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Stress CMR for Risk Reclassification of Suspected CAD
Quick Takes
- Normal stress CMR findings are associated with a low rate of MACE (~1%/year).
- Stress CMR can enhance clinical risk stratification among patients with suspected myocardial ischemia, particularly those with intermediate pretest risk.
Study Questions:
Can vasodilator stress cardiovascular magnetic resonance (CMR) reclassify risk in patients with suspected coronary artery disease (CAD)?
Methods:
The Stress CMR Perfusion Imaging in the United States Registry was a retrospective, multicenter study including patients undergoing stress CMR from 2008-2013, meeting the following criteria: 1) age 35-85 years at the time of stress CMR imaging, 2) clinical presentation suspicious for myocardial ischemia, and 3) presence of ≥2 coronary risk factors (age >50 years for men and >60 years for women, diabetes, hypertension, hyperlipidemia, family history of premature CAD, obesity, and peripheral vascular disease). Among the exclusion criteria were history of CAD, severe valvular disease, left ventricular ejection fraction (LVEF) <40%, and infiltrative or hypertrophic cardiomyopathy. Vasodilator stress agents used were regadenoson, adenosine, and dipyridamole. Clinical follow-up data were obtained for ≥4 years after stress CMR.
The outcome of interest was a composite of cardiovascular (CV) death or nonfatal myocardial infarction (MI). The secondary outcome was major adverse CV events (MACE), including CV death, nonfatal MI, hospitalization for unstable angina or heart failure, and unplanned coronary artery bypass grafting >6 months after stress CMR. Multivariable clinical models were used to assess pretest risk: Model 1, based on the CAD Consortium score (including age, sex, and type of chest pain); and Model 2, including the CAD Consortium score, history of hypertension, smoking, and diabetes. Post-test risk was assessed by adding CMR-assessed LVEF, late gadolinium enhancement (LGE), and ischemia to both models. As per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, in stable CAD, low risk was defined as <1% annual risk of CV death or MI, while high risk was >3%.
Results:
Of the total 2,349 patients in the registry, 1,698 patients had no history of CAD and formed the study cohort. The cohort was 51.4% male. Mean age was 62 ± 11 years. Median follow-up was 5.4 years. Most patients were at low or intermediate pretest risk for CV death/nonfatal MI (55.5% and 43.7%, respectively). CV death or nonfatal MI occurred in 67 patients (3.9%), and MACE occurred in 190 patients (11.2%). Ischemia on stress CMR was found in 227 patients (13.4%). Among patients with ischemia, 126 (55.5%) had ≥2 ischemic segments; within this group, 82 patients (65.1%) underwent coronary angiography, and 59 patients undergoing angiography (72.0%) were revascularized.
The absence of ischemia and LGE was associated with low rates of CV death/nonfatal MI (0.4% vs. 1.7% per year among patients with LGE/ischemia, p < 0.01) and MACE (1.3% vs. 5.0%, p < 0.01). For CV death/MI, C statistic values were 0.622 and 0.659 for Models 1 and 2, respectively; these were improved to 0.731 and 0.745, respectively, by the addition of CMR ischemia, LGE, and LVEF. The addition of these CMR data to Model 2 resulted in a net reclassification index of 0.266 (95% confidence interval, 0.091-0.441). Stress CMR reclassified 568 patients (33.5% of the overall cohort) to a more appropriate post-test risk group for CV death and nonfatal MI, including 432/716 patients (60.3%) at intermediate pretest risk. For MACE, 498 of 832 patients (59.9%) at intermediate pretest risk were reclassified based on stress CMR data.
Conclusions:
The absence of ischemia and LGE on vasodilator stress CMR is associated with low rates of CV death and MACE. Stress CMR can enhance clinical risk stratification among patients with suspected myocardial ischemia, particularly those with intermediate pretest risk.
Perspective:
Vasodilator stress CMR is a modality that is relatively underutilized in clinical practice, largely due to limited availability. Strengths of stress CMR include precise assessment of left and right ventricular size and systolic function, myocardial tissue characterization (particularly useful for working up undifferentiated cardiomyopathies), and potential to detect subendocardial ischemia. Limitations of the present study include its retrospective design and relative dearth of patients with high pretest risk. Especially in the post-ISCHEMIA era, an emphasis on risk reclassification, rather than test sensitivity and specificity, seems appropriate.
Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Magnetic Resonance Imaging, Nuclear Imaging, Hypertension, Smoking
Keywords: Acute Coronary Syndrome, Angina, Unstable, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Imaging, Dyslipidemias, Gadolinium, Heart Failure, Hypertension, Magnetic Resonance Imaging, Myocardial Infarction, Myocardial Ischemia, Myocardial Perfusion Imaging, Risk Factors, Secondary Prevention, Smoking, Vasodilator Agents
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