Long-term outcomes in patients with normal coronary arteries, nonobstructive, or obstructive coronary artery disease on invasive coronary angiography.

BACKGROUND: Normal or near normal coronary arteries (NNCA) or nonobstructive coronary artery disease (CAD) are commonly found on invasive coronary angiography (ICA). HYPOTHESIS: We aimed to determine long-term outcomes by severity of CAD in a contemporary cohort of patients undergoing ICA for evaluation for ischemic heart disease. METHODS: We assessed a consecutive cohort of 925 patients who underwent non-emergent ICA over 24 months. Cardiac death (CD), nonfatal myocardial infarction (NFMI), late revascularization, and medication use were assessed. RESULTS: Follow-up data was available in 850 patients. Of patients without heart failure, at a median of 6.0 years, there was a significant decrease in survival free from CD or NFMI, and from all cardiac events, for those with obstructive CAD compared with patients with NNCAs or nonobstructive CAD (p < .001 for both). No differences between NNCA and nonobstructive CAD patients in rates of CD or NFMI (2.0% vs. 2.1%/year, p = .58) or all cardiac events (2.4% vs. 2.9%/year, p = .84) were observed. CONCLUSION: Long-term follow-up in a contemporary cohort of consecutive patients undergoing non-emergent ICA for detection of CAD showed no difference in annual rates of CD or NFMI, or total cardiac events, in patients with NNCAs versus those with nonobstructive CAD, whereas patients with obstructive CAD had significantly more events. Event rates were low and similar by gender. Use of aspirin, lipid lowering therapy, and beta-blockers increased in all subgroups after ICA. We speculate this may explain the low incidence of subsequent cardiac events, and similar event rates in patients with NNCA and nonobstructive CAD, even in patients presenting with non-ST-elevation MI.

Lead aVR predicts early revascularization but not long-term events in patients referred for stress electrocardiography.

BACKGROUND: Exercise stress electrocardiography (ExECG) is recommended as a first-line tool to assess ischemia, but standard ST-analysis has limited diagnostic accuracy. ST elevation in lead aVR has been associated with left main and LAD disease in the population undergoing coronary angiography but has not been studied in the general population undergoing stress testing for the initial evaluation of CAD without coronary angiography. We sought to determine the predictive value of lead aVR elevation for ischemia, early revascularization, and subsequent cardiac events in consecutive patients undergoing ExECG. METHODS AND RESULTS: The study cohort included 641 subjects referred for ExECG who were dichotomized by presence or absence of aVR elevation ≥1mm and compared for prevalence and predictors of ischemia and a composite of cardiac death, nonfatal myocardial infarction, and late revascularization. The cohort had a median age of 57 and 57% were male. The prevalence of aVR elevation was 11.5%. The prevalence of significant ischemia on patients who received imaging was significantly higher with aVR elevation (14.3% vs 2.3%, p<0.001). Early revascularization occurred in 10.9% with vs 0.2% without aVR elevation, p<0.001. No subjects without aVR elevation or ST-depression underwent early revascularization. However, cardiac event rates were similar over a median 4.0 years of follow-up with and without aVR elevation (2.8% vs. 2.6%, p = 0.80). aVR elevation did not predict long-term cardiac events by Kaplan-Meier survival analysis (p = 0.94) or Cox proportional hazards modeling (p = 0.35). CONCLUSIONS: aVR elevation during ExECG predicts ischemia on imaging and early revascularization but not long-term outcomes and could serve as a useful adjunct to standard ST-analysis and potentially reduce the need for concurrent imaging.

A high exercise workload of ≥ 10 METS predicts a low risk of significant ischemia and cardiac events in older adults.

BACKGROUND: Patients who achieve ≥ 10 METS during exercise SPECT myocardial perfusion imaging (MPI) have very low rates of significant ischemia and major adverse cardiac events (MACE). It is unknown how many older adults can achieve ≥ 10 METS, and if low risk extends to this subgroup. METHODS AND RESULTS: We examined the workload achieved, prevalence and predictors of ischemia, and MACE (cardiac death, non-fatal MI, late revascularization) in a cohort of 382 patients ≥ 65 years of age who underwent exercise 99mTc SPECT MPI. The cohort was 64.4% male and 36.9% had known coronary artery disease (CAD). All achieved ≥ 85% of maximum age-predicted heart rate. A workload of ≥ 10 METS was achieved in 25.4%; 50.3% attained 7-9 METS, and 24.4% reached < 7 METS. There was a stepwise decrease in prevalence of any ischemia and significant ischemia (≥ 10% of the left ventricle (LV)) as workload increased (P = 0.037). Patients achieving ≥ 10 METS had a 3.1% prevalence of ≥ 10% LV ischemia (1.2% in those without ST depression). Cardiac death and MACE rates in the ≥ 10 METS subgroup were 0.6%/year and 2.6%/year over a median 7.0 years of follow-up. CONCLUSIONS: A substantial proportion of older adults who undergo exercise SPECT MPI can achieve ≥ 10 METS. This subgroup has low rates of significant LV ischemia and MACE. The favorable diagnostic and prognostic implications of achieving a high workload in an older adult population suggest it is feasible, with certain exceptions, to include this subgroup in workload-based strategies of provisional imaging.

High-frequency QRS analysis to supplement ST evaluation in exercise stress electrocardiography: Incremental diagnostic accuracy and net reclassification.

