Benjamin J.W. Chow

Age- and Sex-Related Differences in All-Cause Mortality Risk Based on Coronary Computed Tomography Angiography Findings Results From the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 Patients Without Known Coronary Artery Disease

OBJECTIVES We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). BACKGROUND Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. METHODS We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. RESULTS At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. CONCLUSIONS Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis.

Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia.

OBJECTIVES We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 ((82)Rb) positron emission tomography (PET) in patients assessed for ischemia. BACKGROUND The clinical value of MFR quantification using (82)Rb PET beyond relative myocardial perfusion imaging remains uncertain. METHODS We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. RESULTS For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). CONCLUSIONS MFR quantified using (82)Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of (82)Rb PET-quantified MFR could improve risk stratification for patients being investigated for ischemia.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction

OBJECTIVES We sought to determine the prognostic and incremental value of coronary artery disease (CAD) severity, coronary atherosclerosis, and left ventricular ejection fraction (LVEF) measured with cardiac computed tomography angiography (CTA). BACKGROUND CTA is an emerging tool used for the detection of obstructive CAD. However, there are limited data supporting the prognostic value of 64-slice CTA and its ability to predict all-cause mortality and major adverse cardiac events such as cardiac death and nonfatal myocardial infarction. METHODS Consecutive patients (without history of revascularization, heart transplantation, and congenital heart disease) were prospectively enrolled. Each CTA was evaluated for CAD severity, total plaque score, and LVEF. Patients were followed, and all events were confirmed with death certificates or hospital or physician records and reviewed by a clinical events committee. RESULTS Between February 2006 and February 2008, 2,076 consecutive patients were prospectively enrolled and followed for a mean of 16 +/- 8 months. At follow-up, a total of 31 (1.5%) patients had cardiac death or nonfatal myocardial infarction and 47 (2.3%) had all-cause mortality or nonfatal myocardial infarction. Multivariate analysis showed that CAD severity (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.89 to 4.83) was a predictor of major adverse cardiac events and that LVEF (HR: 1.47; 95% CI: 1.17 to 1.86) had incremental value over CAD severity. Total plaque score had incremental value over CAD severity and LVEF for all-cause mortality and nonfatal myocardial infarction (HR: 1.17; 95% CI: 1.06 to 1.29). CONCLUSIONS Using CTA, CAD severity, LVEF, and total plaque score seems to have prognostic and incremental value over routine clinical predictors. Cardiac CTA seems to be a promising noninvasive modality with prognostic value.

Prevalence and Severity of Coronary Artery Disease and Adverse Events Among Symptomatic Patients With Coronary Artery Calcification Scores of Zero Undergoing Coronary Computed Tomography Angiography Results From the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) Registry

OBJECTIVES The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). BACKGROUND The frequency and clinical relevance of CAD in patients without CAC are unclear. METHODS We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed. RESULTS Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). CONCLUSIONS In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA.

Patient management after noninvasive cardiac imaging: Results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease)

OBJECTIVES This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. BACKGROUND Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear. METHODS We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography. RESULTS Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results. CONCLUSIONS Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomys Role in Coronary Artery [CAD] [SPARC]; NCT00321399).

Coronary Computed Tomographic Angiography and Risk of All-Cause Mortality and Nonfatal Myocardial Infarction in Subjects Without Chest Pain Syndrome From the CONFIRM Registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)

Background— The predictive value of coronary computed tomographic angiography (cCTA) in subjects without chest pain syndrome (CPS) has not been established. We investigated the prognostic value of coronary artery disease detection by cCTA and determined the incremental risk stratification benefit of cCTA findings compared with clinical risk factor scoring and coronary artery calcium scoring (CACS) for individuals without CPS. Methods and Results— An open-label, 12-center, 6-country observational registry of 27 125 consecutive patients undergoing cCTA and CACS was queried, and 7590 individuals without CPS or history of coronary artery disease met the inclusion criteria. All-cause mortality and the composite of all-cause mortality and nonfatal myocardial infarction were measured. During a median follow-up of 24 months (interquartile range, 18–35 months), all-cause mortality occurred in 136 individuals. After risk adjustment, compared with individuals without evidence of coronary artery disease by cCTA, individuals with obstructive 2- and 3-vessel disease or left main coronary artery disease experienced higher rates of death and composite outcome (P<0.05 for both). Both CACS and cCTA significantly improved the performance of standard risk factor prediction models for all-cause mortality and the composite outcome (likelihood ratio P<0.05 for all), but the incremental discriminatory value associated with their inclusion was more pronounced for the composite outcome and for CACS (C statistic for model with risk factors only was 0.71; for risk factors plus CACS, 0.75; for risk factors plus CACS plus cCTA, 0.77). The net reclassification improvement resulting from the addition of cCTA to a model based on standard risk factors and CACS was negligible. Conclusions— Although the prognosis for individuals without CPS is stratified by cCTA, the additional risk-predictive advantage by cCTA is not clinically meaningful compared with a risk model based on CACS. Therefore, at present, the application of cCTA for risk assessment of individuals without CPS should not be justified.

Potential Clinical and Economic Consequences of Noncardiac Incidental Findings on Cardiac Computed Tomography

OBJECTIVES We sought to determine the incidence, clinical significance, and potential financial impact of noncardiac incidental findings (IF) identified with cardiac computed tomography (CT). BACKGROUND Cardiac CT is gaining acceptance and may lead to the frequent discovery of extracardiac IF. METHODS Consecutive patients undergoing cardiac CT had noncardiac structures evaluated after full field of view (32 to 50 cm) reconstruction. IF were categorized as clinically significant (CS), indeterminate, or clinically insignificant. Patient follow-up was performed by telephone, and verified with hospital records and/or communication with physicians. RESULTS Of 966 patients (58 +/- 16 years of age, 55.4% men, >98% outpatients), 401 (41.5%) patients had noncardiac IF. A total of 12 (1.2%) patients had CS findings, and 68 (7.0%) patients had indeterminate findings. At follow-up (18.4 +/- 7.6 months), none of the indeterminate findings became CS. Although 3 patients with indeterminate findings were diagnosed with malignant lesions, they were unrelated to the IF. After adjusting for age, IF were not an independent predictor of noncardiac death. Noncardiac death and cancer death in patients with and without IF were not statistically different. One patient suffered a major complication related to the investigation of an IF. The total direct cost associated with investigating IF was Canadian

Prognostic Value of Stress Myocardial Perfusion Positron Emission Tomography: Results From a Multicenter Observational Registry

57,596 (U.S.

Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography.

83,035). CONCLUSIONS Although noncardiac IF are common, clinically significant or indeterminate IF are less prevalent. Rates of death were similar in patients with and without IF, and IF was not an independent predictor of noncardiac death. The investigation of IF is not without cost or risk. Larger studies are required to assess the potential mortality benefit of identifying IF.