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Introduction: Hydroxychloroquine (HCQ) is known to cause QTc prolongation, however its association with other ECG changes and how those are related to markers of myocardial injury in COVID-19 patients (pts) are not well described. Hypothesis: To study ECG changes in COVID-19 pts with or without troponin (Tn) elevation >3X normal (Tn +/-), who were or were not treated with HCQ (+/-). Methods: This is an observational study of pts admitted with COVID-19. All had at least 3 ECGs during admission; on day 1, day 2-3 and day 4-6. Pre-admission and final ECGs were included when available. Pts were excluded if they had atrial fibrillation, paced QRS, QRS>120msec, STEMI, or end stage renal disease. QRS, QTc, PR, P wave duration, QRS amplitude and the sum of T wave deflections in both limb and precordial leads were measured. Data were collected on medical history, illness severity, electrolytes, and medications within the 12-hour window of each ECG. Results: A total of 116 pts were included: 85 HCQ+ (40% Tn+) and 31 HCQ- (48% Tn+). There were no differences between the two groups in baseline characteristics, illness severity or mortality. Significant QTc prolongation was noted only in the HCQ+ group (p Conclusions: HCQ related ECG effects extend beyond QTc prolongation. These are most notable in pts with evidence of myocardial injury.

Background— With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated. Methods and Results— We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics. Genetic diagnosis was reached and reported with a success rate of 26.5% (53 of 200 patients). This compares to 18% (36 of 200) that would have been diagnosed using commercially available genetic panels ( P =0.04). Whole exome sequencing was particularly useful for clinical diagnosis in patients with aborted sudden cardiac death, in whom the primary insult for the presence of both depressed cardiac function and prolonged QT had remained unknown. The analysis of the remaining cases using genome annotation and disease segregation led to the discovery of novel candidate genes in another 14% of the cases. Conclusions— Whole exome sequencing is an exceptionally valuable screening tool for its capability to establish the clinical diagnosis of inherited CVDs, particularly for poorly defined cases of sudden cardiac death. By presenting novel candidate genes and their potential disease associations, we also provide evidence for the use of this genetic tool for the identification of novel CVD genes. Creation and sharing of exome databases across centers of care should facilitate the discovery of unknown CVD genes.