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Heart Failure: New Diagnostic and Therapeutic Approaches

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

Deadline for manuscript submissions: 31 July 2025 | Viewed by 11576

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Dr. Anand Prakash Singh

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Institute for Heart and Brain Health, University of Michigan, Ann Arbor, MI 48109, USA
Interests: cardiotoxicity; cardio oncology; heart failure; pharmacovigilance; targeted therapy; protein kinase inhibitors; cardiac inflammation; immune checkpoint inhibitors; cell junctions

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 relies heavily 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, which 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 are seeking basic and translational studies providing rationale for new treatments for heart failure. This Special Issue will also consider studies showing 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 (9 papers)

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Research

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15 pages, 1487 KiB

Open AccessArticle

The Effect of Early Spironolactone Administration on 2-Year Acute Graft Rejection in Cardiac Transplant Patients

by Dragos-Florin Baba, Alina Danilesco, Horatiu Suciu, Calin Avram, Marius Mihai Harpa, Mircea Stoian, Diana-Andreea Moldovan, Laurentiu Huma, Gabriel Rusu, Tunde Pal, Adina Stoian and Anca-Ileana Sin

Biomedicines 2025, 13(5), 1164; https://doi.org/10.3390/biomedicines13051164 - 10 May 2025

Viewed by 274

Abstract

Background: The objective of our study was to investigate the impact of mineralocorticoid receptor antagonists (MRAs), such as spironolactone, administrated early after cardiac transplantation on the occurrence of acute graft rejection (AGR) in the first 2 years post-transplant. Methods: This retrospective research was conducted in the Emergency Institute for Cardiovascular Diseases and Transplantation of Targu Mures, Romania. After applying the inclusion criteria, between January 2011 and December 2023, 36 patients fit the study design. Using Cox proportional hazards regression and Kaplan–Meier curves, we determined the time-to-event distribution, for which the first episode of AGR was considered an event, with a significance threshold of 0.05. Results: The 1-year rate of AGR was 38.9% and was 47.2% at 2 years, with a 2-year mortality of 11.1%. The interpretation of the Cox regression indicated that early initiation of spironolactone represents a protective factor against the 2-year AGR (HR: 0.263; 95%CI: 0.076–0.922; p = 0.037 by the log-rank test). Conclusions: These results might suggest a possible benefit of the early administration of spironolactone after a heart transplant, but further prospective studies need to be performed for the validation of our findings. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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11 pages, 1222 KiB

Open AccessArticle

The Effect of Pulmonary Hypertension on Renal Function Dynamics in Left-Heart Failure Patients

by Robert Dragu, Adrian Abramovici and Kasem Abu Zeid

Biomedicines 2025, 13(3), 684; https://doi.org/10.3390/biomedicines13030684 - 10 Mar 2025

Viewed by 590

Abstract

Objectives: Cardiorenal syndrome (CRS) is a complex disorder characterized by concurrent dysfunction of the heart and kidneys, with their detrimental effects perpetuating a bidirectional cycle. This study aimed to examine the clinical and hemodynamic factors associated with changes in renal function in patients with pulmonary hypertension (PH) secondary to chronic heart failure (HF). Methods: A total of 108 patients with HF were evaluated using right-heart catheterization. Results: 75 patients (69.4%) were diagnosed with PH. The mean baseline estimated GFR (beGFR) was similar in noPH (64 ± 21 mL/min/1.73 m²) and PH group (63 ± 23 mL/min/1.73 m²) (p = 0.71). After a median follow-up of 7 months, the last eGFR (leGFR) in the noPH and PH groups was comparable (49 ± 24 vs. 52 ± 25 mL/min/1.73 m² respectively; p = 0.62). However, in the PH group, for patients with baseline Cr (bCr) < 1.5 mg/dL, the reduction in eGFR showed a graded inverse relationship to serum creatinine, as compared with bCr ≥ 1.5 mg/dL, for whom beGFR and leGFR demonstrated large overlap. In a multivariable regression analysis, the primary independent predictors of leGFR were baseline creatinine, age, diabetes mellitus, left ventricular ejection fraction below 45%, and use of mineralocorticoids antagonists. The model explained 66% of the variance in leGFR. Conclusions: In a cohort of left HF and PH, an inverse non-linear and graded association between the baseline serum creatinine levels and the variation in estimated GFR was demonstrated, contrary to those without PH, for whom this relationship was linear and constant. The distinct patterns of GFR decline influenced by age, low ejection fraction, diabetes, and mineralocorticoid underscore the need for individualized treatment strategies. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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17 pages, 2761 KiB

