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Advanced Research on Heart Failure and Heart Transplantation

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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 December 2025 | Viewed by 8271

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Dr. Nandan Kumar Mondal

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Michael E. DeBakey Department of Surgery, Division of Cardiothoracic Transplantation and Circulatory Support, Baylor College of Medicine, Houston, TX 77030, USA
Interests: cardiothoracic transplantation; organ care system; heart failure and mechanical circulatory support; non-physiological high shear stress; extracorporeal membrane oxygenation; robotic-assisted minimally invasive cardiac surgery; cardiopulmonary bypass

Special Issue Information

Dear Colleagues,

This Special Issue explores the critical advancements and ongoing challenges in heart failure, particularly focusing on heart transplantation and organ donation. As the prevalence of heart failure rises globally, innovative strategies in donor selection and preservation techniques become increasingly vital. We invite contributions that delve into various aspects of heart transplantation, including the implications of donation after brain death (DBD) and donation after cardiac death (DCD), as well as the impact of ischemic time on donor heart viability. Furthermore, we encourage authors to discuss the complexities of reperfusion injury and myocardial damage, highlighting emerging research and clinical practices to minimize graft failure. We welcome studies investigating the molecular mechanisms underlying transplant rejection, cellular interactions within the transplanted organ, and innovations in molecular therapy and regenerative medicine on heart transplant outcomes. The role of post-transplant care in improving patient outcomes will also be a central theme, fostering a comprehensive understanding of the transplantation process. Ultimately, this Special Issue seeks to provide a platform for researchers, clinicians, and healthcare professionals to share innovative ideas, recent findings, and collaborative approaches that can enhance the effectiveness of heart transplantation and address the pressing needs in managing heart failure.

Dr. Nandan Kumar Mondal
Guest Editor

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Keywords

heart failure
heart transplantation
DBD (donation after brain death)
DCD (donation after cardiac death)
cardiac arrest
ischemic time and reperfusion injury
myocardial damage
preservation techniques
post-transplant outcomes

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Published Papers (8 papers)

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15 pages, 956 KB

Open AccessArticle

Personalized Response to Empagliflozin in Heart Failure: Association of BDNF and ATP2A2 Variants in a South Asian Cohort

by Qura Tul Ain, Abida Shaheen, Umer Ijaz, Sagheer Ahmed, Muhammad Usman, Mushood Ahmed, Muhammad Ali, Fahad Azam, Asaad Akbar Khan, Ali Hasan and Raheel Ahmed

Biomedicines 2025, 13(9), 2095; https://doi.org/10.3390/biomedicines13092095 - 28 Aug 2025

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Abstract

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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10 pages, 223 KB

Open AccessArticle

Cardiogenic Shock Due to Progressive Heart Failure—Clinical Characteristics and Outcomes Compared to Other Aetiologies

by Dominik Krupka, Michał Fułek, Julia Drewniowska, Kamila Florek, Mateusz Milewski, Michał Nnoli, Katarzyna Grunwald, Adam Chełmoński, Karolina Karska, Kacper Cicirko, Katarzyna Mazur, Jakub Ptak, Mikołaj Błaziak, Robert Zymliński, Waldemar Goździk, Barbara Barteczko-Grajek, Maciej Bochenek, Roman Przybylski, Michał Zakliczyński, Mateusz Sokolski and Wiktor Kuliczkowski Show full author list Hide full author list

Biomedicines 2025, 13(8), 1856; https://doi.org/10.3390/biomedicines13081856 - 30 Jul 2025

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Abstract

Background: The prevalence of cardiogenic shock (CS) resulting from the progression of heart failure (PHF) is increasing and remains associated with high mortality. This study aimed to compare the clinical characteristics and outcomes of patients who developed CS due to PHF versus those whose CS was caused by other aetiologies (non-PHF). Methods: We retrospectively analysed 280 patients admitted to a Polish tertiary care centre between January 2021 and April 2024. The cohort was divided into two groups: PHF (n = 84, 30%) and non-PHF (n = 196, 70%). Results: Compared to the non-PHF group, PHF patients more frequently had chronic kidney disease (30% vs. 15%, p < 0.01), and significant valvular disease (30% vs. 13%, p < 0.01). PHF patients exhibited significantly lower white blood cell counts (9.4 [6.9–16.4] vs. 13.3 [10.4–17.6], p < 0.01) and troponin T levels (188 [61–1392] vs. 10,921 [809–45,792], p < 0.01). In-hospital mortality was significantly lower among PHF patients (52% vs. 65%, p = 0.04). Although the overall use of mechanical circulatory support (MCS) did not differ between groups, significant differences in the types of MCS applied were observed (p < 0.01). Additionally, PHF patients underwent fewer coronary revascularisation procedures (15% vs. 70%, p < 0.01). Conclusions: Patients with PHF-related CS exhibit distinct clinical profiles and may experience lower in-hospital mortality when appropriately diagnosed and treated with a personalised approach. Further prospective, multicentre studies are warranted to optimize the management of this growing subgroup of CS patients. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

