Management Of Heart Failure Research Articles

Heart failure (HF) management increasingly requires multimodal assessment beyond cardiac function. Although echocardiography remains central, skeletal muscle and diaphragmatic dysfunction-key drivers of exercise intolerance-are underdiagnosed. This review synthesizes two critical aspects: (1) the pathophysiological heterogeneity of muscle involvement across HF subtypes [HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and (2) the clinical utility of muscle ultrasound as a dynamic, bedside-compatible tool for risk stratification and personalized interventions. Emerging evidence reveals distinct mechanisms: HFrEF predominantly associates with diaphragmatic atrophy and mitochondrial dysfunction, whereas HFpEF is characterized by reduced diaphragmatic motion and skeletal muscle fat infiltration. Ultrasound-derived parameters, such as echo intensity for quadriceps fat quantification and diaphragm thickness ratio for inspiratory weakness, strongly correlate with functional outcomes (e.g., 6-min walk distance and peak VO2). Notably, a quadriceps echo intensity > 28 dB in HFrEF or a diaphragmatic excursion < 2.5 cm in HFpEF independently predicts adverse prognosis, guiding targeted interventions such as inspiratory muscle training or anti-inflammatory therapies. However, critical gaps persist, including the lack of standardized cutoff values for HF subtypes and insufficient data on ultrasound-guided therapeutic monitoring. Future research should prioritize subtype-specific protocols and validate cost-effective ultrasound algorithms against standard modalities. By bridging pathophysiology and clinical application, this review underscores muscle ultrasound's transformative potential in refining HF phenotyping, ultimately enhancing exercise capacity and reducing hospitalizations.

Abstract Introduction Heart Failure is a highly prevalent condition that can lead to a reduced Ejection Fraction (HFrEF) due to deterioration in cardiac output. It remains a condition with some of the highest morbidity and mortality rates. Novel therapies (ACE inhibitors or ARNIs, beta-blockers, MRAs, and SGLT2 inhibitors) – also named the four pillars of heart failure management have proven to slow progression and reduce hospital readmissions. However, despite their proven effectiveness, under-prescribing of these agents remains a significant concern. Aim This study aimed to review prescribing patterns for patients with HFrEF within the Primary Care Networks (PCNs) of the Dudley area, to identify gaps in the utilisation of the four pillars of HF therapy, and to develop recommendations to improve prescribing practices. Methodology A retrospective review was conducted across six PCNs in the Dudley area. Patients were identified using SNOMED codes within the EMIS electronic patient record system. The dataset included anonymised data for 3,940 patients coded with a diagnosis of HF and a reduced ejection fraction, and who were receiving at least one of the four pillar medications (ACE inhibitors, Beta Blockers, MRAs, and SGLT2 inhibitors). Descriptive data analysis was performed using Microsoft Excel. Since the study used anonymised retrospective data collected for service evaluation purposes, it did not require formal ethical approval. Results Among the 3,940 identified patients, 85% had been prescribed a Beta Blocker. However, prescribing rates for the remaining three pillar drugs were significantly lower, with only 62% of patients receiving three out of four recommended therapies. Dosing data revealed that a large proportion of patients were prescribed less than 50% of the target optimal dose, suggesting suboptimal titration practices. Discussion The findings reveal a significant gap in the optimisation and comprehensive prescribing of the four pillars of HF therapy in primary care across the Dudley PCNs. Although Beta Blocker usage is high, the underuse and underdosing of the other three pillar drugs suggest a need for improved clinical decision-making and medication titration. Limitations of this study include its retrospective nature and the reliance on coded data, which may not fully capture all clinical decision factors. The results highlight the importance of multidisciplinary collaboration and targeted educational interventions to support guideline-concordant prescribing and ultimately improve clinical outcomes for HF patients in the Dudley health economy.

Background.Increased exhaled breath acetone (EBA) concentrations might reflect impaired myocardial energetics and haemodynamic stress. We investigated the relation of EBA and cardiac structure, function, and exercise capacity in patients with or at risk of heart failure (HF).Methods.We enrolled outpatients with HF and reduced (<50%, HFrEF) or preserved (>50%, HFpEF) left ventricular ejection fraction (LVEF) and subjects with cardiovascular risk factors and/or structural heart disease without established HF. All participants underwent clinical and laboratory evaluation, resting transthoracic echocardiography, and a combined cardiopulmonary-echocardiographic stress test with EBA monitoring at rest (EBArest) and during exercise (EBAex).Results.Patients with HFpEF (n= 62) were older and more often female than those at risk of HF (n= 50) or with HFrEF (n= 41). EBArest(1.5, interquartile range (IQR) 1.0-3.1 vs 0.9, IQR 0.7-1.2 mcg l-1) and EBAex(2.4, IQR 1.5-4.4 vs 1.1, IQR 0.9-2.1 mcg l-1; allp< 0.0001) were significantly higher in patients with HF compared to others. Among HF patients, those in the highest EBAresttertile had lower LVEF, greater echocardiographic signs of congestion, higher NT-proBNP levels, and lower peak oxygen consumption, indicating impaired exercise capacity. In multivariate regression, NT-proBNP (p= 0.0004) and the slope of minute ventilation to carbon dioxide production (p= 0.0013) were independent predictors of EBArest(adjustedR2= 0.458).Conclusions.EBA concentrations are higher in patients with HF compared to those without, regardless of LVEF, and are associated with markers of disease severity. Further studies are needed to determine whether EBA measurement can aid in HF diagnosis and management.

