Murillo O. Antunes

Obstructive Sleep Apnea Is Common and Independently Associated With Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy

BACKGROUND Hypertrophic cardiomyopathy (HCM) is associated with arrhythmias and cardiovascular death. Left atrial enlargement and atrial fibrillation (AF) are considered markers for death due to heart failure in patients with HCM. Obstructive sleep apnea (OSA) is independently associated with heart remodeling and arrhythmias in other populations. We hypothesized that OSA is common and is associated with heart remodeling and AF in patients with HCM. METHODS We evaluated 80 consecutive stable patients with a confirmed diagnosis of HCM by sleep questionnaire, blood tests, echocardiography, and sleep study (overnight respiratory monitoring). RESULTS OSA (apnea-hypopnea index [AHI] > 15 events/h) was present in 32 patients (40%). Patients with OSA were significantly older (56 [41-64] vs 38.5 [30-53] years, P < .001) and presented higher BMI (28.2 +/- 3.5 vs 25.2 +/- 5.2 kg/m(2), P < .01) and increased left atrial diameter (45 [42-52.8] vs 41 [39-47] mm, P = .01) and aorta diameter (34 [30-37] vs 29 [28-32] mm, P < .001), compared with patients without OSA. Stepwise multiple linear regression showed that the AHI (P = .05) and BMI (P = .06) were associated with left atrial diameter. The AHI was the only variable associated with aorta diameter (P = .01). AF was present in 31% vs 6% of patients with and without OSA, respectively (P < .01). OSA (P = .03) and left atrial diameter (P = .03) were the only factors independently associated with AF. CONCLUSIONS OSA is highly prevalent in patients with HCM and it is associated with left atrial and aortic enlargement. OSA is independently associated with AF, a risk factor for cardiovascular death in this population.

Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy

BACKGROUND 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 São 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.

Sleep Quality and Quality of Life in Patients with Hypertrophic Cardiomyopathy

Objectives: To evaluate clinical predictors of poor sleep quality and quality of life (QOL) in patients with hypertrophic cardiomyopathy (HCM). Methods: Consecutive stable patients with HCM were evaluated for the risk of obstructive sleep apnea (OSA) by the Berlin Questionnaire, daytime sleepiness by the Epworth Sleepiness Scale, sleep quality by the Pittsburgh Sleep Questionnaire Index and QOL by the Minnesota Living with Heart Failure Questionnaire. Asymptomatic subjects without HCM were used as controls. Results: We studied 84 patients with HCM and 42 controls who were similar with regard to gender (49 vs. 50% males), age [52 (38–62) vs. 47 (33–58) years] and body mass index (27 ± 4 vs. 27 ± 5). HCM diagnosis, high risk for OSA and female gender were independently associated with poor sleep quality in the entire population. Among patients with HCM, poor QOL was independently associated with poor sleep quality, New York Heart Association functional class and diuretic therapy. Conclusion: Poor sleep quality is very common in patients with HCM and may have a negative impact on the QOL, which in turn is an important marker of prognosis in patients with cardiomyopathies.

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE: 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/m2) 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.

Cheyne-stokes respiration associated with hypertrophic cardiomyopathy and normal left ventricular ejection fraction

Cheyne‐Stokes respiration (CSR) is a form of periodic breathing in which central apneas and hypopneas alternate with periods of hyperventilation, producing a waxing and waning pattern of tidal volume. This brief case described an interesting association of CSR and hypertrophic cardiomyopathy (HCM) in a patient with normal left ventricular ejection fraction, providing physiological insights for the genesis of CSR.

Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy.

BACKGROUND/PURPOSE Patients with hypertrophic cardiomyopathy (HCM) have elevated risk for sudden cardiac death (SCD). Our study aimed to quantitatively characterize microvolt T-wave alternans (TWA), a potential arrhythmia risk stratification tool, in this HCM patient population. METHODS TWA was analyzed with the quantitative modified moving average (MMA) in 132 HCM patients undergoing treadmill exercise testing, grouped according to Maron score risk factors as high-risk (H-Risk, n=67,), or low-risk (L-Risk, n=65, without these risk factors). RESULTS TWA levels were much higher for the H-Risk than for the L-Risk group (101.40±75.61 vs. 54.35±46.26μV; p<0.0001). A 53μV cut point, set by receiver operator characteristic (ROC), identified H-Risk patients (82% sensitivity, 69% specificity). CONCLUSIONS High TWA levels were found for hypertrophic cardiomyopathy patients. Abnormal TWA associated with major risk factors for SCD: non-sustained ventricular tachycardia on Holter (p=0.001), family history of SCD (p=0.006), septal thickness ≥30mm (p<0.001); and inadequate blood pressure response to effort (p=0.04).

