Mahi L. Ashwath

Pathophysiology and Clinical Implications of Cardiac Memory

Altering the pattern of activation of the ventricle causes remodeling of the mechanical and electrical properties of the myocardium. The electrical remodeling is evident on the surface electrocardiogram as significant change in T‐wave polarity following altered activation; this phenomenon is ascribed to as “T‐wave memory” or “cardiac memory.” The electrophysiological remodeling following altered activation is characterized by distinct changes in regions proximal (early‐activated) versus distal (late‐activated) to the site of altered activation. The early‐activated region exhibits marked attenuation of epicardial phase 1 notch due to reduced expression of the transient outward potassium current (Ito). This is attributed to electrotonic changes during altered activation, and angiotensin‐mediated regulation of Kv4.3 (the pore‐forming α subunit responsible for Ito). The late‐activated region exhibits the most significant action potential prolongation due to markedly increased mechanical strain through a mechano‐electrical feedback mechanism. Consequently, regionally heterogeneous action potential remodeling occurs following altered activation. This enhances regional repolarization gradients that underlie the electrophysiological basis for T‐wave memory. Further, recent clinical studies highlight detrimental consequences of altered activation including worsening mechanical function and increased susceptibility to arrhythmias. Future studies to identify molecular mechanisms that link electrotonic and mechanical strain‐induced changes to cellular electrophysiology will provide important insights into the role of altered activation in regulating cardiac repolarization and arrhythmogenesis. (PACE 2010; 33:346–352)

Cardiac and Pulmonary Function Variability in Duchenne/Becker Muscular Dystrophy: An Initial Report

The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks and then progressively declines. In this report, the authors quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers’ peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. The authors concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in their clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for the use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

Usefulness of left ventricular end-systolic dimension by echocardiography to predict reverse remodeling in patients with newly diagnosed severe left ventricular systolic dysfunction

In many patients with left ventricular (LV) systolic dysfunction, the LV ejection fraction (LVEF)-a surrogate for reverse remodeling-fails to improve despite optimal medical therapy. The early identification of such patients would allow instituting aggressive treatment, including early therapy with implantable cardioverter defibrillators. We sought to establish the predictors of reverse remodeling in patients with LV systolic dysfunction receiving optimal medical therapy. Patients (n = 568) with newly documented LVEF of ≤0.35, who had ≥1 follow-up echocardiogram after ≥3 months, were evaluated. Reverse remodeling was defined as improvement in LVEF to >0.35. The clinical, laboratory, and echocardiographic data were compared between patients with (n = 263) and without (n = 305) reverse remodeling. The mean follow-up was 27 ± 16 months. Patients who demonstrated reverse remodeling had a significantly greater mean follow-up LVEF (0.51 ± 0.09 vs 0.25 ± 0.08; p <0.001). On multivariate analysis, the baseline LV end-systolic diameter index was the strongest predictor of reverse remodeling (odds ratio 5.79; 95% confidence interval 1.82 to 18.46; p <0.001). Other independent predictors of reverse remodeling were female gender (odds ratio 1.88; 95% confidence interval 1.19 to 2.98; p = 0.007), and nonischemic cardiomyopathy (odds ratio 1.65; 95% confidence interval 1.05 to 2.58; p = 0.03). Baseline LVEF was not an independent predictor of reverse remodeling. In conclusion, among patients with newly diagnosed LV systolic dysfunction, the LV end-systolic diameter index, but not the LVEF, at diagnosis, was a strong predictor of reverse remodeling. Patients with a low likelihood of reverse remodeling might benefit from more aggressive heart failure therapy, including the possible early use of implantable cardioverter defibrillators.