Heart failure remains a major cause of hospitalization and recurrent healthcare utilization worldwide. Patients with heart failure with reduced ejection fraction (HFrEF) are particularly vulnerable to early clinical deterioration after discharge because of persistent hemodynamic abnormalities, neurohormonal activation, comorbid disease, incomplete decongestion, and difficulties in optimizing evidence-based therapy. Contemporary guidelines define HFrEF as heart failure with a left ventricular ejection fraction of 40% or less [1]. The current therapeutic foundation includes four major classes of disease-modifying therapy: renin-angiotensin system inhibition, preferably with an angiotensin receptor-neprilysin inhibitor where appropriate; an evidence-based beta-blocker; a mineralocorticoid receptor antagonist; and a sodium-glucose cotransporter-2 inhibitor [1,2]. Despite these therapeutic advances, 30-day readmission remains common. Early readmission is clinically important because it is associated with disease progression, increased mortality, reduced quality of life, and greater healthcare costs [7-10]. Readmission is rarely attributable to a single factor. Rather, it reflects interaction between disease severity, residual congestion, renal dysfunction, comorbidities, medication tolerance, adherence, socioeconomic constraints, and quality of post-discharge care. Traditional predictors of readmission have included advanced age, renal impairment, low ejection fraction, elevated natriuretic peptide levels, hyponatremia, diabetes, anemia, atrial fibrillation, prior hospitalization, and greater comorbidity burden [3,4]. More recent studies have also highlighted the importance of frailty, nutritional status, sarcopenia, and incomplete implementation of guideline-directed medical therapy. Contemporary HFrEF management has changed substantially with increased use of angiotensin receptor-neprilysin inhibitors and SGLT2 inhibitors. Therefore, predictors derived from older cohorts may not fully reflect current clinical practice. There is limited contemporary Indian evidence evaluating a combined set of clinical, laboratory, echocardiographic, congestion-related, and treatment-related determinants of 30-day readmission specifically among patients with HFrEF. The present study was therefore conducted to identify contemporary predictors of 30-day readmission in patients hospitalized with HFrEF at a tertiary-care cardiology center in North India. Aim To identify contemporary predictors of 30-day all-cause readmission among patients hospitalized with heart failure with reduced ejection fraction. Objectives 1. To determine independent predictors of unplanned all-cause readmission within 30 days after discharge among patients with HFrEF. 2. To determine the 30-day readmission rate. 3. To compare demographic and clinical characteristics between readmitted and non-readmitted patients. 4. To evaluate the relationship of renal function, serum sodium, hemoglobin, and NT-proBNP with readmission. 5. To assess the influence of LVEF and NYHA functional class. 6. To determine the impact of persistent congestion at discharge. 7. To assess the association between prior HF hospitalization and early readmission. 8. To evaluate whether discharge prescription of contemporary GDMT was associated with lower readmission risk.

Study Design This was a prospective observational cohort study. Study Setting The study was conducted in the Department of Cardiology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India. Study Duration The study was conducted from October 2024 to September 2025. Sample Size A total of 250 patients were enrolled. Study Population Consecutive adult patients admitted with acute decompensated heart failure or worsening chronic HFrEF were screened. Definition of HFrEF HFrEF was defined as symptomatic heart failure with LVEF ≤40%, in accordance with contemporary guideline classification [1]. Inclusion Criteria 1. Age ≥18 years. 2. Established diagnosis of HFrEF. 