Usefulness of Genetic Study by Next-generation Sequencing in High-risk Arrhythmogenic Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. RESULTS: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. CONCLUSIONS: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

Comparison of the new risk prediction model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator.

AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. METHODS AND RESULTS: This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events (P < 0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.

Factors predicting and having an impact on the need for a permanent pacemaker after CoreValve prosthesis implantation using the new Accutrak delivery catheter system.

OBJECTIVES: The purpose of this study was to evaluate the need for a permanent pacemaker after transcatheter aortic valve implantation with the CoreValve prosthesis (Medtronic, Inc., Minneapolis, Minnesota) using the new Accutrak delivery system (Medtronic, Inc.). BACKGROUND: The need for a permanent pacemaker is a recognized complication after transcatheter aortic valve implantation with the CoreValve prosthesis. METHODS: Between April 23, 2008 and May 31, 2011, 195 consecutive patients with symptomatic aortic valve stenosis underwent transcatheter aortic valve implantation using the self-expanding CoreValve prosthesis. In 124 patients, the traditional delivery system was used, and in 71 patients, the Accutrak delivery system was used. RESULTS: There were no significant differences in baseline electrocardiographic characteristics between the traditional system and the Accutrak patients: PR interval: 153 ± 46 mm versus 165 ± 30 mm, p = 0.12; left bundle branch block: 22 (20.2%) versus 8 (12.7%), p = 0.21; right bundle branch block: 21 (19.3%) versus 8 (12.7%), p = 0.26. The depth of the prosthesis in the left ventricular outflow tract was greater with the traditional system than with the Accutrak system (9.6 ± 3.2 mm vs. 6.4 ± 3 mm, p < 0.001) and the need for a permanent pacemaker was higher with traditional system than with Accutrak (35.1% vs. 14.3%, p = 0.003). The predictors of the need for a pacemaker were the depth of the prosthesis in the left ventricular outflow tract (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 1.08 to 1.34, p < 0.001), pre-existing right bundle branch block (HR: 3.5, 95% CI: 1.68 to 7.29, p = 0.001), and use of the traditional system (HR: 27, 95% CI: 2.81 to 257, p = 0.004). CONCLUSIONS: The new Accutrak delivery system was associated with less deep prosthesis implantation in the left ventricular outflow tract, which could be related to the lower rate of permanent pacemaker requirement.

Changes in atrioventricular conduction and predictors of pacemaker need after percutaneous implantation of the CoreValve®. Aortic valve prosthesis.

INTRODUCTION AND OBJECTIVES: Although changes in atrioventricular conduction frequently occur after percutaneous implantation of an aortic valve prosthesis, little is known about the mechanisms involved or how these changes progress. We investigated ECG abnormalities and predictors of pacemaker need after percutaneous implantation of the CoreValve® aortic valve prosthesis. METHODS: Between April 2008 and October 2009, 65 patients with symptomatic severe aortic stenosis received a CoreValve® prosthesis. Clinical and ECG parameters were recorded and predictors of pacemaker need due to advanced atrioventricular block were investigated. The analysis excluded three patients because they had pacemakers and a fourth who died during the procedure. RESULTS: The patients' mean age was 79 ± 7.8 years and their logistic EuroSCORE was 20 ± 14%. Implantation was successful in 98.4%. After implantation, 47.5% had left bundle branch block and 21 patients (34.4%) required a permanent pacemaker. The need for a pacemaker was associated with a greater depth of prosthesis implantation in the left ventricular outflow tract (LVOT): 13 ± 2.5 mm vs. 8.8 ± 2.8 mm (P< .001). Moreover, depth was the only predictor: odds ratio 1.9, 95% confidence interval 1.19-3.05 (P< .007). A cutpoint of 11.1 mm for the prosthesis depth in the LVOT had a sensitivity of 81% and a specificity of 84.6% for predicting the need for a pacemaker. CONCLUSIONS: After CoreValve® aortic valve prosthesis implantation, a high percentage of patients needed a permanent pacemaker for advanced atrioventricular block. The only independent predictor was the depth of the prosthesis in the LVOT, which could serve as an early indicator of pacemaker need.

