Amlodipine reduces myocardial ischaemia during exercise without compromising left ventricular function in patients with silent ischaemia: a randomised, double-blind, placebo-controlled study

BACKGROUND: Left ventricular systolic function is reduced during episodes of silent ischaemia in patients with coronary artery disease (CAD). In most normal subjects left ventricular ejection fraction (LVEF) increases at least 5% during exercise whereas LVEF often remains unchanged or decreases in patients with CAD. The anti-ischaemic effect of calcium antagonists is well documented including a capability to reduce exercise-induced electrocardiographic ST-depressions, whereas the effect of these drugs on LV volume changes during exercise in patients with silent ischaemia is unknown. AIM: The aim of this study was to evaluate the effect of amlodipine on rest and exercise LVEF in patients with silent ischaemia. METHODS: Twenty-one patients completed a double-blind placebo-controlled cross-over study. Conventional exercise test and radionuclide cardiographies during exercise were used for determining haemodynamic parameters. RESULTS: Exercise-induced electrocardiographic ST-depressions were reduced in 83% of the patients having ST-deviations during placebo even though 10 patients were already treated with a beta-blocker. Amlodipine did not affect left ventricular systolic function compared to placebo, neither at rest nor during exercise. CONCLUSION: The results indicated that amlodipine is a safe anti-ischaemic drug in patients with silent ischaemia concerning cardiac function.     

Long-term effect of inducible silent ischaemia on left ventricular systolic function

Silent myocardial ischaemia is readily detected by exercise radionuclide ventriculography in patients with coronary artery disease. In those who remain asymptomatic and event-free, it is not known whether silent ischaemia which is inducibledespite anti-ischaemic medication exerts an insidious detrimental effect on left ventricular function. To study this, 34 medically treated patients (mean age 57; 26 men) underwent prospective measurement of left ventricular ejection fraction (LVEF) during rest and exercise radionuclide ventriculography without interruption of anti-ischaemic medication at baseline and 12 months later.There was no significant mean (standard deviation, 95% confidence interval) deterioration from baseline to 12 months in LVEF at rest (50% v 49%, SD 5; 95% CI=–3 to+1), peak exercise (44% v 45%, SD 8; 95% CI=–1 to + 4) and the change in LVEF from rest to exercise (–6% v – 4%, SD 7; 95% CI=–1 to + 5).Thus, in coronary artery disease patients who remain asymptomatic and event-free on medical therapy, silent myocardial ischaemia which is readily inducible at baseline despite medication does not leadper se to deterioration of left ventricular systolic function at rest or exercise over 12 months.     

Asymptomatic coronary artery disease in diabetes: associated with autonomic neuropaphy?

To elucidate the potential association of diabetic autonomic neuropathy with increased prevalence of silent coronary artery disease (CAD), 138 asymptomatic diabetic subjects were screened using exercise ECG. 24-h ambulatory ECG and dynamic thallium scintigraphy. Fourteen patients with exercise-induced myocardial ischaemia and angiographically confirmed CAD (50% coronary artery narrowing) were found using this protocol. Their autonomic nervous function was assessed using standard cardiovascular tests and compared with that of 23 consecutive diabetic patients catheterised because of symptomatic CAD (mean New York Heart Association class 3.0). The diabetic patients with symptomatic CAD had more severe coronary atherosclerosis than the diabetic patients with asymptomatic CAD assessed by jeopardy score (P<0.01). The groups did not, however, differ with respect to autonomic function tests. Five patients (22%) with symptomatic CAD and 3 patients (21%) with asymptomatic CAD had definite autonomic dysfunction, i.e. two or more abnormal tests. Thus, our results suggest that the frequency of autonomic neuropathy is not increased in diabetic patients with asymptomatic CAD. The contribution of diabetic autonomic neuropathy to the absence of cardiac pain needs further clinical and pathological studies.     

