The potential of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes

Patients with diabetes, in particular patients with type 2 diabetes, are at a 2- to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic peers. Patients with diabetes are also more likely to have silent ischemia and less likely to survive a myocardial infarction than nondiabetic patients. Recent studies with electron beam computed tomography (EBCT) have shown that subclinical atherosclerosis is common in patients with diabetes, and studies with myocardial perfusion scintigraphy (with single-photon emission computed tomography) or stress echocardiography have demonstrated that between 25% and 50% of asymptomatic diabetic patients have ischemia during exercise or pharmacological stress and that a substantial proportion of these patients go on to develop major cardiovascular events within several years. Clearly, asymptomatic diabetic patients include a subset of individuals at high risk of cardiovascular disease who would benefit from improved risk stratification beyond that possible with risk factor scoring systems alone. Single-photon emission computed tomography, stress echocardiography, and possibly EBCT or multi-slice computed tomography, are emerging as valuable diagnostic tools for identifying asymptomatic diabetic patients who might require early and aggressive intervention to manage their cardiovascular risk.     

Vascular ultrasound for cardiovascular risk stratification in asymptomatic patients with type-2 diabetes

AimsTo identify new independent vascular markers to predict cardiovascular events in patients with type-2 diabetes (T2D), and their incremental value compared to the Swedish National Diabetes Register (NDR) risk score.MethodsA retrospective cohort study was conducted on 1332 asymptomatic patients with T2D, free from prior CV event, assessed for a cardiovascular work-up, including Duplex ultrasonography to detect plaque on carotid and femoral arteries. The extent of atherosclerosis was rated as atherosclerosis burden score (ABS). Patients were followed up to 5 years and the occurrence of cardiovascular events recorded.ResultsA total of 82 patients (6.2%) experienced a cardiovascular event, including 34 (2.6%) myocardial infarction, 18 (1.4%) cardiac revascularisation and 17 (1.3%) stroke. The independent determinants of these events were male sex (HR = 1.81 [1.13–2.88], p = 0.013) and ABS ≥ 2 (HR = 1.98 [1.21–3.25], p = 0.007). The NDR risk score performed poorly to predict cardiovascular events (area under the curve = 0.56 [0.49–0.63], p = 0.11), whereas screening for atherosclerotic plaques provided significant incremental prognostic value over the NDR score (model χ2 increase: +231%, p = 0.002).ConclusionDuplex ultrasonography to screen for atherosclerotic plaques improve the estimation of cardiovascular prognosis on top of clinical data and could be routinely used to improve cardiovascular risk stratification.     

Application of support vector machine classifiers to preoperative risk stratification with myocardial perfusion scintigraphy

BACKGROUND: Myocardial perfusion single-photon emission computed tomography (SPECT) has been used for risk stratification before non-cardiac surgery. However, few authors have used mathematical models for evaluating the likelihood of perioperative cardiac events. METHODS AND RESULTS: This retrospective cohort study collected data of 1,351 patients referred for SPECT before non-cardiac surgery. We generated binary classifiers using support vector machine (SVM) and conventional linear models for predicting perioperative cardiac events. We used clinical and surgical risk, and SPECT findings as input data, and the occurrence of all and hard cardiac events as output data. The area under the receiver-operating characteristic curve (AUC) was calculated for assessing the prediction accuracy. The AUC values were 0.884 and 0.748 in the SVM and linear models, respectively in predicting all cardiac events with clinical and surgical risk, and SPECT variables. The values were 0.861 (SVM) and 0.677 (linear) when not using SPECT data as input. In hard events, the AUC values were 0.892 (SVM) and 0.864 (linear) with SPECT, and 0.867 (SVM) and 0.768 (linear) without SPECT. CONCLUSION: The SVM was superior to the linear model in risk stratification. We also found an incremental prognostic value of SPECT results over information about clinical and surgical risk.     

Abnormal myocardial perfusion and risk of heart failure in patients with type 2 diabetes mellitus

BACKGROUND:

Diabetes is a major risk factor for heart failure (HF), although the pathophysiological processes have not been clarified.

OBJECTIVE:

To determine the prevalence of HF and of abnormal myocardial perfusion in diabetic patients evaluated using technetium (99m) sestamibi single-photon emission computed tomography.

METHODS:

An observational cross-sectional study was conducted that included patients with type 2 diabetes mellitus who underwent echocardiography to diagnose HF and a pharmacological stress test with intravenous dipyridamole to examine cardiac scintigraphic perfusion abnormalities. Clinical and biochemical data were also collected.

