Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease.

OBJECTIVES: To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD). METHODS: An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing ExECG. Next, the ExECG-CL model was applied in a CAD validation cohort undergoing ExECG and clinically driven invasive coronary angiography and a prognosis validation cohort and compared with the risk factor-weighted clinical likelihood (RF-CL) model for obstructive CAD discrimination and prognostication, respectively.In the CAD validation cohort, obstructive CAD was defined as >50% diameter stenosis on invasive coronary angiography. For prognosis, the endpoint was non-fatal myocardial infarction and death. RESULTS: The training cohort consisted of 1214 patients (mean age 57 years, 57% males). In the CAD (N=408; mean age 55 years, 53% males) and prognosis validation (N=3283; mean age 57 years, 57% males) cohorts, 11.8% patients had obstructive CAD and 4.4% met the endpoint. In the CAD validation cohort, discrimination of obstructive CAD was similar between the ExECG-CL and RF-CL models: area under the receiver-operating characteristic curves 83.1% (95% CIs 77.5% to 88.7%) versus 80.7% (95% CI 74.6% to 86.8%), p=0.14. In the ExECG-CL model, more patients had very low (≤5%) clinical likelihood of obstructive CAD compared with the RF-CL (42.2% vs 36.0%, p<0.01) where obstructive CAD prevalence and event risk remained low. CONCLUSIONS: ExECG incorporated into a clinical likelihood model improves reclassification of patients to a very low clinical likelihood group with very low prevalence of obstructive CAD and favourable prognosis.

Gender Differences in Patients With Stable Chest Pain.

This study sought to investigate gender differences in clinical presentation, presence, and extent of coronary artery disease (CAD), and all-cause mortality in patients with stable chest pain who underwent coronary computed tomography angiography (CCTA). Patients who visited the fast-track outpatient clinic of the Erasmus Medical Center and underwent CCTA were analyzed. Clinical characteristics of chest pain, CAD on CCTA, coronary artery calcium scores, and survival were collected retrospectively and compared between men and women. Logistic regression was used to identify independent risk factors for the presence of CAD and Cox regression for all-cause mortality. In 1,835 included patients, 966 (52.6%) were female. Men and women were similar in age (55 vs 56 years). Compared with men, women had a lower frequency of typical pain (22.8% vs 31.1%, p <0.001), lower prevalence of significant CAD (22.2% vs 38.1%, p <0.001), and lower coronary artery calcium scores (p <0.001). CAD was more prevalent in men than in women with typical pain (67.4% vs 35.9%, p <0.001) and also with nontypical pain (24.9% vs 18.1%, p = 0.002). After adjustment for baseline characteristic, male sex was associated with all-cause mortality (adjusted hazard ratio 1.87, 95% confidence interval 1.25 to 2.80, p = 0.002). The additional risk of mortality because of CAD was similar between men and women. Stratifying by typical and nontypical pain, women again had a better prognosis. Our study identifies gender-related differences in characteristics, CCTA-findings, and outcomes for women compared with men presenting for CCTA with chest pain. Women have less CAD and a better prognosis than men, the clinical implications of which require further study.

Determinants of changes in pulmonary artery pressure in patients with severe aortic stenosis treated by transcatheter aortic valve implantation.

BACKGROUND: Elevated pulmonary artery pressure (PAP) in patients with severe aortic stenosis (AS) is a strong predictor of adverse prognosis. This study sought to assess the relation between PAP and clinical and echocardiographic parameters in elderly patients with severe AS, as well as to identify the determinants of the change in PAP after transcatheter aortic valve implantation (TAVI). METHODS: The study included 170 subjects (age 81 ± 7 years, 45% men) with symptomatic severe AS who were treated by TAVI. They underwent a clinical evaluation and a transthoracic echocardiography before the TAVI procedure and 6 months after. RESULTS: In a multivariable analysis, the independent predictors for baseline PAP were the body mass index (BMI) (ß = 0.21, p = .006), COPD GOLD class (ß = 0.20; p = .009), the E/e' ratio (ß = 0.20; p = .02) and the degree of aortic regurgitation (ß = 0.20; p = .01). After TAVI, there was significantly less (51% vs. 29%, p<.0001) pulmonary hypertension, defined as a tricuspid regurgitation velocity ≥2.8 m/s. The baseline variables related to an improvement in PAP were the tricuspid regurgitation velocity (p = .0001) and the E/e' (p = .005). From the parameters potentially modified with TAVI, the only independent predictor of PAP variation was the change in the E/e' ratio (ß = 0.23; p = .01). CONCLUSIONS: Independent predictors for baseline PAP in elderly patients with symptomatic AS were the BMI, GOLD class, the aortic regurgitation and the E/e' ratio. The baseline predictors for a change in PAP 6 months after TAVI were the baseline PAP and E/e', with only the change in the E/e' ratio being correlated to the change in PAP.

