Search Results (282)

Heart failure (HF) is a major health issue, affecting up to 2% of the adult population worldwide. Given the increasing prevalence of obesity and its association with various cardiovascular diseases, understanding its role in HFrEF outcomes is crucial. This study aimed to investigate the impact of obesity on in-hospital mortality and prolonged hospital stay in patients with heart failure with reduced ejection fraction (HFrEF). We conducted a retrospective analysis of 425 patients admitted to the cardiology unit at the University Clinical Hospital in Wroclaw, Poland, between August 2018 and August 2020. Statistical analyses were performed to evaluate the interactions between BMI, sex, and comorbidities on in-hospital mortality. Significant interactions were found between sex and BMI as well as between BMI and post-stroke status, affecting in-hospital mortality. Specifically, increased BMI was associated with decreased odds of in-hospital mortality in males (OR = 0.72, 95% CI: 0.55–0.94, p < 0.05) but higher odds in females (OR = 1.18, 95% CI: 0.98–1.42, p = 0.08). For patients without a history of stroke, increased BMI reduced mortality odds (HR = 0.78, 95% CI: 0.64–0.95, p < 0.01), whereas the effect was less pronounced in those with a history of stroke (HR = 0.89, 95% CI: 0.76–1.04, p = 0.12). In conclusion, the odds of in-hospital mortality decreased significantly with each 10% increase in BMI for males, whereas for females, a higher BMI was associated with increased odds of death. Additionally, BMI reduced in-hospital mortality odds more in patients without a history of cerebral stroke (CS) compared to those with a history of CS. These findings should be interpreted with caution due to the low number of observed outcomes and potential interactions with BMI and sex. Full article

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor–neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)–sGC–cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat’s metabolism, molecular mechanisms, and drug–drug interactions. Full article

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized as playing an important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial, driven by the different pathophysiological characteristics of these patients. The type of diet consumed has shown various modifying effects on plasma levels of NPs, irrespective of pharmacological treatment. Full article

This review delves into the most recent therapeutic approaches for pediatric chronic heart failure (HF) as proposed by the International Society for Heart and Lung Transplantation (ISHLT), which are not yet publicly available. The guideline proposes an exhaustive overview of the evolving pharmacological strategies that are transforming the management of HF in the pediatric population. The ISHLT guidelines recognize the scarcity of randomized clinical trials in children, leading to a predominance of consensus-based recommendations, designated as Level C evidence. This review article aims to shed light on the significant paradigm shifts in the proposed 2024 ISHLT guidelines for pediatric HF and their clinical ramifications for pediatric cardiology practitioners. Noteworthy advancements in the updated proposed guidelines include the endorsement of angiotensin receptor-neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and soluble guanylate cyclase (sGC) stimulators for treating chronic HF with reduced ejection fraction (HFrEF) in children. These cutting-edge treatments show potential for enhancing outcomes in pediatric HFrEF. Nonetheless, the challenge persists in validating the efficacy of therapies proven in adult HFrEF for the pediatric cohort. Furthermore, the proposed ISHLT guidelines address the pharmacological management of chronic HF with preserved ejection fraction (HFpEF) in children, marking a significant step forward in pediatric HF care. This review also discusses the future HF drugs in the pipeline, their mechanism of actions, potential uses, and side effects. Full article

