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1.
JAMA Cardiol ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227128

RESUMO

Importance: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. Objective: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. Design, Setting, and Participants: This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. Interventions: CCTA and angina assessment. Main Outcomes and Measures: Sex differences in stress test, CCTA findings, and symptom severity. Results: Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). Conclusions and Relevance: Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. Trial Registration: ClinicalTrials.gov Identifier: NCT01471522.

2.
N Engl J Med ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227755

RESUMO

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

4.
Artigo em Inglês | MEDLINE | ID: mdl-32063545

RESUMO

BACKGROUND AND AIMS: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex. METHODS: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. RESULTS: The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. CONCLUSIONS: PAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32065624

RESUMO

AIMS: In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. METHODS AND RESULTS: Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004). CONCLUSION: Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.

6.
Int J Cardiol ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32037132

RESUMO

BACKGROUND: Women with evidence of ischemia and no obstructive coronary arteries (INOCA) often have coronary microvascular dysfunction (CMD) indicated by impaired coronary flow reserve (CFR) to adenosine. Low CFR is associated with an adverse prognosis, including incident heart failure. Because the CFR calculation relies on the baseline intrinsic coronary vasomotor flow velocity, a major determinate of CFR and the degree of variation in baseline flow alone may be an important contributor to risk of adverse outcomes in women with CMD. A better understanding of baseline blood flow in the setting of low CFR and its association with myocardial performance would be helpful. METHODS: We evaluated 74 women who underwent invasive coronary reactivity testing in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study and had impaired CFR (<2.32). We assessed the relationship between coronary artery baseline average peak velocity (bAPV) at rest and cardiac magnetic resonance imaging measures of left ventricular (LV) structure and function. RESULTS: When stratified as low (<22 cm/s) versus high (≥22 cm/s) bAPV, there were no differences in cardiovascular risk factors, coronary plaque burden, or LV structure. However, low bAPV was associated with higher LV end-diastolic filling pressure (P = 0.04), lower LV ejection fraction (P = 0.001), and differences in late systolic and diastolic strain rates (P = 0.01 to 0.05). CONCLUSIONS: In women with impaired CFR, low resting coronary flow velocity is associated with more adverse myocardial performance, which may contribute to risk for adverse outcomes and particularly heart failure in women with CMD.

7.
J Invasive Cardiol ; 32(2): E18-E26, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32005786

RESUMO

OBJECTIVES: Little information is available on computed tomography (CT)-based predictors of stroke related to transcatheter aortic valve replacement (TAVR). The objective of this study was to determine whether anatomical features of the aortic valve and aorta visualized by CT are predictive parameters of stroke. METHODS: The study included 1270 patients who underwent preprocedural contrast-enhanced CT assessment and TAVR for severe aortic valve stenosis. Twenty-six patients (2.5%) who developed acute strokes that occurred within 48 hours after TAVR and 104 matched patients without strokes were identified, using 1:4 propensity-score matching. The degree of hypoattenuation in the aortic valve leaflets, calcium volume of the aortic valve, and plaque thickness in the aortic wall (the ascending aorta, aortic arch, and descending thoracic aorta) were assessed. RESULTS: There were no differences between the two groups in the degree of hypoattenuation in the aortic valve leaflets and calcium volume of the aortic valve. The plaque thickness of the aortic arch and descending aorta were greater in the stroke group than in the non-stroke group: aortic arch, 2.4 mm (IQR, 1.3-2.8 mm) vs 1.8 mm (IQR, 1.4-2.2 mm), respectively (P<.01); and descending aorta, 2.9 mm (IQR, 2.1-4.2 mm) vs 2.8 mm (IQR, 2.1-3.6 mm); respectively (P=.049). CONCLUSION: Aortic wall plaque thickness measured by contrast-enhanced CT might be a predictive parameter of strokes that occur within 48 hours after TAVR.

8.
Circ Cardiovasc Imaging ; 13(2): e009829, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32063057

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography. METHODS: Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction. RESULTS: At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm3 and coronary artery calcium ≥100 AU and was highest in subjects with both (P<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers. CONCLUSIONS: Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.

9.
J Am Heart Assoc ; 9(5): e013958, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32089046

RESUMO

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP.

10.
JAMA Cardiol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31968065

RESUMO

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31954640

RESUMO

OBJECTIVES: This study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE. BACKGROUND: The PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood. METHODS: We evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics. RESULTS: Mean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups. CONCLUSIONS: Our findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.

