T-wave heterogeneity in standard resting 12-lead ECGs is associated with 90-day cardiac mortality in women following emergency department admission: A nested case-control study.

BACKGROUND: We investigated whether T-wave heterogeneity (TWH) can identify patients who are at risk for near-term cardiac mortality. METHODS: A nested case-control analysis was performed in the 888 patients admitted to the Emergency Department (ED) of our medical center in July through September 2018 who had ≥2 serial troponin measurement tests within 6 hr for acute coronary syndrome evaluation to rule-in or rule-out the presence of acute myocardial infarction. Patients who died from cardiac causes during 90 days after ED admission were considered cases (n = 20; 10 women) and were matched 1:4 on sex and age with patients who survived during this period (n = 80, 40 women). TWH, that is, interlead splay of T waves, was automatically assessed from precordial leads by second central moment analysis. RESULTS: TWHV4-6 was significantly elevated at ED admission in 12-lead resting ECGs of female patients who died of cardiac causes during the following 90 days compared to female survivors (100 ± 14.9 vs. 40 ± 3.6 µV, p < .0001). TWHV4-6 generated areas under the receiver-operating characteristic (ROC) curve (AUC) of 0.933 in women (p < .0001) and 0.573 in men (p = .4). In women, the ROC-guided 48-µV TWHV4-6 cut point for near-term cardiac mortality produced an adjusted odds ratio of 121.37 (95% CI: 2.89-6,699.84; p = .02) with 100% sensitivity and 82.5% specificity. In Kaplan-Meier survival analysis, TWHV4-6  ≥ 48 µV predicted cardiac mortality in women during 90-day follow-up with a hazard ratio of 27.84 (95% CI: 7.29-106.36, p < .0001). CONCLUSION: Elevated TWHV4-6 is associated with near-term cardiac mortality among women evaluated for acute coronary syndrome.

Multimodal mechanisms and enhanced efficiency of atrial fibrillation cardioversion by pulmonary delivery of a novel flecainide formulation.

INTRODUCTION: Inhaled flecainide significantly alters atrial electrical properties with the potential to terminate atrial fibrillation (AF) efficiently by optimizing dose and drug formulation. METHODS: Seventeen Yorkshire pigs were studied. Intrapericardial acetylcholine and burst pacing were used to induce AF. Effects of a novel cyclodextrin formulation (hydroxypropyl-ß-cyclodextrin [HPßCD]) of flecainide (75 mg/mL, 0.5 or 1.0 mg/kg, bolus) instilled intratracheally at 2 minutes after AF initiation were studied. Concentration time-area analyses of flecainide HPßCD were compared to the traditional acetate formulation. RESULTS: Intratracheal instillation of flecainide HPßCD accelerated the conversion of AF to sinus rhythm in a dose-proportional manner, shortening AF duration by 47% (P = .014) and 79% (P = .002) at the lower and higher doses, respectively, compared to intratracheal sterile water placebo. AF dominant frequency was reduced by 11% (P = .04) and 29% (P = .004) respective to dose. At 2 minutes after intratracheal flecainide HPßCD, atrial depolarization (Pa ) duration increased by 12% (P = .02) and 17% (P = .009) at the lower and higher doses, respectively. At this time, the PR interval was prolonged by 9% (P = .04 for the higher dose) and AV node conduction was slowed, decreasing the ventricular rate during AF by 16% (P = .002) and 28% (P = .007) for the lower and higher doses. Flecainide HPßCD achieved the more efficient conversion of AF than the acetate formulation, reflected in a markedly reduced area under the curve (P = .04). CONCLUSION: Intratracheal instillation of the new flecainide HPßCD formulation effectively terminates AF through efficient multimodal actions including slowing of atrial conduction velocity and decreasing AF dominant frequency, allowing reduced net drug delivery and inhalation time.

Pulmonary Delivery of Metoprolol Reduces Ventricular Rate During Atrial Fibrillation and Accelerates Conversion to Sinus Rhythm.

BACKGROUND: Safe, effective pulmonary delivery of cardioactive agents in humans is under development. OBJECTIVES: We examined whether intratracheal delivery of metoprolol can reduce ventricular rate during atrial fibrillation (AF) and accelerate conversion to sinus rhythm. METHODS: In 7 closed-chest, anesthetized Yorkshire pigs, AF was induced by intrapericardial infusion of acetylcholine (1 mL of 102.5-mM solution) followed by atrial burst pacing and was allowed to continue for 2 minutes before intratracheal instillation of sterile water or metoprolol (0.2-mg/kg bolus) using a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms were obtained from catheters fluoroscopically positioned in the right atrium and left ventricle. RESULTS: Rapid intratracheal instillation of metoprolol caused a 32-beat/min reduction in ventricular rate during AF (from 272 ± 13.7 to 240 ± 12.6 beats/min, P = 0.008) and a 2.3-minute reduction in AF duration (from 10.3 ± 2.0 to 8.0 ± 1.4 minutes, P = 0.018) compared with sterile water control. Conversion of AF to sinus rhythm was associated with rapid restoration (5-6 minutes) of heart rate and arterial blood pressure toward control values. Intratracheal metoprolol reduced AF dominant frequency by 31% (from 8.7 ± 0.9 to 6.0 ± 1.1 Hz, P = 0.04) compared with control and resulted in a trend toward a 5% increase in PR interval (from 174 ± 11.2 to 182 ± 11.4 ms, P = 0.07). CONCLUSIONS: Intratracheal delivery of metoprolol effectively reduces ventricular rate during AF and accelerates conversion to normal sinus rhythm in a pig model of acetylcholine-induced AF.

