Search

The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects. [ABSTRACT FROM AUTHOR]

Interventions involving calcium cycling may represent a promising approach to heart failure (HF) therapy because calcium handling is known to be deranged in human and experimental HF. Istaroxime is a sodium-potassium adenosine triphosphatase (ATPase) inhibitor with the unique property of increasing sarcoplasmic reticulum calcium ATPase (SERCA) isoform 2a (SERCA2a) activity. Because this was demonstrated in normal experimental models, we investigated whether istaroxime is able to improve global cardiac function and stimulate SERCA in failing hearts. In guinea pigs with 3-month aortic banding (AoB), echocardiographic results showed that istaroxime intravenous infusion (0.11 mg/kg per min) significantly increased both indices of contraction and relaxation (fractional shortening, +18+/-3.7%; aortic flow rate, +19+/-2.9%; peak myocardial systolic velocity, +36+/-7%; circumferential fiber shortening, +24+/-4.1%; peak atrial flow velocity, +69+/-8.6%; isovolumic relaxation time, +19+/-6.9%; and peak myocardial early diastolic velocity, +42+/-12%). In left ventricular sarcoplasmic reticulum microsomes from AoB animals, 100 nmol/L istaroxime normalized the depressed (-32%) SERCA2a maximum velocity and increased SERCA activity (+17%). In muscle strips from hearts from patients undergoing cardiac transplantation, istaroxime (0.1-1.0 micromol/L) increased (in a concentration-dependent manner) developed tension, the maximum and minimum first derivative of tension, and absolute velocity of contraction, while stimulating SERCA activity in sarcoplasmic reticulum microsomes at physiologic free calcium concentrations. In conclusion, istaroxime is presently the only available compound that stimulates SERCA2a activity and produces a luso-inotropic effect in HF.

The role of transthoracic echocardiography as a predictor of recovery after revascularization has not yet been established. Two-dimensional echocardiography was performed in 15 patients with a healed anterior wall myocardial infarction and severe, isolated stenosis of the left anterior descending coronary artery before, and 3 to 6 months after angiographically confirmed successful revascularization. The asynergic segments were classified into 2 groups according to 2 different echocardiographic patterns: those showing a normal acoustic reflectance with normal end-diastolic thickness (pattern A segments) and those showing an increase in acoustic reflectance and reduced end-diastolic thickness (pattern B segments). We hypothesized that pattern A segments were more likely to recover (viable myocardium) and that pattern B segments were consistent with irreversibility. A total of 240 segments in the 15 patients were evaluated before and after revascularization. Sixty-seven segments were asynergic; of these, 52 were judged to have pattern A and 15 pattern B. Of the 52 pattern A segments, 27 were hypokinetic and 25 akinetic. All of the pattern B segments were akinetic (n = 9) or dyskinetic (n = 6). Pattern A was predictive of postoperative recovery in 39 of 52 segments (75%) (p < 0.0001); pattern B was predictive of irreversibly damaged tissue in 13 of 15 segments (87%) (p < 0.0001). Thus, in patients with healed anterior wall myocardial infarction, resting transthoracic echocardiography is a simple and reliable predictor of the behavior of asynergic segments after revascularization.

After myocardial infarction, regional dysfunction can occur in viable myocardial regions because of the presence of baseline hypoperfusion. Recent evidence suggests that these areas may maintain a residual perfusion reserve. The aim of the present study was to evaluate whether oral nisoldipine can increase regional myocardial blood flow (MBF) in dyssynergic but viable myocardium after myocardial infarction. Patients with isolated left anterior descending coronary stenosis were studied 1 month after the first myocardial infarction. Patients underwent [18F]fluorodeoxyglucose imaging, and MBF was measured, using positron emission tomography and [13N]ammonia, at baseline and following dobutamine administration (10 micrograms/kg/min over 5 minutes). MBF measurements were repeated 24 hours after nisoldipine (10 mg twice daily). Preliminary results suggest that necrotic areas showed the largest reduction in baseline MBF. Dyssynergic-viable regions showed a reduced resting MBF but maintained a residual perfusion reserve in response to inotropic stimulation. Thus, nisoldipine selectively improved basal perfusion in dyssynergic-viable myocardium.

