Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments

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

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 12285

Special Issue Editors


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Guest Editor
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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Guest Editor
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the considerable progress in the prevention and treatment of heart disease, heart failure is still a very important cause of recurring hospitalizations, with relevant social and health care costs, and it is burdened with a 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, pulmonary vascular disease, etc. 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 with telemedicine, in order to reduce the number of hospital admissions and. thus, possibly, social and health care costs.

Therefore, we consider “Heart Failure” an extremely up-to-date and broad topic for which a Special Issue is certainly 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 (10 papers)

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Editorial

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2 pages, 157 KiB  
Editorial
Insulin Resistance with Associated Hyperinsulinemia as a Cause of the Development and Worsening of Heart Failure
by Umberto Attanasio, Valentina Mercurio and Serafino Fazio
Biomedicines 2024, 12(12), 2890; https://doi.org/10.3390/biomedicines12122890 - 19 Dec 2024
Viewed by 420
Abstract
Despite the considerable progress that has been made with regard to the prevention and treatment of cardiovascular diseases, heart failure (HF) remains a particularly important cause of recurring hospitalizations, with relevant social and healthcare costs, and it is a significant cause of mortality; [...] Read more.
Despite the considerable progress that has been made with regard to the prevention and treatment of cardiovascular diseases, heart failure (HF) remains a particularly important cause of recurring hospitalizations, with relevant social and healthcare costs, and it is a significant cause of mortality; as such, there is a need for continuous efforts to improve our understanding of its complex pathophysiology and refine relevant therapeutic strategies [...] Full article

