Heart failure with reduced ejection fraction (HFrEF) is a major cause of hospitalization in adults everywhere, and repeated hospital admission is now known to be a major indicator of disease progression and combines with decreased quality of life and increased mortality risk [1]. Cumulative myocardial injury occurs with each new HF admission and the risk of re-admission is steadily increasing, establishing a vicious cycle with significant burden on patients and health systems [2].

High burden of ischemic heart disease, uncontrolled hypertension, high prevalence of diabetes mellitus, along with restricted availability of structured outpatient HF services and specialist follow-up aggravate the burden of heart failure in Pakistan as is found in many other LMICs [9]. Limited use of guideline-directed medical therapy (GDMT) for heart failure, such as renin-angiotensin-system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransport inhibitors (SGLT2), has been recognized in numerous studies as a modifiable factor to prevent heart failure hospitals admissions [4].

This increased risk is exacerbated by poor adherence to medication, and to sodium and fluid restriction, especially in resource limited areas where nurse-led follow-up programmes and structured heart failure education are not well established [5]. Certain clinical and modifiable factors that might promote recurrent hospitalization of local populations are therefore crucial to identify when developing interventions that might help reduce this burden.

In this study, we aimed to determine the frequency of re-hospitalization within the group of patients with chronic HFrEF who are managed at tertiary medical care cardiology centers in Pakistan, and the factors most strongly associated with re-hospitalization, both clinical and comorbid and modifiable, which can inform the development of structured heart failure management strategy in this context.[15]

Design and setting of the study It was an observational study carried out in the Departments of Cardiology, Ghulam Muhammad Mahar Medical College (GMMMC), Sukkur. Data was collected between March 2025 to March 2026. Ethical Approval The study was duly approved by the Institutional Ethical Review Committees of hospitals where the study was conducted, before enrolling the patients in the study, in line with the principles of the Declaration of Helsinki. All patients enrolled gave written informed consent. Inclusion Criteria ● Adult patients with a known diagnosis of HF with reduced LVEF (≤ 40%) on echocardiogram. ● Patient were on a stable, outpatient heart failure regimen for at least 3 months before entry into the study. ● Clinically-stable patients with complete data records and available follow-up data for the entire study. Exclusion Criteria ● Patients with heart failure with preserved or mild reduced EF (LVEF > 40%). ● Patients with new diagnosis in whom there was insufficient baseline data for follow-up. ● Patients with active non-cardiac terminal illness (e.g. malignancy, end-stage liver disease) that could independently drive hospitalization. Data Collection Upon entry, baseline demographics, clinical and echocardiographic data, such as the NYHA functional class, LVEF, etiology of heart failure, and pertinent co-morbidity, were documented. All hospitalizations for heart failure were recorded in a prospective fashion. Patients who had 2 or more hospitalizations for this condition were defined as recurrent hospitalizations and those who had either 0 or 1 hospitalizations were defined as non-recurrent hospitalizations. At each follow-up visit medication adherence, adherence to dietary sodium and water restrictions and completeness of guideline directed therapy were determined by structured patient interview and looking at prescription records. Outcome Measures The main outcome was defined as recurrent hospitalization – two or more admissions because of heart failure during this study period. Secondary outcomes were the association of recurrent hospitalization with NYHA class, LVEF, comorbidities, medication adherence, dietary compliance, and completeness of guideline-directed medical therapy. Statistical Analysis SPSS software version 26.0 was used in analysis of the data. The mean ± standard deviation values were used for the continuous variables and they were compared with independent samples t-test. Categorical data were presented as numbers with percentages and analyzed by Chi-square test. Statistically significant at the P value < 0.05.

A total of 180 patients with chronic HFrEF were recruited and followed during this study period.82 of these patients (45.6%) had at least one heart failure–related hospitalization and 40 patients (22.2%) were recurrently hospitalized, with ≥2 admissions. No hospitalization was needed in 98 (54.4%) patients, one in 42 (23.3%), two in 24 (13.3%) and 3 or more hospitalizations in 16 (8.9%) patients throughout the study.

As presented in Table 1, patients with recurrent hospitalization were significantly older (64.2 ± 9.8 vs. 59.6 ± 10.4 years, p = 0.014), more likely to be in NYHA class III/IV (80.0% vs. 38.6%, p < 0.001), and had significantly lower LVEF (28.4 ± 6.2% vs. 32.6 ± 7.1%, p = 0.002) compared with the non-recurrent group. Also recurrent hospitalization patients were significantly more likely to have diabetes mellitus (55.0% vs. 34.3%, p = 0.019) and chronic kidney disease (35.0% vs. 15.0%, p = 0.006).

