Inhibition of dipyridamole-induced ischemia by antianginal therapy in humans. Correlation with exercise electrocardiography.

BACKGROUND. Dipyridamole echocardiography test (DET: two-dimensional echocardiographic monitoring with dipyridamole infusion up to 0.84 mg/kg in 10 minutes) is a useful tool for the noninvasive diagnosis of coronary artery disease. Aims of the present study were to assess the effects of antianginal drugs on dipyridamole-induced ischemia and to evaluate whether drug-induced changes in DET response may predict variations in exercise tolerance. METHODS AND RESULTS. Fifty-seven patients with angiographically assessed significant coronary artery disease (greater than 70% lumen reduction in at least one major coronary vessel) performed a DET and an exercise electrocardiography test (EET) in random order both off treatment and on antianginal drugs (beta-blockers, calcium antagonists and nitrates, alone or in various combinations). The criterion for DET positivity was a transient dyssynergy of contraction absent or of a lesser degree in the baseline examination. In DET, two parameters were evaluated: the dipyridamole time (i.e., the time from onset of dipyridamole infusion to obvious dyssynergy) and the wall motion score index. DET sensitivity was 91% off therapy and fell to 65% under therapy (p less than 0.01). In the 37 patients who had a positive DET both off and on therapy, the dipyridamole time increased from 6 +/- 3 (off therapy) to 8 +/- 3 minutes (on therapy) (p less than 0.01). The wall motion score index at peak dipyridamole went from 1.38 +/- 0.14 to 1.31 +/- 0.14 (p less than 0.01). EET and DET yielded concordant (positive versus negative) results in 41 of 57 (71%) patients off and in 35 of 57 (61%) on therapy (p = NS). In the subgroup of 38 patients with both positive DET and EET without treatment, the therapy-induced variations in exercise time were significantly correlated with the variations in dipyridamole time (r = 0.5; p less than 0.01), not with variations in wall motion score index (r = 0.3; p = NS). CONCLUSIONS. 1) Antianginal therapy can protect from dipyridamole-induced ischemia and 2) the therapy-induced changes in DET response parallel variations in exercise tolerance and might be useful for the objective, exercise-independent assessment of the therapy efficacy.     

Involvement and function of the right ventricle in acute myocardial infarct. Hemodynamic, echocardiographic and angioscintigraphic correlations

To assess the acute effects of myocardial infarction on right ventricular function 22 patients were studied utilizing right heart catheterization, radionuclide angiography and two dimensional echocardiography. Thirteen patients had inferior myocardial infarction (Group I) and 9 anteroseptal or anterior (Group II). Hemodynamic findings suggesting right ventricular infarction were present in 3 patients of Group I. Mean radionuclide right ventricular ejection fraction was lower in inferior myocardial patients (38.2 +/- 7.6-Group I vs 50.3 +/- 11.4-Group II, p less than 0.005), while left ventricular ejection fraction in anteroseptal, and anterior myocardial infarction patients (36.8 +/- 10.5-Group II vs 55.9 +/- 7.6-Group I, p less than 0.001). Six patients in Group I presented a depressed radionuclide right ventricular ejection fraction (less than 40%): moreover right ventricular ejection fraction correlated with left ventricular ejection fraction in Group II (r = 0.79, p less than 0.001) but not in Group I (r = 0.55, p = NS). By mean of 2 dimensional echocardiography Group I patients had an increased right ventricular end diastolic area (15.3 +/- 3.8 vs 12.1 +/- 1.2 cm2, p less than 0.05) while Group II an increased right ventricular free wall motion (47.3 +/- 10.7 vs 32.4 +/- 14.1%, p less than 0.005); right ventricular end diastolic area correlated with right ventricular ejection fraction only in Group I (r = 0.60, p less than 0.05). Five patients in Group I and no patients in Group II had an enlarged right ventricular end diastolic area. Therefore, radionuclide and echocardiographic evidence of right ventricular involvement were not always associated with abnormal hemodynamics. Thus, the damaged right ventricular chamber dilates to allow an adequate stroke volume in presence of low ejection fraction; hemodynamic significant right ventricular myocardial infarction becomes evident only in patients with more severe right ventricular compromise; the increase in right ventricular free wall motion in anterior myocardial infarction patients compensates the loss of contribution of interventricular septum contraction.     