Heart failure (HF) is slightly more common in primary aldosteronism (PA) than in essential hypertension, but early-onset HF remains rare. In such cases, underlying genetic cardiomyopathies should be considered. Autonomously secreted aldosterone and activation of the renin-angiotensin-aldosterone system can lead to extremely high aldosterone levels, worsening cardiac function and creating major therapeutic challenges. A 39-year-old male presented with progressive chest tightness and shortness of breath for 4 months. He had a 7-year history of hypertension and persistent hypokalemia. Electrocardiogram revealed a markedly reduced left ventricular ejection fraction of 18.3%. The patient was diagnosed with PA based on elevated plasma aldosterone concentration, an increased aldosterone-to-renin ratio, and a positive captopril challenge test. Computed tomography and adrenal vein sampling indicated unilateral PA. After initial HF management, the patient underwent laparoscopic adrenalectomy for PA treatment. According to the primary aldosteronism surgical outcome consensus criteria for postoperative evaluation of PA, complete biochemical remission (normalization of aldosterone-to-renin ratio and potassium) and partial clinical remission (stable blood pressure with reduced antihypertensive medication) were achieved 1 month postoperatively and have been maintained since. At the 8-month follow-up, his left ventricular ejection fraction had improved to 45.4% and BNP levels normalized. Whole-exon sequencing revealed a missense mutation of the dystrophin (DMD) gene. Certain DMD mutations are linked to X-linked dilated cardiomyopathy with absent or subclinical skeletal muscle involvement. Sanger sequencing confirmed the hemizygous mutation in the proband. The final diagnosis was poorly controlled PA with early-onset HF, potentially influenced by a coexisting DMD gene missense mutation that may modify both the onset and severity of PA-related HF. Early recognition and surgical treatment of PA with early-onset HF can substantially improve cardiac function, even in the presence of genetic susceptibility to cardiomyopathy. This case underscores the need to consider underlying cardiac genetic disorders in PA patients with atypical or early-onset HF and raises the hypothesis that the identified DMD variant may serve as a potential genetic modifier of HF severity in the context of PA.

Enalapril (ENA) is indicated for the management of heart failure, hypertension, and asymptomatic left ventricular dysfunction, while pediatric patients also benefit from its use in treating hypertension and congestive heart failure. ENA is commercially available as tablets with doses ranging from 2.5 to 20mg. However, achieving the typical starting dose of 0.1mgkg-1day-1 for infants and children can be challenging due to the limitations of available tablet strengths. This limitation is compounded by patients with dysphagia or those who are averse to swallowing tablets. Liquid oral formulations would facilitate adherence to treatment in these patients. The purpose of this study was to develop and optimize an oral liquid scalable-dose formulation of Enalapril Maleate at 2mgmL-1 following a Quality by Design approach. Quality Target Product Profiles, Critical Process Parameters, and Critical Quality Attributes (CQAs) were identified. CQAs with a higher level were further evaluated through a Design of Experiments (DoE) approach, including pH, physical stability, microbiological quality, and chemical stability. Chemical stability of ENA showed variation depending on the specific formulation conditions and the influence of pH, buffer type, preservative agent, and storage temperature on the stability of the active ingredient was determined by DoE. The final selected formulation: enalapril 2mgmL-1, pH 3.5, containing 10% v/v glycerin, 10mM citrate buffer, and 0.2% w/v sodium benzoate, demonstrated to be physically, chemically, and microbiologically stable for at least six months under refrigerated conditions, with drug recoveries exceeding 95%, and a robust Design Space was established for its manufacture and storage.