3. LVEF ≤40% on echocardiography during the index admission or within the preceding three months. 4. Hospitalization for acute decompensated HF or worsening chronic HF. 5. Survival to hospital discharge. 6. Availability for 30-day follow-up. Exclusion Criteria 1. LVEF >40%. 2. Cardiogenic shock requiring ongoing mechanical circulatory support at discharge. 3. Acute myocarditis as the primary diagnosis. 4. Severe primary valvular disease requiring immediate surgery. 5. End-stage malignancy with limited life expectancy. 6. End-stage renal disease on chronic dialysis. 7. Inability to complete follow-up. 8. Refusal to participate. Data Collection Baseline information included age, sex, body mass index, smoking status, diabetes mellitus, hypertension, chronic kidney disease, atrial fibrillation, ischemic heart disease, previous myocardial infarction, prior HF hospitalization, NYHA functional class, systolic blood pressure, and heart rate. Laboratory parameters included hemoglobin, serum sodium, serum potassium, serum creatinine, estimated glomerular filtration rate, blood urea nitrogen, serum albumin, and NT-proBNP. Echocardiography Transthoracic echocardiography was performed according to routine departmental protocol. LVEF was calculated using Simpson's biplane method where technically feasible. Additional parameters included left ventricular dimensions, right ventricular function, estimated pulmonary artery systolic pressure, significant mitral regurgitation, and left atrial size. Assessment of Congestion Clinical congestion at discharge was assessed using peripheral edema, elevated jugular venous pressure, pulmonary crepitations, orthopnea, and persistent radiographic congestion where available. Patients with one or more clinically significant signs of ongoing volume overload were categorized as having residual congestion. Guideline-Directed Medical Therapy Discharge treatment was recorded for the four foundational HFrEF medication classes: ACE inhibitor/ARB or ARNI, evidence-based beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor. Current guidelines recommend these four therapeutic pillars in eligible patients with HFrEF [1,2]. Patients receiving all four classes were categorized as receiving quadruple GDMT. Other treatments including loop diuretics, ivabradine, digoxin, anticoagulation, iron therapy, and device therapy were recorded where relevant. Follow-Up and Primary Outcome Patients were followed for 30 days after discharge by outpatient assessment, telephone contact, or review of hospital records. The primary outcome was unplanned all-cause hospital readmission within 30 days of discharge. Readmissions were further classified as heart-failure-related, cardiovascular but non-HF, or non-cardiovascular. Statistical Analysis Continuous variables were expressed as mean ± standard deviation or median with interquartile range depending on distribution. Categorical variables were reported as numbers and percentages. Continuous variables were compared using the independent-samples t-test or Mann-Whitney U test, while categorical variables were compared using chi-square or Fisher's exact test. Variables associated with readmission at p<0.10 on univariable analysis and clinically relevant variables were considered for multivariable logistic regression. Adjusted odds ratios with 95% confidence intervals were calculated. Model discrimination was assessed using receiver-operating-characteristic analysis. A p-value <0.05 was considered statistically significant. Ethical Considerations The study was conducted in accordance with the Declaration of Helsinki. Approval was obtained from the Institutional Ethics Committee of Sarojini Naidu Medical College, Agra. Written informed consent was obtained from all participants.

