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Biomedical subjects

P W Armstrong

Publications and source records attributed to P W Armstrong.

At least 19 recordsLinked to original sources
PubMed1996

Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.

BACKGROUND: The prognosis of patients hospitalized with acute myocardial ischemia is quite variable. We examined the value of serum levels of cardiac troponin T, serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia. METHODS: We studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion at the core laboratory. We used logistic regression to assess the usefulness of baseline levels of cardiac troponin T and CK-MB and the electrocardiographic category assigned at admission-ST-segment elevation, ST-segment depression, T-wave inversion, or the presence of confounding factors that impair the detection of ischemia (bundle-branch block and paced rhythms)-in predicting outcome. RESULTS: On admission, 289 of 801 patients with base-line serum samples had elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days was significantly higher in these patients than in patients with lower levels of troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was the variable most strongly related to 30-day mortality (chi-square = 21, P < 0.001), followed by the electrocardiographic category (chi-square = 14, P = 0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels remained significantly predictive of 30-day mortality in a model that contained the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P = 0.027). CONCLUSIONS: The cardiac troponin T level is a powerful, independent risk marker in patients who present with acute myocardial ischemia. It allows further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level.

Acute Disease↗
PubMed1996

One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. GUSTO-I Investigators.

BACKGROUND: In the randomized Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries (GUSTO-I) trial, 41021 patients received one of four thrombolytic regimens. Patients treated with accelerated tissue plasminogen activator (TPA) had a lower 30-day mortality rate (6.3%) than those treated with the other regimens (7.3%, combined streptokinase groups). METHODS AND RESULTS: Each patient who was alive at 30 days was sent a return postcard to ascertain vital status at 1 year. If the postcard was not returned, the patient (or an alternate specified at randomization) was contacted by telephone. A locator service was used in the United States for patients who could not be located by these methods. Final follow-up was 96% worldwide. One-year mortality rates remained in favor of accelerated TPA (9.1%) over streptokinase with subcutaneous heparin (10.1%, P = .011) and streptokinase with intravenous heparin (10.1%, P = .009). Combination therapy had an intermediate 1-year mortality (9.9%); this outcome was statistically indistinguishable from that with streptokinase (P = .47) but was marginally different from that with accelerated TPA (P = .05). CONCLUSIONS: The 1-year results demonstrated a saving of 10 lives per 1000 patients treated with accelerated TPA versus streptokinase and subcutaneous or intravenous heparin. Combination thrombolytic therapy had an intermediate benefit but offered no advantage over accelerated TPA treatment alone.

Aged↗
PubMed1996

Heart rate variability assessment early after acute myocardial infarction. Pathophysiological and prognostic correlates. GUSTO ECG Substudy Investigators. Global Utilization of Streptokinase and TPA for Occluded Arteries.

BACKGROUND: Diminished heart rate variability is associated with less favorable prognosis after myocardial infarction. However, the prognostic value of early (first 48 hours) measurement and the influence of thrombolytic strategies, myocardial infarction location, left ventricular function, ST-segment shift, and infarct-related artery patency on heart rate variability have not been examined comprehensively. METHODS AND RESULTS: Heart rate variability and ST-segment analysis of 48-hour Holter tapes were performed with the use of a commercial system in 204 patients who were part of an ST-monitoring substudy of the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial. Both time-domain measures (SD of the average normal RR interval for all 5-minute segments of a 24-hour ECG recording [SDANN] and percent difference between adjacent normal RR intervals > 50 ms computed over the entire 24-hour ECG recording [pNN50]) and frequency-domain measures (low frequency [LF], high frequency [HF], and LF/HF ratio) were assessed on days 1 and 2 after acute myocardial infarction. Coronary angiography performed within the first 24 hours was also available in 75% of the patients. All heart rate variability measures decreased between day 1 and day 2 (P = .001) except the LF/HF ratio. There was no difference in heart rate variability among groups assigned to one of four different thrombolytic treatment strategies (streptokinase/subcutaneous heparin, streptokinase/intravenous heparin, accelerated tissue plasminogen activator, and combination streptokinase/tissue plasminogen activator). Heart rate variability measures were lower in anterior versus nonanterior infarcts (SDANN, 53 +/- 21 versus 63 +/- 24 ms; P < .005) and increased with TIMI grade 3 flow (LF, 5.3 +/- 1.0 versus 4.8 +/- 1.2 ms2; P < .01) and better ejection fraction (r = .2, P < .03). An inverse correlation between the duration of ST shift and frequency domain measures was observed (LF, r = -.2, P < .009; HF, r = -2, P < .03). Lower LF/HF ratio by 24 hours after myocardial infarction was seen in those who ultimately died at 30 days (1.0 +/- 0.2 versus 1.3 +/- 0.2, P < .001) or at 1 year (1.17 +/- 0.14 versus 1.26 +/- 0.19, P = .05). CONCLUSIONS: Changes in heart rate variability occurred early after thrombolysis and may be of prognostic value. Heart rate variability measures were improved in patients with better ejection fraction and greater angiographic patency. This suggests a possible mechanism for the enhanced survival observed with TIMI grade 3 flow in the GUSTO angiographic substudy. These data indicate that early heart rate variability assessment after myocardial infarction may be useful in noninvasive risk stratification.

