Evaluating Cost-Effectiveness Models for Pharmacologic Interventions in Adults with Heart Failure: A Systematic Literature Review.

BACKGROUND: Heart failure (HF) is a well-recognized public health concern and imposes high economic and societal costs. Decision analytic models exist for evaluating the economic ramifications associated with HF. Despite this, studies that appraise these modelling approaches for augmenting best-practice decisions remain scarce. OBJECTIVE: Our objective was to conduct a systematic literature review (SLR) of published economic models for the management of HF and describe their general and methodological features. METHODS: This SLR employed a combination of relevant search terms associated with HF, which were used in a number of databases, including MEDLINE, Embase, the National Health Service Economic Evaluation Database, Cost-Effectiveness Analysis Registry, ScHARR Health Utilities Database and Cochrane Library Database. A number of model features (i.e. model structure, specification, outcomes assessed, scenario and sensitivity analysis, key model drivers) were extracted and subsequently summarized. RESULTS: Of 64 publications retained, a selection of modelling approaches were identified, including Markov (n = 28), trial-based analytic (n = 22), discrete-event simulation (n = 6), survival analytic (n = 7) and decision-tree modelling (n = 1) approaches. The bulk of publications employed either a cost-utility (n = 27) or cost-effectiveness (n = 36) analysis and evaluated more than one study outcome, which typically included overall costs (n = 59), incremental cost-effectiveness ratios (n = 55), life-years gained (n = 48) and willingness-to-pay thresholds (n = 37). Most publications focused on patients with chronic HF (n = 40) and used New York Heart Association (NYHA) disease classifications to categorize patients and determine disease severity. Few (n = 19) publications documented the use of hospitalization states for modelling patient outcomes and associated costs. A quality assessment of the included publications revealed most articles demonstrated reasonable methodological value. CONCLUSIONS: We identified numerous decision analytic modelling approaches for evaluating the cost effectiveness of pharmacologic treatments in HF. A Markov cohort model approach was most commonly used, and most models relied on NYHA classes as a proxy of HF severity, disease progression and prognosis.

A Comparison of the Updated Diamond-Forrester, CAD Consortium, and CONFIRM History-Based Risk Scores for Predicting Obstructive Coronary Artery Disease in Patients With Stable Chest Pain: The SCOT-HEART Coronary CTA Cohort.

OBJECTIVES: This study sought to compare the performance of history-based risk scores in predicting obstructive coronary artery disease (CAD) among patients with stable chest pain from the SCOT-HEART study. BACKGROUND: Risk scores for estimating pre-test probability of CAD are derived from referral-based populations with a high prevalence of disease. The generalizability of these scores to lower prevalence populations in the initial patient encounter for chest pain is uncertain. METHODS: We compared 3 scores among patients with suspected CAD in the coronary computed tomographic angiography (CTA) randomized arm of the SCOT-HEART study for the outcome of obstructive CAD by coronary CTA: the updated Diamond-Forrester score (UDF), CAD Consortium clinical score (CAD2), and CONFIRM risk score (CRS). We tested calibration with goodness-of-fit, discrimination with area under the receiver-operating curve (AUC), and reclassification with net reclassification improvement (NRI) to identify low-risk patients. RESULTS: In 1,738 patients (age 58 ± 10 years and 44.0% women), overall calibration was best for UDF, with underestimation by CRS and CAD2. Discrimination by AUC was highest for CAD2 at 0.79 (95% confidence interval [CI]: 0.77 to 0.81) than for UDF (0.77 [95% CI: 0.74 to 0.79]) or CRS (0.75 [95% CI: 0.73 to 0.77]) (p < 0.001 for both comparisons). Reclassification of low-risk patients at the 10% probability threshold was best for CAD2 (NRI 0.31, 95% CI: 0.27 to 0.35) followed by CRS (NRI 0.21, 95% CI: 0.17 to 0.25) compared with UDF (p < 0.001 for all comparisons), with a consistent trend at the 15% threshold. CONCLUSIONS: In this multicenter clinic-based cohort of patients with suspected CAD and uniform CAD evaluation by coronary CTA, CAD2 provided the best discrimination and classification, despite overestimation of obstructive CAD as evaluated by coronary CTA. CRS exhibited intermediate performance followed by UDF for discrimination and reclassification.

Quantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death.

