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Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition

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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: 30 November 2025 | Viewed by 5926

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Dr. Serafino Fazio

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Department of Internal Medicine, School of Medicine, Federico II University, Via Sergio Pansini 5, 80135 Naples, Italy
Interests: hormones and heart; cardiac failure; insulin resistance; hyperinsulinism; metabolic syndrome; nutraceuticals; pulmonary arterial hypertension; COVID-19
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Dr. Valentina Mercurio

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Department of Translational Medical Sciences, Federico II University, Naples, Italy
Interests: heart failure; echocardiography; right ventricular function; pulmonary vascular disease; pulmonary arterial hypertension; cardio-oncology
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Special Issue Information

Dear Colleagues,

Despite the considerable progress in the prevention and treatment of heart disease, heart failure is still a particularly important cause of recurring hospitalizations, with relevant social and healthcare costs, and it is burdened with significant mortality. Notably, while advances in the treatment of acute coronary syndromes with myocardial revascularization and the increased awareness in the management of cardiovascular risk factors have improved the survival of patients with ischemic heart disease, there has been a progressive increase in the number of patients with chronic heart failure.

Heart failure can result from alterations in both the left and right ventricles, which can be not only due to ischemic heart disease but also to other causes, such as valvular abnormalities, systemic hypertension, and pulmonary vascular disease. It is also noteworthy, not only for treatment purposes, to highlight the recent increase in the incidence of heart failure with reduced ejection fraction and that with preserved ejection fraction. Lately, there has also been an effort to improve the follow-up of patients with heart failure through telemedicine to reduce the number of hospital admissions and, thus, possibly, social and healthcare costs.

Therefore, we consider “Heart Failure” an extremely up-to-date and broad topic for which a Special Issue is relevant.

Dr. Serafino Fazio
Dr. Valentina Mercurio
Guest Editors

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Keywords

heart failure with reduced ejection fraction
heart failure with preserved ejection fraction
pathophysiological novelties
treatment advances
pulmonary arterial hypertension
at-home follow-up of patients with heart failure

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Published Papers (8 papers)

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Research

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12 pages, 602 KiB

Open AccessArticle

Effects of SGLT2 Inhibitors on Sleep Apnea Parameters and Cheyne–Stokes Respiration in Patients with Acute Decompensated Heart Failure: A Prospective Cohort Study

by Petar Kalaydzhiev, Tsvetelina Velikova, Yanitsa Davidkova, Gergana Voynova, Angelina Borizanova, Natalia Spasova, Neli Georgieva, Radostina Ilieva, Elena Kinova and Assen Goudev

Biomedicines 2025, 13(6), 1474; https://doi.org/10.3390/biomedicines13061474 - 14 Jun 2025

Viewed by 258

Abstract

Background: Sleep-disordered breathing (SDB), particularly Cheyne–Stokes respiration (CSR), is highly prevalent among patients hospitalized with acute decompensated heart failure (ADHF) and is associated with worse clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in heart failure, but their effects on nocturnal respiratory parameters remain underexplored. Objectives: This study aims to evaluate the impact of SGLT2i therapy on key respiratory and cardiac indices including CSR burden, oxygenation, and right heart function in patients with ADHF and reduced left ventricular ejection fraction. Methods: In this single-center prospective cohort study, 60 patients with ADHF, LVEF < 40%, and a baseline apnea–hypopnea index (AHI) > 5 were assessed before and three months after the initiation of SGLT2i therapy. Sleep respiratory parameters were measured using home polygraphy (ApneaLink^TM), while cardiac and renal indices were evaluated by echocardiography, NT-proBNP, and the estimated glomerular filtration rate (eGFR). Structural and functional echocardiographic changes were analyzed both at baseline and following the 3-month treatment period. Patient-reported outcomes were assessed using the Epworth Sleepiness Scale (ESS) and Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: After 3 months of SGLT2i therapy, significant improvements were observed in daytime sleepiness (ESS: −2.68 points; p < 0.001), CSR index (−5.63 events/h; p < 0.001), AHI (−3.07 events/h; p < 0.001), ODI (−6.11 events/h; p < 0.001), and mean nocturnal SpO₂ (+1.95%; p < 0.001). KCCQ scores increased by 9.16 points (p < 0.001), indicating improved quality of life. Cardiac assessments revealed reductions in NT-proBNP (−329.6 pg/mL; p < 0.001) and E/e′ ratio (−1.08; p < 0.001), with no significant change in LVEF or chamber dimensions. Right ventricular function improved, as evidenced by the increased TAPSE/sPAP ratio (+0.018; p < 0.001). Renal function remained stable, with a non-significant upward trend in eGFR. Conclusions: This exploratory study suggests that SGLT2 inhibitors may be associated with the attenuation of Cheyne–Stokes respiration and an improvement in right heart function in patients with ADHF, warranting further investigation in controlled trials. These findings highlight the potential of SGLT2is to address overlapping cardio-respiratory dysfunction in this high-risk population. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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16 pages, 1615 KiB