Bradycardia↗
PubMed1996

Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure.

OBJECTIVES: This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure. BACKGROUND: Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis. METHODS: The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2). RESULTS: Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05). CONCLUSIONS: Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Acute Disease↗
PubMed1996

Late assessment of thrombolytic efficacy (LATE) study: prognosis in patients with non-Q wave myocardial infarction. (LATE Study Investigators)

OBJECTIVES: We examined the impact of thrombolytic therapy and the prognosis of patients with non-Q wave myocardial infarction in a randomized placebo-controlled trial known as the Late Assessment of Thrombolytic Efficacy (LATE) study. BACKGROUND: Patients with non-Q wave as compared with Q wave myocardial infarction in the era before thrombolytic therapy were traditionally thought to have a higher rate of reinfarction and death between hospital discharge and 1 year such that the overall prognosis for outcome at 1 year was similar in the two groups. METHODS: The study patients began treatment with either recombinant tissue-type plasminogen activator (rt-PA) or matching placebo, 6 to 24 h after the onset of chest pain. Post hoc analysis of mortality and reinfarction was carried out by comparing rt-PA and placebo in various subsets of patients based on the presenting electrocardiogram (ECG) and the evolution of the ECG with respect to the development of Q waves. RESULTS: Among 5,711 participants, 4,759 had a confirmed myocardial infarction, including 1,309 classified as having a non-Q wave infarction at hospital discharge. Irrespective of treatment assignment, all patients with non-Q wave versus Q wave infarction had a lower 1-year mortality rate (13.3% vs. 17.1%, p = 0.001) and a similar 1-year reinfarction rate (8.6% vs. 7.9%, p = 0.7). Of the 4,759 patients with confirmed myocardial infarction, 2,973 presented with ST segment elevation or bundle branch block, 528 with ST depression and 1,258 with neither ST elevation nor depression. No overall benefit from rt-PA versus placebo with respect to mortality rate at 1 year was seen among patients presenting with ST elevation (21.2% vs. 22.4%, p = 0.5 [90% power to detect 20% relative difference]). Patients with ST elevation who were treated with rt-PA versus placebo <3 h after hospital admission had a lower mortality rate at 1 year (15.8% vs. 19.6%, p = 0.028) than did those treated after 3 h (17.6% vs. 13.0%, p = 0.055). Patients presenting initially with ST depression >2 mm had significant benefit from treatment with rt-PA with respect to 1 year mortality rate (20.1% vs. 31.9%, p = 0.006). CONCLUSIONS: Patients with non-Q wave myocardial infarction constitute a heterogeneous group of patients. Although the observations presented here are limited by post hoc analysis, it is apparent that patients classified as having a non-Q wave infarction after thrombolytic therapy have a better prognosis than do those given placebo. Late admission of thrombolytic therapy (after 6 h) may also be beneficial in patients presenting with ST depression >2 mm and confirmed myocardial infarction. These hypotheses require prospective testing in a larger number of patients.

Electrocardiography↗
PubMed1996

Time from symptom onset to treatment and outcomes after thrombolytic therapy. GUSTO-1 Investigators.

OBJECTIVES: This study sought to examine the relations among patient characteristics, time to thrombolysis and outcomes in the international GUSTO-I trial. BACKGROUND: Studies have shown better left ventricular function and decreased infarct size as well as increased survival with earlier thrombolysis, but the relative benefits of various thrombolytic agents with earlier administration are uncertain. METHODS: We evaluated the relations of baseline characteristics to three prospectively defined time variables: symptom onset to treatment, symptom onset to hospital arrival (presentation delay) and hospital arrival to treatment (treatment delay). We also examined the relations of delays to clinical outcomes and to the relative 30-day mortality benefit with accelerated tissue-type plasminogen activator (t-PA) versus streptokinase. RESULTS: Female, elderly, diabetic and hypertensive patients had longer delays at all stages. Previous infarction or bypass surgery was an additional risk factor for treatment delay. Early thrombolysis was associated with lower overall mortality rate (< 2 h, 5.5%; > 4 h, 9.0%), but no additional relative benefit resulted from earlier treatment with accelerated t-PA versus streptokinase (p = 0.38). Longer presentation and treatment delays were both associated with increased mortality rate (presentation delay < 1 h, 5.6% and > 4 h, 8.6%; treatment delay < 1 h, 5.4%, and > 90 min, 8.1%). As time to treatment increased, the incidence of recurrent ischemia or reinfarction decreased, but the rates of shock, heart failure and stroke increased. CONCLUSIONS: Earlier treatment resulted in better outcomes, regardless of thrombolytic strategy. Elderly, female and diabetic patients were treated later, adding to their already substantial risk.

Aged↗
PubMed1996

Biatrial appendage hypertrophy but not ventricular hypertrophy: a unique feature of canine pacing-induced heart failure.

BACKGROUND: The canine model of pacing-induced heart failure is characterized by an absence of ventricular hypertrophy despite severe hemodynamic stress and neurohormonal activation. Given the mode of ventricular pacing, hypertrophy might occur in the atrial appendage. METHODS AND RESULTS: Seventeen dogs underwent continuous right ventricular pacing for 3 weeks to severe heart failure. Twelve normal dogs served as control subjects. Pacing produced marked increases in both pulmonary capillary wedge pressure (7.6 +/- 1.8 mmHg at baseline to 32.6 +/- 7.5 mmHg at 3 weeks, P < .001) and right atrial pressure (6.5 +/- 1.8 to 15.1 +/- 2.4 mmHg, P < .001), marked increases in normalized left ventricular volume (3.0 +/- 0.5 to 4.6 +/- 0.5 mL/kg, P < .001) and left atrial volume (1.0 +/- 0.2 to 2.6 +/- 0.5 mL/kg, P < .001), but no change in left ventricular mass (2.3 +/- 0.4 to 2.6 +/- 0.5 g/kg, differences not significant), indicating no ventricular hypertrophy. Compared to the control dogs, total heart weight in the test animals was similar, but both the left appendage (0.18 +/- 0.04 vs 0.10 +/- 0.03 g/kg, P < .001) and right atrial appendage (0.15 +/- 0.03 vs 0.12 +/- 0.02 g/kg, P = .004) were much heavier than those of the control dogs. CONCLUSIONS: Rapid right ventricular pacing in the dog induces severe heart failure associated with a dichotomous response in the atrial appendage versus the ventricle. Aside from being a useful heart failure model that simulates the human condition, this unique feature may have physiologic implications in terms of atrial mechanical and endocrine functions and have applications for future studies into the mechanisms of cardiac remodeling and hypertrophy.

Animals↗
PubMed1996

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

Arteries↗
PubMed1995

Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the "smoker's paradox" from the GUSTO-I trial, with angiographic insights. Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infarction. BACKGROUND: A paradoxic beneficial effect has been observed in smokers with a myocardial infarction. We analyzed outcomes and baseline characteristics of 11,975 nonsmokers, 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infarction. METHODS: Patients were randomized to one of four thrombolytic protocols. An angiographic substudy in 2,431 patients evaluated reperfusion, reocclusion and ventricular function. Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender. A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking. These processes were performed with data from both the main trial and the angiographic substudy; then angiographic factors (coronary anatomy, patency and ejection fraction) were added to the model. RESULTS: Smokers were significantly younger by a mean of 11 years) and had less comorbidity or severe coronary artery disease than nonsmokers. Nonsmokers had significantly higher hospital and 30-day mortality rates (9.9% and 10.3%, respectively) than smokers (3.7% vs. 4%, respectively, both p < 0.001) and more in-hospital complications. The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 (95% confidence interval [CI] 2.08 to 5.41), 1.21 (95% CI 0.71 to 2.08) after adjustment for age and gender and 1.08 (95% CI 0.59 to 1.96) after adjustment for all clinical baseline characteristics. CONCLUSIONS: Smokers receiving thrombolysis for acute myocardial infarction presented 11 years earlier than nonsmokers, which generally accounted for their better outcome. When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated, no significant difference in mortality was seen between smokers and nonsmokers.

