First-degree atrioventricular block on basal electrocardiogram predicts future arrhythmic events in patients with Brugada syndrome: a long-term follow-up study from the Veneto region of Northeastern Italy.

AIMS: This study was designed to assess the prognostic value of clinical and electrocardiographic parameters in Brugada syndrome (BrS). METHODS AND RESULTS: The study population included 272 consecutive patients (82% males; mean age 43 ± 12 years), with either a spontaneous (n = 137, 50%) or drug-induced (n = 135, 50%) Type 1 Brugada electrocardiogram (ECG) pattern. The study combined endpoint included sudden cardiac death (SCD), cardiac arrest, and appropriate intervention of implantable cardioverter-defibrillator (ICD). A first-degree atrioventricular (AV) block (PR = 219 ± 17 ms) was documented at basal ECG in 45 patients (16.5%); 27 of these underwent an electrophysiological study with recording in 21 (78%) of an HV interval ≥55 ms (mean 61 ± 3 ms). Patients with first-degree AV block had a wider QRS complex (median 110 ms vs. 95 ms; P = 0.04) and more often showed a left anterior hemiblock pattern (n = 13, 29% vs. n = 35, 16%; P = 0.056). During a mean follow-up of 85 ± 55 months, 17 patients (6.3%) experienced ≥1 major arrhythmic events (appropriate ICD intervention, n = 13 and SCD, n = 4). At univariate analysis, the occurrence of major arrhythmic events was significantly associated with a history of syncope or cardiac arrest (P < 0.001), Type 1 ECG pattern (P = 0.04), and first-degree AV block (P < 0.001). Univariate and multivariable predictors of events included a history of syncope or cardiac arrest [hazard ratio (HR) 5.8, 95% confidence interval (95% CI) 2.04-16.5; P < 0.001; and HR 6.68, 95% CI 2.34-19.1; P < 0.001; respectively], a spontaneous Type 1 ECG pattern (HR 1.56, 95% CI 1.03-4.24; P = 0.033; and HR 1.84, 95% CI 1.01-4.29; P = 0.044; respectively) and a first-degree AV block at baseline ECG (HR 3.84, 95% CI 1.47-9.99; P = 0.006; and HR 4.65, 95% CI 2.34-19.1; P = 0.002; respectively). CONCLUSION: Besides a history of cardiac arrest or syncope, first-degree AV block on basal ECG is an independent predictor of malignant arrhythmic events and a stronger marker of arrhythmic risk than a spontaneous 'coved-type' ECG pattern in patients with BrS.

Slow pathway modification in patients presenting with only two consecutive AV nodal echo beats.

BACKGROUND: Slow pathway modification (SPM) is the therapy of choice for AV-nodal reentry tachycardia (AVNRT). When AVNRT is not inducible, empirical ablation can be considered, however, the outcome in patients with two AV nodal echo beats (AVNEBs) is unknown. METHODS: Out of a population of 3003 patients who underwent slow pathway modification at our institution between 1993 and 2013, we retrospectively included 32 patients with a history of symptomatic tachycardia, lack of paroxysmal supraventricular tachycardia (pSVT) inducibility but occurrence of two AVNEBs. RESULTS: pSVT documentation by electrocardiography (ECG) was present in 20 patients. The procedural endpoint was inducibility of less than two AVNEBs. This was reached in 31 (97%) patients. Long-term success was assessed by a telephone questionnaire (follow-up time 63±9 months). A total 94% of the patients benefited from the procedure (59% freedom from symptoms; 34% improvement in symptoms). Among those patients in whom ECG documentation was not present, 100% benefited (58% freedom from symptoms, 42% improvement). CONCLUSION: This is the first collective analysis of a group of patients presenting with symptoms of pSVT and inducibility of only two AVNEBs. Procedural success and clinical long-term follow-up were in the range of the reported success rates of slow pathway modification of inducible AVNRT, independent of whether ECG documentation was present. Thus, SPM is a safe and effective therapy in patients with two AVNEBs.

Implantable cardioverter defibrillator therapy in young patients with cardiomyopathies and channelopathies: a single Italian centre experience.