Myocardial perfusion measurements were obtained with positron emission tomography under basal conditions and after intravenous dipyridamole infusion (0.56 mg/kg over 4 minutes) to determine if myocardial perfusion is maximized in areas of resting wall motion abnormalities in patients with stable angina. Thirty-three patients with no history of myocardial infarction, and with coronary stenosis > 50% involving the left anterior descending (n = 24) and left circumflex (n = 9) coronary arteries were evaluated. Quantitative perfusion images were recorded twice in each subject using nitrogen-13 ammonia at baseline and after intravenous administration of dipyridamole. Computer-assisted analysis of left ventriculograms showed abnormal wall motion in the stenosis-related regions in 16 patients (group 1), and normal regional function in 17 (group 2). The flow values in the anterior and posterolateral wall were considered to reflect left anterior and left circumflex coronary artery flow, respectively. Quantitative angiography showed that coronary stenosis severity was higher in group 1 than in group 2 (cross-sectional area reduction 94 +/- 7% vs 87 +/- 11%; p < 0.05). Resting blood flow in the stenosis-related areas was significantly lower than in contralateral regions in group 1 (0.66 +/- 0.19 vs 0.77 +/- 0.26 ml/min/g; p < 0.05), but not in group 2 (0.73 +/- 0.18 vs 0.78 +/- 0.21 ml/min/g; p = NS). Dipyridamole significantly (p < 0.01) increased myocardial blood flow in both stenotic and remote regions in both groups 1 (0.95 +/- 0.41 vs 1.57 +/- 0.70 ml/min/g) and 2 (1.54 +/- 0.53 vs 2.01 +/- 0.84 ml/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)

The behavior of myocardial blood flow (MBF) regulation in territories supplied by angiographically normal vessels of patients with coronary artery disease (CAD) has been poorly investigated. Resting MBF and coronary reserve were evaluated in 32 patients with stable angina, no previous myocardial infarction, and isolated left anterior descending or left circumflex coronary artery stenosis (> or = 50% diameter narrowing). MBF was measured, in the absence of any medical therapy, by means of dynamic positron emission tomography and 13N-ammonia. MBF measurements at baseline and after intravenous dipyridamole (0.56 mg/kg administered over 4 minutes), were obtained both in the stenosis-related regions and in contralateral territories. As a control group, 14 normal subjects were evaluated according to the same protocol. At rest, the 32 patients with CAD had similar MBF values in the stenotic and remote regions (0.76 +/- 0.21 and 0.77 +/- 0.19 ml/min/g, respectively, p = NS); both these values were significantly (p < 0.01) reduced with respect to mean MBF in normal subjects (1.03 +/- 0.25 ml/min/g). The dipyridamole study was completed in 30 patients; these patients had lower values of maximal MBF in the stenotic than in the remote regions (1.52 +/- 0.65 vs 1.76 +/- 0.68 ml/min/g, p < 0.05); however, both these values were significantly reduced (p < 0.01) with respect to mean dipyridamole MBF in normal subjects (3.66 +/- 0.92 ml/min/g). Thus, in patients with CAD, resting and maximal MBF can be reduced not only in myocardial territories supplied by stenotic arteries, but also in territories supplied by angiographically normal arteries.

To assess whether myocardial stunning occurs after brief periods of ischemia, global and regional ventricular function assessed by radionuclide angiography was studied in 52 patients. Patients were divided into 3 groups according to the type of ischemic episodes. Group 1 consisted of 15 patients studied before, during and after episodes of angina at rest. Seventeen patients studied immediately before and after coronary angioplasty constituted group 2. Group 3 consisted of 20 patients with stable angina studied before, during and after exercise-induced ischemia. Medical therapy was discontinued 48 hours before the study in all patients except those undergoing coronary angioplasty who were receiving diltiazem 180 mg/day. No difference in baseline ejection fraction was found between groups, whereas peak filling rate was statistically lower in group 3 patients. Evidence of left ventricular dysfunction during ischemia was seen in patients in groups 1 and 3, whereas transient ischemia was documented by ST-segment displacement and/or typical chest pain during balloon inflation in group 2. Persistence of systolic or diastolic dysfunction was not observed in any of the 3 groups in the recovery phase after ischemia. In conclusion, transient ischemia caused either by a primary reduction in oxygen supply (angina at rest, coronary angioplasty) or by an increase in oxygen demand (angina on effort) did not reproduce the phenomenon of systolic and diastolic stunning observed in animal experiments, although in all patients the ischemia was of sufficient duration and severity to induce marked ventricular dysfunction. The search for stunned myocardium should be extended to other different clinical models characterized by prolonged ischemia such as unstable angina or myocardial infarction.

