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Molecular Insights into Heart Failure: From Bench to Bedside
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Molecular Insights into Heart Failure: From Bench to Bedside

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 4624

Special Issue Editor

Dr. Nadia Aspromonte

E-Mail Website
Guest Editor
Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
Interests: biomarkers; heart failure; ischemic heart disease; preserved ejection fraction; cardiology; fibrosis; inflammation; non-coding RNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Significant progress has been made in the understanding of how molecular processes regulate cardiac function and how disruptions in these processes contribute to heart failure. However, there are still some significant gaps in the understanding of disease mechanisms, and further research is needed.

This Special Issue aims to explore the intricate molecular mechanisms that underlie heart failure, bridging the gap between basic research and clinical applications.

Key themes include:

  • Molecular Pathways: This issue aims to examine the complex molecular pathways involved in cardiac hypertrophy, calcium homeostasis, and immune activation during heart failure. We want to highlight the roles of key molecular players, such as signaling molecules, transcriptional regulators, and microRNAs;
  • Translational Research: A strong focus is placed on translating molecular insights into clinical applications, aiming to improve the diagnosis, prognosis, and treatment of heart failure through the development of novel therapeutic targets and strategies based on molecular understanding;
  • Clinical Relevance: This issue addresses the clinical implications of molecular findings, discussing how these insights can be used to personalize medicine and improve patient outcomes.

It also addresses the importance of understanding the molecular differences within different types of heart failure, such as heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

In conclusion, this Special Issue aims to provide a comprehensive overview of the latest advancements in molecular research related to heart failure, highlighting the crucial role of these insights in advancing clinical practice.

Dr. Nadia Aspromonte
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • heart failure
  • cardiac biomarkers
  • medical therapy
  • molecular pathways
  • prognosis
  • target therapy

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Published Papers (3 papers)

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Research

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13 pages, 2092 KB  
Article
Evaluation of the Effects of the Sodium–Glucose Cotransporter 2 Inhibitors and Sacubitril/Valsartan Combined Therapy in Patients with HFrEF: An Echocardiographic Study
by Isabella Fumarulo, Annalisa Pasquini, Giulia La Vecchia, Bianca Pellizzeri, Andriy Sten, Barbara Garramone, Marcello Vaccarella, Salvatore Emanuele Ravenna, Antonella Lombardo, Francesco Burzotta, Dario Pitocco and Nadia Aspromonte
Int. J. Mol. Sci. 2025, 26(12), 5651; https://doi.org/10.3390/ijms26125651 - 12 Jun 2025
Cited by 4 | Viewed by 2194
Abstract
Sodium–glucose cotransporter 2 inhibitors (iSGLT2) have become the fourth pillar of the medical treatment for heart failure with reduced ejection fraction (HFrEF). However, the mechanisms of action of iSGLT2 remain poorly understood. The effectiveness of combined ARNI and iSGLT2 therapy in left ventricular [...] Read more.
Sodium–glucose cotransporter 2 inhibitors (iSGLT2) have become the fourth pillar of the medical treatment for heart failure with reduced ejection fraction (HFrEF). However, the mechanisms of action of iSGLT2 remain poorly understood. The effectiveness of combined ARNI and iSGLT2 therapy in left ventricular (LV) remodeling is still under study. We aim to investigate the effects of ARNI + iSGLT2 combination therapy in patients affected by HFrEF in terms of ventricular remodeling using speckle tracking echocardiography (STE). In this observational study, 136 patients with HFrEF taking ARNI were enrolled. All patients were evaluated at baseline (before iSGLT2), at 3 months and at 12 months from the beginning of iSGLT2 therapy. Echocardiographic parameters, including STE analysis and volumetric and LV contractile function indices, were collected at the three timepoints. The objectives were (1) to evaluate the effects of ARNI + iSGLT2 combination therapy on ultrasound (US) measurements; (2) to evaluate the effects on the variation of laboratory data indicative of HF (NT-pro-BNP); and (3) to evaluate the medium-long term impact of the ARNI + iSGLT2 combination therapy in terms of major cardiovascular events (MACVE). After only three months of combined ARNI + iSGLT2 therapy, we reported a significant improvement in ventricular and atrial volumetric indices, systolic function indices and myocardial deformation parameters assessed by STE. We also reported a significant decrease in NTproBNP levels. This trend was confirmed at 12 months follow-up. Furthermore, narrowing down the analysis to patients who were already treated with ARNI when they started taking iSGLT2, we reported similar results in the improvement of US parameters and NTproBNP levels. Our study has shown that the ARNI + iSGLT2 combination therapy leads to a clinical improvement and positive ventricular remodeling. Even the single introduction of additional iSGLT-2 in HFrEF patients on an otherwise optimized therapy resulted in a significant improvement in US and laboratory variables. The results of our study suggest implementing iSGLT-2 therapy as soon as possible, as the structural and functional cardiac improvements achieved by these drugs are achieved in the short term and maintained in the long term. Full article
(This article belongs to the Special Issue Molecular Insights into Heart Failure: From Bench to Bedside)
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Review

