Interventional therapies for chronic heart failure: An overview of recent developments

Abstract

Heart failure (HF), the final manifestation of most cardiovascular diseases, has become a major global health concern, affecting millions of individuals. Despite basic drug treatments, patients present with high morbidity and mortality rates. However, recent advancements in interventional therapy have shown promising results in improving the prognosis of patients with HF. These advancements include transcatheter aortic valve replacement for severe aortic stenosis, transcatheter mitral valve repair for chronic mitral regurgitation, neuromodulation therapy for multiple targets and measures in the treatment of chronic HF and left ventricular assist device implantation for advanced HF (Figure 1). In this review, we aimed to provide an overview of the current progress in interventional therapies for chronic HF.

Introduction

Heart failure (HF) is a complex clinical syndrome resulting from cardiac remodelling due to multiple pathophysiological mechanisms. It is the final manifestation of most cardiovascular diseases. Chronic HF tends to be complex and presents as a heterogeneous disease, associated with multiple risk factors, symptoms, and complications, as well as pathophysiological mechanisms that remain poorly understood (Figure  1 ). Consequently, the clinical management of HF remains challenging. Despite significant advances in the treatment of chronic HF, its overall prognosis remains poor. Novel interventional treatments, such as adjunctive therapies for selected patients, may improve patients' quality of life and prognosis. Device‐based interventions for HF aim to complement traditional medical treatments by addressing heart valve changes, atrial decompression, ventricular remodelling, myocardial contractility and neurohumoral regulation (Figure  2 ). These interventions include valve interventional technology, interatrial shunt devices, left ventricular interventional technology, neuromodulation therapy and cardiac contractility modulation (CCM).

Figure 1.

The characteristics of various interventional therapies and mechanisms of chronic heart failure, which considers heart recovery, prevention of worsening of heart failure, preserving cardiac function, improving quality of life and prognosis via multidisciplinary treatment using catheter interventions, neuromodulation and mechanical circulatory support devices. CCM, cardiac contractility modulation; CRT, cardiac resynchronization therapy; GSN, great splanchnic nerve; IASDs, interatrial shunt devices; LVAD, left ventricular assist device; M‐TEER, mitral valve transcatheter edge‐to‐edge repair; PADN, pulmonary artery denervation; RDN, renal sympathetic denervation; TAVR, transcatheter aortic valve replacement; VPR, transcatheter ventricular partitioning restoration; VNS, vagus nerve stimulation.

Figure 2.

Advanced interventional therapies in chronic heart failure. Interventional therapies for heart failure involve a variety of innovative approaches that aim to address various targets, such as heart valves (aortic and mitral valves), atrial decompression, ventricular remodelling and myocardial contractility. These include valve interventional technologies (TAVR and M‐TEER), interatrial shunt devices, left ventricular interventional technology and cardiac contractility modulation. CCM, cardiac contractility modulation; IASDs, interatrial shunt devices; LVAD, left ventricular assist device; M‐TEER, mitral valve transcatheter edge‐to‐edge repair; TAVR, transcatheter aortic valve replacement.

Valve interventional technology

Transcatheter aortic valve replacement (TAVR)

Coexistence of aortic stenosis (AS) in patients with chronic HF is not uncommon. Severe symptomatic AS can increase afterload, and afterload reduction through TAVR has revolutionized the management of severe symptomatic AS, with the transfemoral approach preferred according to the 2020 American Heart Association/American College of Cardiology (ACC/AHA) guidelines. ¹ Alternative access routes may be considered in complicated cases. ² Gleason et al. ³ found similar mid‐term survival and stroke rates between TAVR and surgical aortic valve replacement in high‐risk patients. Meanwhile, Van Mieghem et al. ⁴ reported similar 5‐year outcomes for TAVR and surgery in intermediate‐risk patients. Studies ⁵ , ⁶ , ⁷ , ⁸ , ⁹ indicated superiority of TAVR in reducing structural valve deterioration compared to surgical replacement. Despite anatomical challenges, TAVR may be applicable to younger, lower‐risk patients, particularly those with bicuspid aortic valve stenosis. Chen et al. ¹⁰ suggested consensus recommendations for TAVR in these cases. Long‐term durability, postoperative management and complications remain crucial prognostic factors. ¹¹ , ¹² Standardizing processes and advancing techniques could minimize complications and immediately improve left ventricular haemodynamics, making TAVR the preferred treatment for symptomatic HF with severe AS.