13 pages, 762 KB

Open AccessArticle

Implementation of Medical Therapy in Different Stages of Heart Failure with Reduced Ejection Fraction: An Analysis of the VIENNA-HF Registry

by Noel G. Panagiotides, Annika Weidenhammer, Suriya Prausmüller, Marc Stadler, Georg Spinka, Gregor Heitzinger, Henrike Arfsten, Guido Strunk, Philipp E. Bartko, Georg Goliasch, Christian Hengstenberg, Martin Hülsmann and Noemi Pavo

Biomedicines 2025, 13(8), 1846; https://doi.org/10.3390/biomedicines13081846 - 30 Jul 2025

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Background/Objectives: Real-world evidence shows alarmingly suboptimal utilization of guideline directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). One of the barriers of GDMT implementation appears to be concerns about the potential development of drug-related adverse events (AEs), particularly in high-risk patients. This study aimed to evaluate whether advanced HFrEF (AHF) patients can be up-titrated safely and whether AHF predisposes individuals to the occurrence of putatively drug-related AEs. Methods: A total of 373 HFrEF patients with documented baseline, 2 months, and 12 months visits were analyzed for utilization and target dosages (TDs) of HF drugs. Successful up-titration and AEs were evaluated for different stages of HF reflected by N-terminal pro-B type natriuretic peptide (NT-proBNP) (<1000 pg/mL, 1000–2000 pg/mL, >2000 pg/mL). Results: A stepwise increase in HF medications was observed for all drug classes during follow-up. At 12 months, 73%, 75%, 62%, 86%, and 45% of patients received ≥90% of TDs of beta-blockers (BBs), renin–angiotensin system inhibitors (RASis), mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter-2 inhibitors (SGLT2 i), and triple-therapy, respectively. Predictors of successful up-titration in logistic regression were baseline HF drug TDs, estimated glomerular filtration rate (eGFR), and potassium, but not NT-proBNP or age. The development of AEs was rare, with hyperkalemia as the most common event (34% at 12 months). AEs were comparable in all stages of HF. However, the development of hyperkalemia was more frequent in patients with higher NT-proBNP and also accounted for most cases of incomplete up-titration. Conclusions: This study suggests that with dedicated protocols and frequent visits, GDMT can be successfully implemented across all stages of HFrEF, including patients with AHF. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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12 pages, 846 KB

Open AccessArticle

Beating Heart Coronary Artery Bypass Grafting with Preemptive Impella^™ 5.5 Assist Device in Ischemic Cardiomyopathy

by Francesco Cabrucci, Massimo Baudo, Yoshiyuki Yamashita, Amanda Yakobitis, Courtney Murray and Gianluca Torregrossa

Biomedicines 2025, 13(5), 1259; https://doi.org/10.3390/biomedicines13051259 - 21 May 2025

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Background: Choosing the best surgical approach for coronary revascularization in patients with ischemic cardiomyopathy and low EF is complex. Several strategies have been adopted, including on- and off-pump CABG, the use of IABP, and the combination of ECMO or even LVAD with CABG. Recently, the Impella 5.5 micro-axial pump has been used as perioperative temporary left ventricular support in CABG patients. This study aims to report a series of CABG procedures performed with Impella assistance, highlighting its potential benefits in high-risk surgery cases. Methods: Between January 2023 and December 2024, seven consecutive patients underwent on-pump beating CABG with planned central Impella 5.5 support via a 10 mm graft in the ascending aorta. This study focused on assessing perioperative outcomes in patients with reduced ventricular dysfunction (ejection fraction [EF] < 35%) undergoing CABG with Impella-assisted support. Results: Seven patients were included in the study, with a median age of 70 [IQR 57–74.7], and six were male. Hypertension was present in all patients, diabetes in six, and COPD in two, and two were in dialysis. The median preoperative EF was 20% [IQR, 18–29%], and the median STS PROM was 5.5 [IQR: 2.9–8.9]. One patient had preoperative IABP support. Four patients required intraoperative transfusions, but all remained hemodynamically stable upon OR exit. The Impella was removed after an average of 5.6 ± 2.1 days. One patient underwent surgical revision for bleeding. No strokes, myocardial infarctions, repeat revascularizations, or mortality occurred postoperatively. The median postoperative hospital stay was 21 [IQR, 17.5–22] days, with a discharge EF of 38% [IQR 33.5–38%]. One patient died 6 months after the procedure due to sepsis caused by a gangrenous diabetic leg. Conclusions: This initial experience using Impella 5.5 support in CABG patients with reduced EF demonstrated its feasibility in selected cases. The Impella provided effective circulatory support, ensuring stable hemodynamics throughout the postoperative stay without complications. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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18 pages, 1537 KB

