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Biomedicines
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Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition
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Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 3740

Special Issue Editor

Dr. Anand Prakash Singh

E-Mail Website
Guest Editor
Institute for Heart and Brain Health, University of Michigan, Ann Arbor, MI, USA
Interests: cardiotoxicity; cardio oncology; heart failure; pharmacovigilance; targeted therapy; protein kinase inhibitors; cardiac inflammation; immune checkpoint inhibitors; cell junctions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Heart failure is a complex disease that is influenced by several causes and sophisticated pathophysiological pathways. Regrettably, its occurrence is steadily increasing in a concerning manner. Effective therapy of this condition heavily relies on existing treatments. However, the situation has changed, making traditional procedures insufficient. To effectively manage and reduce the impact of heart failure, a comprehensive and interdisciplinary approach is required that includes addressing multiple aspects of the condition. The advancement of heart failure therapy involves investigating unexplored areas, such as molecular, cellular, biomaterial, and genetic pathways, in order to develop more efficient treatments. However, achieving a comprehensive therapy regimen requires conducting thorough and high-quality basic research and clinical investigations. These efforts not only confirm the safety and effectiveness of proposed treatments but also establish a stronger and more dependable method for addressing this difficult condition. In this Special Issue, we seek the submission of basic and translational studies that provide a rationale for new heart failure treatments. This Special Issue will also consider studies that show the potential cardiotoxic effects of treatment regimens for other disease conditions that impact heart function.

Dr. Anand Prakash Singh
Guest Editor

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Keywords

  • heart failure
  • clinical treatment
  • basic cardiac research
  • future perspective
  • heart failure therapy
  • cardiotoxicity

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Published Papers (5 papers)

