Phenotype-Specific Insights From the Korean Acute Heart Failure Registry: Implications for Tailored Management

Acute heart failure (AHF) represents a growing global health burden, particularly among older adults, and remains associated with high in-hospital and post-discharge mortality. Clinical presentation, therapeutic response, and prognosis differ markedly across heart failure (HF) phenotypes—heart failure with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF)—making phenotype-specific understanding essential for optimized management. Recent large-scale European registries have advanced the characterization of HF phenotypes, clinical outcomes, and the real-world implementation of guideline-directed medical therapy (GDMT).¹⁾ Complementing these efforts, the Korean Heart Failure III (KorHF III) registry—a nationwide, prospective cohort enrolling 7,351 patients from 47 tertiary hospitals between 2018 and 2022—provides a valuable platform to examine phenotype-specific characteristics, treatment patterns, and outcomes in an East Asian population.²⁾ The recent KorHF III publication, “Acute Heart Failure Across the Ejection Fraction Spectrum: Phenotypes, Management, and Outcomes from the Nationwide KorHF III Registry,”³⁾ offers comprehensive analyses across the EF continuum.

Among 6,777 patients with available LVEF data, 58.9% had HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Patients with HFpEF were older, more frequently female, and had higher rates of hypertension and atrial fibrillation (AF), whereas those with HFrEF showed greater neurohormonal activation, worse renal function, and higher natriuretic peptide levels. The HFmrEF group demonstrated intermediate clinical features. Compared with Western registries such as ADHERE,⁴⁾ the KorHF III cohort had a slightly younger mean age but similar prevalence of hypertension, diabetes, and AF. Likewise, the Japanese ATTEND registry,⁵⁾ reported comparable proportions of HFrEF (57%), mirroring the Korean data. Collectively, these findings suggest that baseline characteristics of Korean AHF patients are broadly consistent with those observed in major Western and Asian cohorts.

GDMT prescription patterns in KorHF III revealed higher utilization rates among HFrEF patients compared with earlier registries. The overall use of evidence-based therapies increased from admission to discharge, likely reflecting the impact of landmark clinical trials and updated HF guidelines. Nevertheless, direct comparisons across registries should be interpreted with caution due to temporal and regional variations in clinical practice.

Using inverse probability of treatment weighting analysis, the KorHF III registry demonstrated comparable 12-month composite outcomes across HF phenotypes. Interestingly, post-discharge, HFpEF patients exhibited a modestly higher risk of adverse events, while outcomes in HFmrEF were similar to those in HFrEF. These results are clinically significant. The higher post-discharge risk in HFpEF likely reflects older age and greater comorbidity burden rather than intrinsic differences in cardiac dysfunction. Unlike HFrEF, for which evidence-based pharmacologic strategies are well defined, HFpEF remains a heterogeneous syndrome with variable risk profiles and limited standardized management options. This reinforces the need for phenotype-guided, individualized treatment strategies rather than a uniform therapeutic approach.

In terms of phenotype-specific management, for HFrEF, early initiation and timely uptitration of foundational therapies—ARNI or ACE inhibitors, beta-blockers, MRAs, and SGLT2 inhibitors—remain essential. For HFmrEF, these same drug classes can be applied when tolerated, given their emerging benefits in patients with mildly reduced ejection fraction. HFpEF, however, requires a more individualized approach. SGLT2 inhibitors should be prioritized as first-line therapy, with selective use of RAAS blockers or ARNI in hypertensive or congestion-predominant phenotypes. Optimizing comorbidities such as AF, obesity, and chronic kidney disease remains central to improving clinical outcomes.

The higher post-discharge mortality observed in HFpEF also exposes significant gaps in transitional care. Structured care setting—including early follow-up, medication optimization, remote monitoring, and coordinated rehabilitation—should be integrated into multidisciplinary HF clinics. Moreover, addressing modifiable risk factors such as hyponatremia, congestion, chronic kidney disease, and low BMI through targeted interventions could translate risk identification into improved long-term outcomes.

Despite certain limitations, including possible selection bias during the coronavirus disease 2019 period, the KorHF III registry’s strengths are notable. Its nationwide, prospective design with standardized data collection, independent monitoring, and blinded event adjudication enables a detailed assessment of phenotype-specific presentations, treatments, and outcomes. The application of robust analytic methods minimizes confounding and enhances the reliability of the findings.

In summary, the KorHF III registry provides valuable insights into phenotype-specific characteristics and management of AHF in Korea. Future efforts should focus on optimizing pharmacologic therapy in HFpEF, implementing structured post-discharge programs, and validating phenotype-weighted risk tools to support individualized care. Addressing modifiable prognostic factors and improving transitional care may further enhance outcomes. Collectively, these findings highlight the importance of regional and population-specific strategies, supporting a comprehensive, phenotype-aware framework for AHF management in East Asian populations.