Unstable angina associated with factor VIII concentrate therapy for hemophilia A.
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Biomedical subjects
Publications and source records attributed to E M Geltman.
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To assess the contribution of coronary vasospasm to chest pain in patients with nontransmural myocardial infarction, we performed a controlled trial of prophylactic antivasospastic therapy. Fifty patients with nontransmural infarction received either nifedipine or placebo in a double-blind randomized trial. Chest pain occurred in 52% of treated patients (38 episodes on 35 days) compared to 48% of control patients (42 episodes on 33 days). Concurrent therapy was comparable in the two groups. Recurrent infarction occurred in 12% and was comparable between groups. Ejection fraction was similar and was unchanged throughout the study in both groups. Logistic regression failed to identify predictors for recurrent chest discomfort. These data indicate that potent antivasospastic therapy does not reduce the incidence of recurrent chest pain or infarction. Thus, remediable coronary vasospasm is not likely to be a major cause of post infarction ischemia in patients with nontransmural infarction.
Positron emission tomography (PET) is a new technique for noninvasively assessing myocardial metabolism and perfusion. It has provided new insight into the dynamics of myocardial fatty acid and glucose metabolism in normal subjects, patients with ischemic heart disease and those with cardiomyopathies, documenting regionally depressed fatty acid metabolism during myocardial ischemia and infarction and spatial heterogeneity of fatty acid metabolism in patients with cardiomyopathy. Regional myocardial perfusion has been studied with PET using water, ammonia and rubidium labeled with positron emitters, permitting the noninvasive detection of hypoperfused zones at rest and during vasodilator stress. With these techniques the relationship between perfusion and the metabolism of a variety of substrates has been studied. The great strides that have been made in developing faster high-resolution instruments and producing new labeled intermediates indicate the promise of this technique for facilitating an increase in the understanding of regional metabolism and blood flow under normal and pathophysiologic conditions.
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To elucidate the factors involved in the reduced survival rate of diabetic patients after acute myocardial infarction (AMI), we prospectively evaluated 100 patients with well-documented diabetes and 426 control patients. We characterized infarct size and analyzed the incidence and severity of congestive heart failure (CHF) and subsequent death with respect to infarct size. The extent of the index infarct was less in diabetic compared to nondiabetic patients, 16.2 +/- 2.2 CK-gm-eq/m2 compared with 19.2 +/- 0.9 (p less than 0.02). However, CHF was more prevalent in diabetic patients (31.2% of the diabetic patients compared to 15.7%). The difference was most prominent in diabetic patients who had sustained prior infarction (50% compared to 16%), but was evident also in diabetic patients with initial infarction (26% compared to 16%). The mortality rate was greater in diabetic patients (p less than 0.04). When diabetic and nondiabetic patients were stratified with respect to the presence or absence of CHF, survival curves were comparable. The increased incidence of CHF despite a smaller infarct size suggests that additional factors must contribute to myocardial dysfunction and the resultant excess in mortality.
Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevated levels of these proteins in plasma have been used as sensitive indicators of platelet degranulation. Clearance of platelet factor IV is much faster than that of beta-thromboglobulin after release of the proteins in vivo. Although increases of platelet factor IV have been observed in patients with infarction, the implication that they reflect pathogenetic phenomena such as coronary thrombosis has not been assessed explicitly. Accordingly, plasma samples obtained serially from 52 patients with acute myocardial infarction under rigorous conditions verified to minimize platelet degranulation in vitro were evaluated prospectively. Correlative studies were performed to detect left ventricular mural thrombus, and coronary thrombosis was assessed independently in selected patients with indium-111 platelet scintigraphy. Platelet factor IV was normal at the time of admission in patients with infarction, averaging 6.3 +/- 3.3 ng/ml, similar to values in 44 other patients with chest pain without subsequent infarction (5.7 +/- 2.7 ng/ml) and in 25 normal subjects (4.3 +/- 1.6 ng/ml). Platelet factor IV generally did not increase during hospitalization in patients with infarction despite recurrent chest pain, development of left ventricular thrombus or documented recurrent infarction. However, platelet factor IV increased consistently after invasive procedures, accounting for 104 of the total of 110 increases due to platelet activation in vivo as reflected by persistence of elevated levels of beta-thromboglobulin. Thus, platelet factor IV values generally remain normal despite acute myocardial infarction. Rare increases that occur reflect platelet degranulation in vitro due to sampling artifact or perturbations of platelets in vivo due to invasive procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the effects on the heart itself of coronary thrombolysis induced with either tissue-type plasminogen activator (t-PA) or streptokinase (SK), we performed positron emission tomography with 11C-palmitate in 19 patients with initial transmural myocardial infarction immediately after admission and again within 48 to 72 hr after intracoronary administration of t-PA (n = 2) or SK (n = 17). Clots were persistent in eight patients treated with SK despite an average dose of 336,000 IU, sufficient to markedly deplete fibrinogen. In the absence of lysis, favorable tomographic changes did not occur. In contrast, in each of the 11 patients in whom lysis was induced (two with t-PA and nine with SK) myocardial accumulation of 11C-palmitate improved by an average of 29% in late compared with early studies (p less than .001). Results were comparable in patients with anterior and those with inferior infarction. Thus clot lysis induced with either t-PA or SK led to improved regional myocardial metabolism.