Open AccessArticle

Reduced Expression of UPRmt Proteins HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L Is Associated with Accelerated Heart Failure in Humans

by Petra Bakovic, Vid Mirosevic, Tomo Svagusa, Ana Sepac, Ana Kulic, Davor Milicic, Hrvoje Gasparovic, Igor Rudez, Marjan Urlic, Suncana Sikiric, Sven Seiwerth, Drazen Belina, Matija Bakos, Monika Karija Vlahovic, Rea Taradi, Rado Zic, Ivana Ilic, Borislav Belev, Bosko Skoric, Dora Fabijanovic, Ivo Planinc, Maja Cikes and Filip Sedlic Show full author list Hide full author list

Biomedicines 2025, 13(5), 1142; https://doi.org/10.3390/biomedicines13051142 - 8 May 2025

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Abstract

Background/Objectives: The mitochondrial unfolded protein response (UPRmt) is one of the mitochondrial quality control mechanisms that is responsible for reparation and removal of damaged proteins in mitochondria. Methods: Here we investigated the role of the UPRmt in the myocardium of humans with and without heart failure and in the cell culture model. Results: The analysis of myocardial samples by ELISA from patients with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), as well as healthy donors, revealed a significantly reduced expression of the UPRmt proteins HSP10, CLPP, LONP1, OMA1, and SPG7 in patients with DCM and ICM. Furthermore, patients with DCM and ICM exhibited elevated levels of myocardial reactive oxygen species (ROS, tested by 4-hydroxynonenal) compared to controls, and a positive correlation between ROS production and mt-HSP70, OMA1, and SPG7 protein expression. The correlation analysis indicated a negative correlation between cardiomyocyte hypertrophy and the expression of several UPRmt genes. The inhibition of four tested UPRmt effector proteins exacerbated the injury of cultured cells under oxidative stress. The patients with ICM, DCM, or both, who showed lower myocardial expression of HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L, underwent heart transplantation or implantation of a left ventricular assist device earlier in life compared to those with the higher protein expression. Conclusions: In conclusion, our findings indicate that the reduced expression of several UPRmt effector proteins is associated with accelerated heart failure in patients, which, together with other results, indicates that impaired UPRmt may contribute to the pathogenesis of heart failure in humans. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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12 pages, 862 KB

Open AccessArticle

Prediction of Kidney Function Improvement After Heart Transplantation

by Jakub Ptak, Mateusz Sokolski, Mateusz Wilk, Mateusz Waloszczyk, Kacper Wiśniewski, Dominik Krupka, Paulina Makowska, Magdalena Cielecka, Maciej Szwajkowski, Mateusz Rakowski, Maciej Bochenek, Roman Przybylski and Michał Zakliczyński

Biomedicines 2025, 13(4), 933; https://doi.org/10.3390/biomedicines13040933 - 10 Apr 2025

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Abstract

Background/Objectives: Patients with advanced heart failure (HF) often suffer from impaired kidney function. Based on the pathophysiology of types I and II of cardiorenal syndrome, heart transplantation (Htx) may restore renal function. The aim of this study was to identify predictors of improvement in kidney function after HTx. Methods: Htx patients from a tertiary hospital were retrospectively divided into three groups—improvement (n = 24), deterioration (n = 31) and no significant change in eGFR (n = 45)—based on changes in their mean estimated glomerular filtration rate (eGFR) within the first three postoperative months, compared to the last three preoperative months. The threshold for eGFR improvement was defined as a ≥20% increase, while deterioration was defined as a ≥20% decrease. The no significant change group was defined as any change falling between these two values. Results: The median age of analyzed cohort was 54 (45–63) years, and 82% were male. Preoperatively, the improvement group was more frequently treated with inotropes or vasopressors and had significantly higher blood urea and total bilirubin levels before Htx. In the multivariate analysis, total bilirubin before Htx (OR 1.66; 95% CI; 1.24–2.69; p = 0.002) and no need for RRT early after Htx (OR 0.46; 95% CI 0.24–0.88; p = 0.02) were independent predictors of improved kidney function in the first three months after HTx. Conclusions: The improvement in renal function after HTx is uncommon. It could be expected in patients suffering from more severe forms of HF, with impaired kidney and liver function but who did not need RRT after the surgery. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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12 pages, 4367 KB