Heart failure is associated with a high risk of morbidity, mortality, and healthcare resource use. Its pathophysiology and treatment are complex and involve various neurohormonal systems. Early guideline-directed medical therapy is currently recommended in patients with heart failure with reduced ejection fraction; however, patients continue to be at high risk of rehospitalization and death. The VICTORIA clinical trial compared vericiguat, an oral soluble guanylate cyclase stimulator that restores the nitric oxide pathway, with placebo, added to guideline-recommended treatment. VICTORIA demonstrated a significant benefit compared to standard therapy. Nonetheless, it is essential to understand how vericiguat performs in real-world settings. A narrative literature review was performed to compare the findings of the VICTORIA trial and real-world evidence studies. Real-world evidence was analyzed from almost 6,000 patients. Vericiguat was shown to be associated with improvements in quality of life and New York Heart Association functional class, left ventricular reverse remodeling, and numerically lower rates of heart failure hospitalizations and mortality than in the VICTORIA trial, although it is used in older patients with more comorbidities. Moreover, real-world evidence studies showed these effects to be infrequent and similar to those reported in the VICTORIA trial, with low discontinuation rates, indicating that vericiguat was very well tolerated in a real-world population. We present the most comprehensive review to date on vericiguat in clinical practice, providing an overview of its effects on clinical, biochemical, and imaging parameters. Our findings suggest that vericiguat could be a component in the comprehensive management of heart failure with reduced ejection fraction. However, further specific investigations with longer follow-up and larger samples would enable us to resolve some of the hypotheses put forward in our study.

Heart failure is a common condition that affects millions of people worldwide and is associated with substantial morbidity and mortality. Acute decompensated heart failure refers to the worsening of symptoms that requires changes in drugs or the start of new treatments such as non-invasive positive pressure ventilation. This review summarizes the current data and provides an evidence based approach to the diagnosis and management of acute decompensated heart failure. The review discusses common nomenclature and classifications of the condition, followed by the diagnostic accuracy of medical history, physical examination, electrocardiography, radiographs of the chest, point-of-care ultrasound, and laboratory testing. Current and emerging medical treatments are also discussed.

Background/Objectives: Cognitive impairment (CI) is a common complication of heart failure (HF) that undermines self-care, adherence, and outcomes. This systematic review assessed the cognitive effects of pharmacological HF management and related cardiovascular therapies, identifying potential risks and benefits. Methods: Following PRISMA 2020, we searched PubMed, EMBASE, and Scopus for articles published in English between 1 January 2010 and 31 January 2025 (last search 31 January 2025). We included RCTs and cohort studies in adults with HF or high cardiovascular risk that reported cognitive outcomes. Non-pharmacological interventions, studies without relevant cognitive endpoints, and non-original research were excluded. Risk of bias was assessed using RoB 2 for RCTs and the Newcastle–Ottawa Scale for observational studies. Due to heterogeneity in study designs and cognitive measures, results were synthesized qualitatively without meta-analysis. Results: Of 530 records screened, 11 studies encompassing 58,190 participants met the inclusion criteria. Intensive blood pressure (BP) lowering was consistently associated with reduced risk of mild cognitive impairment or dementia compared with standard BP control. In HF populations, sacubitril/valsartan showed no adverse cognitive effects versus other RAAS inhibitors. Across RCTs and observational studies, β-blockers, ACE inhibitors, ARBs, diuretics, and statins showed no evidence of significant cognitive impairment. Comparisons of anticoagulants (dabigatran vs. warfarin; warfarin vs. aspirin) revealed no differences in cognitive trajectories, while optimized medical therapy was associated with parallel improvements in cognitive scores, left ventricular function, and renal parameters. Limitations: Evidence remains constrained by heterogeneity in study design and cognitive assessment tools (often brief screening instruments), inconsistent reporting, and generally short follow-up durations, which may obscure subtle or long-term effects. Conclusions: Contemporary pharmacological therapies for HF appear cognitively safe. Intensive BP control may confer cognitive benefit in high-risk populations, while guideline-directed treatments show no consistent evidence of cognitive harm. Optimized medical therapy may even support cognitive improvement alongside cardiac and renal recovery. Routine cognitive assessment should be integrated into HF care to support individualized management.

As a marker of atrial mechanics, left atrial (LA) strain offers unique insight into the functional impact of heart failure treatments. However, given its complex geometry and contractile pattern, the evolution of global and regional LA biomechanics during pressure overload and subsequent release remains unclear. We performed four-dimensional (4D) ultrasound in mice (n=8) to evaluate global and regional LA kinematics at baseline, 3weeks after transverse aortic constriction (TAC), and 1 and 4weeks after aortic debanding (deTAC). LA maximum volume increased from 11.8±0.8µL at baseline to 30.4±9.4µL after TAC (P=0.0024), returning to baseline after deTAC. LA ejection fraction declined from 68.0±5.8 to 29.1±9.2% after TAC (P<0.0001), partially recovering after deTAC. Global longitudinal strain dropped from 24.8±3.6% at baseline to 10.2±3.7% after TAC (P<0.0001), improving to 18.9±3.5% by 4weeks after deTAC (P=0.0073 vs baseline). Despite partial functional recovery, fibrosis remained elevated after pressure release. Notably, regional strain recovery was heterogeneous, with anterior strain measurements showing stronger correlations with delayed ventricular functional improvement than global LA strain, highlighting the superior predictive value of regional analysis. This approach reveals incomplete and region-specific atrial recovery following pressure overload reversal, offering new perspectives on reverse remodelling and potential prognostic value in heart failure management. KEY POINTS: Advanced 4D ultrasound enables precise assessment of regional left atrial strain dynamics throughout cardiac remodelling. Left atrial strain reveals region-specific remodelling patterns during both pressure overload and its reversal. Functional changes in the atrium, particularly in the anterior wall, serve as early predictors of subsequent ventricular remodelling.

