Biomedical subjects
Publications and source records attributed to M D Cerqueira.
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A patent infarct-related artery (IRA) following myocardial infarction has been associated with lower mortality, increased systolic function, decreased left ventricular remodeling, and electrical stability. The purpose of this study was to determine whether coronary artery patency early after myocardial infarction is associated with greater early diastolic filling than a closed artery. Radionuclide ventriculograms were performed at a central laboratory on 167 patients who received alteplase for an acute myocardial infarction and had infarct artery patency determined by cardiac catheterization. The peak early filling rate (PEFR) was assessed by 4 different methods: (1) PEFR (EDV/s)--normalized to the end-diastolic volume; (2) PEFR (SV/s)--normalized to the stroke volume; (3) PEFR (ml/s/m(2))--an absolute diastolic filling rate; and (4) PEFR (PER)--normalized to the peak ejection rate. Patients with a closed IRA (n = 16, Thrombolysis In Myocardial Infarction [TIMI] 0 or 1 flow) and patients with an open IRA (n = 151, TIMI 2 or 3 flow) had similar ages, ejection fractions, and cardiac volumes. However, among patients with an occluded IRA, the PEFR was decreased by 12% to 18% by the 4 measures of diastolic filling (3 of 4 methods, p <0.05). PEFR (EDV/s) was 1.69 +/- 0.9 in the occluded group versus 2.06 +/- 0.4 EDV/s in the open artery group (p = 0.005). By multivariate analysis, IRA patency was an independent predictor of the PEFR by all 4 methods. Early coronary artery patency after an acute myocardial infarction preserves diastolic filling. Improved diastolic function may in part explain part of the long-term benefits of a patent IRA after thrombolytic therapy when there is no documented improvement in the ejection fraction.
This article focuses on the following areas of myocardial perfusion imaging: radiotracer and protocol options, pharmacologic stress agents, and protocols and functional assessment with ECG-gated single photon emission CT.
Various cardiac sequelae of mediastinal irradiation have been reported, from pericarditis to conduction defects. Despite the potentially fatal nature of some of these abnormalities, many may present with few or no symptoms. In this case report, the patient, who had received 4000 rads to the mediastinum 24 years previously, presented with worsening shortness of breath and two episodes of lightheadedness. Subsequently, he was found to have aortic valve rupture associated with fibrosis. A review of the literature indicates that valve rupture is a novel consequence of mediastinal radiation.
The historical time of acute symptom onset is not always an accurate indication of the timing of onset of an acute myocardial infarction (AMI). Consideration of electrocardiographic (ECG) timing parameters could supplement historical timing alone as a clinical guide for decisions regarding the use of reperfusion therapy. Three hundred ninety-five patients from 4 trials of thrombolytic therapy conducted in the northwestern United States and western Canada are included in the present study. A total of 316 patients received either streptokinase or tissue plasminogen activator, and 79 received no reperfusion therapy. Historical time of symptom onset was acquired by emergency or cardiology department personnel and recorded on patient report forms. An ECG method for estimating the timing of the AMI, the Anderson-Wilkins (AW) acuteness score, was calculated from the initial standard 12-lead recording by investigators blinded to the knowledge of symptom duration or any other study variables. Tomographic thallium-201 imaging 7 weeks after hospital admission was used to measure final AMI size. The ECG timing method achieved a relation with final AMI size similar to that previously reported for historical timing. The AW acuteness score proved most useful for anterior AMI location when there was a > or = 2 hour delay following symptom onset, but was most useful for the inferior AMI location when there was a < 2 hour delay. Despite a longer delay, patients with high AW acuteness scores had 50% lower final anterior AMI size than those with low scores; and despite a shorter delay, those with low ECG acuteness scores had 50% greater final inferior AMI size than those with high scores. The AW acuteness score combined with the historical estimation of symptom duration should provide a more accurate basis for predicting the potential for limitation of final AMI size than either method alone. These results could potentially provide the basis for developing a new method for noninvasive guidance of clinical decisions regarding administration of reperfusion therapy in the initial evaluation of patients with AMI.
The imaging of thrombi and atherosclerotic plaques has great potential for decision making in the management of patients with all types of disease within the circulatory system. This importance is owing to the developments showing that areas of moderate stenosis with underlying atheroma are physiologically reactive and capable of causing reversible clinical symptoms that can progress to irreversible end-organ damage if not effectively treated. Identifying and quantifying areas of smaller vulnerable plaque and areas of acute thrombosis will assist in identification of patients at risk and help determine when and how to treat these patients. Initial efforts in this area used nonspecific constituents of thrombi and atheroma that were radiolabeled using long-lived isotopes, which had high background activity that required imaging over 48 to 72 hours. Newer approaches have focused on the use of small antibody fragments or small peptides, so-called molecular recognition units, that specifically target antigens present only in areas of thrombosis or active atherogenesis. These compounds are labeled Technetium-99 m (99mTc) and provide excellent images. Efforts to image thrombi have been directed at the IIB/IIIA receptor, which is present in low concentration on the cell membrane of circulating quiescent platelets, but on stimulation and active thrombosis, more than 80,000 potential binding sites per platelet appear. One such peptide has been clinically approved for imaging of deep vein thrombophlebitis. Parallel efforts are being made for imaging areas of active atherogenesis by targeting smooth muscle cells and other constituents unique for vulnerable plaques. Efforts in developing these modalities are important to expand the applications to new areas in nuclear cardiology.
