The role of coronary microvascular dysfunction in the genesis of cardiovascular diseases

Positron emission tomography (PET) offers the unique capability of measuring specific flow (flow per unit of mass) in man by means of a regional, tridimensional, noninvasive approach. Using PET, myocardial perfusion abnormalities secondary to microvascular disorders have been investigated in arterial hypertension (AH), dilated and hypertrophic cardiomyopathy (CM), as well as in ischemic heart disease (CAD). In AH, regional perfusion at rest is within the normal range, while the coronary reserve and flow response to increase in metabolic demand are blunted. These flow abnormalities are independent of the degree of cardiac hypertrophy and the severity of AH; appropriate anti-ipertensive therapy is able to improve the perfusion abnormalities after long term treatment, independently of the effect on myocardial hypertrophy. Both dilated and hypertrophic CM demonstrate abnormal vasodilating capability, which has been shown to be present in the subclinical form of dilated DM; the reduction of coronary reserve is not related to the presence and extent of the hemodynamic impairment in dilated CM, and involves also nonhypertropied myocardium in asymmetric hypertrophic CM. These findings indicate a primary involvement of coronary microcirculation in non advanced forms of dilated and hypertrophic CM. Finally, in patients with CAD, myocardial territories supplied by angiographically normal coronary arteries show abnormal coronary reserve and flow during pacing tachycardia, indicating that, even in absence of epicardial coronary artery obstruction, microcirculation is impaired in subjects with coronary atherosclerosis. This abnormality can smooth perfusion differences between control and jeopardized regions. Accordingly, the absence of a perfusion defect during stress might indicate the presence of either a non significant stenosis or a diffuse impairment in microcirculatory function. Nuclear perfusion imaging with conventional perfusion tracers does not allow measurements of absolute blood flow, rather it provides an estimation of perfusion inhomogeneities. Although the agreement with the angiographic documentation of coronary artery disease has been frequently considered to characterize the diagnostic reliability of these techniques, the evaluation of myocardial perfusion provides an independent tool for the functional assessment of patient with heart disease. The possibility to obtain measurements of regional myocardial blood flow, provided by positron emission tomography, helps to identify the mechanisms affecting flow regulation in the myocardium. This tool thus provides a new rationale for the application of perfusion imaging, to obtain a more precise characterization of these patients, beyond the agreement with the morphological angiographic picture.