12.
Eur Heart J Cardiovasc Imaging ; 21(4): 363-374, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31985803

RESUMO

AIMS: There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. METHODS AND RESULTS: A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55-65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41-0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). CONCLUSION: Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01443637.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31897586

RESUMO

PURPOSE: 18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). METHODS: Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. RESULTS: In 50 patients (64% males, 63 ± 7 years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). CONCLUSIONS: Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

14.
Atherosclerosis ; 294: 33-40, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31951880

RESUMO

BACKGROUND AND AIMS: Cardiovascular disease (CVD) and cancer are the two leading causes of death in smokers. Lung cancer screening is recommended in a large proportion of smokers. We examined the implication of coronary artery calcium (CAC) score (quantitative and qualitative) for cardiovascular disease (CVD), coronary heart disease (CHD), and cancer mortality risk prediction among current smokers. METHODS: We included current smokers without known heart disease from the CAC Consortium. Cox regression (for all-cause mortality) and Fine-and-Gray competing-risk regression (for CVD, CHD, and cancer mortality) models, adjusted for traditional CVD risk factors, were used to assess the association between CAC and each mortality outcome, with CAC as a continuous (log2-transformed) or categorical variable (CAC = 0, CAC = 1-99, CAC = 100-399, and CAC ≥400). We used number of vessels with CAC as a surrogate for the qualitative measure of CAC and mortality outcomes. Analyses were repeated for lung cancer screening-eligible population (defined as ever smokers with >30 pack years smoking history) (n = 1,149). Hazard ratios (HR) for all-cause mortality and Subdistribution HRs (sHR) with 95% confidence intervals (CI) were reported. RESULTS: Over a median of 11.9 years (25th-75th percentile: 10.2-13.3) of follow-up, of 5,147 current smokers (mean age 52.5 ± 9.4, 32.4% women) 337 died (102 of CVD, 54 of CHD, and 123 of cancer). A doubling of CAC score was associated with increased HRs of all-cause mortality (1.10 (1.06-1.14)), and sHRs for CVD (1.15 (1.07-1.24)), CHD (1.26 (1.11-1.42)) and cancer mortality (1.06 (1.00-1.13)). Those with CAC ≥400 had increased sHR of CVD (3.55 (1.70-7.41)), CHD (8.80 (2.41-32.10)), and cancer mortality (1.85 (1.07-3.22)), compared with those with CAC = 0. A diffuse CAC pattern significantly increased the risk of all-cause, CVD, and CHD mortality among smokers. Results were consistent for the lung cancer screening-eligible population. CONCLUSIONS: Qualitative and quantitative CAC scores can prognosticate risk of all-cause, CVD, CHD, and cancer mortality beyond traditional risk factors among all smokers as well as those eligible for lung cancer screening.

15.
Diabetes Care ; 43(2): 453-459, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31776140

RESUMO

OBJECTIVE: Prevalence and prognostic impact of cardiovascular disease differ between patients with or without diabetes. We aimed to explore differences in the prevalence and prognosis of myocardial ischemia by automated quantification of total perfusion deficit (TPD) among patients with and without diabetes. RESEARCH DESIGN AND METHODS: Of 20,418 individuals who underwent single-photon emission computed tomography myocardial perfusion imaging, 2,951 patients with diabetes were matched to 2,951 patients without diabetes based on risk factors using propensity score. TPD was categorized as TPD = 0%, 0% < TPD < 1%, 1% ≤ TPD < 5%, 5% ≤ TPD ≤ 10%, and TPD >10%. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, unstable angina, or late revascularization. RESULTS: MACE risk was increased in patients with diabetes compared with patients without diabetes at each level of TPD above 0 (P < 0.001 for interaction). In patients with TPD >10%, patients with diabetes had greater than twice the MACE risk compared with patients without diabetes (annualized MACE rate 9.4 [95% CI 6.7-11.6] and 3.9 [95% CI 2.8-5.6], respectively, P < 0.001). Patients with diabetes with even very minimal TPD (0% < TPD < 1%) experienced a higher risk for MACE than those with 0% TPD (hazard ratio 2.05 [95% CI 1.21-3.47], P = 0.007). Patients with diabetes with a TPD of 0.5% had a similar MACE risk as patients without diabetes with a TPD of 8%. CONCLUSIONS: For every level of TPD >0%, even a very minimal deficit of 0% < TPD < 1%, the MACE risk was higher in the patients with diabetes compared with patients without diabetes. Patients with diabetes with minimal ischemia had comparable MACE risk as patients without diabetes with significant ischemia.

