Search Results (580)

Background: The clinical impact of oral semaglutide on cardiac biomarkers in real-world patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) remains unclear. We evaluated whether initiation of oral semaglutide was associated with a reduction in B-type natriuretic peptide (BNP) levels and explored factors associated with this response. Methods: We retrospectively enrolled 27 patients with HFpEF who initiated oral semaglutide for T2DM management at a single academic center. Clinical data were collected at three time points: three months before treatment initiation (pre-treatment period), at initiation (baseline), and three months after semaglutide initiation (on-treatment period). The primary outcome was the change in the common logarithm of BNP levels (log BNP) during the on-treatment versus pre-treatment period. Results: Median age was 67 (59, 78) years and 21 (77.8%) were men. Log BNP remained stable during the pre-treatment period (p = 0.34) but decreased significantly during the on-treatment period (p < 0.001). The reduction in log BNP during the on-treatment period was significantly greater than during the pre-treatment period (mean difference −0.35, 95% confidence interval −0.44 to −0.11, p < 0.001). Concomitant reductions were observed in HbA1c, body weight, C-reactive protein, left atrial volume index, and left ventricular mass index. Changes in C-reactive protein levels were significantly correlated with those in log BNP (r = 0.46, p = 0.015). Conclusions: In patients with HFpEF and T2DM, three-month oral semaglutide therapy was associated with reductions in BNP, as well as improvements in glycemic control, systemic inflammation, left atrial volume index, and left ventricular mass index. Full article

Background and Objective: Heart failure (HF) is a major cause of morbidity in adults with congenital heart disease (ACHD), who may also have limited access to transplant. Intermittent levosimendan administration has shown benefit in advanced HF due to acquired heart disease, but currently, there are no data on ACHD. We aimed to evaluate the effects of this treatment in ACHD patients with advanced heart failure, focusing on both clinical status and objective outcome measures. Materials and Methods: We conducted a single-center retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥ three intermittent levosimendan infusions (either 12.5 mg once monthly or 6.25 mg every two weeks over a 6 h infusion) between March 2020 and January 2025 at a tertiary ACHD center. Clinical outcomes during follow-up were compared with those in the year preceding treatment. Primary endpoints included safety and HF-related adverse events, particularly HF hospitalizations. Secondary endpoints included changes in New York Heart Association (NYHA) class, nt-pro-B-natriuretic peptide (nt-proBNP) values, and ventricular systolic function assessed by echocardiography. Results: Twelve patients (median age 44.6 years, 25% female) were included, with heterogeneous congenital diagnoses and advanced HF. Five patients had a systemic right ventricle (sRV) and one had a single ventricle with previous Fontan palliation. During a median follow-up of 1.3 years, intermittent levosimendan was well-tolerated, with no treatment-limiting adverse events. Two patients (16%) required hospitalization for HF during follow-up compared with 8 (66%) in the year preceding treatment. The incidence of HF hospitalizations decreased from 0.83 to 0.20 events per person-year during follow-up (p = 0.03), although findings should be interpreted cautiously given the small sample size and retrospective design. NYHA functional class improved significantly (p = 0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with a systemic right ventricle (sRV) showed an increase in right ventricular fractional area change (27 ± 7.4% to 30.6 ± 7%, p = 0.02); however, this observation should be regarded as exploratory given the limited sample size. Two deaths occurred, consistent with the severity of the underlying disease and not directly attributable to levosimendan and the Fontan patient received a successful heart and liver transplant. Conclusions: In a small, real-world cohort of ACHD and advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and signals of enhanced systemic right ventricular function. These hypothesis-generating findings may help inform future multicenter studies in ACHD patients with advanced HF, suggesting a potential role for intermittent levosimendan in selected patients, while highlighting the need for prospective, adequately powered studies to confirm its efficacy and better define optimal patient selection. Full article

