Impaired Coronary Flow Reserve in NIDDM: A Possible Role for Diabetic Cardiopathy in Humans

Abstract

Diabetic cardiopathy represents a cardiac disorder with involvement of myocardial, interstitial, coronary, and neural structures. One of the main manifestations refers to coronary microangiopathy, which has not yet been clearly identified. Coronary hemodynamics, including the determination of coronary flow reserve, were therefore analyzed in normal subjects and in nine patients with NIDDM and clinically suspected coronary heart disease but normal coronary arteriogram. Coronary flow reserve was determined as the quotient of baseline and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood flow was measured quantitatively by the argon method. Systolic left ventricular function was analyzed by ventriculography and diastolic function by M-mode and Doppler echocardiography. Twelve healthy normotensive subjects served as the control group (CON). In the diabetic patients, maximal coronary flow was significantly reduced (172 +/- 50 vs. 395 +/- 103 ml/min x 100 g; P < 0.001), and minimal coronary resistance was increased (0.60 +/- 0.19 vs. 0.24 +/- 0.06 mmHg x min x 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was markedly reduced (1.84 +/- 0.39 vs. 4.23 +/- 0.52; P < 0.001). No difference existed with respect to myocardial oxygen consumption (12.4 +/- 2.3 vs. 11.8 +/- 2.8 ml O2/100 g x min; NS). Global systolic function was normal in all patients (ejection fraction: NIDDM 72 +/- 13 vs. CON 77 +/- 12%, NS; CI: NIDDM 3.2 +/- 0.8 vs. CON 3.3 +/- 1.2 l/min x m2, NS). Diastolic function was impaired in diabetic patients with an increase in relaxation time index (97 +/- 23 vs. 45 +/- 18 ms; P < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between early and late transmitral flow (0.75 +/- 0.14 vs. 1.66 +/- 0.13; P < 0.05). We conclude that the markedly reduced coronary flow reserve in diabetic patients may play a key role in the induction and perpetuation of coronary insufficiency in myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation of diabetic cardiopathy.

Global myocardial perfusion and diastolic function are impaired to a similar extent in patients with type 2 diabetes mellitus and in patients with coronary artery disease—evaluation by contrast echocardiography and pulsed tissue Doppler

“…This limitation is particularly disadvantageous, as the diabetic heart works on a higher level of oxygen demand than the heart of CAD patients, at least as reflected by the rate-pressure product. Our observation that myocardial blood flow during stress and coronary flow reserve are also reduced is in line with the above findings, confirming observations by PET and angiography [10][11][12]. A noteworthy observation, and one not shown before, was that global perfusion in patients with macrovascular CAD was impaired to the same extent as in diabetic patients with microvascular disease (Fig.…”

“…Both abnormalities have also been observed in patients with type 1 and type 2 diabetes using techniques like traditional echocardiography [8,9], angiography and positron emission tomography [10][11][12]. However, there is a lack of evidence-based treatment strategies for these abnormalities in the diabetic heart, probably because the techniques mentioned above are not well suited for sequential studies after pharmacological intervention.…”

Optimum Hypoglycemic Therapy can Improve Coronary Flow Velocity Reserve in Diabetic Patients-Demonstration by Transthoracic Doppler Echocardiography-

“…The baseline CFVR values in this study were concordant with the results of previous studies using positron emission tomography 2,6,7,14,15 and Doppler guidewire. 3,4,16 Coronary microvascular abnormalities and endothelial dysfunction have been reported in diabetic patients even with normal left ventricular systolic function and angiographically normal coronary arteries, 4 and several mechanisms have been suggested to explain the impaired coronary vasodilatory function in diabetic patients, 6 including hyperglycemia, hyperinsulinemia, 7 advanced glycosylation end-products and lipoprotein modification.…”

Detection of myocardial microvascular disease using contrast echocardiography during adenosine stress in type 2 diabetes mellitus: Prospective comparison with single-photon emission computed tomography

“…Changes in myocardial microvasculature in diabetic patients have been demonstrated by histopathological studies 19 and by invasive studies which have shown maximal coronary blood flow reserve and impaired endothelialdependent epicardial coronary vasodilatation. 2,20,21 Furthermore, non-invasive functional studies involving PET have shown significant impairment of MBF during dipyridamole stress in patients with diabetes. 4 In this study, we used a method to determine MCEderived MBF in absolute units of blood volume per time in relation to myocardial mass (ml/min/g) which has been recently developed by Vogel and colleagues.…”

“…These include morphological 1 and functional abnormalities on non-invasive or invasive imaging. [2][3][4][5] Myocardial contrast echocardiography (MCE) utilises compressible membrane-stabilised microbubbles containing gas, which behaves similarly to red blood cells, rendering them an excellent tracer for blood flow measurements. Destruction of microbubbles and observation of the gradual refill into the myocardium is the foundation for the evaluation of myocardial perfusion using real-time MCE.…”