Mitral valve transcatheter edge‐to‐edge repair (M‐TEER)

Mitral regurgitation (MR) is a common valvular heart disease categorized into primary and secondary MR. Secondary MR, ¹³ , ¹⁴ often associated with chronic HF, can stem from various causes including left ventricular remodelling. ¹⁵ , ¹⁶ , ¹⁷ M‐TEER with the MitraClip device (Abbott, Santa Clara, CA, USA) ¹⁸ has exhibited efficacy in reducing HF‐related hospitalizations and mortality in patients with secondary MR, ¹⁹ as demonstrated in the COAPT trial. ²⁰ M‐TEER also holds promise for high‐risk degenerative mitral valve cases. ²¹ , ²² , ²³ Complications during M‐TEER procedures underscore the need for meticulous monitoring. ²⁴ , ²⁵ Transcatheter techniques provide alternatives to surgical interventions, revolutionizing HF management. The MITRA‐FR trial differed from COAPT in assessing MitraClip for severe secondary MR in HF patients. Unlike COAPT, which showed significant benefits of MitraClip in reducing HF hospitalization and mortality, the MITRA‐FR trial demonstrated no such advantages. Despite expectations, MitraClip did not notably reduce HF hospitalization or mortality versus medical therapy alone. ²⁶ These differing results have led to extensive debate in cardiology. Several factors contribute to these differences, including variations in patient populations, trial design and medical therapy optimization. Discrepancies in patient selection, procedural techniques and operator experience may also influence outcomes. The MITRA‐FR trial involved larger left ventricles with less MR, while the COAPT trial involved smaller left ventricles with greater MR. The development and expansion of mitral valve repair devices, including M‐TEER, have revolutionized the management of HF and functional MR, leading to significant reductions in mortality and HF‐related hospitalizations.

Treatment of tricuspid regurgitation

Tricuspid regurgitation (TR) is a significant valvular disorder often overlooked in HF management. Severe TR can lead to right ventricular failure and worsening HF symptoms. Transcatheter tricuspid valve interventional therapies can be divided into two categories: tricuspid valve repair and tricuspid valve replacement. Transcatheter tricuspid valve repair (TTVR) has emerged as a novel intervention to address Severe TR. Devices such as the TriClip (Abbott, Santa Clara, CA, USA) and the Cardioband Tricuspid System (Edwards Lifesciences, Irvine, CA, USA) have shown promise in early clinical trials. These devices aim to reduce regurgitation by approximating the leaflets or reshaping the annulus. Initial studies indicate that TTVR can significantly improve symptoms, reduce hospitalizations and enhance the quality of life for patients with severe TR. The CLASP TR study (NCT03745313) evaluated the safety and efficacy of the tricuspid valve transcatheter edge‐to‐edge repair (T‐TEER) PASCAL system. The PASCAL system demonstrated low complication and high survival rates, with significant and sustained improvements in the severity of TR and quality of life at 1 year. ²⁷ Further large‐scale trials are ongoing to establish the long‐term efficacy and safety of TTVR.

Left ventricular interventional therapy

Durable left ventricular assist device (LVAD)

As the prevalence of advanced or end‐stage HF increases, patients may need to consider treatment strategies, such as heart transplantation or durable LVAD support. Both options can improve the quality of life and prolong survival. ²⁸ The basic principle of a durable LVAD involves drawing blood out through the apical cannula of the left ventricle, transporting it to the aorta through the aortic cannula and reducing the left ventricular load through auxiliary circulation. ²⁹ Durable LVADs, such as the HeartMate 3 (Abbott, Chicago, IL, USA), the HVAD (Medtronic, Minneapolis, MN, USA) and EVA‐Pulsar (EvaHeart, Chongqing, China), are designed for long‐term use and can significantly improve cardiac function and quality of life in patients with advanced HF. ³⁰ The use of these devices can reduce left ventricular pressure and increase total blood flow, offering a bridge to transplantation or serving as destination therapy for patients who are not transplant candidates. ³¹ The STS INTERMACS analysis ³² revealed that LVAD was associated with improved cardiac function, quality of life and fewer complications in older patients; these outcomes were similar to those in younger patients. However, Trombara et al. ³³ found that right ventricular dysfunction may limit improvements in exercise performance after LVAD implantation. Lanmueller et al. ³⁴ summarized LVAD treatment modalities and associated complications, while Miyagi et al. ³⁵ discussed the advantages and limitations of LVAD as well as insights into their safety and feasibility. Salah et al. ³⁶ described the haemodynamic and clinical changes that occur after LVAD implantation. LVAD technology may improve survival and quality of life in patients with advanced HF and alleviate the demand for donor hearts. However, potential complications associated with LVAD use include perioperative bleeding, infection, device thrombosis, gastrointestinal bleeding, right‐sided HF and aortic haemodynamic changes. These complications require careful monitoring and management to ensure optimal patient outcomes.