The diagnostic and prognostic value of echo-dipyridamole in patients with suspected coronary disease: a comparison with the stress test]

The aim of the study was to assess the relative diagnostic and prognostic accuracy of high-dose dipyridamole echocardiography test (DET: 2D-echo monitoring during dipyridamole infusion up to 0.84 mg/kg over 10') vs maximal symptom limited bicycle exercise electrocardiography test (EET) in patients with chest pain addressed to coronary angiography. We initially considered 477 consecutive patients, meeting the following inclusion criteria: 1) history of chest pain; 2) off antianginal therapy; 3) no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction. All patients were submitted to a DET and EET--on different days and in random order--within 1 week of coronary angiography (which was performed independently of test results). DET could not be performed in 32 patients for a poor acoustic window in resting conditions (n = 31) or for asthmatic disease requiring xanthine therapy (n = 1); EET could not be performed in 54 patients for inability to exercise, or resting electrocardiographic abnormalities making the EET interpretable. The overall feasibility was of 445/477 for DET and 423/477 for EET (93 vs 89%, p = ns). Criteria for positivity were: transient regional dyssynergy absent in the baseline examination for DET; ST segment shift greater than .15 m V from baseline for EET. Angiographically assessed coronary artery disease (CAD) was considered present when a luminal reduction greater than or equal to 50% occurred in at least 1 major coronary vessel. There were 135 pts with no significant CAD and 256 with CAD; 137 had single, 70 double, 49 triple and/or left main (15) vessel disease. The specificity was higher in DET vs EET (96 vs 59%, p less than .01). The overall sensitivity of DET was similar to EET (67 vs 69%, p = ns), with no significant differences in the subset with single (56 vs 63%, p = ns), double (74 vs 69%, p = ns) or triple (88 vs 86%, p = ns) vessel disease. Patients were followed-up for 26 +/- 22 (range 1 to 73) months considering only death and myocardial infarction as end-points. A Cox stepwise survival analysis identified the Wall Motion Score Index (an integrated semiquantitative measure of extent and severity of the dyssynergy) at peak dipyridamole as the most powerful prognostic predictor (X2 = 18.5, p less than 0001) of all invasive (number of stenotic coronary vessels, X2 = 5.8, p less than .05) and noninvasive (exercise electrocardiography positivity, p = ns) parameters.(ABSTRACT TRUNCATED AT 400 WORDS)     

Silent ischemia: evaluation by exercise and redistribution tomographic thallium-201 myocardial imaging

To compare the amount of myocardium jeopardized during silent ischemia and painful ischemia, 112 consecutive patients undergoing coronary arteriography with ischemia demonstrated by exercise and redistribution tomographic thallium-201 myocardial imaging (SPECT) were divided into two groups: 84 patients without anginal pain (silent ischemia) and 28 with pain (painful ischemia). The SPECT apical, mid and basal ventricular levels of the short-axis view and the apical portion of the long-axis view were divided into 20 segments. The results were 1) 7.4 +/- 4.7 ischemic segments in silent ischemia and 7.6 +/- 3.7 in painful ischemia (p = NS) with 4.7 +/- 3.6 segments in silent ischemia undergoing total redistribution compared with 5.4 +/- 3.4 in painful ischemia (p = NS); 2) no difference in the incidence of single, double or triple vessel disease between silent and painful ischemic groups; 3) similar anatomic distribution of ischemic segments between the two groups; 4) more positive exercise electrocardiographic (ECG) changes in painful ischemia (70%) than in silent ischemia (32%) (p less than 0.001) with equal amounts of ischemia associated with positive and negative exercise ECG findings. Conclusions: 1) Patients with silent and painful ischemia during exercise have similar amounts of ischemic myocardium demonstrated by tomographic thallium-201 imaging and similar extent of angiographically documented coronary artery disease despite the absence of pain and the lower incidence of positive exercise ECG findings in silent ischemia. 2) Positive and negative exercise ECG findings were associated with similar amounts of ischemic myocardium.     

