Topological data analysis to identify cardiac resynchronization therapy patients exhibiting benefit from an implantable cardioverter-defibrillator

Background Current guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defibrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will benefit from choosing a CRT-D device in terms of survival. Objective We aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. Methods We included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identified multiple phenogroups in the generated network and compared the groups’ clinical characteristics and survival. Results Five- and 10-year mortality were 43 (40–46)% and 71 (67–74)% in patients with CRT-D and 48 (45–50)% and 71 (68–74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate five phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47–0.80], p < 0.001 and adjusted hazard ratio 0.84 [0.71–0.99], p = 0.033, respectively). Conclusions By simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or non-ischemic etiology who will most likely benefit from the implantation of a CRT-D instead of a CRT-P. Graphical abstract Topological data analysis to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. AF atrial fibrillation, CRT cardiac resynchronization therapy, CRT-D cardiac resynchronization therapy defibrillator, CRT-P cardiac resynchronization therapy pacemaker, DM diabetes mellitus, HTN hypertension, LBBB left bundle branch block, LVEF left ventricular ejection fraction, MDS multidimensional scaling, MRA mineralocorticoid receptor antagonist, NYHA New York Heart Association