Joshua Schulman-Marcus

Static and dynamic assessment of myocardial perfusion by computed tomography

Recent developments in computed tomography (CT) technology have fulfilled the prerequisites for the clinical application of myocardial CT perfusion (CTP) imaging. The evaluation of myocardial perfusion by CT can be achieved by static or dynamic scan acquisitions. Although both approaches have proved clinically feasible, substantial barriers need to be overcome before its routine clinical application. The current review provides an outline of the current status of CTP imaging and also focuses on disparities between static and dynamic CTPs for the evaluation of myocardial blood flow.

Long-Term Prognosis after Coronary Artery Calcium Scoring among Low-Intermediate Risk Women and Men

Background—Cardiovascular screening of women using traditional risk factors has been challenging, with results often classifying a majority of women as lower risk than men. The aim of this report was to determine the long-term prognosis of asymptomatic women and men classified at low-intermediate risk undergoing screening with coronary artery calcium (CAC) scoring. Methods and Results—A total of 2363 asymptomatic women and men with traditional risk factors aggregating into a low-intermediate Framingham risk score (6%–9.9%; 10-year predicted risk) underwent CAC scanning. Individuals were followed up for a median of 14.6 years. We estimated all-cause mortality using Cox proportional hazards models; hazard ratios with 95% confidence intervals were calculated. The area under the curve from a receiver operating characteristics curve analysis was calculated. There were 1072 women who were older (55.6 years) when compared with the 1291 men (46.7 years; P<0.0001), resulting in a greater prevalence and extent of CAC; 18.8% of women and 15.1% of men had a CAC score ≥100 (P=0.029). This older group of women had a 1.44-fold higher 15-year adjusted mortality hazard when compared with men (P=0.022). For women, the 15-year mortality ranged from 5.0% for those with a CAC score of 0 to 23.5% for those with a CAC score ≥400 (P<0.001). For men, the 15-year mortality ranged from 3.5% for those with a CAC score of 0 to 18.0% for those with a CAC score ≥400 (P<0.001). Women with CAC scores >10 had a higher mortality risk when compared with men. Conclusions—Our findings extend previous work that CAC effectively identifies high-risk women with a low-intermediate risk factor burden. These data require validation in external cohorts but lend credence to the use of CAC in women to improve risk detection algorithms that are currently based on traditional risk factors.

Prognostic Utility of Coronary Artery Calcium Scoring in Active Smokers: A 15-Year Follow-Up Study