Research

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11 pages, 1196 KiB  
Article
Insights into the Associations Between Systolic Left Ventricular Rotational Mechanics and Left Atrial Peak Reservoir Strains in Healthy Adults from the MAGYAR-Healthy Study
by Attila Nemes, Árpád Kormányos, Nóra Ambrus and Csaba Lengyel
Biomedicines 2024, 12(11), 2515; https://doi.org/10.3390/biomedicines12112515 - 4 Nov 2024
Viewed by 606
Abstract
Introduction: In systole, when the left ventricle (LV) twists, the left atrium (LA) behaves like a reservoir, having a special wall contractility pattern opposite to that of the LV wall. Accordingly, the objective of the present study was to investigate the associations between [...] Read more.
Introduction: In systole, when the left ventricle (LV) twists, the left atrium (LA) behaves like a reservoir, having a special wall contractility pattern opposite to that of the LV wall. Accordingly, the objective of the present study was to investigate the associations between LV rotational mechanics and LA peak (reservoir) strains as assessed simultaneously by three-dimensional speckle-tracking echocardiography (3DSTE) under healthy conditions. Methods: In the present study, 157 healthy adults (mean age: 33.2 ± 12.7 years, 73 men) were involved. Complete two-dimensional Doppler echocardiography with 3DSTE-derived data acquisition were performed in all cases. The 3DSTE-derived LV rotational and LA strain parameters were determined at a later date. Results: Global LA peak reservoir circumferential (22.7 ± 6.4% vs. 27.6 ± 6.8%, p < 0.05) and area (57.8 ± 20.0% vs. 66.0 ± 22.7%, p < 0.05) strains proved to be reduced in the case of the highest vs. lowest basal LV rotation; other LA peak reservoir strains were not associated with increasing basal LV rotation. Global LA peak radial strain was highest in the case of the lowest vs. highest apical LV rotation (−19.2 ± 9.4% vs. −13.0 ± 8.2%, p < 0.05). Global LA peak reservoir 3D strain was lowest in the case of the highest vs. lowest apical LV rotation (−9.9 ± 6.8% vs. −5.0 ± 4.2%, p < 0.05). Only apical LV rotation proved to be significantly reduced in the case of the highest vs. lowest global LA peak reservoir 3D strain (8.12 ± 3.23° vs. 10.50 ± 3.44°, p < 0.05). Other global LA peak reservoir strains were not associated with basal and apical LV rotations. Conclusions: In LV systole, LV rotational mechanics is associated with LA deformation represented by LA peak (reservoir) strains even in healthy circumstances. While basal LV rotation is associated with LA widening, apical LV rotation is associated with LA thinning, suggesting the close cooperation of the LV and LA in systole even in healthy adults. Full article
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13 pages, 2672 KiB  
Article
Evaluation of the Accuracy of Point-of-Care Urine Chloride Measured via Strip Test in Patients with Heart Failure
by Mateusz Guzik, Berenika Jankowiak, Piotr Ponikowski and Jan Biegus
Biomedicines 2024, 12(11), 2473; https://doi.org/10.3390/biomedicines12112473 - 28 Oct 2024
Viewed by 656
Abstract
Background: In clinical practice, patient self-monitoring is crucial in achieving therapeutic goals in various diseases. In heart failure (HF), it is particularly important due to the increasing role of urine composition. Therefore, we proposed this study to assess the accuracy of urine chloride [...] Read more.
Background: In clinical practice, patient self-monitoring is crucial in achieving therapeutic goals in various diseases. In heart failure (HF), it is particularly important due to the increasing role of urine composition. Therefore, we proposed this study to assess the accuracy of urine chloride (uCl) assessment via strip test in relation to chloride and sodium (uNa+) measurements in a gold-standard laboratory method. Methods: Urine samples were collected before administering morning medications. Afterwards, they were analyzed concurrently using the strip test and gold-standard laboratory method. Results: The study cohort comprised 66 patients (82% male, mean age 68 ± 12 years), of whom 65% were diagnosed with HF and 35% without HF. Across the entire cohort, a strong correlation was observed between uCl measured by both methods (r = 0.85; p < 0.001). However, the strip test was found to underestimate uCl relative to the laboratory measurements (mean difference of 18 mmol/L). Furthermore, strong correlations were observed between the methods among patients with HF and without HF (r = 0.88 vs. r = 0.71, respectively; p < 0.001 for both), where they presented similar relationship patterns. Interestingly, in patients with a low glomerular filtration rate (eGFR ≤ 60 mL/min/1.73 m2), the correlation between both methods was greater compared to those with high eGFR (>60 mL/min/1.73 m2) (r = 0.94 vs. r = 0.76, respectively; p < 0.001 for both). The relationship between uCl from the strip test and uNa+ from the laboratory measurement was weaker than for uCl, but it was significant. Conclusions: These findings suggest that point-of-care strip tests for assessing urinary chloride demonstrate high accuracy and potential utility, particularly in patients with reduced eGFR. Full article
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13 pages, 3458 KiB  
Article
Exercise-Induced Proteomic Profile Changes in Patients with Advanced Heart Failure
by Anna Drohomirecka, Joanna Waś, Ewa Sitkiewicz, Bianka Świderska, Anna Lutyńska, Tomasz Rywik and Tomasz Zieliński
Biomedicines 2024, 12(10), 2267; https://doi.org/10.3390/biomedicines12102267 - 5 Oct 2024
Viewed by 1015
Abstract
Background/Objectives: The pathophysiological background of the processes activated by physical activity in patients with heart failure (HF) is not fully understood. Proteomic studies can help to preliminarily identify new protein markers for unknown or poorly defined physiological processes. We aimed to analyse the [...] Read more.
Background/Objectives: The pathophysiological background of the processes activated by physical activity in patients with heart failure (HF) is not fully understood. Proteomic studies can help to preliminarily identify new protein markers for unknown or poorly defined physiological processes. We aimed to analyse the changes in the plasma proteomic profile of HF patients after a cardiopulmonary exercise test (CPET) to define pathways involved in the response to exercise. Methods: The study prospectively enrolled 20 male patients with advanced HF (aged 53.3 ± 8.3 years). Blood samples were taken from the patients before and immediately after the CPET to obtain plasma proteomic profiles. Two-sample t-tests (paired or non-paired) were performed with and without false discovery rate (FDR) correction for multiple testing. Enrichment analysis was performed to associate biological processes and pathways with the study results. Results: A total of 968 plasma proteins were identified, of which 722 underwent further statistical analysis. Of these, 236 proteins showed differential expression when comparing all plasma samples collected before and after CPT (p < 0.05), and for 86 of these the difference remained statistically significant after FDR correction. Proteins whose expression changed after exercise are mostly involved in immune response and inflammatory processes, coagulation, cell adhesion, regulation of cellular response to stimulus and regulation of programmed cell death. There were no differences in resting proteomics according to HF etiology (ischemic vs. non-ischemic). Conclusions: Changes in the proteomic profile revealed a complexity of exercise-induced processes in patients with HF, suggesting that few major physiological pathways are involved. Further studies focusing on specific pathways are needed. Full article
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12 pages, 1878 KiB  
Article
Comparative Temporal Analysis of Morbidity and Early Mortality in Heart Transplantation with Extracorporeal Membrane Oxygenation Support: Exploring Trends over Time
