Cardiac implantable electronic devices (CIEDs) are integral to heart failure (HF) management, providing therapies for bradyarrhythmias, cardiac resynchronization therapy (CRT), sudden cardiac death (SCD) prevention, and remote monitoring. This review summarizes current and potential future indications, emerging technologies, and challenges in the implementation of CIEDs in HF. Conventional right ventricular pacing in HF patients is increasingly being replaced by biventricular pacing (BVP) and left bundle branch area pacing (LBBAP), while leadless pacing pacemakers have emerged as an alternative to conventional transvenous systems, offering the potential to reduce lead- and device-related complications. As BVP remains the standard approach for CRT, recent data bestow LBBAP as a promising alternative and integration platform. Newer implantable cardioverter-defibrillator technologies, including subcutaneous and extravascular systems, may reduce lead-related complications while maintaining effective arrhythmia termination and recognition. Advances in atrial fibrillation management, implantable hemodynamic monitoring, and novel pacing indications such as atrioventricular recoupling and personalized pacing in HF with preserved ejection fraction are expanding the therapeutic potential of CIEDs. However, the adoption of these innovations is challenged by limited randomized evidence, procedural complexity, and substantial disparities in access and implementation across healthcare systems. Ongoing clinical trials will help define the role of emerging device technologies and monitoring strategies, while efforts to improve guideline adherence, value-based procurement, and equitable access remain essential to maximize the benefits of CIED therapy in patients with HF. HF – heart failure; LVEF – left ventricular ejection fraction; BVP – biventricular pacing; CSP – conduction system pacing; LP – leadless pacing; LBBAP – left bundle branch area pacing; RCT – randomized clinical trial; HFrEF – heart failure with reduced ejection fraction; CRT – cardiac resynchronization therapy; LOT-CRT – left optimized resynchronization therapy; AF – atrial fibrillation; TV-ICD – transvenous implantable cardiac defibrillator; SCD – sudden cardiac death; HFpEF – heart failure with preserved ejection fraction
Heart failure (HF) and cardiovascular (CV) diseases (CVD) are closely interconnected through a complex and bidirectional relationship. HF frequently represents the final common pathway of several CV conditions; in contrast, CV comorbidities often act as key drivers of disease progression along the HF continuum, from stage A (individuals at risk) to overt symptomatic HF (stages C–D). The coexistence of multiple CV comorbidities—including arterial hypertension, atrial fibrillation, coronary artery disease, peripheral artery disease, and valvular heart disease—is associated with a more severe clinical profile, reduced functional capacity, impaired quality of life, and increased risk of hospitalization and mortality. Importantly, CV comorbidities may significantly influence the implementation and optimization of guideline-directed medical therapy (GDMT), frequently limiting appropriate up-titration due to haemodynamic instability, drug intolerance, or increased susceptibility to adverse events. The prevalence, pathophysiological interactions, and prognostic impact of CV comorbidities vary across HF phenotypes, contributing to the heterogeneity of disease presentation and clinical outcomes. An integrated and phenotype-oriented approach is therefore essential to optimize risk stratification and personalize therapeutic strategies. Since the publication of the 2019 manifesto on HF comorbidities from the Working Group on Heart Failure of the Italian Society of Cardiology (SIC), substantial new evidence has emerged regarding the epidemiology, pathophysiology, and management of CV comorbidities in HF. In this updated position paper, the SIC Working Group on Heart Failure provides a comprehensive and clinically oriented overview of the current evidence on major CV comorbidities in HF, with the aim of supporting clinicians in improving diagnostic pathways, optimizing therapeutic strategies, and ultimately enhancing clinical outcomes.
The prevalence of heart failure (HF) continues to rise and disproportionately affects disadvantaged populations. This has created an urgent need to concurrently tackle HF prevention and therapeutics, and to look beyond traditional HF risk factors. Several aspects of the social context and environment such as race/ethnicity, social isolation/loneliness, marginalization/segregation, socioeconomic position, air pollution, noise pollution, extreme temperatures, food environment, geographical location and neighborhood socioeconomic status have been recognized as modifiers of HF risk. These factors can be effectively targeted for comprehensive HF prevention. The pathways that link the social context and environment to HF involve psychological, behavioral, and biological mechanisms as well as limited access to care. This review outlines key domains of HF prevention and discusses the evidence linking the social context and environment with HF. We also addressed the mechanistic underpinnings that drive the associations reported and highlight key features of effective HF prevention programs. Finally, we discussed challenges to implementing social and environmental factors as components of HF prevention. To achieve maximal effect, HF prevention should be approached at multiple tiers using a life course approach.