BACKGROUND AND AIMS: Recent advancements in coronary computed tomography angiography (CCTA) have allowed for the quantitative measurement of high-risk lipid rich plaque. Determination of the optimal threshold for Hounsfield units (HU) by CCTA for identifying lipid rich plaque remains unknown. We aimed to validate reliable cut-points of HU for quantitative assessment of lipid rich plaque. METHODS: 8 post-mortem sudden coronary death hearts were evaluated with CCTA and histologic analysis. Quantitative plaque analysis was performed in histopathology images and lipid rich plaque area was defined as intra-plaque necrotic core area. CCTA images were analyzed for quantitative plaque measurement. Low attenuation plaque (LAP) was defined as any pixel < 30, 45, 60, 75, and 90 HU cut-offs within a coronary plaque. The area of LAP was calculated in each cross-section. RESULTS: Among 105 cross-sections, 37 (35.2%) cross-sectional histology images contained lipid rich plaque. Although the highest specificity for identifying lipid rich plaque was shown with <30 HU cut-off (88.2%), sensitivity (e.g. 55.6% for <75 HU, 16.2% for <30 HU) and negative predictive value (e.g. 75.9% for <75 HU, 65.9% for <30 HU) tended to increase with higher HU cut-offs. For quantitative measurement, <75 HU showed the highest correlation coefficient (0.292, p = 0.003) and no significant differences were observed between lipid rich plaque area and LAP area between histology and CT analysis (Histology: 0.34 ±â€¯0.73 mm2, QCT: 0.37 ±â€¯0.71 mm2, p = 0.701). CONCLUSIONS: LAP area by CCTA using a <75 HU cut-off value demonstrated high sensitivity and quantitative agreement with lipid rich plaque area by histology analysis.

Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study.

Aim: The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. Methods and results: From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all). Conclusions: Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

The Coronary Artery Disease-Reporting and Data System (CAD-RADS): Prognostic and Clinical Implications Associated With Standardized Coronary Computed Tomography Angiography Reporting.

OBJECTIVES: This study sought to assess clinical outcomes associated with the novel Coronary Artery Disease-Reporting and Data System (CAD-RADS) scores used to standardize coronary computed tomography angiography (CTA) reporting and their potential utility in guiding post-coronary CTA care. BACKGROUND: Clinical decision support is a major focus of health care policies aimed at improving guideline-directed care. Recently, CAD-RADS was developed to standardize coronary CTA reporting and includes clinical recommendations to facilitate patient management after coronary CTA. METHODS: In the multinational CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, 5,039 patients without known coronary artery disease (CAD) underwent coronary CTA and were stratified by CAD-RADS scores, which rank CAD stenosis severity as 0 (0%), 1 (1% to 24%), 2 (25% to 49%), 3 (50% to 69%), 4A (70% to 99% in 1 to 2 vessels), 4B (70% to 99% in 3 vessels or ≥50% left main), or 5 (100%). Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality or myocardial infarction (MI). Receiver-operating characteristic (ROC) curves were used to compare CAD-RADS to the Duke CAD Index and traditional CAD classification. Referrals to invasive coronary angiography (ICA) after coronary CTA were also assessed. RESULTS: Cumulative 5-year event-free survival ranged from 95.2% to 69.3% for CAD-RADS 0 to 5 (p < 0.0001). Higher scores were associated with elevations in event risk (hazard ratio: 2.46 to 6.09; p < 0.0001). The ROC curve for prediction of death or MI was 0.7052 for CAD-RADS, which was noninferior to the Duke Index (0.7073; p = 0.893) and traditional CAD classification (0.7095; p = 0.783). ICA rates were 13% for CAD-RADS 0 to 2, 66% for CAD-RADS 3, and 84% for CAD-RADS ≥4A. For CAD-RADS 3, 58% of all catheterizations occurred within the first 30 days of follow-up. In a patient subset with available medication data, 57% of CAD-RADS 3 patients who received 30-day ICA were either asymptomatic or not receiving antianginal therapy at baseline, whereas only 32% had angina and were receiving medical therapy. CONCLUSIONS: CAD-RADS effectively identified patients at risk for adverse events. Frequent ICA use was observed among patients without severe CAD, many of whom were asymptomatic or not taking antianginal drugs. Incorporating CAD-RADS into coronary CTA reports may provide a novel opportunity to promote evidence-based care post-coronary CTA.

Incremental role of resting myocardial computed tomography perfusion for predicting physiologically significant coronary artery disease: A machine learning approach.

