Dimitris Tousoulis

Comparison of Dobutamine and Treadmill Exercise Echocardiography in Inducing Ischemia in Patients With Coronary Artery Disease

OBJECTIVESnWe sought to compare the magnitude of ischemia precipitated by both treadmill exercise and dobutamine stress echocardiography.nnnBACKGROUNDnAlthough it is alleged that dobutamine stress produces ischemia similar in degree and extent to that produced during treadmill exercise, a direct comparison with treadmill exercise, the most common form of exercise, has not been performed.nnnMETHODSnEighty-five consecutive patients with known coronary artery disease underwent both stress tests on the same day, in random order.nnnRESULTSnSixty-two patients (73%) had positive results on exercise echocardiography compared with 53 (62%) who had positive results on dobutamine stress (p = NS). Of the 53 patients with positive dobutamine test results, wall motion abnormalities appeared after the addition of atropine in 35 patients (66%). During dobutamine infusion, 22 patients (26%) had a hypotensive response that was reversed in 16 by prompt administration of atropine. At peak dobutamine-atropine stress, heart rate was higher than that at peak exercise (p < 0.001), whereas systolic blood pressure and rate-pressure product were higher at peak exercise than at peak dobutamine-atropine stress (p = 0.0001). In the 53 patients with positive results on both tests, peak wall motion score index was greater with treadmill exercise than with dobutamine-atropine infusion ([mean +/- SD] 1.73 +/- 0.45 vs. 1.57 +/- 0.44, p < 0.001).nnnCONCLUSIONSnEchocardiography immediately after treadmill exercise induces a greater ischemic burden than dobutamine-atropine infusion. In the clinical setting, exercise echocardiography should therefore be chosen over dobutamine echocardiography for diagnosing ischemia, when possible. When dobutamine echocardiography is used as an alternative modality, maximal heart rate should always be achieved by the addition of atropine.

Variant angina pectoris. Role of coronary spasm in the development of fixed coronary obstructions.

BackgroundIt has been suggested that recurring coronary artery spasm may lead to the development of fixed atherosclerotic coronary obstructions. Methods and ResultsWe studied 10 patients with typical Prinzmetals variant angina in whom the disease remained active for years and in whom occlusive coronary spasm occurred reproducibly at the same arterial site during repeat coronary arteriography (25±12 months after initial angiography). At initial evaluation, four patients had significant (≥50% fixed coronary diameter reduction) one-vessel coronary artery disease, and six had nonsignificant disease. Spasm developed at stenotic sites (20–65% diameter reduction) in nine patients and at an angiographically normal site in one patient. Progression of coronary disease was assessed in 62 segments: 10 spastic (of which nine were stenotic) and 52 nonspastic (eight stenotic and 44 angiographically normal), using computerized arteriography. Mean diameters (millimeters) of spastic segments, nonspastic stenoses, and angiographically normal nonspastic segments were not significantly different at first and second arteriograms (1.52±0.14 versus 1.43±0.21, 1.32±0.17 versus 1.12±4-0.23, and 2.40±0.12 versus 2.42±0.12, respectively). Stenosis progression (from 65% diameter reduction to total occlusion) occurred in one patient at a spastic site and in two at nonspastic sites (from 34% to 65% and from 84% to 100%). Complicated stenoses suggestive of plaque fissuring were not observed during the study. ConclusionsIn patients with chronic Prinzmetals variant angina without myocardial infarction, stenosis progression was not frequently observed at spastic sites despite the recurrence of focal coronary spasm over relatively long periods of time.

Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X

The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage.

