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

Luis E Rohde, Muthiah Vaduganathan, Brian L Claggett, Carisi A Polanczyk, Pranav Dorbala, Milton Packer, Akshay S Desai, Michael Zile, Jean Rouleau, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J V McMurray, Scott D Solomon

Journal: European journal of heart failure 2021;23(8):1346-1356

PMID: 33565237

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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 (P < 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.

Address: Division of Cardiovascular, Brigham and Women's Hospital, Boston, MA, USA.; Hospital de Clínicas de Porto Alegre and UFRGS Medical School, Porto Alegre, Brazil.; Division of Cardiovascular, Brigham and Women's Hospital, Boston, MA, USA.; Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.; Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.; Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada.; Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden, London, UK.; Novartis, East Hanover, NJ, USA.; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

DOI: 10.1002/ejhf.2120