Heart failure with preserved ejection fraction represents a clinical challenge, accounting for at least 50
Giant cell myocarditis (GCM) is a rare but devastating inflammatory cardiac disease characterized by rapid hemodynamic deterioration, malignant arrhythmias, and high rates of death or heart transplantation. Without immunosuppressive treatment, median transplant-free survival is approximately three months. Current evidence identifies GCM as a predominantly T cell–mediated autoimmune disorder driven by a breakdown of immune tolerance, with contributions from macrophage-derived multinucleated giant cells and neutrophil extracellular trap formation. Viral infections and environmental factors have been implicated as potential triggers. GCM typically affects middle-aged adults, with concomitant non-cardiac autoimmune diseases present in approximately 20
Cardiac resynchronization therapy defibrillators traditionally require a dedicated right atrial lead to provide atrial sensing and pacing in addition to biventricular pacing. However, the clinical value of routine atrial pacing in CRT recipients without sinus node dysfunction remains uncertain, while additional transvenous leads increase procedural complexity and lead-related complications. The CRT-NEXT trial evaluated whether a simplified two-lead CRT-DX system, capable of atrial sensing through a floating atrial dipole but without atrial pacing, was non-inferior to conventional three-lead CRT-D. In this randomized non-inferiority trial, CRT-DX met the prespecified non-inferiority criterion for the composite endpoint of all-cause mortality, cardiovascular hospitalization, and lead-related complications at 12 months. Mortality, cardiovascular hospitalization, arrhythmic outcomes, reverse remodeling, and functional capacity were comparable between groups, while CRT-DX was associated with shorter procedure time and fewer atrial lead-related complications. Importantly, atrial sensing remained reliable during follow-up, CRT delivery was preserved, and only one patient required late atrial lead implantation. These findings challenge the routine need for atrial pacing support in carefully selected CRT-D candidates and suggest that reliable atrial sensing may be sufficient for most patients without sinus node dysfunction. Future integration of DX-based atrial sensing with conduction system pacing may further advance device simplification toward single-lead CRT-D platforms.
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous myocardial disorders in which disease progression is influenced by secondary modifiers beyond structural gene mutations. Increasing evidence suggests that inflammatory signalling plays a role in modulating disease phenotype and progression. Among inflammatory mediators, interleukin-6 (IL-6) has emerged as a potential contributor to myocardial remodelling and dysfunction.A structured literature review was performed using Ovid MEDLINE and the Cochrane Library for studies published up to 10 October 2025. Findings were synthesised narratively because of substantial heterogeneity in study design, populations, and outcomes.This review synthesises clinical, genetic, and experimental evidence on the role of IL-6 in HCM and DCM, with a focus on its potential therapeutic relevance. Across studies, elevated IL-6 levels are consistently associated with greater disease severity. Mechanistic data indicate that IL-6 signalling via the gp130/STAT3 pathway may promote cardiomyocyte hypertrophy, fibrosis, and apoptosis, with genetic polymorphisms likely influencing disease susceptibility and phenotypic expression. Pharmacological interventions with anti-inflammatory properties, including statins, pentoxifylline, and growth hormone, have been associated with reductions in IL-6 levels and improvements in cardiac function, although these effects are not specific to IL-6 signalling.In summary, current evidence supports IL-6 as an important component of the inflammatory milieu associated with HCM and DCM and suggests potential utility as a biomarker of disease activity. However, evidence supporting a causal pathogenic role remains limited, and IL-6-directed therapies have not been systematically evaluated in cardiomyopathy populations.
