EDMUNDO ARTEAGA FERNANDEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy(2013) NERBASS, Flavia B.; PEDROSA, Rodrigo P.; GENTA, Pedro R.; ANTUNES, Murillo O.; ARTEAGA-FERNANDEZ, Edmundo; DRAGER, Luciano F.; LORENZI-FILHO, GeraldoOBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46 +/- 15 years; body mass index, 26.6 +/- 4.9 kg/m(2)) were included, and obstructive sleep apnea (respiratory disturbance index >= 15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age >= 45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.
- Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy(2013) SHIOZAKI, Afonso Akio; SENRA, Tiago; ARTEAGA, Edmund; MARTINELLI FILHO, Martino; PITA, Cristiane Guedes; AVILA, Luis Francisco R.; PARGA FILHO, Jose Rodrigues; MADY, Charles; KALIL-FILHO, Roberto; BLUEMKE, David A.; ROCHITTE, Carlos EduardoBackground: Myocardial fibrosis (MF) occurs in up to 80% of subjects with asymptomatic or mildly symptomatic hypertrophic cardiomyopathy (HCM) and can constitute an arrhythmogenic substrate for re-entrant, life-threatening ventricular arrhythmias in predisposed persons. Objective: The aim was to investigate whether MF detected by delayed enhancement cardiac CT is predictive of ventricular tachycardia (VT) and fibrillation (VF) that require appropriate therapy by an implantable cardioverter defibrillator (ICD) in patients with HCM. Methods: Twenty-six patients with HCM with previously (for at least 1 year) implanted ICD underwent MF evaluation by cardiac CT. MF was quantified by myocardial delayed enhanced cardiac CT. Data on ICD firing were recorded every 3 months after ICD implantation. Risk factors for sudden cardiac death in patients with HCM were evaluated in all patients. Results: MF was present in 25 of 26 patients (96%) with mean fibrosis mass of 20.5 +/- 15.8 g. Patients with appropriate ICD shocks for VF/VT had significantly greater MF mass than patients without (29.10 +/- 19.13 g vs 13.57 +/- 8.31 g; P = .01). For a MF mass of at least 18 g, sensitivity and specificity for appropriate ICD firing were 73% (95% CI, 49%-88%) and 71% (95% CI, 56%-81%), respectively. Kaplan-Meier curves indicated a significantly greater VF/VT event rate in patients with MF mass >= 18 g than in patients with MF <18 g (P = .02). In the Cox regression analysis, the amount of MF was independently associated with VF/VT in ICD-stored electrograms. Conclusion: The mass of MF detected by cardiac CT in patients with HCM at high risk of sudden death was associated with appropriate ICD firings.
- Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy(2013) MARSIGLIA, Julia Daher Carneiro; CREDIDIO, Flavia Laghi; OLIVEIRA, Theo Gremen Mimary de; REIS, Rafael Ferreira; ANTUNES, Murillo de Oliveira; ARAUJO, Aloir Queiroz de; PEDROSA, Rodrigo Pinto; BARBOSA-FERREIRA, Joao Marcos Bemfica; MADY, Charles; KRIEGER, Jose Eduardo; ARTEAGA-FERNANDEZ, Edmundo; PEREIRA, Alexandre da CostaBackground Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype. Methods We included 268 index patients from Sao Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer. Results We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations. Conclusion The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes.
- Evaluation of the Autonomic Function in Patients with Hypertrophic Cardiomyopathy with and without Syncope(2013) MACATRAO-COSTA, Milena Frota; ARTEAGA-FERNANDEZ, Edmundo; BRITO, Fabio Sandoli de; DARRIEUX, Francisco; MELO, Sissy Lara de; SCANAVACCA, Mauricio; SOSA, Eduardo; HACHUL, DeniseBackground: Several mechanisms may be involved in the trigger of syncope in patients with hypertrophic cardiomyopathy (HCM), including hemodynamic collapses that might be related to an autonomic imbalance. Objective: To evaluate and compare the autonomic function of patients presenting HCM with unexplained syncope (US) to those without syncope. Methods: Thirty-seven patients were included, 16 with US and 21 without syncope. Their autonomic function was assessed by spontaneous and phenylephrine induced baroreflex sensitivity (BRS), by heart rate variability (HRV) in time domain during 24-hour Holter and in frequency domain (spectral analysis), both in supine position and at 70 head-up tilt (HUT). Results: The spontaneous BRS was similar in both groups (16,46 +/- 12,99 vs. 18,31 +/- 9,88 ms/mmHg, p = 0,464), as was phenylephrine-induced BRS (18,33 +/- 9,31 vs. 15,83 +/- 15,48 ms/mmHg, p = 0,521). No differences were observed in SDNN (137,69 +/- 36,62 vs. 145,95 +/- 38,07 ms, p = 0,389). The group presenting syncope had a significantly lower RMSSD (24,88 +/- 10,03 vs. 35,58 +/- 16,43 ms, p = 0,042) and a tendency to lower pNN50 (4,51 +/- 3,78 vs. 8,83 +/- 7,98%, p = 0,085) and lower values of the high frequency component of HRV spectral analysis at rest (637,59 +/- 1.295,53 vs. 782,65 +/- 1.264,14 ms2, p = 0,075). No significant difference was observed in response to HUT (p = 0,053). HUT sensitivity, specificity and accuracy in identifying the etiology of US in HCM patients were 6%, 66% and 40%, respectively. Conclusions: A lower parasympathetic tone was observed in HCM patients with US, but the clinical relevance of this finding remains unclear. HUT is not a valuable tool for evaluating the origin of syncope in these patients, mainly because of its poor specificity.
- Obstructive sleep apnea and hypertrophic cardiomyopathy: A common and potential harmful combination(2013) NERBASS, Flavia B.; PEDROSA, Rodrigo P.; DANZI-SOARES, Naury J.; DRAGER, Luciano F.; ARTEAGA-FERNANDEZ, Edmund; LORENZI-FILHO, GeraldoHypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is characterized by large and asymmetric septal and left ventricle hypertrophy. HCM is a cause of disability, including heart failure, atrial fibrillation, and sudden death, with an annual mortality varying from 1% to 6%. Obstructive sleep apnea (USA) is extremely common among patients with established cardiovascular disease, including hypertension and atrial fibrillation and when present may contribute to worse cardiovascular outcome. Although patients with HCM do not necessarily have typical characteristics of patients with USA, such as obesity and increasing age, there is recent evidence that USA is extremely common among patients with HCM, with a prevalence ranging from 32% to 71%. The presence of USA among patients with HCM is independently associated with worse structural and functional impairment of the heart, including atrial and aorta enlargement, worse New York Heart Association functional class, and worse quality of life. The prevalence of atria fibrillation, an independent marker of mortality among patients with HCM, is significantly higher (similar to four times) in the presence of USA. Therefore, the recognition of USA is a new area of research that may impact the management of patients with HCM.