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Review
. 2021 Aug 31;78(9):931-956.
doi: 10.1016/j.jacc.2021.06.040.

Device Therapy in Chronic Heart Failure: JACC State-of-the-Art Review

Marat Fudim  1 , William T Abraham  2 , Ralph Stephan von Bardeleben  3 , JoAnn Lindenfeld  4 , Piotr P Ponikowski  5 , Husam M Salah  6 , Muhammad Shahzeb Khan  7 , Horst Sievert  8 , Gregg W Stone  9 , Stefan D Anker  10 , Javed Butler  11
Affiliations
Review

Device Therapy in Chronic Heart Failure: JACC State-of-the-Art Review

Marat Fudim et al. J Am Coll Cardiol. .

Abstract

The regulatory landscape for device-based heart failure (HF) therapies has seen a major shift in the last 7 years. In 2013, the U.S. Food and Drug Administration released guidance for early feasibility and first-in-human studies, thereby encouraging device innovation, and in 2016 the U.S. Congress authorized the Breakthrough Devices Program to expedite access for Americans to innovative devices indicated for diagnosis and treatment of serious illnesses, such as HF. Since December 2016, there has been an increase in the number of HF devices for which manufacturers are seeking approval through the breakthrough designation pathway. This has led to a rapid uptake in the development and evaluation of device-based HF therapies. This article reviews the current and future landscape of device therapies for chronic HF and associated comorbidities and the regulatory environment that is driving current and future innovation.