Prognostic implications of symptomatic versus asymptomatic (silent) myocardial ischemia induced by exercise in mildly symptomatic and in asymptomatic patients with angiographically documented coronary artery disease

Patients with coronary artery disease (CAD) may undergo periods of reversible myocardial ischemia without experiencing angina. To study the prognostic implications of "silent" myocardial ischemia induced by exercise, exercise electrocardiography and radionuclide angiography were performed in 131 consecutive patients with CAD, preserved left ventricular (LV) function at rest and mild or no symptoms during medical therapy. All patients who died during medical therapy were in the subgroup of patients with 3-vessel CAD in whom exercise-induced ischemia developed, which was characterized by both a decrease in LV ejection fraction and ST-segment depression. Patients in whom angina pectoris developed during exercise (54% of all patients) had a greater prevalence of this combined ischemic response to exercise than patients without angina (61% vs 27%, p less than 0.001) and also a greater prevalence of left main or 3-vessel CAD (59% vs 25%, p less than 0.001). However, when inducible ischemia was demonstrated, risk stratification and prognosis were the same whether the ischemic episode was symptomatic or silent. Among patients having both a reduction in ejection fraction and a positive ST-segment response, the likelihood of significant left main narrowing (13% vs 26%), 3-vessel CAD (56% vs 51%) and death during subsequent medical therapy (16% vs 9%) was similar in patients with silent compared to those with symptomatic ischemia. These data indicate that patients in whom angina develops during exercise have a greater prevalence of high-risk coronary anatomy and of inducible ischemia than patients without angina. However, once inducible ischemia is documented, the symptomatic response to exercise appears irrelevant for prognostic or risk stratification considerations.     

N‐terminal pro‐B‐type natriuretic peptide: an independent marker for coronary artery disease in asymptomatic diabetic patients

Aims To determine whether plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels, a marker for cardiac failure and potentially for the severity of coronary artery disease (CAD), predicts silent myocardial ischaemia (SMI) and silent CAD in asymptomatic high‐risk diabetic patients. Methods Five hundred and seventeen asymptomatic diabetic patients with ≥ 1 additional cardiovascular risk factor but without heart failure were prospectively screened between 1998 and 2008 for SMI, defined as an abnormal stress myocardial scintigraphy, and subsequently for significant (> 70%) angiographic CAD. The 323 patients with interpretable echocardiography and for whom NT‐proBNP was measured were included in this analysis. Results SMI was found in 108 (33.4%) patients, 39 of whom had CAD. NT‐proBNP was higher in the patients with CAD than in the patients without CAD [45.0 (1–3199) vs. 20.0 (1–1640) pg/ml; P < 0.0001 median (range)], even after adjustment for confounding factors: age, gender, body mass index, glycated haemoglobin (HbA_1c), retinopathy, nephropathy, hypertension, echocardiographic parameters (P < 0.05). NT‐proBNP in the third tertile (≥ 38 pg/ml) predicted CAD with a sensitivity of 59% and a specificity of 67%. In a multiple logistic regression analysis including NT‐proBNP ≥ 38 pg/ml, age, body mass index, gender, HbA_1c, hypertension, retinopathy, nephropathy, peripheral occlusive arterial disease, left ventricular systolic dysfunction, dilatation and hypertrophy and Type 1 transmitral flow, NT‐proBNP ≥ 38 pg/ml was the only significant independent predictor of silent CAD [odds ratio (OR) 3.1 (95% confidence interval 1.3–7.6), P = 0.015]. Conclusions NT‐proBNP measurement helps to better define asymptomatic diabetic patients with an increased likelihood for CAD, independently of cardiac function and structure.     

Cardiac evaluation of candidates for kidney transplantation: value of exercise radionuclide angiocardiography

In view of the high incidence and mortality of coronary artery disease (CAD) in patients with kidney transplantation, a systematic cardiac evaluation was prospectively performed in 103 uraemic patients eligible for transplantation. After clinical examination, 28 patients with symptoms of CAD or diabetes mellitus were referred directly for coronary angiography, whereas the remaining 75 patients had rest and exercise radionuclide angiocardiography for evaluation of possible asymptomatic CAD. Among them, left ventricular ejection fraction was below 40% at rest or fell during exercise by at least 5 EF% in 12 patients; coronary angiography in nine showed CAD in four and hypertensive heart disease in five. In the remaining 63 (of 75) patients without severe resting left ventricular dysfunction or exercise ischaemia, the follow-up of 28 +/- 7 months revealed no clinical manifestation of CAD. Overall incidence of CAD in symptomatic and asymptomatic patients during a follow-up of 27 months after cardiac evaluation was 20 and 25% in nondiabetic and diabetic candidates for kidney transplantation, respectively (P = n.s.). Thus, clinical examination combined with exercise radionuclide angiocardiography in patients without signs or symptoms of heart disease had a high predictive accuracy for presence or absence of late manifestations of CAD. Exercise radionuclide angiocardiography is therefore a useful method for screening kidney transplantation candidates for asymptomatic CAD.     