16.
Eur Heart J ; 41(3): 359-367, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31513271

RESUMO

AIMS: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA). METHODS AND RESULTS: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features. CONCLUSION: A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management.

17.
J Nucl Med ; 61(2): 249-255, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31451490

RESUMO

Cardiac allograft vasculopathy (CAV) is a major cause of graft failure after cardiac transplantation. CAV is characterized by diffuse involvement of epicardial coronary arteries and the microvasculature. PET allows quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR), which may be accurate markers of CAV severity. We compared the diagnostic and prognostic utility of stress MBF and MFR after cardiac transplantation. Methods: This was a cohort study of consecutive cardiac transplant patients undergoing 82Rb PET scans. Semiquantitative regional analysis and global measurement of stress MBF and MFR were performed. Associations with all-cause mortality were assessed with multivariable Cox analysis. The diagnostic accuracy for significant CAV (grade 2/3) and the prognostic accuracy of stress MBF and MFR, corrected and uncorrected for rate-pressure product, were compared. Results: In total, 99 patients, mean age 68.8 y and 75.8% male, were followed for a median of 3.4 y, during which 26 deaths occurred. Stress MBF and MFR had similar diagnostic accuracy for significant CAV. However, uncorrected MFR had improved discrimination for all-cause mortality compared with stress MBF (area under the curve, 0.748 vs. 0.639; P = 0.048). Higher MFR (adjusted hazard ratio, 0.30; P < 0.001), but not stress MBF (adjusted hazard ratio, 1.14; P = 0. 656), was associated with reduced all-cause mortality. Preserved MFR (>2.0) identified relatively low-risk patients (annual mortality, 4.7%), whereas the presence of a left ventricular ejection fraction lower than 45% and MFR lower than 1.7 identified high-risk patients (annual mortality, 51.6%). Conclusion: Quantitative PET analysis, and particularly MFR, has diagnostic and prognostic utility after heart transplantation. Preserved MFR identifies low-risk patients, whereas the presence of multiple abnormal parameters identifies high-risk patients.

18.
Atherosclerosis ; 294: 72-79, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31784032

RESUMO

BACKGROUND AND AIMS: The long-term associations between zero, minimal coronary artery calcium (CAC) and cause-specific mortality are currently unknown, particularly after accounting for competing risks with other causes of death. METHODS: We evaluated 66,363 individuals from the CAC Consortium (mean age 54 years, 33% women), a multi-center, retrospective cohort study of asymptomatic individuals undergoing CAC scoring for clinical risk assessment. Baseline evaluations occurred between 1991 and 2010. RESULTS: Over a mean of 12 years of follow-up, individuals with CAC = 0 (45% prevalence, mean age 45 years) had stable low rates of coronary heart disease (CHD) death, cardiovascular disease (CVD) death (ranging 0.32 to 0.43 per 1000 person-years), and all-cause death (1.38-1.62 per 1000 person-years). Cancer was the predominant cause of death in this group, yet rates were also very low (0.47-0.79 per 1000 person-years). Compared to CAC = 0, individuals with CAC 1-10 had an increased multivariable-adjusted risk of CVD death only under age 40. Individuals with CAC>10 had multivariable-adjusted increased risks of CHD death, CVD death and all-cause death at all ages, and a higher proportion of CVD deaths. CONCLUSIONS: CAC = 0 is a frequent finding among individuals undergoing CAC scanning for risk assessment and is associated with low rates of all-cause death at 12 years of follow-up. Our results support the emerging consensus that CAC = 0 represents a unique population with favorable all-cause prognosis who may be considered for more flexible treatment goals in primary prevention. Detection of any CAC in young adults could be used to trigger aggressive preventive interventions.

19.
JACC Cardiovasc Imaging ; 13(1 Pt 1): 97-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31005540

RESUMO

OBJECTIVES: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. BACKGROUND: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. METHODS: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. RESULTS: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFRCT ≤0.80 and 12 occurred in those with an FFRCT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). CONCLUSIONS: The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679).

20.
JACC Cardiovasc Imaging ; 13(1 Pt 1): 83-93, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31005541

RESUMO

OBJECTIVES: This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date. BACKGROUND: CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000. METHODS: A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999. RESULTS: There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau. CONCLUSIONS: Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy.

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