OBJECTIVESnThis study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity.nnnBACKGROUNDnIn the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before thrombolytic therapy is administered. The relation between this phenomenon, myocardial damage and hemostatic activity is unknown.nnnMETHODSnHolter ST segment recording and pretreatment plasma tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, prothrombin fragment F1 + 2 and soluble fibrin levels were measured in 57 patients with acute evolving myocardial infarction. Spontaneous intermittent myocardial reperfusion, defined as two or more episodes of transient resolution of ST segment elevation to within 0.05 mV of baseline, lasting > or = 1 min, before the start of recombinant t-PA (rt-PA) treatment was present in 28 patients (group 1) and absent in 29 (group 2). Left ventriculography and coronary angiography were performed 90 min after intravenous rt-PA administration. Plasma creatine kinase-MB fraction (CK-MB) levels were measured every 6 h for 24 h, and C-reactive protein levels were measured daily for 3 days.nnnRESULTSnGroup 1 had lower peak plasma CK-MB (141.9 +/- 28.3 vs. 203.8 +/- 23.3 IU/liter [mean +/- SEM], p < 0.014) and C-reactive protein levels (16 +/- 4 vs. 28 +/- 4 mg/liter on day 1; 26.6 +/- 5.5 vs. 61.8 +/- 14.4 mg/liter on day 2; 19.6 +/- 4.2 vs. 40.6 +/- 6.5 mg/liter on day 3, p < 0.012) and a higher left ventricular ejection fraction (62.9 +/- 4% vs. 51.1 +/- 5%, p < 0.04) than group 2. Group 1 had lower plasma t-PA antigen levels (15.6 vs. 27 micrograms/liter, p < 0.006) but higher prothrombin fragment F1 + 2 (1.8 vs. 1.1 nmol/liter, p < 0.003) and soluble fibrin levels (66.8 vs. 31 nmol/liter, p < 0.01). Coronary patency at 90 min was similar.nnnCONCLUSIONSnEarly spontaneous intermittent reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less subsequent myocardial damage. This finding is consistent with a protective effect of intermittency on the myocardium and a procoagulant effect of spontaneous lysis on blood. It may also reflect a different rate of evolution of coronary thrombosis and myocardial infarction in patients with and those without spontaneous intermittent myocardial reperfusion.

Coronary vasomotor effects of serotonin in patients with angina. Relation to coronary stenosis morphology.

BackgroundPrevious experimental studies have shown that the effect of serotonin on a coronary stenosis depends on whether that stenosis is compliant or fixed. However, the relation between coronary stenosis morphology and the response to serotonin in patients with angina is not known. Methods and ResultsUsing computerized quantitative coronary angiography, we studied the effects of intracoronary infusion of serotonin on 38 coronary stenoses of different morphologies (concentric, eccentric, complicated) in 11 patients with stable angina and 4 with variant angina. In response to the maximum infused concentration of serotonin, 100% of complicated stenoses and 50% of concentric stenoses constricted by ≥20% (P≤.05). The magnitude of constriction was greater at eccentric stenoses (32.08±4.1%) than concentric stenoses (15.68±2.8%, P≤.05) and greater in complicated stenoses (57.69±7.6%, P≤.05) than eccentric stenoses. At complicated stenoses, the constriction was greater (0.85±0.16 mm, P≤.05) than at the adjacent reference segments (0.42±0.12 mm). It was similar to the reference segment for both concentric and eccentric stenoses. The constriction at the stenosis was greater for irregular (complicated) lesions than for smooth (concentric and eccentric) lesions in both patients with stable (51.8±73% versus 22.5±4.1%, P≤.001) and those with variant (77±17% versus 28.2±8.1%, P≤.05) angina. There was a weak correlation (r=.39) of magnitude of constriction with stenosis length but not with baseline stenosis severity (minimum diameter). ConclusionsIn these patients, the magnitude of the vasoconstrictor response to serotonin at the site of an atheromatous coronary plaque depends on the morphological characteristics of the plaque and is more closely related to irregular contour than stenosis severity or length. This relation suggests that variations in receptor type or density or in the smooth muscle cell response to stimulation may determine the response to locally released serotonin in patients with coronary disease.

Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris

It has been suggested that a generalized coronary vasomotion disorder is present in variant angina and that evaluation of baseline coronary artery tone may be useful for predicting the occurrence of coronary artery spasm. The vasomotor response of angiographically normal proximal and distal coronary artery segments was studied in 9 patients with atypical chest pain and normal coronary arteriograms (control group), 13 patients with active variant angina and 41 patients with chronic stable angina. Ergonovine (intravenous, 100 to 300 micrograms, or intracoronary, 8 to 20 micrograms, was administered to all 22 patients in the control and variant angina groups and to 11 of the 41 patients with chronic stable angina. All patients also received intracoronary isosorbide dinitrate (1 to 2 mg). Computerized coronary artery diameter measurement of angiographically normal segments was carried out before and after ergonovine and nitrate administration. Mean baseline intraluminal diameter of proximal and distal coronary segments was not significantly different in control patients and those with variant angina (nonspastic segments only) or coronary artery disease (proximal 2.89 +/- 0.15, 2.83 +/- 0.14 and 2.82 +/- 0.09 mm; distal 1.60 +/- 0.08, 1.63 +/- 0.07 and 1.62 +/- 0.06 mm, respectively). After ergonovine, proximal segments constricted by 10 +/- 2%, 15 +/- 3% and 11 +/- 4% and distal segments by 11 +/- 3%, 11 +/- 2% and 14 +/- 3% in control, variant angina and coronary artery disease groups, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular hypercontractility and ST segment depression in patients with syndrome X

