Myocyte enhancer factor 2 and class II histone deacetylases control a gender-specific pathway of cardioprotection mediated by the estrogen receptor.

RATIONALE: Gender differences in cardiovascular disease have long been recognized and attributed to beneficial cardiovascular actions of estrogen. Class II histone deacetylases (HDACs) act as key modulators of heart disease by repressing the activity of the myocyte enhancer factor (MEF)2 transcription factor, which promotes pathological cardiac remodeling in response to stress. Although it is proposed that HDACs additionally influence nuclear receptor signaling, the effect of class II HDACs on gender differences in cardiovascular disease remains unstudied. OBJECTIVE: We aimed to examine the effect of class II HDACs on post-myocardial infarction remodeling in male and female mice. METHODS AND RESULTS: Here we show that the absence of HDAC5 or -9 in female mice protects against maladaptive remodeling following myocardial infarction, during which there is an upregulation of estrogen-responsive genes in the heart. This genetic reprogramming coincides with a pronounced increase in expression of the estrogen receptor (ER)alpha gene, which we show to be a direct MEF2 target gene. ERalpha also directly interacts with class II HDACs. Cardioprotection resulting from the absence of HDAC5 or -9 in female mice can be attributed, at least in part, to enhanced neoangiogenesis in the infarcted region via upregulation of the ER target gene vascular endothelial growth factor-a. CONCLUSIONS: Our results reveal a novel gender-specific pathway of cardioprotection mediated by ERalpha and its regulation by MEF2 and class II HDACs.

Influence of chronic total occlusions on coronary artery bypass graft surgical outcomes.

BACKGROUND: Presence of epicardial coronary artery chronic total occlusion (CTO) predicts higher referral rates for coronary bypass graft surgery (CABG). However, the impact of coronary artery CTO on CABG outcomes has never been systematically studied. METHOD: We examined one-year outcomes in 605 consecutive Veterans, discharged post-CABG between June 2005 and December 2008. RESULTS: A coronary CTO was present in 256 patients (42%), predominantly (48.3%) in the right coronary artery distribution. Baseline clinical characteristics and medical therapy were similar in patients with and without a coronary CTO. A single CTO was present in 73.8%, and 26.2% patients had multiple CTO. All left anterior descending coronary artery CTO were successfully bypassed, as were >92% in left circumflex and right coronary arteries and 85% CTO in multiple coronary artery distributions. During the mean follow-up of 348.9 ± 4.5 days, incidence of all-cause death and myocardial infarction were similar in both groups (7.1% in CTO group and 7.4% in non-CTO group; p = 0.97). CTO >20 mm in length constituted 74.9% and >40 mm 37.8%. One-year survival post-CABG was significantly lower in patients with CTO lengths >40 mm compared to ≤20 mm (p = 0.04). CTO >40 mm was an independent predictor of post-CABG mortality controlling for age, number of CTO, comorbid diseases, clopidogrel use, severity of coronary artery disease, renal failure, and left ventricular ejection fraction. CONCLUSION: CABG achieves high success in grafting epicardial coronary vessels with CTO; however, presence of long coronary CTO (>40 mm) is an independent predictor of post-CABG survival.

Thoracoscopic management of empyema thoracis.

Appropriate management of empyema thoracis is dependent upon a secure diagnosis of the etiology of empyema and the phase of development. Minimal access surgery using video-assisted thoracoscopy (VATS) is one of many useful techniques in treating empyema. Complex empyema requires adjunctive treatment in addition to VATS.

Defining the clinical need and indications: who are the right patients for transcatheter mitral valve replacement.

Mitral regurgitation (MR) can be divided into two major etiologies, primary and secondary MR. Primary MR, also termed degenerative or organic MR, is a disease of the valve itself and is treated routinely by surgical repair in all but prohibitive risk patients. In these patients, transcatheter repair techniques, including edge to edge repair with the MitraClip device have been largely successful and widely adopted. Transcatheter placement of artificial chords has also been performed. The potential role for transcatheter mitral valve replacement (TMVR) in primary MR will likely be quite limited. Secondary or functional MR is due to a disease of the left ventricle and not the valve itself. The MR is a result of dilation of the left ventricle causing distraction of the papillary muscles with tethering of the mitral leaflets and lack of leaflet coaptation. Medical therapy is the mainstay treatment, with resynchronization used in appropriate patients. Surgical repair, usually with an undersized annuloplasty, is used in a limited number of patients. Transcatheter edge to edge repair is used extensively outside the US in secondary MR and is the subject of a pivotal trial in the US. However, it is in this group of patients with secondary MR that there is the largest clinical unmet need and, hence, the greatest potential opportunity for TMVR. At least ten TMVR platforms are in early feasibility, first in human, or preclinical trial stages. Four devices have cumulative early human experience in <100 patients. In this article, we discuss those patients most likely to benefit from TMVR and detail lessons learned from the first human studies regarding patient selection.

Should Transcatheter Aortic Valve Replacement Be Performed in Nonagenarians?: Insights From the STS/ACC TVT Registry.

BACKGROUND: Data demonstrating the outcome of transcatheter aortic valve replacement (TAVR) in the very elderly patients are limited, as they often represent only a small proportion of the trial populations. OBJECTIVES: The purpose of this study was to compare the outcomes of nonagenarians to younger patients undergoing TAVR in current practice. METHODS: We analyzed data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry. Outcomes at 30 days and 1 year were compared between patients ≥90 years versus <90 years of age using cumulative incidence curves. Quality of life was assessed with the 12-item Kansas City Cardiomyopathy Questionnaire. RESULTS: Between November 2011 and September 2014, 24,025 patients underwent TAVR in 329 participating hospitals, of which 3,773 (15.7%) were age ≥90 years. The 30-day and 1-year mortality rates were significantly higher among nonagenarians (age ≥90 years vs. <90 years: 30-day: 8.8% vs. 5.9%; p < 0.001; 1 year: 24.8% vs. 22.0%; p < 0.001, absolute risk: 2.8%, relative risk: 12.7%). However, nonagenarians had a higher mean Society of Thoracic Surgeons Predicted Risk of Operative Mortality score (10.9% vs. 8.1%; p < 0.001) and, therefore, had similar ratios of observed to expected rates of 30-day death (age ≥90 years vs. <90 years: 0.81, 95% confidence interval: 0.70 to 0.92 vs. 0.72, 95% confidence interval: 0.67 to 0.78). There were no differences in the rates of stroke, aortic valve reintervention, or myocardial infarction at 30 days or 1 year. Nonagenarians had lower (worse) median Kansas City Cardiomyopathy Questionnaire scores at 30 days; however, there was no significant difference at 1 year. CONCLUSIONS: In current U.S. clinical practice, approximately 16% of patients undergoing TAVR are ≥90 years of age. Although 30-day and 1-year mortality rates were statistically higher compared with younger patients undergoing TAVR, the absolute and relative differences were clinically modest. TAVR also improves quality of life to the same degree in nonagenarians as in younger patients. These data support safety and efficacy of TAVR in select very elderly patients.