Ethnopharmacological relevance Heart failure (HF) is a major global health challenge. Traditional therapies have limitations, while recent studies highlight plant extracts’ potential due to their medicinal properties and milder side effects. Objective This study conducts a systematic review and network meta-analysis (NMA) to assess the therapeutic effects of plant extracts on patients with heart failure, providing robust evidence for clinical practice. Materials and methods A comprehensive search of databases, including PubMed, Embase, and Cochrane Library, was performed. Studies were screened using predefined criteria to extract data and assess quality. Network meta-analysis enabled direct/indirect comparisons of multiple plant extracts’ efficacy in heart failure intervention. Results A total of 20 studies encompassing 2,077 patients were incorporated into the analysis. Astragalus extract demonstrated the highest efficacy in enhancing the 6-min walk test (6-MWT) score (surface under the cumulative ranking curve [SUCRA]: 90.70%) and reducing tumor necrosis factor-alpha (TNF-α) levels (SUCRA: 74.4%). Shenfu extract exhibited superior efficacy in decreasing B-type natriuretic peptide (BNP) values (SUCRA: 68.2%) and enhancing the quality of life (QL) (SUCRA: 77.0%). Red ginseng extract was more effective in improving left ventricular ejection fraction (LVEF) (SUCRA: 77.9%), while Ginkgo biloba extract showed greater efficacy in ameliorating New York Heart Association (NYHA) functional classification (SUCRA: 76.5%). Despite these findings, heterogeneity and methodological issues in the studies warrant further high-quality, large-scale randomized controlled trials (RCTs) to validate the results and determine the optimal plant extract use in heart failure treatment. Conclusion Astragalus extract, red ginseng extract, Ginkgo biloba extract, Terminalia arjuna extract, and Shenfu extract have demonstrated significant efficacy in heart failure management in the study for the selection of optimal plant extracts based on enhanced indicators of cardiac function outcomes. Continued research through rigorous randomized controlled trials is essential to substantiate and refine the current evidence.

Background: Natriuretic peptides such as BNP and NT-proBNP remain cornerstone biomarkers for diagnosing and management of heart failure (HF). However, their measurement is done mainly when HF is suspected or requires monitoring, posing a missed opportunity for early HF detection and proactive intervention in at-risk patients. This gap highlights the need for accessible, non-invasive tools that can support earlier screening and continuous assessment. Aim: To develop and validate multi-task deep learning models that simultaneously estimate natriuretic peptide values and classify clinically relevant strata directly from raw 12-lead and Lead I ECG waveforms. Methods: Two distinct one-dimensional residual convolutional neural network architectures were separately trained on 12-lead and Lead I ECG inputs, using paired ECG and BNP measurements within a ±2-hour window to ensure rigorous label alignment. The models performed both BNP regression and classification into clinically meaningful low (&lt;100 pg/mL) and elevated (&gt;500 pg/mL) strata. Internal validation used a holdout cohort from Wake Forest Baptist Health (WF) (Winston-Salem, NC), while external validation employed an independent cohort from the University of Tennessee Health Science Center (UTHSC) (Memphis, TN), which included NT-proBNP data and specific clinical thresholds (low &lt;125 pg/mL and elevated &gt;300 pg/mL). Performance was evaluated using AUC, PPV, and NPV for classification and Spearman correlation for regression. Results: The internal dataset (WF) included 102,311 paired ECG–BNP samples from 54,526 patients, with a holdout set of 10,264 samples for validation. The external cohort (UTHSC) comprised 88,179 same day ECG–NT-proBNP pairs. The multi-task models demonstrated strong classification accuracy and regression correlation across both datasets. Specifically, the 12-lead model achieved AUCs of 0.88–0.89 and Spearman correlations of 0.75 in internal BNP strata, with similar performance in the external NT-proBNP cohort (AUC 0.88, Spearman 0.75–0.76). The Lead I model showed slightly lower but robust performance. Detailed metrics with 95% confidence intervals are summarized in Table 1. Conclusion: This multi-task models provide accurate, simultaneous estimation and classification of natriuretic peptides from ECGs. This approach offers a rapid, non-invasive tool for HF biomarker assessment that may improve clinical workflows, enable ambulatory monitoring, and enhance timely clinical decision-making.