Baseline Characteristics A total of 250 patients were included. Mean age was 61.8 ± 12.4 years. Of the patients, 165 (66.0%) were male and 85 (34.0%) were female. Ischemic cardiomyopathy was the most common underlying etiology. Characteristic Total (n=250) Age, years 61.8 ± 12.4 Male 165 (66.0%) Female 85 (34.0%) Diabetes mellitus 104 (41.6%) Hypertension 137 (54.8%) Chronic kidney disease 67 (26.8%) Atrial fibrillation 43 (17.2%) Ischemic etiology 151 (60.4%) Previous HF admission within 12 months 91 (36.4%) NYHA III-IV at admission 194 (77.6%) Mean LVEF 30.8 ± 5.7% Mean serum sodium 136.0 ± 4.1 mmol/L Mean hemoglobin 11.8 ± 2.0 g/dL Median NT-proBNP 4,360 pg/mL eGFR <60 mL/min/1.73 m² 86 (34.4%) Thirty-Day Readmission Within 30 days, 71 of 250 patients (28.4%) experienced unplanned readmission. Among the 71 readmissions, 52 (73.2%) were heart-failure-related, 9 (12.7%) were other cardiovascular readmissions, and 10 (14.1%) were non-cardiovascular. Comparison According to Readmission Status Variable Readmitted (n=71) Not readmitted (n=179) p-value Age, years 64.0 ± 11.8 60.9 ± 12.5 0.071 Male 48 (67.6%) 117 (65.4%) 0.74 Diabetes 35 (49.3%) 69 (38.5%) 0.12 CKD 30 (42.3%) 37 (20.7%) <0.001 Previous HF admission 39 (54.9%) 52 (29.1%) <0.001 NYHA III-IV at discharge 31 (43.7%) 40 (22.3%) 0.001 LVEF, % 28.9 ± 5.3 31.5 ± 5.7 0.001 eGFR <60 37 (52.1%) 49 (27.4%) <0.001 Sodium <135 mmol/L 26 (36.6%) 35 (19.6%) 0.005 NT-proBNP ≥5000 pg/mL 42 (59.2%) 57 (31.8%) <0.001 Residual congestion 34 (47.9%) 33 (18.4%) <0.001 Length of stay >7 days 27 (38.0%) 43 (24.0%) 0.026 Quadruple GDMT at discharge 19 (26.8%) 76 (42.5%) 0.022 Discharge Guideline-Directed Therapy Therapy n (%) ACEI/ARB/ARNI 202 (80.8%) Evidence-based beta-blocker 216 (86.4%) Mineralocorticoid receptor antagonist 190 (76.0%) SGLT2 inhibitor 176 (70.4%) All four foundational therapies 95 (38.0%) Loop diuretic 225 (90.0%) Only 38.0% of patients received all four foundational HFrEF treatment classes at discharge. Univariable Predictors of Readmission Significant univariable predictors included chronic kidney disease, previous HF hospitalization, lower LVEF, NYHA class III-IV at discharge, hyponatremia, elevated NT-proBNP, residual congestion, longer hospital stay, and incomplete quadruple GDMT. Multivariable Analysis Predictor Adjusted OR 95% CI p-value Residual congestion at discharge 2.84 1.42-5.69 0.003 NT-proBNP ≥5000 pg/mL 2.62 1.33-5.15 0.005 Previous HF admission within 12 months 2.47 1.28-4.78 0.007 eGFR <60 mL/min/1.73 m² 2.19 1.14-4.22 0.019 No quadruple GDMT at discharge 1.96 1.01-3.81 0.047 NYHA III-IV at discharge 1.76 0.91-3.41 0.094 Sodium <135 mmol/L 1.58 0.79-3.17 0.196 LVEF <30% 1.52 0.79-2.93 0.207 Predictive Model Performance A multivariable model incorporating residual congestion, NT-proBNP ≥5000 pg/mL, prior HF hospitalization, eGFR <60 mL/min/1.73 m², and absence of quadruple GDMT demonstrated an area under the receiver-operating-characteristic curve of 0.79 (95% CI 0.73-0.85). At the selected threshold, sensitivity was approximately 74% and specificity 72%. Adjusted odds ratios (aORs) with 95% confidence intervals are shown for variables included in the multivariable logistic regression model. The vertical dashed line at an odds ratio of 1.0 represents the null effect. Predictors with confidence intervals not crossing 1.0 were considered statistically significant. Residual congestion at discharge, NT-proBNP ≥5000 pg/mL, previous heart-failure admission within 12 months, eGFR <60 mL/min/1.73 m², and absence of quadruple guideline-directed medical therapy at discharge were independently associated with higher odds of 30-day readmission. HF: heart failure; NT-proBNP: N-terminal pro-B-type natriuretic peptide; eGFR: estimated glomerular filtration rate; GDMT: guideline-directed medical therapy; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction. The model demonstrated an area under the ROC curve (AUC) of 0.79 (95% CI 0.73–0.85), indicating good discrimination between patients who were and were not readmitted within 30 days. The diagonal reference line represents discrimination no better than chance. AUC: area under the curve; CI: confidence interval; HFrEF: heart failure with reduced ejection fraction.

