Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM-HF analysis

Eur J Heart Fail. 2021 Aug;23(8):1346-1356. doi: 10.1002/ejhf.2120. Epub 2021 Mar 9.

Abstract

Aims: Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment.

Methods and results: We studied 8399 patients enrolled in the PARADIGM-HF trial and identified independent predictors of SCD (n = 561, 36% of total deaths) using time-updated multivariable-adjusted Cox models, classification and regression tree (CART), and logistic regression analysis. Compared with patients who were alive or died from non-sudden cardiovascular deaths, patients who suffered a SCD displayed a distinct temporal profile of New York Heart Association (NYHA) class, heart rate and levels of three biomarkers (albumin, uric acid and total bilirubin), with significant differences observed more than 1 year prior to the event (Pinteraction < 0.001). In multivariable models adjusted for baseline covariates, seven time-updated variables independently contributed to SCD risk (incremental likelihood chi-square = 46.2). CART analysis identified that baseline variables (implantable cardioverter-defibrillator use and N-terminal prohormone of B-type natriuretic peptide levels) and time-updated covariates (NYHA class, total bilirubin, and total cholesterol) improved risk stratification. CART-defined subgroup of highest risk had nearly an eightfold increment in SCD hazard (hazard ratio 7.7, 95% confidence interval 3.6-16.5; P < 0.001). Finally, changes over time in heart rate, NYHA class, blood urea nitrogen and albumin levels were associated with differential risk of sudden vs. non-sudden cardiovascular deaths (P < 0.05).

Conclusions: Beyond single time-point assessments, distinct changes in multiple cardiac-specific and systemic variables improved SCD risk prediction and were helpful in differentiating mode of death in chronic heart failure.

Keywords: Clinical predictors; Heart failure; Sudden cardiac death.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology
  • Defibrillators, Implantable*
  • Heart Failure* / epidemiology
  • Heart Failure* / therapy
  • Humans
  • Proportional Hazards Models
  • Risk Factors