Hypertrophic cardiomyopathy in patients with a normal electrocardiogram: A view from the east side of the Atlantic Ocean.

BACKGROUND: Although the 12­lead electrocardiogram (ECG) is abnormal in most patients with hypertrophic cardiomyopathy (HCM), some present normal ECG. This study aimed to analyse the baseline characteristics, clinical presentation and outcomes of HCM patients with normal ECG and to compare them with those with abnormal ECG. METHODS AND RESULTS: Baseline characteristics, clinical presentation, data from complementary exams and clinical outcomes of 1070 consecutive patients included in the Portuguese Registry of HCM (Pro-HCM registry) were compared between two groups of patients: normal Vs. abnormal ECG. Among this population, 98 (9.2%) patients had normal ECG at presentation; they were significantly younger and had lower frequency of hypertension, symptoms at presentation, heart failure, angina, cardiac and non-cardiac diseases. ESC and AHA risk scores for Sudden Cardiac Death (SCD) were not significantly different between the two groups. Patients with normal ECG had higher prevalence of family history of SCD and lower degree of left ventricular (LV) hypertrophy, LV systolic dysfunction, LV outflow tract obstruction and myocardial fibrosis. The combined endpoint of cardiac death, SCD, cardiac arrest, appropriate ICD shocks or evolution to systolic dysfunction, during a mean follow-up of 5 years was significantly less frequent in patients with normal ECG (2.1% Vs. 6.5%; p = 0.043). CONCLUSIONS: A normal ECG is not a marker of an overall benign profile in HCM patients. Though a normal ECG at presentation is associated with a less severe phenotype and a lower probability of evolution to heart failure at 5-years, this finding did not show a protective effect in other clinical outcomes.

Advances in hypertrophic cardiomyopathy: What the cardiologist needs to know.

Hypertrophic cardiomyopathy (HCM) is known as the most common genetic heart disease, characterized by otherwise unexplained left ventricular (LV) hypertrophy. In spite of major advances in whole genome sequence techniques, it is still not possible to identify the causal mutation in approximately half of HCM patients. Consequently, a new HCM concept, "beyond the sarcomere" is being developed, supported by data from recent HCM registries which reveal two distinct HCM subgroups: sarcomere positive HCM subgroup and nonfamilial HCM subgroup. Sarcomere positive HCM patients tend to be younger age at diagnosis, have fewer co-morbidities, present more often with reverse septal morphology, more myocardial fibrosis, less LV outflow tract obstruction, and a worse prognosis when compared to nonfamilial HCM patients. These subgroups, with different molecular basis, phenotypes and clinical profiles, will likely require specific management strategies. Important research advances have also been made concerning diagnosis, sudden cardiac death stratification and therapy. In this article, we seek to review recent relevant knowledge, summarizing the advances in this complex and heterogeneous disease.

Recommendations for genetic testing in cardiology: Review of major international guidelines. / Recomendações para a realização de testes genéticos em cardiologia ­ revisão das principais diretrizes internacionais.

In recent years, the importance of genetic causes of cardiovascular diseases has been increasingly recognized, as the result of significant advances in molecular diagnosis techniques. This growing knowledge has enabled the identification of new phenotypes and the subclassification of clinical syndromes, impacting the therapeutic approach and genetic counseling offered to affected families. This paper describes the state of the art of genetic testing in the main cardiovascular diseases, aiming to provide a useful tool to help cardiologists and other health professionals involved in the care of individuals with hereditary heart diseases and their families.

Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease; there is still a large proportion of patients with no identified disease-causing mutation. Although the majority of mutations are found in the MYH7 and MYBPC3 genes, mutations in Z-disk-associated proteins have also been linked to HCM. METHODS: We assessed a small family with HCM based on family history, physical examination, 12-lead ECG, echocardiogram and magnetic resonance imaging. After exclusion of mutations in eleven HCM disease genes, we performed direct sequencing of the TCAP gene encoding the Z-disk protein titin-cap (also known as telethonin). RESULTS: We present a novel TCAP mutation in a small family affected by HCM. The identified p.C57W mutation showed a very low population frequency, as well as high conservation across species. All of the bioinformatic prediction tools used considered this mutation to be damaging/deleterious. Family members were screened for this new mutation and a co-segregation pattern was detected. Both affected members of this family presented with late-onset HCM, moderate asymmetric left ventricular hypertrophy, atrial fibrillation and heart failure with preserved ejection fraction and low risk of sudden cardiac death. CONCLUSIONS: We present evidence supporting the classification of the TCAP p.C57W mutation, encoding the Z-disk protein titin-cap/telethonin as a new likely pathogenic variant of hypertrophic cardiomyopathy, with a specific phenotype in the family under analysis.

Admission heart rate as a predictor of mortality in patients with acute coronary syndromes.

INTRODUCTION: Heart rate (HR) is a prognostic factor in stable angina. However, in the context of acute coronary syndromes (ACS), it is less studied. AIMS: To evaluate the influence of admission HR as a prognostic factor in patients with ACS. METHODS: We evaluated in-hospital, 30-day and one-year mortality in patients with ACS, according to admission HR. RESULTS: We analysed 1126 patients, 69% males, mean age 64 years, 59% with ST-segment elevation acute myocardial infarction and 15% on medication with a beta-blocker. On admission, 14% presented signs of heart failure. In 10%, left ventricular ejection fraction was < 35%. In-hospital mortality was 7.1%, 30-day mortality 9.1% and one-year mortality 10.7%. The best cut-off of HR to predict mortality was 80 bpm (sensitivity 64-66% and specificity 54-55%). By multivariate analysis, a heart rate ≥ 80 bpm was an independent predictor of all-cause mortality (HR 1.50, 95% CI: 1.01-2.23, P = 0.047). CONCLUSIONS: In a population with ACS, a higher admission HR is an independent predictor of short- and medium-term prognosis, which is also independent of left ventricular function.

[Impact of age on treatment and outcomes after acute myocardial infarction, particularly in very elderly patients]. / Impacto da idade no tratamento e resultados após enfarte agudo do miocárdio em particular nos muito idosos.

INTRODUCTION: The elderly population admitted for acute myocardial infarction is increasing. This group is not well studied in international trials and is probably treated with a more conservative approach. OBJECTIVES: To evaluate the presentation and treatment of myocardial infarction according to age, particularly in very elderly patients. METHODS: We studied 1242 consecutive patients admitted with acute myocardial infarction, assessing in-hospital, 30-day and one-year mortality during follow-up for each age-group. Patients were divided into four groups according to age: <45 years (7.6%); 45-64 years (43.3%); 65-74 years (23.4%); and ≥75 years (25.7%). RESULTS: Elderly patients had a worse risk profile (except for smoking), more previous history of coronary disease and a worse profile on admission, with the exception of lipid profile, which was more favorable. With regard to treatment of the elderly, although less optimized than in other age-groups, it was significantly better compared to other registries, including for percutaneous coronary angioplasty. Both complications and mortality were worse in the older groups. In elderly patients (≥75 years), adjusted risk of mortality was 4.9-6.3 times higher (p<0.001) than patients in the reference age-group (45-64 years). In these patients, the independent predictors of death were left ventricular function and renal function, use of beta-blockers being a predictor of survival. CONCLUSIONS: Elderly patients represent a substantial proportion of the population admitted with myocardial infarction, and receive less evidenced-based therapy. Age is an independent predictor of short- and medium-term mortality.

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope.

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

[Incidence of ventricular arrhythmias in patients with severe left ventricular systolic dysfunction: is there a benefit after cardiac resynchronization therapy?]. / Incidência de arritmias ventriculares em doentes corn disfunção sistólica ventricular esquerda grave: existe benefício após terapêutica de ressincronização cardíaca.