Persistence of secondary mitral regurgitation and response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) improves survival and quality of life in advanced heart failure (HF). Although mitral regurgitation (MR) reduction has been reported, its presence has been associated with non-response to CRT. This study was undertaken to assess the potential role of significant mitral regurgitation (SMR) persistence after CRT on clinical outcome, major arrhythmic events, and echocardiographic response in the mid-long term. METHODS AND RESULTS: Seventy-six patients (28.9% women, 63 +/- 11 years) with dilated cardiomyopathy in advanced HF were included. SMR, defined as regurgitant orifice area > or =0.20 cm(2), was assessed at baseline and its evolution 6 months after CRT. Clinical outcome (cardiovascular death/HF readmission), major arrhythmic events, and echocardiographic response (reverse remodelling) were recorded on follow-up. Thirty-two patients (42.1%) presented baseline SMR, becoming non-significant in 11 of the 32 patients (34.3%) 6 months after CRT. Its persistence was associated with higher rates of clinical events (46.4 vs. 18.7%, P = 0.011), arrhythmic events (35.7 vs. 14.5%, P = 0.034), and less reverse remodelling (28.5 vs. 83.3%, P < 0.001). CONCLUSION: CRT can reduce moderate or severe baseline MR to non-significant in one-third of patients. However, its persistence was associated with worse clinical evolution, greater incidence of arrhythmic events, and less reverse remodelling.

Combined resynchronization therapy and automatic defibrillator in advanced non-ischaemic heart failure: the importance of QRS width.

AIMS: The combined use of an automatic defibrillator in resynchronization therapy for primary prevention in patients with idiopathic dilated cardiomyopathy is controversial. METHODS AND RESULTS: We assessed a series of 46 patients (61 +/- 10 years, 64% male) with idiopathic dilated cardiomyopathy undergoing resynchronization therapy combined with a defibrillator in primary prevention and the potential relationship between baseline characteristics and the onset of ventricular arrhythmic events. Of the 46 patients included, eight (17%) presented episodes of ventricular tachycardia/fibrillation during follow-up (19 +/- 12 months). There were no baseline differences among these patients, except the proportion of males (57.9 vs. 100%, P = 0.02) and QRS width (162 +/- 24 vs. 189 +/- 26 ms, P = 0.008), which was the only independent predictor of arrhythmic events (OR 1.42, 95% CI 1.12-1.68; P = 0.03). CONCLUSION: In patients with idiopathic dilated cardiomyopathy undergoing resynchronization therapy combined with a defibrillator, baseline QRS is an independent predictor of arrhythmic events.

[Benefits of cardiac resynchronization therapy in patients with atrial fibrillation who have not undergone atrioventricular node ablation]. / Beneficio de la terapia de resincronización cardiaca en la fibrilación auricular sin ablación del nodo.

The aim of this study was to compare the effects of cardiac resynchronization therapy on left ventricular function and reverse remodeling in patients in sinus rhythm with the effects in patients with atrial fibrillation who have not undergone atrioventricular node ablation. Echocardiographic and clinical parameters were evaluated at baseline and after 6 months of cardiac resynchronization therapy in 55 patients: 15 had atrial fibrillation and 40 were in sinus rhythm. Device programming was similar in the 2 groups, as were the reductions in QRS interval and echocardiographic measures of asynchrony observed after implantation. However, although significant improvements in end-systolic volume and ejection fraction were seen in both groups, reverse remodeling was greater in patients in sinus rhythm (reduction in end-systolic volume 30.9%+/-24.6% vs 12.5%+/-18.6%; P=.024), as was the relative increase in ejection fraction (15.4%+/-12.6% vs 5.0%+/-7.2%; P=.010). Cardiac resynchronization therapy in patients with atrial fibrillation who had not undergone atrioventricular node ablation resulted in significant improvements in ejection fraction and reverse remodeling, but these were less than those observed in patients in sinus rhythm.