Prognostic Value of Subclinical Coronary Artery Disease in Atrial Fibrillation Patients Identified by Coronary Computed Tomography Angiography.

Identifying coronary artery disease (CAD) in atrial fibrillation (AF) patients improves risk stratification and defines clinical management. However, the value of screening for subclinical CAD with cardiac CT in AF patients is unknown. Between 2011 and 2015, 94 consecutive patients without known or suspected CAD (66 (57-73) years, 68% male), who were referred for AF evaluation, underwent a noncontrast-enhanced coronary calcium scan and a coronary computed tomography angiography (CCTA) at our center. We retrospectively evaluated the coronary calcium score, the prevalence of obstructive CAD (≥50% stenosis) determined by CCTA, compared clinical management and 5-year outcome in patients with and without obstructive CAD on CCTA, and examined the potential impact of a coronary calcium score and obstructive CAD on CCTA as a manifestation of vascular disease on the CHA2Ds2VASc score and for the cardiovascular risk stratification of AF patients. The median coronary calcium score was 57 (0-275) and 24 patients (26%) had obstructive CAD on CCTA. At baseline, patients with obstructive CAD more often used statins than those without obstructive CAD (54% vs 26%, p = 0.011). After a median clinical follow-up of 2.4 (0.5-4.5) years, patients with obstructive CAD more frequently used oral anticoagulant and/or antiplatelet drugs, statins, angiotensin-II-receptor blockers and/or angiotensin-converting-enzyme inhibitors, and less often used class I antiarrhythmic drugs than patients without obstructive CAD (all p <0.050). After a median follow-up of 5.7 (4.8-6.8) years, mortality was higher in patients with obstructive CAD than in those without obstructive CAD (29% vs 11%, log-rank test: p = 0.034). Implementation of a coronary calcium score and/or obstructive CAD on CCTA elevated the CHA2Ds2VASc score and cardiovascular risk stratification in 42 patients (p <0.001) and 47 patients (p = 0.006), respectively. In conclusion, we observed a high prevalence of obstructive CAD on CCTA in AF patients without known or suspected CAD. AF patients with obstructive CAD were managed differently and had a worse prognosis than those without obstructive CAD. Cardiac CT could enhance cardiovascular risk stratification of AF patients.

Impact of machine-learning CT-derived fractional flow reserve for the diagnosis and management of coronary artery disease in the randomized CRESCENT trials.

OBJECTIVE: To determine the potential impact of on-site CT-derived fractional flow reserve (CT-FFR) on the diagnostic efficiency and effectiveness of coronary CT angiography (CCTA) in patients with obstructive coronary artery disease (CAD) on CCTA. METHODS: This observational cohort study included patients with suspected CAD who had been randomized to cardiac CT in the CRESCENT I and II trials. On-site CT-FFR was blindly performed in all patients with at least one ≥ 50% stenosis on CCTA and no exclusion criteria for CT-FFR. We retrospectively assessed the effect of adding CT-FFR to the CT protocol in patients with a stenosis ≥ 50% on CCTA in terms of diagnostic effectiveness, i.e., the number of additional tests required to determine the final diagnosis, reclassification of the initial management strategy, and invasive coronary angiography (ICA) efficiency, i.e., ICA rate without ≥ 50% CAD. RESULTS: Fifty-three patients out of the 372 patients (14%) had at least one ≥ 50% stenosis on CCTA of whom 42/53 patients (79%) had no exclusion criteria for CT-FFR. CT-FFR showed a hemodynamically significant stenosis (≤ 0.80) in 27/53 patients (51%). The availability of CT-FFR would have reduced the number of patients requiring additional testing by 57%-points compared with CCTA alone (37/53 vs. 7/53, p < 0.001). The initial management strategy would have changed for 30 patients (57%, p < 0.001). Reserving ICA for patients with a CT-FFR ≤ 0.80 would have reduced the number of ICA following CCTA by 13%-points (p = 0.016). CONCLUSION: Implementation of on-site CT-FFR may change management and improve diagnostic efficiency and effectiveness in patients with obstructive CAD on CCTA. KEY POINTS: • The availability of on-site CT-FFR in the diagnostic evaluation of patients with obstructive CAD on CCTA would have significantly reduced the number of patients requiring additional testing compared with CCTA alone. • The implementation of on-site CT-FFR would have changed the initial management strategy significantly in the patients with obstructive CAD on CCTA. • Restricting ICA to patients with a positive CT-FFR would have significantly reduced the ICA rate in patients with obstructive CAD on CCTA.