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Research

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18 pages, 524 KB  
Article
Relative Contributions of Functional Capacity and Inflammatory Activity to Quality of Life in Heart Failure with Preserved Ejection Fraction
by Vladimir Zdravković, Đorđe Stevanović, Goran Davidović, Ivan Simić, Marijana Stanojević-Pirković, Željko Ivošević, Nina Uraković, Lidija Stojanović, Isidora Stanković, Neda Ćićarić, Sara Milojević, Mladen Maksić, Katarina Radojević and Marija Popović
Biomedicines 2026, 14(6), 1270; https://doi.org/10.3390/biomedicines14061270 - 2 Jun 2026
Viewed by 287
Abstract
Background/Objectives: Impaired quality of life (QoL) represents one of the most important clinical determinants in heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the incremental explanatory value of functional performance and inflammatory biomarkers for QoL in a clinically [...] Read more.
Background/Objectives: Impaired quality of life (QoL) represents one of the most important clinical determinants in heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the incremental explanatory value of functional performance and inflammatory biomarkers for QoL in a clinically stable HFpEF cohort. Methods: A single-center observational study enrolled 110 consecutive patients with stable HFpEF. Functional capacity was assessed using the six-minute walk test (6MWT), expressed mainly as percentage of predicted distance. Health-related QoL was measured using the EQ-5D-5L utility index (primary outcome). Circulating IL-6, CRP, and NT-proBNP were obtained from peripheral blood. Hierarchical multivariable linear regression was applied to quantify the incremental contribution of clinical variables, functional capacity, and biomarkers. Results: The median age was 72 years, and 52.7% of the participants were women. The median 6MWT distance was 340 m (75.9% of predicted), and the median EQ-5D index was 0.76. The baseline clinical regression model (age, sex, atrial fibrillation, and glomerular filtration rate) explained 23.5% of EQ-5D variance. The addition of functional capacity increased explained variance to 45.2% (ΔR2 = +0.217). The inclusion of IL-6 and NT-proBNP provided a modest additional increase (R2 = 0.468; ΔR2 = +0.042 in addition to Model 2). In the fully adjusted model, functional capacity (β = 0.376, p < 0.001) and IL-6 (β = −0.185, p < 0.05) remained independent predictors, whereas NT-proBNP lost significance. Conclusions: In stable HFpEF, objective functional capacity represents the dominant determinant of QoL, while inflammatory activation provides an independent but smaller contribution. Functional assessment may therefore be central to patient-centered phenotyping and therapeutic targeting. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition)
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14 pages, 456 KB  
Article
Cross-Sectional Associations Between Skeletal Muscle Measurements, Myostatin, and MicroRNA-133a in Heart Failure Patients Undergoing Cardiac Rehabilitation
by Kevin Triangto, Bambang B. Siswanto, Tresia F. U. Tambunan, Teuku Heriansyah, Alida R. Harahap, Aria Kekalih, Hajime Katsukawa, Anwar Santoso and Basuni Radi
Biomedicines 2026, 14(6), 1243; https://doi.org/10.3390/biomedicines14061243 - 29 May 2026
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Abstract
Background: Skeletal myopathy is a common complication of heart failure (HF), contributing to exercise intolerance and impaired physical function. This study explores the relationship between practical skeletal muscle measurements and key biomarkers in HF patients undergoing cardiac rehabilitation. Methods: Sixty-nine stable chronic HF [...] Read more.
Background: Skeletal myopathy is a common complication of heart failure (HF), contributing to exercise intolerance and impaired physical function. This study explores the relationship between practical skeletal muscle measurements and key biomarkers in HF patients undergoing cardiac rehabilitation. Methods: Sixty-nine stable chronic HF patients participated in a 3-month phase II cardiac rehabilitation program. Physical examinations, including the 6-Minute Walk Test (6MWT), chest expansion, inspiratory diaphragm thickness, and handgrip strength, were conducted. Blood samples were analyzed for myostatin and miRNA-133a. Data were analyzed using paired t-tests, Wilcoxon tests, Chi-square/Fisher’s exact tests, and correlation analyses. Results: Significant improvements were observed in 6MWT distance, chest expansion, and inspiratory diaphragm thickness following rehabilitation (p < 0.001). Handgrip strength also significantly improved post-rehabilitation. Myostatin and miRNA-133a levels did not change significantly post-rehabilitation. However, exploratory cross-sectional analysis revealed trends suggesting that lower myostatin levels correlated with better endurance (p = 0.036), while higher myostatin levels were also observed in patients with better 6MWT performance (p = 0.014). Higher miRNA-133a levels were potentially associated with better overall fitness, including endurance and respiratory function (p < 0.05). Conclusions: Readily performed physical assessments can serve as clinical indicators of the systemic impact of HF on skeletal muscle. The study highlights the importance of evaluating extracardiac function in HF patients, demonstrating potential exploratory associations between physical function and key biomarkers. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition)
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18 pages, 6031 KB  
Article
Guideline-Directed Medical Therapy Intensity, Ventricular Remodeling, and Clinical Outcomes After Acute Myocardial Infarction: A Single-Center Real-World Retrospective Cohort Study
by Teodora Mateoc-Sîrb, Ioana-Maria Suciu, Dan Gaiță, Andor Minodora, Roxana Popescu, Tania Vlad, Călin Muntean and Daliborca-Cristina Vlad
Biomedicines 2026, 14(5), 1067; https://doi.org/10.3390/biomedicines14051067 - 8 May 2026
Viewed by 647
Abstract
Background: Guideline-directed medical therapy (GDMT) is recommended after acute myocardial infarction (AMI), particularly in patients with left ventricular systolic dysfunction, yet real-world implementation remains suboptimal. Whether greater early GDMT intensity is associated with post-infarction ventricular remodeling has not been fully established. We aimed [...] Read more.
Background: Guideline-directed medical therapy (GDMT) is recommended after acute myocardial infarction (AMI), particularly in patients with left ventricular systolic dysfunction, yet real-world implementation remains suboptimal. Whether greater early GDMT intensity is associated with post-infarction ventricular remodeling has not been fully established. We aimed to quantify the guideline-to-practice gap and evaluate the association between GDMT intensity, cardiac remodeling, and clinical outcomes after AMI. Methods: In this single-center retrospective cohort study, 186 consecutive patients hospitalized for AMI who underwent successful percutaneous coronary intervention and had baseline plus follow-up transthoracic echocardiography were included. GDMT intensity was defined as the number of prescribed foundational therapy classes at discharge (renin–angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter 2 inhibitors; range 0–4). The primary endpoint was change in left ventricular end-diastolic diameter (ΔLVEDD). Secondary endpoints included changes in left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular mass, and heart failure rehospitalization. Multivariable models adjusted for relevant clinical covariates were applied. Results: Only 18.8% of the overall cohort and 26.2% of patients with baseline left ventricular ejection fraction ≤ 40% received all four GDMT pillars. A graded association was observed between higher GDMT intensity and more favorable remodeling. In adjusted analyses, each additional GDMT pillar was associated with a greater reduction in LVEDD (β = 0.120 cm, p = 0.004). In the prespecified reduced-ejection-fraction subgroup, the association was stronger (β = 0.204 cm, p < 0.001). Higher GDMT intensity was also associated with lower odds of heart failure rehospitalization (odds ratio 0.384, 95% CI 0.195–0.754; p = 0.006). Conclusions: In this real-world post-AMI cohort, broader implementation of foundational GDMT at discharge was associated with more favorable early ventricular reverse remodeling and lower odds of heart failure rehospitalization. These findings highlight a persistent implementation gap and support prospective studies evaluating rapid comprehensive GDMT initiation after AMI. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition)
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10 pages, 684 KB  
Article
Percutaneous Temporary Mechanical Circulatory Support as a Bridge to Heart Transplantation in the Current UNOS Allocation System
by Rohan Goswami, Jose Ruiz, Aarti Desai, Peter Wlodkowski, Basar Sareyyupoglu, Sean Kiley, Anirban Bhattacharyya, Daniel Yip, Melissa Lyle, Jose Nativi-Nicolau, Juan Leoni, Devang Sanghavi, Alfredo Quiñones-Hinojosa, Sanjay Chaudhary, Kevin Landolfo, Si Pham and Parag Patel
Biomedicines 2025, 13(11), 2637; https://doi.org/10.3390/biomedicines13112637 - 28 Oct 2025
Cited by 1 | Viewed by 1218
Abstract
Background: Progressive heart failure cardiogenic shock (HFCS) often requires escalation to temporary or durable mechanical circulatory support (MCS) as a bridge to transplant (BTT). Following the 2018 UNOS allocation changes, our center revised its BTT strategy to optimize support and shorten wait [...] Read more.
Background: Progressive heart failure cardiogenic shock (HFCS) often requires escalation to temporary or durable mechanical circulatory support (MCS) as a bridge to transplant (BTT). Following the 2018 UNOS allocation changes, our center revised its BTT strategy to optimize support and shorten wait times. At our institution, the Impella 5.5 with SmartAssist via the axillary approach was selectively used for patients who remained refractory to guideline-directed medical therapy, failed single-inotrope therapy, and were not considered suitable durable LVAD candidates by our multidisciplinary heart team. We compared transplant-related outcomes of BTT patients supported with Impella 5.5 versus durable LVAD. Methods: We performed a single-center retrospective review of all heart and heart/kidney transplant candidates at Mayo Clinic Florida from October 2018 to February 2021. INTERMACS profile, baseline characteristics, and perioperative data were collected at the time of device implantation and throughout the transplant hospitalization. Results: A total of 87 heart and 4 heart–kidney transplants were completed. Forty-five patients (49%) required MCS as BTT: 27 (60%) with a durable LVAD and 18 (40%) with an Impella 5.5. All eighteen patients with Impella 5.5 as BTT (100%) were transplanted compared to nineteen patients with durable LVAD (70%), p = 0.001. The median time from listing to transplant was substantially shorter with Impella (32 vs. 696 days, p < 0.001), and this difference persisted across INTERMACS profiles. UNOS status at transplant was more urgent for Impella than LVAD (p < 0.001). Transplant surgery following Impella support required shorter cardiopulmonary bypass time (181 vs. 219 min, p < 0.001) and resulted in lower postoperative vasoactive-inotropic requirements (7.9 vs. 13, p = 0.003). No patients in the Impella group died or were delisted while awaiting transplant, whereas 5 LVAD patients (26%) died or were removed due to LVAD complications (p < 0.001). Conclusions: Our data demonstrates that the use of the Impella 5.5 as BTT was associated with significantly shorter waitlist time, higher transplantation rates, reduced perioperative morbidity, and lower postoperative vasoactive support compared with durable LVAD as BTT. These benefits were achieved despite a higher severity of illness at transplantation in the Impella cohort. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition)
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Review

