mRNA PGC-1α levels in blood samples reliably correlates with its myocardial expression: study in patients undergoing cardiac surgery.

OBJECTIVE: Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that has been proposed to play a protective role in mouse models of cardiac ischemia and heart failure, suggesting that PGC-1α could be relevant as a prognostic marker. Our previous studies showed that the estimation of peripheral mRNA PGC-1α expression was feasible and that its induction correlated with the extent of myocardial necrosis and left ventricular remodeling in patients with myocardial infarction. In this study, we sought to determine if the myocardial and peripheral expressions of PGC-1α are well correlated and to analyze the variability of PGC-1α expression depending on the prevalence of some metabolic disorders. METHODS: This was a cohort of 35 consecutive stable heart failure patients with severe aortic stenosis who underwent an elective aortic valve replacement surgery. mRNA PGC-1α expression was simultaneously determined from myocardial biopsy specimens and blood samples obtained during surgery by quantitative PCR, and a correlation between samples was made using the Kappa index. Patients were divided into two groups according to the detection of baseline expression levels of PGC-1α in blood samples, and comparisons between both groups were made by chi-square test or unpaired Student's t-test as appropriate. RESULTS: Based on myocardial biopsies, we found that mRNA PGC-1α expression in blood samples showed a statistically significant correlation with myocardial expression (Kappa index 0.66, p<0.001). The presence of higher systemic PGC-1α expression was associated with a greater expression of some target genes such as silent information regulator 2 homolog-1 (x-fold expression in blood samples: 4.43±5.22 vs. 1.09±0.14, p=0.044) and better antioxidant status in these patients (concentration of Trolox: 0.40±0.05 vs. 0.34±0.65, p=0.006). CONCLUSIONS: Most patients with higher peripheral expression also had increased myocardial expression, so we conclude that the non-invasive estimation of mRNA PGC-1α expression from blood samples provides a good approach of the constitutive status of the mitochondrial protection system regulated by PGC-1α and that this could be used as prognostic indicator in cardiovascular disease.

Artificial chordae in the setting of complex mitral valve repair: early outcomes using the folding leaflet technique.

OBJECTIVES: Neochordal repair is particularly limited in case of large prolapse with absence of a reference point on a nearby segment. Our aim was to overcome these limitations by means of a simple technique: the 'Folding Leaflet'. METHODS: Ninety-six patients underwent this technique between January 2009 and August 2012 from a global mitral valve (MV) repair group of 384 patients. A subgroup of 68 patients with complex lesions, bileaflet, commissural or multisegment prolapse, was selected. These more challenging patients were considered as the study group in order to assess the efficacy of our technique. The neochordae were fixed to the papillary muscle with a simple stitch and then were passed through the free margin of the prolapsing leaflet. Free-edge remodelling was achieved weaving this suture and surpassing the coaptation line. Then, the leaflet was folded and its free margin was temporarily approximated edge-to-edge to the adjacent annulus. This was used as the reference point while the neochordae were tied without the need for adjacent healthy chordae or use of callipers. Complete echocardiographic follow-up was obtained at 6-month intervals. RESULTS: All patients had ≥ 2 prolapsed segments: posterior leaflet (40 patients), anterior leaflet (13 patients) or both leaflets (15 patients). Annuloplasty was routinely used and the mean number of neochordae per patient was 4.1 ± 2.2 (2-13). Mean follow-up was 28 ± 14 months (5-49 months). There was only one in-hospital death. Another patient died by pneumoniae (15th postoperative month). At the first-month follow-up, 51 patients had no mitral regurgitation (MR) and 16 patients had Grade 1 MR. Only 1 patient had more than mild regurgitation at the 6-month follow-up. There was no evidence of Grade 3 or 4 MR in any patient. At the 2-year follow-up, 34 patients remained with no MR or trace MR and 7 patients had Grade 1 MR. CONCLUSIONS: MV repair for complex degenerative MR using this technique of neochordal repair results in excellent early and mid-term outcomes. This technique facilitates the extensive use of neochordae in case of large areas of prolapse.

Minimally invasive aortic valve surgery. A safe and useful technique beyond the cosmetic benefits.

INTRODUCTION AND OBJECTIVES: The aim of this study was to compare the in-hospital clinical outcomes of minimally invasive, isolated aortic valve replacement vs median sternotomy. METHODS: Between 2005 and 2012, 615 patients underwent aortic valve replacement at a single institution, 532 by a median sternotomy (E group) and 83 by a J-shaped ministernotomy (M group). RESULTS: No significant differences were found between the E and M groups in terms of age (69.27 [9.31] years vs 69.40 [10.24] years, respectively), logistic EuroSCORE (6.27 [2.91] vs 5.64 [2.17], respectively), size of implanted valve prosthesis (21.94 [2.04] mm vs 21.79 [2.01] mm, respectively), or the incidence of diabetes, hypercholesterolemia, high blood pressure, or chronic obstructive pulmonary disease. Mean cardiopulmonary bypass time was 102.90 (41.68) min for the E group vs 81.37 (25.41) min for the M group (P<.001). Mean cross-clamp time was 77.31 (29.20) min vs 63.45 (17.71) min for the S and M groups, respectively (P<.001). Mortality in the E group was 4.88% (26). There were no deaths in the M group (P<.05). The E group was associated with longer intensive care unit and hospital stays: 4.17 (5.23) days vs 3.22 (2.01) days (P=.045) and 9.58 (7.66) days vs 7.27 (3.83) days (P<.001), respectively. E group patients had more postoperative respiratory complications (42 [8%] vs 1 [1.2%]; P<.05). There were no differences when postoperative hemodynamic, neurologic, and renal complications, systemic infection, and wound infection were analyzed. CONCLUSIONS: In terms of morbidity, mortality, and operative times, outcomes after minimally invasive surgery for aortic valve replacement are at least comparable to those achieved with median sternotomy. The length of the hospital stay was reduced by minimally invasive surgery in our single-institution experience. The retrospective nature of this study warrants further randomized prospective trials to validate our results.