OBJECTIVESnThis study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X.nnnBACKGROUNDnClinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise.nnnMETHODSnThe pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise.nnnRESULTSnLeft ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients.nnnCONCLUSIONSnThese findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.

Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris.

To assess whether vasoreactivity of significant coronary stenosis (greater than 50% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, 53 patients (40 men, 13 women, mean +/- standard deviation age 55 +/- 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the 53 also before and after 20 to 30 micrograms intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 +/- 1.2% and distal normal coronary segments by 15 +/- 1.7% (p less than 0.01). Significant proximal coronary stenoses dilated by 11 +/- 2.5% and distal stenoses by 23 +/- 2.8% (p less than 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 +/- 1.7% and that of normal distal segments by 15.5 +/- 1.4% (p less than 0.01). Proximal stenoses constricted by 11 +/- 2.2% and distal stenoses by 18.4 +/- 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments by (greater than or equal to 10%), 31 of 63 (49%) distal (p less than 0.05) and 21 of 43 (49%) stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Preangioplasty complicated coronary stenosis morphology as a predictor of restenosis

To assess whether complicated preangioplasty coronary stenosis morphology is associated with restenosis, 41 patients (47 stenoses) who underwent repeat angiography 6 to 8 months after percutaneous transluminal coronary angioplasty (PTCA) were studied. Stenosis diameter and morphology were assessed by computerized quantitative coronary angiography before and immediately after PTCA and at follow-up angiography. Before PTCA 18 stenoses were concentric (symmetric narrowings with smooth borders), 12 were eccentric (asymmetric narrowings with smooth borders), and 17 were complicated (asymmetric with rough borders and overhanging edges). Restenosis occurred in 18 lesions: two (11%) concentric, four (33%) eccentric, and 12 (70%) complicated (p less than 0.05), whereas 29 lesions remained unchanged. Stenosis diameter before and immediately after PTCA was not significantly different in the 18 patients with and the 23 patients without restenosis. Follow-up angiograms showed that 11 (61%) stenoses in the group with restenosis and 18 (63%) in the group without restenosis had morphology similar to that before PTCA. Restenosis occurred in seven (30%) patients who initially had chronic stable angina and in 11 (61%) who were first seen with unstable angina (p less than 0.05). In patients with stable angina 1 of 13 concentric stenoses, two of eight eccentric stenoses, and four of five complicated lesions restenosed. In patients with unstable angina one of five concentric, two of four eccentric, and 8 of 12 complicated lesions had restenosis. Stenoses that were complicated before PTCA tended to adopt an irregular morphology if they recurred, whereas concentric stenoses rarely occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery-phase patterns of ST segment depression in the heart rate domain cannot distinguish between anginal patients with coronary artery disease and patients with syndrome X

Continuous plots of ST segment depression related to heart rate during exercise and recovery (heart rate recovery loops) can differentiate patients with coronary artery disease from clinically normal subjects. To assess whether this method can also distinguish patients with angina and coronary artery disease from those with syndrome X (angina, positive exercise tests, and normal coronary arteries), we studied 75 patients with coronary artery disease and 30 patients with syndrome X. The average heart rate recovery loops for coronary artery disease and syndrome X patients followed similar counterclockwise loop rotations. Individual data analysis, however, showed that in coronary artery disease patients the loop rotation was counterclockwise in 66 (88%) and intermediate in nine (12%), while none had a clockwise loop nine (30%), and intermediate in nine (30%). Thus heart rate recovery loops cannot distinguish patients with angina and coronary artery disease from those with syndrome X.