Patterns of left ventricular dilation during the six months after myocardial infarction.

Changes in left ventricular volume after a first myocardial infarction were studied in 50 patients. Serial radionuclide angiograms were obtained 48 h, 10 days and 1 and 6 months after infarction and left ventricular volume measured by a nongeometric method. Left ventricular dilation (greater than or equal to 20% increase in end-diastolic volume) occurred within 10 days of infarction in 11 patients, who had a mean volume increase of 34 +/- 15% (p = 0.002 versus 48 h) at 10 days and 61 +/- 43% (p = 0.01 versus 10 days) at 6 months. Ten other patients manifested left ventricular dilation between 10 days and 6 months with a lesser volume increase of 42 +/- 18% by 6 months. Among the 21 patients with ventricular dilation, progressive dilation (serial volume increases greater than or equal to 20% on two or more occasions) occurred in 8 patients, who all had a large anterior infarct. Mean volume increases at 10 days and 1 and 6 months were 27 +/- 20%, 49 +/- 40% (p = 0.03 versus 10 days) and 79 +/- 37% (p = 0.006 versus 1 month), respectively, in this group. In patients with progressive dilation, left ventricular ejection fraction decreased from 35 +/- 6% at 48 h to 24 +/- 10% at 1 month (p less than 0.001) and 27 +/- 10% (p = 0.006) at 6 months. Between 1 month and 2 years after infarction six patients died, of whom four had progressive dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans.

OBJECTIVES: The purpose of this study was to assess the extent and reversibility of neuronal abnormalities in patients with an acute myocardial infarction. BACKGROUND: Previous experimental studies have described ischemic injury to sympathetic neurons exceeding the area of myocardial necrosis. Carbon-11 (C-11) hydroxyephedrine (HED) is a norepinephrine analogue that can be used for the noninvasive evaluation of neuronal integrity using positron emission tomography. METHODS: We studied 14 volunteers and 16 patients experiencing a first acute myocardial infarction. Positron emission tomographic imaging was used to quantitatively compare regional perfusion, as assessed with nitrogen-13 ammonia, with myocardial retention of C-11 hydroxyephedrine early after myocardial infarction as well as > 6 months after the acute event. RESULTS: C-11 hydroxyephedrine and flow images demonstrated homogeneous tracer retention in volunteers but were abnormal in all patients. C-11 hydroxyephedrine abnormalities were more extensive than those for blood flow assessed by semiquantitative polar map analysis (31 +/- 15% vs. 17 +/- 17% left ventricle; p < 0.05), particularly in five patients with non-Q wave infarction (31 +/- 11% vs. 3.5 +/- 2.5% left ventricle; p = 0.008). Eleven patients with Q wave infarction had matched defects (28 +/- 17% vs. 21 +/- 17% left ventricle; p = NS). C-11 hydroxyephedrine tissue retention fraction was quantified in three tissue zones: zone 1 (abnormal rest flow) had retention fraction 0.037 +/- 0.022-min; zone 2 (normal rest flow but decreased carbon-11 hydroxyephedrine retention) had retention fraction 0.068 +/- .034-min, and zone 3 (normal flow and carbon-11 hydroxyephedrine retention) had retention fraction 0.087 +/- 0.041-min (p = 0.0004). Follow-up studies at 8 +/- 3 months in eight patients revealed no change in extent of abnormalities or absolute tissue tracer retention in infarct and peri-infarct territories. CONCLUSIONS: The results of abnormal regional sympathetic innervation in patients with infarction confirm previous experimental data and suggest persistent neuronal damage in infarct and peri-infarct territories, without evidence of reinnervation of reversibly injured myocardium.

Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris.

The prognostic significance of exercise testing was compared with clinical and electrocardiographic (ECG) variables in a prospective study of 107 patients with unstable angina discharged from the hospital on medical therapy. During a follow-up period of 12.8 +/- 1.4 months, 10 patients (9%) had a nonfatal myocardial infarction (n = 8) or died (n = 2) and 22 (20%) were readmitted with recurrent unstable angina. The relation between 20 clinical, ECG and exercise test variables and the risk of adverse outcome (death, nonfatal myocardial infarction or recurrent unstable angina) was analyzed using both univariate and multivariate (logistic regression) analysis. Univariate predictors of adverse outcome included diabetes mellitus, evolutionary T wave changes, T wave changes on the preexercise ECG and low maximal rate-pressure product during exercise. Independent predictors of adverse outcome in multivariate analysis included diabetes mellitus, evolutionary T wave changes after admission, rest pain during hospitalization, ST depression during exercise and low maximal rate-pressure product. A predictive model constructed using the regression equation and all independent predictors stratified patients into high and low risk groups (41% and 5% risk of adverse outcome, respectively). The result of a predischarge exercise test adds independent prognostic information to clinical and ECG data in medically treated patients with unstable angina and could be used in combination with clinical and ECG data to identify patients at risk of adverse events.