Background: Many patients with heart failure with reduced ejection fraction (HFrEF) remain undertreated in routine practice. Delayed treatment intensification, poor adherence, and fragmented follow-up are common barriers. Low-cost digital support may help reduce this implementation gap. Objective: This study evaluated whether a simple digital support pathway was associated with better 6-month treatment adherence and guideline-directed medical therapy (GDMT) optimization in ambulatory patients with stable HFrEF. Methods: This single-center matched cohort study compared a prospective digital-support cohort with a historical usual-care cohort. The intervention combined smartphone-based telemanagement, home blood pressure and heart-rate reporting, daily weight surveillance, and scheduled video consultations. The co-primary endpoints were treatment adherence at 6 months and GDMT optimization, assessed by change in foundational HFrEF drug classes and by a prespecified exploratory GDMT optimization score. Results: After 1:1 propensity-score matching, 200 patients were included, with 100 patients in each cohort. Treatment adherence at 6 months was higher in the digital-support cohort than in usual care (82.0% vs. 64.0%, p = 0.004). The intervention cohort also had more frequent class addition, more dose escalation, a greater increase in foundational drug classes, and a larger improvement in GDMT optimization score (all p < 0.001). Heart failure hospitalization and the composite of heart failure hospitalization or all-cause death were less frequent in the digital-support cohort, but these clinical outcomes were exploratory. Conclusions: A pragmatic low-cost digital support pathway was associated with better adherence and more complete GDMT optimization in ambulatory patients with HFrEF. The findings support further prospective multicenter evaluation. Full article

Vericiguat is currently indicated for patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical worsening, based on evidence demonstrating a reduction in cardiovascular death or heart failure hospitalization in a high-risk population. While this positioning is clinically justified, it may underestimate the broader pathophysiological context in which soluble guanylate cyclase (sGC) stimulation may be relevant, particularly in phases of persistent biological activation following apparent clinical stabilization. In routine practice, acute coronary syndromes (ACS), acute heart failure (AHF), and chronic HFrEF are approached as distinct clinical entities. However, these conditions often represent sequential manifestations of a continuous disease trajectory driven by persistent endothelial dysfunction, impaired nitric oxide–sGC–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling, and residual vascular risk. In this perspective, we revisit the mechanistic and clinical rationale for vericiguat and propose a reframing of its therapeutic role. Its greatest utility may lie in patients with recently worsening HFrEF who remain biologically vulnerable after stabilization. Extension of this concept to post-ACS populations remains hypothesis-generating and is not supported by direct clinical evidence. This “post-stabilization vulnerable state” represents a clinically recognizable yet insufficiently targeted phase, characterized by ongoing biological activation despite apparent clinical improvement. Adopting a continuum-based view of cardiovascular disease may improve alignment between pathophysiology and treatment, refine patient selection, and inform future trial design focused on this early post-event window. Importantly, this perspective is hypothesis-generating and reflects an effort to align emerging mechanistic insights with clinical trajectory, rather than to extend current indications beyond the available evidence base. Full article

Background/Objectives: Clozapine is the sole antipsychotic approved for treatment-resistant schizophrenia, but it is a double-edged therapeutic option due to various lethal adverse reactions. This study aimed to assess the risk of long-term clozapine medication-induced cardiotoxicity, which has not yet been fully elucidated. Methods: This study is a multicenter retrospective cohort study of patients with schizophrenia in Japan and China who received clozapine monotherapy. Cases for which serum NT-proBNP concentration and LVEF derived from echocardiography were available in 2025 were included. In addition, blood examinations, including those administered by the Japanese Clozaril Patient Monitoring Service, were statistically analyzed as independent variables. Results: Among a total of 315 cases, including 99 Japanese (clozapine exposure duration: 57.5 ± 4.0 months) and 216 Chinese (208.1 ± 11.0 months) cases, were enrolled. In both Japan and China, age-standardized prevalence of heart failure among patients with prescribed clozapine were higher compared to general population, with odds ratios of 3.2 (95%CI: 1.4–6.4) and 6.9 (95%CI: 3.6–12.0), respectively. The risk factors for stage-B heart failure associated with clozapine were prolonged exposure duration, higher plasma levels of clozapine, and increasing monocytes. Unexpectedly, over 70% of cases with stage-B heart failure associated with clozapine identified in this study did not have metabolic complications. Other than those with cardiomyopathy, myocardial infarction, ileus, or chronic renal failure, no cases with ejection fraction < 50% were observed, suggesting that stage-B heart failure associated with clozapine is speculated to be likely suggestive of HFpEF. Conclusions: Traditionally, psychiatry has focused on myocarditis and cardiomyopathy developing several weeks and months after initiation of clozapine medication; however, this study revealed asymptomatic heart failure as a third cardiac adverse reaction of clozapine that develops years later. Therefore, regular monitoring of NT-proBNP contributes to improving long-term prognosis of treatment-resistant schizophrenia with prescribed clozapine. Full article