Coronary artery calcium (CAC) is a frequent finding in smokers, and it is a marker of accelerated atherosclerosis in this population.1 Prior research has demonstrated a higher rate of five to ten year estimated all-cause mortality in smokers with CAC as compared to smokers without CAC.2,3 However, previous studies have produced limited insight regarding the long-term efficacy of CAC for risk stratification in smokers. This study therefore sought to examine the association between smoking, CAC, and all-cause mortality over a 15-year period. The study population was a cohort of 4,143 consecutive asymptomatic patients aged 55 and older (mean 63.2±6.6 years, range 55–99) without known coronary artery disease (CAD) who had been referred by their physician for CAC testing between 1991 and 2004. All study participants completed a baseline questionnaire of demographic characteristics and baseline cardiovascular risk factors. Cigarette smoking was considered present if a subject was an active smoker at the time of CAC scanning. CAC measurement was performed by electron beam computed tomography (EBCT) at three different centers in the United States using standard methods as previously described.3 Each calcified lesion was scored using the method developed by Agatston et al.4 All individuals provided informed consent for a pre-test interview, CAC testing, and follow-up. The study received approval from the appropriate Human Investigations Committee and conforms to the 1975 Declaration of Helsinki. The primary endpoint was all-cause mortality. Individuals masked to baseline data ascertained mortality status using the Social Security Death Index with 100% mortality ascertainment among study participants. For statistical analyses, the chi-square test was employed for comparison of categorical variables. Between-group comparisons for continuous variables were computed using an independent samples t-test or Mann-Whitney U test as appropriate. A Kaplan-Meier survival curve with log-rank test compared survival rates for smokers versus nonsmokers, according to the presence and severity of CAC. Cox proportional hazard regression reporting hazard ratios (HR) with 95% confidence intervals (95% CI) were used to estimate all-cause mortality adjusting for age, sex, diabetes, hypertension, dyslipidemia, and family history of premature CAD. All Cox models were stratified according to smoking status as well as the presence or absence (Model 1) or severity (Model 2) of CAC. As there was no significant interaction effect between sex and CAC, analyses stratified by sex were not performed. Assumption of proportional hazards was evaluated using Schoenfeld residuals. Statistical analyses were performed using SAS version 9.3 software (SAS Institute Inc., Cary, NC). A two-tailed p-value <0.05 was considered statistically significant. The patients were followed on average for 14.5 years (interquartile range 13.5–15.3). At the time of CAC assessment, 39% were self-reported active smokers. Of 553 deaths that occurred, 270 (16.6%) and 283 (11.3%) were smokers and nonsmokers at the time of CAC scan, respectively. Smokers were more prone to a family history of premature CAD (70.7% vs 65.3%, p<0.001) and diabetes (10.4% vs 8.5%, p=0.04) as compared with nonsmokers (Table 1). Smokers had higher median CAC scores (19 vs 3, interquartile range 0–195, p<0.001) and increased CAC severity (p<0.001 for trend), while nonsmokers were more likely to have a CAC of 0 than smokers (47.8 vs. 38.7%, p<0.001). Table 1 Clinical Characteristics of Subjects Irrespective of smoking status, higher CAC severity was associated with heightened mortality risk over the course of this study (p<0.001 by log-rank) (Figure). In multivariable Cox hazard regression models, smokers with a CAC of zero had a nearly two-fold (HR 1.73, 95% CI = 1.20–2.50, p=0.003) increased risk of mortality (Table 2, Model 1). In the presence of any CAC, the adjusted risk of mortality was more than three-fold (HR 3.07, 95% CI = 2.32–4.07, p<0.001) higher in nonsmokers, while the adjusted risk of mortality was almost five-fold (HR 4.67, 95% CI = 3.52–6.20, p<0.001) higher among smokers. Similar findings were observed in patients without additional cardiac risk factors (e.g. hypertension, diabetes, dyslipidemia, family history of premature CAD). In both smokers and nonsmokers, the adjusted risk of death appeared to increase incrementally according to the severity of CAC (Table 2, Model 2). Figure Cumulative survival among non-smokers and smokers stratified by CAC score Table 2 Risk of all-cause death among non-smokers and smokers according to the presence and severity of coronary artery calcium Overall, we found that across nearly 15 years of follow-up, the presence of CAC remained strongly predictive of all-cause mortality in this cohort of older smokers, even in the absence of other cardiac risk factors. Our findings are consistent with prior studies of shorter duration demonstrating increased mortality in smokers with CAC.2,3 Furthermore, in contrast to the general population for which the absence of CAC (CAC=0) is associated with an excellent prognosis,5 in our study smokers with a CAC=0 remained at an elevated risk of death. As such, for smokers a CAC=0 should not be considered a “negative risk factor.”3 Our study was limited by its observational design. Prior smoking history and smoking intensity as measured by pack years were not obtained. Data were unavailable regarding cause-specific mortality, cardiovascular events, post-test changes in risk factors, downstream pharmacological therapy or smoking cessation. Future long-term prospective cohort studies are needed to address these limitations. However, this is the largest cohort of consecutive patients undergoing CAC screening for which outcome data are available. Our findings are timely in that many smokers aged 55–80 are poised to undergo annual lung cancer screening by low dose computed tomography (CT).6–8 There is a high correlation between CAC discovered by CT and ECG-gated CAC screening protocols.9 This study proposes a potential benefit in highlighting the presence of any CAC detected by CT, rather than considering it as an “incidental” finding. While further research regarding CAC in lung cancer screening cohorts is clearly needed, our findings indicate that smokers with CAC detected by CT are at elevated risk and warrant early and aggressive cardiac risk factor reduction.

Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality A 15-Year Follow-Up Study of 9715 Patients

Background—Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long-term risk stratification of CAC among diabetic compared with nondiabetic individuals. Methods and Results—Nine thousand seven hundred and fifteen asymptomatic individuals undergoing CAC scoring were followed for a median (interquartile range) of 14.7 (13.9–15.6) years. The incidence density rate and hazard ratios with 95% confidence intervals were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve and net reclassification improvement. Diabetics (54.7±10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and nondiabetic individuals for the first 5 years (P>0.05), with a nonlinear increased risk of mortality for diabetics after 5 years (P<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95% confidence interval =3.74–5.76) and 3.41 (95% confidence interval =2.22–5.22) for nondiabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (area under the receiver operator characteristic curve range: 0.73–0.74; P<0.01) and reclassification (category-free net reclassification improvement range: 0.53–0.50; P<0.001) beyond conventional risk factors in nondiabetic and diabetic individuals, respectively. Conclusions—CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and nondiabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0.

