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.

Hemodynamic effects of vasodilator therapy (phentolamine or nitroprusside) were studied in 38 patients with acute myocardial infarction (AMI). Cardiac metabolism was studied in 19 of the 38 patients. According to the initial level of left ventricular filling pressure (LVFP) and left ventricular stroke work index (SWI), patients were divided into three groups: Group I-nine patients with LVFP 15 mm Hg or less; Group II-14 patients with LVFP> 15 mm Hg and SWI > 20 g-m/m'; Group III-15 patients with LVFP > 15 mm Hg and SWI <20 g-m/m2. In Group I most patients were clinically uncomplicated. In Group IL most patients had clinical left ventricular failure including one patient who had clinical features of cardiogenic shock. Group III patients all had severe left ventricular failure, with eight patients in clinical shock.In all groups LVFP, pulmonary artery pressure, right atrial pressure, and systemic and pulmonary vascular resistance decreased significantly with vasodilator therapy with only a slight to moderate decrease in arterial pressure. In Group I patients SVI decreased (-7%) together with an increase in heart rate. Significant improvement in left ventricular performance, however, was observed in Groups II and III as indicated by increased stroke volume index (SVI) and cardiac index (CI) and decreased LVFP. The increase in SVI and CI was of similar magnitude in both Group LI (SVI +18%, CI +24%) and Group III (SVI +28%, CI +29%) patients, a change suggesting that vasodilation thereby may be applicable and beneficial even in the presence of severe depression of cardiac performance.Improved left ventricular performance in group II and III patients was accompanied by a slight decrease in coronary blood flow, myocardial oxygen consumption, and transmyocardial oxygen extraction. There was no change in myocardial lactate metabolism in any group. In vitro studies in isolated cat papillary muscle preparations showed no direct positive inotropic effect of either phentolamine or nitroprusside. Thus, significant improvement in left ventricular performance occurs during vasodilator therapy in patients with AMI and elevated LVFP, even in the presence of severe depression of cardiac performance. Furthermore, this improvement is not accompanied by increased metabolic cost. Vasodilator therapy, therefore, may have an important role in the treatment of pump failure complicating myocardial infarction. Additional Indexing W Cardiac metabolism Myocardial infarction Ventricular function curve Cardiogenic shock Myocardial oxygen consumption Left ventricular filling pressure Nitroprusside Phentolamine not improve the cardiac output.' Inotropic agents,

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Coronary CTA can be used to accurately predict the presence of obstructive disease in > 90% of small and moderate-sized calcified coronary artery plaques. With large calcified coronary artery plaques, CTA correctly predicts the presence of obstructive disease in approximately two thirds of the cases. When errors occur, they are usually due to overestimation of the degree of stenosis.

SUMMARY We developed a radioimmunoassay for plasma thromboxane B,, the metabolite of the coronary vasoconstrictor thromboxane A,. To see if thromboxane A, is produced during myocardial ischemia, we used atrial pacing to study 14 patients with greater than 75% occlusive coronary artery disease proved by arteriography. Paired samples were taken from the coronary sinus (CS) and an artery (A) for lactate and thromboxane B, analysis before pacing. During and after pacing at 140 beats/min, sampling was repeated. Before, during, immediately after and 10 minutes after pacing, percent myocardial lactate extractions (A-CS/A X 100) were 29.3 ± 3.7%, -21.1 ± 12.8%, -74.3 ± 20.3% and 25.1 + 3.5%, respectively (all changes p < 0.01). Before pacing, five patients had detectable coronary sinus or arterial thromboxane levels. During pacing, 18% and 40% increases occurred in coronary sinus and arterial blood, respectively (0.8 ± 0.1 to 0.9 ± 0.2 pmol/ml, and 0.5 0.2 to 0.7 ± 0.2 pmol/ml). Immediately after pacing, increases of 204% and 132% occurred in the coronary sinus and arterial blood (p < 0.05), respectively (2.3 ± 0.9 pmol/ml and 1.2 ± 0.4 pmol/ml). Ten minutes after pacing, thromboxane B, returned to prepacing levels. These data indicate that thromboxane A, is produced during pacing-induced myocardial ischemia and could alter regional coronary blood flow.ATRIAL PACING coupled with coronary sinus blood sampling has been used extensively to study angina pectoris.' During controlled tachycardia, induced myocardial ischemia is accompanied by increased concentrations of lactic acid,6 carbon dioxide,7 hydrogen ion,7 potassium6 and bradykinin.8 Fox et al.9 observed the release of adenosine from human hearts during angina induced by rapid atrial pacing. Subsequently, Berger et al.,10 in a similar experimental setting, reported the release of prostaglandin F from the coronary sinus during anginal provocation.Hamberg, Svensson and Samuelssonll described another prostaglandin, thromboxane A2, which has been found to have potent coronary vasoconstricting and platelet-aggregating ability.'2-14 Our development15 of a radioimmunoassay to measure thromboxane B,, the stable but inactive metabolite of thromboxane A2, led us to design an investigative protocol using rapid atrial pacing to determine if thromboxane release is involved in the cardiovascular response to ischemia. This study documents increases in both coronary sinus and arterial thromboxane B, concentrations during and after ischemia in patients with arteriographically proved, fixed coronary artery disease.Materials December of 1978 were studied by atrial pacing using a method previously reported,'6 followed by coronary arteriography and ventriculography. Descriptions of these patients are shown in table 1. All were judged to have unstable or accelerating angina pectoris and were candidates for emergency myocardial revascularization. After informed consent was obtained, catheterization of the coronary sinus was performed by means of a #7 Gorlin pacing catheter. An 18-gauge Te...