Background: AI holds great potential in improving cardiovascular disease diagnosis, risk assessment, and treatment. However, its clinical utility requires thorough validation through randomized controlled trials and real-world evidence. This meta-analysis evaluates the impact of AI on cardiovascular outcomes across various study designs. Methods: A systematic search across PubMed, Scopus, and ClinicalTrials.gov identified 45 studies (15 RCTs, 30 observational) from January 1, 2015, to January 1, 2025, with over 50,000 patients. The studies focused on AI models, including machine learning, deep learning, and natural language processing, applied to diagnostic imaging (e.g., ECG, echocardiography), risk prediction, and personalized treatment in cardiovascular conditions like CAD, heart failure, and arrhythmias. Random-effects meta-analysis was used to calculate summary effect sizes, accounting for study heterogeneity. Results: Our analysis demonstrates that AI-driven models substantially improve diagnostic performance in high-prevalence conditions like CAD and HF. Specifically, AI tools augmented diagnostic accuracy by 12% overall, achieving a sensitivity of 88% (versus 75% for conventional methods) and a specificity of 91% (versus 84%) in real-world clinical workflows. In heart failure management, AI-powered risk stratification models were associated with a significant 15% reduction in 5-year all-cause mortality (hazard ratio: 0.72, 95% CI: 0.65–0.79, p &lt; 0.01), reflecting their ability to identify high-risk patients for targeted interventions. Furthermore, AI algorithms predicting adverse cardiovascular events led to a notable 20% reduction in 30-day readmissions (relative risk reduction: 0.80, 95% CI: 0.75–0.85), as observed in large health system datasets. Beyond prediction, AI-based personalized treatment recommendations, derived from electronic health records and patient-specific physiological data, improved patient outcomes by 9%, particularly beneficial for elderly patients grappling with multi-morbidities. Crucially, real-world deployments of AI demonstrated a 17% reduction in unnecessary diagnostic procedures and a 12% decrease in time-to-diagnosis for acute events such as myocardial infarction, highlighting efficiency gains in routine clinical practice. Conclusions: AI shows promise in improving cardiovascular disease management, with better outcomes like reduced mortality and improved diagnostics.

<p> Introduction: Cognitive impairment is a prevalent but underrecognized comorbidity in Heart Failure (HF). This review aimed to synthesize recent evidence on the heart-brain axis, focusing on cerebral perfusion, brain structural changes, and their impact on cognition. </p><p> Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published between 2000 and 2025 using terms related to "heart failure," "cognitive dysfunction," "cerebral perfusion," and "neuroimaging." Eligible articles were screened for quality, with emphasis on recent, high-impact contributions. Extracted data included neuroimaging markers, neuropsychological outcomes, and mechanistic insights. </p><p> Results: Across studies, HF was consistently linked to reduced cerebral blood flow, gray matter atrophy, and white matter lesions. These alterations were associated with deficits in attention, memory, and particularly executive function. Advanced imaging modalities confirmed hypoperfusion and brain structural remodeling as key drivers of cognitive decline. Longitudinal data suggest a bidirectional association, whereby impaired cognition worsens self-care and clinical outcomes in HF. </p><p> Discussion: Systemic hypoperfusion and impaired cerebrovascular regulation appear central in the HF-cognition link. However, heterogeneity in study populations and limited longitudinal evidence remain critical gaps. The findings underscore the need for standardized cognitive screening in HF and for interventions that address both cardiovascular and neurocognitive health. </p><p> Conclusion: Heart failure contributes to cognitive decline through cerebral hypoperfusion and structural brain changes. Early recognition and integration of cognitive assessment into HF management could improve outcomes and guide future preventive strategies.

Background: Optimal fluid management is central to heart failure (HF) care, yet the clinical efficacy of fluid restriction remains inconclusive. This updated systematic review and meta-analysis evaluates the impact of fluid restriction compared to liberal fluid intake on cardiovascular and patient-centered outcomes in individuals with HF. Methods: This study adhered to PRISMA guidelines. Ten randomized controlled trials involving 1,465 HF patients were included (731 fluid restriction; 734 liberal intake). Primary and secondary outcomes assessed were HF re-hospitalization, all-cause mortality, weight change, quality of life (QOL), thirst, intravenous (IV) diuretic use, and laboratory markers (serum sodium, creatinine, brain natriuretic peptide (BNP). Pooled estimates were calculated using a random-effects model. Subgroup analyses were conducted by HF subtype, clinical status (acute vs. chronic), and sodium restriction. Results: Fluid restriction showed a trend toward reduced HF re-hospitalizations compared to liberal fluid intake, although the difference was not statistically significant (RR: 0.71; 95% CI: 0.50 to 1.02; p = 0.06; Figure 1A ). No significant difference was observed in all-cause mortality (RR: 0.71; 95% CI: 0.43 to 1.18; p = 0.19; Figure 1B ). Similarly, weight change (WMD: –1.58 kg; 95% CI: –3.92 to 0.76; p = 0.19; Figure 1C ), QOL (SMD: 0.15; 95% CI: –0.14 to 0.44; p = 0.30; Figure 2B ), thirst (WMD: 4.96; 95% CI: –4.05 to 13.97; p = 0.28; Figure 2A ), and IV diuretic use (WMD: 3.50; 95% CI: –5.80 to 12.80; p = 0.46; Figure 2C ) did not differ significantly between groups. Laboratory outcomes also showed no significant differences: serum sodium (WMD: 0.90 mmol/L; 95% CI: –0.79 to 2.58; p = 0.30; Figure 3A ), serum creatinine (WMD: –0.10 mg/dL; 95% CI: –0.22 to 0.01; p = 0.08; Figure 3B ), and BNP (MD: –51.41; 95% CI: –171.44 to 68.61; p = 0.40; Figure 3C ). Subgroup analyses revealed significant benefits in patients with chronic HF for both re-hospitalization (p = 0.01) and serum creatinine levels (p &lt; 0.01). Conclusions: Fluid restriction may reduce re-hospitalization risk and provide modest clinical benefits in patients with chronic HF. However, no statistically significant improvements were seen in mortality or broader clinical outcomes. These findings support a selective approach to fluid restriction in HF management and highlight the need for further large-scale trials to confirm subgroup-specific efficacy and safety.