Transcatheter ventricular partitioning restoration (TVPR)

TVPR treats left ventricular wall motion abnormalities, including dilated bulge or aneurysm, left ventricular dilatation, systolic dysfunction post‐anterior myocardial infarction, HFrEF secondary to myocardial infarction and post‐myocardial infarction ventricular septal rupture. It utilizes a ventricular partitioning device Parachute (CardioKinetix, Inc., Menlo Park, CA, USA) delivered transcatheterally to the left ventricular apex, reducing ventricular volume and enhancing function, thus improving ischaemic HF. ³⁷ Su et al. ³⁸ presented 1‐year follow‐up echocardiographic data in patients receiving the device Heartech (Xinrui Medical Equipment Co. Ltd., Shanghai, China), showing no deterioration in left ventricular diastolic function or strain parameters, while systolic function significantly improved. Sazzad et al. ³⁹ reported the potential of transcatheter endocardial injection of hydrogels for treating chronic HF, reducing ventricular wall stress and improving left ventricular dilatation and remodelling. Similarly, Wang et al. ⁴⁰ conducted first‐in‐human transcatheter endocardial alginate‐hydrogel implantation, resulting in significant left ventricular ejection fraction (LVEF) improvement and patient recovery. Hamid et al. ⁴¹ evaluated the echocardiographic and clinical outcomes after TVPR, concluding that the TVPR system resulted in left ventricular volume reduction and improved quality of life and exercise tolerance among HF patients who had optimal medical therapy and no overt mitral regurgitation. A study ⁴² demonstrated the safety and effectiveness of the device in reducing left ventricular volume and enhancing function, maintained even after 12 months of follow‐up. Though the efficacy and safety of TVPR in treating chronic HF are confirmed, longer follow‐up periods are needed for a comprehensive assessment of its long‐term prognosis.

By concentrating on durable LVADs and their application in advanced or end‐stage HF, and clearly distinguishing these from short‐term mechanical circulatory support devices, the revised text aligns with the comment and maintains clarity in discussing the appropriate interventions for chronic HF.

Neuromodulation therapy

The interaction between neurohormonal, sympathetic and inflammatory factors contributes to the pathophysiological development of cardiac remodelling in chronic HF. Neuromodulation therapy has shown promising results in improving cardiac remodelling, quality of life and prognosis in these patients. Neuromodulation interventions have multiple targets and measures in the treatment of HF, including renal sympathetic denervation (RDN), ablation of the great splanchnic nerve (GSN), vagus nerve stimulation (VNS) and pulmonary artery denervation (PADN). Notably, neuromodulation therapy can help treat arrhythmia, hypertension, pulmonary hypertension and coronary heart disease (Figure  3 ).

Figure 3.

Neuromodulatory interventions have multiple targets and measures in the treatment of chronic heart failure. (A) RDN delivers two to three doses of 360° ultrasound energy, lasting 7 s each, to denervate the sympathetic nerves surrounding each of the main renal arteries. (B) The GSN ablation catheter enters the superior vena cava above the right atrium, travels through the azygos vein and is gradually delivered to the intercostal vein at the 10th and 11th thoracic vertebrae near the right GSN. Radiofrequency energy is released for at least 90 s. (C) VNS is most performed by surgical implantation of a stimulator to act on the vagus nerve in the neck or below the diaphragm. It consists of an implantable pulse generator and electrodes. The vagus nerve below the diaphragm can be targeted by implanting electrodes into the ventral and/or dorsal vagus nerve trunk. (D) PADN can significantly reduce pulmonary artery pressure when the ablation site is determined using pulmonary trunk angiography (left and right pulmonary artery bifurcation close to 5 mm or the distal bifurcation area). The initial ablation energy is 6–8 W, and the radiofrequency energy is generally ≤20 W. GSN, great splanchnic nerve; PADN, pulmonary artery denervation; RDN, renal sympathetic denervation; VNS, vagus nerve stimulation.

Renal sympathetic denervation (RDN)

RDN is a safe and effective method for reducing sympathetic overactivation through radiofrequency ablation of the renal nerves, which results in a systemic reduction of renal afferent and efferent sympathetic activity in the kidneys. Sympathetic activation, particularly norepinephrine release, is strongly associated with morbidity and mortality. ⁴³ RDN was initially designed to lower the arterial blood pressure in patients with uncontrolled hypertension by regulating sympathetic overactivation. However, numerous studies have recently examined the effect of RDN in patients with HFpEF and HFrEF. According to the ACC/AHA, HFrEF is characterized by systolic dysfunction with a LVEF of less than 40%, with or without congestive symptoms. ⁴⁴ Norepinephrine release during sympathetic activation is closely associated with morbidity and mortality in HF. RDN may reduce renal norepinephrine content and circulating angiotensin I and II levels while increasing circulating natriuretic peptide levels. ⁴⁵