Iron overload cardiomyopathy (IOC) remains an important cause of morbidity and mortality in patients with hereditary haemochromatosis and transfusion-dependent conditions such as haemoglobinopathies. The condition arises when excess iron, due to increased intestinal iron absorption or repetitive transfusions, saturates transferrin-binding capacity, generating non-transferrin-bound iron. This form of iron enters cardiomyocytes through L-type and T-type calcium channels, divalent metal transporter 1, and ZIP14 and triggers oxidative stress via the Fenton reaction, mitochondrial dysfunction, calcium dysregulation, and ferroptosis. The resulting clinical spectrum ranges from diastolic dysfunction to overt heart failure and fatal arrhythmias. Cardiac magnetic resonance T2* has revolutionized diagnosis and risk stratification, enabling MRI-guided chelation strategies that have dramatically reduced cardiac mortality over the past decades. Phlebotomy remains the cornerstone of treatment in primary haemochromatosis, while iron chelators, including deferoxamine, deferiprone and deferasirox, is the standard for transfusion-dependent patients. Adjunctive amlodipine has also emerged as a strategy to reduce myocardial iron accumulation. Novel disease-modifying or curative treatments for thalassaemia, such as luspatercept, mitapivat and gene therapy offer the prospect of addressing the root cause of iron loading. This review provides an updated comprehensive, evidence-based overview of the pathophysiology, diagnosis, and management of IOC.
Treatment for heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) has evolved significantly in recent years. This period of therapeutic progress follows a span of over two decades during which randomized controlled trials (RCTs) of neurohormonal blockade and other therapies failed to definitively demonstrate clinical benefits. As such, traditionally, management guidelines for HFmrEF and HFpEF were limited to recommendations focused on optimization of volume status with diuretics, management of comorbidities, and consideration of certain medications such as angiotensin receptor-neprilysin inhibitor (ARNi) or steroidal mineralocorticoid receptor antagonists (MRA) to subsets of patients. After definitive results from multiple RCTs, sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently a main pillar in treating HFmrEF and HFpEF in European and American guidelines. However, other therapies, including non-steroidal mineralocorticoid receptor antagonists (nsMRA) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), are proving to be additional effective treatments for HFmrEF and HFpEF and preventing the progression of cardiovascular-kidney-metabolic (CKM) syndrome. There is now increasing justification for combining multiple proven treatments for HFmrEF and HFpEF to maximize potential benefits. Treatment for different types of heart failure has improved significantly in recent years. For many years, there were few treatments that clearly helped people with heart failure whose heart still pumps normally or nearly normally. Care mainly focused on treating symptoms, helping the body remove excess fluid, and managing related health conditions such as high blood pressure, diabetes, and obesity. Today, research has expanded the available treatment options. One important group of medicines helps the body remove excess sugar and salt through the urine, which also reduces excess fluid and lowers the strain on the heart. Newer studies have shown that medicines that block the effects of a hormone called mineralocorticoid can improve outcomes while causing fewer side effects than older steroid-based treatments. For people who also have obesity, another newer group of medicines that acts on natural gut hormones has been shown to improve symptoms, physical activity, and quality of life. Overall, using a combination of these newer treatments may help people with heart failure whose heart still pumps normally or nearly normally feel better, improve their quality of life, and achieve better long-term health outcomes.
Heart failure (HF) represents a major burden on healthcare systems globally, driven by high rates of hospitalizations and readmissions, as well as prolonged length of stay (LOS). To address this, a wide range of innovative strategies have emerged and evolved in recent years. These approaches span a broad spectrum, ranging from novel routes of medication administration to digital health technologies such as telemonitoring, wearable devices, as well as implantable devices. Given the rapid expansion of available innovations, it can be challenging for clinicians to remain fully up to date with emerging tools and evidence. At the 2026 ESC Heart Failure Congress in Barcelona, Spain, global experts in the field highlighted different technologies and the key clinical trials supporting them. This review aims to synthesize the most recent innovative strategies aimed at reducing HF hospitalizations (HFH), as presented during the congress.