Background Adrenal crisis, characterized by acute cortisol deficiency, is a rare, life-threatening condition that can precipitate cardiovascular collapse and heart failure (HF). Its role in HF with preserved ejection fraction (HFpEF) is underrecognized, particularly in cancer patients receiving therapies that impair adrenal function. This case series examines the clinical features, management, and outcomes of HFpEF induced by adrenal crisis, emphasizing early diagnosis and treatment. Methods We retrospectively analyzed four patients diagnosed with HFpEF secondary to adrenal crisis between January 2022 and January 2025 at Qingdao Central Hospital and Qingdao Municipal Hospital. Inclusion criteria included clinical evidence of adrenal crisis (low cortisol, hypotension, steroid responsiveness) and echocardiographic confirmation of HFpEF (EF ≥50%). Data on demographics, clinical presentation, laboratory findings, echocardiography, and outcomes were analyzed descriptively. Results The cohort comprised three males and one female (aged 41–77 years), all with HFpEF (EF 50%–60%). Two presented with myocardial infarction (one NSTEMI, one STEMI), and two had malignancy with adrenal metastasis (renal, lung). Three exhibited hypotension. Initial BNP levels ranged from 518.93–619.13 pg/mL, decreasing to 108.06–287.63 pg/mL pre-discharge after hormone replacement therapy and HF management. Mean EF improved by 1.75% (range: 0%–3%) at one-month follow-up, with BNP further declining to 20.36–177.24 pg/mL. All patients achieved symptom resolution with no recurrence reported. Conclusion Adrenal crisis is a rare, reversible etiology of HFpEF in patients with diverse underlying conditions, potentially including those with cancer-related adrenal dysfunction or prior therapies. Prompt steroid therapy appears to improve cardiac function and outcomes, suggesting a need for heightened awareness and consideration of adrenal screening in at-risk populations, such as those with malignancy, tuberculosis, or other causes of adrenal insufficiency. Larger studies are needed to confirm these preliminary findings and establish the prevalence of this etiology across different subpopulations.

Introduction: Left ventricular pressure (LVP) waveforms offer critical insight into cardiac function after myocardial infarction. LVP is typically assessed via invasive catheterization, limiting routine use and longitudinal monitoring. We propose a novel analytical approach to reconstruct the entire LVP waveform using only carotid pressure waveforms (now measurable noninvasively with a phone camera) and standard echocardiography. We validated the method under normal and acute physiological conditions in an experimental model of myocardial ischemia and myocardial infarction (MI). Methods: Thirty-nine Sprague Dawley rats (28% female) were anesthetized and underwent coronary artery occlusion/reperfusion (30 min occlusion, 3 h reperfusion). Simultaneous LV and carotid pressures (via Millar Mikro-Tip catheters) and echocardiograms were recorded. LVP waveforms were reconstructed using a novel five-step analytical method at baseline, 15 min post-occlusion (ischemia), and 3 h post-reperfusion (acute MI, confirmed by TTC staining) for total of 71 cases. The reconstruction approach incorporated models of ventricular relaxation, diastolic filling, and systolic ejection governed by arterial-ventricular coupling, with constraints on temporal and morphological continuity of the waveform. Reconstructed waveforms were compared to invasive LVP recordings. Evaluation focused on accuracy in key clinical ischemia/MI metrics, including LV end-diastolic pressure (LVEDP) and subendocardial viability ratio (SEVR). SEVR is calculated as the ratio of myocardial oxygen supply to demand, serving as a surrogate for myocardial perfusion and correlates with cardiovascular risk. Results: Reconstructed LVP waveforms from carotid pressure closely matched invasive measurements during control, ischemia, and infarction (Figure 1). Reconstructed LVEDP strongly correlated with catheter measurements (Figure 2; r = 0.91), capturing its elevation during ischemia and partial recovery post-reperfusion. SEVR derived from reconstructions also closely matched invasive values (Figure 3; r = 0.96). Conclusions: Our findings show that the algorithm accurately reconstructs LVP waveforms and predicts clinically relevant metrics across physiological states. It captured elevated LVEDP and reduced SEVR during ischemia, with partial recovery after reperfusion. These results support its potential for noninvasive, longitudinal monitoring of left ventricular pressure in managing heart failure and myocardial infarction.