BACKGROUND: Exercise stress electrocardiography (ECG) alone is underutilized in part due to poor diagnostic accuracy. High-frequency QRS analysis (HF-QRS) is a novel tool to supplement ST evaluation during stress ECG. We compared the diagnostic accuracy and net reclassification of HF-QRS analysis compared with ST evaluation for substantial myocardial ischemia by exercise SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: Exercise SPECT MPI was performed in 257 consecutive eligible patients (mean age 59 ± 12, 67% male). An ischemic HF-QRS pattern was defined as a ≥ 1 µV absolute reduction and a ≥ 50% relative reduction of the root-mean-square of the 150-250 Hz band signal in ≥ 3 leads. Left ventricular ischemia of ≥ 10% on SPECT MPI was the diagnostic standard for substantial myocardial ischemia. HF-QRS analysis demonstrated incremental diagnostic value to ST evaluation plus clinical risk factors (AUC 0.804 vs 0.749, P < .0001). A HF-QRS + ST -analysis strategy identified 92.3% of subjects with substantial ischemia and no abnormality in 59.9% of the cohort. No cardiac events occurred in patients without substantial ischemia identified by HF-QRS analysis. CONCLUSIONS: In this prospective analysis, exercise stress ECG with HF-QRS analysis identified any and substantial ischemia with high diagnostic accuracy and may allow more than half of referred patients to safely avoid imaging.

Clinical Characteristics, Sex Differences, and Outcomes in Patients With Normal or Near-Normal Coronary Arteries, Non-Obstructive or Obstructive Coronary Artery Disease.

BACKGROUND: Normal or near-normal coronary arteries (NNCAs) or nonobstructive coronary artery disease (CAD) are found on invasive coronary angiography in ≈55% of patients. Some attribute this to frequent referral of low-risk patients. We sought to identify the referral indications, pretest risk, key clinical characteristics, sex, and outcomes in patients with NNCAs and nonobstructive CAD versus obstructive CAD on nonemergent invasive coronary angiography. METHODS AND RESULTS: Over 24 months, 925 consecutive patients were classified as having NNCAs (≤20% stenosis), nonobstructive CAD (21-49% stenosis), or obstructive CAD (≥50% stenosis). Outcomes included cardiac death, nonfatal myocardial infarction, and late revasclarization. NNCAs were found in 285 patients (31.0%), nonobstructive CAD in 125 (13.5%), and obstructive CAD in 513 (55.5%). NNCAs or nonobstructive CAD was found in 40.5% with stress ischemia, 27.9% after a non-ST-elevation myocardial infarction, and in 55.5% with stable or unstable angina. More women than men (53.5% versus 37.2%; P<0.001) had NNCAs or nonobstructive CAD across all referral indications. Pretest risk was high and ICA appropriate in 75.5% and 99.2% of patients, respectively. Annual rates of cardiac death or nonfatal myocardial infarction were 1.0%, 1.1%, and 6.7%, respectively, for patients with NNCAs, nonobstructive CAD, and obstructive CAD (P<0.001). No sex differences in outcomes were observed with either NNCAs, nonobstructive CAD, or obstructive CAD (P=0.84). CONCLUSIONS: Many (44.5%) patients undergoing nonemergent invasive coronary angiography have NNCAs or nonobstructive CAD despite high pretest risk, including ischemia and troponin elevation. Although women had more NNCAs or nonobstructive CAD, there were no differences in event rates by sex. Patients with NNCAs and nonobstructive CAD had very low event rates.

Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology.

Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a "coronary risk equivalent," implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data.

TOWARDS THE DEVELOPMENT OF NOVEL THERAPEUTICS FOR PERIPHERAL ARTERY DISEASE.

Atherosclerosis is the leading cause of morbidity and mortality in the Western world. Peripheral artery disease (PAD) has been less studied then coronary artery disease but is nearly as common. PAD impairs blood flow to the leg(s) and causes functional impairment, leg pain, and amputation. The last drug approved for PAD was in 1999. Blood flow to leg proceeds through one major artery and in PAD total occlusions in the course of that vessel are common. Thus, the extent of new blood vessel growth determines a patients' clinical course. Promoting the growth of new blood vessels (therapeutic angiogenesis) was a major goal of therapy. Results from studies using cytokine growth factors have shown disappointing results. Using clinical and preclinical studies, our laboratory has identified several novel therapeutic approaches. One, a modulator of innate immunity, will be reviewed as an approach that has the potential to create new therapies for PAD.

Value of Exercise ECG for Risk Stratification in Suspected or Known CAD in the Era of Advanced Imaging Technologies.

Exercise stress electrocardiography (ExECG) is underutilized as the initial test modality in patients with interpretable electrocardiograms who are able to exercise. Although stress myocardial imaging techniques provide valuable diagnostic and prognostic information, variables derived from ExECG can yield substantial data for risk stratification, either supplementary to imaging variables or without concurrent imaging. In addition to exercise-induced ischemic ST-segment depression, such markers as ST-segment elevation in lead aVR, abnormal heart rate recovery post-exercise, failure to achieve target heart rate, and poor exercise capacity improve risk stratification of ExECG. For example, patients achieving ≥10 metabolic equivalents on ExECG have a very low prevalence of inducible ischemia and an excellent prognosis. In contrast, cardiac imaging techniques add diagnostic and prognostic value in higher-risk populations (e.g., poor functional capacity, diabetes, or chronic kidney disease). Optimal test selection for symptomatic patients with suspected coronary artery disease requires a patient-centered approach factoring in the risk/benefit ratio and cost-effectiveness.