Regadenoson-induced T-wave heterogeneity complements coronary stenosis detection by myocardial perfusion imaging in men and women.

AIMS: We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL). METHODS AND RESULTS: Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N = 59) had angiographically significant FLL (≥50% of left main or ≥70% of other epicardial coronary arteries ≥2 mm in diameter); controls (N = 44) were normal or had non-FLL. TWH, i.e., interlead splay of T waves, was assessed from precordial leads V4-6 by second central moment analysis. Maximum TWHV4-6 levels during regadenoson stress were 68% higher in cases than in controls (P < 0.0001). TWHV4-6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P < 0.0001) and 0.71 in women (P = 0.007). In men, the ROC-guided 54-µV TWHV4-6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3-41.5, P = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-µV TWHV4-6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1-18.9, P = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4-6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2-21.4, P = 0.001) with specificity of 78% in men and 86% in women. CONCLUSION: This observational study is the first to demonstrate the benefit of combining TWHV4-6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women.

The Effect of Low-Fat and Low-Carbohydrate Diets on Weight Loss and Lipid Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: The rise in obesity has emphasised a focus on lifestyle and dietary habits. We aimed to address the debate between low-carbohydrate and low-fat diets and compare their effects on body weight, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol, and triglycerides in an adult population. METHOD: Medline and Web of Science were searched for randomised controlled trials (RCTs) comparing low-fat and low-carbohydrate diets up to September 2019. Three independent reviewers extracted data. Risk of bias was assessed using the Cochrane tool. The meta-analysis was stratified by follow-up time using the random-effects models. RESULTS: This meta-analysis of 38 studies assessed a total of 6499 adults. At 6-12 months, pooled analyses of mean differences of low-carbohydrate vs. low-fat diets favoured the low-carbohydrate diet for average weight change (mean difference -1.30 kg; 95% CI -2.02 to -0.57), HDL (0.05 mmol/L; 95% CI 0.03 to 0.08), and triglycerides (TG) (-0.10 mmol/L; -0.16 to -0.04), and favoured the low-fat diet for LDL (0.07 mmol/L; 95% CI 0.02 to 0.12) and total cholesterol (0.10 mmol/L; 95% CI 0.02 to 0.18). Conclusion and Relevance: This meta-analysis suggests that low-carbohydrate diets are effective at improving weight loss, HDL and TG lipid profiles. However, this must be balanced with potential consequences of raised LDL and total cholesterol in the long-term.

Preimplantation interlead ECG heterogeneity is superior to QRS complex duration in predicting mechanical super-response in patients with non-left bundle branch block receiving cardiac resynchronization therapy.

BACKGROUND: Reliable quantitative preimplantation predictors of response to cardiac resynchronization therapy (CRT) are needed. OBJECTIVE: We tested the utility of preimplantation R-wave and T-wave heterogeneity (RWH and TWH, respectively) compared to standard QRS complex duration in identifying mechanical super-responders to CRT and mortality risk. METHODS: We analyzed resting 12-lead electrocardiographic recordings from all 155 patients who received CRT devices between 2006 and 2018 at our institution and met class I and IIA American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines with echocardiograms before and after implantation. Super-responders (n=35, 23%) had ≥20% increase in left ventricular ejection fraction and/or ≥20% decrease in left ventricular end-systolic diameter and were compared with non-super-responders (n=120, 77%), who did not meet these criteria. RWH and TWH were measured using second central moment analysis. RESULTS: Among patients with non-left bundle branch block (LBBB), preimplantation RWH was significantly lower in super-responders than in non-super-responders in 3 of 4 lead sets (P=.001 to P=.038) and TWH in 2 lead sets (both, P=.05), with the corresponding areas under the curve (RWH: 0.810-0.891, P<.001; TWH: 0.759-0.810, P≤.005). No differences were observed in the LBBB group. Preimplantation QRS complex duration also did not differ between super-responders and non-super-responders among patients with (P=.856) or without (P=.724) LBBB; the areas under the curve were nonsignificant (both, P=.69). RWHV1-3LILII ≥ 420 µV predicted 3-year all-cause mortality in the entire cohort (P=.037), with a hazard ratio of 7.440 (95% confidence interval 1.015-54.527; P=.048); QRS complex duration ≥ 150 ms did not predict mortality (P=.27). CONCLUSION: Preimplantation interlead electrocardiographic heterogeneity but not QRS complex duration predicts mechanical super-response to CRT in patients with non-LBBB.