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25 pages, 626 KB  
Review
Gut Microbiota-Derived Trimethylamine N-Oxide and NT-proBNP in Heart Failure: A Critical Review of Diagnostic and Prognostic Value
by Natalia Anna Suchecka, Patrycja Popławska, Patrycja Obrycka, Agnieszka Frątczak, Ewa Tokarz, Julia Soczyńska and Sławomir Woźniak
Biomedicines 2026, 14(2), 287; https://doi.org/10.3390/biomedicines14020287 - 28 Jan 2026
Viewed by 945
Abstract
Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide [...] Read more.
Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is frequently affected by non-cardiac physiological variables, including adiposity, advanced age, and renal clearance rates. Consequently, there is a compelling need for additional biomarkers. This analysis investigates TMAO as a critical mediator within the gut–heart axis, reflecting systemic inflammation and myocardial fibrosis secondary to intestinal dysbiosis. Methods: A comprehensive literature search was conducted using PubMed. Keywords such as “trimethylamine N-oxide”, “heart failure”, “heart failure with preserved ejection fraction” and “N-terminal pro-B-type natriuretic peptide” were used. The inclusion criteria comprised original research and literature reviews describing the pathophysiological mechanisms and clinical utility of TMAO in the context of HF diagnosis and prognosis. Results: The analyzed literature suggests that TMAO functions as an independent predictor of major adverse cardiovascular events, correlating with all-cause mortality and rehospitalization risk across all HF phenotypes. Furthermore, data indicate that using TMAO alongside NT-proBNP measurements may predict patient risk more accurately, particularly in patients where natriuretic peptide interpretation is traditionally obscured by comorbidities such as diabetes mellitus and chronic kidney disease. Conclusions: Although NT-proBNP remains the gold standard for acute diagnosis, TMAO provides significant value for long-term clinical management. By serving as a metabolic–inflammatory indicator, TMAO complements standard diagnostic panels, offering deeper insights into the prognostic trajectory and the underlying intestinal barrier integrity of patients with HF. Full article
(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches, 2nd Edition)
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