Open AccessArticle

A Word of Caution—Potential Limitations of Pulmonary Artery Pressure Monitoring in Detecting Congestion Caused by Right-Sided Heart Failure

by Ester Judith Herrmann, Eva Herrmann, Khodr Tello, Kathleen Mantzsch, Meaza Tekeste, Stephan Fichtlscherer, Christian W. Hamm and Birgit Assmus

Biomedicines 2025, 13(6), 1469; https://doi.org/10.3390/biomedicines13061469 - 14 Jun 2025

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Abstract

Background/Objectives: Patients with New York Heart Association (NYHA) class III heart failure (HF) suffer from frequent hospitalizations. Non-invasive pulmonary artery pressure (PAP) sensor-guided HF care has been shown to reduce hospitalizations. However, it is unknown whether the PAP changes prior to hospitalization differ between clinical right, left or global cardiac decompensation. Methods: Sensor-derived PAP data and HF hospitalization records from 41 patients with NYHA class III HF were classified retrospectively into predominantly left, right or global decompensation. Linear mixed-effect regression models were used for statistical evaluations of the PAP in selected hospitalizations for which admission was at least 28 days after the last admission and 14 days after the last hospital discharge and with readings in between. Results: During 24.4 months of follow-up, 127 hospitalizations in 38 patients were evaluated. The global cardiac decompensation (n = 13) had the highest PAP before hospitalization, followed by left-sided (n = 20) decompensation. Patients with right-sided decompensation (n = 9) had comparable PAP values before hospitalization to the cohort without any cardiac decompensation (n = 85). The diastolic PAP showed a significant increase of 0.035 mmHg/day (p = 0.0097) in left-sided decompensation and of 0.13 mmHg/day (p < 0.0001) in global cardiac decompensation, whereas no significant change in the diastolic PAP occurred prior to the right-sided decompensation. The baseline right ventricular function and right ventricle–pulmonary arterial coupling (TAPSE/PASP ratio) were impaired in patients with subsequent global cardiac decompensation. Conclusion: PAP telemonitoring-guided therapy can reliably detect early signs of left and global cardiac decompensation but may be limited in detecting right-sided cardiac congestion. The routine assessment of RV–PA coupling may improve the detection of global cardiac decompensation, as severe impairments could indicate impending deterioration. In contrast, monitoring the RV contractility may aid in identifying isolated right-sided congestion and imminent decompensation. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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19 pages, 1703 KiB

Open AccessArticle

Sex-Specific Impact of 17β-Estradiol and Testosterone Levels on Inflammation and Injury in Acute Myocardial Infarction—Preliminary Results

by Niya E. Semerdzhieva, Adelina D. Tsakova and Vesela V. Lozanova

Biomedicines 2025, 13(6), 1466; https://doi.org/10.3390/biomedicines13061466 - 13 Jun 2025

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Abstract

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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9 pages, 1463 KiB

Open AccessArticle

Three-Dimensional Speckle-Tracking Echocardiography-Derived Left Ventricular Global Longitudinal Strain and Mitral Annular Plane Systolic Excursion Are Associated in Healthy Adults—Insights from the MAGYAR-Healthy Study

by Attila Nemes, Nóra Ambrus and Csaba Lengyel

Biomedicines 2025, 13(3), 625; https://doi.org/10.3390/biomedicines13030625 - 4 Mar 2025

Cited by 2 | Viewed by 562

Abstract

Introduction: Mitral annular plane systolic excursion (MAPSE) is a quantitative feature of left ventricular (LV) function that can be easily measured by M-mode echocardiography. The more recent LV strains represent LV contractility, and they can be determined for the three main directions in the radial (RS), longitudinal (LS), and circumferential (CS) directions. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) seems to be ideal for the simultaneous assessment of all LV strains from the same acquired 3D dataset. Their associations, however, have not been fully analyzed in clinical settings in healthy volunteers yet. Therefore, the present study aimed to find associations between MAPSE and 3DSTE-derived LV strains in healthy circumstances. Methods: The present study consisted of 106 healthy adult volunteers (mean age 28.1 ± 6.3 years, 48 men). Complete two-dimensional Doppler echocardiography with MAPSE assessment and 3DSTE-derived LV strain measurements were performed in all cases. Results: Tendentiously reduced LV volumes with preserved LV ejection fraction were present in the case of mean MAPSE as compared to decreased/increased MAPSE. Global and regional LV-RS and LV-CS did not differ if MAPSE was increased, mean or decreased. Global LV-LS was reduced in the case of decreased MAPSE, mainly due to tendentiously higher apical LV-LS. MAPSE did not differ if global LV-RS and LV-CS were increased, mean or decreased. MAPSE was tendentiously increased in the presence of increased global LV-LS. Conclusions: Only 3DSTE-derived global LV-LS and MAPSE are associated in healthy adults; LV global strains in other directions show no relationship with MAPSE. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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15 pages, 1213 KiB