Open AccessArticle

Structured Cardiac Assessment and Treatment Following Exacerbations of COPD (SCATECOPD): A Pilot Randomised Controlled Trial

by Joseph Kibbler, Eduwin Pakpahan, Stephen McCarthy, Rebecca Webb-Mitchell, Arun Prasad, David P. Ripley, Joanne Gray, Stephen C. Bourke and John Steer

Biomedicines 2025, 13(3), 658; https://doi.org/10.3390/biomedicines13030658 - 7 Mar 2025

Viewed by 758

Abstract

Background/Objectives: Heart disease is common in COPD, yet it is underdiagnosed and undertreated. Heart failure (HF) is undiagnosed in up to 20% of hospital inpatients. Hospitalised exacerbations of COPD (ECOPD) confer high mortality and readmission rates, with an elevated temporal cardiac risk. We performed a pilot randomised controlled trial examining the feasibility and effect of inpatient structured cardiac assessment (SCA) to diagnose and prompt guideline-recommended treatment of heart disease. Methods: A total of 115 inpatients with ECOPD were randomised 1:1 to receive usual care (UC) or SCA, comprising transthoracic echocardiography, CT coronary artery calcium scoring, 24 h ECG, blood pressure, and diabetes assessment. Follow-up was for 12 months. The prevalence of underdiagnosis and undertreatment of heart disease were captured, and potential outcome measures for future trials assessed. Results: Among patients undergoing SCA, 42/57 (73.7%) received a new cardiac diagnosis and 32/57 (56.1%) received new cardiac treatment, compared with 11/58 (19.0%; p < 0.001) and 5/58 (8.6%; p < 0.001) in the UC group. More patients in the SCA group were newly diagnosed with HF (36.8% vs. 12.1%; p = 0.002). When heart disease was diagnosed, the proportion receiving optimal treatment at discharge was substantially higher in SCA (35/47 (74%) vs. 4/11 (34%); p = 0.029). The occurrence of a major adverse cardiovascular event (MACE) showed promise as an appropriate clinical outcome for a future definitive trial. MACEs occurred in 17.2% in usual care vs. 10.5% in SCA in one year, with a continued separation of survival curves during follow up, although statistical significance was not shown. Conclusions: A structured cardiac assessment during ECOPD substantially improved diagnosis and treatment of heart disease. HF and coronary artery disease were the most common new diagnoses. Future interventional trials in this population should consider MACEs as the primary outcome. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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16 pages, 1257 KiB

Open AccessArticle

Acupuncture and Kinesitherapy Improve Physical Activity More than Kinesitherapy Alone in Patients with Acute Decompensated Chronic Heart Failure with Reduced Ejection Fraction Who Are Already on Optimal Drug Therapy: A Randomized, Sham-Controlled, Double-Blind Clinical Study

by Dejan Ilic, Zoran Jovic, Zorica Mladenovic, Vesna Pejovic, Branislava Lung, Aleksandra Kozic and Slobodan Obradovic

Biomedicines 2025, 13(1), 176; https://doi.org/10.3390/biomedicines13010176 - 13 Jan 2025

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Abstract

Background/Objectives: It is unknown how early exercise therapy combined with acupuncture (AP) affects the speed of recovery in patients suffering from heart failure with reduced ejection fraction (HFrEF) who are hospitalized due to worsening HF. Methods: A prospective, sham-procedure-controlled, double-blind, randomized clinical trial with three patient groups was conducted. The study included patients with HFrEF who were hospitalized for worsening HF. After initial stabilization, patients were randomly assigned to three groups, the controls (C) treated with optimal drug therapy (ODT); E1 received ODT with kinesitherapy, and sham AP; E2 received ODT, kinesitherapy, and needle AP aiming to enhance compensation. Improvement in physical activity was measured by the modified Barthel index (A test), 2 or 6 min walking tests, an endurance walking test, and decrease of blood brain natriuretic peptide (BNP). Results: A total of 120 patients completed the study. The average age was 74 years, 73.3% were male, median EF was 32%, and 83.3% were New York Heart Association (NYHA) Class III. After the fifth day of therapy, the E2 group showed the greatest improvement in the A test compared to other groups (p = 0.022). After 5 days, 80%, 50%, and 10% achieved an A test score of 30 or higher, demonstrating functional independence, (p < 0.01) in the E2, E1, and C groups, respectively. At hospital discharge, the E2 group showed significantly better walking endurance compared to the E1 and C groups (p < 0.001). At discharge, BNP decreased significantly more in both E groups, compared to the C group. Conclusions: Short-term early rehabilitation with AP and kinesitherapy significantly improves the functional status of HFrEF decompensated patients when compared to kinesitherapy alone and ODT. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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14 pages, 4751 KiB

