Clinical Phenotypes in Relation to Outcomes in Heart Failure Patients With Cardiac Resynchronization Therapy and Defibrillators (CRT-D): An Unsupervised Cluster Analysis

Background: Patients with heart failure undergoing cardiac resynchronization therapy (CRT) are a heterogenous and complex population. Objective: To identify different clusters of patients with CRT-D and to evaluate the associations with clinical outcomes, using cluster analysis (CAs). Methods: Three agglomerative hierarchical CAs were performed in CRT-D patients seen between 2010 and 2019 in French hospitals. Associations between clusters and death at 1 year and death during the whole follow-up (FU) were evaluated. Results: The study included 23 029 CRT-D patients, who were analyzed in three ways, as follows: the first group was a 50% random sample of all patients (n = 11 514), the second group included patients who were dead at 1 year (n = 1604) and the third group included those alive at 3 years FU (n = 14 228). A CA was performed on each group of patients. Four clusters were identified: Cluster 1 corresponded to the low-risk phenotype; Cluster 2 to patients with coronary artery disease (CAD) with few cardiovascular (CV) risk factors and comorbidities; Cluster 3 included patients with CV risk factors and comorbidities, but low CAD; Cluster 4 corresponded to clinically complex phenotype (CAD with CV risk factors and comorbidities). Compared with Cluster 1, Clusters 2, 3, and 4 were independently associated with an increased risk of all-cause death at 1-year FU and during the whole FU (Cluster 2: hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.08-1.36; Cluster 3: HR 1.15, 95% CI 1.04-1.26; and Cluster 4: HR 1.79, 95% CI 1.65-1.96). Conclusion: CAs identified four statistically driven groups of CRT recipients, with specific clinical phenotypes and associated with different risks for all-cause death.