15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly

INTRODUCTION Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. METHODS A consecutive series of 9715 individuals underwent CAC scoring and were followed for a mean of 14.6 ± 1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). RESULTS Of the overall study sample, 728 (7.5%) adults (mean age 74.2 ± 4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84-6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P < 0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P < 0.001) when added to RFs. CONCLUSION In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death.

Characteristics of Patients Undergoing Cardiac Catheterization Before Noncardiac Surgery: A Report From the National Cardiovascular Data Registry CathPCI Registry

IMPORTANCE Many patients undergo cardiac catheterization and/or percutaneous coronary intervention (PCI) before noncardiac surgery even though these procedures are not routinely indicated. Data on this cohort of patients are limited. OBJECTIVE To describe the characteristics, angiographic findings, and treatment patterns of clinically stable patients undergoing cardiac catheterization and/or PCI before noncardiac surgery in a large national registry. DESIGN, SETTING, AND PARTICIPANTS This study is a retrospective, descriptive analysis of National Cardiac Data Registry CathPCI Registry diagnostic catheterization and PCI data from July 1, 2009, through December 31, 2014. Data analysis was performed from April 21, 2015, to January 4, 2016. The study included 194 444 patients from 1046 sites who underwent coronary angiography before noncardiac surgery. Patients with acute coronary syndrome, cardiogenic shock, cardiac arrest, or emergency catheterization were excluded. MAIN OUTCOMES AND MEASURES Demographic characteristics, preprocedure noninvasive testing results, angiographic findings, and treatment recommendations are summarized. Among the 27 838 patients who underwent PCI, procedural details, inpatient outcomes, and discharge medications are reported. RESULTS Of the 194 444 included patients, 113 590 (58.4%) were male, the median age was 65 years (interquartile range, 57-73 years), and 162 532 (83.6%) were white. Most were overweight or obese (152 849 [78.6%]), and 78 847 (40.6%) had diabetes mellitus. Most patients were asymptomatic (117 821 [60.6%]), although 112 302 (57.8%) had been taking antianginal medications within 2 weeks of the procedure. Prior noninvasive stress testing was reported in 126 766 (65.2%), and results were positive in 109 458 (86.3%) of those with stress data. Obstructive disease was present in 93 447 (48.1%). After diagnostic angiography, revascularization with PCI or bypass surgery was recommended in 46 380 patients (23.8%) in the overall cohort, 27 191 asymptomatic patients (23.1%), and 45 083 patients with obstructive disease (48.3%). In the 27 191 patients undergoing PCI, 367 treated lesions (1.3%) were in the left main artery and 3831 (13.8%) in the proximal left anterior descending artery. A total of 11 366 patients (40.8%) received drug-eluting stents. Complications occurred in a few patients, with a catheterization-related mortality rate of 0.05%. CONCLUSIONS AND RELEVANCE In the largest contemporary US cohort reported to date, most patients undergoing diagnostic catheterization before noncardiac surgery are asymptomatic. The discovery of obstructive coronary artery disease is common, and although randomized clinical trials have found no benefit in outcomes, revascularization is recommended in nearly half of these patients. The overall findings highlight management patterns in this population and the need for greater evidence-based guidelines and practices.

Comparison of Trends in Incidence, Revascularization, and In-Hospital Mortality in ST-Elevation Myocardial Infarction in Patients With Versus Without Severe Mental Illness.

Patients with severe mental illness (SMI), including schizophrenia and bipolar disorder, are at elevated risk of ST-elevation myocardial infarction (STEMI) but have previously been reported as less likely to receive revascularization. To study the persistence of these findings over time, we examined trends in STEMI incidence, revascularization, and in-hospital mortality for patients with and without SMI in the National Inpatient Sample from 2003 to 2012. We further used multivariate logistic regression analysis to assess the odds of revascularization and in-hospital mortality. SMI was present in 29,503 of 3,058,697 (1%) of the STEMI population. Patients with SMI were younger (median age 58 vs 67 years), more likely to be women (44% vs 38%), and more likely to have several co-morbidities, including diabetes, chronic pulmonary disease, substance abuse, and obesity (p <0.001 for all). Over time, STEMI incidence significantly decreased in non-SMI (p for trend <0.001) but not in SMI (p for trend 0.14). Revascularization increased in all subgroups (p for trend <0.001) but remained less common in SMI. In-hospital mortality decreased in non-SMI (p for trend = 0.004) but not in SMI (p for trend 0.10). After adjustment, patients with SMI were less likely to undergo revascularization (odds ratio 0.59, 95% CI 0.52 to 0.61, p <0.001), but SMI was not associated with increased in-hospital mortality (odds ratio 0.97, 95% CI 0.93 to 1.01, p = 0.16). In conclusion, in contrast to the overall population, the incidence of STEMI is not decreasing in patients with SMI. Despite changes in the care of STEMI, patients with SMI remain less likely to receive revascularization therapies.