Preliminary studies indicate that RDN can lower blood pressure, heart rate and sympathetic nervous system activity and improve glucose tolerance and microalbuminuria in patients with chronic HF. RDN has positive effects on managing water and electrolyte metabolism in patients with chronic HF. ⁴⁶ RDN also reduces renal sympathetic nerve activity, inhibits the renin–angiotensin–aldosterone system and improves left ventricular remodelling, thereby improving cardiac function in patients with HFrEF without causing hypotension or syncope. ⁴⁷ Recent meta‐analyses suggest that bilateral RDN is safe and well tolerated in patients with HFrEF, effectively increasing the LVEF and exercise tolerance, without affecting renal function. Although systolic and diastolic blood pressures may be slightly reduced, NYHA cardiac function is significantly improved, 6‐min walk test results are increased, and NT‐proBNP levels are decreased. However, larger sample sizes and longer follow‐up studies are required to confirm any reduction in left ventricular end‐systolic and end‐diastolic diameters. ⁴⁸ HFpEF is characterized by a normal LVEF, elevated left ventricular filling pressure and increased ventricular and arterial stiffness. Unlike for HFrEF, therapies targeting neurohormonal pathways are less beneficial for HFpEF. Studies have shown that RDN is a feasible therapeutic strategy for the treatment of HFpEF. Kresoja et al. ⁴⁹ found that patients with HFpEF receiving RDN had altered haemodynamics, increased cardiac output and vascular and left ventricular stiffness compared to patients without HF. Similarly, Mahfoud et al. ⁵⁰ demonstrated significant improvements in the global longitudinal strain and left ventricular diastolic function in patients with HFpEF who underwent RDN. RDN reduces sympathetic nerve activity, ventricular afterload and arterial stiffness and helps restore ventricular‐arterial coupling. ⁵¹ In addition, patients with chronic HF are at a higher risk of various types of ventricular arrhythmias and may prevent cardiac sympathetic overactivation, ventricular remodelling and ventricular fibrillation and reduce the occurrence of ventricular arrhythmias. ⁵² Howson et al. ⁵³ demonstrated that RDN significantly reduced the need for implantable cardiac defibrillator therapy and the number of ventricular arrhythmia episodes, anti‐tachycardia pacing and defibrillator shocks. RDN may hold promise as a therapeutic option for HFpEF and its related complications. RDN is a safe, feasible and effective treatment option for patients with chronic HF.

Ablation of the great splanchnic nerve (GSN)

Chronic HF results in the excessive activation of the sympathetic nervous system, which sends signals to the splanchnic vascular bed through the splanchnic nerves. This leads to splanchnic vasoconstriction and increased heart return blood volume, diverting blood to the heart and lungs and increasing heart rate, preload and central venous pressure. Ablation of the GSN can selectively block sympathetic nerve signals of the splanchnic circulation, reducing sympathetic nerve stimulation and redistributing the blood volume. This treatment is currently only applicable for increasing the blood supply capacity of the heart, improving the quality of life of patients with chronic HF and managing volume changes in patients with HFpEF. ⁵⁴ In these patients, resection or ablation of the right GSN can effectively reduce excessive splanchnic vasoconstriction and venous return and improve quality of life and exercise capacity. Consequently, it may reduce blood return to the heart and cardiac preload and improve the management of volume changes in patients with HFpEF. ⁵⁵

Permanent ablation of the right GSN involves sending an ablation catheter to the intercostal vein at the level of the 10th and 11th thoracic vertebrae near the right GSN using radiofrequency, cryoablation or pulsed electric field ablation. This method can improve HF haemodynamics, reduce pulmonary capillary wedge pressure and heart filling pressure during exercise and improve cardiac output and exercise capacity. Changes can occur 24 h after surgery; this method is also called splanchnic ablation for volume management. ⁵⁶ The first human study included 11 patients with HFpEF and NYHA class II or III cardiac function, who underwent right GSN ablation. Follow‐up assessments conducted between 1 and 12 months after the ablation procedure confirmed the safety and effectiveness of the right GSN ablation. It improved clinical indicators such as NYHA cardiac functional class and the 6‐min walk test in patients with HFpEF. No ablation‐related adverse cardiac events or clinical sequelae were observed. ⁵⁷ Another study verified the safety and effectiveness of right GSN ablation in patients with HFpEF. This study involved cardiopulmonary exercise testing and an invasive haemodynamic assessment. Right GSN ablation reduced pulmonary artery pressure and pulmonary capillary wedge pressure, improved the 6‐minute walk test, and significantly enhanced NYHA cardiac function. It improved cardiac output and cardiopulmonary exercise results. ⁵⁸ Physiological side effects such as gastrointestinal hypermotility, diarrhoea, abdominal cramps, transient hypotension, nausea, and vomiting can occur after ablation of the large splanchnic nerve, mostly within 72 h after surgery. However, these effects were temporary and tolerable. ⁵⁹ Recent studies have confirmed the effectiveness and safety of right GSN ablation for the treatment of patients with HFpEF. However, the current study had a short follow‐up period and was small scale. However, long‐term effects of the ablation in patients with HFpEF remain unclear. Long‐term, large, randomized trials are required to confirm the risk of any late effects.

