal section of an intercostal vein of the patient.8. The method of cardiac treatment set forth in paragraph 7, wherein said ablating a greater splanchnic nerve comprises delivering radiofrequency energy to the greater splanchnic nerve via the greater splanchnic nerve ablation catheter.9. The method of cardiac treatment set forth in any one of paragraphs 1 to 8, wherein said ablating a greater splanchnic nerve comprises ablating a right-sided greater splanchnic nerve to reduce pulmonary capillary wedge pressure (PCWP) and promote an environment for cardiac remodeling.10. A cardiac therapy system configured to perform the method set forth in any one of paragraphs 1 to 9.11. A method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the method comprising: ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and ablating at least one of pulmonary artery nerves of the patient to reduce cardiac sympathetic activity, and pulmonary vein nerves of the patient to reduce arrhythmias.12. The method of cardiac treatment set forth in paragraph 11, wherein said ablating renal sympathetic nerves and said ablating at least one of pulmonary artery nerves and pulmonary vein nerves are performed simultaneously.13. The method of cardiac treatment set forth in paragraph 11, wherein said ablating renal sympathetic nerves and said ablating at least one of pulmonary artery nerves and pulmonary vein nerves are performed consecutively.14. The method of cardiac treatment set forth in any one of paragraphs 11 to 13, wherein said ablating renal sympathetic nerves comprises ablating the renal sympathetic nerves.Attorney Docket No. A0012938W00115. The method of cardiac treatment set forth in paragraph 14, wherein said ablating the renal sympathetic nerves is performed using an ablation catheter configured to be delivered into a renal artery of the patient.16. The method of cardiac treatment set forth in paragraph 15, wherein said ablating the renal sympathetic nerves comprises delivering radiofrequency energy to the renal sympathetic nerves via the ablation catheter.17. The method of cardiac treatment set forth in any one of paragraphs 11 to 16, comprising said ablating pulmonary artery nerves of the patient, wherein said ablating pulmonary artery nerves of the patient comprises delivering a PADN catheter into the pulmonary artery and delivering energy to the pulmonary artery nerves suitable for ablating the pulmonary artery nerves.18. The method of cardiac treatment set forth in paragraph 15, wherein said delivering energy comprises delivering radiofrequency energy.19. The method of cardiac treatment set forth in paragraph 17, wherein said ablating pulmonary artery nerves reduces Serum NE, ANG II, and increases RVOT ERP, thereby resulting in an improvement of cardiac hemodynamics.20. A cardiac therapy system configured to perform the method set forth in any one of paragraphs 11 to 19.21. A cardiac therapy system to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the cardiac therapy system comprising: a renal ablation system arranged to ablate renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and at least one of: a greater splanchnic nerve ablation system arranged to ablate a greater splanchnic nerve to reduce stressed blood volume with exertion; and a pulmonary denervation system arranged to ablate at least one of a pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and a pulmonary vein nerve of the patient to reduce arrhythmias.22. The cardiac therapy system set forth in paragraph 21, comprising the greater splanchnic nerve ablation system.Attorney Docket No. A0012938W00123. The cardiac therapy system set forth in paragraph 22, wherein the renal ablation system and greater splanchnic nerve ablation system are arranged to simultaneously and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney and ablate a greater splanchnic nerve to reduce stressed blood volume.24. The cardiac therapy system set forth in paragraph 22, wherein the renal ablation system and greater splanchnic nerve ablation system are arranged to consecutively and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney and ablate a greater splanchnic nerve to reduce stressed blood volume.25. The cardiac therapy system set forth in any one of paragraphs 21-24, wherein the greater splanchnic nerve ablation system is arranged to reduce pulmonary capillary wedge pressure in the patient to induce remodeling of hypertrophy of the left ventricle of the patient's heart.26. The cardiac therapy system set forth in any one of paragraphs 21-26, wherein the greater splanchnic nerve ablation system includes a great splanchnic nerve ablation catheter arranged to be inserted into a distal section of an intercostal vein of the patient.27. The cardiac therapy system set forth in any one of paragraphs 21-26, comprising the pulmonary denervation system.28. The cardiac therapy system set forth in paragraph 27, wherein the renal ablation system and the pulmonary denervation system are arranged to simultaneously and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, and ablate at least one of the pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and the pulmonary vein nerve of the patient to reduce arrhythmias.29. The cardiac therapy system set forth in paragraph 27, wherein the renal ablation system and the pulmonary denervation system are arranged to consecutively and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, and ablate at least one of the pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and the pulmonary vein nerve of the patient to reduce arrhythmias.30. The cardiac therapy system set forth in any one of paragraphs 27-29, wherein the pulmonary denervation system is arranged to ablate the pulmonary artery nerves to reduce oxygen demand on the patient's right side heart to induce remodeling of hypertrophy.Attorney Docket No. A0012938W001