BACKGROUND: Evaluation of resting myocardial computed tomography perfusion (CTP) by coronary CT angiography (CCTA) might serve as a useful addition for determining coronary artery disease. We aimed to evaluate the incremental benefit of resting CTP over coronary stenosis for predicting ischemia using a computational algorithm trained by machine learning methods. METHODS: 252 patients underwent CCTA and invasive fractional flow reserve (FFR). CT stenosis was classified as 0%, 1-30%, 31-49%, 50-70%, and >70% maximal stenosis. Significant ischemia was defined as invasive FFR < 0.80. Resting CTP analysis was performed using a gradient boosting classifier for supervised machine learning. RESULTS: On a per-patient basis, accuracy, sensitivity, specificity, positive predictive, and negative predictive values according to resting CTP when added to CT stenosis (>70%) for predicting ischemia were 68.3%, 52.7%, 84.6%, 78.2%, and 63.0%, respectively. Compared with CT stenosis [area under the receiver operating characteristic curve (AUC): 0.68, 95% confidence interval (CI) 0.62-0.74], the addition of resting CTP appeared to improve discrimination (AUC: 0.75, 95% CI 0.69-0.81, P value .001) and reclassification (net reclassification improvement: 0.52, P value < .001) of ischemia. CONCLUSIONS: The addition of resting CTP analysis acquired from machine learning techniques may improve the predictive utility of significant ischemia over coronary stenosis.

Achieving target SBP for lowering the risk of major adverse cardiovascular events in persons with diabetes mellitus.

AIM: To test the efficacy of achieving target SBP less than 120 mmHg, or less than 140 mmHg, for lowering the risk of major adverse cardiovascular events (MACE) in persons with diabetes mellitus. METHOD: The study comprised 4732 [mean ±â€ŠSD age: 63 ±â€Š7 years; 2258 (48%) women] persons with advanced diabetes mellitus. Participants randomly assigned to achieve intensive (<120 mmHg) or standard (<140 mmHg) SBP control were grouped according to whether or not they achieved their respective SBP goal. MACE consisted of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular causes. RESULTS: During a median 5.0 (interquartile range: 4.2-5.7) years, 1939 (82%) and 2038 (86%) persons achieved SBP targets less than 120 and less than 140 mmHg in each treatment arm, respectively. Overall, 208 (9%) and 237 (10%) persons in the intensive and standard treatment arms experienced MACE. In the intensive treatment arm, multivariable Cox regression revealed no significant reduction in risk of MACE for those who achieved a target SBP less than 120 mmHg. In the standard treatment arm, those who achieved a target SBP less than 140 mmHg displayed a substantial reduction in risk of MACE (hazard ratio = 0.65, P = 0.005), all-cause death (hazard ratio = 0.64, P = 0.02), and nonfatal stroke (hazard ratio = 0.47, P = 0.02) as compared with those whose achieved SBP was 140 mmHg or higher. CONCLUSION: Achieving a standard SBP goal between 120 and 140 mmHg may prove useful for lowering cardiovascular risk in persons with diabetes mellitus. Achieving a target SBP less than 120 mmHg does not appear to mitigate risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT00000620 (https://clinicaltrials.gov/ct2/results?term=NCT00000620&Search=Search).

Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Obstructive Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography: A Meta-Analysis.

OBJECTIVES: The current meta-analysis aimed to evaluate the diagnostic performance of hybrid cardiac imaging techniques compared with stand-alone coronary computed tomography angiography (CTA) for assessment of obstructive coronary artery disease (CAD). BACKGROUND: The usefulness of coronary CTA for detecting obstructive CAD remains suboptimal at present. Myocardial perfusion imaging encompasses positron emission tomography, single-photon emission computed tomography, and cardiac magnetic resonance, which permit the identification of myocardial perfusion defects to detect significant CAD. A hybrid approach comprising myocardial perfusion imaging and coronary CTA may improve diagnostic performance for detecting obstructive CAD. METHODS: PubMed and Web of Knowledge were searched for relevant publications between January 1, 2000 and December 31, 2015. Studies using coronary CTA and hybrid imaging for diagnosis of obstructive CAD (a luminal diameter reduction of >50% or >70% by invasive coronary angiography) were included. In total, 12 articles comprising 951 patients and 1,973 vessels were identified, and a meta-analysis was performed to determine pooled sensitivity, specificity, and summary receiver-operating characteristic curves. RESULTS: On a per-patient basis, the pooled sensitivity of hybrid imaging was comparable to that of coronary CTA (91% vs. 90%; p = 0.28). However, specificity was higher for hybrid imaging versus coronary CTA (93% vs. 66%; p < 0.001). On a per-vessel basis, sensitivity for hybrid imaging against coronary CTA was comparable (84% vs. 89%; p = 0.29). Notably, hybrid imaging yielded a specificity of 95% versus 83% for coronary CTA (p < 0.001). Summary receiver-operating characteristic curves displayed improved discrimination for hybrid imaging beyond coronary CTA alone, on a per-vessel basis (area under the curve: 0.97 vs. 0.93; p = 0.047), although not on a per-patient level (area under the curve: 0.97 vs. 0.93; p = 0.132). CONCLUSIONS: Hybrid cardiac imaging demonstrated improved diagnostic specificity for detection of obstructive CAD compared with stand-alone coronary CTA, yet improvement in overall diagnostic performance was relatively limited.