RESULTS:

Of the 160 diabetic patients included, 92 (57.6%) were in HF and 68 (42.5%) were not. When patients were stratified according to the presence of abnormal myocardial perfusion, those with abnormal perfusion had a higher prevalence of HF (93%) than those with normal perfusion (44.4%) (P<0.0001). Patients with HF weighed more (P=0.03), used insulin less frequently (P=0.01), had lower total cholesterol (P=0.05) and high-density lipoprotein cholesterol concentrations (P=0.002), and a greater number of their myocardial segments showed abnormal perfusion (P≤0.001). More HF patients had a history of myocardial infarction (P<0.001) compared with those without HF. In a logistic regression analysis, the number of segments exhibiting abnormal myocardial perfusion was an independent risk factor for HF.

CONCLUSIONS:

The prevalence of HF in diabetic patients was high and HF predominantly occured in association with myocardial ischemia.     

Stress myocardial scintigraphy and dobutamine echocardiography in the detection of coronary disease in asymptomatic patients with type 2 diabetes

OBJECTIVE: The aims of this prospective study were: (1) to compare stress thallium-201 single photon emission computed tomography (SPECT) and dobutamine echocardiography (DE) in the detection of silent myocardial ischemia (SMI) in asymptomatic high risk diabetic patients; (2) to analyse long-term outcome after intensive care of SMI in these patients. METHODS: SPECT was performed in 100 high risk diabetic patients and DE in the first 75 patients. Coronary angiography was realized in patients with SMI, with revascularization for suitable lesions. Intensive treatment of atherosclerosis risk factors was performed in all patients. Patients were followed 2 +/- 0.5 years for the subsequent occurrence of cardiac death, myocardial infarction and revascularization. RESULTS: SMI was detected by SPECT in 62% and by DE in 10% of the patients (p < 0.0001), whereas significant coronary stenosis at angiography was detected by SPECT in 26% and by DE in 5% of the patients (p < 0.02). Independent predictive factors of significant coronary stenosis were male gender (p < 0.03) and peripheral arterial disease (p < 0.007). Nonfatal acute coronary syndrome occurred during follow-up in 2 patients (2%). Subsequent revascularization procedure was needed in 9 patients. Baseline patients' characteristics, as well as SMI, were not predictive of cardiac event during follow up. CONCLUSION: SPECT seems more accurate than DE to detect significant coronary stenosis in high risk asymptomatic diabetic patients. In this population, aggressive treatment of SMI with systematic revascularization combined with intensive care of risk factors is associated with a favorable long-term prognosis, similar in diabetic patients with and without initial SMI.     

Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy.

AIMS: To determine the prevalence and clinical predictors of subclinical atherosclerosis and myocardial ischaemia in uncomplicated type 2 diabetes and assess their relationship to short-term outcome. METHODS AND RESULTS: Established risk factors and coronary artery calcium (CAC) scores were prospectively measured in 510 asymptomatic type 2 diabetic subjects (mean age 53+/-8 years, 61% males) without prior cardiovascular disease. Myocardial perfusion scintigraphy (MPS) was performed in all subjects with CAC > 100 Agatston units (AU) (n=127), and a random sample of the remaining patients with CAC < or = 100 AU (n=53). Significant CAC (> 10 AU) was found in 46.3%. Twenty events occurred (two coronary deaths, nine non-fatal myocardial infarctions, three acute coronary syndromes, three non-haemorrhagic strokes, and three late revascularisations) during a median follow-up of 2.2 years (25th-75th percentile = 1.9-2.5 years). The age, systolic blood pressure, the duration of diabetes, United Kingdom Prospective Diabetes Study risk score, CAC score, and extent of myocardial perfusion abnormality were significant predictors of time to cardiovascular events in a univariable Cox proportional hazard model. No cardiac events or perfusion abnormalities occurred in subjects with CAC < or = 10 AU up until 2 years of follow-up. CAC and MPS findings were synergistic for the prediction of short-term cardiovascular events. CONCLUSION: Subclinical atherosclerosis, measured by CAC imaging, is superior to the established cardiovascular risk factors for predicting silent myocardial ischaemia and short-term outcome. Further studies evaluating the impact of CAC imaging on clinical outcomes and its cost effectiveness are warranted.     