BACKGROUND: Cardiac resynchronization therapy (CRT) has significant benefits in selected patients (P). The impact of this modality in the incidence of ventricular tachyarrhythmias remains controversial. We analysed the occurrence of appropriate therapies in P submitted to CRT combined with a cardioverter-defibrillator (ICD). METHODS: Study of 123 P with left ventricular ejection fraction (LVEF) < 35%, submitted to successful implantation of CRT-ICD or ICD alone (primary prevention). RESULTS: Mean age was 63 +/- 12 years, LVEF of 25 +/- 6%, median follow-up of 372 days. CRT-ICD implanted in 63P (group A) and ICD alone in 60P (group B). Group A has 86% of clinical responders, lower prevalence of ischemic cardiomyopathy (30% vs. 72%), and more P in class III of the NYHA before device implantation (90% vs. 7%) compared with ICD alone patients. There were no differences in the incidence of appropriate therapies (19% vs. 12%) or in the time for first therapy (305 days vs. 293 days). Total mortality was 11% in group A and 12% in group B. Kaplan-Meier curves for arrhythmic events in patients with CRT showed no significant differences (HR 3.02, 95% CI 0.82 - 11.09, p = NS) when compared to patients without CRT. CONCLUSIONS: In P submitted to CRT-ICD for primary prevention, despite a higher rate of responders, the incidence of appropriate therapies is not different from those with an ICD alone.

[Thoracic fluid content - a possible determinant of ventilatory efficiency in patients with heart failure]. / Fluido torácico total - Um possível determinante da eficácia ventilatória em doentes com insuficiência cardíaca.

UNLABELLED: Ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), has considerable prognostic value in patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD). Its determinants nevertheless remain controversial. AIM: To investigate the possible correlation between parameters of ventilatory efficiency obtained by CPET and thoracic fluid content (TFC), assessed by thoracic electrical bioimpedance (TEB), in patients with CHF due to LVSD. METHODS: We studied 120 patients with LVSD and CHF, referred to our laboratory for CPET: 76% male, age 52.1 ± 12.1 years, 37% of ischemic etiology, left ventricular ejection fraction 27.6 ± 7.9%, 83% in sinus rhythm, 96% receiving ACEIs and/or ARBs and 79% beta-blockers, and 20% treated with a cardiac resynchronization device. TEB studies were performed after 15 minutes of rest, prior to symptom-limited treadmill CPET, using the modified Bruce protocol. CPET-derived peak oxygen consumption (pVO(2)), the slope of the relationship between minute ventilation (VE) and carbon dioxide production (VCO(2)), VE/VCO(2) at the anaerobic threshold (AT), and TFC assessed by TEB were considered for analysis. RESULTS: TFC ranged between 20.6 and 45.8kOhm-1, mean 32.2, SD=5.7, median 32.7, pVO(2) 8.9-40.6 ml/kg/min, mean 21.0, SD 6.2, median 20.2, VE/VCO(2) slope 19.8-60.7, mean 30.7, SD 7.9, median 29.1 and VE/VCO(2) at AT 21-62, mean 33.1, SD 7.5, median 31.5. By linear regression, TFC did not correlate with pVO(2) (r=0.05, p=0.58), but showed correlation with parameters of ventilatory efficiency: r=0.20, p=0.032, r(2)=0.04 for VE/VCO(2) slope and r=0.25, p=0.009, r(2)=0.06 for VE/VCO(2) at AT. CONCLUSION: TFC correlates with CPET parameters of ventilatory efficiency in patients with CHF due to LVSD, suggesting that it may be one of its determinants.

Impact of body mass index in the results after primary angioplasty in patients with ST segment elevation acute myocardial infarction.