Enzymatic estimates of infarct size based on the analysis of either plasma total or CK-MB activity are substantially larger in patients who succumb to myocardial infarction compared with survivors. Similarly, if patients are stratified according to infarct size calculations, mortality increases as infarct size increases. Enzymatic markers of infarction are closely related to other indicators of prognosis, including infarct type (transmural versus nontransmural), infarct location (anterior versus inferior), the degree of left and right ventricular dysfunction, and the frequency of ventricular dysrhythmia. Hence, at least some of the prognostic impact of these variables may be due to the initial extent of infarction sustained. Multivariate analysis has been employed by several groups to analyze the independent contribution of these clinical descriptors to prognosis after infarction. These analyses have consistently indicated a substantial independent impact of enzymatic estimates of infarct size on prognosis. In studies of patients with initial myocardial infarction, infarct size index calculated from total plasma CK time activity curves had the greatest independent influence on survival. Unfortunately, the utility of enzymatic estimates of infarction as prognostic indicators in individual patients is attenuated by alterations in the strength of the apparent association between CK infarct size and prognosis in specific clinical situations. Thrombolytic therapy is now employed with increasing frequency during acute myocardial infarction. It has become abundantly clear that plasma CK release kinetics are profoundly modified by this procedure. Peak plasma total and CK-MB activity is markedly increased compared with that of patients undergoing routine therapy for infarction, with a profoundly altered CK time activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was performed to determine whether positron emission tomography performed after intravenous injection of 11C-palmitate permits detection and characterization of congestive cardiomyopathy. Positron emission tomography was performed after the intravenous injection of 11C-palmitate in 13 normal subjects, 17 patients with congestive cardiomyopathy, and six patients with initial transmural myocardial infarction (defined electrocardiographically). Regionally depressed accumulation of 11C-palmitate was assessed, characterized, and quantified in seven parallel transaxial reconstructions in each patient. Normal subjects exhibited homogeneous accumulation of 11C-palmitate within the left ventricular myocardium, with smooth transitions in regional content of radioactivity. Patients with cardiomyopathy exhibited marked spatial heterogeneity of the accumulation of palmitate throughout the myocardium, easily distinguishable from that in normal subjects and distinct from that observed in patients with transmural infarction, in whom discrete regions of depressed accumulation of palmitate were observed with residual viable myocardium accumulating palmitate homogeneously. Patients with cardiomyopathy exhibited a larger number of discrete noncontiguous regions of accumulation of palmitate within the myocardium than either control subjects or patients with transmural infarction (17.4 +/- 0.6 [SEM] versus 11.8 +/- 0.7 versus 10.3 +/- 0.6, p less than 0.005). Similarly, regions of accumulation of palmitate were irregularly shaped in patients with cardiomyopathy, with a longer normalized perimeter than either control subjects or patients with transmural infarction (2.0 +/- 0.05 versus 1.8 +/- 0.06 versus 1.9 +/- 0.09, p less than 0.05). Regional abnormalities of the accumulation of 11C-palmitate could not be explained by regional differences in left ventricular wall motion or myocardial perfusion. Thus, marked heterogeneity of regional myocardial accumulation of 11C-palmitate is detectable and quantifiable in patients with congestive cardiomyopathy by positron emission tomography and may be particularly valuable for early detection and characterization of cardiomyopathy.