Open AccessArticle

Changes in the Release of Endothelial Extracellular Vesicles CD144+, CCR6+, and CXCR3+ in Individuals with Acute Myocardial Infarction

by Alexa Moreno, Pedro Alarcón-Zapata, Enrique Guzmán-Gútierrez, Claudia Radojkovic, Héctor Contreras, Estefanía Nova-Lampeti, Felipe A. Zúñiga, Llerenty Rodriguez-Alvárez, Carlos Escudero, Paola Lagos and Claudio Aguayo

Biomedicines 2024, 12(9), 2119; https://doi.org/10.3390/biomedicines12092119 - 18 Sep 2024

Viewed by 1086

Abstract

Acute myocardial infarction (AMI) results from vulnerable plaque rupture, causing ischemic cardiomyocyte necrosis and intense inflammation. Paradoxically, this inflammation releases factors that aid heart repair. Recent findings suggest a role for extracellular vesicles (EVs) in intercellular communication during post-AMI cardiac repair. However, EVs’ tissue origin and chemokine profile in the blood of patients with AMI remains unclear. This study characterized the tissue origin and chemokine receptor profile of EVs in the coronary and peripheral blood of patients with AMI. The results reveal that vesicles isolated from coronary and peripheral blood plasma are enriched in tetraspanin (CD9) and express CD81⁺, CD90⁺, and CD144⁺. The vesicle size ranged between 145 and 162 nm, with the control group exhibiting smaller vesicles (D10) than the AMI group. Furthermore, all vesicles expressed CCR6 and CXCR3, whereas a small percentage expressed CCR4. In addition, a decrease in CXCR3 and CCR6 expression was observed in coronary and peripheral AMI blood vesicles compared with the control; however, no difference was found between AMI coronary and AMI peripheral blood vesicles. In conclusion, our study demonstrates, for the first time, changes in the number of extracellular vesicles expressing CD144⁺, CXCR3, and CCR6 in the peripheral circulation of patients with AMI. Extracellular vesicles present in the circulation of patients with AMI hold excellent promise as a potential diagnostic tool. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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11 pages, 2592 KiB

Open AccessArticle

The Impact of Frailty Components and Preoperative Mechanical Cardiac Support Changes with Time after Heart Transplantation

by Rita Szentgróti, Dmitry Khochanskiy, Balázs Szécsi, Flóra Németh, András Szabó, Kinga Koritsánszky, Alexandra Vereb, Zsuzsanna Cserép, Balázs Sax, Béla Merkely and Andrea Székely

Biomedicines 2024, 12(5), 1114; https://doi.org/10.3390/biomedicines12051114 - 17 May 2024

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Abstract

Background: Frailty has been proven to be associated with mortality after orthotopic heart transplantation (OHT). The aim of our study was to determine the impact of frailty on mortality in the current era using pretransplant mechanical cardiac support (MCS). Methods: We retrospectively calculated the frailty scores of 471 patients undergoing OHT in a single institution between January 2012 and August 2022. The outcome was all-cause mortality. Results: The median survival time was 1987 days (IQR: 1487 days) for all patients. In total, 266 (56.5%) patients were categorized as nonfrail, 179 (38.0%) as prefrail, and 26 (5.5%) as frail. The survival rates were 0.73, 0.54, and 0.28 for nonfrail, prefrail, and frail patients, respectively. The frailty score was associated with mortality [HR: 1.34 (95% CI: 1.22–1.47, p < 0.001)]. Among the components of the frailty score, age above 50 years, creatinine ≥ 3.0 mg/dL or prior dialysis, and hospitalization before OHT were independently associated with mortality. Continuous-flow left ventricular assist devices (CF-LVAD) were associated with an increased risk for all-cause mortality [AHR: 1.80 (95% CI: 1.01–3.24, p = 0.047)]. Conclusions: The components of the frailty score were not equally associated with mortality. Frailty and pretransplant MCS should be included in the risk estimation. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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13 pages, 481 KiB

