Decreased levels of BAG3 in a family with a rare variant and in idiopathic dilated cardiomyopathy.

The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy

Early experience with minimally invasive direct coronary artery bypass grafting with the internal thoracic artery

AbstractObjective: Minimally invasive direct coronary artery bypass is performed under direct vision without sternotomy or cardiopulmonary bypass. The technique can be used in both primary and reoperative cases by employing the internal thoracic artery to perform arterial revascularization of the anterior surface of the heart. Methods: Patients were selected who had significant coronary artery disease limited to 1 or 2 coronary distributions on the anterior surface of the heart. Coronary target vessels were grafted with the internal thoracic artery through a small anterior thoracotomy. After partial heparinization the anastomosis was facilitated by local coronary occlusion and handheld stabilization. Results: Between August 1994 and July 1997, 162 patients underwent minimally invasive direct coronary artery bypass grafting with the internal thoracic artery. The left and right internal thoracic arteries were used for grafting of the left anterior descending artery in 142 patients (88%), the proximal right coronary artery in 7 patients (4%), existing saphenous vein grafts in 5 patients (3%), and diagonal branches in 2 patients (1%). Sequential grafting with the left internal thoracic artery was performed in 2 patients (1%) and bilateral internal thoracic artery grafting was performed in 4 patients (3%). Eight patients (4.9%) died within 30 days after the operation, 3 of cardiac causes. Seven additional patients died during the follow-up period. Nine patients (5.6%) required reintervention for graft stenosis or occlusion during follow-up. Of 141 patients seen 2 or more weeks after the operation, 135 (96%) had resolution of their anginal symptoms at a mean follow-up of 12 months (range 0-31 months). Conclusions: Anterior minimally invasive direct coronary artery bypass grafting with the internal thoracic artery avoids the risks of repeated sternotomy, aortic manipulation, and cardiopulmonary bypass. There was a low rate of reintervention, and patients had excellent resolution of anginal symptoms. Postoperative length of stay was comparatively short, and continued follow-up will be essential to evaluate long-term graft patency and patient survival. (J Thorac Cardiovasc Surg 1999;117:873-80

Fibrinolytic activity after vessel wall injury

AbstractThe goal of this study was to assess fibrinolytic activity after vessel wall injury and to correlate changes in fibrinolytic activity with angiographic and histologic findings. Accordingly, in 18 atherosclerotic rabbits, vessel wall injury was produced by means of iliac artery balloon angioplasty (the injury group), whereas 8 atherosclerotic rabbits served as a control group. In all rabbits from the injury group, deep vessel wall injury was documented by either angiography or histologic study. Plasminogen activator inhibitor-1 activity in plasma increased significantly, from 21.79 ± 1.29 arbitrary units/ml (AU/ml) at baseline study to 32.05 ± 1.47 AU/ml at 6 h after vessel wall injury (p < 0.01), whereas activity remained unchanged throughout the 24h period in the control group. Plasma levels of tissue plasminogen activator activity were similar in both groups. Intravascular thrombus was found in five of six additional rabbits 6 h after vessel wall injury, that is, at the time of impaired fibrinolytic activity, whereas no thrombus was found in the control group (p < 0.05).It is concluded that deep vessel wall injury is associated with reduced fibrinolytic activity. In addition to other procoagulant factors, elevated plasminogen activator inhibitor-1 activity may lead to intravascular thrombosis and impaired resolution of thrombus