Keywords: U.S. Food and Drug Administration; device therapy; heart failure.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Fudim has received support from National Heart, Lung, and Blood Institute (NHLBI) grant K23HL151744, American Heart Association grant 20IPA35310955, the Mario Family Award, the Duke Chair’s Award, the Translating Duke Health Award, Bayer, and BTG Specialty Pharmaceuticals; and has received consulting fees from AstraZeneca, AxonTherapies, CVRx, Daxor, Edwards LifeSciences, Galvani, and NXT Biomedical. Dr Abraham has received personal fees from Abbott during the conduct of the study; has received consulting fees from Boehringer Ingelheim, CVRx, Edwards Lifesciences, Impulse Dynamics, and Respicardia; has received salary support from V-Wave Medical; and has received research support from the NHLBI, all for studies performed within the heart failure arena. Dr von Bardeleben has received grants from Abbott Structural Heart. Dr Lindenfeld has received grant funding from AstraZeneca, Volumetrix, and Sensible Medical; and has received consulting fees from AstraZeneca, Abbott, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards LifeSciences, Impulse Dynamics, and V-Wave. Dr Ponikowski has received consulting fees and speaker honoraria from AstraZeneca, Boehringer Ingelheim, Vifor Pharma, Amgen, Servier, Novartis, Berlin Chemie, Bayer, Pfizer, Cibiem, Coridea, Impulse Dynamics, Renal Guard Solutions, BMS, and Abbott Vascular; is a co-principal investigator for the RESHAPE-HF trial for AbbottVascular; and has received a research grant from Vifor Pharma. Dr Sievert has served as a consultant for 4tech Cardio, Abbott, Ablative Solutions, Ancora Heart, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Carag, Cardiac Dimensions, Celonova, Cibiem, CGuard, Comed BV, Contego, CVRx, Edwards, Endologix, Hemoteq, InspireMD, Lifetech, Maquet Getinge Group, Medtronic, Mitralign, Nuomao Medtech, Occlutech, pfm Medical, Recor, Renal Guard, Rox Medical, Terumo, Vascular Dynamics, Vivasure Medical, Venus, and Veryan. Dr Stone has received speaker or other honoraria from Cook, Terumo, QOOL Therapeutics, and Orchestra Biomed; has served as a consultant for Valfix, TherOx, Cardiomech, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, and Matrizyme; and holds equity in or has options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr Anker has received grants from Vifor Int and Abbott; and has received personal fees from Vifor, Bayer, Boehringer Ingelheim, Novartis, Servier, Abbott, Cardiac Dimensions, Impulse Dynamics, V-Wave, and Occlutech. Dr Butler has served as a consultant for Abbott, Adrenomed, American Regent, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, Cardiac Dimension, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Occlutech, Roche, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Central Illustration:
Central Illustration:
FDA-approved and breakthrough designated device therapies. FDA-approved and breakthrough designated devices in the heart failure space split out by heart failure subtype (HFrEF, HFpEF and LVEF independent) Abbreviations: HFrEF= heart failure with reduced ejection fraction, HFpEF= heart failure with preserved ejection fraction. FDA= food and drug administration, LVEF= left ventricular ejection fraction. TR= tricuspid regurgitation
Figure 1.
Figure 1.
Device therapy for mitral valve regurgitation Mitral regurgitation development and progression in heart failure is mostly secondary to annular dilatation and leaflet tethering, papillary muscle desynchrony, and valve tenting due to increased left atrial pressure (A). MitraClip is a cobalt-chrome implant that allows for an edge-to-edge repair of the mitral valve (B). (C) Results of the COAPT trial (17). Abbreviations: AO= Aorta, LA= left atrium, LV= left ventricle.
Figure 2.
Figure 2.
Baroreflex activation therapy and vagus nerve stimulation Baroreflex activation therapy: (A) The baroreflex signals mainly originate from the carotid sinus and aortic arch (stimulated by arterial distention). These signals inhibit the rostral ventrolateral medulla. Consequently, the sympathetic activity in various organs decreases. From (38). (B) The effect of baroreflex activation therapy on exercise capacity, quality of life, and the level of N-terminal pro-brain natriuretic peptide. From (42). Vagus Nerve Stimulation: (C) Device-based stimulation of the vagus nerve can counteract the excessive activation of the sympathetic nervous system (SNS) and decreased parasympathetic nervous system (PNS) activity seen in heart failure. (D) INOVATE-HF trial as well as other trials showed that vagus nerve stimulation can improve quality of life. From (49). Abbreviations: BS= brain stem, SA= sino-atrial, AV= atrioventricular.
Figure 3.
Figure 3.
Splanchnic nerve modulation The splanchnic vascular compartment is a major a reservoir for intravascular blood volume and has an important role in volume redistribution in heart failure (A). Splanchnic nerves control the arterial and venous vascular tone of this vascular compartment; and therefore, splanchnic nerve block can be a potential treatment modality in heart failure (B). Fudim et al showed improvement in right atrial pressure, mean arterial pressure, pulmonary arterial mean pressure, and wedge pressure after a temporary block of the splanchnic nerve in patients with heart failure (C).
Figure 4.
Figure 4.
Cardiac contractility modulation and phrenic nerve stimulation OPTIMIZER System delivers a biphasic, long-duration, high-voltage electrical signals to the septum of the right ventricle during the absolute refractory period, resulting in myocardial changes that lead to enhancement of contractility (A). The results of the OPTIMIZER system on peak VO2 are shown in (B). Phrenic Nerve Stimulation: (C) Device-based phrenic nerve stimulation during sleep in patients with central sleep apnea leads to diaphragmatic contraction, and thus, restoring normal breathing and stabilizing the level of oxygen and cardon dioxide throughout sleep. (D) Device-based phrenic nerve stimulation (using remedē System) results in improvement in the apnea-hypopnea index (AHI). From Costanzo MR, Ponikowski P, Javaheri S, Augostini R, Goldberg L, Holcomb R, Kao A, Khayat RN, Oldenburg O, Stellbrink C, Abraham WT and remede System Pivotal Trial Study G. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet. 2016;388:974-82.
Figure 5.
Figure 5.
Interatrial shunt devices. Patients with heart failure typically have increased left atrial pressure with subsequent pulmonary congestion. Creating a permanent, dynamic, controlled left-to-right shunt can decompress the left atrium in heart failure (A). Different interatrial shunt devices are shown in (B). Interatrial shunt devices result in a decrease in the pulmonary capillary wedge pressure, and thus, improvement in pulmonary congestion (C) (94).
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References

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