ST segment depression elicited by dipyridamole infusion in asymptomatic hypertensive patients

In asymptomatic patients with essential hypertension, electrocardiographic changes suggestive of myocardial ischemia can be elicited by rapid pressure lowering or by pronounced coronary arteriolar dilation. The aim of this study was to assess whether dipyridamole infusion might induce ischemic-like electrocardiographic changes in asymptomatic essential hypertensive patients and to describe the clinical and echocardiographic correlates possibly associated with this response. We therefore studied a control group of 20 normotensive individuals and a group of 28 asymptomatic patients with mild-to-moderate essential hypertension. All underwent dipyridamole-echocardiography testing (12-lead electrocardiogram and two-dimensional echocardiographic monitoring with dipyridamole infusion, 0.84 mg/kg over 10'). No patient showed transient regional dyssynergy during dipyridamole infusion. None of the normotensive and 10 of 28 of the hypertensive participants had horizontal or downsloping ST segment depression more than 0.1 mV during dipyridamole (0% versus 36%, p less than 0.01). Hypertensive patients with ("responders") (n = 10) and without ("nonresponders") (n = 18) ST segment depression showed similar values of percent fractional shortening in baseline conditions (32 +/- 5 versus 33 +/- 6, p = NS) and at peak dipyridamole infusion (45 +/- 8 versus 43 +/- 5, p = NS). The peak early to peak late velocity ratio values (evaluated from transmitral flow tracings by Doppler technique) were also similar in baseline conditions (0.86 +/- 0.14 versus 0.94 +/- 0.30, p = NS) and at peak dipyridamole (0.72 +/- 0.15 versus 0.78 +/- 0.32, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient myocardial dysfunction during pharmacologic vasodilation as an index of reduced coronary reserve: a coronary hemodynamic and echocardiographic study

Regional coronary flow reserve and regional myocardial contractility were evaluated in 29 patients after maximal pharmacologic coronary vasodilation (intravenous dipyridamole, 0.56 mg/kg body weight, administered over 4 minutes). Nineteen patients had a severe (80 to 99%) proximal and isolated stenosis of the left anterior descending coronary artery and 10 patients had normal coronary arteries; all had normal ventricular function under rest conditions. Myocardial contractility was assessed by means of continuous two-dimensional echocardiographic monitoring; coronary reserve was evaluated by coronary sinus thermodilution. After dipyridamole infusion, 9 of the 19 patients with left anterior descending artery stenosis had transient myocardial asynergy involving the septum or apex, or both (Group IA), whereas 10 patients showed no asynergy (Group IB). No impairment of contractility was observed in the 10 patients with normal coronary arteries (Group II). Coronary blood flow was measured under basal conditions and up to 10 minutes after the end of dipyridamole infusion. In patients in Group II, dipyridamole induced an increase in great cardiac vein flow of 167 +/- 68% (mean +/- SD). The 10 patients in Group IB showed a response comparable with that of the control group (Group II) (136 +/- 45% increase in great cardiac vein flow; NS versus Group II), whereas the 9 patients in Group IA had an increase of 46 +/- 30% (p less than 0.01 versus both Group IB and Group II). No significant difference was found in the angiographic severity of the stenosis expressed in terms of minimal cross-sectional area (Group IA = 0.30 +/- 0.13 mm2, Group IB = 0.34 +/- 0.18 mm2; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Silent myocardial ischemia in middle-aged asymptomatic patients with type 2 diabetes in Turkish population

The authors investigated silent myocardial ischemia in unselected consecutive middle-aged asymptomatic patients with type 2 diabetes without any evidence of coronary heart disease documented by treadmill exercise test. Ninety asymptomatic patients with type 2 diabetes (48 men; mean age: 49 +/-6 years) were included in the study. Mean duration of diabetes in the study group was 4 +/-4.2 years (range 1 to 21 years); 38% of the study population, diabetes duration was only 1 year). All patients were subjected to treadmill exercise test with Bruce protocol. A positive test was noted in 4 of 90 (4%) study patients. Two male patients (4%) and 2 (4%) women patients developed exercise-induced ST-segment depression, but none had concomitant chest pain. Diabetics with silent myocardial ischemia were older (55 +/-3 years vs 49 +/-6 years, p = 0.04) than those without silent myocardial ischemia. Also, diabetics with silent myocardial ischemia had higher fibrinogen level (372 +/-51 vs 307 +/-71 mg/dL, p = 0.04) than diabetics without silent myocardial ischemia. In treadmill exercise test, diabetics with silent myocardial ischemia had lower total exercise time and peak workload (375 +/-30 vs 474 +/-115 seconds, p = 0.04; 7.3 +/-0.5 vs 8.9 +/-1.9, p = 0.04, respectively) than without silent myocardial ischemia. Insulin resistance is associated with a variety of atherosclerosis risk factors. Exercise test findings show increased cardiac sympathetic activity and parasympathetic withdrawal in increased insulin resistance.     