[0044] It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the techniques). In addition, while certain aspects of this disclosure are described as being performed by a single module or unit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units or modules associated with, for example, a medical device.

[0045] In one or more examples, the described techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0046] Instructions may be executed by one or more processors, such as one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements.

[0047] When introducing elements of the present disclosure or the preferred embodiment(s) thereof, the articles "a", "an", "the" and "said" are intended to mean that there are one or more of the elements. The terms "comprising", "including" and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0048] In view of the above, it will be seen that the several objects of the disclosure are achieved and other advantageous results attained.

[0049] As various changes could be made in the above products and methods without departing from the scope of the disclosure, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

Claims

Attorney Docket No. A0012938W001WHAT IS CLAIMED IS:

1. A method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the method comprising: ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and ablating a greater splanchnic nerve to reduce stressed blood volume with exertion.

2. The method of cardiac treatment set forth in claim 1, wherein said ablating renal sympathetic nerves and said ablating a greater splanchnic nerve are performed simultaneously.

3. The method of cardiac treatment set forth in claim 1, wherein said ablating renal sympathetic nerves and said ablating a greater splanchnic nerve are performed consecutively.

4. The method of cardiac treatment set forth in any one of claims 1 to 3, wherein said ablating renal sympathetic nerves comprises ablating the renal sympathetic nerves.

5. The method of cardiac treatment set forth in claim 4, wherein said ablating the renal sympathetic nerves is performed using an ablation catheter figured to be delivered into a renal artery of the patient.

6. The method of cardiac treatment set forth in claim 5, wherein said ablation catheter is a radiofrequency ablation catheter.

7. The method of cardiac treatment set forth in any one of claims 1 to 6, wherein said ablating a greater splanchnic nerve comprises delivering a greater splanchnic nerve ablation catheter into a distal section of an intercostal vein of the patient.

8. The method of cardiac treatment set forth in claim 7, wherein said ablating a greater splanchnic nerve comprises delivering radiofrequency energy to the greater splanchnic nerve via the greater splanchnic nerve ablation catheter.Attorney Docket No. A0012938W0019. The method of cardiac treatment set forth in any one of claims 1 to 8, wherein said ablating a greater splanchnic nerve comprises ablating a right-sided greater splanchnic nerve to reduce pulmonary capillary wedge pressure (PCWP) and promote an environment for cardiac remodeling.

10. A cardiac therapy system configured to perform the method set forth in any one of claims 1 to 9.

11. A method of cardiac treatment to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the method comprising: ablating renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and ablating at least one of pulmonary artery nerves of the patient to reduce cardiac sympathetic activity, and pulmonary vein nerves of the patient to reduce arrhythmias.

12. The method of cardiac treatment set forth in claim 11, wherein said ablating renal sympathetic nerves and said ablating at least one of pulmonary artery nerves and pulmonary vein nerves are performed simultaneously.

13. The method of cardiac treatment set forth in claim 11, wherein said ablating renal sympathetic nerves and said ablating at least one of pulmonary artery nerves and pulmonary vein nerves are performed consecutively.