Frequency and Significance of Coronary Artery Disease and Myocardial Bridging in Patients With Hypertrophic Cardiomyopathy.

The etiology of chest pain in hypertrophic cardiomyopathy (HC) is diverse and includes coronary artery disease (CAD) as well as HC-specific causes. Myocardial bridging (MB) has been associated with HC, chest pain, and accelerated atherosclerosis. We compared HC patients with age-, gender- and CAD pre-test probability-matched outpatients presenting with chest pain to investigate differences in the presence of MB and CAD using coronary computed tomography angiography (CCTA). We studied 84 HC patients who underwent CCTA and compared these with 168 matched controls (age 54 ± 11 years, 70% men, pre-test probability 12% [5% to 32%]). MB, calcium score, plaque morphology and presence and extent of CAD were assessed for each patient. Linear mixed models were used to assess differences between cases and controls. MB was more often seen in HC patients (50% vs 25%, p <0.001). Calcium score and the presence of obstructive CAD were similar in both groups (9 [0 to 225] vs 4 [0 to 82] and 18% vs 19%; p = 0.22 and p = 0.82). In the HC group, MB was associated with pathogenic DNA variants (p = 0.04), but not with the presence of chest pain (74% vs 76%, p = 0.8), nor with worse outcome (log-rank p = 0.30). In conclusion, the prevalence and extent of CAD was equal among patients with and without HC, demonstrating that pre-test risk prediction using the CAD Consortium clinical risk score performs well in HC patients. MB was twice as prevalent in the HC group compared with matched controls, but was not associated with chest pain or decreased event-free survival in these patients.

Relation between calcium burden, echocardiographic stent frame eccentricity and paravalvular leakage after corevalve transcatheter aortic valve implantation.

AIMS: Paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) is a complication with potentially severe consequences. The relation between native aortic root calcium burden, stent frame eccentricity and PVL was not studied before. METHODS AND RESULTS: Two-hundred-and-twenty-three consecutive patients with severe aortic stenosis who underwent TAVI with a Medtronic CoreValve System© and who had available pre-discharge transthoracic echocardiography were studied. Echocardiographic stent inflow frame eccentricity was defined as major-minor diameter in a short-axis view >2 mm. PVL was scored according to the updated Valve Academic Research Consortium (VARC-2) recommendations. In a subgroup of 162 (73%) patients, the calcium Agatston score was available. Stent frame eccentricity was seen in 77 (35%) of patients. The correlation between the Agatston score and stent frame eccentricity was significant (ρ = 0.241, P = 0.003). Paravalvular leakage was absent in 91 cases (41%), mild in 67 (30%), moderate in 51 (23%), and severe in 14 (6%) cases. The correlation between stent frame eccentricity and PVL severity was significant (ρ = 0.525, P < 0.0001). There was a relation between particular eccentric stent frame shapes and the site of PVL. CONCLUSION: Calcification of the aortic annulus is associated with a subsequent eccentric shape of the CoreValve prosthesis. This eccentric shape results in more PVL, with the localization of PVL related to the shape of stent frame eccentricity.

Quantitative Doppler for Estimation of Paravalvular Leakage after Transcatheter Aortic Valve Implantation.

BACKGROUND: The echocardiographic grading of paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) severity is challenging. The study aim was to assess the value of quantitative Doppler echocardiography to monitor PVL severity. METHODS: A total of 100 subjects was enrolled in the study, including 65 consecutive patients who had undergone TAVI with a CoreValve prosthesis and without valvular aortic regurgitation, and 35 normal controls. The PVL volume was calculated using the quantitative Doppler method as the difference of left and right ventricular stroke volume (SV). PVL severity was assessed both visually and quantitatively as the circumferential extent on a short-axis view (SAX). RESULTS: The inter-observer variabilities for SVs in TAVI patients were disappointing: 14 ± 11% for the left ventricular SV and 18 ± 14% for right ventricular SV. The correlation (r2) between the averaged regurgitant PVL volume and circumferential SAX extent of PVL was 0.02 (p = NS). The relationship between PVL volumes and categories, defined quantitatively by the circumferential SAX extent of PVL and qualitatively by visual assessment of severity of PVL were poor. The results improved when only patients with optimal quality images were included but were still statistically non-significant. CONCLUSIONS: The relationship between calculated PVL volume in TAVI patients and other estimates of PVL severity was poor, most likely due to intrinsic errors made in the quantitative Doppler method. Therefore, one should be prudent to include the quantitative Doppler method in TAVI patients in clinical trials and clinical decision-making, in particular in patients with reduced image quality.

