Association of genotype with treatment response and prognosis in dilated cardiomyopathy.
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Mora-Ayestarán Nerea, Ochoa Juan Pablo, Espinosa-Castro María Ángeles, Navarro-Peñalver Marina, Villacorta Eduardo, Crespo-Leiro María G, Climent-Payá Vicente, Lacuey-Lecumberri Gemma, Peña-Peña María Luisa, Bermúdez-Jiménez Francisco J, García-Pinilla José M, Mogollón-Jiménez María Victoria, Limeres-Freire Javier, García-Álvarez Ana, Bayés-Genís Antoni, Palomino-Doza Julián, Tirón Coloma, Ripoll-Vera Tomás, López Javier, Brion María, Vilches-Soria Silvia, Sabater-Molina María, García-Berrocal Belén, Larrañaga-Moreira José M, García-Álvarez María I, Basurte-Elorz María Teresa, Llamas-Gómez Helena, Méndez-Fernández Irene, Garrido-Bravo Iris Paula, González-López Esther, Gallego-Delgado María, Barriales-Villa Roberto, Lara-Pezzi Enrique, García-Pavía Pablo, Domínguez Fernando
Аннотация
METHODS: We analyzed genotyped DCM patients with serial echocardiograms from the Spanish DCM study. The main objective was to assess the influence of genotype on LVRR, defined by improvement in ejection fraction within 12± 6 months. Secondary endpoints included major adverse cardiovascular events, end-stage heart failure (HF), and major ventricular arrhythmias.
RESULTS: A total of 711 patients were included (67% male, mean age 50.8 years, baseline ejection fraction 31%, 44% genotype positive). LVRR occurred in 39% of genotype-positive vs 47% of genotype-negative patients (P=.036). Independent predictors of LVRR were TTN variants, lower baseline ejection fraction, and HF admission at diagnosis. In contrast, desmosomal, nuclear envelope and motor sarcomeric gene variants were associated with a lower likelihood of LVRR. During a median follow-up of 4.5 years, 26% of patients with initial LVRR showed subsequent deterioration, which was more frequent among genotype-positive individuals (32% vs 22%, P=.054). Compared with patients with sustained LVRR, those with deterioration had worse outcomes, including higher rates of major cardiovascular events (25% vs 7%), end-stage HF (18% vs 1%), and ventricular arrhythmia (12% vs 4%) (all P <.05).
CONCLUSIONS: Genotype is a major determinant of both initial and long-term LVRR. Loss of ejection fraction improvement is common and strongly associated with adverse outcomes.