The value of genetic testing in the diagnosis and risk stratification of arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by risk of malignant ventricular arrhythmias (VA). ARVC is diagnosed using an array of clinical tests in the consensus-based task force criteria (TFC), one of which is genetic testing. OBJECTIVE: To investigate the value of genetic testing in diagnosing ARVC and its relation to the occurrence of first malignant VA. METHODS: A multicenter cohort of ARVC patients was scored using the revised 2010 TFC with and without genetic criterion, analyzing any resulting loss or delay of diagnosis. Malignant VA was defined as sustained ventricular arrhythmia (≥30s duration at ≥100 bpm or requiring intervention). RESULTS: We included 402 subjects (55% male, 54% proband, 40 [27-51] years old at presentation) who were diagnosed with definite ARVC. A total of 232 (58%) subjects fulfilled genetic testing criteria. Removing the genetic criterion caused loss of diagnosis in 18 (4%) patients (11/216 [5%] probands, 7/186 [4%] relatives), and delay of diagnosis ≥30 days in 22 (5%) patients (21/216 [10%] probands, 1/186 [0.5%] relative). A first malignant VA occurred in no patients who lost diagnosis and in 3 patients (3/216 [1%] probands and no relatives) during their diagnosis delay, none fatal. Time to event analysis showed no significant difference in time from diagnosis to malignant VA between pathogenic variant carriers and non-carriers. CONCLUSION: Disregarding the genetic criterion of the TFC caused loss or delay of diagnosis in 10% (n=40/402) of ARVC patients. Malignant VA occurred in 1% (n=3/402) of cases with lost or delayed diagnosis, none fatal

An initial exploration of subtraction electrocardiography to detect myocardial ischemia in the prehospital setting

Background: In the prehospital triage of patients presenting with symptoms suggestive of acute myocardial ischemia, reliable myocardial ischemia detection in the electrocardiogram (ECG) is pivotal. Due to large interindividual variability and overlap between ischemic and nonischemic ECG-patterns, incorporation of a previous elective (reference) ECG may improve accuracy. The aim of the current study was to explore the potential value of serial ECG analysis using subtraction electrocardiography. Methods: SUBTRACT is a multicenter retrospective observational study, including patients who were prehospitally evaluated for acute myocardial ischemia. For each patient, an elective previously recorded reference ECG was subtracted from the ambulance ECG. Patients were classified as myocardial ischemia cases or controls, based on the in-hospital diagnosis. The diagnostic performance of subtraction electrocardiography was tested using logistic regression of 28 variables describing the differences between the reference and ambulance ECGs. The Uni-G ECG Analysis Program was used for state-of-the-art single-ECG interpretation of the ambulance ECG. Results: In 1,229 patients, the mean area-under-the-curve of subtraction electrocardiography was 0.80 (95%CI: 0.77–0.82). The performance of our new method was comparable to single-ECG analysis using the Uni-G algorithm: sensitivities were 66% versus 67% (p-value >.05), respectively; specificities were 80% versus 81% (p-value >.05), respectively. Conclusions: In our initial exploration, the diagnostic performance of subtraction electrocardiography for the detection of acute myocardial ischemia proved equal to that of state-of-the-art automated single-ECG analysis by the Uni-G algorithm. Possibly, refinement of both algorithms, or even integration of the two, could surpass current electrocardiographic myocardial ischemia detection