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) promote beneficial effects on cardiac reverse remodeling (RR) in heart failure (HF). However, most imaging evidence focuses on single chambers, mainly the left ventricle (LV) or left atrium (LA), whereas integrated biventricular and atrial remodeling remains less explored. Moreover, real-world data are limited, and myocardial–flow coupling markers, such as hemodynamic forces (HDFs), are scarcely investigated, with uncertain sex-related differences. Purpose: To evaluate multi-chamber cardiac RR after SGLT2i initiation in a real-world HF population. Secondary aims are to assess whether changes in HDFs provide additional functional insight into myocardial–flow coupling beyond conventional echocardiographic indices, and to descriptively explore sex-related differences in echocardiographic remodeling. Methods: Patients with HF and ejection fraction (EF) ≤ 45%, naive to SGLT2i and on stable guideline-directed medical therapy for ≥3 months, were enrolled. Standard and advanced echocardiography were performed at baseline and follow-up, including speckle-tracking and HDFs assessment. NYHA class and NT-proBNP were collected. Analyses were performed overall and stratified by sex. Results: Sixty-eight patients were included. After 6 months, RR was observed across all chambers: LV-RR in 33 patients (49%), right ventricular (RV) RR in 35 (52%), biventricular RR in 18 (27%), and LA-RR in 14 (21%). HDFs showed significant realignment, suggesting association with improved myocardial–flow coupling. RR effects were comparable between sexes (p > 0.05). NT-proBNP significantly decreased. Conclusions: In this real-world cohort, SGLT2i therapy was associated with significant multi-chamber RR and HDFs realignment, supporting improved myocardial–flow coupling beyond conventional indices. Exploratory sex-related analyses showed no significant differences. Larger and longer-term randomized studies are warranted. Full article

Background: Dietary interventions in heart failure (HF) remain limited, with current guidance focused largely on sodium restriction. Ketone metabolism has emerged as a potential therapeutic target in HF, with ketone supplementation shown to improve cardiac function. However, there are currently no studies investigating factors affecting adherence to a ketogenic diet (KD) in HF. Aim: To explore the factors influencing adherence to a KD in patients with HF to inform future dietary interventions. Method: This qualitative study was embedded within the KETO-HF pilot randomised controlled trial, in which participants with HF with reduced ejection fraction undertook a 4-month KD. Consenting participants were invited to complete semi-structured interviews. Interviews were audio-recorded, deidentified and transcribed verbatim. Data were analysed using thematic analysis with a mixed inductive–deductive strategy. Results: Fifteen participants were interviewed. Facilitators of adherence were: (1) personal motivation and self-regulation; (2) improved well-being; (3) interpersonal support and; (4) adaptive strategies and improved nutritional literacy. Barriers included: (1) early-phase physiological and psychological challenges; (2) social and cultural friction; (3) competing family and work demands and; (4) limited availability of suitable foods, particularly difficulty managing social situations and dining out. Conclusions: Adherence to a KD in people with HF is shaped by a combination of individual and social factors. These findings highlight the need for improved education, support, and increased food options to optimise implementation of dietary ketosis in HF. Full article