Open AccessArticle

The Role of the Estimated Plasma Volume Variation in Assessing Decongestion in Patients with Acute Decompensated Heart Failure

by Andreea-Maria Grigore, Mihai Grigore, Ana-Maria Balahura, Gabriela Uscoiu, Ioana Verde, Camelia Nicolae, Elisabeta Bădilă and Adriana-Mihaela Ilieșiu

Biomedicines 2025, 13(1), 88; https://doi.org/10.3390/biomedicines13010088 - 2 Jan 2025

Cited by 1 | Viewed by 933

Abstract

Introduction and Aim: Assessing decongestion in patients with acute decompensated heart failure (ADHF) is challenging, requiring multiple parameters and often remaining imprecise. The study aimed to investigate the utility of indirectly estimating plasma variation (∆ePVS) for evaluating decongestion in ADHF patients in relation to natriuretic peptides. Materials and Methods: This prospective, observational, single-center study included 111 patients (mean age 74 years, 40% female) hospitalized with ADHF and treated with intravenous diuretics along with optimized medical therapy. Patients were clinically and echocardiographically evaluated at admission, with blood tests performed at both admission and discharge. A decrease of ≥30% in NT-proBNP at discharge was considered a marker of decongestion. ∆ePVS was calculated using the Strauss formula: ∆ePVS (%) = 100 × [(Hb admission/Hb discharge) × (1 − Hct discharge)/(1 − Hct admission)] − 100. A negative ∆ePVS (<0%) at discharge was considered a marker of hemoconcentration. Patients were divided into two groups: G1 (∆ePVS < 0%, 81 patients) and G2 (∆ePVS ≥ 0%, 30 patients). Results: Both groups had similar left ventricular ejection fraction (LVEF) values of 46%, mean hemoglobin (Hb) (12 g/dL), and creatinine (1.16 ± 0.65 mg/dL). NT-proBNP decreased in 88% patients in G1 and in 26% patients in G2 (p < 0.001). During hospitalization, five patients from G2 died. At 6 months, rehospitalization occurred in 35% of G2 and 21% of G1 (p = 0.04), with mortality rates of 37% in G2 and 11% in G1 (p = 0.012). Multivariate regression identified ∆ePVS as the only significant predictor of NT-proBNP decrease (OR 0.11, 95% CI 0.04–0.33, p < 0.001). Conclusions: Indirect estimation of plasma volume and its variation are valuable, accessible, and cost-effective parameters for assessing decongestive treatment in ADHF patients, complementing natriuretic peptides. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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12 pages, 1860 KiB

Open AccessArticle

The Usefulness of Soluble ST2 Concentration in Heart Failure with Reduced Ejection Fraction to Predict Severe Impairment in Exercise Capacity Assessed in Cardiopulmonary Exercise Testing

by Magdalena Dudek, Marta Kałużna-Oleksy, Filip Sawczak, Agata Kukfisz, Aleksandra Soloch, Jacek Migaj, Maciej Lesiak and Ewa Straburzyńska-Migaj

Biomedicines 2025, 13(1), 60; https://doi.org/10.3390/biomedicines13010060 - 30 Dec 2024