Limitations and difficulties of echocardiographic short-axis assessment of paravalvular leakage after corevalve transcatheter aortic valve implantation.

To make assessment of paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) more uniform the second Valve Academic Research Consortium (VARC) recently updated the echocardiographic criteria for mild, moderate and severe PVL. In the VARC recommendation the assessment of the circumferential extent of PVL in the short-axis view is considered critical. In this paper we will discuss our observational data on the limitations and difficulties of this particular view, that may potentially result in overestimation or underestimation of PVL severity.

Severe Systolic Anterior Motion After Aortic Valve Replacement and Cox MAZE Surgery.

Surgical aortic valve replacement may be complicated by severe dynamic left ventricular outflow tract obstruction and cardiogenic shock in the postoperative period. We present a patient who developed severe anterior motion following aortic valve and Cox MAZE surgery which necessitated a mitral valve replacement. doi: 10.1111/jocs.12763 (J Card Surg 2016;31:429-431).

Importance of the left ventricular outflow tract in the need for pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: The interaction of left ventricular outflow tract (LVOT) and transcatheter heart valve (THV) is complex and may be device design specific. We sought to study LVOT characteristics and its relation with permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR). METHODS: We studied 302 patients with a median age of 81years [75-84]. Computed tomography was used to assess LVOT in terms of amount of calcium, perimeter and device size relative to LVOT. RESULTS: We implanted a Medtronic CoreValve (MCS) in 203 patients, Edwards-Sapien XT (ESV-XT) in 38, Edwards-Sapien S3 (ESV-S3) in 26 and Lotus in 35 patients. Sixty-eight patients (22.5%) received a new PPI within 30days after the index procedure. The incidence of PPI was 22.7% with MCS, 10.5% with ESV-XT, 26.9% with ESV-S3 and 31.4% with Lotus. By multivariate analysis RBBB at baseline (OR 2.9 [1.2-6.9, p=0.014), second generation valves (OR 2.1 [1.0-4.5], p=0.048), DOI (OR 1.20 per 1mm increment, [1.09-1.31], p<0.001) and LVOT sizing (OR per 1% increment 1.03 [1.01-1.07], p=0.022) were associated with need for PPI. Sensitivity analyses suggest that a lesser degree of LVOT oversizing triggers PPI with second generation THVs vs. first generation THVs. CONCLUSIONS: More LVOT oversizing is associated with a higher need for permanent pacemaker implantation after TAVR, even more so with deeper THV implants and next generation devices (ESV-S3 and Lotus). Sizing algorithms should focus more on LVOT dimensions to reduce PPI.

Relation between E/e' ratio and NT-proBNP levels in elderly patients with symptomatic severe aortic stenosis.

BACKGROUND: Symptoms in the elderly patients with severe aortic stenosis (AS) and co-morbidities seem to lack in specificity. Therefore, objective parameters for increased left ventricular(LV) filling pressures are needed. The aim of this study was to investigate the correlation between the septal, lateral and average E/e' ratio and the value of the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP). METHODS: Two-hundred-fifty consecutive symptomatic patients (mean age 80 ± 8 years, 52% men) with severe AS underwent transthoracic echocardiography and NT-proBNP measurement. RESULTS: In the overall population the septal E/e' (r = 0,459, r(2) = 0,21, P <0,0001), lateral E/e' (r = 0,322, r(2) = 0,10, P <0,0001), and the average E/e' (r = 0,432, r(2) = 0,18, P <0,0001) were all significantly correlated to NT-proBNP. After the exclusion of patients with confounders (more than mild aortic or mitral regurgitation, severe renal dysfunction, obesity or severe COPD) the septal E/e' (r = 0,584, r(2) = 0,34, P <0,0001), lateral E/e' (r = 0,377, r(2) = 0,14, P <0,0001), and the average E/e' (r = 0,487, r(2) = 0,24, P <0,0001) were all significantly better correlated to NT-proBNP. In obese patients no significant correlations were seen. Previous bypass surgery did not alter the correlations. CONCLUSIONS: In elderly patients with severe symptomatic AS there is a significant correlation between the E/e' ratio and NT-proBNP, in particular after exclusion of confounders. The correlation was best for the septal E/e' ratio and was preserved in patients with a history of bypass surgery.

