External validation of the CRAX2MACE model.

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion is frequently used to predict risk of major adverse cardiovascular events (MACE). We performed an external validation of the CRAX2MACE score, developed to estimate 2-year risk of MACE in patients with suspected coronary artery disease (CAD). METHODS: Patients who underwent clinically indicated SPECT with available follow-up for MACE were included (N = 2,985). The prediction performance for MACE (revascularization, myocardial infarction, or death) within 2 years for CRAX2MACE was compared with stress and ischemic total perfusion deficit (TPD) using area under the receiver operating characteristic curve (AUC). Calibration was assessed with calibration plots, Brier score, and the Hosmer-Lemeshow test. RESULTS: MACE occurred within 2 years in 243 (8.1%) patients. The AUC for CRAX2MACE (0.710, 95% CI 0.677-0.743) was significantly higher compared to stress TPD (AUC 0.669, 95% CI 0.632-0.706, P = .010) and ischemic TPD (AUC 0.664, 95% CI 0.627-0.700, P < .001). The model had acceptable goodness-of-fit (P = .103) and was well-calibrated with Brier score of 0.071. CONCLUSION: CRAX2MACE had higher predictive performance for 2-year MACE than quantitative perfusion in an external population. The current model is simple to use and could be implemented to assist physicians when estimating patient risk.

Impact of myocardial perfusion and coronary calcium on medical management for coronary artery disease.

AIMS: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) remains one of the most widely used imaging modalities for the diagnosis and prognostication of coronary artery disease (CAD). Despite the extensive prognostic information provided by MPI, little is known about how this influences the prescription of medical therapy for CAD. We evaluated the relationship between MPI with computed tomography (CT) attenuation correction and prescription of acetylsalicylic acid (ASA) and statins. METHODS AND RESULTS: We performed a retrospective analysis of consecutive patients who underwent SPECT MPI at a single centre between 2015 and 2021. Myocardial perfusion abnormalities and coronary calcium burden were assessed, with attenuation correction imaging 77.8% of patients. Medication prescriptions before and within 180 days after the test were compared. Associations between abnormal perfusion and calcium burden with ASA and statin prescription were assessed using multivariable logistic regression. In total, 9908 patients were included, with a mean age 66.8 ± 11.7 years and 5337 (53.9%) males. The prescription of statins increased more in patients with abnormal perfusion (increase of 19.2 vs. 12.0%, P < 0.001). Similarly, the presence of extensive CAC led to a greater increase in statin prescription compared with no calcium (increase 12.1 vs. 7.8%, P < 0.001). In multivariable analyses, ischaemia and coronary artery calcium were independently associated with ASA and statin prescription. CONCLUSION: Abnormal MPI testing was associated with significant changes in medical therapy. Both calcium burden and perfusion abnormalities were associated with increased prescriptions of medical therapy for CAD.

Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.

CONTEXT: Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. OBJECTIVE: To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. DESIGN, SETTING, AND PATIENTS: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction (MI). RESULTS: The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. CONCLUSION: In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00769275.

Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study.

OBJECTIVE: To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines. RESEARCH DESIGN AND METHODS: In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50-75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission-computed tomography myocardial perfusion imaging. RESULTS: A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia. CONCLUSIONS: Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.

Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome.

Combined hyperlipidemia predisposes subjects to coronary heart disease. Two lipid abnormalities--increased cholesterol and atherogenic dyslipidemia--are potential targets of lipid-lowering therapy. Successful management of both may require combined drug therapy. Statins are effective low-density lipoprotein (LDL) cholesterol-lowering drugs. For atherogenic dyslipidemia (high triglycerides, small LDL, and low high-density lipoprotein [HDL]), fibrates are potentially beneficial. The present study was designed to examine the safety and efficacy of a combination of low-dose simvastatin and fenofibrate in the treatment of combined hyperlipidemia. It was a randomized, placebo-controlled trial with a crossover design. Three randomized phases were employed (double placebo, simvastatin 10 mg/day and placebo, and simvastatin 10 mg/day plus fenofibrate 200 mg/day). Each phase lasted 3 months, and in the last week of each phase, measurements were made of plasma lipids, lipoprotein cholesterol, plasma apolipoproteins B, C-II, and C-III and LDL speciation on 3 consecutive days. Simvastatin therapy decreased total cholesterol by 27%, non-HDL cholesterol by 30%, total apolipoprotein B by 31%, very low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL) cholesterol by 37%, VLDL + IDL apolipoprotein B by 14%, LDL cholesterol by 28%, and LDL apolipoprotein B by 21%. The addition of fenofibrate caused an additional decrease in VLDL + IDL cholesterol and VLDL + IDL apolipoprotein B by 36% and 32%, respectively. Simvastatin alone caused a small increase in the ratio of large-to-small LDL, whereas the addition of fenofibrate to simvastatin therapy caused a marked increase in the ratio of large-to-small LDL species. Simvastatin alone produced a small (6%) and insignificant increase in HDL cholesterol concentrations. When fenofibrate was added to simvastatin therapy, HDL cholesterol increased significantly by 23%. No significant side effects were observed with either simvastatin alone or with combined drug therapy. Therefore, a combination of simvastatin 10 mg/day and fenofibrate 200 mg/day appears to be effective and safe for the treatment of atherogenic dyslipidemia in combined hyperlipidemia.

Indications, safety and image quality of cardiovascular magnetic resonance: experience in >5,000 North American patients.

