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Heart Failure: Challenges and Future Options

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

Deadline for manuscript submissions: 15 May 2026 | Viewed by 2901

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Special Issue Editors

Dr. Pedro Caravaca-Pérez

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Guest Editor

1. Heart Failure and Transplant Unit. Hospital Clinic Barcelona, Barcelona, Spain
2. Institut d'Investigacions Biomèdiques August Pi i Sunyer—IDIBAPS, Barcelona, Spain
Interests: heart failure; cardiorenal syndrome; heart transplantation; ventricular assist devices; biomarkers; diuretic resistance

Dr. Marta Farrero-Torres

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Guest Editor

Special Issue Information

Dear Colleagues,

Heart failure remains one of the greatest challenges in cardiovascular medicine, representing a major cause of morbidity, mortality, and healthcare burden worldwide. Despite remarkable advances in pharmacological and device-based therapies, the prognosis of patients with heart failure continues to be poor, and the unmet clinical needs remain substantial.

In recent years, new therapeutic strategies, innovative technologies, and refined diagnostic tools have significantly expanded our ability to treat and monitor patients with heart failure. From disease-modifying drugs to advanced devices, from biomarkers to imaging modalities, the field is evolving rapidly. Yet, several questions persist: How can we best personalize therapy? Which patients are most likely to benefit from emerging treatments? How should we optimize long-term management and integrate multidisciplinary care?

In this Special Issue, “Heart Failure: Challenges and Future Options”, we aim to provide a platform for original research articles, clinical studies, and comprehensive reviews that address the evolving landscape of heart failure care. We particularly welcome contributions focused on the following:

Novel pharmacological and device-based therapies;
Biomarkers and imaging in risk stratification and treatment guidance;
Cardiorenal interactions and comorbidities;
Advanced heart failure, transplantation, and mechanical circulatory support;
Implementation of precision medicine and multidisciplinary approaches.

We look forward to your valuable contributions that will help to shape the future directions of heart failure research and clinical practice.

Dr. Pedro Caravaca-Pérez
Dr. Marta Farrero-Torres
Guest Editors

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Keywords

heart failure
cardiorenal syndrome
heart transplantation
ventricular assist devices
biomarkers
precision medicine
advanced therapies
diuretic resistance
risk stratification
multidisciplinary care

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Published Papers (5 papers)

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Research

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15 pages, 1261 KB

Open AccessArticle

Combined Prognostic Value of the PROFUND Index and Serum Albumin for One-Year Mortality in Elderly Patients with Acute Heart Failure

by Aladin Abdelhady Kishta Kishta, Marta M. Dolcet-Negre, María Jesús Rivas-López, Rocío García Alonso, Nuria Muñoz Rivas, Alicia Guzmán Carreras, Juan Igor Molina Puente and Manuel Méndez Bailón

J. Clin. Med. 2026, 15(9), 3219; https://doi.org/10.3390/jcm15093219 (registering DOI) - 23 Apr 2026

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Abstract

Background: Older adults hospitalized with acute heart failure frequently present with multimorbidity, frailty, and reduced physiological reserve. This makes accurate prognostic assessment particularly challenging in internal medicine. Traditional heart failure risk models often fail to capture this multidimensional vulnerability. The PROFUND index, developed to estimate medium-term mortality in multimorbid patients, and serum albumin, an established biomarker of nutritional and inflammatory status, may provide complementary prognostic information. This formed the aim of the present study. This study’s objective is to evaluate the individual and combined prognostic value of the PROFUND index and serum albumin for one-year mortality in patients admitted with AHF. Methods: We conducted a prospective, multicenter cohort study within the PROFUNDIC registry. We included consecutive adults hospitalized with AHF or decompensated chronic heart failure who met European Society of Cardiology diagnostic criteria and had NT-proBNP levels > 1500 pg/mL. PROFUND scores were obtained at admission, and hypoalbuminaemia was dichotomized as ≤3.5 g/dL. The primary outcome was one-year mortality, analyzed using Kaplan–Meier survival estimates, Cox proportional hazards models, and time-dependent ROC curves. Results: Among 544 included patients (mean age 85 years; 60% women), high PROFUND scores (>7) were present in 39% and hypoalbuminaemia in 55%. Both variables independently predicted one-year mortality, with the highest risk observed in patients presenting both high PROFUND scores (HR 2.26; 95% CI 1.66–3.09; p < 0.001) and hypoalbuminaemia (HR 1.70; 95% CI 1.18–2.46; p = 0.0046). The combined use of these markers modestly improved discriminatory performance compared with the PROFUND index alone (HR 2.83; 95% CI 1.72–4.64; p < 0.000). Conclusions: These findings suggest that integrating clinical complexity, assessed by the PROFUND index, with serum albumin provides a simple and clinically meaningful approach to early risk stratification in very elderly multimorbid patients treated in internal medicine wards. Full article