INTRODUCTION: Obese patients submitted to elective coronary angioplasty have a paradoxical reduction in hospital and long-term mortality. In primary angioplasty setting, the relation with Body Mass Index (BMI) is less studied. OBJECTIVES: To evaluate the impact of obesity in the results after ST-segment elevation acute myocardial infarction treated by primary angioplasty. METHODS: Study of 539 consecutive patients with ST-segment elevation acute myocardial infarction (STEMI) submitted to primary angioplasty. We evaluated in-hospital, 30-day and one-year all-cause mortality according to BMI: 'normal', <25 kg/m(2); 'overweight', 25-29.9 kg/m(2) and 'obese', ≥ 30 kg/m(2). RESULTS: Obese patients were younger, had more hypertension and hyperlipidemia. There were no differences in previous cardiac history and hospital data. In-hospital mortality was 8.0% for patients with normal BMI, 4.4% for overweight patients and 5.9% for obese patients (P=0.296). At 30 days, 9.6%, 5.2% and 6.9% (P=0.212) and at first year, 11.2%, 5.2% and 6.9% (P=0.064), respectively. Overweight was the only group with decreased risk (OR: 0.44, 95% CI: 0.21-0.90, P=0.015), even after adjustment for confounding variables (OR: 0.37, 95% CI: 0.15-0.95, P=0.038). CONCLUSIONS: Overweight patients had a better prognosis after primary angioplasty for STEMI compared with other BMI groups.

Combining ventilatory efficiency and peak oxygen consumption in the prognostic assessment of patients with chronic heart failure.

UNLABELLED: Cardiopulmonary exercise testing (CPET) is an objective method for assessment of functional capacity and for prognostic stratification of patients with chronic heart failure (CHF). In this study, we analyzed the prognostic value of a recently described CPET-derived parameter, the minute ventilation to carbon dioxide production slope normalized for peak oxygen consumption (VE/VCO2 slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and dilated cardiomyopathy who performed maximal CPET using the modified Bruce protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared with traditional CPET parameters. RESULTS: During follow-up 37 patients died and 12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12-36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or = 2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory response to exercise for peak oxygen consumption appears to increase the prognostic value of CPET in patients with CHF.

Usefulness of tissue Doppler imaging to predict arrhythmic events in adults with repaired tetralogy of Fallot.