Incidence and predictors of debris embolizing to the brain during transcatheter aortic valve implantation.

OBJECTIVES: The aim of this study was to identify variables associated with tissue fragment embolization during transcatheter aortic valve replacement (TAVR). BACKGROUND: Brain magnetic resonance imaging and transcranial Doppler studies have revealed that cerebrovascular embolization occurs frequently during TAVR. Embolized material may be r thrombotic, tissue derived, or catheter (foreign material) fragments. METHODS: A total of 81 patients underwent TAVR with a dual filter-based embolic protection device (Montage Dual Filter System, Claret Medical, Inc., Santa Rosa, California) deployed in the brachiocephalic trunk and left common carotid artery. Both balloon-expandable and self-expanding transcatheter heart valves (THVs) were used. Filters were retrieved after TAVR and sent for histopathological analysis. RESULTS: Overall, debris was captured in 86% of patients. Captured material varied in size from 0.1 to 9.0 mm. Thrombotic material was found in 74% of patients and tissue-derived debris in 63%. Tissue fragments were found more often with balloon-expandable THVs (79% vs. 56%; p = 0.05). The embolized tissue originated from the native aortic valve leaflets, aortic wall, or left ventricular myocardium. On multivariable logistic regression analysis, balloon-expandable THVs (odds ratio: 7.315; 95% confidence interval: 1.398 to 38.289; p = 0.018) and cover index (odds ratio: 1.141; 95% confidence interval: 1.014 to 1.283; p = 0.028) were independent predictors of tissue embolization. CONCLUSIONS: Debris is captured with filter-based embolic protection in the vast majority of patients undergoing TAVR. Tissue-derived material is found in 63% of cases and is more frequent with the use of balloon-expandable systems and more oversizing.

Restriction of the referral of patients with stable angina for CT coronary angiography by clinical evaluation and calcium score: impact on clinical decision making.

OBJECTIVE: To investigate the value of the calcium score (CaSc) plus clinical evaluation to restrict referral for CT coronary angiography (CTCA) by reducing the number of patients with an intermediate probability of coronary artery disease (CAD). METHODS: We retrospectively included 1,975 symptomatic stable patients who underwent clinical evaluation and CaSc calculation and CTCA or invasive coronary coronary angiography (ICA). The outcome was obstructive CAD (≥50 % diameter narrowing) assessed by ICA or CTCA in the absence of ICA. We investigated two models: (1) clinical evaluation consisting of chest pain typicality, gender, age, risk factors and ECG and (2) clinical evaluation with CaSc. Discrimination of the two models was compared. The stepwise reclassification of patients with an intermediate probability of CAD (10-90 %) after clinical evaluation followed by clinical evaluation with CaSc was assessed by clinical net reclassification improvement (NRI). RESULTS: Discrimination of CAD was significantly improved by adding CaSc to the clinical evaluation (AUC: 0.80 vs. 0.89, P < 0.001). CaSc and CTCA could be avoided in 9 % using model 1 and an additional 29 % of CTCAs could be avoided using model 2. Clinical NRI was 57 %. CONCLUSION: CaSc plus clinical evaluation may be useful in restricting further referral for CTCA by 38 % in symptomatic stable patients with suspected CAD. KEY POINTS: • CT calcium scores (CaSc) could proiritise referrals for CT coronary angiography (CTCA) • CaSc provides an incremental discriminatory value of CAD compared with clinical evaluation • Risk stratification is better when clinical evaluation is combined with CaSc • Appropriate use of clinical evaluation and CaSc helps avoid unnecessary CTCA referrals.

Coronary CT angiography outperforms calcium imaging in the triage of acute coronary syndrome.