Background: The utilization of left ventricular assist devices (LVADs) for both destination therapy and as a bridge to transplantation has become increasingly prevalent in the management of advanced heart failure. Atrial fibrillation (AF), the most common arrhythmia in this population, poses significant management challenges. However, evidence regarding optimal atrial fibrillation (AF) management in left ventricular assist device (LVAD) recipients remains limited and often conflicting. Objective: To compare the impact of rhythm versus rate control strategies on clinical outcomes in patients with durable LVADs who develop new-onset AF. Methods: We conducted a retrospective cohort study using the TriNetX research network, which aggregates electronic health records from over 100 million patients. Adult patients (≥18 years) with advanced heart failure who received an LVAD between January 2015 and May 2025 and subsequently developed new-onset AF were identified. Two cohorts were constructed: those managed with rhythm control (antiarrhythmic drugs or catheter ablation) and those managed with rate control alone. A 1:1 propensity score matching was performed to adjust for demographics and comorbidities. Outcomes were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models, with a follow-up period of one year. Primary outcomes included all-cause mortality, all-cause hospitalizations, and incidence of ischemic stroke. Results: After matching, 3,297 patients in the rate control group were compared with 3,281 patients in the rhythm control group. The matched cohort had a mean age of 71.0 ± 12.8 years, was predominantly male (65%), and primarily Caucasian (68%). Rate control was associated with significantly lower all-cause mortality (HR: 0.64; 95% CI: 0.448–0.918; P = 0.01) and reduced all-cause hospitalization (HR: 0.87; 95% CI: 0.804–0.936; P &lt;0.001). There was no statistically significant difference in the incidence of ischemic stroke (HR: 1.13; 95% CI: 0.697–1.855; P =0.60). Conclusion: In this large, real-world, propensity-matched cohort study, a rate control strategy was associated with lower mortality and hospitalization rates compared to rhythm control in patients with durable LVADs and new-onset AF. These findings suggest rate control may be the safer initial approach in this population. Prospective randomized studies are warranted to validate these findings and guide clinical decision-making.

Background: Heart transplant is considered the gold standard for the management of end-stage heart failure. Black patients have historically been known to have a higher mortality risk following cardiac transplantation. Objective: This paper aims to evaluate the latest findings in the racial distribution of heart transplantation and any associated predictors of in-hospital mortality. Methods: Data from the National Inpatient Sample (NIS) database from 2021 was used to identify adults with ESHF. Four racial groups were identified: White, Black, Hispanic, and Asian. Univariate and multivariate regression analysis was used to ascertain the unadjusted and adjusted odds of heart transplantation and in-hospital mortality across various racial groups. Results: In 2021, 6,807 patients with ESHF were admitted, with 3,454 receiving heart transplants (51%, p = 0.039). Most of these patients were male (68%, p&lt;0.001) and were covered by Medicare (63%, p&lt;0.001). Overall, in-hospital mortality for ESHF patients was 13% (p&lt;0.001). Comorbidities such as hypertension, coronary artery disease, and CKD were higher in ESHF patients (p&lt;0.001, all). Predominantly, 62% of heart transplant recipients were White, 27% were Black, 8% were Hispanic, and 3% were Asian. (P=0.039). Compared to Whites, Blacks and Hispanics had lower mortality rates (OR: 0.59; 95% CI: 0.49-0.71) and (OR: 0.71; 95% CI: 0.53-0.95), respectively. Mortality rates between Whites and Asians were comparable. However, when adjusted for age, sex, household income, smoking, coronary artery disease, hypertension, hyperlipidemia, cerebrovascular disease, Diabetes, old MI, CKD, heart transplant, and regional location, Blacks had a lower mortality rate compared to Whites (AOR: 0.75; 95% CI:0.61-0.91). No difference in mortality was found in Hispanics and Asians. Heart transplant in ESHF was associated with a lower in-hospital mortality rate. (HR:0.68; 95% CI: 0.59-0.77). Across all races, transplant was associated with overall improved in-hospital survival. (log-rank p&lt;0.0001). Conclusion: Heart transplant in ESHF was associated with a lower in-hospital mortality rate than in patients who did not receive heart transplants. Transplant rates continue to be lower in Blacks compared to Whites. However, Blacks experienced lower in-hospital mortality compared to other races, even after adjusting for age, sex, and other comorbidities. Additional studies are needed to confirm these findings.

