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Figure 1. Survival analysis. A Kaplan-Meier curve depicting gender-related survival free from cardiac events (defined as sudden cardiac or heart failure death, transplant, appropriate implantable cardioverter defibrillator therapy, and stroke) in carriers of null variants (frameshift, nonsense, and intronic ones affecting the splicing process) in FLNC and TTN. Information was extracted from the Health in Code (HIC) proprietary database, which collects clinical and genetic data from more than 15,000 published manuscripts about inherited cardiovascular diseases, and information from > 25,000 probands and families genetically studied at HIC. In carriers of null FLNC variants, events start in males in their 20’s, progressively increase and become more frequent after age 40. In women, events are unusual before age 30 but become more frequent after age 40. Prognosis is better in females: by age 60, 50% of men and 25%-30% of women had died of a cardiovascular cause (log-rank 0.0001). The main event in carriers of both genders is sudden death. In contrast, events are infrequent at early ages in carriers of null TTN variants. By the beginning of the fifth decade, only 10% of carriers suffered an adverse event, but after that, there is a trend to a higher number of events in males. By age 70, significantly more males (50%) compared with females (30%) had suffered an event (P = 0.02). The events are composed of both deaths from heart failure and transplantation and major arrhythmic events (sudden death/appropriate defibrillator therapy). More than 95% of carriers of TTN null variants who suffered an event had overt cardiomyopathy. In contrast, 51% of patients with an FLNC null variant who had events had absent or mild LV dysfunction.