Oberdan Parodi

“Variant” angina: One aspect of a continuous spectrum of vasospastic myocardial ischemia: Pathogenetic Mechanisms, Estimated Incidence and Clinical and Coronary Arteriographic Findings in 138 Patients☆

Abstract From January 1970 to December 1977, transient reversible episodes of S-T segment elevation were documented in 138 patients (80 with angina only at rest, 58 with angina both on exertion and at rest). Electrocardiographic monitoring in 33 patients with hemodynamic monitoring revealed that (1) during 6,009 transient episodes of myocardial ischemia, pain was always a late phenomenon and, in some patients, often did not occur; (2) during such transient episodes, ST-T wave behavior was often variable in the same patient with alternation of elevation, depression or only T wave changes with or without pain; (3) independent of the direction of the S-T segment and T wave changes, the episodes were never preceded by an increase of the hemodynamic determinants of myocardial demand but were associated with obvious impairment of left ventricular function. Thallium scintigraphy in 32 patients revealed a regional massive and localized reduction of myocardial perfusion during S-T segment elevation and pseudonormalization of T waves. During S-T segment depression the reduction of thallium uptake was diffuse with fuzzy limits. Coronary angiography revealed no significant stenosis in 8 patients and single, double and triple vessel disease in 38, 34 and 26 patients, respectively. Angiography in all 37 patients studied during angina revealed a severe coronary vasospasm involving vessels with extremely variable extent of atherosclerosis. Severe arrhythmias were recorded in 27 patients, and a myocardial infarction occurred in 28. A total of five patients died within 1 month of hospital admission. Thus, variable intensity and extension of coronary vasospasm and the presence of collateral vessels may result in different degrees of ischemia and various electrocardiographic patterns with or without anginal pain. Vasospastic angina can occur in the presence of extremely variable degrees of coronary atherosclerosis and in any phase of ischemie heart disease. It may evolve into acute myocardial infarction and sudden death: Variant angina appears to be only its most striking electrocardiographic manifestation. When vasospastic angina is appropriately searched for, its incidence rate appears to be high.

Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction" angina.

To investigate the pathogenesis of myocardial infarction we undertook a systematic study of patients with angina at rest, a syndrome known to evolve frequently into infarction. Among 187 consecutive patients, 37 had infarction, all in the area that showed electrocardiographic changes during angina. In all 76 patients who underwent hemodynamic monitoring, 201thallium myocardial scintigraphy or angiography during angina, a vasospastic origin of the attacks was documented. In six patients with infarction shortly after these studies and in two in whom the infarction developed during hemodynamic monitoring or during angiography the onset of infarction was indistinguishable from the onset of anginal attacks. One patient in whom spasm was observed at the onset of infarction died six hours later; at post-mortem examination, a fresh laminar thrombus was found at the site of the spasm. After infarction, complete thrombotic occlusion of the branch shown to undergo vasospasm was documented in two patients by angiography.

Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: A study with nitrogen-13 ammonia and positron emission tomography

To assess regional coronary reserve in hypertrophic cardiomyopathy, regional myocardial blood flow was measured in 23 patients with hypertrophic cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and dynamic positron emission tomography. In patients with hypertrophic cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/- 0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and 0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the nonhypertrophied (10 +/- 2 mm) left ventricular free wall. These were not statistically different from the corresponding values in control subjects (1.04 +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS). After pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg intravenously over 4 min), regional myocardial blood flow in patients with hypertrophic cardiomyopathy increased significantly less than in control subjects both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than 0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p less than 0.001). In addition, patients with hypertrophic cardiomyopathy who had a history of chest pain had more pronounced impairment of coronary vasodilator reserve than did those without a history of chest pain. After dipyridamole, coronary resistance in the septum decreased by 38% in patients without a history of chest pain, but decreased by only 14% in those with such a history (p less than 0.05). Coronary resistance in the free wall decreased by 45% in patients without and by 27% in those with a history of chest pain (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

CORONARY VASOSPASM IN ANGINA PECTORIS

Abstract Coronary angiography was performed during 34 anginal attacks in thirty patients admitted because of recurrent angina at rest. Nineteen (seventeen with S-T segment elevation and two with S-T depression) had angiograms during a spontaneous attack, eleven (nine with S-T elevation and two with S-T depression) during an attack induced by intravenous ergonovine maleate. Control coronary angiograms showed a wide range of atherosclerotic obstruction, from normal vessels to severe triple-vessel disease. During the anginal attack, all patients with S-T segment elevation had vasospasm localised to one of the major branches, often resulting in complete occlusion. Attacks with S-T segment depression were seen only in patients with double or triple vessel disease, and here the vasospasm generally affected coronary branches without causing complete occlusion. When appropriately searched for, vasospastic angina seems to be common.

Value of rest thallium-201/technetium-99m sestamibi scans and dobutamine echocardiography for detecting myocardial viability