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29 pages, 623 KB  
Review
Biomarkers for Screening and Diagnosis of Heart Failure in Cardiovascular–Kidney–Metabolic Syndrome: A Narrative Review
by Anda-Maria Pintea, Ioan-Alexandru Minciună and Dana Pop
Int. J. Mol. Sci. 2026, 27(5), 2462; https://doi.org/10.3390/ijms27052462 - 7 Mar 2026
Viewed by 768
Abstract
Cardiovascular–kidney–metabolic syndrome is a novel concept defined by the American Heart Association, highlighting the complex interactions between the cardiovascular system, kidney function and metabolic risk factors. Poor cardiovascular–kidney–metabolic health is increasingly prevalent worldwide, giving rise to a need to optimize early detection of [...] Read more.
Cardiovascular–kidney–metabolic syndrome is a novel concept defined by the American Heart Association, highlighting the complex interactions between the cardiovascular system, kidney function and metabolic risk factors. Poor cardiovascular–kidney–metabolic health is increasingly prevalent worldwide, giving rise to a need to optimize early detection of cardiovascular dysfunction. Heart failure is one of the most prevalent forms of cardiovascular disease in patients with chronic kidney disease and metabolic risk factors, but screening and diagnostic strategies remain challenging. Current guidelines endorse the use of prediction scores, as well as a biomarker-based strategy in patients at increased risk. Despite evidence supporting the use of biomarkers such as natriuretic peptides, there are considerable limitations to their use in the setting of cardiovascular–kidney–metabolic syndrome. Moreover, there is mounting evidence supporting the use of other biomarkers reflecting underlying mechanisms leading to heart failure. The aim of this review is to assess current approaches to screening for and diagnosing heart failure in cardiovascular–kidney–metabolic syndrome, highlighting the strengths and pitfalls of gold-standard and emerging biomarkers, while also addressing gaps in evidence and future research directions. Validation of screening biomarkers and development of multimarker prediction scores could impact clinical practice and reduce the growing morbidity and mortality in cardiovascular–kidney–metabolic syndrome. Full article
(This article belongs to the Special Issue Molecular Insights into Heart Failure: From Bench to Bedside)
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28 pages, 1218 KB  
Review
Potential Biomarker and Therapeutic Tools for Pathological Cardiac Hypertrophy and Heart Failure: Extracellular Vesicles
by Jinpeng Sun, Dongli Zhou and Min Cheng
Int. J. Mol. Sci. 2026, 27(1), 95; https://doi.org/10.3390/ijms27010095 - 22 Dec 2025
Cited by 3 | Viewed by 1240
Abstract
Cardiovascular disease remains the leading global cause of death. Pathological cardiac hypertrophy is a key precursor to heart failure (HF), a condition with high morbidity and mortality. Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, carrying bioactive cargoes that reflect [...] Read more.
Cardiovascular disease remains the leading global cause of death. Pathological cardiac hypertrophy is a key precursor to heart failure (HF), a condition with high morbidity and mortality. Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, carrying bioactive cargoes that reflect cellular state and influence recipient cell function. This review provides a focused and integrative perspective distinct from broader overviews, by dissecting the dynamic, cell-type-specific roles of EVs across the continuum from pathological hypertrophy to overt HF. We critically synthesize evidence on how EVs derived from cardiomyocytes, fibroblasts, immune cells, and adipocytes orchestrate maladaptive remodeling. Furthermore, we evaluate their dual utility as emerging diagnostic biomarkers and as engineerable therapeutic vectors. By highlighting recent advances in EV engineering for targeted delivery and discussing persistent translational challenges, this article offers a unique mechanistic-to-translational viewpoint aimed at advancing the therapeutic application of EVs in cardiovascular medicine. Full article
(This article belongs to the Special Issue Molecular Insights into Heart Failure: From Bench to Bedside)
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