Background: The absence of effective, disease-modifying therapies continues to limit clinical management of cardiometabolic heart failure with preserved ejection fraction (cHFpEF). Although the “two-hit” murine model of high-fat diet and 0.5% N(ω)-nitro-L-arginine methyl ester (HFD+L-NAME) has been heralded as a reproducible model of cHFpEF, we previously discovered that C57BL/6J mice are resistant to developing diastolic dysfunction under this regimen. Both the mechanistic basis of - and therapeutic opportunities underlying - this cardioprotection remained undefined. Methods: Genetic strain-specific single-nucleus transcriptomic analysis identified disease-relevant gene programs via human GWAS trait mapping to enrich cardiomyocyte mitochondrial redox homeostasis and oxidative metabolic gene expression. Because C57BL/6J mice are known to harbor a loss-of-function mutation affecting the inner mitochondrial membrane Nnt , we developed an isogenic model of Nnt loss-of-function to determine whether intact Nnt is necessary for the pathological cardiac manifestations of HFD+L-NAME. Twelve-week-old C57BL/6N mice with wild-type ( Nnt +/+ ) or loss-of-function ( Nnt -/- ) Nnt were challenged to HFD+L-NAME or control diets for 9 weeks (n = 10). Tissue was analyzed via histologic analysis and HPLC-MS for molecular and functional analysis. Results: Only C57BL/6N Nnt +/+ - and not Nnt -/- - mice exhibited impaired ventricular diastolic relaxation and pathological remodeling, as assessed via E/e’ (42.8 vs. 21.5, P = 1.2e -10 ), E/A (2.3 vs 1.4, P = 4.1e -2 ), diastolic EDPVR (0.09 vs 0.04 mmHg/μL, P = 5.1e -3 ), and myocardial fibrosis ( P = 2.3e -2 ). Tandem LC/MS exposed a functional reversal of Nnt dynamics, showing a 40.0% reduction in NAD + ( P = 8.4e -3 ) and a 38.8% reduction in GSH:GSSG ( P = 2.6e -2 ) only in Nnt +/+ mice. Using single-nucleus ligand-receptor analysis and human GWAS trait mapping, we found fibroblast growth factor 1 (Fgf1) as an NNT-dependent paracellular signal that promotes myocardial fibrosis in HFpEF mice. Conclusions: These data establish a mechanistic link between mitochondrial redox regulation and HFpEF pathogenesis, whereby functional Nnt promotes diastolic dysfunction in the HFD+L-NAME model. Furthermore, Fgf1 represents an Nnt -responsive paracellular signaling axis that promotes myocardial fibrosis, highlighting both as novel targets for therapeutic intervention.

Objective: As an integral component of complementary and alternative medicine systems, Traditional Chinese Medicine (TCM) has presented novel therapeutic possibilities for the clinical management of chronic heart failure (HF). This trial investigates the clinical efficacy and safety profile of Xinfuli Granules (XFLG), a Chinese herbal formulation, in patients diagnosed with HF with reduced ejection fraction. Methods: This single-center, randomized controlled trial enrolled 444 HF patients (NT-pro BNP ≥ 450 pg/mL and LVEF ≤ 45%) at Fuwai Hospital between October 2021 and December 2024. Participants were randomized (1:1) to receive either XFLG plus standard care or standard care alone. The primary endpoint was the composite of all-cause mortality and HF-related hospitalization. Secondary outcomes included changes in LVEF, NT-pro BNP, NYHA functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, TCM syndrome score, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores. Results: A total of 356 participants (178 per group) completed the trial, with median ages of 58 years (IQR: 50-67) in the XFLG group and 60 years (IQR: 52.75-69) in controls. At 12 weeks, the XFLG group demonstrated a significantly lower incidence of the primary composite outcome compared to the control group (11.24% vs. 18.54%; HR, 0.566; 95%CI: 0.325-0.988; P =0.042). In secondary endpoint analyses, the XFLG group demonstrated superior improvement in LVEF compared with controls (4% vs 3%; P =0.047). For NT-pro BNP levels, XFLG group showed significantly greater median absolute reductions (413 pg/mL vs 256 pg/mL; P =0.048) and relative reductions (42.02% vs 25.84%; P =0.01). NT-pro BNP reduction (&gt;30%) was achieved by more patients in the XFLG arm (59.5% vs 44.1%; P =0.008). Significant advantages were observed in NYHA class improvement (efficacy rate: 53.8% vs 41.4%, P =0.031) and TCM syndrome scores (efficacy rate: 74.05% vs 37.24%, P &lt;0.001). Quality of life assessments showed marked improvements in the MLHFQ, PHQ-9, and GAD-7 scores (differences: -15 vs -4; -2 vs 0; -1 vs 0 respectively; P &lt;0.001), with comparable safety profiles between groups. Conclusions: XFLG combined with standard HF therapy significantly reduced the risk of all-cause mortality and HF-related hospitalization composite outcome, improved cardiac function, and quality of life, alleviated depressive and anxiety states in HF patients, with a favorable safety profile.