Although the increased risk of cardiac complications in surgical patients with diminished left ventricular ejection fraction (LVEF) is well-established, this method has been supplanted in recent years by assessment of ischaemic burden using myocardial perfusion imaging (MPI). This study was conducted to determine if MPI and LVEF determination provide complementary or redundant information in preoperative evaluation of vascular surgery patients. A total of 101 patients were studied with dipyridamole MPI and radionuclide ventriculography before surgery. Single photon emission tomographic MPI images were scored for defect severity and categorized as either fixed or reflecting ischaemia. Resting left ventricular cavity was also categorized as normal or dilated. LVEF was subdivided into normal (> or = 50%) and abnormal (< 50%). Seventeen patients had cardiac events. Events were more frequent in patients with ischaemia, in patients with a LVEF < 50% and in those with dilated left ventricular chambers. The mean number of ischaemic segments was also higher in the cardiac event group. Higher event rates were seen when a combination of these factors was present. A history of myocardial infarct, congestive heart failure or coronary artery disease was also a significant predictor of subsequent events. Thus, both abnormal left ventricular function and extent of ischaemic myocardium have independent and complementary predictive power for cardiac events in vascular surgery patients.
Local information on permeability of the alveolar-capillary barrier (PACB) can be ascertained by parametric images, after inhalation of radioarosols and computer processing. Our aim is to compare the results of 99mTc-HMPAO aerosols on PACB studies with those of 99mTc-DTPA aerosols, a standard technique. We compared the two techniques in separate samples: normal controls and patients with severe lung interstitial pathologies. Perfusion studies using 99mTc-MAA have also been performed in all patients. The aerosols were produced using ultrasound and lowered surface tension solution of 99mTc-HMPAO and 99mTc-DTPA. The time-activity curves (TACs) for every pixel on the lung area were used to calculate the half-disappearance times (T1/2). Parametric images were then generated with those times. The comparison of the results obtained with 99mTc-HMPAO and 99mTc-DTPA aerosols suggests that the first ones are more specific for local alterations of the lung epithelial transport in the pathologies studied. This method distinguishes between permeability deficiency due to local perfusion decrease and ACB deterioration.
Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.
BACKGROUND: Patients with acute myocardial infarction (AMI) who are not eligible for thrombolytic therapy or primary coronary angioplasty are distinguished by advanced age, complicated medical histories, relatively frequent use of prior revascularization procedures, and worse outcomes than their counterparts who are eligible for reperfusion therapy. METHODS AND RESULTS: The purpose of this randomized, controlled trial was to determine whether RheothRx, a hemorheologic agent, reduced myocardial infarct size and improved left ventricular function in patients who had suspected AMI at the time of hospital admission and were not eligible for reperfusion therapy. Patients were randomly assigned to RheothRx (n = 97) or placebo (n = 99). Patients in the two groups were similar with respect to age, sex, medical history, and clinical presentation. Enzyme evidence of AMI was present in 69% of the treatment group and 70% of the placebo group. Infarct size measured before hospital discharge was similar in the two groups (14.1% +/- 18.5% vs 11.7% +/- 14.1%, p = 0.60), although left ventricular ejection fraction was lower in the treatment group (47 +/- 14 vs 52 +/- 11, p = 0.026). Hospital mortality rate was 11.3% and 7.1% in patients receiving RheothRx and patients receiving placebo, respectively (p = 0.30). There was a higher occurrence of acute renal dysfunction in the RheothRx group (12% vs 2%, p = 0.005). Because of changes in drug dosage necessitated by the occurrence of acute renal dysfunction, the trial was stopped. CONCLUSIONS: In this study of patients who had suspected AMI and were not eligible for thrombolytic therapy, RheothRx did not decrease infarct size or favorably alter outcome. The need for effective treatment for this large patient population remains largely unmet.
