Josh Klein

Association Between Coronary Vascular Dysfunction and Cardiac Mortality in Patients With and Without Diabetes Mellitus

Background— Diabetes mellitus increases the risk of adverse cardiac outcomes and is considered a coronary artery disease (CAD) equivalent. We examined whether coronary vascular dysfunction, an early manifestation of CAD, accounts for increased risk among diabetics compared with nondiabetics. Methods and Results— A total of 2783 consecutive patients (1172 diabetics and 1611 nondiabetics) underwent quantification of coronary flow reserve (CFR; CFR=stress divided by rest myocardial blood flow) by positron emission tomography and were followed up for a median of 1.4 years (quartile 1–3, 0.7–3.2 years). The primary end point was cardiac death. Impaired CFR (below the median) was associated with an adjusted 3.2- and 4.9-fold increase in the rate of cardiac death for diabetics and nondiabetics, respectively (P=0.0004). Addition of CFR to clinical and imaging risk models improved risk discrimination for both diabetics and nondiabetics (c index, 0.77–0.79, P=0.04; 0.82–0.85, P=0.03, respectively). Diabetic patients without known CAD with impaired CFR experienced a rate of cardiac death comparable to that for nondiabetic patients with known CAD (2.8%/y versus 2.0%/y; P=0.33). Conversely, diabetics without known CAD and preserved CFR had very low annualized cardiac mortality, which was similar to patients without known CAD or diabetes mellitus and normal stress perfusion and systolic function (0.3%/y versus 0.5%/y; P=0.65). Conclusions— Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and nondiabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to those of patients with prior CAD, whereas those with preserved CFR have event rates comparable to those of nondiabetics.

Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography

Myocardial perfusion imaging has limited sensitivity for the detection of high-risk coronary artery disease (CAD). We tested the hypothesis that a normal coronary flow reserve (CFR) would be helpful for excluding the presence of high-risk CAD on angiography. Methods: We studied 290 consecutive patients undergoing 82Rb PET within 180 d of invasive coronary angiography. High-risk CAD on angiography was defined as 2-vessel disease (≥70% stenosis), including the proximal left anterior descending artery; 3-vessel disease; or left main CAD (≥50% stenosis). Patients with prior Q wave myocardial infarction, elevated troponin levels between studies, prior coronary artery bypass grafting, a left ventricular ejection fraction of less than 40%, or severe valvular heart disease were excluded. Results: Fifty-five patients (19%) had high-risk CAD on angiography. As expected, the trade-off between the sensitivity and the specificity of the CFR for identifying high-risk CAD varied substantially depending on the cutoff selected. In multivariable analysis, a binary CFR of less than or equal to 1.93 provided incremental diagnostic information for the identification of high-risk CAD beyond the model with the Duke clinical risk score (>25%), percentage of left ventricular ischemia (>10%), transient ischemic dilation index (>1.07), and change in the left ventricular ejection fraction during stress (<2) (P = 0.0009). In patients with normal or slightly to moderately abnormal results on perfusion scans (<10% of left ventricular mass) during stress (n = 136), a preserved CFR (>1.93) excluded high-risk CAD with a high sensitivity (86%) and a high negative predictive value (97%). Conclusion: A normal CFR has a high negative predictive value for excluding high-risk CAD on angiography. Although an abnormal CFR increases the probability of significant obstructive CAD, it cannot reliably distinguish significant epicardial stenosis from nonobstructive, diffuse atherosclerosis or microvascular dysfunction.

