Vidya S. Banka

Nitroglycerin to Unmask Reversible Asynergy Correlation with Post Coronary Bypass Ventriculography

The value of nitroglycerin in determining the potential reversibility of asynergy was examined in 35 patients with coronary heart disease. Ventriculograms performed at rest and after sublingual nitroglycerin were analyzed for (1) location of asynergy relative to distribution of the 3 major coronary arteries and (2) severity of asynergy. Of the 41 hypokinetic zones, 30(73%) improved following nitroglycerin. Of 28 akinetic zones, 16 (57%) improved (7 of the 16 segments becoming normal) following nitroglycerin. None of 7 dyskinetic zones showed change following nitroglycerin. Twelve patients were restudied following coronary bypass surgery. There was an excellent over-all correlation between the segments that responded to nitroglycerin and bypass surgery in those segments with open grafts. Eighteen segments which improved following nitroglycerin had patent postoperative grafts, and in 15 segments there was a corresponding improvement following bypass surgery. Two segments which were unresponsive to nitroglycerin preoperatively had patent postoperative bypass grafts. Neither segment improved despite graft patency. In summary, sublingual nitroglycerin is useful in unmasking residual contractile ability in asynergic zones. A positive response to nitroglycerin appears to be predictive of corresponding beneficial effect from a coronary bypass graft. The data strongly suggest that the use of nitroglycerin to determine residual contractile ability may be of considerable value in better defining the potential risks and benefits of coronary bypass surgery.

Reversible asynergy. Histopathologic and electrographic correlations in patients with coronary artery disease.

Histopathologic-electrographic studies of ventriculography depicted nitroglycerin responsive and unresponsive asynergic areas were performed in 25 patients. Of 29 areas, 12 improved with nitroglycerin, showing < 10% muscle loss. Seventeen unimproved zones demonstrated significant fibrosis. Epicardial electrograms showed R waves in eight of nine improved zones. Of 11 unimproved zones, eight had Q waves.Histopathologic-electrographic data from five responders showed < 10% muscle loss, of whom four had epicardial R waves. Six unresponsive areas had significant fibrosis, with a QS over four.Thus, nitroglycerin responsive asynergic areas are generally comprised of histologically intact myocardium and are associated with epicardial R waves.

Electrophysiologic effects of coronary occlusion and reperfusion. Observations of dispersion of refractoriness and ventricular automaticity.

UNLABELLED In order to determine the electrophysiological changes that occur during coronary occlusion and following reperfusion, 19 mongrel dogs were studied. Refractory periods were determined by the extrastimulus method in nonischemic and ischemic zones prior to and after variable periods of left anterior descending artery occlusion and reperfusion. After 15-30 minutes of occlusion, refractory periods in the nonischemic zones remained unchanged while in the ischemic zone they shortened by 17%, resulting in a dispersion of refractoriness. Within three minutes of reperfusion, arrhythmias appeared together with a marked directional change of refractory periods to a prolongation by 34% (P less than 0.001) in the ischemic zone and by 3% (P less than 0.02) in the nonischemic zone. Refractory periods returned to baseline values after 60 minutes of reperfusion. After 60-90 minutes of occlusion, refractory periods in the nonischemic zones were unchanged whereas in the ischemic zone they demonstrated a decrease by 28% (P less than 0.01), again resulting in a dispersion of refractoriness. Within five minutes of reperfusion, refractory periods in the ischemic zone prolonged by 44% (P less than 0.001). Similar but smaller directional changes were also seen in nonischemic zones. Concomitant with the observed prolongation in refractory periods frequent ventricular ectopic activity was again documented. In addition, refractory periods did not return to control values after periods of observation up to 120 minutes in this group. In seven dogs, complete heart block was induced to ascertain the rate of idioventricular pacemaker and the effect of ventricular overdrive on the escape interval. Control ventricular rates (53.3 +/- 5.7 beats/min) remained unchanged (52.3 +/- 5.6) following coronary occlusion, but decreased to 48.0 +/- 4.4 (P less than 0.05) during reperfusion. Mean control escape intervals (1.8 +/- 0.2 sec) did not change after occlusion (1.7 +/- 0.2 sec) but prolonged to 2.1 +/- 0.2 sec (P less than 0.05) following reperfusion. IN CONCLUSION 1) sudden prolongation in refractory periods following reperfusion leads to an overshoot resulting in a dispersion of refractoriness temporally related to the onset of ventricular arrhythmias and 2) re-entry, and not enhanced automaticity, appears to be the mechanism for postperfusion arrhythmias.