AIMS: This study was designed to prospectively evaluate the risk-benefit ratio of implantable cardioverter defibrillator (ICD) therapy in young patients with cardiomyopathies and channelopathies. METHODS AND RESULTS: The study population included 96 consecutive patients [68 men, median age 27 (22-32) years] with cardiomyopathies, such as arrhythmogenic right ventricular cardiomyopathy (n = 35), dilated cardiomyopathy (n = 17), hypertrophic cardiomyopathy (n = 15), Brugada syndrome (n = 14), idiopathic ventricular fibrillation (n = 5), left ventricular noncompaction (n = 4), long-QT syndrome (n = 4) and short-QT syndrome (n = 2), who were 18-35 years old at the time of ICD implantation. During a mean follow-up of 72.6 ±â€Š53.3 months, one patient with end-stage hypertrophic cardiomyopathy died because of acute heart failure, and 11 patients underwent orthotopic heart transplantation. Twenty patients (20.8%) had a total of 38 appropriate ICD interventions (4%/year), and 26 patients (27.1%) experienced a total of 49 adverse ICD-related events (5.4%/year), including 23 inappropriate ICD interventions occurring in nine patients (9.4%) and 26 device-related complications requiring surgical revision occurring in 20 patients (20.8%). Lead failure/fracture requiring lead extraction was the most common complication (n = 9). A threshold for ICD therapy less than 300 ms was associated with a borderline significant lower probability of inappropriate ICD interventions (hazard ratio = 0.2; 95% confidence interval 0.02-1.2; P = 0.07), whereas underweight status was an independent predictor of device-related complications (hazard ratio = 5.4; 95% confidence interval 1.5-19.4; P = 0.01). CONCLUSION: In young patients with cardiomyopathies and channelopathies, ICD therapy provided life-saving protection by effectively terminating life-threatening ventricular arrhythmias. However, because ICD-related adverse events are common, the risk/benefit ratio should be carefully assessed when considering ICD implantation in young people.

Management of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder, predisposing to sudden cardiac death (SCD), particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; a biventricular involvement is often observed. The diagnosis of ARVC (prevalence 1:5.000 in the general population) does not rely on a single gold standard test but is achieved using a scoring system, proposed in 2010 by an International Task Force, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of SCD. Implantable cardioverter defibrillator (ICD) is the only proven "lifesaving" therapy; however, it is associated with a significant morbidity due to device-related complications and inappropriate ICD interventions. Other treatment options such as life style changes, antiarrhythmic drugs, beta-blockers and catheter ablation may reduce the arrhythmic burden and alleviate symptoms, without evident impact on prevention of SCD. Selection of patient candidates to ICD implantation is the most challenging issue in the clinical management of ARVC. This article reviews the current perspective on management of ARVC, focusing on clinical manifestations, diagnostic criteria, risk stratification and therapeutic strategies of affected patients.

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.

OBJECTIVE: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). METHODS: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. RESULTS: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. CONCLUSIONS: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

Physicochemical parameters and sensory properties of honeys from Buenos Aires region.

The physicochemical parameters (moisture, hydroxymethyl furfural, colour, electrical conductivity, free acidity, glucose, fructose and sucrose) and the sensory properties(aroma, taste, appeareance, texture) were determined in honeys from apiaries of the agricultural, hills and meadow zones of the south east region of Buenos Aires province (Argentina). The analysis of variance showed significant differences among zones in the mean value of hydroximethyl furfural, colour, electrical conductivity and sucrose content. The principal component analysis explained the 70% of the variance among samples with the first two principal components in both cases. The cluster analysis and linear discriminant analysis showed that samples were grouped in relation to the sampling region coinciding with the results of the principal component analysis. Results suggest that could be possible to classify honeys according to the geographic origin based on the physicochemical parameters; however, the sensory properties were not good predictors.

Electrocardiographic predictors of electroanatomic scar size in arrhythmogenic right ventricular cardiomyopathy: implications for arrhythmic risk stratification.

INTRODUCTION: The extent of right ventricular (RV) electroanatomic scar (EAS) detected by endocardial voltage mapping (EVM) is a powerful invasive predictor of arrhythmic outcome in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Electrocardiogram (ECG) and signal-averaged ECG are noninvasive tools of established clinical value for the diagnosis of electrical abnormalities in ARVC. This study was designed to assess the role of ECG and SAECG abnormalities for noninvasive estimation of the extent and regional distribution of RV-EAS and prediction of scar-related arrhythmic risk. METHODS AND RESULTS: The study population included 49 consecutive patients (38 males, median age 35 years) with a definite diagnosis of ARVC and an abnormal EVM by CARTO system. At univariate analysis, the presence of epsilon waves, the degree of RV dilation, the severity of RV dysfunction, and the extent of negative T waves correlated with RV-EAS% area. Normal T-waves were associated with a median RV-EAS% area of 4.9% (4.5-6.4), negative T waves in V1-V3 of 22.0% (8.5-30.6), negative T waves in V1-V3 extending to lateral precordial leads (V4-V6) of 26.8% (11.5-35.2), and negative T waves in both precordial (V2-V6) and inferior leads of 30.2% (24.8-33.0) (P < 0.001). At multivariate analysis, the extent of negative T waves remained the only independent predictor of RV-EAS% area (B = 4.4, 95%CI 1.3-7.4, P = 0.006) and correlated with the arrhythmic event-rate during follow-up (P = 0.03). CONCLUSIONS: In patients with ARVC, the extent of negative T-waves across 12-lead ECG allows noninvasive estimation of the amount of RV-EAS and prediction of EAS-related arrhythmic risk.

