The advent of novel angiogenic therapies for ischemic heart disease has created the need for innovative strategies of ischemia detection that will accurately direct the application of these therapies in the settings in which they are administered. This investigation tests the accuracy of two new methods of ischemia detection, contrast echocardiography and endocardial catheter mapping of electromechanical coupling, as compared to established nuclear perfusion studies. Furthermore, it will test molecular and clinical measures of ischemia and inflammation is a component of all forms of heart failure. Patients with ischemic cardiomyopathy will each be evaluated by dobutamine thallium perfusion studies, adenosine sestaMIBI studies, contrast echocardiography, and endocardial catheter mapping of electromechanical coupling. The results of contrast echocardiography and endocardial catheter mapping will be compared to the two standard nuclear perfusion techniques to evaluate agreement in definition of zones of ischemia, infarction, and viable myocardium. A cohort of patients with ischemia cardiomyopathy and a matched group of patients with patent coronary arteries and left ventricular failure will under go endomyocardial biopsy. Quantification of gene expression of angiogenic factors, mediators of inflammation, and markers of left ventricular dysfunction will be performed by Real Time PCR on the endomyocardial biopsy samples. These measures will be compared between the two groups for evidence of similar ischemic and inflammatory mechanisms despite differences in coronary occlusive disease. The two groups will be compared in terms of the four clinical markers of ischemia to further test for the role of functional ischemia in patients with cardiomyopathy and patent coronary arteries as well as those with ischemic cardiomyopathy. A similar group of patients with and without patent coronary arteries will undergo seventy-two hour dobutamine infusions which purportedly augments subendocardial blood flow. This intervention serves as a model in which to test the relative capacity of the techniques examined in this protocol to detect significant changes in myocardial ischemia in these different patient groups. This protocol will thus provide the foundation for implementing effective novel measures of ischemia that provide immediate information for implementing effective novel measures of ischemia that provide immediate information for the targeting of and evaluation of response to novel angiogenic therapies in setting in which they are administered. This, in addition to the definition of a potential role of ischemia in all forms of heart failure, will amplify the role of these new strategies for revascularization making them feasible for a broad range of patients including those compromised by chronic ventricular systolic dysfunction.
| Doshi, Amit A; Ziolo, Mark T; Wang, Honglan et al. (2010) A promoter polymorphism of the endothelial nitric oxide synthase gene is associated with reduced mRNA and protein expression in failing human myocardium. J Card Fail 16:314-9 |