Detection of coronary heart disease using radionuclide determined regional ejection fraction at rest and during handgrip exercise: correlation with coronary arteriography.

SUMMARY The detection of regional asynergy provides strong evidence for a critical reduction of coronary blood flow to that zone. In the present study, the usefulness of combining computer-assisted radionuclide angiography and isometric handgrip exercise testing to detect coronary heart disease (CHD) was evaluated. One hundred twenty-nine patients with chest pain undergoing cardiac catheterization were evaluated using radionuclide angiography. Thirty-four patients were found to have severe contraction abnormalities during the initial radionuclide angiographic study. Of these, 33 had significant CHD. Ninety-five patients had normal or borderline normal left ventricular contraction and therefore underwent a second radionuclide angiogram during handgrip. Radionuclide angiogram data were quantitatively analyzed by computer to determine regional left ventricular contribution to ejection fraction during handgrip stress. Of the 95 patients, 30 had normal coronary arteries of whom 26 (87%) had normal relative regional ejection fraction. Sixty-five patients had CHD; 20 had single and 45 had two or three vessel obstructive disease. Of the 20 with single vessel disease, 16 (nine at rest and an additional seven during handgrip) had an area of decreased relative regional ejection fraction ranging from 31-87% in the corresponding segment during radionuclide angiography. Of the 45 patients with two or three vessel disease, 40 had regional abnormalities in ejection fraction during handgrip of from 31-100% (24 at rest and an additional 16 during handgrip). Moreover, 24 of these patients had multiple abnormalities in relative regional ejection fraction indicating multivessel disease. Overall, of the 95 patients who underwent isometric handgrip stress, sensitivity was 86% for detection of CHD and specificity was 87% for accurately defining the patients with normal coronary arteries.The results of the present study suggest that the radionuclide angiographic assessment of relative regional ejection fraction during isometric handgrip exercise may provide a useful new diagnostic approach for patients with suspected CHD as well as providing important additional data concerning its location and severity.

Determinants of Reversible Asynergy Effect of Pathologic Q Waves, Coronary Collaterals, and Anatomic Location

To determine which factors may be of value in determining whether or not asynergic zones have residual contractile ability, the responsiveness of these zones to sublingual nitroglycerin (1/150 grs) was studied angiographically in 36 patients. The responsiveness of asynergy was correlated with the presence or absence of pathologic Q waves and coronary collaterals in the corresponding zones, as well as with anatomic location. Of the 25 asynergic segments which had corresponding pathologic Q waves, 11 (44.0%) responded to nitroglycerin while 14 (56%) remained unresponsive. In contrast, 30 (83.3%) of the 36 segments which did not have associated Q waves improved while only 6 (16.4%) did not (P < 0.005). Akinetic segments with Q waves were associated with a significant decrease in responsiveness (P < 0.02) compared to hypokinetic segments. Of the 26 segments with angiographically demonstrable collaterals, 22 (84.6%) improved and only 4 (15.4%) remained unchanged (P < 0.02). In contrast, of the 35 segments without collaterals, 19 (54.3%) were responsive and 16 (45.7%) did not respond. Seven (77.8%) of the 9 akinetic segments with collaterals exhibited improvement compared to only 5 (33%) of the 15 segments without collaterals (P < 0.05). In segments with pathologic Q waves, 70% of those associated with collaterals improved compared to only 27% without collaterals (P < 0.02). Relative to anatomic location, of 29 anterior wall segments, 24 (82.8%) responded compared to only 11 (45.8%) of 24 apical segments (P < 0.005). These data indicate that the presence of coronary collaterals and absence of pathologic Q waves in the corresponding zones are associated with a higher incidence of residual contractile ability of asynergic segments. Apical asynergy responds less frequently than asynergy in other anatomic zones.