The relation between radioisotopic and echocardiographic markers of myocardial viability and postrevascularization recovery of function is still to be defined. To this purpose, 14 patients (11 men, 3 women, aged 35 to 64 years, mean 54 +/- 7) with ventricular dysfunction were studied by a multiparametric approach. Each patient underwent, on separate days, rest thallium-201 and technetium-99m sestamibi scintigraphy, dobutamine echocardiography and coronary angiography. Coronary angiography was analyzed by a quantitative approach. Thallium uptake at rest was quantified from planar early (10-minute) and delayed (16-hour) thallium-201 images and expressed as a percentage of maximal activity in each projection using a 13-segment model. Sestamibi uptake was expressed in the same way. Dobutamine (up to 10 micrograms/kg/min) echocardiography was analyzed using a score index ranging from 1 (normokinesia) to 4 (dyskinesia) and a similar segmental model. Before revascularization 50 segments were grouped as normal (coronary stenosis < 50% and normal function, group 1); of the remaining 132 segments with > 50% coronary stenosis, 57 had normal wall motion (group 2) and 75 showed regional dyssynergies (group 3). Early and delayed thallium-201 regional percent activities did not differ in group 1 and in group 2 but were significantly less in group 3 segments. Sestamibi percent activity was more in group 1 and significantly reduced both in group 2 and 3 segments. Segments with improved wall motion after dobutamine had more early, delayed thallium-201 and sestamibi percent activities than unresponsive segments. Postrevascularization echocardiography was performed in all patients. Delayed thallium-201 scans and dobutamine echocardiography showed good sensitivity and specificity in detecting viable myocardium. (ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial Blood Flow Response to Pacing Tachycardia and to Dipyridamole Infusion in Patients With Dilated Cardiomyopathy Without Overt Heart Failure A Quantitative Assessment by Positron Emission Tomography

BACKGROUND Myocardial blood flow (MBF) impairment has been documented in advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to severe ventricular dysfunction, may limit myocardial perfusion. To assess whether MBF impairment in DCM may also be present independent of hemodynamic factors, the present study was designed to quantify myocardial perfusion in patients with mild disease without overt heart failure. METHODS AND RESULTS Absolute regional MBF (milliliters per minute per gram) was measured by positron emission tomography and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in 13 healthy subjects. Patients were in New York Heart Association functional class I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg; range, 2 to 20 mm Hg). There were no differences in arterial blood pressure, heart rate, and rate-pressure product between patients and control subjects in the three study conditions. Compared with control subjects, DCM patients had lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P < .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min-1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/- 0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end-diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P < .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely depressed both at baseline and in response to stress. CONCLUSIONS In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

Management of unstable angina at rest by verapamil. A double-blind cross-over study in coronary care unit.

A therapeutic trial with verapamil, a calcium-antagonist drug, was performed in 12 patients admitted to our coronary care unit because of frequent daily attacks of angina at rest attributed to coronary vasospasm. After a 48-hour run-in period, oral verapamil 480 mg/day and placebo were administered alternately during 4 randomised 48-hour periods. Transient ischaemic attacks with ST segment elevation or depression, with or without pain, were documented by continuous electrocardiographic monitoring. The number of attacks during the run-in and 2 placebo periods were 128, 123, and 130, respectively, and 31 and 23 during the 2 treatment periods (P less than 0.006 and P less than 0.003). This drug therefore appears to be effective in the management of patients with frequent attacks of angina at rest.

Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of spasm in the pathogenesis of ischemic heart disease

Abstract The role of coronary arterial vasospasm in the pathogenesis of ischemic heart disease is reviewed on the basis of investigations carried out in our laboratory. Patients were selected because they had angina either at rest or both at rest and during exercise. With continuous hemodynamic and electrocardiographic monitoring of these patients, as well as thallium-201 scintigraphy and coronary arteriography during ischemic episodes, we were able to demonstrate a vasospastic origin for the attacks. During anginal episodes, electrocardiographic changes were variable, with S-T segment elevation, S-T segment depression, a rise in T wave potential and pseudonormalization of inverted T waves corresponding to various distributions of myocardial ischemia in different patients and even in the same patient at different times. Increases in hemodynamic variables that control myocardial oxygen consumption never preceded the onset of ischemic episodes, which challenges the theory that the limitation of a possible increase in flow caused by critical organic stenosis is the only cause of myocardial ischemia. In some patients in whom myocardial infarction developed, the lesion was always found in the same area in which the vasospastic phenomena had been seen angiographically. Vasospasm led to serious arrhythmias in some patients. We therefore believe that independent of atherosclerosis or superimposed on it, vasospasm plays an important role in producing myocardial ischemia—angina, myocardial infarction and possibly sudden death. Elucidation of its mechanisms will lead to more appropriate therapy.

Cardiac emission computed tomography: underestimation of regional tracer concentrations due to wall motion abnormalities

Possible effects of regional wall motion abnormalities on apparent regional myocardial tracer concentrations on emission tomographic images were evaluated in six open chest dogs. Each dog was studied twice: In Run 1, 13N ammonia and microspheres were injected during a 6 min coronary occlusion, and serial images acquired by positron emission tomography during occlusion and reperfusion. In Run 2, 1 h later, 13N ammonia and microspheres were reinjected at control, and serial images recorded at control, during a repeat 6 min coronary occlusion, and after reperfusion. Segmental function was monitored with ultrasonic crystals, and 13N tissue concentrations determined in vivo from the tomographic images and postmortem by well counting. In Run 1, fractional shortening in ischemic segments fell by 89 ± 16% SD from control. The ischemic versus control segment ratio for 13N activity concentrations averaged 0.29 ± 0.08 and for microspheres 0.20 ± 0.15. In Run 2 the ischemic versus control segment ratio was at control 0.77 ± 0.12 for 13N tissue activity and 0.85 ± 0.07 for microspheres. Fractional shortening fell during occlusion by 131 ± 29% from control, returned to control early, and fell again by 11 ± 16% late during reperfusion. These changes were paralleled by changes in apparent regional 13N tissue concentrations of the prelabeled myocardium. Compared with control, they were 37 ± 9% lower during occlusion and rose to 94 ± 20% early and to 89 ± 16% at control late during reperfusion. In vitro determined tissue concentration ratios of ischemic to control myocardium were similar for 13N and microsphere activity (0.83 and 0.85), which ruled out loss of 13N ammonia from tissue during occlusion or reperfusion. Our results indicate that regional wall motion abnormalities cause artifactual segmental defects in tracer concentrations on emission tomographic images of the heart, which must be considered for qualitative and quantitative analysis of regional tracer tissue concentrations.