Background: There is evidence that right ventricular (RV) contractile function, especially its coupling with the pulmonary circulation, has an important prognostic value in patients with left ventricular dysfunction. Aims: This study aimed to identify the best echocardiographic parameters of RV function and pulmonary artery systolic pressure (PASP) alone or in the form of the index of right ventricular-pulmonary artery coupling (RV-PA coupling) to determine the best predictor of 1-year major adverse cardiovascular events (MACE), which were defined as cardiovascular death and cardiac decompensation in heart failure patients with reduced ejection fraction (HFrEF). Methods and results: The study enrolled 191 HFrEF patients (mean age 62.28 ± 12.79 years, 74% males, mean left ventricular ejection fraction (LVEF) 25.53 ± 6.87%). All patients underwent clinical, laboratory, and transthoracic echocardiographic (TTE) evaluation, focusing on assessing RV function and non-invasive parameters of RV-PA coupling. RV function was evaluated using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and peak tricuspid annular systolic velocity (TAS’). PASP was estimated by peak tricuspid regurgitation velocity (TRVmax) and corrected by assumed right atrial pressure relative to the dimension and collapsibility of the inferior vena cava. The TAPSE/PASP and TAS’/PASP ratios were taken as an index of RV-PA coupling. During the follow-up (mean period of 340 ± 84 days), 58.1% of patients met the composite endpoint. The independent predictors of one-year outcome were shown to be advanced age, atrial fibrillation, indexed left atrial systolic volume (LAVI), LVEF, TAPSE/PASP, and TAS’/PASP. TAS’/PASP emerged as the strongest independent predictor of prognosis, with a hazard ratio (HR) of 0.67 (0.531–0.840), p < 0.001. Reconstructing the ROC curve 0.8 (0.723–0.859), p < 0.001, we obtained a threshold value of TAS’/PASP ≤ 0.19 (cm/s/mm Hg) (sensitivity 74.0, specificity 75.2). Patients with TAS’/RVSP ≤ 0.19 have a worse prognosis (Log Rank p < 0.001). Conclusions: This study confirmed previously known independent predictors of adverse outcomes in patients with HfrEF—advanced age, atrial fibrillation, LAVI, and LVEF—but non-invasive parameters of RV-PA coupling TAPSE/PASP and TAS’/PASP improved risk stratification in patients with HFrEF. Variable TAS’/PASP has been shown to be the most powerful, independent predictor of one-year outcome. Full article

This review article examines the mechanism of action of Angiotensin Receptor–Neprilysin Inhibitors (ARNIs) and Sodium–Glucose Co-Transporter 2 Inhibitors (SGLT2is) in managing chronic right ventricular (RV) dysfunction. Despite advancements in heart failure (HF) treatment, RV dysfunction remains a significant contributor to morbidity and mortality. This article explores the The article explores the impact of ARNIs and SGLT2is on RV function based on clinical and preclinical evidence, and the potential benefits of combined therapy. It highlights the need for further research to optimize patient outcomes and suggests that RV function should be considered in future clinical trials as part of risk stratification for HF therapies. This review underscores the importance of the early initiation of ARNIs and SGLT2is as per guideline-directed medical therapy for eligible HFrEF and HFpEF patients to improve co-existing RV dysfunction. Full article

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19–0.82]) and glomerular filtration rate (HR 0.98 [0.98–0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16–0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study. Full article

Background and Objectives: Heart failure with reduced ejection fraction (HFrEF) remains a significant burden. Traditional herbal medicines have shown cardioprotective effects in treating HFrEF. However, the implications of herbal formulation considering the dynamic immunohistological changes in the myocardium following acute ischemic injury have been insufficiently discussed. This review investigated the efficacy and mechanisms reported in studies using rat or mouse models of HFrEF induced by left descending coronary artery ligation. Materials and Methods: A systematic search was conducted using PubMed, Embase, AMED, CINAHL, and CENTRAL databases. Information was extracted regarding study characteristics, disease model induction protocols, intervention characteristics, treatment protocols, outcomes, and suggested mechanisms. Hierarchical cluster analysis of test drugs was performed based on constituent herb similarities. The risk of bias (RoB) was assessed using the Systematic Review Center for Laboratory animal Experimentation RoB tool. Results: Overall, 26 studies met the eligibility criteria. HF model induction periods after LADCA ligation ranged from 1 day to 12 weeks. Most studies administered the test drug for four weeks. Commonly used herbs included Panax ginseng, Astragalus membranaceus, Salvia miltiorrhiza, Carthamus tinctorius, and Lepidium apetalum, which demonstrated anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through various signaling pathways. The overall RoB was relatively high. No significant association was found between model induction periods and herbal formulations or examined mechanisms. Conclusions: Future research should consider the time-dependent immunohistological features of the myocardium during HF treatment. Full article