14. The method of cardiac treatment set forth in any one of claims 11 to 13, wherein said ablating renal sympathetic nerves comprises ablating the renal sympathetic nerves.

15. The method of cardiac treatment set forth in claim 14, wherein said ablating the renal sympathetic nerves is performed using an ablation catheter configured to be delivered into a renal artery of the patient.Attorney Docket No. A0012938W00116. The method of cardiac treatment set forth in claim 15, wherein said ablating the renal sympathetic nerves comprises delivering radiofrequency energy to the renal sympathetic nerves via the ablation catheter.

17. The method of cardiac treatment set forth in any one of claims 11 to 16, comprising said ablating pulmonary artery nerves of the patient, wherein said ablating pulmonary artery nerves of the patient comprises delivering a PADN catheter into the pulmonary artery and delivering energy to the pulmonary artery nerves suitable for ablating the pulmonary artery nerves.

18. The method of cardiac treatment set forth in claim 17, wherein said delivering energy to the pulmonary artery nerves comprises delivering radiofrequency energy to the pulmonary artery nerves.

19. The method of cardiac treatment set forth in claims 17 or 18, wherein said ablating pulmonary artery nerves reduces Serum NE, ANG II, and increases RVOT ERP, thereby resulting in an improvement of cardiac hemodynamics.

20. A cardiac therapy system configured to perform the method set forth in any one of claims 11 to 19.

21. A cardiac therapy system to provide a synergetic therapeutic effect of lowering the hyperactive sympathetic response observed in microvascular disease (MVD) and heart failure (HF) pathologies and promoting cardiac remodeling of left ventricular hypertrophy in a patient, the cardiac therapy system comprising: a renal ablation system arranged to ablate renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, thereby reducing blood pressure; and at least one of: a greater splanchnic nerve ablation system arranged to ablate a greater splanchnic nerve to reduce stressed blood volume with exertion; and a pulmonary denervation system arranged to ablate at least one of a pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and a pulmonary vein nerve of the patient to reduce arrhythmias.Attorney Docket No. A0012938W00122. The cardiac therapy system set forth in claim 21, comprising the greater splanchnic nerve ablation system.

23. The cardiac therapy system set forth in claim 22, wherein the renal ablation system and greater splanchnic nerve ablation system are arranged to simultaneously and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney and ablate a greater splanchnic nerve to reduce stressed blood volume.

24. The cardiac therapy system set forth in claim 22, wherein the renal ablation system and greater splanchnic nerve ablation system are arranged to consecutively and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney and ablate a greater splanchnic nerve to reduce stressed blood volume.

25. The cardiac therapy system set forth in any one of claims 21-24, wherein the greater splanchnic nerve ablation system is arranged to reduce pulmonary capillary wedge pressure in the patient to induce remodeling of hypertrophy of the left ventricle of the patient's heart.

26. The cardiac therapy system set forth in any one of claims 21-26, wherein the greater splanchnic nerve ablation system includes a great splanchnic nerve ablation catheter arranged to be inserted into a distal section of an intercostal vein of the patient.

27. The cardiac therapy system set forth in any one of claims 21-26, comprising the pulmonary denervation system.

28. The cardiac therapy system set forth in claim 27, wherein the renal ablation system and the pulmonary denervation system are arranged to simultaneously and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, and ablate at least one of the pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and the pulmonary vein nerve of the patient to reduce arrhythmias.Attorney Docket No. A0012938W00129. The cardiac therapy system set forth in claim 27, wherein the renal ablation system and the pulmonary denervation system are arranged to consecutively and respectively ablate the renal sympathetic nerves of the patient to reduce sympathetic afferent and efferent activity to the kidney, and ablate at least one of the pulmonary artery nerve of the patient to reduce cardiac sympathetic activity, and the pulmonary vein nerve of the patient to reduce arrhythmias.

30. The cardiac therapy system set forth in any one of claims 27-29, wherein the pulmonary denervation system is arranged to ablate the pulmonary artery nerves to reduce oxygen demand on the patient's right side heart to induce remodeling of hypertrophy.

Images