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.