Clinical predictors of a positive genetic test in hypertrophic cardiomyopathy in the Brazilian population

BackgroundHypertrophic cardiomyopathy is a genetic autosomal dominant disease characterized by left ventricular hypertrophy. The molecular diagnosis is important but still expensive. This work aimed to find clinical predictors of a positive genetic test in a Brazilian tertiary centre cohort of index cases with HCM.MethodsIn the study were included patients with HCM clinical diagnosis. For genotype x phenotype comparison we have evaluated echocardiographic, electrocardiographic, and nuclear magnetic resonance measures. All patients answered a questionnaire about familial history of HCM and/or sudden death. β-myosin heavy chain, myosin binding protein C, and troponin T genes were sequenced for genetic diagnosis.ResultsThe variables related to a higher probability of a positive genetic test were familial history of HCM, higher mean heart frequency, presence of NSVT and lower age. Probabilities of having a positive molecular genetic test were calculated from the final multivariate logistic regression model and were used to identify those with a higher probability of a positive molecular diagnosis.ConclusionsWe developed an easy and fast screening method that takes into account only clinical data that can help to select the patients with a high probability of positive genetic results from molecular sequencing of Brazilian HCM patients.

Prevention of Sudden Death in Hypertrophic Cardiomyopathy

DOI: 10.5935/abc.20180101 Hypertrophic cardiomyopathy (HCM) is the most common congenital disease, and sudden death (SD), its most feared complication, was already mentioned by Donald Teare1 in the first description of the disease, being observed in 7 out of 8 patients. SD occurs during daily activities, after exercises and even during sleep; it may affect young athletes, which has a great impact on the media. This has required considerable effort by researchers in defining clinical factors and complementary tests that could be used in the screening of individuals at higher risk that could benefit from implantable cardioverter defibrillator (ICD) and also to prevent SD, since it is caused by tachycardia and ventricular fibrillation.2 HCM favors the occurrence of ventricular arrythmias – hypertrophy causes repolarization dispersion; myocyte disarray and increased fibrosis create areas of conduction block and predispose to reentry arrhythmias; and abnormalities in ion fluxes, such as calcium, during repolarization may also trigger arrhythmias. In addition, this complex arrhythmogenic substrate may be modulated by impaired autonomic response, myocardial ischemia and left ventricular outflow tract obstruction.2-4 If we consider deaths from cardiovascular causes, in patients with HCM, they account for 0.5%-1.5% deaths a year, which is near to that of the general population.2 In HCM patients considered as high risk, SD may reach 2.5% of deaths a year.5 However, the accurate identification of these patients for preventive therapy with ICD may be challenging. Before the guidelines were published,3 it was known that manifestations of HCM in children younger than 10 years old with diastolic or systolic dysfunction, SD in first-degree relatives younger than 50 years, nonsustained ventricular tachycardia, syncope and myocardial hypertrophy > 30 mm were factors associated with SD, and the last four fully considered as indications for ICD in the first guideline (2011).2 Today, we know that the positive predictive value of each of these factors is low, and there is little evidence suggesting a higher predictive value of any of these factors. However, some authors have considered only one risk factor for indication of ICD.6 The two largest multicentric studies grounded in the American guidelines2 – one of adults (n = 506, mean age of 42; mean follow-up period of 3.7 years) showed that for primary prevention ICD indication, in 75% of cases, the devices were used in 4%/year, whereas for the secondary prevention, intervention rates were 12%/year in 25% of cases. Therapies were found in 20% of patients and inappropriate shocks in 27%, with 7% of complications.7 The other study involved 224 children and adolescents (mean age of 14 years; mean follow-up of 4.3 years). Primary prevention was indicated in 84% of cases and secondary prevention indicated for 16% of cases. Intervention rates were similar to those in adults, with therapies and inappropriate shocks in 19% and 41% of cases, respectively.8

Apparent Non-Cited Overlap between Two Published Articles by the Same Group of Authors

Because review and decision had not been completed for the first article before the second manuscript was submitted, we could not provide a reference for the first paper in the second. (Editors’ note: it might have been appropriate to notify the journal so that the first paper could have been cited in the second, once the first paper had been accepted, but this was not done.) Though the study population was the same for both papers, we studied the effect of homocysteine-induced oxidative stress on endothelial function in coronary slowflow in the first paper, a subject that we continue to believe is not sufficiently related to the effect of thyroid hormone on slow coronary flow, reported in the second paper, to justify their inclusion in a single report. We believe it is common to report unrelated results of interest from single populations.

Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death

Relatamos a rara associacao entre sindrome Leopard e miocardiopatia hipertrofica em mulher de 27 anos, pouco sintomatica, que veio para estratificacao e prevencao de risco de morte subita. Portadora de uma sindrome rara, que se manifesta com pequenas maculas disseminadas pelo corpo, alem de alteracoes oculares, genitais, cardiacas e de crescimento. A associacao de miocardiopatia hipertrofica com fatores de risco de morte subita determinou a indicacao do implante de cardiodesfibrilador (CDI) para prevencao primaria.We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD) for primary prevention.