Noninvasive screening for coronary atherosclerosis and silent ischemia in asymptomatic type 2 diabetic patients: is it appropriate and cost-effective?

Coronary artery disease (CAD) accounts for 65% to 80% of deaths in diabetic patients. The merits of screening asymptomatic type 2 diabetic patients for either (A) the presence of coronary atherosclerosis by imaging of coronary calcification using cardiac computed tomography or (B) silent ischemia by stress myocardial perfusion imaging (MPI) remain controversial. Some observers have advocated for such noninvasive screening in at least the subset of the diabetic population who have significant clinical CAD risk factors, so that the highest risk patients for future cardiac events can be identified and offered more aggressive intensive medical therapy or coronary revascularization and optimum medical therapy. Computed tomography coronary calcium scanning could be the first noninvasive screening test in these clinically high-risk diabetic patients, followed by stress MPI to detect silent ischemia in those who exhibit high coronary calcium scores.     

Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic patients with stable ischaemic heart disease

OBJECTIVE: Hypercholesterolaemia is associated with a loss of endothelium-dependent vasodilation, which may facilitate the occurrence of myocardial ischaemia in patients with coronary artery disease (CAD). The improvement of endothelial dilator function after 4 to 6 weeks of oral lipid-lowering therapy has been documented. Whether this early restoration of endothelial function by statins translates into anti-ischaemic effects is unknown. This study was designed to determine the effect of 4 weeks' treatment with 80 mg atorvastatin daily on exercise-induced ischaemia in patients with stable ischaemic heart disease (IHD) receiving standard anti-anginal drug therapy. METHODS AND RESULTS: A total of 41 patients with documented CAD, exercise-induced ischaemia and LDL-cholesterol > 130 mg/dl underwent exercise ECG, angina score and lipid level assessment at baseline, after 4 weeks of placebo treatment, and after 4 weeks of therapy with atorvastatin 80 mg. Primary endpoint was the change in time to 1 mm ST-segment depression (= ischaemic threshold) between placebo and treatment period. Atorvastatin treatment resulted in a 55% reduction of low-density lipoprotein (LDL) cholesterol (from mean of 162 (SD 32) to 72 (20) mg/dl). For a comparable rate-pressure product, the average time to 1 mm ST-segment depression was 295 (112) s at baseline, 314 (149) s after placebo and 301 (131) s after atorvastatin, indicating that the ischaemic threshold was not significantly modulated after 4 weeks of atorvastatin treatment. There was also no significant change in global angina score or in time to maximal ST-segment depression. CONCLUSIONS: High-dose atorvastatin treatment for 4 weeks drastically reduced LDL-cholesterol. However, the present study did not demonstrate a significant effect on the ischaemic threshold in patients with stable IHD already under treatment with anti-ischaemic agents.     

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.     

Prognostic significance of asymptomatic coronary artery disease in patients with diabetes and need for early revascularization therapy.