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)

In patients with coronary artery disease and left ventricular impairment, the distinction between ventricular dysfunction due to myocardial fibrosis and postischemic, viable, although dys-synergic, myocardium has important clinical implications. Experimental studies have shown that dipyridamole can increase myocardial function in stunned segments, outlining a potential role of dipyridamole-induced functional recovery as an ultrasonic marker of myocardial viability. The aim of this study was to assess whether the increase of regional left ventricular function early during dipyridamole infusion in basally asynergic segments could identify viable myocardium recognized by rest injected, delayed (greater than 14 hours from tracer injection) thallium and (in a subset of patients) late functional recovery evaluated by a follow-up echocardiogram at rest. Twenty-two patients with angiographically documented coronary artery disease and regional dysfunction in resting conditions (average left ventricular ejection fraction 43 +/- 8%) were studied by echocardiography. All patients underwent a dipyridamole-echocardiographic test (up to 0.84 mg/kg over 10 minutes) and a delayed planar thallium study. A 13-segment model was used for both techniques. A score index ranging from 1 (normokinesia) to 4 (dyskinesia) was used for echocardiography. Thallium-201 activity was expressed in each segment as the percentage of maximal activity in the corresponding view. After dipyridamole, the wall motion score was assigned to each segment in resting conditions and at peak hyperkinesia before possible mechanical signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study investigated whether the lack of enzyme increase is reason enough to exclude necrosis in patients with ischemic heart disease who develop electrocardiographic sustained ST-T changes in the absence of Q waves. In 15 consecutive patients with angina who developed sustained ST-T changes during hospitalization, the presence of myocardial necrosis was investigated by a prospective multiparametric approach. Serum enzymes and myoglobin, pyrophosphate uptake, 2-dimensional echocardiography, perfusion scintigraphy, left ventriculography and coronary angiography were evaluated. According to creatine kinase and creatine kinase-MB peak at twice the upper normal value, the diagnosis of acute myocardial infarction applied only to 40% of patients. However, myoglobin was positive in 80% and a perfusion defect could be documented by an electrocardiographic gated microsphere technique in 100% of patients. The positivity of myoglobin increased to 100% and of creatine kinase and creatine kinase-MB to 87 and 60%, respectively, when a peak value twice the individual lowest value was considered for positivity. The 100% presence of perfusion defects associated with the high prevalence of both positive pyrophosphate uptake (87%) and regional dyssynergies (87 and 73%, respectively, by left ventriculography and echocardiography) strongly suggest that sustained (greater than or equal to 7 days) ST-T changes in this population were indicative of myocardial necrosis. Thus, by conventional enzymatic approach, diagnosis of non-Q-wave infarction can be missed in a sizable number of patients and present important clinical implications.

The clinical responses to 12 months' treatment with verapamil were evaluated in 63 patients with stable and unstable angina pectoris in whom the effectiveness of verapamil had been established in short-term double-blind placebo-controlled randomized clinical trials. In 41 patients with effort-related angina, long-term responses were sustained for periods exceeding 1 year. Twenty patients were evaluated by clinical history and showed a sustained reduction in frequency of anginal attacks and consumption of nitroglycerin with verapamil compared with the initial placebo control periods; the magnitude of this benefit was similar to that observed during double-blind treatment with the drug. Twenty-one patients were evaluated by serial treadmill exercise testing and showed a sustained improvement in exercise duration after 4, 8, 16, 24, and 52 weeks of verapamil treatment; withdrawal of the drug resulted in a deterioration of exercise performance to levels similar to those seen before initiation of therapy. In 22 patients with unstable angina at rest, verapamil produced an amelioration of anginal symptoms that was sustained in most patients for longer than 1 year. However, these patients continued to have a high incidence of death and myocardial infarction in a frequency similar to that previously reported in large clinical studies using either combinations of verapamil and nitrates, nifedipine and propranolol, or propranolol and nitrates. Calcium-channel antagonists may decrease the number of patients requiring coronary artery bypass surgery for relief of refractory angina, but they do not appear to alter the natural history of the disease.