Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

Importance: QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown. Objective: To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. Design, Setting, and Participants: This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. Exposure: QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). Main Outcomes and Measures: Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. Results: A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. Conclusions and Relevance: These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

MR assessment of myocardial perfusion, viability, and function after intramyocardial transfer of VM202, a new plasmid human hepatocyte growth factor in ischemic swine myocardium.

PURPOSE: VM202, a newly constructed plasmid human hepatocyte growth factor, was transferred intramyocardially after infarction for the purpose of evaluating this strategy as a therapeutic approach for protection from left ventricular (LV) remodeling. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. Pigs underwent coronary artery occlusion and reperfusion and served as either control (n = 8) or VM202-treated (n = 8) animals. VM202 was transferred intramyocardially into four infarcted and four periinfarcted sites. Cardiac magnetic resonance (MR) imaging (cine, perfusion, delayed enhancement) was performed in acute (3 days) and chronic (50 days +/- 3 [standard error of the mean]) infarction. Histopathologic findings were used to characterize and quantify neovascularization. The t test was utilized to compare treated and control groups and to assess changes over time. RESULTS: In acute infarction, MR imaging estimates of function, perfusion, and viability showed no difference between the groups. In chronic infarction, however, VM202 increased maximum signal intensity and upslope at first-pass perfusion imaging and reduced infarct size at perfusion and delayed-enhancement imaging. These changes were associated with a decrease in end-diastolic (2.15 mL/kg +/- 0.12 to 1.73 mL/kg +/- 0.10, P < .01) and end-systolic (1.33 mL/kg +/- 0.07 to 0.92 mL/kg +/- 0.08, P < .001) volumes and an increase in ejection fraction (38.2% +/- 1.3 to 47.0% +/- 1.8, P < .001). In contrast, LV function deteriorated further in control animals. Compared with control animals, VM202-treated animals revealed peninsulas and/or islands of viable myocardium in infarcted and periinfarcted regions and greater number of capillaries (218 per square millimeter +/- 19 vs 119 per square millimeter +/- 17, P < .05) and arterioles (21 per square millimeter +/- 4 vs 3 per square millimeter +/- 1, P < .001). CONCLUSION: Intramyocardial transfer of VM202 improved myocardial perfusion, viability, and LV function.

Left septal atrial flutter: electrophysiology, anatomy, and results of ablation.

BACKGROUND: We describe the clinical and electrophysiological characteristics of a novel macroreentrant form of left atrial flutter circuit. METHODS AND RESULTS: A total of 11 patients were included in the study. The mean tachycardia cycle length was 278+/-41 ms. Nine of the 11 patients were treated with antiarrhythmic drugs at the time of the study for concomitant atrial fibrillation. With the use of entrainment pacing and either the CARTO Biosense mapping system (9 patients) or conventional mapping (2 patients), the flutter circuit was found to rotate around the left septum primum with a critical isthmus located between the pulmonary veins posteriorly and/or mitral annulus anteriorly and the septum primum. In 5 patients, radiofrequency ablation was performed from the septum primum to the right inferior pulmonary vein (group 1), and in 6 patients, a lesion was made from the septum primum to the mitral annulus (group 2). After a follow-up of 13+/-6 months, 2 patients in group 1 and all patients in group 2 remained in sinus rhythm without recurrence. CONCLUSIONS: Slowing of electric conduction in the left atrial septum due to antiarrhythmic drugs and/or atrial myopathy seems to promote left septal atrial flutter. Radiofrequency ablation of this arrhythmia is usually effective and safe. A line of block between the septum primum and the mitral annulus proved to be effective for cure of tachycardia.