Viewed by 862

Abstract

Background/Objectives: Heart failure (HF) constitutes a complex clinical syndrome that is highly prevalent worldwide, comprises a serious prognosis, and results in a reduced quality of life. Exercise capacity is one of the most significant parameters involved in the prognosis in HF patients. Our objective was to evaluate the relationship between the selected cardiopulmonary exercise testing (CPET) parameters and the concentration of novel biomarker sST2 in a group of patients with heart failure with reduced ejection fraction (HFrEF). Methods: A group of 135 patients with HFrEF was enrolled in this prospective cohort study. Patients were in the stable phase of the disease in the prior 4 weeks and received optimal medical treatment. Clinical and biochemical parameters were investigated. All patients performed maximal CPET. Results: The mean (SD) concentration of sST2 was 45.5 ± 39.2 ng/mL. Based on the CPET results, the cut-off value (52.377 ng/mL) was established, optimal for the discrimination of relative peakVO₂ < 12 mL/kg/min. Patients were divided into two groups according to sST2 cut-off values determined with an ROC curve (AUC 0.692, 95% CI: 0.567–0.816). The mean relative peakVO₂ in patients with higher sST2 was 14.5 ± 4.6 mL/kg/min, while in the second group, it was 17.6 ± 5.2 (p = 0.002). In the sST2 ≥ 52.377 ng/mL group, 55.6% of patients achieved VO₂ < 50%. Subjects with lower sST2 values obtained higher values of PETCO₂ (p < 0.001) and higher values of pulse O₂ (p = 0.01). VE/VCO₂slope (p = 0.002) was higher in patients with increased sST2 concentration. Conclusions: The concentration of sST2 protein is substantially associated with the clinical severity of heart failure with reduced left ventricular ejection fraction assessed by functional capacity through CPET. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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Review

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24 pages, 1461 KiB

Open AccessReview

The Microbiome Connection: A Common Pathway Linking Cancer and Heart Failure

by Ioannis Paraskevaidis, Elias Tsougos and Christos Kourek

Biomedicines 2025, 13(6), 1297; https://doi.org/10.3390/biomedicines13061297 - 25 May 2025

Viewed by 413

Abstract

In humans, heart failure (HF) and cancer are among the leading causes of morbidity and mortality. A growing body of evidence highlights a bidirectional relationship between these conditions, underpinned by shared risk factors and overlapping pathophysiological pathways. This review aims to explore the emerging role of the intestinal microbiome as a common mechanistic link between HF and cancer. Specifically, we examine how microbial dysbiosis and its metabolic products—such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, lipopolysaccharides (LPS), and branched-chain amino acids (BCAAs)—contribute to inflammation, immune dysregulation, oxidative stress, and metabolic dysfunction. These mechanisms promote multiorgan impairment and establish a vicious cycle that fuels both tumorigenesis and cardiac deterioration. HF, cancer, and the gut microbiome are not isolated entities but are deeply interconnected through shared biological mechanisms—including chronic inflammation, microbial dysbiosis, immune and neurohumoral modulation, and metabolic derangement. These findings support the concept of a microbiome-centered axis involving the gut, heart, and tumors, which may underlie many chronic disease processes. Understanding these interactions may provide novel insights into disease pathogenesis and uncover promising therapeutic targets that leverage microbiome modulation to prevent or treat HF, cancer, and other systemic diseases. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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19 pages, 1629 KiB

Open AccessReview

Targeting Inflammation and Iron Deficiency in Heart Failure: A Focus on Older Adults

by Daniela Maidana, Andrea Arroyo-Álvarez, Guillermo Barreres-Martín, Andrea Arenas-Loriente, Pedro Cepas-Guillen, Raphaela Tereza Brigolin Garofo, Pedro Caravaca-Pérez and Clara Bonanad

Biomedicines 2025, 13(2), 462; https://doi.org/10.3390/biomedicines13020462 - 13 Feb 2025

Viewed by 1641

Abstract

Background/Objectives: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, with a higher prevalence among older adults. Iron deficiency (ID), affecting up to 50% of HF patients, is closely linked to chronic inflammation, exacerbating HF outcomes. This review aims to explore the interplay between inflammation, ID, and HF, focusing on older patients, and to identify therapeutic gaps and emerging treatment strategies. Methods: A comprehensive review of the literature was conducted, emphasizing the pathophysiological mechanisms of inflammation and ID in HF, the challenges of current diagnostic criteria, and the limitations of available treatments. Emerging pharmacological and diagnostic approaches were analyzed. Results: Chronic inflammation in HF, particularly in older adults, promotes functional ID through elevated hepcidin levels, impairing iron availability and worsening anemia. Current diagnostic criteria, relying heavily on ferritin, often misclassify ID due to inflammation. Intravenous (IV) iron therapy shows clinical benefits in patients with <50% left ventricular ejection fraction (LVEF), but the evidence is limited in heart failure with preserved ejection fraction (HFpEF). Emerging therapies, such as Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) and prolyl hydroxylase inhibitors like Roxadustat, offer promising avenues to improve iron metabolism and outcomes. Conclusions: ID and inflammation significantly impact HF progression, particularly inolder adults. Refining diagnostic criteria and exploring innovative therapies are critical to addressing these challenges. Future research should prioritize personalized approaches targeting inflammation and ID, especially in underrepresented populations, such as HFpEF and elderly patients. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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