by Raquel López-Vilella, Manuel Pérez Guillén, Borja Guerrero Cervera, Ricardo Gimeno Costa, Iratxe Zarragoikoetxea Jauregui, Francisca Pérez Esteban, Paula Carmona, Tomás Heredia Cambra, Mónica Talavera Peregrina, Azucena Pajares Moncho, Carlos Domínguez-Massa, Víctor Donoso Trenado, Luis Martínez Dolz, Pilar Argente, Álvaro Castellanos, Juan Martínez León, Salvador Torregrosa Puerta and Luis Almenar Bonet
Biomedicines 2024, 12(9), 2109; https://doi.org/10.3390/biomedicines12092109 - 16 Sep 2024
Viewed by 912
Abstract
Background/Objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare [...] Read more.
Background/Objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline. Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection. Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality (p = 0.822), hospital discharge (p = 0.972), one-year mortality (p = 0.706), or five-year mortality (p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods (p = 0.004 and p = 0.0001, respectively). Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant. Full article
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13 pages, 1628 KiB  
Article
Three-Dimensional Combined Atrioventricular Coupling Index—A Novel Prognostic Marker in Dilated Cardiomyopathy
by Aura Vîjîiac, Alina Ioana Scărlătescu, Ioana Gabriela Petre, Cristian Vîjîiac and Radu Gabriel Vătășescu
Biomedicines 2024, 12(2), 302; https://doi.org/10.3390/biomedicines12020302 - 28 Jan 2024
Cited by 1 | Viewed by 1242
Abstract
Atrioventricular coupling has recently emerged as an outcome predictor. Our aim was to assess, through three-dimensional (3D) echocardiography, the role of the left atrioventricular coupling index (LACI), right atrioventricular coupling index (RACI) and a novel combined atrioventricular coupling index (CACI) in a cohort [...] Read more.
Atrioventricular coupling has recently emerged as an outcome predictor. Our aim was to assess, through three-dimensional (3D) echocardiography, the role of the left atrioventricular coupling index (LACI), right atrioventricular coupling index (RACI) and a novel combined atrioventricular coupling index (CACI) in a cohort of patients with dilated cardiomyopathy (DCM). One hundred twenty-one consecutive patients with DCM underwent comprehensive 3D echocardiographic acquisitions. LACI was defined as the ratio between left atrial and left ventricular 3D end-diastolic volumes. RACI was defined as the ratio between right atrial and right ventricular 3D end-diastolic volumes. CACI was defined as the sum of LACI and RACI. Patients were prospectively followed for death, heart transplant, nonfatal cardiac arrest and hospitalization for heart failure. Fifty-five patients reached the endpoint. All three coupling indices were significantly more impaired in patients with events, with CACI showing the highest area under the curve (AUC = 0.66, p = 0.003). All three indices were independent outcome predictors when tested in multivariable Cox regression (HR = 2.62, p = 0.01 for LACI; HR = 2.58, p = 0.004 for RACI; HR = 2.37, p = 0.01 for CACI), but only CACI showed an incremental prognostic power over traditional risk factors such as age, left ventricular strain, right ventricular strain and mitral regurgitation severity (likelihood ratio χ2 test = 28.2, p = 0.03). CACI assessed through 3D echocardiography, reflecting both left and right atrioventricular coupling, is an independent predictor of adverse events in DCM, yielding an incremental prognostic power over traditional risk factors. Full article
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12 pages, 1317 KiB  
Article
Association between Serum Free Fatty Acids and Clinical and Laboratory Parameters in Acute Heart Failure Patients
by Iva Klobučar, Helga Hinteregger, Margarete Lechleitner, Matias Trbušić, Gudrun Pregartner, Andrea Berghold, Wolfgang Sattler, Saša Frank and Vesna Degoricija
Biomedicines 2023, 11(12), 3197; https://doi.org/10.3390/biomedicines11123197 - 1 Dec 2023
Viewed by 1195
Abstract
Very little is known about the association between individual serum free fatty acids (FFAs) and clinical and laboratory parameters (indicators of heart failure severity) in acute heart failure (AHF) patients. Here, the baseline serum levels of FFAs, 16:0 (palmitic acid), 16:1 (palmitoleic acid), [...] Read more.
Very little is known about the association between individual serum free fatty acids (FFAs) and clinical and laboratory parameters (indicators of heart failure severity) in acute heart failure (AHF) patients. Here, the baseline serum levels of FFAs, 16:0 (palmitic acid), 16:1 (palmitoleic acid), 18:0 (stearic acid), 18:1 (oleic acid), 18:2 (linoleic acid), 18:3 (alpha-linolenic acid or gamma-linolenic acid), 20:4 (arachidonic acid), 20:5 (eicosapentaenoic acid), and 22:6 (docosahexaenoic acid), were determined in 304 AHF patients (94.7% belonged to New York Heart Association functional class IV) using gas chromatography. Spearman correlation coefficients were used to examine the associations between the individual and total (the sum of all FFAs) FFAs and clinical and laboratory parameters. After applying a Bonferroni correction to correct for multiple testing, the total FFAs, as well as the individual FFAs (except FFAs 18:0, 20:5, and 22:6), were found to be significantly positively correlated with serum albumin. Only a few additional associations were found: FFA 16:0 was significantly negatively correlated with systolic pulmonary artery pressure, FFA 18:3 was significantly negatively correlated with C-reactive protein and body mass index, and FFA 20:4 was significantly negatively correlated with blood urea nitrogen. Based on our results, we conclude that in patients with severe AHF, individual and total serum FFAs are slightly associated with established laboratory and clinical parameters, which are indicators of heart failure severity. Full article
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14 pages, 3822 KiB  
Article
Role of Pericytes in Cardiomyopathy-Associated Myocardial Infarction Revealed by Multiple Single-Cell Sequencing Analysis
by Yanqiao Lu, Huanhuan Huo, Feng Liang, Jieyuan Xue, Liang Fang, Yutong Miao, Lan Shen and Ben He
Biomedicines 2023, 11(11), 2896; https://doi.org/10.3390/biomedicines11112896 - 26 Oct 2023
Viewed by 1874
Abstract
Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular death worldwide. AMI with cardiomyopathy is accompanied by a poor long-term prognosis. However, limited studies have focused on the mechanism of cardiomyopathy associated with AMI. Pericytes are important to the microvascular [...] Read more.
Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular death worldwide. AMI with cardiomyopathy is accompanied by a poor long-term prognosis. However, limited studies have focused on the mechanism of cardiomyopathy associated with AMI. Pericytes are important to the microvascular function in the heart, yet little attention has been paid to their function in myocardial infarction until now. In this study, we integrated single-cell data from individuals with cardiomyopathy and myocardial infarction (MI) GWAS data to reveal the potential function of pericytes in cardiomyopathy-associated MI. We found that pericytes were concentrated in the left atrium and left ventricle tissues. DLC1/GUCY1A2/EGFLAM were the top three uniquely expressed genes in pericytes (p < 0.05). The marker genes of pericytes were enriched in renin secretion, vascular smooth muscle contraction, gap junction, purine metabolism, and diabetic cardiomyopathy pathways (p < 0.05). Among these pathways, the renin secretion and purine metabolism pathways were also found in the process of MI. In cardiomyopathy patients, the biosynthesis of collagen, modulating enzymes, and collagen formation were uniquely negatively regulated in pericytes compared to other cell types (p < 0.05). COL4A2/COL4A1/SMAD3 were the hub genes in pericyte function involved in cardiomyopathy and AMI. In conclusion, this study provides new evidence about the importance of pericytes in the pathogenesis of cardiomyopathy-associated MI. DLC1/GUCY1A2/EGFLAM were highly expressed in pericytes. The hub genes COL4A2/COL4A1/SMAD3 may be potential research targets for cardiomyopathy-associated MI. Full article
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Review

