Marcio Sommer Bittencourt

Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events

Background—The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. Methods and Results—All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive (<50% stenosis), or obstructive (≥50%). Based on the number of segments with disease, extent of CAD was classified as nonextensive (⩽4 segments) or extensive (>4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1–5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5–6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3–6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2–7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. Conclusions—Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment.

Outcomes After Coronary Computed Tomography Angiography in the Emergency Department: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials

OBJECTIVES The aim of the study was to systematically review and perform a meta-analysis of randomized, controlled trials of coronary computed tomography angiography (CCTA) versus usual care (UC) triage of acute chest pain in the emergency department (ED). BACKGROUND CCTA allows rapid evaluation of patients presenting to the ED with acute chest pain syndromes; however, the impact of such testing on patient management and downstream testing has emerged as a concern. METHODS We systematically searched for randomized, controlled trials of CCTA in the ED and performed a meta-analysis of clinical outcomes. RESULTS Four randomized, controlled trials were included, with 1,869 patients undergoing CCTA and 1,397 undergoing UC. There were no deaths and no difference in the incidence of myocardial infarction, post-discharge ED visits, or rehospitalizations. Four studies reported decreased length of stay with CCTA and 3 reported cost savings; 8.4% of patients undergoing CCTA versus 6.3% of those receiving UC underwent invasive coronary angiography (ICA), whereas 4.6% of patients undergoing CCTA versus 2.6% of those receiving UC underwent coronary revascularization. The odds ratio of ICA for CCTA patients versus UC patients was 1.36 (95% confidence interval [CI]: 1.03 to 1.80, p = 0.030), and for revascularization, it was 1.81 (95% CI: 1.20 to 2.72, p = 0.004). The absolute increase in ICA after CCTA was 21 per 1,000 CCTA patients (95% CI: 1.8 to 44.9), and the number needed to scan was 48. The absolute increase in revascularization after CCTA was 20 per 1,000 patients (95% CI: 5.0 to 41.4); the number needed to scan was 50. Both percutaneous coronary intervention and coronary artery bypass graft surgery independently contributed to the significant increase in revascularization. CONCLUSIONS Compared with UC, the use of CCTA in the ED is associated with decreased ED cost and length of stay but increased ICA and revascularization.

Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis)

BACKGROUND The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy. OBJECTIVES This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not. METHODS MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein <70 mg/dl from the analysis. RESULTS The study population consisted of 4,758 participants (age 59 ± 9 years; 47% males). A total of 247 (5.2%) ASCVD and 155 (3.3%) hard coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years. CONCLUSIONS Significant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.

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.

Carotid intima–media thickness value distributions in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

OBJECTIVE Carotid intima-media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture. METHODS The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35-74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors. RESULTS We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (β = 0.058; P < 0.001). This association remained for low-risk individuals (β = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (β = -0.034 and β = -0.054, respectively; P < 0.001) and low-risk individuals (β = -0.027; P = 0.013 and β = -0.035; P < 0.001, respectively). CONCLUSION We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals.

Clinical Outcomes After Evaluation of Stable Chest Pain by Coronary Computed Tomographic Angiography Versus Usual Care A Meta-Analysis

Background—Limited data exist on how noninvasive testing options compare for evaluating patients with suspected stable coronary artery disease. In this study, we have performed a meta-analysis of randomized controlled trials comparing the use of coronary computed tomographic angiography (CTA) with usual care. Methods and Results—We systematically searched databases for randomized clinical trials comparing coronary CTA with usual care for the evaluation of stable chest pain with follow-up for cardiovascular outcomes. The primary outcomes were myocardial infarction and all-cause mortality. We identified 4 randomized clinical trials, including a total of 7403 patients undergoing coronary CTA and 7414 patients undergoing usual care with various functional testing approaches. When compared with usual care, the use of coronary CTA was associated with a significant reduction in the annual rate of myocardial infarction (rate ratio, 0.69; 95% confidence interval, 0.49–0.98; P=0.038), but no difference was found in all-cause mortality. There was a trend toward more invasive coronary angiographies among patients undergoing coronary CTA (odds ratio, 1.33; 95% confidence interval, 0.95–1.84; P=0.09) and higher use of coronary revascularizations (odds ratio, 1.77; 95% confidence interval, 1.14–2.75). Significant heterogeneity for invasive coronary angiography and revascularization was noted, which was attributable to the Scottish Computed Tomography of the HEART (SCOT-HEART) study. We found no difference in the rate of admission for cardiac chest pain (rate ratio, 1.21; 95% confidence interval, 0.95–1.54). Conclusions—In comparison to usual care, an initial investigation of suspected stable coronary artery disease using coronary CTA resulted in a significant reduction in myocardial infarction, an increased incidence of coronary revascularization, and no effect in all-cause mortality. Future studies should further define whether the potential reduction in myocardial infarction identified justifies the increased resource utilization associated with coronary CTA.

Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease

OBJECTIVE To evaluate the prognostic value and test characteristics of coronary artery calcium (CAC) score for the identification of obstructive coronary artery disease (CAD) in comparison with coronary computed tomography angiography (CCTA) among symptomatic patients. METHODS Retrospective cohort study at two large hospitals, including all symptomatic patients without prior CAD who underwent both CCTA and CAC. Accuracy of CAC for the identification of ≥ 50% and ≥ 70% stenosis by CCTA was evaluated. Prognostic value of CAC and CCTA were compared for prediction of major adverse cardiovascular events (MACE, defined as non-fatal myocardial infarction, cardiovascular death, late coronary revascularization (>90 days), and unstable angina requiring hospitalization). RESULTS Among 1145 included patients, the mean age was 55 ± 12 years and median follow up 2.4 (IQR: 1.5-3.5) years. Overall, 406 (35%) CCTA were normal, 454 (40%) had <50% stenosis, and 285 (25%) had ≥ 50% stenosis. The prevalence of ≥ 70% stenosis was 16%. Among 483 (42%) patients with CAC zero, 395 (82%) had normal CCTA, 81 (17%) <50% stenosis, and 7 (1.5%) ≥ 50% stenosis. 2 (0.4%) patients had ≥ 70% stenosis. For diagnosis of ≥ 50% stenosis, CAC had a sensitivity of 98% and specificity of 55%. The negative predictive value (NPV) for CAC was 99% for ≥ 50% stenosis and 99.6% for ≥ 70% stenosis by CCTA. There were no adverse events among the 7 patients with zero calcium and ≥ 50% CAD. For prediction of MACE, the c-statistic for clinical risk factors of 0.62 increased to 0.73 (p < 0.001) with CAC versus 0.77 (p = 0.02) with CCTA. CONCLUSION Among symptomatic patients with CAC zero, a 1-2% prevalence of potentially obstructive CAD occurs, although this finding was not associated with future coronary revascularization or adverse prognosis within 2 years.

Cardiac sarcoidosis—state of the art review

Sarcoidosis is a multi-system inflammatory disorder of unknown etiology resulting in formation of non-caseating granulomas. Cardiac involvement-which is associated with worse prognosis-has been detected in approximately 25% of individuals based on autopsy or cardiac imaging studies. Nevertheless, the diagnosis of cardiac sarcoidosis is challenging due to the low yield of endomyocardial biopsy, and the limited accuracy of various clinical criteria. Thus, no gold standard diagnostic criterion exists. This review will summarize the pathophysiology, diagnosis, and treatment of cardiac sarcoidosis with a focus on advanced cardiovascular imaging, We review the evidence to support a role for cardiac magnetic resonance (CMR) imaging in the initial evaluation of selected patients with suspected cardiac sarcoidosis, with cardiac positron emission tomography (PET) as an alternative or complementary initial diagnostic test in a subgroup of patients in whom CMR may be contra-indicated or when CMR is negative with continued clinical concern for myocardial inflammation. In addition to the diagnostic value of these tests, CMR and PET are also useful in identifying patients who have higher risk of adverse events such as ventricular tachycardia or death, in whom preventive therapies such as defibrillators should be more strongly considered. Although no randomized controlled trials for treatment of cardiac sarcoidosis exist, immunosuppressive therapy is often used. We review emerging evidence regarding the use of cardiac PET to identify and quantity the amount of myocardial inflammation as well as to guide the use of immunotherapy. Future studies are needed to determine the benefit of imaging guided therapies aimed at improving patient outcomes.

Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis: A Systematic Review and Meta-Analysis

Background—Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis. Methods and Results—We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men).One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7; P=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34–86.3]; P=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68–143]; P=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47–15.6]; P<0.001). There was no significant heterogeneity for any outcomes. Conclusions—LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis.

European Society of Cardiology–Recommended Coronary Artery Disease Consortium Pretest Probability Scores More Accurately Predict Obstructive Coronary Disease and Cardiovascular Events Than the Diamond and Forrester Score

Background: The most appropriate score for evaluating the pretest probability of obstructive coronary artery disease (CAD) is unknown. We sought to compare the Diamond-Forrester (DF) score with the 2 CAD consortium scores recently recommended by the European Society of Cardiology. Methods: We included 2274 consecutive patients (age, 56±13 years; 57% male) without prior CAD referred for coronary computed tomographic angiography. Computed tomographic angiography findings were used to determine the presence or absence of obstructive CAD (≥50% stenosis). We compared the DF score with the 2 CAD consortium scores with respect to their ability to predict obstructive CAD and the potential implications of these scores on the downstream use of testing for CAD, as recommended by current guidelines. Results: The DF score did not satisfactorily fit the data and resulted in a significant overestimation of the prevalence of obstructive CAD (P<0.001); the CAD consortium basic score had no significant lack of fitness; and the CAD consortium clinical provided adequate goodness of fit (P=0.39). The DF score had a lower discrimination for obstructive CAD, with an area under the receiver-operating characteristics curve of 0.713 versus 0.752 and 0.791 for the CAD consortium models (P<0.001 for both). Consequently, the use of the DF score was associated with fewer individuals being categorized as requiring no additional testing (8.3%) compared with the CAD consortium models (24.6% and 30.0%; P<0.001). The proportion of individuals with a high pretest probability was 18% with the DF and only 1.1% with the CAD consortium scores (P<0.001) Conclusions: Among contemporary patients referred for noninvasive testing, the DF risk score overestimates the risk of obstructive CAD. On the other hand, the CAD consortium scores offered improved goodness of fit and discrimination; thus, their use could decrease the need for noninvasive or invasive testing while increasing the yield of such tests.