Introduction: Adipose tissue (AT) is increasingly recognized as an active endocrine and immunological organ involved in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Dysfunctional AT, particularly visceral, promotes chronic low-grade inflammation, endothelial dysfunction, and microvascular damage. At the same time, higher body mass is associated with paradoxically lower natriuretic peptide (NP) levels, which may impact diagnostic accuracy in HFpEF. Methods: This narrative review summarizes the current evidence on the interplay between adipose tissue, NPs, and HFpEF, focusing on pathophysiological mechanisms, AT distribution, and clinical implications. Results: Adipokine-mediated inflammation contributes to the myocardial stiffness, fibrosis, and cardiac remodeling characteristic of HFpEF. Visceral adipose tissue, including epicardial fat, exhibits a more proinflammatory profile than subcutaneous fat. Obesity is associated with decreased NP levels due to increased clearance and decreased production. Consequently, lower NP levels may lead to underdiagnosis or misclassification of HFpEF, particularly in diagnostic algorithms such as HFA-PEFF and H₂FPEF. Patients with low BMI or cachexia exhibit elevated NP levels, reflecting advanced disease and catabolic states. Conclusions: The obesity-natriuretic paradox poses a key diagnostic challenge in HFpEF. Interpretation of natriuretic peptide levels should take body composition into account, and refinement of biomarker cutoff values may improve diagnostic accuracy. Full article

Bacground/Objectives: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. We aimed to analyze the clinical efficacy of oral semaglutide in terms of health status and change in body weight in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Methods: This observational, retrospective, real-world study included patients treated with oral semaglutide (Oral-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was heart failure status, defined as a ≥5 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 24 months. Results: After 1:1 propensity score matching, 162 patients were included in each group (mean age 71.0 years, mean body mass index 32.1, 52.9% females). Patients in the Oral-Sema Group were more likely to have improvement in heart failure health status from baseline to 24 months (OR: 2.45; 95%CI: 1.25–3.65; p = 0.012). The mean change in body weight was −8.0 ± 2.1 kg in patients with oral semaglutide and −1.9 ± 1.0 kg in control patients (p < 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and body weight (r = −0.558, p < 0.01) and glycated hemoglobin (r = −0.491, p = 0.017). It had good tolerability and safety. Conclusions: Oral semaglutide was associated with an improvement in heart failure health status and weight loss in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with reduced ejection fraction is needed. Full article