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Glyceryl trinitrate was previously said to be contraindicated in patients with acute myocardial infarction. Its intravenous administration during acute infarction, however, was associated with a beneficial effect as determined by ST segment mapping. Most recently in a selected group of patients with acute infarction and abnormal haemodynamics, intravenous glyceryl trinitrate was shown to reduce infarct size estimated by enzymes. The present study was performed to verify the safety of intravenous glyceryl trinitrate in patients with infarction under conventional clinical conditions without invasive monitoring and to determine its effect on infarct size in a prospective randomised trial involving 85 patients with infarction (43 treated and 42 control). Treated patients received glyceryl trinitrate within 10 hours of the onset of symptoms (mean 6.0 hours), and the dose was titrated to preset limits for changes in heart rate and blood pressure. In patients with inferior infarction, infarct size estimated by enzymes in the treated was only 12.2 +/- 1.8 versus 19.1 +/- 3.6 CK gram equivalents per metre squared in the placebo group. A similar but statistically insignificant trend was observed for subendocardial infarction but no difference was observed for anterior infarction. Ventricular arrhythmias determined from 24 hour tapes were more frequent in treated patients though this was not statistically significant. Lignocaine requirements in treated and control (1692 +/- 250 vs 1512 +/- 232 mg/24 h) were similar, as were the requirements for morphine (11.4 +/- 1.8 vs 12.2 +/- 2.2 mg/24 h). Results indicate that intravenous glyceryl trinitrate can be administered safely during evolving infarction without invasive monitoring and reduces infarct size in patients with inferior infarction.
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Twenty-five hemodialysis patients were randomized into comparable exercising (E, N = 14) and sedentary control (N = 11) groups. After baseline testing, training was 3 to 5 times weekly for a mean of 12 +/- 4 (SD) months. Maximal aerobic capacity increased 21% (P less than 0.01), and the durations for the graded exercise stress test improved 19% (P less than 0.01) in E, but did not change in controls (8 +/- 4 months). Declining blood pressures in 8 hypertensive E led to reductions in antihypertensive medications; no changes occurred in 9 hypertensive controls. Exercise lowered plasma total triglyceride levels 33% (280 +/- 258 to 175 +/- 95 mg/dl; P less than 0.01), but no change occurred in total and low-density lipoprotein cholesterol concentrations. High-density lipoprotein cholesterol levels rose 16% in E (31 +/- 9 to 36 +/- 12 mg/dl; P less than 0.02), but did not change in controls. An increase in the affinity of insulin for receptors on mononuclear cells was associated with a 20% decrease in fasting plasma insulin levels (24 +/- 7 to 19 +/- 2 microU/ml, N = 8; P less than 0.05) and a 42% improvement in glucose disappearance rates (1.9 +/- 1.0 to 2.6 +/- 1.2% per min, N = 6) in E. There were no changes in the body weights or diets of the patients. A 27% increase in red blood cell mass (P less than 0.02) with no change in plasma volume resulted in a 27% increase in hematocrit (24 +/- 3% to 31 +/- 5%, P less than 0.01) and a 20% increase in hemoglobin (8 +/- 1 to 10 +/- 2 g/dl; P less than 0.01) in E.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with nontransmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 +/- 7.8 PET-g-Eq/m2 [+/- SEM SEM]) compared with those with nontransmural infarction (19 +/- 4 PET-g-Eq, p less than 0.01). Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 +/- 1 vs 39 +/- 1% maximal myocardial radioactivity, p less than 0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.
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Gated radionuclide imaging with 99mTc-labeled red blood cells was employed to assess changes in right atrial (RA) volume in 17 subjects. Studies were repeated within two hours in five of 12 normal subjects and at two and ten days after infarction in five patients. Time-activity curves were generated for the RA and right ventricle (RV) from variable regions of interest defined by automatic edge detection. The RA time-activity curve exhibited four phases: filling, early emptying, equilibration, and late emptying. Repeated measurements of RA early emptying rates correlated closely in normals (r = 0.93). Early RA emptying and RV filling rates corresponded closely (r = 0.89). In four patients with infarction, the RA emptying rate was slowed on the first study but had normalized by 10 days. In a patient with inferior infarction and suspected RV infarction, the RA emptying rate was depressed and remained so for 10 days. Thus, relative changes in right atrial volume can be assessed reproducibly by a radionuclide technique, which is relatively independent of geometric assumptions. This technique offers great promise as a method to assess atrial function in health and disease.