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.

Predictores de mortalidad y recuperación funcional a largo plazo en el reemplazo valvular por estenosis aórtica severa con disfunción ventricular / Long-term predictors of mortality and functional recovery after aortic valve replacement for severe aortic stenosis with left ventricular dysfunction

Introducción y objetivos. El tratamiento quirúrgico de la estenosis aórtica severa es el único efectivo recomendado actualmente para esta patología, pero el riesgo quirúrgico aumenta con la disfunción ventricular izquierda. Nuestro objetivo fue identificar predictores de mortalidad y mejoría funcional en el postoperatorio y a largo plazo tras reemplazo valvular en pacientes con estenosis aórtica y disfunción ventricular severa. Métodos. Entre 1996 y 2008, 635 pacientes con estenosis aórtica severa fueron intervenidos, 82 con fracción de eyección < 40%, con mortalidad postoperatoria precoz del 19,5%. Identificamos como predictores independientes de mortalidad postoperatoria precoz el sexo femenino (OR = 2,60; IC del 95%, 2,20-89; p = 0,004), la regurgitación mitral no severa (OR = 2,38; IC del 95%,1,40-80; p = 0,020) y las lesiones coronarias (OR = 2,09;IC del 95%, 1,26-51; p = 0,027).Resultados. Tras seguimiento medio de 42,59 ± 40,83meses, la mortalidad global fue del 18,8% y la cardiovascular, del 11,3%. Sólo el bajo gasto cardiaco postoperatorio(OR = 4,40; IC del 95%, 1,20-15,50; p = 0,02)se relacionó con mayor mortalidad en el seguimiento. El70,5% presentó mejoría precoz de la función ventricular, siendo predictores de ausencia de mejoría el infarto previo(p = 0,04), las lesiones coronarias no revascularizadas (p = 0,04) y un gradiente aórtico reducido (p = 0,02). El93,4% mejoró su grado funcional significativamente durante el seguimiento. Conclusiones. Pese a la considerable mortalidad postoperatoria precoz de los pacientes con estenosis aórtica y disfunción ventricular izquierda, a largo plazo se observa una supervivencia elevada junto a mejora de la función ventricular y del grado funcional (AU)

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 of42.59±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 allow 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 (AU)

[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.

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

Introducción y objetivos. La influencia pronóstica del sexo de los pacientes sometidos a sustitución valvular aórtica por estenosis severa tiene un papel controvertido, y algunos estudios le atribuyen un papel relevante como marcador de riesgo independiente. El objetivo del estudio es valorar la influencia pronóstica perioperatoria del sexo de los pacientes sometidos a sustitución valvular por estenosis aórtica severa. Métodos. Estudio retrospectivo en el que se analizó una cohorte de 577 pacientes sometidos a cirugía de reemplazo valvular aórtico por estenosis aórtica entre 1996 y abril de 2007. Resultados. Las mujeres (44%) tenían mayor edad (70,3 ± 7,9 frente a 66,8 ± 9,8 años; p < 0,001), menos superficie corporal (1,68 ± 0,15 frente a 1,83 ± 0,16 m2; p < 0,001), más hipertensión arterial (el 73 frente al 49%; p < 0,001), diabetes mellitus (el 33,5 frente al 24,5%; p = 0,001) e hipertrofia ventricular (el 89,1 frente al 83,1%; p < 0,001), menos enfermedad coronaria (el 19,1 frente al 31,8%; p < 0,001) y menos disfunción ventricular severa (el 7,9 frente al 17,4%; p < 0,001). A pesar de esto, las mujeres tuvieron más infarto agudo de miocardio perioperatorio (el 3,9 frente al 0,9%; p = 0,016), bajo gasto en el postoperatorio (el 30,3 frente al 22,3%; p = 0,016) y mortalidad perioperatoria que los varones (el 13 frente al 7,4%; p = 0,019). El sexo femenino no se mostró, al ajustar por los diferentes factores de confusión, como factor independiente relacionado con la mortalidad (odds ratio = 2,4; intervalo de confianza del 95%, 0,79-7,26; p = 0,119). Conclusiones. La mortalidad perioperatoria de las mujeres con estenosis aórtica severa sometidas a sustitución valvular es alta. Al ajustar por potenciales factores de confusión, especialmente superficie corporal, el sexo femenino no se comporta como factor independiente de mortalidad (AU)

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 m2 vs. 1.83±0.16 m2; 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 (AU)