Repercussion of functional mitral regurgitation on reverse remodelling in cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) reduces the degree of functional mitral regurgitation (FMR). However, FMR has also been associated with a lack of clinical response to CRT. We undertook this study to determine whether the presence of FMR influences the reverse remodelling induced by CRT. METHODS AND RESULTS: We used Doppler echocardiography to assess 20 patients with dilated cardiomyopathy before and 6 months after undergoing CRT. We evaluated the effect of reverse remodelling (reduction > or = 10% in end-systolic volume) according to the presence or absence of important FMR, defined as a regurgitant orifice area (ROA) of > or = 0.20 cm(2). Of the 20 patients (mean age, 64.7 +/- 8.2 years, eight women), 9 had marked FMR (ROA 0.40 +/- 0.12 cm(2)), 6 mild FMR (ROA 0.15 +/- 0.02 cm(2)), and 5 had trivial or no FMR. CRT reduced the presence of mitral regurgitation by 33.3% and induced reverse remodelling in 60% of the patients. A ROA > or = 0.20 cm(2) was associated with a lack of reverse remodelling, despite presenting similar baseline characteristics and a reduction in asynchrony to the other patients. Reverse remodelling was produced in all the other patients, with a significant reduction in end-systolic volume (41.7 +/- 21%; P = 0.003), accompanied by improvement in the ejection fraction (P = 0.003) and myocardial performance index (P = 0.027). CONCLUSION: CRT improved FMR, although the baseline presence of important mitral regurgitation, with a ROA > or = 0.20 cm(2), in patients undergoing CRT was associated with a lack of response in reverse remodelling.

[Long-term prognosis value of anemia in a non-selected population with heart failure]. / Significado pronóstico a largo plazo de la anemia en una población no seleccionada de pacientes con insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: Prevalence of anemia in heart failure is variable. Many studies have established a relation between anemia and prognosis in selected patients with heart failure. We have poor information anout the long-term prognosis in non- selected populations. PATIENT AND METHOD: We analyze the presence of anemia during 2 month in 100 consecutive patients in our hospital with a main diagnosis of heart failure (Cardiology or Internal Medicine departments). We defined anemia according to WHO criteria: hemoglobin level lower than 130 g/l (men) and 120 g/l (women). We studied the influence of anemia in long-term prognosis (follow-up of 25+/-18 m). RESULTS: Mean age was 71.8 (9) years. 41% of patients had anemia. Values of hemoglobin were related to age and creatinine, but not with cardiovascular risk factors. Patients who died (38%) had lower hemoglobin than patients who survived (121 [22] gr/dl vs 130 [17] gr/dl; p<0.02). Mortality in the anemia group was 52.5% vs 32.1% (p<0.04). In the Cox multivariable analisis, anemia was a predictor factor of mortality in the follow-up (RR = 1,55; CI 95%, 1.05-2.47; p<0.04) and functional class (III/IV) (RR=2.52; CI 95%, 1.56-4.07; p<0.001). CONCLUSIONS: In a non-selected population of patients with heart failure, the prevalence of anemia is high and has independiente prognostic value in long-term mortality with functional advanced class.

[Dynamic left ventricular outflow tract obstruction induced by exercise]. / Obstrucción dinámica intraventricular izquierda inducida por esfuerzo.

INTRODUCTION AND OBJECTIVES: Dynamic left intraventricular outflow tract obstruction occurs occasionally in patients without hypertrophic cardiomyopathy. We hypothesized that dynamic intraventricular obstruction might occur during effort in patients with angina or dyspnea without evident disease. The objective of this prospective study was to investigate: a) whether it appears with effort; b) its incidence, magnitude and determining factors, and c) its clinical course. PATIENTS AND METHOD: We performed baseline and stress Doppler echocardiography in 211 patients with angina, dyspnea or both with exercise. Patients with previous myocardial infarction, valvular heart disease, ventricular dysfunction or ventricular hypertrophy without hypertension were excluded. Dynamic intraventricular obstruction was defined as intracavitary flow velocity > or =2.5 m/s. RESULTS: 134 patients (59 women) were included: mean age was 58 (9) years; history of hypertension was present in 69.7%, dyslipidemia in 35.8% and diabetes in 24.6%. Dynamic intraventricular obstruction appeared in 18 patients (13.4%), with gradients ranging between 25 and 53 mmHg (mean 32.19 [6.6]). Demographic variables, cardiovascular risk factors and exercise performed were similar in group A (with obstruction) and group B (without obstruction). No patient in group A had evidence of ischemia. Five patients in this group had symptoms during exercise; the gradients were greater in these patients (42.65 [10.5] vs 28.15 [2.37] mmHg; P<.0001) than in the remaining group A patients. Left ventricular outflow tract size was found to be the only independent predictive factor in the multivariate analysis. After 369.9 (133.5) days of follow-up, no cardiac events were recorded. CONCLUSIONS: Our study suggests that some patients with angina or dyspnea without evidence of ischemia may develop dynamic left ventricular outflow tract obstruction induced by effort.