As shown in Table 2, recurrent hospitalization was strongly associated with medication non-adherence (60.0% vs. 22.9%, p < 0.001), non-compliance with dietary sodium and fluid restriction (50.0% vs. 18.6%, p < 0.001), anemia (40.0% vs. 17.9%, p = 0.003), and incomplete guideline-directed medical therapy (45.0% vs. 15.7%, p < 0.001).

Table 1: Baseline Demographic and Clinical Characteristics (n = 180).

Table 2: Association Between Recurrent Hospitalization and Modifiable Risk Factors

In this study, almost half of the patients with chronic HFrEF had at least one hospital admission in the six months, and just more than one-fifth fulfilled the criteria for recurrent hospitalization, indicating the high and persistent level of burden of admission for heart failure among this patient population. This is in line with international registry data, in which heart failure hospitalizations occur often as part of a series and a large minority of patients account for a disproportionate part of the total hospitalizations [6,7]. This was consistent with previous studies showing that severity of NYHA class at baseline was one of the most powerful predictors of subsequent hospitalization; more advanced myocardial dysfunction and decreased physiological reserve indicate greater disease severity [6]. Likewise, robust correlations with diabetes mellitus and chronic kidney disease highlight the well-documented cardiorenal-metabolic axis that drives the trajectory of heart failure progression and the management of heart failure in the outpatient setting in this subset of patients [8]. In the local setting, a study in a tertiary cardiac care centre in Karachi showed similar characteristics whereby NYHA functional status and renal impairment were independently associated with readmission of heart failure patients within six months of the index admission [9]. Investigators from a cardiology unit in Lahore, who also found medication non-adherence and sub-optimal uptake of GDMT to be important modifiable factors associated with recurrent hospitalization for HF, very similar to the associations identified in the current study [10]. Of particular importance, as these are directly modifiable targets for interventions, is their strong relationship between medication non-adherence, incomplete guideline-directed medical therapy, and recurrent hospitalization identified herein. Structured heart failure clinics, nurse-led medication counselling, and simplified follow-up scheduling have all been effective in improving adherence, and potentially have the promise of being a practical way of reducing recurrent admissions in resource-limited tertiary care centres, as in this study, without substantially increasing resource expenditure [5,11]. Likewise, systematic attempts to refine the quality of GDMT by uptitration during outpatient visits as an alternative to just initiating treatment in the hospital would have meaningfully reduced the number of patients presenting with suboptimal pharmacologic management of their therapy. The link between dietary non-compliance and anemia and the increased risk of recurrent hospitalization also illustrates the multifactorial approach to the risk of decompensation in HFrEF –recurrent hospitalization is not solely driven by medication factor. Diet-based counseling and anticipatory anemia screening and correction (when clinically indicated) may be other opportunities to mitigate the risk of hospitalisation in these individuals [12]. From a health-systems perspective, these findings highlight the importance of risk-stratifying HFrEF patients at the time of outpatient follow-up when resources for counselling and monitoring are limited so that these resources can be targeted to those who would benefit most — patients in advanced NYHA classes, those with co-existing diabetes or chronic kidney disease, and those with confirmed non-adherence to prescribed therapy. Using a checklist at every outpatient visit to ask about adherence with medication and diet changes along with complete guideline directed therapy could help identify high-risk patients early in the course of treatment and identify those who should get more intensive follow-up before decompensation requires hospitalization. Such pervasiveness can be expected with an approach that has relatively lower resource demands than more technology-intensive approaches could potentially entail, and thus may be suitable especially for tertiary settings in the cardiology sector of Pakistan, where lowering the prevalence of re-admissions without significant investments would be desirable. Limitations of Study This was an observational study, so there can be no definitive conclusions about possible causal relationships between the identified risk factors and recurrent hospitalization, and there is residual confounding to consider. The follow-up period is adequate to see short-term recurrent admission rates, but not long-term outcomes like one-year mortality. Larger, multi-center, longitudinal studies are suggested to further define the factors leading to re-hospitalization and to test the effects of a structured approach to the management of heart failure in this patient population.

A significant number of chronic HFrEF patients treated at tertiary cardiology centers in Pakistan have recurrent hospitalisation, which has significant correlation with NYHA class, lower LVEF, diabetes, chronic kidney disease, and obvious but modifiable factors such as poor adherence to treatment, non-compliance to diet and incomplete guideline directed medical therapy. These findings identify clear and actionable targets for structured heart failure management programs, such as nurse-led adherence counselling, systematic outpatient up-titration of guideline-directed therapy and proactive management of key heart failure comorbidities. Routine use of these structured programs in Pakistan's tertiary care facilities, with measures to fit the resource limitations of these centers, could have a significant impact in reducing recurrent hospitalizations for heart failure and improving long term outcomes for these high-risk patients.