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Role of Nuclear Cardiology Techniques in Ischemia Assessment with Exercise Imaging in Asymptomatic Diabetes
Closed for proposals
Project Type
Project Code
E13031CRP
1367Approved Date
Status
Start Date
Expected End Date
Completed Date
28 January 2013Description
Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Longer-term complications include cardiovascular disease (double risk), chronic renal failure (it is the main cause for dialysis) retinal damage with eventual blindness, nerve damage and eventual gangreene with risk of amputation of toes, feet, and even legs.
In 2002, diabetes mellitus was the 4th leading cause of death in most developed countries. It is also one of the leading causes of disability and reduced life expectancy. In the year 2030 it is anticipated that 300 million people worldwide will suffer from diabetes. Increased urbanization, increased obesity, decreased exercise, physical inactivity and ageing are likely to be some of the factors contributing to that increase. The predominant cause of death in diabetes is coronary artery disease since cardiac complications due to diabetes often are asymptomatic and cardiac ischemia and myocardial infarction are more common in diabetic than in non-diabetic patients.
While most clinicians are likely to approach a symptomatic diabetic patient in a similar manner to a non-diabetic patient, little is known about appropriate strategies for asymptomatic diabetic patients, because these patients may have significant heart disease and yet they are asymptomatic (silent ischemia).
Myocardial SPECT imaging after stress has a high sensitivity and accuracy, and a good reproducibility for detecting coronary artery disease. SPECT is the most extensively imaging technique used and provides images of the heart using minute amounts of radiotracer that is injected intravenously. Itsa images depict myocardial perfusion and could delineate any ischemia or infarction in terms of site, severity or extent. Its prognostic impact has been demonstrated in a large body of literature. It is a readily available imaging modality, of relatively low cost.
The purpose of our study is to examine the prevalence of ischemia by SPECT perfusion imaging performed during symptom limited treadmill or bicycle exercise and compare it to an age and sex-matched control group with no diabetes but with multiple coronary risk factors.
Expected outcomes are information not currently available on epidemiology of coronary artery disease in asymptomatic diabetic patients. This study will have a major impact on guidelines and patient management, especially in developing countries where the main increase in diabetes is expected over the next decade.
Objectives
This CRP was planned towards a project on “Nuclear medicine imaging in the management of non-communicable diseases”. Among non-communicable diseases (NCDs), cardiovascular diseases, and particularly coronary artery disease (CAD), are on the rise, particularly in the developing world. Diabetes Mellitus (DM) is well known to be a major risk factor for developing CAD. It is expected that by 2030 more than 300 millions of people will be affected by DM in the developing world and 80% of them are predicted to die of CAD.
While most clinicians are likely to approach a symptomatic diabetic patient in a similar manner to a non-diabetic patient, little is known about appropriate strategies for asymptomatic diabetic patients, because these patients may have significant heart disease and yet they are asymptomatic (silent ischemia) as a result of a damaged autonomous nervous system which prevents patients from experiencing chest pain in case of heart attacks. As the predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD) silent ischemia might become a serious public health problem. Particularly, little is known about prevalence of silent ischemia in developing nations.
The purpose of this study is to examine the prevalence of ischemia by SPECT perfusion imaging performed during symptom limited treadmill or bicycle exercise in asymptomatic diabetic patient enrolled in developing countries and compare it to an age and sex-matched control group with no diabetes but with coronary risk factors.
Specific objectives
The predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD). Little is known about prevalence of silent ischemia in developing nations. The purpose of this study is to examine the prevalence of ischemia by SPECT perfusion imaging performed during symptom limited treadmill or bicycle exercise in asymptomatic diabetic patient enrolled in developing countries and compare it to an age and sex-matched control group with no diabetes but with coronary risk factors.
The primary hypothesis is that ischemia, as detected by SPECT imaging, is more common in diabetic than in non-diabetic patients. We specifically will select asymptomatic patients because: Silent ischemia is of major concern in this group; asymptomatic patients by far represent a much larger number of patients than symptomatic ones
The secondary hypotheses are:
1. Ischemia is more commonly detected by SPECT than by ECG
2. Men and women with DM have lower exercise capacity than men and women without DM, respectively.
3. Left ventricular (LV) function abnormalities, assessed as Ejection Fraction (EF) and volumes measured by gated SPECT, are worse in DM than in patients without DM.
4. The prevalence of ischemia will increase in proportion to the number of risk factors and the effectiveness of treatment.
5. Although this study is not powered to look at outcome, we hypothesise that at a minimum of 1 year follow up, patients with SPECT ischemia will have more hard events, defined as death of any cause, cardiac death, myocardial infarction (MI), need for revascularization, and hospitalisation for heart failure or stroke.
To determine the change and predictors of ECG exercise parameters (ST and non ST) over a period of time among patients with DM enrolled in IAEA 1.
To determine the change and predictors of MPI parameters over a period of time among the patients with DM enrolled in IAEA 1.
To determine the change and predictors of LV function parameters over a period of time among the patients with DM enrolled in IAEA 1.
To examine the interaction between the exercise parameter (ST and non ST) and MPI and LV function parameters.
To examine the association between exercise parameter (ST and non ST), MPI and LV function parameters and the three-year outcome on patients enrolled in IAEA 1.