Vagus nerve stimulation (VNS)

Imbalanced autonomic regulation, excessive sympathetic activation and reduced vagal tone are important components of HF pathophysiology. VNS is a neuromodulatory therapy including auricular, cervical and aortic modality for arrhythmia, cardiac arrest, myocardial ischaemia/reperfusion injury and HF. It regulates autonomic nerve activity and counteracts sympathetic nerve over‐excitability. ⁶⁰

The INOVATE‐HF trial assessed the safety and efficacy of VNS by increasing vagal tone in patients with HFrEF. However, our results showed that VNS did not reduce mortality or HF events in these patients. ⁶¹ Decreased vagal activity is associated with decompensation and increased mortality rates in chronic HF. Combining baroreflex activation therapy with VNS has been shown to improve left ventricular function, survival rate and clinical parameters of HFrEF, including NYHA cardiac function class, LVEF and other indicators. ⁶² Arterial blood pressure is commonly considered the primary indicator of left ventricular afterload. VNS can enhance cardiac function in patients with chronic HF by increasing vagal tone, reducing arterial blood pressure and left ventricular afterload and preventing acute decompensation. ⁶³ In the ANTHEM‐HF study, ⁶⁴ patients received VNS (LivaNova USA, Inc., Houston, TX, USA) on either the left or the right cervical vagus nerve, autonomic regulation therapy using cervical VNS was found to be safe and effective, improving autonomic tone, clinical symptoms and cardiac function in patients with HFrEF. The ANTHEM‐HFpEF study ⁶⁵ aimed to assess the safety and feasibility of VNS in patients with symptomatic HF with preserved (LVEF ≥50%) or mildly reduced (LVEF 40%–49%) ejection fraction. The study included 52 patients with HFpEF or HFmrEF, NYHA class II–III cardiac function and LVEF ≥40%. After a 12‐month follow‐up, improvements were observed in NYHA cardiac functional class, 6‐min walk test results and quality of life, with a low incidence of adverse events. The development of HFpEF is influenced by the systemic inflammatory status. Elkholey et al. ⁶⁶ demonstrated that low levels can reduce blood pressure, heart rate variability, inflammatory cytokines, macrophage infiltration and fibrosis. VNS may reverse the dysregulated inflammatory signalling pathways in HFpEF, leading to improved cardiac function in a rat model of HFpEF. In a human study, Stavrakis et al. ⁶⁷ showed that low‐level VNS significantly improved left ventricular global longitudinal strain, inflammatory factors, quality of life and exercise capacity in patients with HFpEF, as observed through echocardiography. VNS has been found to have positive effects on autonomic nervous function, LVEF, 6‐min walk test, NYHA cardiac function classification and cardiac electrical stability. VNS protects myocardial cells and slows the progression of HF by reducing oxidative stress, apoptosis and inflammatory responses. It also reduces the risk of malignant ventricular arrhythmia and autonomic nervous system. ⁶⁸

Recent studies have shown that VNS can be beneficial in both HFpEF and HFrEF patients. However, the clinical efficacy and safety of neurostimulation, particularly VNS, remain to be determined. Large‐scale randomized controlled trials are necessary to optimize VNS dosage and stimulation properties, identify potential adverse reactions and select appropriate patients with HF.

Pulmonary artery denervation (PADN)

Patients with chronic HF experience an increase in left ventricular filling pressure, which leads to an increase in pulmonary venous pressure due to reverse pressure conduction. As the disease progresses and pulmonary vascular remodelling occurs, it can eventually result in pulmonary hypertension, which is associated with pulmonary vascular remodelling and overactivation of the sympathetic nerve. ⁶⁹ , ⁷⁰ Pulmonary hypertension is categorized into five groups based on its underlying cause, with the two most common forms being pulmonary arterial hypertension and pulmonary hypertension due to left heart disease, which is its leading cause. The diagnostic criteria for pulmonary hypertension due to left heart disease include a mean pulmonary artery pressure of >20 mmHg measured through right heart catheterization, a pulmonary capillary wedge pressure of >15 mmHg and a pulmonary vascular resistance of ≤3 Wood. ⁷¹