Limitations of myocardial revascularization in restoration of regional contraction abnormalities produced by coronary occlusion

Abstract The effect of reperfusion instituted from 30 minutes to 3 hours after coronary occlusion on the contractile characteristics of the ischemic zone, border zone and nonischemic myocardium was studied in 29 dogs using Walton-Brodle strain gauge arches and mercury-in-Silastic ® tubing segment length gauges. After 30 and 45 minutes of coronary occlusion, reperfusion resulted in an immediate reversal of abnormalities in segment length and tension of the ischemic zone to near normal. Preejection tension Increased from 32.3 ± 5.1 to 95.2 ± 4.7 percent of control level, ejection tension from zero to 71.7 ± 7.0 percent, total tension from 27.5 ± 2.5 to 87.1 ± 6.2 percent and dT dt from 42.1 ± 4.1 to 100.0 ± 4.5 percent. Phasic segment length decreased from 150.2 ± 5.1 percent to 100.0 ± 5.0 percent of control value. Aneurysmal bulging disappeared completely. However, after 1 hour of coronary occlusion, reperfusion resulted In a significant ( P decrease in all contraction variables In the ischemic zone. Preejection tension decreased from 58.7 ± 7.9 to 31.2 ± 5.5 percent, ejection tension decreased initially but recovered to prereperfusion levels, total tension decreased from 48.5 ± 5.9 to 24.0 ± 4.0 percent and dT dt declined from 60.7 ± 7.2 to 30.9 ± 5.7 percent of control levels. Phasic segment length gradually decreased from 162.5 ± 6.0 to 137.5 ± 12.5 percent of control value. The border zone exhibited similar decreases in function In four studies, and improved in two. After 2 and 3 hours of coronary occlusion, reperfusion was uniformly followed by further decreases In function of both ischemic and border zones. In conclusion, contraction abnormalities produced by 45 minutes of coronary occlusion are reversible with reperfusion. However, when reperfusion is instituted after 1 hour of occlusion, the abnormalities are often accentuated and this becomes invariable after 2 hours of occlusion. Thus, the myocardial impairment appears to be functionally irreversible after this time period.

Comparative sensitivity of the exercise electrocardiogram, thallium imaging and stress radionuclide angiography to detect the presence and severity of coronary heart disease.

The relative sensitivity and specificity of individual and combined noninvasive tests to detect coronary heart disease were evaluated in 75 patients with chest pain admitted for cardiac catheterization and coronary arteriography. Of the 75 patients, 56 had coronary heart disease. Exercise-induced ST-segment abnormalities (>1 mm) were found in 58%. In contrast, computer-processed exercise thalliuim-201 perfusion imaging detected 82% (p < 0.01) and assessment of regional ejection fraction determined at rest and during isometric exercise by radionuclide angiography detected 82% (p < 0.02). Pathologic Q waves were present in 20%. Of nine patients with single-vessel disease, only one had exercise ST-segment abnormalities, while four had abnormalities in thallium-201 perfusion and five in regional ejection fraction. Of 16 patients with twovessel disease, 10 had ST-segment abnormalities, 14 had defects on thallium-201 imaging and 13 had abnormalities in regional ejection fraction. Similarly, of 31 patients with three-vessel coronary heart disease, 23 had exercise-induced ST-segment changes, while 28 had thallium-201 perfusion defects and 28 had abnormalities in regional ejection fraction. Combined noninvasive testing using pathologic Q waves and exercise ST-segment abnormalities detected 71% of patients with coronary heart disease. Addition of exercise thallium-201 imaging resulted in 88% of patients being detected, and addition of regional ejection fraction detected 96%. If an abnormality in any of the four tests was considered, 55 of 56 patients (98%) with coronary heart disease were detected. In 19 patients with normal coronary arteries, the specificity of the exercise ECG was 84%, exercise thallium-201 imaging 89% and assessment of regional ejection fraction 79%. However, if all noninvasive tests were considered, the specificity decreased to 58%. Thus, either exercise thallium-201 imaging or assessment of regional ejection fraction is superior to exercise-induced ST-segment abnormalities. Combined testing results in a very high sensitivity, but there is a concomitant reduction in specificity.