This narrative review examines the clinical value of cognitive assessment in heart failure, highlighting optimal timing, practical tools, and the epidemiology, pathophysiology, and clinical implications of cognitive impairment. The relationship between heart failure (HF) and cognitive impairment (CI) increasingly represents a growing challenge at the intersection of the heart and brain. Current hypotheses suggest a bidirectional relationship driven by multifactorial mechanisms, including chronic cerebral hypoperfusion, blood-brain barrier disruption, neuroinflammation, while shared proteinopathy remains a preliminary and unconfirmed hypothesis. Although CI affects approximately 41
Dyspnea is a key symptom of heart failure (HF), particularly in its acute form, where it represents the most common cause of hospitalization. Although traditionally attributed to pulmonary congestion, dyspnea in HF is a multidimensional phenomenon resulting from complex interactions among elevated cardiac filling pressures, hemodynamic alterations, fluid redistribution, impaired gas exchange, activation of mechano- and chemoreceptors, and maladaptive neurohormonal activation. Comorbidities, including chronic lung disease, obesity, cachexia, renal dysfunction, anemia, and chronic inflammation, further modulate symptom perception and lower the threshold for its occurrence. In this review, we synthesize current knowledge on the pathophysiological mechanisms underlying dyspnea in HF, emphasizing its heterogeneity and the complex interplay between hemodynamics, ventilatory regulation, and peripheral factors. We discuss available dyspnea assessment tools, highlighting their strengths and methodological limitations in clinical practice and randomized trials. Despite the use of standardized scales, dyspnea remains a subjective and dynamically evolving symptom. Data from large clinical trials in acute HF indicate that early improvement in dyspnea is common but does not translate into reduced mortality or rehospitalization, whereas residual dyspnea identifies patients at higher risk of adverse events. A better understanding of its multidimensional pathophysiology, measurement limitations, and prognostic significance has important implications for the interpretation of clinical trial results and for optimizing the assessment and management of this fundamental symptom.
Heart failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure and is characterized by high morbidity, limited therapeutic options, and marked biological heterogeneity. Coronary microvascular dysfunction (CMD) has emerged as a central pathophysiological mechanism linking cardiometabolic comorbidities to myocardial remodeling and clinical HFpEF phenotypes. Impaired coronary flow reserve, endothelial dysfunction, reduced nitric oxide bioavailability, and microvascular rarefaction contribute to myocardial stiffening, energetic inefficiency, and ultimately diastolic dysfunction, often preceding overt structural heart disease in the setting of HFpEF. Notably, HFpEF disproportionately affects females, yet the biological mechanisms underlying this sex difference remain incompletely understood. Accumulating evidence suggests that sex-specific differences in vascular biology, immune–metabolic signaling, hormonal regulation, and myocardial–vascular coupling modulate susceptibility to CMD and influence the progression from vascular dysfunction to myocardial disease. Females exhibit a higher prevalence of CMD in the absence of obstructive coronary artery disease, distinct inflammatory and metabolic profiles, and accelerated vascular and ventricular stiffening, particularly after menopause. In contrast, males more frequently display eccentric remodeling and obstructive epicardial coronary disease. This narrative review synthesizes current evidence on the mechanistic role of CMD in HFpEF, with a specific focus on sex-specific biological pathways that shape disease trajectory. Understanding how sex modifies CMD may inform improved diagnostic strategies, risk stratification, and the development of precision-based therapeutic approaches in HFpEF.
Cardiovascular disease represents the leading cause of death in patients with Anderson-Fabry disease (FD), with sudden cardiac death (SCD) being one of the most frequently reported causes of mortality. However, a significant diagnostic gap persists in identifying patients at risk, as current stratification tools are inadequate for predicting lethal arrhythmic events. This narrative review resumes the existing peer-reviewed literature regarding the pathophysiology of FD arrhythmias and evaluates the diagnostic limitations of the current standard intermittent monitoring tools, such as the 24-hour Holter. Standard monitoring tools, such as the 24-hour Holter often miss paroxysmal, asymptomatic arrhythmias. Recent studies using implantable loop recorders (ILRs) show a significantly higher burden of arrhythmias than previously recognized. Myocardial fibrosis, identified as late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), is strongly associated with malignant arrhythmias, together with the degree of left ventricular hypertrophy (LVH). Current consensus statements may underestimate the need for continuous monitoring in FD. By providing a comprehensive narrative synthesis of available observational and registry data, this paper proposes an updated, exploratory risk-stratification clinical guide for the extension of countinuous rhythm monitoring in high-risk subgroups of FD.
Acute heart failure (AHF) is a major cause of hospitalisation worldwide and remains associated with substantial early rehospitalisation and short-term mortality. Accurate assessment of congestion remains challenging because symptoms, physical signs, body weight, and conventional biomarkers may not fully capture the severity, distribution, or persistence of haemodynamic congestion. This limitation contributes to incomplete decongestion and may partly explain recurrent decompensation after discharge. In this review, we examine the complementary roles of three point-of-care ultrasound modalities in residual congestion assessment: lung ultrasound for pulmonary congestion, venous Doppler/VExUS for systemic venous and end-organ congestion, and focused transthoracic echocardiography for cardiac and haemodynamic profiling. We propose the ICON (Integrated Congestion-Oriented Navigation) framework as a pragmatic bedside model that translates these modalities into a three-phase acute heart failure workflow: initial assessment, inpatient monitoring, and predischarge reassessment. Within this workflow, ICON supports phenotype-based interpretation of residual congestion, including pulmonary-dominant, systemic venous/RV-dominant, mixed, cold-wet/low-output, and near-decongested profiles. Current evidence supports the prognostic value of residual congestion and suggests that ultrasound-guided strategies may improve congestion assessment, but the evidence remains heterogeneous. The ICON framework should therefore be viewed as a proposed physiology-based model requiring prospective validation before adoption as a standard-of-care pathway.