Aims: The aims of this study were to compare global longitudinal strain of the left ventricle (LV-GLS) and reservoir strain of the left atrium (R-LAS) values between patients with acute decompensation of chronic heart failure (HF) and a control group. Methods: Sixteen patients admitted to our ward for acute decompensation of HF were enrolled in this study. Transthoracic echocardiography (TTE) with two-dimensional speckle-tracking analysis (2D ST) was performed in each patient. The patients were divided into two subgroups according to the value of left ventricular ejection fraction (EF) using a cut-off value of ≤40% to distinguish heart failure with reduced ejection fraction (HFrEF) from heart failure with preserved ejection fraction (HFpEF). The control group consisted of 16 individuals without a history of cardiovascular disease, each of whom underwent 2D ST analysis as well. Results: We found that LV-GLS and R-LAS were significantly lower in both the HFrEF and HFpEF subgroups in comparison with the control group (LV-GLS: −13.4 ± 4.7% vs. −19.7 ± 2.5%, p ˂ 0.05; R-LAS: +12.2 ± 6.9% vs. +40.3 ± 7.4%, p ˂ 0.05). Furthermore, there was a significant difference in LV-GLS (−9.6 ± 3.2% vs. −15.2 ± 4.3%, p ˂ 0.05) but not in R-LAS (+13.7 ± 8.6% vs. +11.4 ± 6.2%) between the HFrEF and HFpEF subgroups. Conclusions: Our study demonstrated a significant difference in LV-GLS and R-LAS in all enrolled HF patients compared to the control group. There was also a significant difference in LV-GLS between the HFrEF and HFpEF subgroups. Full article

Hypertension represents one of the primary and most common risk factors leading to the development of heart failure (HF) across the entire spectrum of left ventricular ejection fraction. A large body of evidence has demonstrated that adequate blood pressure (BP) control can reduce cardiovascular events, including the development of HF. Although the pathophysiological and epidemiological role of hypertension in the development of HF is well and largely known, some critical issues still deserve to be clarified, including BP targets, particularly in HF patients. Indeed, the management of hypertension in HF relies on the extrapolation of findings from high-risk hypertensive patients in the general population and not from specifically designed studies in HF populations. In patients with hypertension and HF with reduced ejection fraction (HFrEF), it is recommended to combine drugs with documented outcome benefits and BP-lowering effects. In patients with HF with preserved EF (HFpEF), a therapeutic strategy with all major antihypertensive drug classes is recommended. Besides commonly used antihypertensive drugs, different evidence suggests that other drugs recommended in HF for the beneficial effect on cardiovascular outcomes exert advantageous blood pressure-lowering actions. In this regard, type 2 sodium glucose transporter inhibitors (SGLT2i) have been shown to induce BP-lowering actions that favorably affect cardiac afterload, ventricular arterial coupling, cardiac efficiency, and cardiac reverse remodeling. More recently, it has been demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Other proposed agents, such as endothelin receptor antagonists, have provided contrasting results in the management of hypertension and HF. A novel, promising strategy could be represented by small interfering RNA, whose actions are under investigation in ongoing clinical trials. Full article

Objectives: Dapagliflozin has shown efficacy in clinical trials in patients with heart failure and reduced ejection fraction (HFrEF). However, real-world data on its use and outcomes in routine clinical practice are limited. We aimed to evaluate the utilisation and safety profile of dapagliflozin in a real-world population of HFrEF patients within the Marche region. Methods: Nine cardiology departments within the Marche region retrospectively included HFrEF patients who were initiated on dapagliflozin therapy in an outpatient setting. Data on medical history, comorbidities, echocardiographic parameters, and laboratory tests were collected at baseline and after 6 months. Telephone follow-up interviews were conducted at 1 and 3 months to assess adverse events. We defined the composite endpoint score as meeting at least 50% of four objective measures of improvement among: weight loss, NYHA decrease, ≥50% Natriuretic peptides (NP) decrease, and guideline/directed medical therapy (GDMT) up titration. Results: We included 95 HFrEF patients aged 66 ± 12 years, 82% were men, 48% had ischemic heart disease, and 20% had diabetes. At six months, glomerular filtration rate declined (p = 0.03) and natriuretic peptides levels decreased, on average, by 23% (p < 0.001). Echocardiographic measurements revealed a decrease in pulmonary artery pressure (p < 0.001) and E/e’ (p < 0.001). In terms of drug therapy, furosemide dosage decreased (p = 0.001), and the percentage of the target dose achieved for angiotensin receptor–neprilysin inhibitors increased (p = 0.003). By multivariable Cox regression, after adjustment for age, sex, the presence of diabetes/prediabetes, and HF duration, higher baseline Hb concentrations (HR 1.347, 95% CI 1.038–1.746, p = 0.025), and eGFR levels (HR 1.016, 95% CI 1.000–1.033, p = 0.46). Conclusions: In a real-life HFrEF population, dapagliflozin therapy is safe and well-tolerated, improves echocardiographic parameters and biomarkers of congestion, and can also facilitate the titration of drugs with a prognostic impact. Full article

