Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization

AbstractObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction.BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively.MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m2. Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria.ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m2 (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m2 (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m2 (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562).ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595

Myocardial Viability Assessment Before Surgical Revascularization in Ischemic Cardiomyopathy: JACC Review Topic of the Week

Ischemic cardiomyopathy results from the combination of scar with fibrosis replacement and areas of dysfunctional but viable myocardium that may improve contractile function with revascularization. Observational studies reported that only patients with substantial amounts of myocardial viability had better outcomes following surgical revascularization. Accordingly, dedicated noninvasive techniques have evolved to quantify viable myocardium with the objective of selecting patients for this form of therapeutic intervention. However, prospective trials have not confirmed the interaction between myocardial viability and the treatment effect of revascularization. Furthermore, recent observations indicate that recovery of left ventricular function is not the principal mechanism by which surgical revascularization improves prognosis. In this paper, the authors describe a more contemporary application of viability testing that is founded on the alternative concept that the main goal of surgical revascularization is to prevent further damage by protecting the residual viable myocardium from subsequent acute coronary events

Effects of ammonium-based ionic liquids and 2,4-dichlorophenol on the phospholipid fatty acid composition of zebrafish embryos

<div><p>Ionic liquids consisting of a combination of herbicidal anions with a quaternary ammonium cation act as efficient herbicides, which are under consideration to be used in the agriculture. In the present study, we used embryos of the zebrafish (<i>Danio rerio</i>) as a model to assess the toxic potential of ammonium-based ionic liquids for aquatic organisms. As we assumed interference of the partially hydrophobic ionic liquid cation with lipids, we investigated the adaptation response in the lipid composition of the zebrafish embryos, triggered by the ionic compound. Therefore, the impact of ammonium-based ionic liquids with different lengths of the alkyl chain ([C₆,C₆,C₁,C₁N][Br], [C₈,C₈,C₁,C₁N][Br]) on the phospholipid fatty acid (PLFA) profile of zebrafish embryos up to 72 hours post fertilization (hpf) was examined. Furthermore, the changes in the unsaturation index (UI) of PLFAs, as the sum parameter of membrane fluidity in eukaryotic cells, were presented. The PLFA’s UI in the zebrafish embryos upon exposure to quaternary ammonium salts was compared to the UI of the embryos upon exposure to nonionic 2,4-dichlorophenol, which has a similar hydrophobicity but is structurally different to [C₈,C₈,C₁,C₁N][Br]. It was shown that for ammonium-based ionic liquid precursors non-specific mode of action occurs and the toxic effect on lipid composition of zebrafish embryos can be well predicted based on chemical properties, like hydrophobicity. Furthermore, the changes in PLFAs, expressed by the UI, can be useful to study toxic effects of organic contamination. However, for zebrafish embryos, after ionic liquids and 2,4-DCP exposure, the changes were observed at high lethal concentrations, which caused the incidence of lethality of 30 and 50% of a group of test animals.</p></div

Summary of acute toxicity data for each compound.

<p>Summary of acute toxicity data for each compound.</p