Iron deficiency (ID) is a highly prevalent and clinically significant comorbidity in heart failure with preserved ejection fraction (HFpEF), affecting 40–60
Paediatric obstructive hypertrophic cardiomyopathy (oHCM) is a rare inherited cardiac disease that may present from childhood through adolescence and is associated with substantial long-term morbidity and mortality. Its management is based largely on observational studies and clinical experience and currently focusses on symptom improvement through medical therapy and, when indicated, septal reduction therapy to alleviate left ventricular outflow tract (LVOT) obstruction. In adult oHCM, mavacamten has established cardiac myosin inhibition as an effective strategy to reduce LVOT obstruction, but paediatric trial evidence has been lacking. The SCOUT-HCM trial is the first randomised placebo-controlled trial in adolescents to investigate the efficacy and safety of mavacamten for symptomatic oHCM. Among 44 adolescents (mean age 14.7 ± 1.7 years) mavacamten significantly reduced Valsalva-provoked LVOT gradients at 28 weeks, confirming short-term physiological efficacy. Secondary and exploratory findings, including NYHA functional class, cardiac structure and biomarkers, showed a trend to improvement, without a signal of left ventricular systolic dysfunction. The positive results of SCOUT-HCM, align with larger and longer adult oHCM trials and are likely to influence clinical practice, supporting a cautious integration of mavacamten in adolescent oHCM management. Longer follow-up and broader paediatric studies should determine durability of benefit, validated patient-reported outcomes, exercise capacity, arrhythmia burden, long-term safety and the need for septal reduction therapy in paediatric oHCM.
The most common hereditary transthyretin (ATTRv) amyloidosis variant in the United States, Val122Ile (p.Val142Ile), is predominantly detected in populations of African ancestry. In this narrative review, we highlight the current challenges and discuss priority focus areas to improve the timely diagnosis and treatment of p.Val142Ile ATTRv amyloidosis across populations. Studies suggest geographic, economic, and socio-economic discordance in timely diagnosis, treatment access, and outcomes in regions with a high proportion of at‑risk individuals. Many ATTR amyloidosis symptoms overlap with other diseases due to their nonspecific and heterogenous nature. Consequently, optimized screening tools for biomarker identification and specialty care services/networks are required to determine at-risk individuals and improve clinical outcomes. However, access to genetic screening can be limited and diagnosis is complicated by variable p.Val142Ile ATTRv amyloidosis penetrance coupled with phenotypic evolution. To enhance existing treatment guidelines, regular monitoring of “at-risk” patients, multidisciplinary management, and purposeful clinical trial recruitment of minority populations are recommended.
Pulmonary hypertension complicating heart failure with preserved ejection fraction (HFpEF), particularly the combined post- and pre-capillary form (CpcPH), has lacked any mechanism-specific therapy, as repeated trials of pulmonary vasodilators have failed or caused harm. This mini-review highlights findings from the Phase 2 CADENCE study evaluating sotatercept, an activin signaling inhibitor that targets vascular remodeling rather than vascular tone. Sotatercept met its primary endpoint by reducing pulmonary vascular resistance at 24 weeks and produced concordant improvements in mean pulmonary artery pressure, wedge pressure, 6-minute walk distance, NYHA class, and NT-proBNP, without the compensatory rise in left-sided filling pressure that characterizes vasodilator therapy. Notably, the lower 0.3 mg/kg dose appeared to outperform the 0.7 mg/kg dose across several hemodynamic and functional endpoints while offering a more favorable safety profile. These findings position sotatercept as the first non-vasodilatory, potentially disease-modifying option for advanced HFpEF-associated pulmonary hypertension, and a confirmatory Phase 3 trial is warranted to determine whether this hemodynamic benefit translates into durable clinical outcomes.