Resultados a corto y mediano plazo del tratamiento de la obstrucción al tracto de salida del ventrículo izquierdo mediante miectomía videoasistida / Video assisted myectomy for relief of left ventricular tract obstruction in patients with Obstructive Hypertrophic Cardiomyopathy

Objetivo: Describir nuestra experiencia y evaluar los resultados a corto y mediano plazo de la miecto-mía videoasistida en el tratamiento de la obstrucción del tracto de salida del ventrículo izquierdo (OTSVI) en pacientes con miocardiopatía hipertrófica. Materiales y métodos: 52 pacientes con edad media de 56,2 (rango 12 - 83) y Euroscore de riesgo de 4,1 +/- 1,92 con diagnóstico de OTSVI fueron intervenidos de manera consecutiva en un mismo centro mediante miectomía videoasistida. Se realizó seguimiento clínico y ecocardiográfico con controles al mes y al año del postoperatorio. Resultados: Entre las patologías asociadas encontramos 11 pacientes con valvulopatía aórtica, 2 con valvulopatía mitral, 3 con cardiopatía isquémica, 1 con aneurisma de aorta ascendente y 1 con foramen oval permeable resueltos en el mismo acto quirúrgico. La mortalidad hospitalaria global fue de 5,8 por ciento (3 pacientes). En el momento de la intervención, 8 (15,4 por ciento) se encontraban en clase funcional II de la NYHA, 42 (80,8 por ciento) en clase III y 2 (3,8 por ciento) en clase IV. El gradiente máximo subaórtico disminuyó de 80,7 mmHg +/- 29,43 en el preoperatorio a 19,0 mmHg +/- 15,57 (p<0,001) en el postoperatorio inmediato, manteniéndose en 14,6 mmHg +/- 8,88 al mes (p<0,001 en relación al preoperatorio) y al año en 13,9 mmHg +/- 7,69 (p<0,001 en relación al preoperatorio). Además, se registró una disminución del grosor del tabique interventricular en diástole de 19,4 mm +/- 3,78 en el preoperatorio a 12,9 mm +/- 2,35 (p<0,001) en el postoperatorio. Todos los pacientes se encontraban en clase funcional I-II al final del seguimiento. Conclusión: Los resultados demuestran que la miectomía videoasistida es un tratamiento seguro para la OTSVI con el que se obtienen resultados favorables a corto y mediano plazo, tanto en parámetros clínicos, como ecocardiográficos.

Aim: To report a clinical experience and to evaluate early and mid term results of video assisted myec-tomy for relief of left ventricular tract obstruction (LVOTO) in patients with Obstructive Hypertrophic Cardiomyopathy. Methods: 52 patients with Obstructive Car-diomyopathy and a mean age 56.2 years (12 - 83) carrying a Euro score risk of 4.1 +/- (SD 1.92), were consecutively operated on in a single center. Relief of LVOTO was performed with video assisted myec-tomy. Clinical and echocardiographic follow up to 1 year postoperatively was carried out. Results: Apart from the Obstructive Cardiomyo-pathy, 11 patients had aortic valve disease, 2 mitral valve disease, 3 ischemic heart disease, 1 an ascending aortic aneurysm and 1 a patent foramen ovale. All these lesions were surgically repaired in the same surgical act. In hospital mortality was 5.8 percent (3 patients). Pre-operatively 15.4 percent of patients were in NYHA Class II, 80.8 per cent in Class III and 3.8 percent in Class IV. After surgery peak sub aortic gradient decreased from 80.7+/-29.43mmHg to 19.0 +/- 15.57 (p<0.001). Corresponding values were 14.6 +/- 8.88 at 1month and 13.9 +/- 7.69 at 1 year post operatively. Interven-tricular septal thickness in diastole decreased from 19.4 +/- 3.78 mm to 12.9 +/- 2.35 mm after surgery (p<0.001). All patients were Class I or II at the end of follow up. Conclusion: Video assisted myectomy is safe and effective for relief of LVOTO in patients with hypertrophic cardiomyopathy. Good results are maintained one year after surgery.

Incidence and prognostic value of FLT3 internal tandem duplication and D835 mutations in acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Cytogenetics is the most important prognostic factor in acute myeloid leukemia (AML). However, a high proportion of patients show normal or intermediate-risk karyotypes. In these patients, other determinants could help to identify those with a higher risk of relapse. Recently, internal tandem duplications (ITD) and D835 mutations in FLT3 tyrosine kinase receptor have been shown to confer a bad prognosis in AML. DESIGN AND METHODS: We analyzed the incidence of these mutations in a total of 208 patients of different AML subsets and their prognostic relevance in non-promyelocytic de novo AML. RESULTS: FLT3 mutations were detected in 24% of de novo AML, 42% of acute promyelocytic leukemia (APL) and 17% of secondary AML. Four patients showed both ITD and D835 mutations. Ninety-four per cent of the patients with FLT3 alterations were classified into the intermediate-risk group. There was no association between the presence of FLT3 alterations and response to induction while the alterations were associated with a worse disease-free survival and event-free survival in both the overall and intermediate-risk patients. INTERPRETATION AND CONCLUSIONS: Our data confirm that any of the mutations in FLT3 confer a bad prognosis in AML. Because of the high prevalence of these mutations within the intermediate-risk group, their detection could be useful to identify patients with a poor prognosis.