Transmitral flow changes during dipyridamole-induced ischemia. A Doppler-echocardiographic study

Myocardial ischemia results in altered left ventricular (LV) diastolic compliance, reflected by an abnormal mitral inflow pattern on Doppler echocardiography. To investigate the relationship of Doppler echocardiography and regional myocardial systolic function during dipyridamole infusion, we evaluated transmitral flow changes detected by pulsed Doppler technique during a high-dose dipyridamole echocardiography test (DET, two-dimensional echo monitoring with dipyridamole infusion, up to 0.84 mg/kg over 10 min). The DET response produced two groups: group 1 (34 patients) with negative DET, and group 2 (35 patients) with positive DET, defined as the development of a newly onset LV regional asynergy. The E/A values overlapped at baseline (1.07 +/- .32 vs .92 +/- .22; p = NS) but differed at peak changes (.92 +/- .26 vs. 75 +/- .25; p less than .01). Heart rate changes could not account for the observed Doppler changes, since the values of R-R interval were similar in the groups, both basally (.927 +/- .226 vs .867 +/- .143 s; p = NS) and at peak dipyridamole (.754 +/- .100 vs. 681 +/- .112; p = NS). Transient myocardial ischemia induced by dipyridamole administration is accompanied by changes in transmitral flow, which consist of an increase in the relative atrial contribution to LV filling, possibly owing to an acute impairment in LV relaxation.     

Oral vs intravenous dipyridamole echocardiography for detecting coronary artery disease.

The usefulness of the intravenous dipyridamole-echocardiography test (12-lead and two-dimensional [2-D] echo monitoring during dipyridamole infusion) in the diagnosis of coronary artery disease recently has been suggested. However, the intravenous form of dipyridamole is not available for clinical use in some countries and therefore the administration of oral dipyridamole has been employed in combination with echocardiography. In order to evaluate the relative usefulness of the oral (300 mg of pulverized tablets) vs the intravenous (up to 0.84 mg/kg in 10 min) dipyridamole-echocardiography test, we performed the two tests, on different days and in random order, in 28 inhospital patients: 21 had coronary artery disease (seven had one-vessel disease, eight had two-vessel disease, and six had three-vessel disease); seven patients had no significant coronary artery disease. For both tests, the diagnostic end-point was the development of a transient dyssynergy of contraction. Sensitivity was 95 percent for the intravenous and 52 percent for the oral dipyridamole-echocardiography test (p < 0.01); in positive cases, the dyssynergy after the dipyridamole administration appeared at 6.5 +/- 2.5 min for the intravenous and at 27.8 +/- 12.4 min for the oral test (p < 0.01). Specificity was 100 percent for both the intravenous and oral dipyridamole-echocardiography test. One or more extracardiac side effects (headache, gastrointestinal upset, flushing, etc) occurred in 61 percent of the intravenous and 68 percent of the oral tests (p = ns). Nine patients with a positive intravenous and oral dipyridamole-echocardiography test also had a positive exercise-electrocardiography test. A significant correlation between exercise time (ie, the time from onset of exercise and 0.1 m V of ST segment shift) and dipyridamole time (ie, the time from onset of dipyridamole administration and the development of frank dyssynergy) was present for the intravenous (r = 0.6, p < 0.05) but not for the oral test. We conclude that the oral dipyridamole-echocardiography test, in comparison with the intravenous dipyridamole-echocardiography test, has a lower sensitivity and requires a substantially longer imaging time. The dipyridamole time is related to exercise time for intravenous but not for the oral dipyridamole-echocardiography test.     