Geometric predictors of left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a 3D computed tomography analysis.

Aims: To establish geometric predictors of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) patients by use of cardiac computed tomography (CT). Methods and results: A total of 141 consecutive patients with HCM who underwent cardiac CT comprised the analytic sample. The degree, pattern, and extent of left ventricular (LV) hypertrophy were evaluated using 3D CT. Abnormality of papillary muscle (PM), mitral valve, and aorto-mitral angle were evaluated quantitatively. Multivariable logistic regression analysis and sensitivity analysis were performed to reliably identify predictors of LVOTO. LVOTO was present among 40 (28.4%) patients. Those with LVOTO displayed a higher prevalence for having a spiral pattern of LV hypertrophy (e.g. 51 vs. 16%, P < 0.001), a longer anterior mitral leaflet (AML) length (e.g. 18.0 vs. 15.6 mm, P = 0.007), and a longer distance from lateral PM base to LV apex (e.g. 26.4 vs. 22.0 mm, P < 0.001), as compared with the non-LVOTO group. Multivariable logistic regression revealed all three variables [i.e. spiral pattern (95% confidence interval (CI), 3.75, 1.59-8.84); AML length (95% CI, 1.20, 1.03-1.40); the distance between lateral PM base and LV apex (95% CI, 1.09, 1.01-1.19)] retained significance after adjustment for numerous covariates. Conclusion: Spiral pattern of LV hypertrophy, the length of AML, and the distance between lateral PM base and LV apex were independent predictors of LVOTO in patients with HCM.

Comparative diagnostic accuracy of dual-energy CT myocardial perfusion imaging by monochromatic energy versus material decomposition methods.

PURPOSE: To compare the diagnostic value of monochromatic and material decomposition (MD) dual- energy computed tomography (DECT) imaging for the evaluation of ischemia. METHODS: Patients with suspected coronary artery disease underwent rest-stress DECT and SPECT perfusion imaging. DECT images were reconstructed between 40 and 140keV and through MD of iodine/muscle. RESULTS: MD and monochromatic imaging had a sensitivity, specificity, negative predictive, positive predictive value, and accuracy of 89%, 40%, 67%, 73% and 71%; and 91%, 67%, 67%, 91% and 86%, respectively (p=0.05). CONCLUSION: DECT using monochromatic energy displayed a non-significantly higher diagnostic accuracy for myocardial ischemia as compared with DECT MD.

Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring.

OBJECTIVES: The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults. BACKGROUND: Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted. METHODS: In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS. RESULTS: A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration. CONCLUSIONS: A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Women Versus Men: Long-Term Outcomes From the CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) Registry.

BACKGROUND: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined. METHODS AND RESULTS: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque. CONCLUSION: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts.

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. METHODS: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. RESULTS: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) and 2.2 (95% CI 1.6-3.0), respectively]. CONCLUSIONS: Patients without luminal narrowing but with CAC experience greater risk of 5-year mortality. Patients with CAC score ≥100 and no coronary luminal narrowing experience death rates similar to those with non-obstructive CAD.

Dense calcium and lesion-specific ischemia: A comparison of CCTA with fractional flow reserve.