Q waves and ventricular asynergy: Predictive value and hemodynamic significance of anatomic localization

Two hundred sixteen consecutive patients were evaluated to determine the value of pathologic Q waves in predicting the presence and severity of ventricular asynergy. Of 64 patients with pathologic Q waves, 95 percent demonstrated asynergy. Q waves in the anterior leads denoted asynergy in 30 of 30 patients, anterior asynergy in 29 of 30 and an anterior aneurysm in 25. Q waves in the inferior leads indicated asynergy in 30 of 33 patients, inferior asynergy in 25 of 30 and an associated aneurysm in 19. Conversely, of 52 patients with an aneurysm, 44 also had pathologic Q waves. If Q waves were present, 72 percent of asynergic zones exhibited akinesis or dyskinesis; however, in the absence of Q waves an aneurysm was present in only 22 percent (P less than 0.0001). Hemodynamically, anterior asynergy, whether defined by Q waves or by ventriculography, was associated with more left ventricular dysfunction than was inferior asynergy (P less than 0.01). Of 21 patients with a cardiomyopathy, none had pathologic Q waves. The data indicate that pathologic Q waves can aid significantly in predicting the presence and location of a severely asynergic zone. Although their absence does not exclude the possibility of asynergy, the latter is much less likely and, if present, amy be of milder form.

Intervention ventriculography. Comparative value of nitroglycerin, post-extrasystolic potentiation and nitroglycerin plus post-extrasystolic potentiation.

The comparative value of nitroglycerin (TNG), postextrasystolic potentiation (PESP) and their combination (TNG + PESP) to unmask asynergic residual contraction was examined, each patient serving as his own control. Twelve of 13 hypokinetic zones improved both with TNG and PESP. One remained unchanged with either. Of 15 akinetic zones, four improved with both TNG and PESP, while ten remained unchanged. One akinetic zone, although improved with TNG, remained unchanged with PESP. Four dyskinetic zones did not change with either. Six asynergic zones responding to TNG alone demonstrated further augmentation with TNG + PESP. However, none of 13 TNG unresponsive zones improved with TNG + PESP. Thus, TNG, PESP, and TNG + PESP are each equally capable of unmasking asynergic residual contractile ability.

Relationship between regional myocardial perfusion and the presence, severity and reversibility of asynergy in patients with coronary heart disease.

SUMMARY In this study, the interrelationship of regional myocardial perfusion at rest and after exercise, the presence, severity and reversibility of asynergy and the severity of the corresponding coronary arterial obstruction was examined. Forty-five patients underwent exercise testing with thallium-201, cardiac catheterization including intervention (nitroglycerin) ventriculography and coronary arteriography. Of the 45 patients, 13 were normal by catheterization while 32 had coronary heart disease (CHD). Of the 32 with CHD, 21 had asynergy and 11 had normal ventricular contraction. Eighteen of 21 patients with asynergy also had a myocardial perfusion abnormality after exercise, while only three of the 11 without asynergy had a perfusion abnormality (P < 0.001). Of the 21 hypokinetic zones, only 67% had a myocardial perfusion abnormality, while all of the akinetic and dyskinetic zones had a perfusion defect (P < 0.025).Twenty-seven left ventricular zones demonstrated perfusion abnormalities after exercise, of which 19 had either normal or improved myocardial perfusion at rest. Fifteen of these 19 had reversible asynergy on nitroglycerin ventriculography while three had normal contraction. In contrast, the eight zones with myocardial perfusion defects, both at rest and with exercise, all had associated asynergy which was irreversible.A significant relationship was also observed between the severity of the coronary arterial obstruction, asynergy and a perfusion abnormality. Thus, of 39 myocardial zones supplied by 2 90% coronary arterial lesions, 24 had asynergy and 21 of these also had a corresponding myocardial perfusion defect. However, of the remaining 15 without asynergy, only three had a perfusion abnormality (P < 0.001). In addition, of 17 zones subserved by coronary vessels having 75-89% obstructive lesions, three of seven with asynergy had an associated perfusion abnormality, while none of the 10 without asynergy had a perfusion defect (P < 0.025).In summary, the findings of the present study indicate that there is a close interrelationship between the severity of a coronary arterial obstruction and both decreased regional myocardial perfusion and contraction in man. Myocardial perfusion, which is adequate at rest but abnormal with stress, is associated with less severe and reversible asynergy, while perfusion, which is abnormal even at rest, appears to be associated with more severe and irreversible asynergy.