Background: Heart failure (HF) remains a major early complication following myocardial infarction (MI), contributing significantly to morbidity and adverse clinical outcomes. Reliable early risk stratification is essential for optimizing post-MI management. This study aimed to evaluate the prognostic performance and incremental value of the HALP (Hemoglobin–Albumin–Lymphocyte–Platelet) score and the AHEAD score in predicting 1-month HF after MI. Methods: This retrospective cohort study included 3205 consecutive patients with MI. The primary endpoint was the development of HF within one month. Three multivariable logistic regression models were constructed: a baseline clinical model (Model 1), a HALP-integrated model (Model 2), and an AHEAD-integrated model (Model 3), with component variables excluded to avoid collinearity. Model performance was assessed using odds ratios (ORs), 95% confidence intervals (CIs), and discrimination metrics (AUC). Incremental predictive value was further evaluated using net reclassification improvement (NRI). Internal validation was performed using bootstrapping and 5-fold cross-validation. A predefined subgroup analysis was conducted in patients with preserved ejection fraction (EF ≥ 40%), excluding EF from the models. Results: In the full cohort, all models demonstrated high discriminative ability for 1-month HF (AUC range: 0.950–0.954), with minimal differences between models. The AHEAD-based model showed the highest point estimate (AUC = 0.954, 95% CI: 0.944–0.963), but ROC curves were largely overlapping. Despite limited changes in AUC, the AHEAD score provided moderate improvement in risk reclassification (NRI = 0.287), whereas the HALP score showed minimal incremental value (NRI = 0.152) and was not independently associated with HF in multivariable analysis. In the EF ≥ 40 subgroup, HF incidence was lower (1.9%), and model performance was attenuated but remained robust (AUC range: 0.839–0.882), with the AHEAD score retaining strong independent predictive value. Peak CKMB and creatinine were consistently associated with increased HF risk. Although the odds ratio for CKMB appeared close to unity, this reflects unit scaling, and clinically meaningful increases corresponded to substantial risk increments. A clear dose–response relationship between AHEAD score and HF probability was observed. Conclusions: While both HALP and AHEAD scores are associated with post-MI HF risk, only the AHEAD score provides consistent independent and incremental prognostic value beyond established clinical predictors. Its simplicity and ability to capture comorbidity burden make it a practical adjunct for early risk stratification, particularly in patients with preserved EF. However, given the minimal differences in discrimination metrics and lack of external validation, these findings should be interpreted cautiously and considered hypothesis-generating. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a highly prevalent multisystem disorder and is strongly associated with increased cardiovascular risk. Cardiovascular diseases represent the leading cause of mortality in this population. As the hepatic manifestation of systemic metabolic dysfunction, MASLD is initiated by excess lipid accumulation driven by increased dietary fatty acid intake and accelerated de novo lipogenesis. This triglyceride overload induces lipotoxicity, triggering hepatocellular injury, immune activation, and mitochondrial dysfunction. Excessive mitochondrial reactive oxygen species (ROS) generation acts as a critical second hit, promoting inflammatory cytokine production and disease progression. Beyond lipid dysregulation, impaired hepatic insulin signaling leads to hyperglycemia and compensatory hyperinsulinemia, further stimulating lipogenesis and reinforcing a self-perpetuating metabolic cycle. Persistent ROS production overwhelms antioxidant defenses and depletes hepatic glutathione (GSH), resulting in systemic redox imbalance. These disturbances extend beyond the liver, contributing to atherogenic dyslipidemia and chronic inflammation. In parallel, gut dysbiosis and increased intestinal permeability amplify immune activation. Reduced circulating GSH further weakens systemic antioxidant capacity; oxidative stress may represent a central mechanistic link between MASLD and CVD. In concert with metabolic and inflammatory mediators, ROS disrupt pathways governing vascular and myocardial homeostasis, leading to coronary atherosclerosis, microvascular dysfunction, left ventricular remodeling, hypertrophy, and impaired relaxation. Clinically, this translates into an increased burden of coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction. Given this integrated pathophysiology, early identification of subclinical cardiovascular involvement is essential. We highlight emerging biomarkers, advocate for multidisciplinary screening strategies, and discuss integrated pharmacological approaches targeting shared metabolic pathways. Recognizing MASLD as a cardiovascular risk amplifier is critical for improving risk stratification and enabling the development of effective, co-targeted therapeutic strategies. Full article

Background: Heart failure with preserved ejection fraction (HFpEF) has multiple phenotypic manifestations with heterogeneous treatment responses. Objective: To evaluate the effect of sacubitril/valsartan (Sac/Val) on functional capacity and cardiac remodeling in overweight/obese HFpEF patients with concentric left ventricular hypertrophy (LVH). Methods: Sixty-one overweight/obese HFpEF patients (body mass index ≥ 25 kg/m²) with hypertensive LVH (LV mass index ≥ 115 g/m² for men or ≥94 g/m² for women) were randomized to Sac/Val (100–400 mg a day; n = 30) versus the usual care group (n = 31) for 6 months. Changes in six-minute walk test distance (6MWTD) were the primary outcomes. Secondary outcomes included changes in echocardiographic parameters of cardiac structure and function, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: After 6 months of Sac/Val therapy, 6MWTD increased, and E/e′ ratio, LV mass index, LA volume index, and NT-proBNP levels decreased compared with the usual care group (p < 0.05 for all). Conclusions: In overweight/obese patients with HFpEF and LVH, Sac/Val significantly improved functional capacity and reduced LV mass and filling pressure compared with standard medical therapy. Full article