Left ventricular cavity (LVC) enlargement during SPET dipyridamole 201Tl myocardial perfusion imaging studies is a proven marker of severity of coronary artery disease. Nevertheless, the influence of the extent of myocardial infarct and ischaemia on the degree of LVC enlargement both at rest and with dipyridamole has not been clearly analysed. One hundred and one patients were studied by both dipyridamole myocardial perfusion imaging and radionuclide ventriculography within 1 week. The left ventricular ejection fraction (LVEF) was 57 +/- 9 in normal resting LVC patients (group I), 43 +/- 8 in mild LVC enlargement patients (group II) and 28 +/- 5 in moderate-to-severe LVC enlargement patients (group III). The number of fixed defects was increased in patients in group II and group III, but there was no significant differences in the number of ischaemic segments among groups. The number of ischaemic segments was much higher in patients with transient cavity dilatation than those without cavity change; nonetheless, both LVEF and the numbers of fixed segments were unchanged. The degree of LVC enlargement at rest strongly reflects the resting left ventricular systolic function as well as the extent of previous myocardial infarct. On the other hand, transient cavity dilatation during dipyridamole infusion can only reflect the extent of viable myocardium at risk.
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BACKGROUND: Myocardial salvage is most likely to occur when thrombolytic therapy is administered within 4 to 6 hours of the onset of symptoms of myocardial infarction. The impact of delays within this early time period on final myocardial infarct size are unknown. The purpose of this study was to quantitate the relation between final myocardial infarct size and duration of symptoms before initiation of thrombolytic therapy in patients treated within 6 hours of symptom onset. METHODS AND RESULTS: The findings from patients in four prospective randomized trials of thrombolytic therapy were combined for analysis. The study population consisted of 432 patients presenting within 6 hours of onset of symptoms of first acute myocardial infarction who met ECG criteria that allowed estimation of myocardial area at risk before treatment with thrombolytic therapy and who had thallium-201 myocardial infarct-size measurements performed several weeks after infarction. ECG analysis revealed no difference in myocardium at risk for infarction as a function of duration of symptoms before initiation of thrombolytic therapy. In contrast, univariate and multivariate analysis showed that final infarct size was highly dependent on duration of symptoms before initiation of therapy. Each 30-minute increase in symptom duration before thrombolytic therapy was associated with an increase in infarct size of 1% of the myocardium. Final infarct size in patients treated 4 to 6 hours after symptom onset was indistinguishable from patients who did not receive thrombolytic therapy. CONCLUSIONS: These findings suggest that for patients treated within 4 to 6 hours of the onset of symptoms, there is a progressive decline in the extent of myocardium salvaged as the duration of symptoms before therapy increases. These results support efforts to minimize the time delay between symptom onset and initiation of reperfusion therapy in all eligible patients.
BACKGROUND: Annexin V is a human phospholipid binding protein that binds to activated platelets in vitro. We sought to determine the potential of this agent for imaging intracardiac thrombi in swine. METHODS AND RESULTS: Left atrial thrombi were formed by crush injury. In initial nonimaging experiments using intravenous 125I-labeled human annexin V, the mean thrombus/whole blood ratio was 13.4 +/- 4.8 for the entire thrombus using well counting of resected specimens (n = 8). Using intravenously injected 99mTc-labeled human annexin V, the left atrial thrombus/blood ratio by well counting was similar (14.2 +/- 10.6 for the entire thrombus and 26.2 +/- 14.9 for the peak section) (n = 12). The ratio for a control protein, 125I-ovalbumin, was only 1.0 +/- 0.2. 99mTc tomographic imaging was positive (n = 10) or equivocal (n = 2) in all experiments with but negative in 10 controls without left atrial thrombi. By region-of-interest analysis of the tomographic images, the mean left atrial appendage/blood ratio at 2 hours in animals with a thrombus was 3.90 +/- 1.12 compared with 0.84 +/- 0.10 in closed chest controls and 1.01 +/- 0.23 in open chest controls (P < .001). CONCLUSIONS: We conclude that 99mTc-labeled human annexin V detects acute left atrial thrombi in vivo in swine. The combination of a new thrombus detection agent, annexin V, with a 99mTc label may allow in vivo imaging of thrombi in humans.
Early reports of the prevalence, diagnosis, and outcomes of coronary artery disease (CAD) in women have led to the acceptance of several myths concerning noninvasive diagnostic studies in women. Many of the myths can be explained by age-related differences in prevalence, methodological errors that exclude women from enrollment, worse clinical baseline risk profiles, comorbid diseases at the time of interventions, and smaller coronary vessels. Awareness of these age-related prevalence factors in women and the potential for delaying the onset of CAD by estrogen treatment in postmenopausal women must be considered in assessing the accuracy of diagnostic studies. The critical role of noninvasive testing in women is to diagnose CAD accurately in a population with a lower prevalence of disease prior to the development of more severe clinical manifestations when therapeutic interventions have a high risk and a poor outcome. Exercise radionuclide ventriculography has lower specificity in women, which may be due to gender differences in the response to exercise. Radionuclide perfusion imaging for the detection of CAD is accurate, there is extensive published literature, and it is used widely. High-dose dipyridamole in combination with echocardiography is not widespread in the United States; most pharmacologic echocardiographic studies are performed using dobutamine, and there are no reports on gender differences using dobutamine echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
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