(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)

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13 pages, 456 KB

Open AccessArticle

Urinary Albumin-to-Creatinine Ratio as an Independent Predictor of 90-Day Outcomes in Patients Hospitalized for Acute Decompensated Heart Failure

by Claudia Andreea Palcău, Livia Florentina Păduraru and Ana Maria Alexandra Stănescu

J. Clin. Med. 2026, 15(7), 2690; https://doi.org/10.3390/jcm15072690 - 2 Apr 2026

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Abstract

Background: Albuminuria reflects systemic endothelial dysfunction and cardiorenal interaction in heart failure (HF), yet its short-term prognostic value in acute decompensated HF (ADHF) remains incompletely characterized. Methods: We conducted a prospective observational cohort study including 144 patients with complete follow-up hospitalized for ADHF. Urinary albumin-to-creatinine ratio (ACR), NT-proBNP, and estimated glomerular filtration rate (eGFR) were measured within 24 h of admission. Prior HF hospitalization within 12 months was recorded. The primary endpoint was a 90-day post-discharge composite of all-cause mortality or HF rehospitalization. Associations were examined using logistic regression, and discrimination was assessed using ROC curves with AUC comparisons. Results: Twenty-six patients (18.1%) experienced the 90-day composite endpoint. In univariable analysis, log₁₀-transformed ACR was strongly associated with events (OR 3.90, 95% CI 1.92–7.91; p < 0.001). In multivariable analysis, ACR remained independently associated with the endpoint in Model 1 (ACR + prior HF hospitalization: OR 4.21, 95% CI 1.93–9.17; p < 0.001) and Model 2 (additional adjustment for log₁₀ NT-proBNP: OR 3.49, 95% CI 1.54–7.91; p = 0.003). NT-proBNP was not independently associated with outcome in the fully adjusted model (p = 0.080). Discrimination improved from AUC 0.724 for ACR alone to 0.821 for Model 1 and 0.836 for Model 2; the AUC difference between Model 1 and Model 2 was not statistically significant (p = 0.404). Conclusions: Urinary ACR independently predicts 90-day adverse outcomes after ADHF hospitalization and improves discrimination when combined with recent HF hospitalization history; NT-proBNP did not provide significant incremental discrimination beyond this model. Full article

(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)

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18 pages, 2257 KB

Open AccessArticle

Femoral Plaque Burden and Left Ventricular–Arterial Coupling in Patients with Chronic Heart Failure

by Vadim Genkel, Sergey Ershov, Evgeny Lebedev, Yana Zaripova and Igor Shaposhnik

J. Clin. Med. 2026, 15(5), 2014; https://doi.org/10.3390/jcm15052014 - 6 Mar 2026

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Abstract

Background/Objectives: Lower extremity peripheral artery disease (PAD) is recognized as a significant public health issue, particularly due to its strong association with adverse cardiovascular events. Despite this, little attention has been given to its influence on left ventricular (LV) and left atrial (LA) function in patients with chronic heart failure (CHF). This study aims to examine the relationship between femoral plaque burden and structural and functional properties of the LV and LA in patients with CHF. Methods: Study design: cross-sectional observational single-center study. A total of 89 patients with CHF underwent comprehensive assessments, including duplex ultrasonography of lower extremity arteries and two-dimensional echocardiography. Analysis focused on evaluating femoral plaque burden, left ventricular deformation, and ventricular–arterial coupling. Results: Findings indicated that increased femoral plaque burden was associated with reductions in LA deformation and increases in LA stiffness. Similarly, there was evidence of impaired LV mechanics and elevated arterial loading, suggesting impaired ventricular–arterial coupling in patients with CHF and significant lower extremity atherosclerosis. Conclusions: Femoral plaque burden is closely linked to detrimental changes in LA and LV function, as well as disturbances in ventricular–arterial coupling, underscoring the importance of addressing lower extremity atherosclerosis in managing CHF patients. Full article

(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)