Open AccessArticle

Effect of SGLT2-Inhibitors on Polygraphic Parameters in Elderly Patients Affected by Heart Failure, Type 2 Diabetes Mellitus, and Sleep Apnea

by Giuseppe Armentaro, Corrado Pelaia, Valentino Condoleo, Giandomenico Severini, Giulia Crudo, Mario De Marco, Carlo Alberto Pastura, Valeria Tallarico, Rita Pezzella, Domenico Aiello, Sofia Miceli, Raffaele Maio, Gianluigi Savarese, Giuseppe M. C. Rosano and Angela Sciacqua

Biomedicines 2024, 12(5), 937; https://doi.org/10.3390/biomedicines12050937 - 23 Apr 2024

Cited by 4 | Viewed by 1939

Abstract

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t-test and Mann–Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO₂ improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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15 pages, 549 KiB

Open AccessArticle

Unraveling the Predictors for Delirium and ICU Stay Duration in Patients with Heart Failure and Reduced Ejection Fraction (HFrEF) Undergoing Coronary Artery Bypass Grafting—A Multicentric Analysis

by Christian Jörg Rustenbach, Stefan Reichert, Rafal Berger, Julia Schano, Attila Nemeth, Helene Haeberle, Christophe Charotte, Tulio Caldonazo, Ibrahim Saqer, Shekhar Saha, Philipp Schnackenburg, Ilija Djordjevic, Ihor Krasivskyi, Stefanie Wendt, Lina Maria Serna-Higuita, Torsten Doenst, Christian Hagl, Thorsten Wahlers, Christian Schlensak and Rodrigo Sandoval Boburg

Biomedicines 2024, 12(4), 749; https://doi.org/10.3390/biomedicines12040749 - 28 Mar 2024

Viewed by 1609

Abstract

Objective: This study assesses predictors for postoperative delirium (POD) and ICU stay durations in HFrEF patients undergoing CABG, focusing on ONCAB versus OPCAB surgical methods. Summary Background Data: In cardiac surgery, especially CABG, POD significantly impacts patient recovery and healthcare resource utilization. With varying incidences based on surgical techniques, this study provides an in-depth analysis of POD in the context of HFrEF patients, a group particularly susceptible to this complication. Methods: A retrospective analysis of 572 patients who underwent isolated CABG surgery with a preoperative ejection fraction under 40% was conducted at four German university hospitals. Patients were categorized into ONCAB and OPCAB groups for comparative analysis. Results: Age and Euro Score II were significant predictors of POD. The ONCAB group showed higher incidences of re-sternotomy (OR: 3.37), ECLS requirement (OR: 2.29), and AKI (OR: 1.49), whereas OPCAB was associated with a lower incidence of delirium. Statistical analysis indicated a significant difference in ICU stay durations between the two groups, influenced by surgical complexity and postoperative complications. Conclusions: This study underscores the importance of surgical technique in determining postoperative outcomes in HFrEF patients undergoing CABG. OPCAB may offer advantages in reducing POD incidence. These findings suggest the need for tailored surgical decisions and comprehensive care strategies to enhance patient recovery and optimize healthcare resources. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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Review

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13 pages, 3959 KiB

Open AccessReview

Diagnostic and Therapeutic Approaches for Heart Failure in Long-Term Survivors of Childhood Cancer

by Consuelo Fernandez-Aviles, Rafael Gonzalez-Manzanares, Soledad Ojeda, Juan C. Castillo, Ainhoa Robles-Mezcua, Manuel Anguita, Dolores Mesa and Manuel Pan

Biomedicines 2024, 12(8), 1875; https://doi.org/10.3390/biomedicines12081875 - 16 Aug 2024

Viewed by 1124

Abstract

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies. This review aims to summarize the latest findings in the diagnosis and treatment of cancer therapy-related cardiac disease in long-term survivors of childhood cancer, with a focus on heart failure. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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