Currently, conventional treatments for pulmonary hypertension consist of targeted drug therapy, atrial septostomy, balloon pulmonary angioplasty and lung transplantation. However, in patients with pulmonary hypertension due to HF, the benefits of targeted drug therapy remain unclear. ⁷² PADN is a percutaneous pulmonary artery interventional therapy that uses catheter ablation technology (radiofrequency ablation, cryoablation and ultrasound shock) to disrupt the afferent and efferent fibres of the baroreceptor reflection in the main pulmonary artery and its branches. This approach inhibits sympathetic nerve activity, increases cardiac output, reduces pulmonary artery pressure, inhibits pathological remodelling of the pulmonary artery and improves exercise tolerance and cardiac function of patients. ⁷³ Decreased pulmonary arterial compliance may be an early indicator of pulmonary hypertension due to HF. The global longitudinal strain of the pulmonary artery can be measured to assess the prognosis of patients with pulmonary hypertension. ⁷⁴ , ⁷⁵ In the PADN‐CFDA study, ⁷⁶ 128 patients with pulmonary arterial hypertension were randomly divided into the PADN and sham operation groups at a 1:1 ratio. Over a 6‐month follow‐up period, PADN reduced pulmonary artery pressure in patients with pulmonary arterial hypertension and improved exercise capacity in patients with intermediate‐ and high‐risk pulmonary arterial hypertension. It also significantly reduced clinical progression, improved haemodynamic status and had positive clinical outcomes during a 1‐year follow‐up period. ⁷⁷ In the PADN‐5 study, ⁷⁸ 98 patients with pulmonary hypertension secondary to HF were randomly assigned to receive either PADN or sildenafil. Both groups received standard HF medication. After a 6‐month follow‐up, PADN was found to improve haemodynamics and clinical outcomes compared to the medication group in patients with pulmonary hypertension secondary to HF. PADN was associated with significant improvements in exercise capacity, cardiac function and clinical outcomes during a 3‐year follow‐up. ⁷⁹ Witkowski et al. ⁸⁰ conducted a study to examine the effectiveness of PADN in patients with pulmonary hypertension secondary to HF. They applied ring radiofrequency around the distal main pulmonary artery, left pulmonary artery and right pulmonary artery, with each ablation point being heated to a temperature of 45°C. The energy used was 10 W. The results demonstrated that PADN increased the distance covered in the 6‐min walk test while reducing pulmonary artery systolic pressure and the rate of clinical deterioration. In addition, PADN help improve pulmonary artery remodelling, haemodynamics and cardiac function, improving patient prognosis. ⁸¹ Meanwhile, Romanov et al. ⁸² used PADN in a randomized clinical trial of 50 patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary endarterectomy. The patients were randomly assigned to receive either PADN or drug treatment. The 12‐month follow‐up results revealed that the PADN group exhibited a significant reduction in pulmonary vascular resistance along with an improvement in cardiopulmonary exercise capacity.

However, the current application of this technology is limited owing to the absence of large‐scale randomized controlled clinical trial and data covering a period longer than 1 year. Although PADN effectively reduces pulmonary artery pressure and pulmonary vascular resistance, it does not fully normalize pulmonary haemodynamics, and further research is needed to elucidate the impact of PADN on pulmonary microcirculation. Nonetheless, PADN appears to be a safe and effective surgical option for treating pulmonary hypertension secondary to HF.

Other treatments

Interatrial shunt devices (IASDs)

The IASDs creates a left‐to‐right shunt, reducing left atrial pressure and improving HF symptoms. As a result, pulmonary congestion and dyspnea are reduced, improving HF symptoms and prognosis, exercise tolerance and overall quality of life. ⁸³ Elevated left atrial pressure exacerbates HF symptoms; however, IASDs may reduce the left atrial filling pressure during physical exertion. ⁸⁴ This method is currently available only for patients with HF with preserved ejection fraction (HFpEF).

In a study, ⁸⁵ the feasibility, safety and efficacy of the IASDs were evaluated in 53 patients with HFpEF and HF with reduced ejection fraction (HFrEF) who were followed up for 1 year after device implantation. The shunt diameter was previously fixed; however, the long‐term use of the shunt could lead to endothelialization and pore size reduction, decreasing shunt flow. ⁸⁶ When left atrial pressure increases due to exercise, stress or other factors, a small amount of excess left atrial volume is displaced into the right atrium. ⁸⁷ Several atrial shunt devices are available, including the V‐Wave Shunt (V‐Wave Ltd., Agoura Hills, CA, USA), ⁸⁸ Corvia IASD (Corvia Medical, Tewksbury, MA, USA) ⁸⁹ and Occlutech AFR device (Occlutech, Helsingborg, Sweden). ⁹⁰ A Chinese research team has developed two atrial shunt devices: the NoYA‐adjustable non‐implantable device (NoYA MedTech, Hangzhou, China) and the D‐Shant retrievable reintervention device (Wuhan Vickor Medical Technology Co. Ltd., Wuhan, China). Early research suggests that these devices are safe and effective for treating HF. ⁹¹ , ⁹² However, the large‐scale clinical REDUCE LAP‐HF II study found no benefit in HF events for atrial bypass devices in patients with ejection fraction ≥40%. ⁹³ A recent meta‐analysis demonstrated effectiveness in reducing pulmonary capillary wedge pressure and improving cardiac output and exercise capacity. ⁹⁴ Guimaraes et al. ⁹⁵ provided a clinical perspective on atrial shunt therapy, while Riccard et al. ⁹⁶ highlighted its safety and efficacy in improving haemodynamics. Rosalia et al. ⁹⁷ discussed recent findings and challenges in atrial shunt translation. Sivakumar et al. ⁹⁸ tested atrial shunts in severe pulmonary arterial hypertension. Interatrial shunts are not recommended in certain conditions. Novel left atrial to coronary sinus shunting approaches aim to address limitations of atrial shunts. ⁹⁹ , ¹⁰⁰ Long‐term antiplatelet and anticoagulant therapy are necessary post‐surgery. The RELIEVE‐HF study (NCT03499236) ¹⁰¹ is a significant addition to this field. It aimed to evaluate the efficacy of the IASDs in patients with HFpEF or HF with mid‐range ejection fraction (HFmrEF). Subgroup analysis results indicated the IASDs were beneficial for patients with HFrEF but detrimental for those with HFpEF. Although the study showed promising improvements in exercise capacity and quality of life, the full potential and limitations of IASDs require further exploration. Furthermore, the ongoing RESPONDER‐HF randomized trial (NCT05425459) ¹⁰² and the ongoing randomized RELIEVE‐HF trial (NCT03499236) ¹⁰¹ are expected to provide more robust data on patient selection criteria and long‐term outcomes, addressing current evidence gaps. Further research is needed to determine optimal patient selection, suitable for atrial shunt volume, effects on cardiopulmonary function and haemodynamics after implantation and clinical outcomes.