Coronary Artery Disease Detected by Coronary Computed Tomographic Angiography Is Associated With Intensification of Preventive Medical Therapy and Lower Low-Density Lipoprotein Cholesterol

Background—Coronary computed tomographic angiography (CCTA) is an accurate test for the identification of coronary artery disease (CAD), yet the impact of CCTA results on subsequent medical therapy and risk factors has not been widely reported. Methods and Results—We identified consecutive patients aged >18 years without prior CAD who underwent CCTA from 2004 to 2011 and had complete data on medications before and after CCTA. CCTA results were categorized as no CAD, <50% stenosis, and ≥50% stenosis. Based on the number of involved segments, extent of disease was categorized as nonextensive (⩽4 segments) or extensive CAD (>4 segments). Electronic medical records and patient interviews were reviewed blinded to CCTA findings to assess initiation of aspirin and intensification of lipid-lowering therapies. Survival analysis was performed to evaluate intensification of lipid therapy as a predictor of cardiovascular death or nonfatal myocardial infarction. Among 2839 patients with mean follow-up of 3.6 years, the odds of physician intensification of lipid-lowering therapy significantly increased for those with nonobstructive CAD (odds ratio, 3.6; 95% confidence interval, 2.9–4.9; P<0.001) and obstructive CAD (odds ratio, 5.6; 95% confidence interval, 4.3–7.3; P<0.001). Low-density lipoprotein cholesterol levels declined significantly in association with intensification of lipid-lowering therapy after CCTA in all patient subgroups. In a hypothesis-generating analysis, among patients with nonobstructive but extensive CAD, statin use after CCTA was associated with a reduction in cardiovascular death or myocardial infarction (hazards ratio, 0.18; 95% confidence interval, 0.05–0.66; P=0.01). Conclusions—Abnormal CCTA findings are associated with downstream intensification in statin and aspirin therapy. In particular, CCTA may lead to increased use of prognostically beneficial therapies in patients identified as having extensive, nonobstructive CAD.

Prognostic Interplay of Coronary Artery Calcification and Underlying Vascular Dysfunction in Patients With Suspected Coronary Artery Disease

OBJECTIVES This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes. BACKGROUND The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown. METHOD A total of 901 consecutive patients underwent (82)Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure. RESULTS At baseline, CFR decreased (2.15 ± 0.72, 2.02 ± 0.65, and 1.88 ± 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and ≥400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with ≥2.0 (1.9 vs. 5.5%/year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and ≥400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification. CONCLUSIONS In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events.

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all-cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2-1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log-transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all-cause and cardiovascular mortality in patients with dd-ESRD.

Study of young patients with myocardial infarction: Design and rationale of the YOUNG-MI Registry

The YOUNG‐MI registry is a retrospective study examining a cohort of young adults age ≤ 50 years with a first‐time myocardial infarction. The study will use the robust electronic health records of 2 large academic medical centers, as well as detailed chart review of all patients, to generate high‐quality longitudinal data regarding the clinical characteristics, management, and outcomes of patients who experience a myocardial infarction at a young age. Our findings will provide important insights regarding prevention, risk stratification, treatment, and outcomes of cardiovascular disease in this understudied population, as well as identify disparities which, if addressed, can lead to further improvement in patient outcomes.

TYPE 2 MYOCARDIAL INFARCTION IN YOUNG PATIENTS PORTENDS A WORSE LONG-TERM SURVIVAL

Background: Recent data suggests that patients with Type 2 Myocardial Infarction (T2-MI) have a worse prognosis than previously appreciated. Yet, little is known about the implications of having a T2-MI at a young age. Methods: Using clinical & billing data, we identified all patients presenting

Change in Statin Therapy after CCTA is Associated with Lower LDL-Cholesterol without Change in Three-Year Prognosis

Coronary Computed Tomography Angiography (CCTA) is an accurate test for coronary artery disease (CAD), yet the impact of the CCTA results upon subsequent medical therapy and risk factors has not been widely reported. We identified consecutive patients >18 years of age without known prior CAD who

Long Term Prognostic Value of Coronary CT Angiography for Prediction of Cardiovascular Events and Mortality

Apresentado no 62nd Annual Scientific Session of the American College of Cardiology, realizado em 09-11 de marco de 2013 em San Francisco, CA.