AIMS: Information on the clinical outcome of patients with diabetes with silent myocardial ischaemia is limited. We compared the clinical and angiographic characteristics, and the clinical outcomes of diabetic patients with asymptomatic or symptomatic coronary artery disease (CAD). METHODS: Three hundred and ten consecutive diabetic patients with CAD were divided into two groups according to the presence of angina and followed for a mean of 5 years. Fifty-six asymptomatic patients with a positive stress test and CAD on coronary angiography were compared with 254 symptomatic patients, 167 with unstable angina and 87 with chronic stable angina. RESULTS: Although the severity of coronary atherosclerosis was similar in asymptomatic and symptomatic patients, revascularization therapy was performed less frequently in the asymptomatic than the symptomatic patients (26.8 vs. 62.0%; P < 0.001). Asymptomatic patients experienced a similar number of major adverse cardiac events (MACEs; death, non-fatal myocardial infarction, and revascularization; 32 vs. 28%; P = 0.57), but had higher cardiac mortality than symptomatic patients (26 vs. 9%; P < 0.001). However, patients who underwent revascularization therapy at the time of CAD diagnosis in these two groups showed similar MACE and cardiac mortality (20.0 vs. 22.5%, 6.7 vs. 5.3%, respectively; all P > 0.05). CONCLUSIONS: This study suggests that diabetic patients with asymptomatic CAD have a higher cardiac mortality risk than those with symptomatic CAD, and that lack of revascularization therapy may be responsible for the poorer survival.     

The Troms? study: the prevalence of exercise-induced silent myocardial ischaemia and relation to risk factors for coronary heart disease in an apparently healthy population.

A random population sample of 294 men and 312 women aged 20-64 years, all apparently healthy, were examined following a screening to determine the prevalence of silent ischaemia and its relations to coronary risk factors. Based on exercise testing, the prevalence of silent ischaemia was 2.5% in men and 3.4% in women. In men, silent ischaemia was positively related to systolic blood pressure (P less than 0.001). The other risk factors did not show any significant associations with silent ischaemia. However, the men with silent ischaemia had a higher coronary heart disease risk score, and a tendency towards more symptoms and signs suggesting a poorer health status than the other men and the women. In the 21 men classified as 'hypertensives', silent ischaemia was more common than in the normotensive men (14% versus 2%, P less than 0.001). No such difference was observed in women. In conclusion, silent ischaemia may be a sign of hypertension and a generally increased risk of coronary heart disease in men, but probably not in the majority of women. This further supports that exercise electrocardiography has no role in screening asymptomatic persons for coronary heart disease, probably with the exception of middle-aged men with an increased risk.     

Silent coronary artery disease in patients with type 2 diabetes mellitus

Abstract. The purpose of this study was to estimate the prevalence and risk factors of silent CAD in asymptomatic type 2 diabetic patients aged over 40 years. A total of 172 asymptomatic type 2 diabetic patients, mean age 54.42 years, with normal resting electrocardiogram were included in the study. Technetium-99m (Tc-99m) tetrofosmin cardiac single photon emission computed tomography myocardial scintigraphy with exercise testing or dipyridamole injection was performed on all patients. If this test was positive, coronary angiography was carried out and was considered to be positive with a stenosis of 70%. Abnormal perfusion pattern was found in 14 patients (8.14%). Significant coronary artery stenosis was found in 13 subjects (7.56%), confirming a high positive predictive value (92.86%) of this diagnostic procedure. A significant correlation was observed between silent CAD and male sex, retinopathy, hypertension, post-prandial blood glucose level, and low HDL-cholesterol level. Sex (OR=4.026; 95% CI, 1.187–13.659), hypertension (OR=5.564; 95% CI, 1.446–21.400) and retinopathy (OR=3.766; 95% CI, 1.096–12.948) were risk factors for CAD. Overall, 14.06% of asymptomatic male patients with type 2 diabetes mellitus presented silent CAD with significant angiographically documented coronary stenosis. This finding, along with the high positive predictive value of a noninvasive technique, indicates that routine screening for silent CAD would be useful in this patient subgroup especially when they have retinopathy or hypertension.     

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does exercise-induced ST-segment depression predict benefit of medical intervention in patients recovering from acute myocardial infarction?

Abstract. The present study tested the hypothesis that the increased risk in patients with exercise-provoked ST-segment depression recovering from acute myocardial infarction could by abolished by anti-ischaemic medical intervention. Prior to discharge a symptom-limited exercise test was carried out. Patients were then double-blindly randomized to treatment with either verapamil 120 mg t.i.d. or placebo, and observed for up to 18 months (mean 17 months). End-point was first major event: i.e. non-fatal reinfarction or death. Two-hundred-and-ninety-eight patients were included. Forty-four patients with and 111 without exercise-induced ischaemia were randomized to verapamil and 39 and 104 respectively, to placebo. The overall number of events was 12.5%. In patients without ST-segment depression, 12.5% in the placebo group (hazard = 1) and 12.6 % in the verapamil group (hazard = 1.13) had an event (NS). In patients with ST-segment depression 15.4% in the placebo group (hazard = 1.20) and 9.1% in the verapamil group (hazard = 0.85) had an event (NS). The latter reduction (41%) supports the hypothesis that patients with ST-segment depression, i.e. residual myocardial ischaemia, are those who benefit from anti-ischaemic intervention after myocardial infarction.     

Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.     

High-sensitivity C-reactive protein and silent myocardial ischemia in Chinese with type 2 diabetes mellitus

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. When diabetes exists in patients with established CAD, absolute risk for future events is very high. Diabetic patients often have severe, yet asymptomatic, CAD. Although high-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, there is an unclear association between it and silent myocardial ischemia in diabetic patients. In this study, we assess the relationship between hsCRP and silent myocardial ischemia in Chinese with type 2 diabetes mellitus. We designed a cross-sectional study with 225 asymptomatic diabetic patients having no known CAD. Ischemia was assessed by myocardial perfusion imaging. A total of 109 patients (48.4%) was found to have silent myocardial ischemia. Logistic regression analysis revealed age (odds ratio = 4.01, P = .002) (95% confidence interval, 1.98-7.44) and hsCRP (odds ratio = 2.58, P = .005) (95% confidence interval, 1.33-5.01) to be associated with greater risk of silent myocardial ischemia. Using the American Diabetes Association screening guidelines to evaluate risk, we found silent myocardial ischemia to be equally distributed between diabetic patients with 2 or more cardiac risk factors and those with less than 2 risk factors. Twenty-seven (24.8%) patients with silent myocardial ischemia were missed when the American Diabetes Association guidelines were used alone. High-sensitivity C-reactive protein was associated with silent myocardial ischemia in our study. High-sensitivity C-reactive protein might help detect silent myocardial ischemia in diabetic Chinese who may need aggressive treatment to reduce future CAD morbidity and mortality in Taiwan.     

Progression to Overt or Silent CAD in Asymptomatic Patients With Diabetes Mellitus at High Coronary Risk: Main Findings of the Prospective Multicenter BARDOT Trial With a Pilot Randomized Treatment Substudy

ObjectivesThe purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk.BackgroundDespite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking.MethodsProspective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management.ResultsAn abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001).ConclusionsHigh-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a 7-fold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patients’ outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632).     

Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus.

In type 2 diabetes mellitus (DM2) patients, coronary artery disease (CAD) generally is detected in an advanced stage, whereas an asymptomatic stage is commonly missed. Abnormal myocardial perfusion during stress myocardial contrast echocardiography (MCE) and significant CAD were similar, irrespective of risk factor (RF) profile in our patients, but coronary anatomy differed. An "aggressive" diagnostic approach, requiring coronary angiography in asymptomatic DM2 patients with < or = 1 associated RF for CAD and abnormal MCE, identified silent CAD, characterized by a more favorable angiographic anatomy. The criterion of > or = 2 RFs did not help to identify patients with a higher prevalence of CAD and is only related to a more severe coronary atherosclerosis with unfavorable anatomy.OBJECTIVES: We sought to verify the effectiveness of current American Diabetes Association screening guidelines in identifying asymptomatic patients with coronary artery disease (CAD) in type 2 diabetes mellitus (DM2). BACKGROUND: In DM2 patients, CAD generally is detected in an advanced stage with an extensive atherosclerosis and poor outcome, whereas CAD in an asymptomatic stage is commonly missed. METHODS: This study included 1,899 asymptomatic DM2 patients (age < or = 60 years). Of these, 1,121 had > or = 2 associated risk factors (RFs), group A, and the remaining 778 had < or = 1 RF, group B, for CAD. All patients underwent dipyridamole myocardial contrast echocardiography (MCE), and in those with myocardial perfusion defects, the anatomy of coronary vessels was analyzed by selective coronary angiography. RESULTS: In the two study groups, the prevalence of abnormal MCE (59.4% vs. 60%, p = 0.96) and of a significant CAD (64.6% vs. 65.5%, p = 0.92) was similar, irrespective of RF profile. But coronary anatomy differed: group B had a lower prevalence of three-vessel disease (7.6% vs. 33.3%, p < 0.001), of diffuse disease (18.0% vs. 54.9%, p < 0.001), and of vessel occlusion (3.8% vs. 31.2%, p < 0.001), whereas one-vessel disease was more frequent (70.6% vs. 46.3%, p < 0.001). Coronary anatomy did not allow any revascularization procedure in 45% of group A patients. CONCLUSIONS: An "aggressive" diagnostic approach, requiring coronary angiography in asymptomatic DM2 patients with < or =1 associated RF for CAD and abnormal MCE, identified patients with a subclinical CAD characterized by a more favorable angiographic anatomy. The criterion of > or =2 RFs did not help to identify asymptomatic patients with a higher prevalence of CAD and is only related to a more severe CAD with unfavorable coronary anatomy.     