BACKGROUND: CMR offers accurate assessment of structure and function with high resolution. Although the use of CMR has been well established in Europe, information is lacking for the extent of this emerging modality in North America. OBJECTIVES: This study aimed to summarize indications, safety, image quality, extent of contrast use and extent of stress tests performed in a high-volume CMR centre. METHODS: Consecutive patients scanned from July 2005 to November 2010 were included, with duplicates and research subjects removed. Original clinical referrals were categorized into 10 main indications. RESULTS: Retrospective analysis was performed on 6463 patients (mean±SD age=50±17). The most common clinical indications were non-ischemic cardiomyopathies (28%), including myocarditis (18%), coronary artery disease (17%), ARVD and/or other RV disease (12%), and congenital heart disease (11%). Gadolinium-based contrast was given to 89.5% of patients as part of their CMR protocol. Of 10.9% (703/6463) of patients that underwent stress CMR, adenosine was administered most commonly. Of 703 patients, 1 (0.14%) suffered ventricular tachycardia during adenosine stress, and transient, asymptomatic AV block was occasionally observed. Moderate to severe complications after contrast agent administration occurred in 9 (0.16%) of 5782 contrast-enhanced studies, characterized by nausea and vomiting in 6 (0.12%) and by symptoms of acute systemic allergic reaction in 2 (0.04%). Image quality was good (82.0%), moderate but diagnostic (16.6%) and poor in 1.4% of cases. CONCLUSION: In the high-volume CMR centre, main clinical indications were for myocarditis/cardiomyopathies, coronary artery disease and RV-related queries. CMR showed an excellent safety profile and high image quality in 99% of cases.

Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.

Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria").

Abnormalities in T2-weighted cardiovascular magnetic resonance images of hypertrophic cardiomyopathy: regional distribution and relation to late gadolinium enhancement and severity of hypertrophy.

PURPOSE: To explore if focal T2 abnormalities accompany late gadolinium enhancement (LGE) lesions in hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: All studies were performed under the guidelines of the local ethics committee, which approved the study, and a written informed consent was obtained from each subject. We studied 27 patients (24 males, 51 +/- 18 years) with HCM and evidence for myocardial injury as defined by LGE. The following sequences were performed: steady-state free precession (SSFP) (ventricular volumes, mass, and function), T2-weighted triple inversion-recovery spin-echo and inversion-recovery gradient-echo 10 minutes after intravenous (IV) gadolinium-DTPA (late enhancement). RESULTS: Focal high T2 signal intensity (SI) frequently matching areas of LGE was observed in nine patients (33%). The presence of these abnormalities correlated with more severe left ventricular hypertrophy (1.5 +/- 0.6 vs. 1.0 +/- 0.4 g/cm; P < 0.05). CONCLUSION: In this observational study, we identified focal T2 abnormalities in a subgroup of HCM patients. T2 abnormalities are associated with severe left ventricular hypertrophy. This may provide new insights into the mechanisms of focal irreversible injury in HCM and help in managing these patients.

Resolution of asymptomatic myocardial ischemia in patients with type 2 diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.

OBJECTIVE: The purpose of this study was to assess whether the prevalence of inducible myocardial ischemia increases over time in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study underwent repeat adenosine-stress myocardial perfusion imaging 3 years after initial evaluation. Patients with intervening cardiac events or revascularization and those who were unable or unwilling to repeat stress imaging were excluded. RESULTS: Of the initial 522 DIAD patients, 358 had repeat stress imaging (DIAD-2), of whom 71 (20%) had ischemia at enrollment (DIAD-1). Of 287 patients with normal DIAD-1 studies, 259 (90%) remained normal in DIAD-2, whereas 28 (10%) developed new ischemia in DIAD-2. Of the 71 patients with abnormal DIAD-1 studies, 56 (79%) demonstrated resolution of ischemia, whereas 15 (21%) remained abnormal. During this 3-year interval, medical treatment was intensified, with more patients using statins, aspirin, and ACE inhibitors than at baseline. Patients with resolution of ischemia had significantly greater increases in these medications than patients who developed new ischemia (P = 0.04). CONCLUSIONS: Thus, the majority of asymptomatic patients with type 2 diabetes demonstrated resolution of ischemia upon repeat stress imaging after 3 years. This resolution was associated with more intensive treatment of cardiovascular risk factors.

A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether gated adenosine Tc-99m sestamibi single-photon emission computed tomography (ADSPECT) could accurately define risk and thereby guide therapeutic decision making in stable survivors of acute myocardial infarction (AMI). BACKGROUND: Controversy continues as to the role of noninvasive stress imaging in stratifying risk early after AMI. METHODS: The INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) trial is a prospective multicenter trial which enrolled 728 clinically stable survivors of AMI who had gated ADSPECT within 10 days of hospital admission and subsequent 1-year follow-up. Event rates were assessed within prospectively defined INSPIRE risk groups based on the adenosine-induced left ventricular perfusion defect size, extent of ischemia, and ejection fraction. RESULTS: Total cardiac events/death and reinfarction significantly increased within each INSPIRE risk group from low (5.4%, 1.8%), to intermediate (14%, 9.2%), to high (18.6%, 11.6%) (p < 0.01). Event rates at 1 year were lowest in patients with the smallest perfusion defects but progressively increased when defect size exceeded 20% (p < 0.0001). The perfusion results significantly improved risk stratification beyond that provided by clinical and ejection fraction variables. The low-risk INSPIRE group, comprising one-third of all enrolled patients, had a shorter hospital stay with lower associated costs compared with the higher-risk groups (p < 0.001). CONCLUSIONS: Gated ADSPECT performed early after AMI can accurately identify a sizeable low-risk group who have a <2% death and reinfarction rate at 1 year. Identifying these low-risk patients for early hospital discharge may improve utilization of health care resources at considerable cost savings.

An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown. METHODS: A prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (> or =20%) and ischemic (> or =10%) adenosine-induced left ventricular perfusion defects and an ejection fraction > or =35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics. RESULTS: Both intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (-16.2 +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function.