Natural history of left ventricular size and function after acute myocardial infarction. Assessment and prediction by echocardiographic endocardial surface mapping

To investigate the natural history of regional dyssynergy and left ventricular size after myocardial infarction, 57 patients with a first Q wave myocardial infarction (18 anterior, 35 inferior, and four apical by echocardiography) were studied by two-dimensional echocardiography and compared with 30 control patients. Measurements from the echocardiograms were used to construct maps of the left ventricular endocardial surface from which the endocardial surface area index (ESAi) and the percent of the endocardial surface area involved by abnormal wall motion (%AWM) were calculated. The maps from entry and 3-month echocardiograms were used to classify patients based on changes in ESAi and abnormal wall motion. Two subgroups of patients were identified at entry--those with a normal ESAi (group 1, n = 50) and those with an increased ESAi (group 2, n = 7). Group 1 patients was subdivided at 3 months by changes occurring in ESAi (1A, 5% increase [n = 19]; 1B, no change [n = 23]; 1C, 5% decrease [n = 8]). The increase in ESAi (64.9 +/- 5.2 to 75.4 +/- 7.5 cm2/m2, p less than 0.0001) in group 1A was associated with global ventricular dilatation (n = 11) and clinically silent infarct extension (n = 8). Groups 1B and 1C were composed predominantly of patients with inferior infarctions, and all exhibited either no change or a significant decrease in infarct size (infarct regression). Group 2 patients demonstrated a continued increase in ESAi by 3 months (88.2 +/- 10.0 to 101.4 +/- 15.5 cm2/m2, p less than 0.007). This group comprised only patients with anterior infarctions, and all exhibited infarct expansion at the left ventricular apex. The changes in left ventricular size and functional infarct size are heterogeneous after acute myocardial infarction and relate to the initial endocardial surface area, infarct location, and functional infarct size.     

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.     

Dipyridamole-dobutamine echocardiography: A novel test for the detection of milder forms of coronary artery disease

Objectives. This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography.Background. Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine).Methods. One hundred fifty patients (mean [±SD] age 51 ± 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamoledobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 μg/kg body weight per min) was performed on a separate day.Results. Significant coronary artery disease (>50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamoledobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 ± 30) and was comparable during the dobutamine (186 ± 59) and dipyridamole-dobutamine tests (179 ± 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all).Conclusions. Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.     

Effect of beta-blockade on thallium-201 dipyridamole myocardial scintigraphy

The effect of beta-blockade on dipyridamole thallium-201 images was assessed in 8 patients with coronary artery disease and positive dipyridamole test. Three dipyridamole thallium-201 tests were performed, the first in basal conditions, the second 30' after propranolol and the third with propranolol and atrial pacing. After dipyridamole heart rate and double product increased respectively from 75 +/- 7 to 98 +/- 15 b/min (p less than 0.01 vs starting values) and from 10 551 +/- 1255 to 11 740 +/- 4542 mmHg X b/min (p less than 0.05 vs starting values). Propranolol reduced heart rate to 64 +/- 6 b/min (p less than 0.05 vs basal conditions), systolic blood pressure to 136 +/- 13 and double product to 8733 +/- 1248 (p less than 0.05 vs basal conditions). Dipyridamole when infused after propranolol, induced an increase in heart rate to 70 +/- 5 b/min (p less than 0.05 vs starting values) while double product was 9133 +/- 1189 mmHg X b/min (p = NS vs starting values). Atrial pacing prevented the fall in heart rate and double product induced by propranolol so during dipyridamole infusion double product increased to 13 271 +/- 1868 (p less than 0.05 vs propranolol treatment; p less than 0.05 vs starting values). Segmental score calculated after dipyridamole was 5.2 +/- 2.0 in basal conditions, 5.1 +/- 1.3 after propranolol (p = NS) and 4.8 +/- 1.3 after propranolol plus atrial pacing (p = NS). Thus the results of the study show that beta-blockade does not worsen dipyridamole thallium-201 images. Furthermore the steal phenomenon seems to be the main mechanism of the dipyridamole induced ischemia. In fact, also when the increase, oxygen consumption is blunted with beta-blockade the disparity in myocardial blood flow resulted unaffected.     

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of limited treadmill exercise on adenosine Tc-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging in coronary artery disease.