Positron emission tomography detects evidence of viability in rest technetium-99m sestamibi defects.

OBJECTIVES: The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium. BACKGROUND: Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability. METHODS: Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia. RESULTS: Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had > or = 60% F-18 deoxyglucose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity < 40%. There was no significant difference in the mean (+/- SD) technetium-99m sestamibi activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007). CONCLUSIONS: Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used.

Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography.

OBJECTIVES: The purpose of this investigation was to evaluate the sympathetic nervous system of the heart by positron emission tomographic (PET) imaging in patients with diabetes mellitus with and without diabetic autonomic neuropathy. BACKGROUND: The clinical assessment of cardiac involvement in diabetic autonomic neuropathy has been limited to cardiovascular reflex testing. With the recent introduction of radiolabeled catecholamines such as carbon (C)-11 hydroxyephedrine, the sympathetic innervation of the heart can be specifically visualized with PET imaging. METHODS: Positron emission tomographic imaging was performed with C-11 hydroxyephedrine and rest myocardial blood flow imaging with nitrogen-13 ammonia. Three patient groups were studied, including healthy volunteers as control subjects, diabetic patients with normal autonomic function testing and diabetic patients with varying severity of autonomic neuropathy. Homogeneity of cardiac tracer retention as well as absolute tracer retention was determined by relating myocardial tracer retention to an arterial C-11 activity input function. RESULTS: Abnormal regional C-11 hydroxyephedrine retention was seen in seven of eight patients with autonomic neuropathy. Relative tracer retention was significantly reduced in apical, inferior and lateral segments. The extent of the abnormality correlated with the severity of conventional markers of autonomic dysfunction. Absolute myocardial tracer retention index measurements showed a 45 +/- 21% decrease in distal compared with proximal myocardial segments in autonomic neuropathy (0.069 +/- 0.037 min-1 vs. 0.13 +/- 0.052 min-1, p = 0.02). CONCLUSIONS: This study demonstrates a heterogeneous pattern of neuronal abnormalities in patients with diabetic cardiac neuropathy. The extent of this abnormality correlated with the severity of neuropathy assessed by conventional tests. Future studies in larger groups of patients are required to define the relative sensitivity of this imaging approach in detecting cardiac neuropathy and to determine the clinical significance of these scintigraphic findings in comparison with conventional markers of autonomic innervation.

Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy.

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.

Determination of extent and location of coronary artery disease in patients without prior myocardial infarction by thallium-201 tomography with pharmacologic stress.

Seventy-six patients undergoing pharmacologic stress 201TI tomography and coronary angiography within 14 +/- 12 days were studied to determine how well coronary artery disease extent and location could be determined by this scintigraphic technique. No patient had prior myocardial infarction or revascularization. Scintigrams were scored visually and quantitatively. Angiographic lesions > or = 50% were considered significant. Receiver operating characteristic curves were generated for the scintigrams against the angiographic gold standard. Predictive accuracies were determined and compared with the quantitative results. Predictive accuracy was 0.49 for visual and 0.58 for computer identification of single-vessel disease, 0.52 for both visual and computer identification of multivessel disease, 0.64 for both in correctly localizing left anterior descending artery disease, 0.78 versus 0.70 for the right coronary artery and 0.72 versus 0.68 for the left circumflex artery. For the overall detection of disease, the predictive accuracies were 0.79 and 0.80. Although high diagnostic accuracy for detection of coronary artery disease by this approach has been previously documented, the assessment of extent of disease in patients without prior myocardial infarction appears limited.

Regression and progression of cardiac sympathetic dysinnervation complicating diabetes: an assessment by C-11 hydroxyephedrine and positron emission tomography.