This prospective study of 250 patients with HFrEF demonstrated that 28.4% experienced unplanned readmission within 30 days of discharge. The principal independent predictors were residual congestion at discharge, elevated NT-proBNP, renal dysfunction, a recent history of HF hospitalization, and failure to achieve all four foundational components of GDMT. These findings reinforce the concept that early readmission is multifactorial and reflects both intrinsic disease severity and potentially modifiable features of discharge readiness and treatment optimization. Residual Congestion Residual congestion was the strongest predictor of readmission. Even after symptomatic improvement, patients may remain hemodynamically congested. Persistent elevation of filling pressures may subsequently result in recurrent pulmonary or systemic congestion shortly after discharge. This finding emphasizes the importance of assessing decongestion beyond symptomatic improvement alone. Clinical assessment can be complemented, where available, by natriuretic peptide trends, lung ultrasound, inferior vena cava assessment, body-weight trajectory, renal function, and urine output. NT-proBNP A discharge NT-proBNP concentration ≥5000 pg/mL independently predicted early readmission. Natriuretic peptides reflect ventricular wall stress and provide integrated information regarding hemodynamic burden. High levels at discharge may indicate incomplete stabilization despite apparent clinical improvement [3,4]. Renal Dysfunction Renal dysfunction was independently associated with readmission. Cardiorenal interactions are especially relevant in HFrEF. Reduced renal perfusion, venous congestion, neurohormonal activation, diuretic resistance, and underlying chronic kidney disease may all increase the likelihood of recurrent decompensation [3]. Previous Heart-Failure Admission Recent prior HF hospitalization was another strong predictor. Repeated admission likely identifies a particularly vulnerable phenotype characterized by advanced disease, incomplete recovery, recurrent congestion, greater comorbidity burden, treatment intolerance, poor adherence, and socioeconomic barriers. Prior healthcare utilization therefore remains a simple and clinically useful marker of future risk. Guideline-Directed Medical Therapy Patients who were not receiving all four foundational HFrEF medication classes at discharge had greater adjusted odds of readmission. Current recommendations identify renin-angiotensin system inhibition, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors as core HFrEF therapies [1,2]. Failure to achieve complete GDMT may reflect hypotension, renal dysfunction, hyperkalemia, clinician inertia, delayed initiation, financial barriers, or medication intolerance. Therefore, absence of quadruple therapy may function both as a modifiable risk factor and as a marker of greater disease complexity. Contemporary Relevance The present study differs from older readmission analyses because it evaluates HFrEF in the era of SGLT2 inhibitors and broader use of ARNI-based treatment. Despite modern therapy, readmission remained high. This reinforces the need for systematic transitional-care strategies and early post-discharge reassessment. Clinical Implications A practical predischarge risk-assessment approach could incorporate five readily identifiable variables: residual congestion, elevated NT-proBNP, renal impairment, HF hospitalization during the preceding year, and incomplete foundational GDMT. Patients with multiple risk factors could receive earlier outpatient review, rapid GDMT titration, closer renal/electrolyte monitoring, daily weight and symptom surveillance, telephonic follow-up, structured education, dietary counseling, medication reconciliation, and early HF-clinic referral. Strengths The study focused specifically on HFrEF rather than combining all HF phenotypes. It incorporated contemporary GDMT, including SGLT2 inhibitors. Clinical, laboratory, echocardiographic, biomarker, treatment, and utilization variables were evaluated simultaneously, and all patients had a defined 30-day follow-up period. Limitations The study was conducted at a single tertiary-care center, limiting external generalizability. The sample size of 250 restricted the number of variables that could reliably be incorporated into multivariable models. NT-proBNP availability and timing may have varied between patients. Medication use was assessed at discharge, but subsequent adherence and dose titration were not fully captured. Socioeconomic status, health literacy, dietary adherence, and caregiver support were not quantified comprehensively. Readmissions occurring at hospitals outside the study network could potentially have been missed despite follow-up contact. The study assessed 30-day readmission but did not evaluate longer-term mortality or recurrent-event burden.

Thirty-day readmission remains common among patients hospitalized with HFrEF despite contemporary treatment. Residual congestion, markedly elevated NT-proBNP, renal dysfunction, recent previous HF hospitalization, and incomplete implementation of foundational GDMT were the most important independent predictors of early readmission. These variables are readily identifiable before discharge and may therefore support practical risk stratification. Greater emphasis on complete decongestion, optimized evidence-based therapy, structured discharge planning, and intensified early follow-up may help reduce preventable readmissions among high-risk HFrEF patients.

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