Cardiac contractility modulation (CCM)

CCM is an emerging therapy designed to improve myocardial contractility in patients with HF, particularly those with reduced ejection fraction. ¹⁰³ , ¹⁰⁴ It is particularly beneficial for patients who remain symptomatic despite optimal medical therapy and are not suitable candidates for other device‐based therapies, such as cardiac resynchronization therapy (CRT). ¹⁰⁵ , ¹⁰⁶ The CCM involves high‐voltage (7.5 V) and high‐duration (20 ms) biphasic stimulation to the right ventricular septum, targeting the absolute refractory phase of the action potential to enhance myocardial contractility without triggering new contractions. CCM results in a sustained increase in contractility without increasing myocardial oxygen consumption by increasing the influx of calcium ions into cardiomyocytes. CCM is primarily used to treat chronic systolic HF. ¹⁰⁷

The FIX‐HF‐5C study highlighted the advantages of CCM in patients with HF with mild to moderate LVEF (25%–45%), QRS complex <130 ms and NYHA III/IV symptoms. The study results demonstrated sustained improvements in peak oxygen uptake, 6‐min walk test and NYHA functional class following CCM treatment. ¹⁰⁸ In a preliminary study, ¹⁰⁹ 20 patients with symptomatic HFrEF, NYHA class III or IV and LVEF ≤35% were included. After a 12‐month follow‐up, CCM was found to improve clinical symptoms, exercise tolerance and quality of life in HF patients and to reduce hospitalization rates in patients with HFrEF, even in the presence of atrial fibrillation, implanted cardioverter defibrillators and CRT. Previous studies have focused on CCM therapy in patients with HFrEF. In the CCM‐HFpEF study, ¹¹⁰ 47 patients with NYHA class II or III HFpEF were included. This study evaluated the efficacy and safety of CCM in patients after 24 weeks of follow‐up. The results demonstrated that CCM treatment can improve the health status and symptoms of patients with HFpEF while maintaining a safety profile similar to that of patients with systolic dysfunction treated with CCM. A MAINTAINED observational study also suggested that CCM therapy may benefit patients with NYHA functional class II HF. ¹¹¹ Furthermore, emerging evidence indicates that CCM therapy is beneficial for patients with HFpEF and HFmrEF. ¹¹² In conclusion, these studies confirmed the safety and effectiveness of CCM treatment in improving exercise tolerance and NYHA cardiac function class and reducing the risk of hospitalization for worsening HF in patients with chronic HF. CCM may be useful for the treatment of HF in patients with narrow QRS complexes. In addition, clinical research is underway on CCM combined with implantable cardioverter defibrillator, Optimizer IntegraCCM‐D (Impulse Dynamics, Orangeburg, NY, USA) and anti‐bradycardia pacing functions, which may reduce the risk of sudden death, improve cardiac function, increase heart rate and reduce complication rates associated with implanted cardioverter defibrillators and CCM implantation. ¹¹³

CCM implantation has been shown to effectively improve cardiac function and reverse cardiac remodelling in patients with chronic HF, primarily in those with HFrEF. However, compared to CRT, CCM requires more evidence‐based support. Studies ¹¹⁴ , ¹¹⁵ evaluating the role of CCM in HFpEF are currently ongoing to clarify the efficacy and safety of CCM in patients with HFpEF, forced ventricular pacing and atrial arrhythmia.

Future perspectives

Chronic HF progresses over time and its management requires a multifaceted approach. Interventional therapy is crucial for saving lives, preserving cardiac function and improving patient quality of life and prognosis. ¹¹⁶ The benefits of interventional therapy for chronic HF include reducing the need for multiple drug treatments and improving patient compliance with drug therapy. Novel device‐based interventional therapies include technologies that target heart valves, atrial decompression, ventricular remodelling, myocardial contractility and neurohumoral regulation, aimed at relieving symptoms and improving the quality of life in patients with chronic HF (Table  1 ). However, the long‐term performance and safety of these devices must be verified. With the rapid development of interventional therapy for structural heart diseases, the potential and scope of interventional therapy are expanding, bringing great hope to the management and treatment of chronic HF.