BACKGROUND: In this prospective study we determine the diagnostic value of coronary CT angiography (CTA) and calcium imaging in low to intermediate risk acute chest pain patients. METHODS: One hundred and eleven consecutive patients (57 ± 11 years, 71 males) presenting to the emergency department with chest pain suggestive of acute coronary syndrome (ACS), but without indication for immediate catheter angiography, underwent both coronary CTA and calcium imaging without disclosure of the findings to the treating physicians. RESULTS: ACS was diagnosed in 19 patients (17%). Coronary calcium was present in 71 patients (64%). Coronary CTA identified 74 (67%) patients with coronary plaque and 36 (32%) patients with obstructive (≥ 50%) plaque. The sensitivity and specificity of the calcium scan were: 89% and 41%. The sensitivity and specificity of coronary CTA were: 100% and 40% based on the presence of any plaque and 89% and 79% based on the presence of >50% stenosis. C-statistics of the GRACE risk score (0.77 [95% CI 0.66-0.89]) improved after addition of coronary CTA (0.93 [0.88-0.98], p<0.01), though not after addition of calcium scores (0.81 [0.71-0.91], p=0.52). Follow-up at 3 months revealed four late revascularizations (no deaths or myocardial infarctions), all of whom had obstructive CAD with calcium on CT at presentation. CONCLUSIONS: Coronary CTA outperforms calcium imaging in the triage of patients suspected of developing ACS. Absence of plaque on coronary CTA allows safe discharge. Coronary CTA has incremental value to clinical risk scores and has the potential to reduce unnecessary hospital admissions.

Coronary computed tomography versus exercise testing in patients with stable chest pain: comparative effectiveness and costs.

BACKGROUND: To determine the comparative effectiveness and costs of a CT-strategy and a stress-electrocardiography-based strategy (standard-of-care; SOC-strategy) for diagnosing coronary artery disease (CAD). METHODS: A decision analysis was performed based on a well-documented prospective cohort of 471 outpatients with stable chest pain with follow-up combined with best-available evidence from the literature. Outcomes were correct classification of patients as CAD- (no obstructive CAD), CAD+ (obstructive CAD without revascularization) and indication for Revascularization (using a combination reference standard), diagnostic costs, lifetime health care costs, and quality-adjusted life years (QALY). Parameter uncertainty was analyzed using probabilistic sensitivity analysis. RESULTS: For men (and women), diagnostic cost savings were €245 (€252) for the CT-strategy as compared to the SOC-strategy. The CT-strategy classified 82% (88%) of simulated men (women) in the appropriate disease category, whereas 83% (85%) were correctly classified by the SOC-strategy. The long-term cost-effectiveness analysis showed that the SOC-strategy was dominated by the CT-strategy, which was less expensive (-€229 in men, -€444 in women) and more effective (+0.002 QALY in men, +0.005 in women). The CT-strategy was cost-saving (-€231) but also less effective compared to SOC (-0.003 QALY) in men with a pre-test probability of ≥ 70%. The CT-strategy was cost-effective in 100% of simulations, except for men with a pre-test probability ≥ 70% in which case it was 59%. CONCLUSIONS: The results suggest that a CT-based strategy is less expensive and equally effective compared to SOC in all women and in men with a pre-test probability <70%.

Copeptin in acute chest pain: identification of acute coronary syndrome and obstructive coronary artery disease on coronary CT angiography.

OBJECTIVE: To determine the diagnostic accuracy of copeptin in patients with suspected acute coronary syndrome (ACS) and its correlation with obstructive coronary artery disease (CAD) on coronary CT angiography (CTA). METHODS: Copeptin was measured at arrival in 65 consecutive patients (56 ± 10 years, 45 men) suspected of ACS and no indication for immediate invasive angiography. All patients underwent coronary CTA without disclosure of the results to the treating physician, and outcomes were classified as obstructive CAD (>50% stenosis) or no obstructive CAD (≤ 50%) in one or more vessel. RESULTS: The final diagnosis of ACS was established in 10 (15%) patients, 6 myocardial infarctions and 4 unstable angina pectoris. Coronary CTA detected obstructive CAD in all patients with ACS and in 10 (15%) patients with no ACS. Copeptin concentrations were higher in patients with ACS (median 7.42 pmol/l (IQR 3.71-18.72)) vs patients with no ACS (3.40 pmol/l (1.13-6.27), p=0.02). Copeptin was not higher in patients with obstructive CAD on coronary CTA (4.87 pmol/l (2.90-8.51) vs 3.60 pmol/l (1.21-6.23), p=0.20) compared with patients with no obstructive CAD. CONCLUSIONS: Copeptin seems to be elevated in patients with ACS while there is no strong correlation with obstructive coronary disease on CTA.

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.

OBJECTIVES: To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. DESIGN: Retrospective pooled analysis of individual patient data. SETTING: 18 hospitals in Europe and the United States. PARTICIPANTS: Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). MAIN OUTCOME MEASURES: Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. RESULTS: We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. CONCLUSIONS: Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.