Adult↗
PubMed1995

Regional variation across the United States in the management of acute myocardial infarction. GUSTO-1 Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

BACKGROUND: Differences in the management of acute myocardial infarction have been reported among countries, but few studies have investigated this issue in regions of the United States. METHODS: We compared the management of acute myocardial infarction among census regions across the United States, using data from the first Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-1) comprising 21,772 patients, and from the American Hospital Association. RESULTS: We found substantial regional variation in the management of acute myocardial infarction in the United States. Beta-blockers (prescribed for a range of 55 to 81 percent of patients in the various regions), nitrates (prescribed for 61 to 77 percent), and angiotensin-converting-enzyme inhibitors (prescribed for 18 to 23 percent) were used most often in New England, whereas calcium-channel blockers (31 to 42 percent) and lidocaine (14 to 43 percent) were used least often there. Similarly, the proportion of patients undergoing various cardiac procedures differed among regions (range for angiography, 52 to 81 percent of patients; angioplasty, 22 to 35 percent; and coronary-artery bypass surgery, 9 to 17 percent) and was lowest in New England. The regional use of cardiac procedures was closely related to their availability, except in New England. After the analysis was adjusted for clinical and hospital variables, patients in New England were found to be less likely to undergo angiography than patients in the other regions (odds ratio, 0.37; 95 percent confidence interval, 0.32 to 0.42). There was no apparent relation between the use of cardiac procedures and rates of recurrent infarction or death at 30 days or 1 year. CONCLUSIONS: There is substantial regional variation in the use of cardiac medications and procedures to manage acute myocardial infarction in the United States. The use and availability of cardiac procedures are closely related. The management of acute myocardial infarction in New England is atypical in that the relatively limited availability of cardiac procedures does not account for their relatively low use in that region.

Angioplasty↗
PubMed1995

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult↗
PubMed1995

Usefulness of ischemic response to mental stress in predicting silent myocardial ischemia during ambulatory monitoring.

To evaluate the relation of mental stress-induced ischemia to silent ischemia on ambulatory monitoring, 46 patients with stable coronary artery disease underwent standardized laboratory mental stress and exercise treadmill testing according to National Institutes of Health protocol during which left ventricular ejection fraction (EF) was determined using the nuclear VEST. Life stress, type A behavior, and hostility were determined using standard interviews. Subsequently, 48-hour ambulatory electrocardiographic monitoring was performed. Twenty-three patients (50%) had an ischemic response (left ventricular EF decrease > or = 5%) to mental stress, which was associated with ambulatory ischemia (13 of 19 with ambulatory ischemia had mental stress-induced ischemia vs 10 of 27 without ambulatory ischemia, p = 0.04). Left ventricular EF response to mental stress was a significant predictor of ambulatory ischemia independent of EF response to exercise (F = 4.8, p = 0.03). Patients with mental stress-induced ischemia had longer total duration (31.4 +/- 57.0 vs 8.3 +/- 18 minutes, p = 0.06) and more frequent episodes of ambulatory ischemia (3.1 +/- 4.6 vs 0.9 +/- 1.9 episodes, p = 0.03). Life stress, type A behavior, and hostility were not associated with prevalence or severity of ambulatory ischemia. In conclusion, an ischemic response to mental stress is significantly associated with higher prevalence, longer duration, and more frequent episodes of ambulatory ischemia.

Aged↗
PubMed1995

Maximizing the benefits of thrombolytic therapy for acute myocardial infarction.

Thrombolytic therapy is a huge advance in the management of acute myocardial infarction (AMI). The results of large clinical trials over the past 9 years have unequivocally demonstrated its benefit: of every 1000 patients treated 30 will be saved, at a cost of two cases of nonfatal cerebral hemorrhage and seven of noncerebral major hemorrhage. The concurrent use of acetylsalicylic acid increases the benefit of thrombolytic therapy. Sales figures for thrombolytic agents indicate that their use in Canada is less than optimal and lags behind that in several European countries. Major educational efforts are needed to promote awareness of the efficacy of thrombolytic therapy and of optimal approaches for maximizing its potential benefit for patients with AMI.

Clinical Trials as Topic↗
PubMed1995

Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia.

OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/- 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation.

3-Iodobenzylguanidine↗