Cardiovascular denervation complicating diabetes has been implicated in sudden cardiac death potentially by altering myocardial electrical stability and impairing myocardial blood flow. Scintigraphic evaluation of cardiac sympathetic integrity has frequently demonstrated deficits in distal left ventricular (LV) sympathetic innervation in asymptomatic diabetic subjects without abnormalities on cardiovascular reflex testing. However, the clinical significance and subsequent fate of these small regional defects is unknown. This study reports the results of a prospective observational study in which positron emission tomography (PET) with (-)-[11C]-meta-hydroxyephedrine ([11C]-HED) was used to evaluate the effects of glycemic control on the progression of small regional LV [11C]-HED retention deficits in 11 insulin-dependent diabetic subjects over a period of 3 years. The subjects were divided into two groups based on attained glycemic control during this period: group A contained six subjects with good glycemic control (individual mean HbA1c <8%), and group B contained five subjects with poor glycemic control (individual mean HbAlc > or =8%). Changes in regional [11C]-HED retention were compared with reference values obtained from 10 healthy aged-matched nondiabetic subjects. At baseline, abnormalities of [11C]-HED retention affected 7.3%+/-1.4% and 9.9%+/-6.6% of the LV in group A and B subjects, respectively, with maximal deficits of LV [ C]-HED retention involving the distal myocardial segments. At the final assessment in group A, the extent of the deficits in [11C]-HED retention decreased to involve only 1.7%+/-0.7% of LV (P<.05 v. baseline scan), with significant increases in [11C]-HED retention occurring in both the distal and proximal myocardial segments. In contrast, in group B with poor glycemic control, the extent of [11C]-HED deficits increased to involve 34%+/-3.5% of the LV (P<.01 v. baseline), with retention of [11C]-HED significantly decreasing in the distal segments ([11C]-HED retention index, 0.066+/-0.003 v. 0.057+/-0.002, P<.05, at baseline and final assessment, respectively). Poor glycemic control was associated with increased heterogeneity of LV [11C]-HED retention, since three of five group B subjects developed abnormally increased [11C]-HED retention in the proximal myocardial segments. In conclusion, defects in LV sympathetic innervation can regress or progress in diabetic subjects achieving good or poor glycemic control, respectively. In diabetic subjects with early cardiovascular denervation, institution of good glycemic control may prevent the development of myocardial sympathetic dysinnervation and enhanced cardiac risk.

Prognostic significance of right ventricular ejection fraction following inferior myocardial infarction.

The prognostic significance of right ventricular ejection fraction, measured by radionuclide ventriculography, was assessed in 168 consecutive patients with inferior myocardial infarction. Right ventricular ejection fraction was 0.40 or less in 35 patients. Over a follow-up period of 40 months, there were 15 deaths in the total group of 168 patients, eight (23%) in the 35 with right ventricular ejection fraction of 0.40 or less, and seven (5%) in the remainder of the group. The one year survival of patients with right ventricular impairment (84 +/- 6%) was significantly worse (P less than 0.01) than those with a right ventricular ejection fraction over 0.40 (95 +/- 2%). A multivariate Cox model analysis showed age (P less than 0.001), left ventricular ejection fraction (P less than 0.01), and right ventricular ejection fraction (P less than 0.03) to be independent predictors of survival. Impaired right ventricular function is an adverse prognostic factor in patients with inferior infarction, particularly in those with impaired left ventricular function.

Abnormal Tl-201 myocardial scintigraphy associated with administration of sodium aurothiomalate.

A patient with strikingly reduced Tl-201 myocardial retention after intramuscular administration of gold therapy (sodium aurothiomalate) is described. Following a routine Bruce protocol exercise test, postexercise scintigraphy was normal; an abnormal scan of the thorax was obtained on delayed imaging at 3 hours. This scan showed no demonstrable myocardial retention of tracer. In between the two acquisitions, the patient received 50 mg intramuscular sodium aurothiomalate for rheumatoid arthritis. A repeat scan obtained 3 days later showed a normal myocardial scintigram. It is recommended that patients receiving intramuscular gold therapy should not undergo such treatment close to the timing of Tl-201 myocardial scans.

Tc-99m stannous colloid-labeled leukocyte scintigraphy in the evaluation of the painful arthroplasty.

The aim of this study was to evaluate the utility of scintigraphy using leukocytes labeled with Tc-99m stannous colloid in the assessment of painful arthroplasties. The results of three-phase bone scintigraphy and imaging with Tc-99m-labeled leukocytes in 40 patients with painful joint prostheses, requiring the exclusion of infection are reported. Results were compared with microbiologic culture and/or long-term clinical review. Bone scintigraphy had a sensitivity of 100%, a specificity of 64%, and a diagnostic accuracy of 73% in detecting prosthetic infection. Tc-99m-labeled leukocytes yielded a sensitivity of 70%, a specificity of 100%, and a diagnostic accuracy of 93%. Leukocyte scintigraphy improves the specificity of bone scintigraphy in the assessment of the painful prosthetic joint. A positive study is highly suggestive of infection and warrants appropriate treatment.