Prognostic value of endocardial voltage mapping in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Endocardial voltage mapping (EVM) identifies low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). METHODS AND RESULTS: We studied 69 consecutive ARVC/D patients (47 males; median age 35 years [28-45]) who underwent electrophysiological study and both bipolar and unipolar EVM. The extent of confluent bipolar (<1.5 mV) and unipolar (<6.0 mV) low-voltage electrograms was estimated using the CARTO-incorporated area calculation software. Fifty-three patients (77%) showed ≥1 RV electroanatomic scars with an estimated burden of bipolar versus unipolar low-voltage areas of 24.8% (7.2-31.5) and 64.8% (39.8-95.3), respectively (P=0.009). In the remaining patients with normal bipolar EVM (n=16; 23%), the use of unipolar EVM unmasked ≥1 region of low-voltage electrogram affecting 26.2% (11.6-38.2) of RV wall. During a median follow-up of 41 (28-56) months, 19 (27.5%) patients experienced arrhythmic events, such as sudden death (n=1), appropriate implantable cardioverter defibrillator interventions (n=7), or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included previous cardiac arrest or syncope (hazard ratio=3.4; 95% confidence interval, 1.4-8.8; P=0.03) and extent of bipolar low-voltage areas (hazard ratio=1.7 per 5%; 95% confidence interval, 1.5-2; P<0.001), whereas the only independent predictor was the bipolar low-voltage electrogram burden (hazard ratio=1.6 per 5%; 95% confidence interval, 1.2-1.9; P<0.001). Patients with normal bipolar EVM had an uneventful clinical course. CONCLUSIONS: The extent of bipolar RV endocardial low-voltage area was a powerful predictor of arrhythmic outcome in ARVC/D, independently of history and RV dilatation/dysfunction. A normal bipolar EVM characterized a low-risk subgroup of ARVC/D patients.

Imaging study of ventricular scar in arrhythmogenic right ventricular cardiomyopathy: comparison of 3D standard electroanatomical voltage mapping and contrast-enhanced cardiac magnetic resonance.

BACKGROUND: The hallmark lesion of arrhythmogenic right ventricular cardiomyopathy (ARVC) is fibrofatty scar replacement. We compared endocardial voltage mapping (EVM) and contrast-enhanced cardiac magnetic resonance (CE-CMR) for imaging scar lesions in ARVC patients. METHODS AND RESULTS: We studied 23 consecutive ARVC patients (16 males; mean age, 38±12 years) who underwent RV EVM and CE-CMR and 37 control subjects. In 21 (91%) of 23 ARVC patients, RV EVM was abnormal, with a total of 45 electroanatomical scars (EAS): 17 (38%) in the inferobasal region, 12 (26.6%) in the anterolateral region, 8 (17.7%) in the RV outflow tract (RVOT), and 8 (17.7%) in the apex. RV delayed contrast enhancement (DCE) was found in 9 (39%) of 23 patients, with a total of 23 RV DCE scars: 4 (17.4%) in the inferobasal region, 9 (39.1%) in the anterolateral region, 4 (17.4%) in the RVOT, and 6 (26.1%) in the apex. There was a mismatch in 24 RV scars, with 22 EAS not confirmed by DCE and 2 DCE scars (both in the RVOT) undetected by EVM. In 9 (75%) of 12 patients with abnormal RV EVM/normal RV DCE, ≥1 DCEs were identified in the left ventricle (LV). Overall, ventricular DCE was detected in 78% of patients. No control subjects showed either EAS or DCE. CONCLUSIONS: EVM and CE-CMR allow identification of RV scar lesions in most ARVC patients. CE-CMR is less sensitive than EVM in identifying RV scar lesions. The high prevalence of LV DCE confirms the frequent biventricular involvement and indicates the diagnostic relevance of LV scar detection by CE-CMR.

Clinical management of arrhythmogenic right ventricular cardiomyopathy: an update.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic heart muscle disease characterized by the peculiar right ventricular (RV) involvement. Distinctive pathologic features are myocardial atrophy and fibro-fatty replacement of the RV free wall, and clinical presentation is usually related to ventricular tachycardias with a left bundle branch block pattern or ventricular fibrillation leading to cardiac arrest, mostly in young people and athletes. Later in the disease evolution, progression and extension of RV muscle disease and left ventricular involvement may result in right or biventricular heart failure. In the 1994 an International Task Force proposed standardized diagnostic criteria designed to guarantee an adequate specificity and based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphofunctional, histopathologic, and genetic factors; more recently, Task Force criteria have been modified to increase their diagnostic sensitivity. Retrospective analysis of clinical and pathologic series including fatal cases identified a series of risk factors such as malignant familial background, youthful age, previous syncope or cardiac arrest, competitive sport activity, severe RV disease with left ventricular involvement, and episodes of complex ventricular arrhythmias or VT. The therapeutic options include beta blockers, antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillator (ICD). The ICD is the most effective safe-guard against arrhythmic sudden death. In patients in whom ARVC has progressed to severe RV or biventricular systolic dysfunction with risk of thromboembolic complications, treatment consists of current therapy for heart failure including anticoagulant therapy. In case of refractory congestive heart failure, patients may become candidates for heart transplantation.