A S Iskandrian’s research while affiliated with Cardiovascular Research Foundation and other places

The determination or assessment of myocardial viability has, over the past decade, captured the imagination and interest of many investigators in basic and clinical research using state-of-the-art technologies such as PET, SPECT, MRI and two-dimensional echocardiography (2-DE). The emphasis in these studies has been to determine the absolute and comparative accuracy of these techniques. There are recent studies addressing the evaluation of the effect of viability assessment on patient outcome. The use of biochemical agents and other imaging methods in viability assessment is complex with many unresolved issues to be considered in the design and implementation of clinical protocols and in routine patient care.

This study examined the effects of inira-aortic balloon counterpulsation on left ventricular (LV) performance in 12 patients with coronary artery disease (CAD) using a multiwire camera and Ta178 (tVi'9.5 min). First-pass radionuclide angiograms were obtained at baseline, 1:1 and 1:2 balloon pumping at both 50% and 100% balloon inflation. The changes in LV ejection fraction (EF), cardiac output (CO by (hermodilution); peak filling rate (PFR, EDV/sec); puhnonary artery diastolic pressure (PAD); aortic systolic (AO) and augmented diastolic pressure (AD) are shown in the table. 100 50 Bastlint lil IS 1-1 IS? PAD 26±10 23±9 25±9 25±H 24±10 LVEF 37±15 42±10% 34±11 36±13 36±13 PFR 2.0±0.6 2.2±0.6 1.7±0.4 1.8±OJ 1.8±0.7 AO 109±12 99±J8 101±19 101±17 107±19 AD 66±11 112±12' 116±13< 95±15 93±12 P < O.OS vs 50% inflation The results show that 1:1 counterpulsation at 100% inflation produced improvement in both systolic and diastolic LV performance. These effects were not seen with other modes of counterpulsation. Thus, intra-aortic balloon counterpulsation results in improvement in systolic and diastolic LV performance in patients with CAD at a set up of 100% inflation and 1:1 counterpulsation. These effects are not seen with 1:2 counterpulsation or with 50% balloon inflation. The multiwire camera and short half-lived Ta-178 is ideally suited for these serial measurements at the bedside.

To examine coronary revucularization and consider improvement of outcome of patients (pts) with one or two occluded coronary arteries and no significant stenosis in the remaining artery, we examined the events in 115 such pts with normal left ventricular function, no previous myocardial infarction or coronary revascularizatioD (Group 1) and 227 pts with prior myocardial infarction (Group 2), There were 90 pts with one- and 25 pts with two-vessel occlusion in Group 1 and 164 pts with one- and 63 pts with two-vessel occlusion in Group 2. During a mean follow-up of 60 months, there were 3 deaths and 6 myocardial infarctions in Group 1, and 14 deaths in Group 2. The pts with events did not differ from those without: in number of occluded arteries, collaterals, age, diabetes mellitus, hypertension or medications. Thus, the event rate was low in pts with one- or two-vessel occlusions and normal left ventricular function (death 0.5%/year and myocardial infarction 1.5%/year). Even in pts with left ventricular dysfunction, the death rate was only 1.2%/year. Coronary revascularization is unlikely to improve survival in such pts and, thus, should be reserved for those with serious symptoms.

Iodine-123-phenylpentadecanoic acid (IPPA) is a synthetic fatty acid suitable for myocardial imaging. This study is the result of a Phase I/II trial to evaluate IPPA's ability to predict functional recovery in patients undergoing coronary revascularization. Twenty-three patients with documented coronary disease underwent sequential SPECT imaging with IPPA before and radionuclide ventriculography both before and 8 wk after revascularization. Software was developed to evaluate myocardial IPPA metabolism and to determine the fraction of the left ventricle with intermediate metabolism. There was a significant correlation between initial IPPA uptake and final LVEF. The fractional area of the left ventricle demonstrating IPPA metabolism in the intermediate metabolic range was significantly higher in patients who demonstrated a 5% or greater increase in EF after revascularization (0.90 +/- 0.08 versus 0.78 +/- 0.17, p = 0.04). When only the patients who received complete revascularization were evaluated, there was a more significant difference (improved 0.92 +/- 0.05 versus 0.74 +/- 0.17, p = 0.011). Taking a lower limit of 1 s.d. from the mean, (87%) the six patients who had > or = 5% increase in LVEF after revascularization had more than 87% of the left ventricle in the intermediate metabolic range, whereas seven of ten patients whose change in LVEF was < 5% had less than 87% in the intermediate metabolic range (p = 0.011). In this initial experience, the amount of myocardium in the intermediate metabolic range is associated with improvement in LVEF after revascularization, especially in patients receiving complete revascularization.

Myocardial viability is a clinically important issue in patients after acute myocardial infarction and in patients with left ventricular dysfunction in the presence or absence of symptoms. With these broad criteria, roughly 10% to 20% of patients with coronary artery disease will be suitable candidates for myocardial viability studies. Techniques that predict improvement in regional or global left ventricular function must be able to detect hibernating myocardium. The improvement observed following coronary revascularization represents a complex interaction between compensatory mechanisms, coronary anatomy, surgical outcome and patient selection.

Adenosine myocardial perfusion imaging is useful in diagnosis of coronary artery disease (CAD) and risk assessment in patients who have exercise limitations. As a pharmacologic stressor, adenosine acts on two cell-surface purine receptors, A1 and A2. Activation of A2 receptors cause coronary vasodilation. Unlike other pharmacologic stressors, such as dipyridamole and dobutamine, adenosine is an endogenous biochemical. Adenosine perfusion studies have a relatively high sensitivity and specificity (80%-90%) for identifying CAD. Images from adenosine studies are comparable to, or better than, images from exercise myocardial perfusion studies. The side effects are common, but not serious; they are short-lived and rarely require the administration of aminophylline.

There are currently four common types of stress used with thallium-201 imaging in the diagnosis of coronary artery disease and risk assessment. The objective of this study was to examine the thallium biokinetics during exercise, adenosine, dipyridamole and dobutamine stress testing in 15 healthy volunteers. Each subject underwent planar 201Tl imaging during maximal treadmill exercise testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40 micrograms/kg/min). Absolute myocardial thallium activity was greater after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517 counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and liver were also greater with pharmacologic stress testing than exercise (p < 0.05). Thus, thallium biokinetics are different during pharmacologic stress testing with adenosine, dipyridamole and dobutamine than during exercise. Diagnostic criteria for quantitative analysis of myocardial perfusion imaging must therefore be specific for the type of stress used.