Dipyridamole thallium-201 scintigraphy for early risk stratification of patients after uncomplicated myocardial infarction

Objective—To determine the safety and prognostic value of dipyridamole thallium-201 scintigraphy performed in patients within three to five days of acute myocardial infarction, including those receiving thrombolytic treatment.
Design—A prospective study of dipyridamole thallium-201 scintigraphy in patients early after acute myocardial infarction.
Setting—University hospital.
Patients—200 patients who were clinically uncomplicated at day 3 after infarction, 92 (46%) of whom had received thrombolysis.
Main outcome measures—Incidence of cardiac death, non-fatal reinfarction, readmission to hospital for unstable angina, or non-elective revascularisation procedure within six months' follow up.
Results—No patient had a serious complication from the dipyridamole study. At six month follow up, 55 patients (28%) had suffered a defined cardiac event. Patients who received thrombolysis had the same extent of thallium-201 redistribution and the same occurrence of subsequent cardiac events as those not receiving thrombolysis. Patients who subsequently had an event had more myocardial segments showing thallium-201 redistribution than event free patients: 2.7 (SD 1.9) v 1.2 (1.4), respectively (p < 0.001). Among all clinical and scintigraphic variables, multivariate analysis identified the extent of thallium-201 redistribution as the only independent predictor of outcome (p < 0.001). Among 63 patients (32%) of the study cohort who showed more than two myocardial segments with thallium-201 redistribution, the adjusted risk ratio for a cardiac event was 7.5 (95% confidence interval 2.9 to 19.1) compared with patients without any redistribution.
Conclusions—Dipyridamole thallium-201 scintigraphy can be performed safely within a few days of the event in patients with uncomplicated myocardial infarction, including those who received thrombolysis, and can identify a subgroup of patients at high risk of future ischaemic events.

Keywords: dipyridamole; thallium; myocardial infarction; prognosis     

Silent myocardial ischemia in middle-aged asymptomatic patients with type 2 diabetes in Turkish population

The authors investigated silent myocardial ischemia in unselected consecutive middle-aged asymptomatic patients with type 2 diabetes without any evidence of coronary heart disease documented by treadmill exercise test. Ninety asymptomatic patients with type 2 diabetes (48 men; mean age: 49 +/-6 years) were included in the study. Mean duration of diabetes in the study group was 4 +/-4.2 years (range 1 to 21 years); 38% of the study population, diabetes duration was only 1 year). All patients were subjected to treadmill exercise test with Bruce protocol. A positive test was noted in 4 of 90 (4%) study patients. Two male patients (4%) and 2 (4%) women patients developed exercise-induced ST-segment depression, but none had concomitant chest pain. Diabetics with silent myocardial ischemia were older (55 +/-3 years vs 49 +/-6 years, p = 0.04) than those without silent myocardial ischemia. Also, diabetics with silent myocardial ischemia had higher fibrinogen level (372 +/-51 vs 307 +/-71 mg/dL, p = 0.04) than diabetics without silent myocardial ischemia. In treadmill exercise test, diabetics with silent myocardial ischemia had lower total exercise time and peak workload (375 +/-30 vs 474 +/-115 seconds, p = 0.04; 7.3 +/-0.5 vs 8.9 +/-1.9, p = 0.04, respectively) than without silent myocardial ischemia. Insulin resistance is associated with a variety of atherosclerosis risk factors. Exercise test findings show increased cardiac sympathetic activity and parasympathetic withdrawal in increased insulin resistance.     

Myocardial perfusion abnormalities in asymptomatic type 2 diabetic patients

Objective

The prevalence of coronary artery disease (CAD) is high in patients with diabetes. Because ischemia and infarction are often silent in diabetic patients, diagnosis of CAD occurs inevitably late. It is essential to identify the presence of CAD in diabetic patients to start early treatment. Therefore, the aim of this study was to determine the prevalence of abnormal myocardial perfusion in asymptomatic type 2 diabetic patients using myocardial perfusion imaging.

Risk stratification for asymptomatic patients with Brugada syndrome.

Ventricular fibrillation (VF) is induced in some asymptomatic patients with Brugada syndrome (BS), but the prognostic value of programmed electrical stimulation (PES) in such patients is controversial. The clinical characteristics of 41 asymptomatic BS patients, divided into 2 groups according to whether VF was induced by PES (inducible VF group: n=13, non-inducible VF group: n=28) were evaluated. ST levels in the right precordial leads were measured before and after administration of pilsicainide and the abnormal late potential (LP) was evaluated on the signal-averaged electrogram. The ST level at V(2) at baseline in the inducible VF group was significantly higher than that in the non-inducible VF group (p<0.05). Pilsicainide induced significant ST segment elevation in both groups and the ST level after pilsicainide in the inducible VF group was higher than that in the non-inducible VF group (p<0.01). LP was more frequent in the inducible VF group than in the non-inducible VF group. The criterion of ST level >0.15 mV at baseline with pilsicainide-induced additional ST elevation >0.10 mV and positive LP showed high sensitivity (92%) and specificity (89%) for detection of PES-induced VF in asymptomatic BS patients.     

Value of pharmacologic stress myocardial perfusion imaging for preoperative risk stratification for aortic surgery.