INTRODUCTION: Adults with repaired tetralogy of Fallot (TOF) may be at risk for progressive right ventricular (RV) dilatation and dysfunction, which is commonly associated with arrhythmic events. In frequently volume-overloaded patients with congenital heart disease, tissue Doppler imaging (TDI) is particularly useful for assessing RV function. However, it is not known whether RV TDI can predict outcome in this population. OBJECTIVE: To evaluate whether RV TDI parameters are associated with supraventricular arrhythmic events in adults with repaired TOF. METHODS: We studied 40 consecutive patients with repaired TOF (mean age 35 +/- 11 years, 62% male) referred for routine echocardiographic exam between 2007 and 2008. The following echocardiographic measurements were obtained: left ventricular (LV) ejection fraction, LV end-systolic volume, LV end-diastolic volume, RV fractional area change, RV end-systolic area, RV end-diastolic area, left and right atrial volumes, mitral E and A velocities, RV myocardial performance index (Tei index), tricuspid annular plane systolic excursion (TAPSE), myocardial isovolumic acceleration (IVA), pulmonary regurgitation color flow area, TDI basal lateral, septal and RV lateral peak diastolic and systolic annular velocities (E' 1, A' 1, S' 1, E' s, A' s, S' s, E' rv, A' rv, S' rv), strain, strain rate and tissue tracking of the same segments. QRS duration on resting ECG, total duration of Bruce treadmill exercise stress test and presence of exercise-induced arrhythmias were also analyzed. The patients were subsequently divided into two groups: Group 1--12 patients with previous documented supraventricular arrhythmias (atrial tachycardia, fibrillation or flutter) and Group 2 (control group)--28 patients with no previous arrhythmic events. Univariate and multivariate analysis was used to assess the statistical association between the studied parameters and arrhythmic events. RESULTS: Patients with previous events were older (41 +/- 14 vs. 31 +/- 6 years, p = 0.005), had wider QRS (173 +/- 20 vs. 140 +/- 32 ms, p = 0.01) and lower maximum heart rate on treadmill stress testing (69 +/- 35 vs. 92 +/- 9%, p = 0.03). All patients were in NYHA class I or II. Clinical characteristics including age at corrective surgery, previous palliative surgery and residual defects did not differ significantly between the two groups. Left and right cardiac chamber dimensions and ventricular and valvular function as evaluated by conventional Doppler parameters were also not significantly different. Right ventricular strain and strain rate were similar between the groups. However, right ventricular myocardial TDI systolic (Sa: 5.4+2 vs. 8.5 +/- 3, p = 0.004) and diastolic indices and velocities (Ea, Aa, septal E/Ea, and RV free wall tissue tracking) were significantly reduced in patients with arrhythmias compared to the control group. Multivariate linear regression analysis identified RV early diastolic velocity as the sole variable independently associated with arrhythmic history (RV Ea: 4.5 +/- 1 vs. 6.7 +/- 2 cm/s, p = 0.01). A cut-off for RV Ea of < 6.1 cm/s identified patients in the arrhythmic group with 86% sensitivity and 59% specificity (AUC = 0.8). CONCLUSIONS: Our results suggest that TDI may detect RV dysfunction in patients with apparently normal function as assessed by conventional echocardiographic parameters. Reduction in RV early diastolic velocity appears to be an early abnormality and is associated with occurrence of arrhythmic events. TDI may be useful in risk stratification of patients with repaired tetralogy of Fallot.

Expression of subclinical atherosclerosis for different cardiovascular risk factors in young populations.

INTRODUCTION: Carotid intima-media thickness (cIMT) is considered an early marker for atherosclerosis, but there are few studies on the expression of this marker in younger populations. OBJECTIVES: To evaluate cIMT in younge patients (aged 30-50 years) and its expression according to cardiovascular risk factors. METHODS: We analyzed individuals admitted for an invasive cardiac procedure. Normal cIMT was defined as < 0.90 mm, thickened as 0.90-1.50 mm and atherosclerotic plaque as > 1.50 mm. Lipid profile, anthropometric parameters, fasting blood glucose and estimated GFR were also determined. RESULTS: A total of 106 patients were included (59% male), with a mean age of 43 +/- 5 years, 36% with hypertension, 22% smokers, 32% with known hyperlipidemia, 16% with diabetes, 39% under statin therapy and 40% with metabolic syndrome (AHA/NHLBI definition). Mean cIMT was 0.69 +/- 0.26 mm, and was normal in 74% of the patients, thickened in 20% and with atherosclerotic plaques in 6%. cIMT correlated directly with age (r = 0.26, p = 0.007), log fasting glucose (r = 0.21, p = 0.04), and log triglycerides (r = 0.24, p = 0.017), and tended to correlate with the number of components of metabolic syndrome (r = 0.17, p = 0.08). However, on multivariate analysis, only age remained as an independent predictor (r = 0.29, p = 0.005). Diabetic patients had greater cIMT (0.81 +/- 0.22 vs. 0.67 +/- 0.26 mm, p = 0.039) and there was a trend for greater cIMT in those with metabolic syndrome (0.75 +/- 0.29 vs. 0.66 +/- 0.23 mm, p = 0.09). There were no differences for the other risk factors, A higher number of risk factors in a single patient showed a trend for increased cIMT (p = 0.083) CONCLUSIONS: Age is the only independent determinant of cIMT in a young population. Diabetic patients have greater cIMT and a trend was seen in those with metabolic syndrome, possibly influenced by its relation with diabetes, one of the components of the metabolic syndrome.