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16 pages, 666 KiB  
Review
Cancer Therapy-Related Cardiac Dysfunction: A Review of Current Trends in Epidemiology, Diagnosis, and Treatment
by Panagiotis Theofilis, Panayotis K. Vlachakis, Evangelos Oikonomou, Maria Drakopoulou, Paschalis Karakasis, Anastasios Apostolos, Konstantinos Pamporis, Konstantinos Tsioufis and Dimitris Tousoulis
Biomedicines 2024, 12(12), 2914; https://doi.org/10.3390/biomedicines12122914 - 21 Dec 2024
Viewed by 238
Abstract
Cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a significant concern with the rise of effective cancer treatments like anthracyclines and targeted therapies such as trastuzumab. While these therapies have improved cancer survival rates, their unintended cardiovascular side effects can lead to heart [...] Read more.
Cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a significant concern with the rise of effective cancer treatments like anthracyclines and targeted therapies such as trastuzumab. While these therapies have improved cancer survival rates, their unintended cardiovascular side effects can lead to heart failure, cardiomyopathy, and arrhythmias. The pathophysiology of CTRCD involves oxidative stress, mitochondrial dysfunction, and calcium dysregulation, resulting in irreversible damage to cardiomyocytes. Inflammatory cytokines, disrupted growth factor signaling, and coronary atherosclerosis further contribute to this dysfunction. Advances in cardio-oncology have led to the early detection of CTRCD using cardiac biomarkers like troponins and imaging techniques such as echocardiography and cardiac magnetic resonance (CMR). These tools help identify asymptomatic patients at risk of cardiac events before the onset of clinical symptoms. Preventive strategies, including the use of cardioprotective agents like beta-blockers, angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors have shown promise in reducing the incidence of CTRCD. This review summarizes the mechanisms, detection methods, and emerging treatments for CTRCD, emphasizing the importance of interdisciplinary collaboration between oncologists and cardiologists to optimize care and improve both cancer and cardiovascular outcomes. Full article
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Other

