Background-The results of angiographic studies have suggested that calcium channel-blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. Methods and Results-The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (Pϭ0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0.0126-mm decrease in the amlodipine group (Pϭ0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. Conclusions-Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.

Quantitative coronary arteriography has been shown to be useful in assessing the extent of coronary disease, its functional significance, and its response to therapeutic interventions. ed. The purposes of this investigation were (1) to assess the performance in vivo of a new, fully automatic, rapid coronary quantitation program by evaluating its accuracy compared with known stenosis dimensions in a range approaching dimensions likely to be encountered clinically and by comparing the analysis of biplane, on-line digital images to the analysis of cinearteriograms and (2) to determine the relationship between morphologic measurements and both predicted and measured coronary flow reserve. MethodsSixteen mongrel dogs weighing 21.4 to 40.9 kg were anesthetized with sodium pentobarbital (35 mg/kg), intubated, and ventilated with a Harvard ventilator. Supplemental oxygen and bicarbonate were administered and ventilatory rates were adjusted to maintain pH, Po2, and Pco2 within normal ranges. A left thoracotomy was performed in the fifth intercostal space and the heart was suspended in a pericardial cradle. The proximal left anterior descending and circumflex coronary arteries were dissected free and encircled by appropriately sized and calibrat-

This investigation was designed to determine whether the rate of isovolumic left ventricular pressure decline is affected by load in man. Fourteen patients were instrumented with micromanometer left ventricular and right atrial pacing catheters to maintain a constant heart rate during control conditions and infusion of methoxamine or nitroprusside. The isovolumic relaxation period was defined as the time from peak (-)dP/dt to 5 mm Hg above left ventricular end-diastolic pressure of the following beat. The rate of isovolumic relaxation was calculated as time constants (Tau) from the linear regression of natural log pressure vs time (Tln) and instantaneous (-)dP/dt vs pressure (TD), which includes a variable asymptote (PB). The mean heart rates and average (+)dP/dt values normalized at 40 mm Hg development pressure (DP40) did not differ significantly, despite 33% and 43% increases in left ventricular peak and end-diastolic pressures during the infusion of methoxamine (p less than .001 and p less than .01, respectively) and 24% and 29% decreases during the infusion of nitroprusside (p less than .001 and p less than .01, respectively). The average Tln and TD values were not significantly affected by these alterations in load. In two patients, an inverse linear relationship was demonstrated between decreases in Tau and increases in contractile state produced by an infusion of dobutamine, as shown by correlation of Tln and TD with (+)dP/dt/DP40 (r = -.88 and -.83, respectively). We conclude that the time constants of left ventricular isovolumic relaxation are unaffected by modest alterations in loading conditions in man when heart rate is maintained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary flow reserve, exercise thallium-201 scintigraphy and exercise radionuclide ventriculography were compared in 18 patients with chest pain and angiographically normal coronary arteries. Regional exercise thallium-201 perfusion was abnormal in three patients, regional exercise wall motion was abnormal in three other patients and results of both tests were abnormal in one additional patient. Left ventricular ejection fraction responses were abnormal in five of these seven patients. The coronary flow reserve of arterial distributions with abnormal perfusion or regional dysfunction was significantly lower than that of distributions associated with normal radionuclide results (1.42 +/- 0.23 versus 2.58 +/- 0.83, p less than 0.001). All patients with abnormal scintigraphic results had low coronary flow reserve (less than 1.95) in at least one distribution. Perfusion abnormalities appeared to be more localized in the arterial distributions with the lowest flow reserve. Only two patients had low flow reserve (less than 1.95) with normal scintigraphic results; both were hypertensive. These data suggest that abnormal exercise scintigraphic findings in patients with angiographically normal coronary arteries and chest pain are indicative of true blood flow or perfusion abnormalities.

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