Limited exercise combined with dipyridamole increases myocardial perfusion defect severity compared with dipyridamole alone. The impact of limited exercise combined with adenosine on myocardial perfusion defect severity is unknown. This study compares myocardial perfusion defect severity with adenosine alone and adenosine combined with limited exercise. Thirty-two patients with coronary artery disease underwent on separate days and in randomized order technetium-99m sestamibi (25 to 30 mCi) single-photon emission computed tomographic imaging at rest, after adenosine (140 microg/kg/min x 6 minutes), and after adenosine (140 microg/kg/min x 4 minutes) during 6 minutes of modified Bruce treadmill exercise (adenosine-exercise). Radiopharmaceutical was injected at 3 and 5 minutes during adenosine and adenosine-exercise, respectively. Images were interpreted by a consensus agreement of 3 nuclear cardiologists without knowledge of patient identity, stress protocol, or clinical data using a 17-segment model and 5-point scoring system. A summed stress score (SSS), summed rest score (SRS), and summed difference (SSS-SRS) score (SDS) were calculated for each image. Peak stress heart rate and rate-pressure product were higher for adenosine-exercise than adenosine (102 +/- 19 vs 81 +/- 11 beats/min and 13,972 +/- 4,265 vs 10,623 +/- 2,131, respectively; both p <0.001). Sensitivity for detection of > or = 50% coronary stenosis was 75% and 72% for adenosine-exercise and adenosine, respectively (p = NS). There were no differences in SSS and SDS between adenosine-exercise and adenosine (8.2 +/- 5.9 vs 8.1 +/- 6.3 and 4.9 +/- 4.1 vs 5.2 +/- 4.6, respectively; both p = NS). Thus, in patients with coronary artery disease, limited treadmill exercise combined with adenosine does not increase myocardial perfusion defect severity compared with standard adenosine technetium-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging.     

Aggressive surgical management of post-infarction angina: results of myocardial revascularization early after transmural infarction

In our Division of Cardiothoracic Surgery between 1970 and 1982, 110 patients (88 males and 22 females) had coronary artery bypass grafts (CABG) performed for unstable angina pectoris after acute transmural myocardial infarction. Fifty-one patients (mean age 59 years) had CABG within 2 weeks of myocardial infarction (Group 1); and 59 patients (mean age 56 years) (p = NS) within 6 weeks of myocardial infarction (Group 2). The incidence of preoperative arrhythmias, left ventricular ejection fraction, end-diastolic pressure, and the number of vessels diseased were similar in Groups 1 and 2. The incidence of cardiogenic shock was higher in Group 1 (16/51, 31% vs 2/59, 3% [p < 0.001]). This was also the case with the use of the intraaortic balloon (32/51, 63% vs 12/59, 20% [p < 0.001]), and the need for emergency operation (29/51, 57% vs 4/59, 7% [p < 0.001]). The mean number of grafts was 2.8 in Group 1 and 3.0 in Group 2 (p = NS). Operative mortality was 20% (10/51) in Group 1 and 7% (4/59) in Group 2 (p < 0.01). Excluding patients in cardiogenic shock, operative mortality was 0% (0/35) in Group 1 and 5% (3/57) in Group 2 (p = NS). Incidences of late death, recurrent angina, and permanent disability were similar during mean follow-up times of 3.2 years in Group 1 and 4.1 years in Group 2. Actuarial probability of survival was 96% at 1 year and 83% at 5 years. Myocardial revascularization early after transmural myocardial infarction has a low risk, especially in the absence of cardiogenic shock. These results justify an aggressive approach to unstable angina, including patients within 2 weeks of transmural infarction.     

Significance of ST segment depression in the precordial leads during the acute phase of inferior myocardial infarction

Reciprocal changes of the ST segment in the acute phase of inferior myocardial infarction are common but their significance remain controversial. We studied this problem by comparing the ECG on admission of 83 patients with acute inferior myocardial infarction, with the clinical outcome and haemodynamic and angiographic data obtained on average 3 weeks after the onset of symptoms. Fifty nine patients (Group I) had ST depression greater than or equal to 1 mm in at least one of the leads V1 to V4; 24 patients (Group II) had no ST depression in this territory. The patients in Group I were older (59.6 +/- 6.4 vs 54 +/- 5.3 years, p less than 0.01), had higher total CPK (1 835 +/- 940 vs 875 +/- 305, p less than 0.01) and MB fractions (269 +/- 102 vs 95 +/- 35), more complications during the hospital period (80%, mainly haemodynamic vs 38%, p less than 0.01) and more severe left ventricular dysfunction: ejection fraction 52.2 +/- 6% vs 59.2 +/- 7%, p less than 0.05; cardiac index 2.75 +/- 0.4 l/min/m2 vs 3.25 +/- 0.3 l/min/m2, p less than 0.005). There was no difference in left ventricular wall motion between the groups on biplane angiography. However, coronary angiography showed left coronary disease to be more common in Group I (84%) than in Group II (37%), p less than 0.005. Left anterior descending and left circumflex disease was equally common. Patients with persistent ST depression after 48 hours had lower ejection fractions than those in whom it regressed within 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dipyridamole-induced myocardial ischaemia increases ANF release in man.