BACKGROUND AND AIMS: Studies evaluating the relationship between dense coronary calcium (DC) and myocardial ischemia have had incongruent results. We sought to clarify whether DC, as detected by computed coronary tomographic angiography (CCTA), is an independent predictor of ischemia as measured by invasive fractional flow reserve (FFR). METHODS: In total, 249 (399 lesions) stable patients undergoing CCTA and invasive FFR were enrolled for this post-hoc analysis. DC was defined as plaque with ≥350 HU using quantification software, and ischemia was defined as FFR ≤0.80. We evaluated the relationship of dense calcium volume (DCV), lesion plaque volume (LPV), non-calcified plaque volume (NCV), and area stenosis (AS) with ischemia using logistic regression reporting odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Mean age was 63.0 ± 8.6 years, and 73 (29.3%) were female. Mean DCV was higher in lesions with FFR ≤0.80 (57.0 ± 54.7 mm3vs. 37.6 ± 49.5 mm3, [p < 0.001]). DCV and LPV were closely correlated (Pearson's coefficient = 0.49 [p < 0.001]). After adjustment for AS, LPV (OR 1.01, 95% CI 1.00-1.04, p < 0.001) but not DCV (OR 1.01, 95% CI 0.96-1.06, p = 0.69) was independently associated with ischemia. CONCLUSIONS: Dense calcium is not an independent predictor of ischemia, but rather a marker of aggregate LPV, which in turn, is predictive of ischemia.

Clinical Implications of Three-Dimensional Real-Time Color Doppler Transthoracic Echocardiography in Quantifying Mitral Regurgitation: A Comparison with Conventional Two-Dimensional Methods.

BACKGROUND: Automatic quantification of real-time three-dimensional (3D) full-volume color Doppler transthoracic echocardiography (FVCD) has been proposed as a feasible and accurate method for quantifying MR. We aimed to explore the clinical implications of real-time 3D-FVCD for mitral regurgitation (MR) with various clinical manifestations, in comparison with the conventional two-dimensional (2D) proximal isovelocity surface area (PISA) and volumetric method and cardiac magnetic resonance imaging (CMR) methods. METHODS: A total 186 patients with MR were enrolled prospectively. Based on exclusion criteria and image quality review, 152 patients were included in the final analysis for 3D-FVCD and 2D transthoracic echocardiography. Among them, 37 patients underwent subsequent CMR for the validation of 3D-FVCD. RESULTS: MR volume from 3D-FVCD demonstrated a better agreement (r = 0.94) with CMR than 2D-PISA or the 2D volumetric method (VM; r = 0.87 vs 0.56). Overall, 2D methods underestimated MR when compared with 3D-FVCD (35.4 ± 28.4 mL for 2D-VM vs 43.8 ± 24.6 mL for 2D-PISA vs 64.6 ± 35.1 mL for 3D-FVCD; P < .001). In subgroup analysis, multijet MR (odds ratio [OR], 6.30; 95% CI, 2.52-15.72) and dilated left ventricular end-systolic diameter ≥40 mm (OR, 2.90; 95% CI, 1.12-7.50) were predictors of significant difference in MR volume (>30 mL for primary MR and >15 mL for secondary MR) between 2D-PISA and 3D-FVCD. In identifying surgical candidates, patients with multijet MR (OR, 4.53, 95% CI, 1.99-10.35) demonstrated a higher risk of discrepancy between 2D-PISA and 3D-FVCD, which were consistent in both primary and secondary MR, respectively. CONCLUSIONS: MR quantification with 3D-FVCD showed better correlation and agreement than conventional 2D methods. MR was underestimated by 2D methods, especially in multijet and dilated left ventricle. Multijet MR demonstrated higher risk of discrepancy for the identification of surgical candidate, regardless of MR etiology.

Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

BACKGROUND: Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). METHODS: From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. RESULTS: Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. CONCLUSION: CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD.

Prevalence and severity of coronary artery calcification based on the epidemiologic pattern: A propensity matched comparison of asymptomatic Korean and Chinese adults.

