Innovation in device-based therapies for heart failure (HF) has seen a major shift in the last decade, driven by regulatory changes and a growing understanding of the condition's complexities. These therapies are becoming an integral part of managing different phenotypes of HF, addressing structural and neurohormonal abnormalities that are not directly amendable to pharmacological interventions. Device-based approaches also offer the advantage of operating independently of patient adherence, a significant factor in chronic disease management. Several device-based therapies have recently been approved for HF, presenting new options for patients with persistent symptomatic or progressive disease despite optimal guideline-directed medical therapy (GDMT).
Regulatory Landscape and Breakthrough Device Program
In 2013, the Food and Drug Administration (FDA) released guidance encouraging device innovation, particularly when alternative treatments are unavailable or ineffective. The Breakthrough Device Program, authorized in 2016, further expedited access to innovative devices for serious illnesses like HF. This program has led to a rapid increase in the development and evaluation of device-based HF therapies. The program aims to balance pre- and post-market evidence generation while meeting safety and effectiveness requirements. Novel clinical trial designs, including the use of patient-centered outcomes and surrogate endpoints, may be considered for early market access. The Centers for Medicare and Medicaid Services (CMS) have also increased hospital reimbursement for these technologies, further incentivizing their adoption.
Valve Therapies
Mitral Regurgitation
Mitral regurgitation (MR), whether primary or secondary, significantly impacts HF prognosis. More than 60 transcatheter mitral valve repair or replacement devices have been developed to address MR in HF patients. The MitraClip device, approved for both primary and secondary MR, allows for edge-to-edge repair of the mitral valve. The COAPT trial demonstrated that MitraClip reduced HF hospitalizations and all-cause mortality in patients with moderate-severe or severe secondary MR, with left ventricular ejection fraction (LVEF) of 20–50%, and New York Heart Association (NYHA) class II-IV symptoms despite maximally-tolerated GDMT and cardiac resynchronization therapy (CRT). Other edge-to-edge devices, such as the PASCAL device, and indirect percutaneous devices, like the Carillon Mitral Contour System (CMCS), are also under investigation. Transcatheter mitral valve replacement (TMVR) systems, including Medtronic’s Intrepid and Abbott’s Tendyne, are rapidly evolving fields with several other devices in development.
Tricuspid Regurgitation
Severe tricuspid regurgitation (TR) is associated with right ventricular dysfunction and poor outcomes. The TriClip, similar to MitraClip, is a minimally invasive, device-based, transcatheter edge-to-edge repair system. The TRILUMINATE trial showed that TriClip reduced TR severity in most patients, with a low rate of major adverse events. Transcatheter tricuspid valve replacement is also a growing field with devices like Edwards EVOQUE and Neovasc Tiara™ under investigation.
Autonomic Modulation
Baroreflex Activation Therapy
Baroreflex activation therapy (BAT) stimulates carotid baroreceptors to decrease sympathetic activity and increase parasympathetic outflow. The Barostim™ neo™ system has shown improvements in NYHA class, quality of life, and 6-minute walk distance in patients with NYHA class III HF with LVEF ≤35%. Based on the BeAT-HF trial, the FDA approved the Barostim™ neo™ system in 2019 for improving HF symptoms in select patients.
Vagus Nerve Stimulation
Vagus nerve stimulation (VNS) aims to counter the long-term deleterious effects of excessive sympathetic nervous system activation and decreased parasympathetic nervous system activity. The VITARIA system is CE marked and has received breakthrough designation. Trials like ANTHEM-HFrEF and ANTHEM-HFpEF are ongoing to evaluate its efficacy in HFrEF and HFpEF patients, respectively.
Splanchnic Nerve Modulation
Modulation of splanchnic nerves, which control the arterial and venous vascular tone of the splanchnic vascular compartment, is a potential therapy for HF. Temporary splanchnic nerve blockade (SNB) has shown improvements in cardiac output and filling pressures. Ongoing efforts are investigating the safety and efficacy of minimally invasive, long-term SNB in HFpEF.
Electrophysiologic Modulation
Cardiac Contractility Modulation
Cardiac contractility modulation (CCM) therapy delivers electrical signals to the right ventricular septum during the absolute refractory period, leading to structural and functional changes in the myocardium. The OPTIMIZER System has received FDA approval based on the FIX-HF-5C trial, which showed improvements in peak VO2, quality of life, and NYHA class in patients with NYHA class III-IV symptoms and LVEF 25–45%.
Electrical Microcurrent Therapy
Electrical microcurrent therapy involves microcurrent stimulation of cardiomyocytes, resulting in intracellular and extracellular changes that can lead to reverse remodeling. The C-MIC system is under investigation and has shown promising results in early studies.
Respiratory Modulation
Phrenic Nerve Stimulation for Central Sleep Apnea
Phrenic nerve stimulation (PNS) during sleep leads to diaphragmatic contraction, restoring normal breathing and stabilizing PaO2 and PaCO2. The remedē System is FDA-approved for treating moderate to severe central sleep apnea (CSA) based on the remedē System Pivotal Trial Study, which demonstrated significant reductions in apnea-hypopnea index (AHI) and improvements in quality of life.
Asymptomatic Diaphragmatic Stimulation
Asymptomatic diaphragmatic stimulation (ADS) involves delivering diaphragmatic stimulation pulses gated with cardiac cycles, resulting in modulation of intrathoracic pressure. The VisONE ADS system is under investigation and has shown preliminary improvements in cardiac output and LVEF.
Structural Interventions
Inter-Atrial Shunting
Creating a small left-to-right shunt may reduce exercise-related increases in left atrial pressure. Devices like the InterAtrial Shunt Device (IASD) and the V-Wave® interatrial shunt device are under investigation. The REDUCE LAP-HF II and RELIEVE-HF trials are ongoing to assess their safety and effectiveness.
Basilar Ventriculoplasty
The Accucinch System is a direct device-based, catheter-delivered basilar ventriculoplasty system that involves the implantation of anchors under the posterior mitral annulus, resulting in reduction of the septal-free wall dimension. The FDA has granted this device breakthrough device designation status, and a series of studies are underway to evaluate its safety and performance.
Left Ventricular Reconstruction
The Revivent TC ventricular enhancement system is a less invasive ventricular reconstruction system that excludes regions of transmural infarction. It has shown improvements in LVEF and LV volumes in HFrEF patients. The ALIVE trial is ongoing to establish its effectiveness and safety.
Volume Management
Peritoneal Direct Sodium Removal
Peritoneal direct sodium removal (DSR) is a non-renal approach to prevent and treat volume overload in HF. The RED DESERT study is ongoing to investigate the feasibility and safety of the Alfapump DSR system in HF patients resistant to diuretic therapy.
Conclusion
Device-based therapies for HF are not replacing pharmacological therapies but rather complement them or fill gaps in areas without proven medical therapies, such as HFpEF. Given the more invasive nature and inherent risks, these therapies are primarily developed and approved for patients with persistent symptomatic or progressive disease despite optimal GDMT. As innovation continues, device-based therapies will likely play an increasingly important role in the comprehensive management of HF.