Assessment of myocardial perfusion with thallium-201 scintigraphy in exercise-induced left bundle branch block: diagnostic value and clinical significance.

Myocardial perfusion scintigraphy with thallium-201 was performed in 33 subjects (mean age 45 years, range 28-61) with exercise-induced, rate-dependent left bundle branch block (LBBB) in order to assess both the value of Thallium-201 myocardial imaging for the diagnosis of coronary artery disease (CAD) and the pathogenesis (ischaemic or not) of the conduction defect. Of the 33 patients evaluated, 16 had chest pain suggestive of CAD and 17 were asymptomatic. None had a history of prior myocardial infarction or clinical and echocardiographic signs of heart disease. LBBB appeared at a heart rate ranging from 70 to 160 b.min-1. Eighteen patients showed repolarization abnormalities (ST segment depression with deep inverted T waves) compatible with ischaemia, after QRS normalization. Thallium-201 myocardial uptake was normal in 12 subjects; in the remaining 21, reversible Thallium-201 defects were demonstrated in the septum (18 patients), septum and apex (2), and septum and infero-apical wall (1). No patient had irreversible defects and all had normal coronary angiography, with negative ergonovine tests for coronary artery spasm. The patients were followed up for a mean of 43 months (range 16-80). One patient died from sudden death, but no cardiac event occurred in the other patients. In conclusion, exercise Thallium-201 myocardial scintigraphy showed a high prevalence (64%) of reversible perfusion defects in a group of patients with exercise-induced LBBB without any evidence of CAD at angiography or coronary spasm at ergonovine test. Moreover, follow-up showed a relatively low rate of major cardiac events.     

Silent myocardial ischemia: diagnosis, clinical significance and management

With the inception of continuous ECG monitoring with high-fidelity reproduction of the ST-segment, silent myocardial ischemia has been regarded with increasing importance in the detection and management of coronary artery disease. With the aid of a variety of invasive and noninvasive methods, the validity of ST-segment depression as indicative of myocardial ischemia, even in the absence of symptoms, has been adequately documented. In completely asymptomatic subjects with positive evidence of silent ischemia in the exercise ECG or Holter monitoring, the risk of developing a future manifestation of coronary artery disease may be up to ten-fold higher than in individuals with negative tests In patients with established coronary artery disease, concomitant use of continuous ECG monitoring and exercise testing, methods which complement each other rather than being mutually exclusive, a substantial number of patients with otherwise typical angina pectoris may be found to have silent ischemic episodes. An adequate differentiation between those with symptomatic and those who are asymptomatic based on characterization with respect to age, sex, hypertension, coronary anatomy, etc., has not been successful. Patients with silent ischemia during exercise may also exhibit more episodes of silent ischemia during daily activities and up to 75% of ischemic episodes may be asymptomatic. In general, however, silent ischemia during exercise appears more common than silent ischemia only during daily activities. In the latter case, since there is usually no increase in heart rate, the pathophysiology is regarded as dissimilar from that associated with exercise-induced ischemia. While the presence of silent ischemia appears quite common in patients after acute myocardial infarction, its occurrence, to date, has not been confirmed to carry additional risk, whereas in unstable angina, the association of silent ischemia is indicative of a higher probability of subsequent cardiac events.