BACKGROUND: Lifestyle, environmental, and genetic factors substantially influence cardiovascular disease (CVD) risk. We aimed to explore epidemiologic trends in coronary artery calcium scores (CACS), as a marker of CVD, along with possible differences by geographic area and study period in separate East Asian populations. METHODS: We generated 3 matched groups (n=702) using a propensity scoring approach derived from a Korean (N=48,901) and Chinese cohort (N=927) as follows: (1) A recent Chinese group and (2) recent Korean group, both of whom underwent CACS scanning from 2012-2014; and (3) a past Korean group who underwent CACS scanning 8-10years before the index group (2002-2006). We used logistic regression to generate odds ratios (OR) with 95% confidence intervals (95% CI) to estimate the likelihood of having CACS between the groups, based on CACS stratified by severity: >0 (any), >100 (moderate), and >400 (severe). RESULTS: The prevalence of any, moderate, or severe CACS did not differ significantly between the recent Chinese and Korean groups. Notably, the odds of the presence of moderate CACS in the recent Chinese group (OR: 3.05, 95% CI: 1.49-6.71, P-value<0.001) and the presence of any CACS in the recent Korean group (OR: 1.58, 95% CI: 1.17-2.15, P-value<0.001) were significantly higher than in the past Korean group. CONCLUSIONS: In this study involving separate East Asian populations, there were no geographic differences in the prevalence of CACS. However, changes in other unmeasured factors over time are likely the culprits for the elevated prevalence of CACS in asymptomatic East Asians.

Assessment of Coronary Artery Calcium Scoring for Statin Treatment Strategy according to ACC/AHA Guidelines in Asymptomatic Korean Adults.

PURPOSE: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines advocate the use of statin treatment for prevention of cardiovascular disease. We aimed to assess the usefulness of coronary artery calcium (CAC) for stratifying potential candidates of statin use among asymptomatic Korean individuals. MATERIALS AND METHODS: A total of 31375 subjects who underwent CAC scoring as part of a general health examination were enrolled in the current study. Statin eligibility was categorized as statin recommended (SR), considered (SC), and not recommended (SN) according to ACC/AHA guidelines. Cox regression analysis was employed to estimate hazard ratios (HR) with 95% confidential intervals (CI) after stratifying the subjects according to CAC scores of 0, 1-100, and >100. Number needed to treat (NNT) to prevent one mortality event during study follow up was calculated for each group. RESULTS: Mean age was 54.4±7.5 years, and 76.3% were male. During a 5-year median follow-up (interquartile range; 3-7), there were 251 (0.8%) deaths from all-causes. A CAC >100 was independently associated with mortality across each statin group after adjusting for cardiac risk factors (e.g., SR: HR, 1.60; 95% CI, 1.07-2.38; SC: HR, 2.98; 95% CI, 1.09-8.13, and SN: HR, 3.14; 95% CI, 1.08-9.17). Notably, patients with CAC >100 displayed a lower NNT in comparison to the absence of CAC or CAC 1-100 in SC and SN groups. CONCLUSION: In Korean asymptomatic individuals, CAC scoring might prove useful for reclassifying patient eligibility for receiving statin therapy based on updated 2013 ACC/AHA guidelines.

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.

Effect of a Long-Term Physical Activity Intervention on Resting Pulse Rate in Older Persons: Results from the Lifestyle Interventions and Independence for Elders Study.

OBJECTIVES: To assess the utility of a long-term physical activity (PA) intervention for reducing resting pulse rate (RPR) in older persons. DESIGN: Community. SETTING: Lifestyle Interventions and Independence for Elders Study. PARTICIPANTS: Individuals aged 70 to 89 (N = 1,635, 67.2% women) were randomized to a moderate-intensity PA intervention (n = 818) or a health education-based successful aging (SA) intervention (n = 817). MEASUREMENTS: RPR was recorded at baseline and 6, 18, and 30 months. Longitudinal changes in RPR of intervention groups were compared using a mixed-effects analysis of covariance model for repeated-measure outcomes, generating least squares means with standard errors (SEs) or 95% confidence intervals (CIs). RESULTS: Mean duration of the study was 2.6 years (median 2.7 years, interquartile range 2.3-3.1 years). The average effect of the PA intervention on RPR over the course of the study period was statistically significant but clinically small (average intervention difference = 0.84 beats/min; 95% CI = 0.17-1.51; Paverage = .01), with the most pronounced effect observed at 18 months (PA, 66.5 beats/min (SE 0.32 beats/min); SA, 67.8 beats/min (SE 0.32 beats/min); difference = 1.37 beats/min, 95% CI = 0.48-2.26 beats/min). The relationship became somewhat weaker and was not statistically significant at 30 months. There were no significant differences between several prespecified subgroups. CONCLUSION: A long-term moderate-intensity PA program was associated with a small and clinically insignificant slowing of RPR in older persons. Whether PA can deliver a beneficial reduction in RPR requires further examination in older adults.