GDF-15: a novel biomarker of heart failure predicts short-term and long-term heart-failure rehospitalization and short-term mortality in patients with acute heart failure syndrome.

BACKGROUND: Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Growth Differentiation Factor-15 (GDF-15) is a distant member of the transforming growth factor-ß. The increased expression of GDF-15 has been observed during heart failure (HF) and is associated with worse outcomes. However, the relationship between GDF-15 and AHF is not well understood with limited evidence among Thai patients. PURPOSE: Investigate the correlation between biomarker levels (measured upon admission and discharge) and short- and long-term adverse outcomes, encompassing all-cause mortality and heart-failure (HF) rehospitalization (at 30, 90, and 180 days, as well as throughout the entire follow-up duration) in individuals experiencing acute HF. METHODS: This is a prospective single-center investigation involving patients admitted for AHF. Biomarkers, including GDF-15, high-sensitivity troponin T (hsTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were assessed upon admission and discharge. Outcomes, including all-cause mortality and HF rehospitalization, were examined. Logarithmic transformations were applied to the biomarker variables for subsequent analysis. Univariate and multivariate analyses of cause-specific hazards were conducted using the Cox proportional hazards regression model, while subdistribution hazards were assessed using the Fine-Gray regression model to evaluate outcomes. RESULTS: A total of 84 patients were enrolled (mean age of 69 years, 52% females). The GDF-15 level significantly decreased during admission (median at the time of admission 6,346 pg/mL, median at the time of discharge 5,711 pg/mL; p < 0.01). All-cause mortality at 30 days and 180 days were 6.0% and 16.7%, respectively. HF rehospitalization at 30 days and 180 days were 15.5% and 28.6%, respectively. Univariate analysis showed that total orthoedema congestion score (p = 0.02) and admission GDF-15 level (p = 0.01) were associated with 30-day all-cause mortality, whereas hsTnT or NT-proBNP levels did not show significant associations. However, higher levels of NT-proBNP upon admission were associated with all-cause mortality when considering the entire follow-up period (p < 0.01). Both univariate and multivariate analyses demonstrated that lower discharge GDF-15 levels and a greater reduction in GDF-15 levels from admission to discharge were associated with a lower risk of 30-day rehospitalization. Similarly, univariate analysis revealed that a greater reduction in NT-proBNP levels from admission to discharge was associated with lower 30-day rehospitalization rates. At 180 days, a greater reduction in GDF-15 levels remained associated with lower hazards and incidence of rehospitalization. CONCLUSION: The significant decrease in Growth Differentiation Factor-15 (GDF-15) levels during hospitalization suggests its potential as a dynamic marker reflecting the course of AHF. Importantly, higher GDF-15 levels at admission were associated with an increased risk of 30-day all-cause mortality, highlighting its prognostic value in this patient population. Moreover, lower discharge GDF-15 levels, reductions in GDF-15 from admission to discharge, and decreases in NT-proBNP from admission to discharge were associated with a reduced risk of 30-day rehospitalization.

Predicting arrhythmic event score in Brugada syndrome: Worldwide pooled analysis with internal and external validation.

BACKGROUND: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). Risk predictive scores were previously developed with various performances. OBJECTIVE: The purpose of this study was to create a novel score-Predicting Arrhythmic evenT (PAT)-with internal and external validation. METHODS: A systematic review was performed to identify risk factors for MAE. The odds ratios (ORs) of each factor were pooled across studies. The PAT scoring scheme was developed based on pooled ORs. The PAT score was internally validated with published 105 Asian patients (follow-up 8.0 ± 4.1 [SD] years) and externally validated with unpublished 164 multiracial patients (82.3% White, 14.6% Asian, 3.2% Black; mean follow-up 8.0 ± 6.9 years) with Brugada syndrome. Performances were assessed and compared with previous scores using receiver operating characteristic curve (ROC) analysis. RESULTS: Sixty-seven studies published between 2002 and 2022 from 26 countries (7358 patients) were included. Pooled ORs were estimated, indicating that 15 of 23 risk factors were significant. The PAT score was then developed accordingly. The PAT score had significantly better discrimination (ROC 0.9671) than the BRUGADA-RISK score (ROC 0.7210; P = .006), Shanghai Score System (ROC 0.7079; P = .003), and Sieira et al score (ROC 0.8174; P = .026) in an external validation cohort. PAT score ≥ 10 predicted the first MAE with 95.5% sensitivity and 89.1% specificity (ROC 0.9460) and the recurrent MAE (ROC 0.7061) with 15.4% sensitivity and 93.3% specificity. CONCLUSION: The PAT score was shown to be useful in predicting MAE for primary prevention in patients with Brugada syndrome.