13 pages, 643 KiB  
Opinion
The Negative Impact of Insulin Resistance/Hyperinsulinemia on Chronic Heart Failure and the Potential Benefits of Its Screening and Treatment
by Serafino Fazio, Valentina Mercurio, Flora Affuso and Paolo Bellavite
Biomedicines 2023, 11(11), 2928; https://doi.org/10.3390/biomedicines11112928 - 30 Oct 2023
Cited by 5 | Viewed by 2793
Abstract
This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event [...] Read more.
This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event of several different cardiovascular diseases. Its incidence has been increasing over the last decades because of increased survival from ischemic heart disease thanks to improvements in its treatment (including myocardial revascularization interventions) and the increase in life span. In particular, incidence of HF with preserved ejection fraction (HFpEF) is significantly increasing, and patients with HFpEF often are also affected by diabetes mellitus and insulin resistance (IR), with a prevalence > 45%. Concentric left ventricular (LV) remodeling and diastolic dysfunction are the main structural abnormalities that characterize HFpEF. It is well documented in the literature that IR with chronic hyperinsulinemia, besides causing type 2 diabetes mellitus, can cause numerous cardiovascular alterations, including endothelial dysfunction and increased wall thicknesses of the left ventricle with concentric remodeling and diastolic dysfunction. Therefore, it is conceivable that IR might play a major role in the pathophysiology and the progressive worsening of HF. To date, several substances have been shown to reduce IR/hyperinsulinemia and have beneficial clinical effects in patients with HF, including SGLT2 inhibitors, metformin, and berberine. For this reason, an early screening of IR could be advisable in subjects at risk and in patients with heart failure, to promptly intervene with appropriate therapy. Future studies aimed at comparing the efficacy of the substances used both alone and in association are needed. Full article
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