EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy.

The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R = -0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N = 40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes' cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium.

Clinical and hemodynamic outcomes of "all-comers" undergoing transapical aortic valve implantation: results from the Italian Registry of Trans-Apical Aortic Valve Implantation (I-TA).

OBJECTIVE: The aim of this study was to assess clinical and hemodynamic outcomes of transapical aortic valve implantation (TA-TAVI) in patients enrolled in the Italian Registry of Trans-Apical Aortic Valve Implantation (I-TA). METHODS: From April 2008 until November 2010, 504 patients from 20 Italian centers were enrolled in the I-TA registry. Mean logistic EuroSCORE and Society of Thoracic Surgeons score were 24% ± 16% and 11% ± 4%, respectively. Mean follow-up was 9.2 ± 6.5 months (range, 1-26 months). Outcomes were analyzed according to intraoperative complications, procedural volume (high-volume centers, >20 cases; low-volume centers, < 20 cases) and learning curve (first 50% cases vs second 50% cases of each center). RESULTS: All-cause overall mortality was 8.3% (42 patients). Device success was 99% (500/504 patients). Intraoperative severe complications occurred in 24 (4.8%) patients. Overall 2-year survival was 71.5% ± 6.2%. At discharge, peak and mean gradients were 16.4 ± 11.2 and 8.7 ± 4.1 mm Hg, respectively, and effective orifice area was 1.67 cm(2). These values remained stable at 3, 6, and 12 months after surgery. Independent risk factors for mortality after TA-TAVI were as follows: New York Heart Association class III and IV (odds ratio [OR], 4.43; 95% confidence intervals [CI], 1.28-15.40; P = .02); logistic EuroSCORE greater than 20 (OR, 1.83; 95% CI, 1.02-3.29; P = .04); creatinine concentration greater than 200 µmol/L (OR, 2.56; 95% CI, 1.07-6.15; P = .03), and intraoperative complications (OR, 5.80; 95% CI, 2.68-12.55; P < .001). There were no significant differences in outcomes between high- and low-volume centers and between the first and the second 50% of cases. CONCLUSIONS: TA-TAVI represents a safe and effective alternative treatment for patients who are inoperable or at high risk for surgery. The occurrence of an intraoperative complication significantly affects survival. Procedural volume and learning curve have no impact on patient survival.