Ventricular Electrograms Duration Map to Detect Ventricular Arrhythmia Substrate: the VEDUM Project Study.

BACKGROUND: The analysis of the wave-front activation patterns is crucial for the comprehension and treatment of ventricular tachycardia (VT). The ventricular electrograms duration map (VEDUM) is a potential method to identify areas (VEDUM area) with slow and inhomogeneous activation. There is no available data on the characteristics and the arrhythmogenic role of VEDUM areas identified during sinus/paced rhythm. METHODS: Patients referred for VT ablation were enrolled at 3 different centers. VEDUM maps during sinus/paced rhythm as well as substrate and functional maps were created; activation mapping was performed for all hemodynamically tolerated VT. RESULTS: Thirty-two patients (mean age:70.1±9.4 years; males 93.8%) were enrolled. The VEDUM approach was achieved in all patients and the mean size of the VEDUM area was 12.1±6.9 cm2 (interquartile range, 7.8-14.9 cm2). A significative difference was observed between the electrogram duration in the VEDUM area and the normal tissue (163.7 ms [interquartile range, 142.3-199.2 ms]; versus 65.5 ms [interquartile range, 59.5-76.2 ms]; P<0.001). The VEDUM area was visualized in a dense scar (<0.5 mV) in 19 (59.4%) patients. A deceleration zone and late potentials were recorded inside the VEDUM area in 56.3% and 81.3%, respectively. When a complete VT activation mapping was available, the isthmus projected in the VEDUM area in 93.5% of patients; 8 of them had multiple VTs mapped and in the 87.5% all VT isthmuses were included in the VEDUM area. CONCLUSIONS: VEDUM maps allow the identification of discrete areas of inhomogeneous and slow conduction. They represent a potential target for VT ablation, including patients with multiple morphologies.

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies.

BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.

Troponin levels within the normal range and probability of inducible myocardial ischemia and coronary events in patients with acute chest pain.

BACKGROUND/OBJECTIVES: Patients with suspected acute coronary syndromes and negative cardiac troponin (cTn) levels are deemed at low risk. Our aim was to assess the effect of cTn levels on the frequency of inducible myocardial ischemia and subsequent coronary events in patients with acute chest pain and cTn levels within the normal range. METHODS: We evaluated 4474 patients with suspected acute coronary syndromes, nondiagnostic electrocardiograms and serial cTnI levels below the diagnostic threshold for myocardial necrosis using a conventional or a sensitive cTnI assay. The end points were the probability of inducible myocardial ischemia and coronary events (i.e., coronary death, myocardial infarction or coronary revascularization within 3 months). RESULTS: The probability of inducible myocardial ischemia was significantly higher in patients with detectable peak cTnI levels (25%) than in those with undetectable concentrations (14.6%, p<0.001). These results were consistent regardless of the type of cTnI assay, the type of stress testing modality, or the timing for cTnI measurement, and remained significant after multivariate adjustment (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.21-1.79, p<0.001). The rate of coronary events at 3 months was also significantly higher in patients with detectable cTnI levels (adjusted OR 2.08, 95% CI 1.64-2.64, p<0.001). CONCLUSIONS: Higher cTnI levels within the normal range were associated with a significantly increased probability of inducible myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and seemingly negative cTnI.

Incremental value of exercise echocardiography over exercise electrocardiography in a chest pain unit.

BACKGROUND: Limited data are available on the added value of exercise echocardiography (ExEcho) over exercise electrocardiography (ExECG) in patients with suspected acute coronary syndromes (ACS) referred to a chest pain unit. We aimed to assess the incremental value of ExEcho over ExECG in this setting. METHODS: ExECG and ExEcho were performed in parallel in 1052 patients with suspected ACS, nondiagnostic but interpretable electrocardiograms, and negative serial troponin results. The primary outcome was a composite of coronary death, nonfatal myocardial infarction or unstable angina with angiographic documentation of significant coronary artery disease within 6 months. RESULTS: The primary outcome occurred in 2/614 patients (0.3%) with both negative ExECG and ExEcho, 3/60 (5%) with positive ExECG and negative ExEcho, 73/135 (54.1%) with negative ExECG and positive ExEcho, 106/136 (77.9%) with both positive ExECG and ExEcho, and 8/107 (7.5%) with inconclusive results. The addition of ExEcho data to a model based on clinical and ExECG data significantly increased the c statistic from 0.898 to 0.968 (change +0.070, 95% confidence interval 0.052-0.092), with a continuous net reclassification improvement of 1.56 and an integrated discrimination improvement of 22% (p<0.001). Decision curve analysis showed that a strategy of referral to coronary angiography based on ExEcho was associated with the highest net benefit and with the largest reduction in unnecessary coronary angiographies. CONCLUSION: ExEcho provides significant incremental prognostic information and higher net clinical benefit than a strategy based on ExECG in patients referred to a chest pain unit for suspected ACS and negative troponin levels.