Background/Objectives: Revascularization of chronic total occlusions (CTO) in patients with heart failure and reduced ejection fraction (HFrEF) remains controversial, as randomized trials have not demonstrated a clear prognostic benefit. Methods: We present an imaging-guided case series of patients with ischemic HFrEF who underwent CTO percutaneous coronary intervention (PCI) following myocardial viability assessment using single-photon emission computed tomography (SPECT). Contemporary antegrade and retrograde techniques were employed. Results: At 6- and 12-month follow-ups, all patients demonstrated marked improvement in NYHA (New York Heart Association) functional class, significant reductions in NT-proBNP (N-terminal pro-brain natriuretic peptide) levels, and substantial improvement in quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). These benefits occurred despite only modest improvement in left ventricular (LV) ejection fraction (EF) and limited reverse remodeling. SPECT enabled identification of viable but ischemic myocardium, supporting individualized revascularization decisions. Conclusions: In selected high-risk patients with ischemic HFrEF, CTO-PCI was associated with meaningful clinical and biomarker improvement independent of substantial EF recovery. Careful patient selection, incorporating myocardial viability assessment, may refine individualized clinical decision-making in selected patients. These findings support an imaging-guided approach and warrant further prospective evaluation. Full article

Background/Objectives: Carvedilol is an adrenergic blocker FDA-approved to improve outcomes in heart failure with reduced ejection fraction. Clinical trials examining whether carvedilol may be cardioprotective in the setting of cancer therapy-induced heart failure have generated mixed results that may depend on the cancer regimen, tumor, or comorbidities. Methods: To investigate the therapeutic potential of carvedilol to mitigate doxorubicin cardiotoxicity in cardiomyocytes, myocardial tissue, and in vivo, independent of confounding factors in clinical studies, we utilized disease-free cardiac slices and cardiomyocytes from mice, dogs, and human in vitro, and in wildtype mice injected with doxorubicin in vivo. We further evaluated the impact of carvedilol in dogs with cancer receiving doxorubicin. Results: In primary canine and murine cardiac slices, carvedilol treatment restored autophagy and prevented apoptosis from doxorubicin. Carvedilol restored mitochondrial energetics in human, canine, and murine models. In wildtype mice challenged with doxorubicin, carvedilol prevented declines in cardiac function and alterations in cardiac structure. In pet dogs with cancer and undergoing doxorubicin treatment, carvedilol was beneficial in preserving cardiac function and structure. Conclusions: Carvedilol activates cardioprotective autophagy, arrests doxorubicin-induced cell death, and improves energetics and cardiac structure and function across species. Full article

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem affecting approximately 1–2% of the adult population in highly developed countries. It is a heterogeneous condition with cardiometabolic disorders such as obesity, insulin resistance, diabetes mellitus, and hypertension. Pathophysiologically, HFpEF is currently recognized as a systemic disease characterized not only by impaired left ventricular relaxation and increased ventricular stiffness but also by chronic inflammation, endothelial dysfunction, myocardial fibrosis, and multi-organ involvement. This study aims to investigate the role of metabolic organ crosstalk and nutritional modulation in different HFpEF phenotypes. This review analyzes the current literature to investigate the interactions between the heart, adipose tissue, liver, and spleen in the pathophysiology of HFpEF. Chronic low-grade inflammation and adipose tissue dysfunction play central roles in the progression of HFpEF by activating the immune system, favoring ectopic lipid accumulation, and exacerbating fibrosis. The identification of specific HFpEF phenotypes (e.g., obesity-related versus aging-related) requires the application of distinct nutritional strategies that target metabolic inflammation and organ crosstalk, which may improve both myocardial and systemic function. HFpEF is a complex systemic disorder that requires phenotype-specific therapeutic approaches. Precision nutrition based on specific biomarkers, together with comprehensive cardiovascular management, may enhance therapeutic efficacy and complement pharmacological treatment in patients with HFpEF. Full article