Open AccessArticle

Exploring the Potential of Voxel-Mirrored Homotopic Connectivity (VMHC) and Regional Homogeneity (ReHo) in Understanding Cognitive Changes After Heart Transplantation

by Qian Qin, Jia Liu, Wenliang Fan, Xinli Zhang, Jue Lu, Xiaotong Guo, Ziqiao Lei and Jing Wang

Biomedicines 2025, 13(4), 873; https://doi.org/10.3390/biomedicines13040873 - 3 Apr 2025

Viewed by 746

Abstract

Objective: This study aimed to investigate the application value of voxel-mirrored homotopic connectivity (VMHC) and regional homogeneity (ReHo) in evaluating cognitive impairment after heart transplantation. Methods: A total of 68 heart transplant patients and 56 healthy controls were included. ReHo and VMHC were calculated using DPARSF software. A two-sample t-test was applied to compare the differences in ReHo and VMHC between the two groups, and a Pearson correlation analysis was performed by extracting the VMHC and ReHo values of different brain regions and correlating them with cognitive scale scores of the patient groups. Results: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were lower in the heart transplant group than in the control group (MMSE: t = 4.028, p < 0.001; MoCA: t = 4.914, p < 0.001). Compared with the control group, the ReHo values of Frontal_Sup_R (t = −4.422, p < 0.001), Thalamus_L (t = −3.911, p < 0.001), and Calcarine_L (t = −3.640, p < 0.001) were lower in the heart transplantation group, while the ReHo of Temporal_Sup_L was higher (t = 4.609, p < 0.001). VMHC was elevated for bilateral Cerebellum_Crus1 (t = 3.803, p < 0.001) and decreased for bilateral calcarine (t = −3.424, p < 0.001). The ReHo of Frontal_Sup_R was positively correlated with MMSE (r = 0.345, p = 0.004) and MoCA (r = 0.376, p = 0.002). The ReHo of Temporal_Sup_L was also positively correlated with MMSE (r = 0.397, p < 0.001) and MoCA (r = 0.542, p < 0.001). The VMHC of bilateral calcarine showed a positive correlation with MMSE (r = 0.513, p < 0.001) and MoCA (r = 0.398, p < 0.001). Other differential brain regions showed no significant correlation with the MMSE and MoCA scale scores. Conclusions: Cognitive decline was observed in heart transplant patients. Heart transplant patients exhibited altered ReHo and VMHC in several brain regions compared with healthy controls. These changes may underlie impaired cognitive function in heart transplant patients. These findings may contribute to understanding the neural mechanisms of cognitive changes in heart transplant patients and could inform future research on potential intervention strategies. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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13 pages, 686 KB

Open AccessSystematic Review

Thyroid Hormone Therapy for Potential Heart Donors: A Comprehensive Review of Clinical Trials

by Mushood Ahmed, Eeshal Zulfiqar, Sonia Hurjkaliani, Aimen Shafiq, Hafsa Arshad Azam Raja, Areeba Ahsan, Aemen Kamran, Laveeza Fatima, Amna Nadeem, Muhammad Abdullah Naveed, Faizan Ahmed, Hritvik Jain, Tallal Mushtaq Hashmi, Muath Baniowda, Mansimran Singh Dulay, Sivaram Neppala, Himaja Dutt Chigurupati, Ali Hasan, Peter Collins and Raheel Ahmed

Biomedicines 2025, 13(7), 1622; https://doi.org/10.3390/biomedicines13071622 - 2 Jul 2025

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Abstract

Background: Due to neurohormonal disturbances that occur following brain death, thyroid hormone therapy has been proposed as a means to enhance cardiac function in brain-dead organ donors. However, it remains unclear whether thyroid hormone administration improves clinical outcomes in potential heart donors. Methods: A comprehensive review of clinical trials was conducted to evaluate the impact of thyroid hormone therapy on heart viability and transplantation outcomes. A total of nine randomized controlled trials (RCTs) involving 1189 potential heart donors were included. Results: Thyroid hormone supplementation effectively restored circulating thyroid hormone levels in brain-dead donors. However, findings regarding improvements in cardiac function and transplantation outcomes were inconsistent across studies. While some RCTs reported marginal improvements in hemodynamic parameters and heart transplant viability, these results were not consistently replicated. Furthermore, most studies did not demonstrate a significant enhancement in recipient survival or graft function associated with thyroid hormone therapy. Conclusion: Although thyroid hormone therapy restores thyroid hormone levels in brain-dead donors, current evidence does not consistently support its effectiveness in improving donor heart viability or recipient outcomes. Further research is necessary to clarify the role of thyroid hormone therapy in donor management and its impact on long-term transplant success. Full article

(This article belongs to the Special Issue Advanced Research on Heart Failure and Heart Transplantation)

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