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.     

Long-term clinical impact of coronary-collateral vessels after acute myocardial infarction.

BACKGROUND: The positive impact of coronary collateral vessels in the acute phase of myocardial infarction (AMI) is already well established. However, their impact on longterm clinical outcome of these patients is still unclear. AIM: To study the impact of the presence of well established coronary collateral vessels on long-term clinical outcome of post-AMI patients. POPULATION AND METHODS: We analyzed the clinical evolution (mean follow-up time of 15.66.8 months) of 70 patients who underwent coronary angiography shortly after AMI. According to the angiogram, the patients were divided into 2 groups: those with well developed coronary collateral vessels (n = 35) and those who did not show developed collateral circulation (n = 35). RESULTS: Both groups had similar baseline characteristics (regarding demography, coronary artery disease risk factors and predischarge evolution). The group with collaterals had more severe coronary disease compared with the group without collaterals (2.31 +/- 0.61 vs. 1.57 +/- 0.7; p = 0.00001). Moreover, this group more frequently showed significant lesions on the left anterior descending artery (83% vs. 74%; p = NS), left circumflex (71% vs. 43%; p = 0.02) and right coronary arteries (74% vs. 40%; p = 0.003). Primary percutaneous coronary intervention was more often performed in patients without coronary collateral vessels (58% vs. 30%; p = 0.02). Left ventricular function was similar in both groups. During follow-up, both groups underwent similar levels of revascularization by percutaneous coronary intervention and/or coronary artery bypass graft (70% vs. 76%; p = NS). Despite these characteristics, the group with collaterals showed a significantly better clinical outcome, with fewer events (combined endpoint of unstable angina, non-fatal AMI, heart failure and death) after hospital discharge (40% vs. 69%; p = 0.02) and a lower CCS functional class at the end of follow-up (1.26 +/- 0.63 vs. 1.730.71; p = 0.03). CONCLUSION: After acute myocardial infarction, the presence of collateral vessels is associated with a better long-term clinical outcome.     

Impact of chronic patency of infarct-related coronary artery on prevalence of myocardial ischemia during the pharmacologic and exercise stress test

Background: Even late restoration of anterograde coronary flow may have beneficial effects on left ventricular function, electrophysiology, and survival in postinfarction patients. Hypothesis: The patency or occlusion of an infarct-related coronary artery in the chronic phase may also be associated with myocardial ischemia provoked by pharmacologic and physiologic stress tests. Methods: High-dose dipyridamole echocardiography test (DET) (up to 0.84 mg/kg over 10 min), exercise electrocardiography (EET), and coronary angiographic data in a group of 127 in-hospital patients who had survived an acute myocardial infarction were analyzed. Patients who had only angiographic evidence of infarct-related single artery disease (≥50% luminal diameter reduction) and no previous revascularization were enrolled in the study. DET and EET were performed (DET in all, EET in 118 patients) within 5 days before coronary angiography. Fifty-seven patients had total occluded infarct arteries (Group 1) with various degrees of collateral circulation (2.6±1.1 collateral score, by a 3 grading system), whereas the other 70 patients had patent infarct arteries (Group 2) with significant residual stenoses (82±13% diameter reduction). Results: The prevalence of rest angina or effort angina and topography of the infarct-related coronary artery did not differ between the two groups (all p = NS). There were more patients with Q wave in Group 1 than in Group 2 (72 vs. 57%, p = 0.08) compared with non-Q wave infarction (Group 1 = 28 vs. Group 2 = 43%, p = 0.08). Ischemia in the infarct-related artery territory detected by DET (defined as new wall motion dyssynergy or marked worsening of resting hypokinesia) was 61% in Group 1 and 41% in Group 2 (p = 0.025). EET was positive in 26 of 54 (48%) Group 1 and in 21 of 64 (33%) Group 2 patients (p = 0.09). Conclusions: Patients with occluded infarct-related arteries have a higher prevalence of ischemia during DET and EET regardless of the presence of collateral flow. These results suggest that the presence of partial anterograde flow in the prolonged period could have a favorable influence on prevalence of residual ischemia in these patients.