To investigate the role of autonomic neuropathy and CPR and GFR to events, as well as to perfusion patterns and LV function
The study population consisted of 597 participants (392 DM and 205 control subjects). The most common reasons for exclusion (n=74) included an abnormal ECG (n=27), missing or uninterpretable MPI (n=19), pharmacologic stress (n=12), age _40 years (n=7), absence of risk factors in control group (n=3), abnormal coronary angiography (n=2), and MI (n=1). CAD risk factors were more prevalent in the control group. DM participants achieved lower workload than control participants and had lower peak heart rate even after accounting for age. ECG data were not available for 12 of 597 subjects (8 DM and 4 controls). ECG was not diagnostic in response to exercise for 88 of 585 subjects (15%), and more DM participants had non-diagnostic ECGs than control participants (17% vs 10%, p=0.03). Among participants with diagnostic ECGs similar proportion of DM and control participants had ischemic ECG changes (15% vs 12%, p=0.5). Except for 1 participant in each group who experienced ST elevation with exertion, ischemic ECG represented ST depression. In participants with ischemic ECG, severe ischemia (>2-mm ST shift) occurred more frequently in DM participants (56% vs 27%, p=0.03). Summed Stress Score (SSS) for each participant stratified by DM status and exercise ECG findings is shown in Figure 1. A higher proportion of DM than control participants had abnormal perfusion (SSS >3) on SPECT imaging (26% vs 14%, p <0.001). Both SSS and SDS were higher in DM than control participants (Table 2). In participants with SSS >3, SRS was not different between groups (2.0 _ 3.5 vs 1.2 _3.1, p ¼ 0.08). In the control group, a similar proportion of participants had ischemia by ECG and MPI (14% vs 11%, p ¼ 0.50). In the DM group, more participants had ischemia by MPI than by ECG (26 vs 15%, p <0.001).
More DM than control participants had perfusion abnormalities that were moderate or large (p ¼0.002). These findings were unchanged when SDS was used instead of SSS. The DM group also had larger defects when assessed as the number of myocardial segments involved (Table 2). Majority of participants with MPI ischemia had negative rather than non-diagnostic ECGs in both groups.
In a multivariable logistic regression model, DM was independently associated with presence of MPI ischemia (SSS >3). This association was homogenous across recruiting centres and was unchanged when individual risk factors were replaced by number of risk factors each participant had (OR for DM 2.1, 95% CI 1.2e3.4, p <0.001) or when participants with SRS >3 (n=30) were excluded (OR for DM 1.9, 95% CI 1.1e3.3, p=0.02). In a separate model that included DM participants, DM duration was independently associated with ischemia on MPI. In participants with ischemia by MPI, only 17% had ischemia by ECG (67% negative, 17% non-diagnostic), and in those without ischemia by MPI, 10% had ischemia by ECG (75% negative, 15% non-diagnostic). These distributions were similar for DM and control groups but showed differences between genders. Women were less likely to have ischemia by MPI (10% vs 30%, p <0.001) and more likely to have non-diagnostic ECG (20% vs 12%, p ¼ 0.01), and concordance between ECG and MPI was much worse in women. In particular, the proportion of women with ischemia by MPI did not depend on ECG result (w10% of women had MPI ischemia regardless of ECG result, p=0.9), whereas for men, more MPI ischemia was observed among ECG positives (41% among positives, 25% among non-diagnostic, and 26% among negatives, p=0.02). Accordingly, the proportion of participants with ischemic ECG changes with no MPI ischemia was higher in women (90% vs 59%, p=0.03). In a logistic regression model, participants with ischemic ECG changes were more likely to have MPI ischemia compared with those with negative or non-diagnostic results, but the association was not statistically significant (OR=1.54, 95% CI 0.85-2.86, p=0.2). Importantly, after accounting for both gender and ECG ischemia, DM continued to be significantly associated with MPI ischemia (OR 2.0, 95% CI 1.2-3.3, p <0.001), and there was no interaction between DM and ECG ischemia for prediction of MPI ischemia (p for interaction 0.7).
Impact
The major findings of the study are as follows: (1) DM participants had more ischemia by MPI than controls, and DM was independently associated with presence of ischemia by MPI, (2) DM participants had more ischemia by MPI than by ECG during exercise, (3) there was no difference in prevalence of ischemia by ECG between DM and controls, (4) exercise ECG was not predictive of MPI findings especially in women, and (5) women with DM had less ischemia than men.
While other studies reported a similar incidence of ischemia in asymptomatic diabetics as compared to non-diabetics with other risk factors, we have shown that this does not apply to populations from the developing world and that clinical research from countries and high level centres where patients get the best possible treatments.
Some countries presented the preliminary results at national consensus meetings to help policy makers for better management of health resources in diabetic population.
In addition, this CRP stimulated to carry out detailed study on this subject in some countries such as Algeria where the Hospital of Bab El Oued of Algiers, has undertaken a National Project to find out strategy of early detection of Myocardial Ischemia in diabetic patients.
Relevance
Taking into account that Diabetes Mellitus is a serious health problem and by the year 2030 it is anticipated that more than 300 million people worldwide will suffer from diabetes, and that 80% of those patients will die of cardiovascular complications, the outcome of this CRP was found to have significant relevance for early detection and the management of CAD in asymptomatic diabetic patients.