Human cardiac tissue induces transdifferentiation of adult stem cells towards cardiomyocytes.

BACKGROUND AIMS: The goal was to induce the transdifferentiation (or conversion) of human adipose-derived stem cells to cardiomyocytes using an intracellular extract obtained from adult human heart tissue. METHODS: Human adult stem cells from lipoaspirates were transiently permeabilized, exposed to human atrial extracts and allowed to recover in culture. RESULTS: After 21 days, the cells acquired a cardiomyocyte phenotype, as demonstrated by morphologic changes (appearance of binucleate, striated cells and branching fibers), immunofluorescence detection of cardiac-specific markers (connexin-43, sarcomeric alpha-actinin, cardiac troponin I and T, and desmin) and the presence of cardiomyocyte-related genes analyzed by reverse transcription-polymerase chain reaction (cardiac myosin light chain 1, alpha-cardiac actin, cardiac troponin T and cardiac beta-myosin). CONCLUSIONS: We have demonstrated for the first time that adult cardiomyocytes obtained from human donors retain the capacity to induce cardiomyocyte differentiation of mesenchymal stromal cells. The use of autologous extracts for reprogramming adult stem cells may have potential therapeutic implications for treating heart disease.

Long-term predictors of mortality and functional recovery after aortic valve replacement for severe aortic stenosis with left ventricular dysfunction.

INTRODUCTION AND OBJECTIVES: At present, surgery is the only recommended effective treatment for severe aortic stenosis. However, the surgical risk is increased when left ventricular dysfunction is present. The aim of this study was to identify predictors of postoperative and long-term mortality and functional improvement after valve replacement in patients with severe aortic stenosis and left ventricular dysfunction. METHODS: Between 1996 and 2008, 635 consecutive patients with severe aortic stenosis underwent surgery. Early postoperative mortality in the 82 with an ejection fraction <40% was 19.5%. The following independent predictors of early postoperative mortality were identified: female sex (odds ratio [OR]=2.60; 95% confidence interval [CI], 2.20-89.0; P=.004), mild mitral regurgitation (OR=2.38; 95% CI, 1.40-80.0; P=.020) and coronary artery disease (OR=2.09; 95% CI, 1.26-51.0; P=.027). RESULTS: During the mean follow-up period of 42.59+/-40.83 months, overall mortality was 18.8% and cardiovascular mortality was 11.3%. The only factor associated with increased mortality during follow-up was a low postoperative cardiac output (OR=4.40; 95% CI, 1.20-15.5; P=.02). In total, 70.5% showed early improvement in ventricular function, the predictors of which were: no improvement following a previous myocardial infarction (P=.04), no revascularized coronary lesions (P=.04), and a low aortic valve pressure gradient (P=.02). Functional class improved significantly during follow-up in 93.4% of patients. CONCLUSIONS: Despite considerable early postoperative mortality in patients with aortic stenosis and left ventricular dysfunction, over the long term there was evidence of better survival coupled to improved ventricular function and functional class.

[Influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis]. / Influencia del sexo en el pronóstico perioperatorio de pacientes sometidos a sustitución valvular por estenosis aórtica severa.

INTRODUCTION AND OBJECTIVES: The influence of sex on the prognosis of patients undergoing aortic valve replacement for severe stenosis is unclear. Nevertheless, a number of studies have regarded sex as an independent risk factor. The aim of this study was to evaluate the influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis. METHODS: This retrospective study involved 577 consecutive patients who underwent aortic valve replacement surgery for severe aortic stenosis between 1996 and April 2007. RESULTS: Women (44% of patients) were older than men (70.3+/-7.9 years vs. 66.8+/-9.8 years; P< .001), had a smaller body surface area (1.68+/-0.15 m(2) vs. 1.83+/-0.16 m(2); P< .001), more often had arterial hypertension (73% vs. 49%; P< .001), diabetes mellitus (33.5% vs. 24.5%; P=.001) and ventricular hypertrophy (89.1% vs. 83.1%; P< .001), and less often had coronary artery disease (19.1% vs. 31.8%; P< .001) and severe ventricular dysfunction (7.9% vs. 17.4%; P< .001). Nevertheless, women more often suffered acute myocardial infarction perioperatively (3.9% vs. 0.9%; P=.016), had a low cardiac output in the postoperative period (30.3% vs. 22.3%; P=.016) and experienced greater perioperative mortality (13% vs. 7.4%; P=.019) than men. However, after adjustment for various confounding factors, female sex was not a significant independent risk factor for mortality (odds ratio = 2.40; 95% confidence interval, 0.79-7.26; P=.119). CONCLUSIONS: Perioperative mortality in women with severe aortic stenosis who underwent valve replacement was high. However, after adjustment for potential confounding factors, particularly body surface area, female sex was not an independent risk factor for mortality.