Table 1.

Comparative overview of different interventional therapies for chronic heart failure

Device category	TAVR	M‐TEER	IASDs	LVAD	TVPR	Neuromodulation	CCM
Physiological Target	Aortic valve	Mitral Valve	Atrial decompression	Ventricular remodelling	Ventricular compliance	Autonomic balance	Myocardial contractility
Devices	Sapien 3 (Edwards Lifesciences, Irvine, CA, USA) CoreValve (Medtronic Minneapolis, USA) TaurusOne (Peijia Medical, Suzhou, China)	MitraClip (Abbott, Santa Clara, CA, USA) ValveClamp (Hanyu Medical Technology, Shanghai, China) Cardiovalve (Venus Medtech, Hangzhou, China)	Corvia IASD (Corvia Medical, Tewksbury, MA, USA) V‐Wave Shunt (V‐Wave Ltd., Agoura Hills, CA, USA) Occlutech AFR (Occlutech, Helsingborg, Sweden)	HVAD (Medtronic, Minneapolis, MN, USA) HeartMate 3 (Abbott Inc, Chicago IL, USA) EVA‐Pulsar (EvaHeart, Chongqing, China)	Heartech (Xinrui Medical Equipment Co. Ltd., Shanghai, China). Parachute (CardioKinetix, Inc., Menlo Park, CA, USA)	Corveus (Corveus Medical, Houston, USA) PADN (Pulnovo Medical, Wuxi, China) Simplicity Spyral (Medtronic Minneapolis, USA)	Optimizer Smart (Impulse Dynamics, Orangeburg, NY, USA) Optimizer IntegraCCM‐D (Impulse Dynamics, Orangeburg, NY, USA)
Description	Effective treatment for intermediate‐ and high‐risk patients with aortic stenosis	Clamp reducing the mitral orifice area and converting the single orifice of the valve into a double orifice	Conduit from the left atrium to the right atrium to reduce left atrial pressure	Pump providing adaptive and pulsatile flow circulatory support	Ventricular partitioning device delivered through the aortic valve, was placed at the apex of the left ventricle	Treatment of autonomic neuromodulatory dysfunction and abnormal cardiac electrical activity	Non‐excitatory stimulation to enhance myocardial contractility
Advantages	TAVR improves survival and quality of life for patients with severe, symptomatic aortic stenosis	M‐TEER has significant reductions in mortality of mitral regurgitation and HF hospitalizations	IASDs improves symptoms of pulmonary congestion and exercise capacity for patients with HFpEF	LVAD has reduced adverse events and improved quality of life for patients with end‐stage HF (HFrEF)	TVPR is safe and effective in the reduction of the left ventricular wall stress by shrinking the ventricular cavity of ischaemic HF (HFrEF)	Neuromodulation improves the quality of life and prognosis and reduces the need for multiple medications and patient adherence to medication	CCM improves exercise tolerance and NYHA cardiac function classification and reduces the risk of hospitalization for worsening heart failure
Disadvantages	The long‐term durability of bioprosthetic valves, thrombosis, conduction block, paravalvular leak, post‐TAVR reintervention and bioprosthetic valve failure	M‐TEER device design and operation are relatively complex, and the learning curve is long. It is not feasible in all patients with limited indications, such as valve stenosis and valve calcification	Atrial arrhythmias, paradoxical embolism, shunt occlusion or stenosis and the need for anticoagulation therapy. It is only suitable for HFpEF patients, not for patients with severe right heart failure	Perioperative bleeding, infection, infective endocarditis, device thrombosis, gastrointestinal bleeding, right heart failure and aortic haemodynamic change	Perioperative infection, thromboembolism, high cost, high technical requirements for implantation, patients need aspirin and anticoagulation therapy after device implantation	Further studies are needed to evaluate the long‐term clinical impact and safety of neuromodulation therapy techniques	CCM still requires more evidence‐based support. Future studies will provide further clarification on the efficacy and safety of CCM in patients with HFpEF and atrial arrhythmia

CCM, cardiac contractility modulation; CRT, cardiac resynchronization therapy; GSN, great splanchnic nerve; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IASDs, interatrial shunt devices; LVAD, left ventricular assist device; M‐TEER, mitral valve transcatheter edge‐to‐edge repair; PADN, pulmonary artery denervation; RDN, renal sympathetic denervation; TAVR, transcatheter aortic valve replacement; TVPR, transcatheter ventricular partitioning restoration; VNS, vagus nerve stimulation.

Funding

This work was supported by the Scientific Research Foundation for Postdoctoral Heilongjiang Province of China (LBH‐Q19037), and Research Project of the First Affiliated Hospital of Harbin Medical University (2024M32).

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