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23 pages, 707 KB

Open AccessArticle

Prognostic Value of Different Iron Status Definitions in Congestive Heart Failure: A Retrospective MIMIC-IV Analysis of Risk Stratification and Mortality

by Abdulla Zahi Hourani, Arman David Sürmeli and Sai Keertana Devarapalli

J. Clin. Med. 2026, 15(1), 244; https://doi.org/10.3390/jcm15010244 - 28 Dec 2025

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Abstract

Background: Iron deficiency (ID) is prevalent in congestive heart failure (CHF), worsening outcomes. While European guidelines recommend screening using ferritin and transferrin-saturation (TSAT), inconsistent diagnostic criteria, especially regarding functional deficiency (ferritin 100–299 μg/L + TSAT < 20%) and hyperferritinemia, limit prognostic accuracy. This study evaluated iron status definitions, including guideline criteria and a combined Ferritin-TSAT model, for predicting 365-day mortality in hospitalised CHF patients. Methods: This retrospective analysis used MIMIC-IV data from 1839 CHF patients. Iron status within 24 h of admission was categorised using: (1) Guideline ID vs. non-ID; (2) Ferritin categories; (3) TSAT categories; (4) Combined Ferritin-TSAT model (Low: guideline ID; Intermediate: ferritin 100–299 + TSAT ≥ 20%; High: ferritin ≥ 300 μg/L). Adjusted Cox models assessed mortality associations. Results: Guidelines-defined iron deficiency (33.66% prevalence) independently associated with higher 1-year mortality (56.1% vs. 29.4%; adjusted HR 4.36, 95% CI 3.35–5.34). The combined Ferritin-TSAT model showed significant prognostic value, differentiating true iron deficiency (reference) from hyperferritinemia (adjusted HR 0.50 vs. iron deficiency) and intermediate group (adjusted HR 0.36 vs. ID), indicating varying risk relative to the most deficient group. This combined model better distinguished hyperferritinemic and iron-replete subgroups than the binary guideline definition. Conclusions: Iron status, including deficiency and hyperferritinemia, independently predicts 1-year mortality in CHF. While guideline iron deficiency is a strong predictor, a combined Ferritin-TSAT classification offers finer risk stratification by identifying distinct phenotypes (true deficiency, hyperferritinemia, intermediate). Nuanced iron status assessment could improve prognostic evaluation and guide personalised therapies (e.g., IV iron for deficiency, investigation for hyperferritinemia) to enhance CHF outcomes. Full article

(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)

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10 pages, 2063 KB

Open AccessCase Report

MELAS Syndrome Presenting with Hypertrophic Cardiomyopathy and Advanced Heart Failure: A Multisystem Diagnostic Challenge

by Jozef Dodulík, Marie Lazárová, Eva Kapsová and Jan Václavík

J. Clin. Med. 2026, 15(3), 1109; https://doi.org/10.3390/jcm15031109 - 30 Jan 2026

Viewed by 666

Abstract

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare multisystem disorder caused by mitochondrial DNA mutations, most commonly the m.3243A>G variant in the MT-TL1 gene. Although neurological manifestations predominate, cardiac involvement, including hypertrophic cardiomyopathy (HCM), heart failure (HF), and arrhythmias, may be the initial or dominant presentation and often remains underrecognized. Case Presentation: We report a 43-year-old man with chronic kidney disease (CKD) and long-standing bilateral sensorineural hearing loss who presented with progressive dyspnea and acute decompensated HF. Transthoracic echocardiography revealed severe left ventricular (LV) systolic dysfunction with diffuse hypertrophy. Cardiac magnetic resonance showed non-ischemic cardiomyopathy with diffuse late gadolinium enhancement and increased LV wall thickness. Coronary angiography excluded obstructive disease. Initial endomyocardial biopsy performed at a referring center showed nonspecific hypertrophy and fibrosis without diagnostic features. Given the multisystem involvement, a metabolic or genetic etiology was suspected. Whole-exome sequencing identified the pathogenic m.3243A>G MT-TL1 mutation, confirming MELAS syndrome. The patient was managed with guideline-directed HF therapy, received an implantable cardioverter-defibrillator for primary prevention, and was subsequently evaluated for heart transplantation. Conclusions: This case highlights the importance of considering mitochondrial disorders in the differential diagnosis of unexplained cardiomyopathy, particularly when cardiac dysfunction coexists with renal impairment and auditory deficits. Comprehensive multimodality evaluation and genetic testing are essential to establishing a unifying diagnosis and optimizing management. Full article

(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)

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