Polimorfismos en genes no sarcoméricos, influencia en el remodelado cardíaco e implicaciones pronósticas en pacientes con miocardiopatía hipertrófica

Resumen

? ABSTRACT Objectives: 1. To study the effect of several polymorphisms located in non sarcomeric genes in cardiac fibrosis in patients with hypertrophic cardiomyopathy (HCM): 1.1 To study the association of polymorphisms with the degree of myocardial fibrosis by cardiac MRI using gadolinium enhancement. 1.2 To study the involvement of the polymorphisms in the degree of myocardial fibrosis observed in myocardial tissues obtained from patients with HCM by septal myectomy. 2. Study the effect of several polymorphisms located in non sarcomeric genes in the development of atrial fibrillation in patients with HCM. 3. Study the effect of several polymorphisms located in non sarcomeric genes in urgent hospitalization in patients with HCM. Methods: A cohort study including patients with stable HCM in three tertiary hospitals in southeastern Spain was performed. All patients older than 18 years diagnosed with HCM were consecutively included after completion of a cardiac MRI. All patients underwent a clinical evaluation: anamnesis, clinical examination and complementary examinations (electrocardiogram, echocardiography, Holter-ECG, effort test and cardiac MRI). The presence of nine polymorphisms in non sarcomeric genes were determined (ACE D/I, AGTR1 1166A>C, CYP11B2 -344C>T, COL1A1 2046G>T, RETN -420C>G, ADRB1 1165G>C, PPARGC1A 1444G>A, NOS3 894T>G y CALM3 -34T>A). The serum resistin concentration is determined by ELISA (Enzyme-linked immunosorbent assay). Aldosterone levels in serum were determined by direct radioinmuinoassay. The fibrosis is determined in tissue samples from myocardial septal myectomy using the Masson's trichrome staining. Results: The study population was constituted by 168 patients and 136 controls with a median follow up of 49.5 months (IQR 25.8 to 77.0). The presence of the polymorphism RETN -420C>G gene remained an independent predictor of the number of segments with late gadolinium enhancement in the multivariate analysis (adjusted R² 0.031, p: 0.038). The association between polymorphism RETN -420C>G gene and interstitial fibrosis in myocardial tissue was statistically significant [B coefficient: 0.488 (95% CI 0.015 to 0.962), p: 0.044]. In the multivariate analysis, the presence of the polymorphism in the promoter region of CYP11B2 (-344T> C) [HR: 3.02 (95% CI 1.01 to 8.99); p = 0.047], the history of previous AF [HR: 2.81 (95% CI 1.09 to 7.23); p = 0.033] and the diameter of the AI ?42 mm [HR: 2.69 (95% CI 1.01 to 7.18); p = 0.048] remained independent predictors of the development of AF. In the multivariate analysis, both age [HR 1.03 (95% CI 1.00-1.05); p = 0.047] and the absence of COL1A1 gene polymorphism (genotype 2046G / G) [HR: 2.76 (1.26 to 6.05), p = 0.011] remained independently associated with hospitalization. Conclusions: CONCLUSION 1: The polymorphism in the promoter region of the resistin gene, RETN -420C> G, was significantly associated with cardiac fibrosis in patients with hypertrophic cardiomyopathy. Conclusion 1.1: The polymorphism in the promoter region of the resistin gene, RETN -420C> G, was significantly associated with an increase in the number of segments presenting late gadolinium enhancement on cardiac MRI. Conclusion 1.2: The polymorphism in the promoter region of resistin gene, RETN -420C> G is associated significantly with the degree of myocardial fibrosis in myocardial tissue samples obtained by Myectomy. CONCLUSION 2: The presence of the polymorphism in the promoter region of aldosterone synthase gene, CYP11B2 -344C> T, was significantly associated with the development of atrial fibrillation in patients with hypertrophic cardiomyopathy. CONCLUSION 3: The polymorphism of ?1 chain of type I collagen, COL1A1 2046G> T, is an independent predictor of prognosis in patients with hypertrophic cardiomyopathy, assessed by the need for urgent hospitalization.