Relationship Between Endothelial Wall Shear Stress and High‐Risk Atherosclerotic Plaque Characteristics for Identification of Coronary Lesions That Cause Ischemia: A Direct Comparison With Fractional Flow Reserve

Background Wall shear stress (WSS) is an established predictor of coronary atherosclerosis progression. Prior studies have reported that high WSS has been associated with high‐risk atherosclerotic plaque characteristics (APCs). WSS and APCs are quantifiable by coronary computed tomography angiography, but the relationship of coronary lesion ischemia—evaluated by fractional flow reserve—to WSS and APCs has not been examined. Methods and Results WSS measures were obtained from 100 evaluable patients who underwent coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve. Patients were categorized according to tertiles of mean WSS values defined as low, intermediate, and high. Coronary ischemia was defined as fractional flow reserve ≤0.80. Stenosis severity was determined by minimal luminal diameter. APCs were defined as positive remodeling, low attenuation plaque, and spotty calcification. The likelihood of having positive remodeling and low‐attenuation plaque was greater in the high WSS group compared with the low WSS group after adjusting for minimal luminal diameter (odds ratio for positive remodeling: 2.54, 95% CI 1.12–5.77; odds ratio for low‐attenuation plaque: 2.68, 95% CI 1.02–7.06; both P<0.05). No significant relationship was observed between WSS and fractional flow reserve when adjusting for either minimal luminal diameter or APCs. WSS displayed no incremental benefit above stenosis severity and APCs for detecting lesions that caused ischemia (area under the curve for stenosis and APCs: 0.87, 95% CI 0.81–0.93; area under the curve for stenosis, APCs, and WSS: 0.88, 95% CI 0.82–0.93; P=0.30 for difference). Conclusions High WSS is associated with APCs independent of stenosis severity. WSS provided no added value beyond stenosis severity and APCs for detecting lesions with significant ischemia.

State-of-the-Art Updates on Cardiac Computed Tomographic Angiography for Assessing Coronary Artery Disease

Opinion statementCardiac computed tomographic angiography (CCTA) is a noninvasive imaging modality that is increasingly useful for the evaluation of coronary artery disease (CAD). Over the past decade, CCTA has consistently demonstrated an excellent sensitivity for the detection and exclusion of coronary atherosclerosis in patients with stable or acute chest pain symptoms. Large prospective registries have repeatedly demonstrated the prognostic significance of the presence, extent, or absence of CAD by CCTA. In response to initial concerns, technical advances have permitted a dramatic reduction in patient radiation exposure with preserved image quality. For many patients, the radiation dose of CCTA is less than half of that with conventional myocardial perfusion imaging while providing significantly more anatomic information. Furthermore, CCTA’s excellent spatial resolution is increasingly being used for noninvasive assessment of coronary plaque, including the detection of higher-risk vulnerable plaque and association between plaque characteristics and ischemia. Finally, new promising techniques that incorporate physiology with anatomy, such as CT-based fractional flow reserve (FFR-CT) and CT perfusion (CTP), are allowing for the noninvasive hemodynamic assessment of coronary stenoses and improvements in the specificity of CCTA findings. Such advances augur a coming transition when CCTA will be a first-line test for the detection, exclusion, and even management of CAD in many patients.

Coronary revascularization vs. medical therapy following coronary-computed tomographic angiography in patients with low-, intermediate- and high-risk coronary artery disease: results from the CONFIRM long-term registry.

Abstract Aims To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA). Methods and results We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11–0.47) and 5 years (HR 0.31, 95% CI 0.18–0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22–0.93) but not 5 years (HR 0.63, 95% CI 0.33–1.20). For low-risk CAD, there was no survival benefit at either time point. Conclusions Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD.