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Heart Failure: Treatment and Clinical Perspectives

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 2277

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Special Issue Editors

Dr. Geza Halasz

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Guest Editor

Cardiology Department, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy
Interests: heart failure; echocardiography; clinical cardiology; cardiac rehabilitation; cardiomyopathies

Prof. Dr. Domenico Gabrielli

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Cardiology Department, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy
Interests: heart failure; clinical cardiology; cardiac rehabilitation; cardiomyopathies

Prof. Dr. Francesco Grigioni

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Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
Interests: heart failure; echocardiography; clinical cardiology; cardiomyopathies
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Special Issue Information

Dear Colleagues,

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, representing a complex clinical syndrome with heterogeneous phenotypes, trajectories, and responses to therapy. Despite significant advances in pharmacological and non-pharmacological management, HF continues to pose major challenges for healthcare systems—both in terms of clinical outcomes and healthcare resource utilization. In recent years, novel diagnostic tools, including advanced cardiac imaging, biomarkers, and cardiopulmonary exercise testing (CPET), have improved our ability to phenotype HF patients more precisely and to tailor therapies accordingly. Of particular interest is the integration of CPET with stress echocardiography (CPET-TTE), which offers a comprehensive, dynamic assessment of central and peripheral determinants of exercise intolerance. This combined approach is emerging as a powerful tool to refine risk stratification, distinguish between cardiac and extracardiac limitations, and guide the selection of optimal therapeutic strategies in both HF with reduced and preserved ejection fraction. Moreover, the incorporation of artificial intelligence, remote monitoring, and multidisciplinary care models is reshaping the landscape of HF management, with promising implications for precision medicine. With this Special Issue, we aim to capture cutting-edge research and clinical perspectives on the treatment of HF.

We welcome original research, reviews, and expert opinions on topics such as disease-modifying therapies in HFrEF and HFpEF, the evolving role of SGLT2 inhibitors, device-based therapies, management of comorbidities, and cardiac rehabilitation. Special attention will also be given to innovations in imaging, omics-based personalization of therapy, digital health solutions, and the physiological insights offered by tools such as CPET-TTE.

We invite you to contribute your most innovative work to this Special Issue, with the hope of advancing our collective understanding and improving the lives of patients living with heart failure.

Dr. Geza Halasz
Prof. Dr. Domenico Gabrielli
Prof. Dr. Francesco Grigioni
Guest Editors

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Keywords

heart failure
chronic heart failure
acute heart failure
treatment
cardiac imaging
diagnostics
patient outcomes
prognosis

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13 pages, 815 KB

Open AccessArticle

Sodium–Glucose Cotransporter 2 Inhibitors in Underweight Patients with Heart Failure: A Case Series

by Masaki Nakagaito, Teruhiko Imamura, Toshihide Izumida, Makiko Nakamura and Koichiro Kinugawa

J. Clin. Med. 2026, 15(5), 2027; https://doi.org/10.3390/jcm15052027 - 6 Mar 2026

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Abstract

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality and morbidity in patients with heart failure (HF). However, their efficacy and safety in underweight patients remain uncertain. This study aimed to evaluate the efficacy and safety of SGLT2i in underweight patients with HF. Methods: This study was a single-center, prospective observational study designed to assess the efficacy of SGLT2i therapy in underweight patients with HF. The primary outcome was a composite of unplanned hospitalization for HF or death from cardiovascular causes. A key secondary outcome was hospitalization from any cause. Results: This study enrolled 131 consecutive patients with a body mass index (BMI) > 18.5 kg/m² hospitalized for HF between December 2020 and October 2023. The median age of the study population was 81 (73–87) years, and 60% were female. Baseline BMI was 17.2 (16.0–17.9) kg/m². Of these, 28 patients initiated SGLT2i during index hospitalization, while the remaining 103 did not receive SGLT2i. Over a median of 20.4 months of follow-up, the primary outcome occurred in 6 of 28 patients (21.4%) with SGLT2i and 22 of 103 patients (21.4%) without SGLT2i (p = 0.758). All-cause hospitalizations occurred in 23 of 28 patients (82.1%) with SGLT2i and 65 of 103 patients (63.1%) without SGLT2i (p = 0.009). Patients receiving SGLT2i showed a significant decrease in BMI at discharge, 1 month after discharge, and 3 months after discharge compared with those without SGLT2i (p < 0.05 for each time point). Conclusions: SGLT2i in underweight patients with HF may not reduce cardiovascular event risk and may be associated with a higher rate of overall hospitalizations. Full article

(This article belongs to the Special Issue Heart Failure: Treatment and Clinical Perspectives)

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15 pages, 658 KB

Open AccessArticle

Association Between Mitral Annular Calcification and Ventricular Tachycardia in Patients with Reduced and Mildly Reduced Ejection Fraction

by Müjgan Ayşenur Şahin, Ahmet Seyda Yılmaz, Elif Ergül, Hakan Duman, Hüseyin Durak, Abuzer Duran, Şuayp Osmanoğlu and Mustafa Çetin

J. Clin. Med. 2026, 15(3), 1172; https://doi.org/10.3390/jcm15031172 - 2 Feb 2026

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Abstract

Objective: This study aimed to evaluate the association between mitral annular calcification (MAC) and ventricular tachycardia (VT) in patients with reduced and mildly reduced ejection fraction and to identify independent predictors of VT. Materials and Methods: A total of 143 patients with heart failure and left ventricular ejection fraction (LVEF) under 50% were included in this retrospective cross-sectional study. Patients were classified into two groups according to the presence of VT. Clinical, biochemical, and echocardiographic variables were compared between groups. Independent predictors of VT were identified using multivariable logistic regression analysis. Results: MAC was significantly more prevalent in the VT group compared with controls (43.6% vs. 17.4%, p < 0.001) and was the strongest independent predictor of VT (OR: 2.74; 95% CI: 1.13–6.65; p = 0.026). Higher inflammatory activity, lower serum albumin levels, increased left atrial volume, renal dysfunction, and elevated diastolic filling pressures were also associated with VT. Conclusions: MAC is a strong and independent predictor of ventricular tachycardia in patients with reduced and mildly reduced ejection fraction. Incorporating MAC into the overall arrhythmic risk profile alongside inflammatory, metabolic, and structural parameters may improve risk stratification in this population. Full article

(This article belongs to the Special Issue Heart Failure: Treatment and Clinical Perspectives)

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13 pages, 452 KB

Open AccessArticle

Physical Frailty Versus the MECKI Score in Risk Stratification of Patients with Advanced Heart Failure: Simpler Measure, Similar Insights?

by Francesco Curcio, Rosaria Chiappetti, Cristiano Amarelli, Irene Mattucci, Allegra Di Somma, Francesca Maria Stagnaro, Federica Trotta, Gennaro Alessio, Seyedali Ghazihosseini, Ciro Abete, Ciro Maiello, Pasquale Abete and Francesco Cacciatore

J. Clin. Med. 2026, 15(2), 513; https://doi.org/10.3390/jcm15020513 - 8 Jan 2026

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Abstract

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

(This article belongs to the Special Issue Heart Failure: Treatment and Clinical Perspectives)

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Open AccessStudy Protocol

Rationale and Design of the PREDICT-CCM Study: Predictive Value of Dobutamine Stress Echocardiography for Clinical Response to Cardiac Contractility Modulation Therapy in a Multicenter Italian Cohort

by Francesco Zanon, Carlo Uran, Vincenzo Bonfantino, Natale Di Belardino, Antonio Lupo, Marzia Giaccardi, Procolo Marchese, Angelo Antonio Di Grazia, Luca Santini, Luigi Di Lorenzo, Giovanni Carreras, Luca Sgarra, Matteo Ziacchi, Leonardo Marinaccio, Luigi Mancini, Giovanni Bisignani, Mariateresa Manes, Stefano Guarracini, Amir Kol, Roberto Floris, Antonio Rossillo, Gabriele Zanotto, Lina Marcantoni and Franco Noventa Show full author list Hide full author list

J. Clin. Med. 2026, 15(9), 3223; https://doi.org/10.3390/jcm15093223 - 23 Apr 2026

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Abstract

Background/Objectives: Heart failure (HF) is associated with substantial morbidity, impaired quality of life (QOL), and reduced functional capacity. In selected patients with symptomatic HF despite Optimal Medical Therapy (OMT), Cardiac Contractility Modulation (CCM) may be a therapeutic option. Identifying patients most likely to benefit from CCM remains an unmet need. The Predict-CCM study aims to evaluate long-term clinical and objective outcomes after CCM therapy and to assess the predictive value of pre-implant low-dose dobutamine stress echocardiography (LDDSE). Methods and Results: Predict-CCM is an independent, non-profit, multicenter, observational cohort study conducted in Italy, with both retrospective and prospective enrollment. The primary endpoint is the proportion of subjects with a clinical response to CCM at 12 months, defined as a ≥1-class reduction in NYHA class. Secondary clinical endpoints include reductions in HF-related hospitalizations, changes in QOL assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and changes in NT-proBNP levels from baseline to follow-up. Outcomes will be evaluated in the overall cohort and in two subcohorts stratified by pre-implant LDDSE response: (1) reduction in left ventricular end systolic volume (LVESV) ≥ 15% (DeltaLVESV ≥ 15%); and (2) reduction in LVESV < 15% (DeltaLVESV < 15%). Assuming a 70% clinical response rate at 12 months, the estimated sample size is 120 patients. The study was approved by the Ethics Committee in March 2025. Enrollment will continue for 2 years, with a 12-month follow-up period after implant for each subject. Conclusions: This study may provide new criteria for patient selection and outcome assessment in CCM therapy. Left ventricular contractile reserve assessed by stress echocardiography may be a promising predictor of response. Full article

(This article belongs to the Special Issue Heart Failure: Treatment and Clinical Perspectives)

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