BACKGROUND: Aortic surgery is an invasive, high-risk noncardiac procedure and the patients who require it have a high prevalence of coronary artery disease. Therefore, preoperative risk stratification for this subset is essential. METHODS AND RESULTS: To assess the perioperative risk for aortic surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 302 patients: aortic dissection in 56, thoracic aortic aneurysm in 124, and abdominal aortic aneurysm in 122. Not only was the presence or absence of perfusion defects analyzed, but also the 20-segment model. Pharmacologic thallium SPECT revealed negative findings in 210 patients and positives in 92. Perioperative cardiac events occurred in 9 patients: 7 occurred in patients with positive SPECT, and in only 2 of those with negative SPECT (2/210 vs 7/92; p<0.05). Multivariate analysis using logistic regression model revealed that a summed stress score>or=14 was the most important factor to identify patients who subsequently had perioperative cardiac events. CONCLUSIONS: Pharmacologic stress SPECT has significant value in the risk stratification of patients before aortic surgery. In patients with positive SPECT, an aggressive approach to reduce the preoperative risk is necessary, whereas aortic surgery can be performed safely in patients with negative SPECT.     

Preoperative risk stratification with myocardial perfusion imaging in intermediate and low-risk non-cardiac surgery.

BACKGROUND: Perioperative cardiac risk in high risk surgery is often stratified with myocardial perfusion single-photon emission computed tomography (SPECT). However, little and no data are available about intermediate and low-risk surgery, respectively. METHODS AND RESULTS: A total of 1,220 consecutive patients underwent electrocardiography-gated dipyridamole stress SPECT to evaluate myocardial perfusion and cardiac function before intermediate or low risk non-cardiac surgery. Variables predictive of perioperative cardiac events were determined and the usefulness of combining pretest information and the incremental prognostic value of SPECT was estimated. The frequency of all cardiac events depended on clinical risk factors and type of surgical procedures. After sorting the patients with clinical risk factors and surgical risk, assessment of myocardial perfusion or cardiac function yielded significant risk stratification in intermediate, but not in low-risk surgery. Adding functional data to perfusion variables offered an incremental prognostic value for patients with an intermediate clinical risk and scheduled intermediate risk surgery. CONCLUSIONS: Integrating information about clinical risk factors, type of surgery, myocardial perfusion and cardiac function allows detailed preoperative risk stratification. Preoperative SPECT provides an incremental prognostic value in intermediate, but not in low-risk surgery.     

Myocardial perfusion scintigraphy in type 2 diabetic patients with atypical chest pain

To verify the prevalence of ischemic myocardial abnormalities, 67 patients with type 2 diabetes mellitus (DM2) with normal basal electrocardiogram (EKG) or with ventricular repolarization abnormalities were evaluated by a perfusional myocardial scintigraphy. The average age was 63.5 +/- 9 years. Twenty-one (31.3%) were male and 46 (68.7%) female. A significant part of the sample (62.7%) had a normal myocardial scan, 37.3% were positive for ischemia. The majority of the sample (91%; n = 61) was submitted to an EKG during exercise which was positive for ischemia in 31.1%. The concordance between myocardial scintigraphy and the EKG during exercise demonstrated a low correlation between the two procedures (Kappa = 0.49; P = 0.0001). We conclude that perfusional myocardial scan is a highly valuable tool for evaluation and diagnosis of coronary artery disease in DM2 patients with atypical angina.     

Comparison of dipyridamole stress echocardiography and perfusion scintigraphy for cardiac risk stratification in vascular surgery patients

Dipyridamole single-photon emission computed tomography (SPECT) has a high negative predictive value for perioperative cardiac events, but events are infrequent in patients with a positive test. In contrast, dipyridamole echocardiography is more selective for detection of multivessel disease and thus may have a greater specificity for cardiac events. We therefore compared the ability of dipyridamole SPECT and echocardiography to predict perioperative and long-term cardiac events in 133 patients referred for vascular surgery. The group was also evaluated based on clinical features and ejection fraction. Four patients had surgery cancelled because of high risk and were excluded from further analysis. Among the 129 remaining patients, 21 had coronary revascularization (n = 12) or an early cardiac end point (n = 9). The sensitivity of SPECT for the prediction of early events (90%) was not significantly different from that of echocardiography (66%, p = NS). The specificity of SPECT (68%) was less than that of echocardiography (88%, p <0.001%), as was the accuracy (72% vs 84%, p = 0.02). These findings were replicated after exclusion of patients with treatment end points. During long-term follow-up, 12 patients experienced ≥1 event: 6 died from cardiac causes, 4 underwent revascularization, and 3 had myocardial infarction. Thus, the specificity of SPECT and echocardiography for late events were 58% and 80%, respectively (p <0.001). The 3-year survival of patients without ischemia during echocardiography or at SPECT was not different (93% vs 94%, p = NS).