Background: Heart failure (HF) patients experience reduced functional fitness level (determining the performance of routine, daily activities) and diminished exercise capacity (linked to more effortful activities). Aim: The aim of the study is to assess this relationship using functional fitness tests compared to peak VO2 and VE/VCO2 slope in the context of exercise capacity and ventilatory response to exercise. Methods: A total of 382 men with stable HFrEF (age: 61 ± 10, NYHA class I/II/III/IV: 16/50/32/2%, LVEF: 30.5 ± 8.3%) underwent cardiopulmonary exercise testing (CPX) and a Senior Fitness Test (SFT). Afterwards, the patients were divided according to the 2capacity with peak VO2 ≥ 18 mL/kg/min, those with higher or lower ventilatory responses (VE/VCO2 slope ≥ 35 vs. <35) to the exercise were compared. Results: Patients who covered shorter distances in the 6 min walking test showed worse results in the functional tests (‘stand up and go’, ‘chair stand’ and ‘arm curl’) and CPX (lower peak VO2, shorter exercise time and higher VE/VCO2 slope). Subjects classified into Class D demonstrated the worst results in all elements of SFT; those in Class A demonstrated the best results. Significant differences that were analogous occurred also between classes B and C. Among the participants who reached peak VO2 ≥ 18 mL/kg/min (n = 170), those with VE/VCO2 slope ≥ 35 were characterized by worse physical fitness as compared to those with VE/VCO2 < 35. Conclusion: Reduced exercise tolerance led to worsening physical function in patients with HFrEF. Moreover, limitations in physical fitness seem to be distinctive for those patients showing excessive ventilatory response to exercise slope VE/VCO2 (≥35). The Senior Fitness Test may be considered as a useful tool for assessing comprehensive functional and clinical status and risk stratification in patients with HFrEF, especially those with extremely low exercise capacity. Full article

Heart failure (HF) is characterized by low-grade immune-mediated inflammation due to increased Toll-like receptor (TLR) expression as response to endotoxin increase and dysregulated gut barrier permeability. We investigated TLR expression and possible gut dysbiosis in HF patients compared to a control group. We enrolled 80 Caucasian HF patients and 20 controls. Low-grade immune-mediated inflammation was evaluated by TLR expression, while gut dysbiosis by the detection of zonulin and bacterial endotoxin activity in a semi-quantitative (endotoxin activity assay [EAA]) and quantitative (limulus amebocyte lysate [LAL] test) way. Compared to controls, patients with HF showed significantly higher age and blood pressure values, worse metabolic profile and kidney function, higher inflammatory biomarkers levels, and lower levels of zonulin and endotoxin activity. When dividing failing patients in those with reduced ejection fraction (HF-rEF) and those with preserved ejection fraction (HF-pEF), HF-rEF patients showed significantly higher values of inflammatory biomarkers and TLR expression than HF-pEF patients. Gut permeability biomarkers inversely correlated with the severity of HF and positively with renal function. eGFR was retained as an independent predictor of zonulin variation in all the three groups of failing patients. Present data work to extend current knowledge about the role of gut microbiota in immune-mediated inflammation in HF. Full article

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3⁺ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. Full article