Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study.

BACKGROUND: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. OBJECTIVE: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. METHODS: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). RESULTS: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LIMITATIONS: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. CONCLUSION: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls.

Exercise-based cardiac rehabilitation in stable angina pectoris: a narrative review on current evidence and underlying physiological mechanisms.

Stable angina pectoris (SAP) is a prevalent condition characterised by a high disease burden. Based on recent evidence, the need for revascularisation in addition to optimal medical treatment to reduce mortality and re-events is heavily debated. These observations may be explained by the fact that revascularisation is targeted at the local flow-limiting coronary artery lesion, while the aetiology of SAP relates to the systemic, inflammatory process of atherosclerosis, causing generalised vascular dysfunction throughout the entire vascular system. Moreover, cardiovascular events are not solely caused by obstructive plaques but are also associated with plaque burden and high-risk plaque features. Therefore, to reduce the risk of cardiovascular events and angina, and thereby improve quality of life, alternative therapeutic approaches to revascularisation should be considered, preferably targeting the cardiovascular system as a whole with a physiological approach. Exercise-based cardiac rehabilitation fits this description and is a promising strategy as a first-line treatment in addition to optimal medical treatment. In this review, we discuss the role of exercise-based cardiac rehabilitation in SAP in relation to the underlying physiological mechanisms, we summarise the existing evidence and highlight future directions.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease.

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( Pinteraction=0.318) or iFR ( Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( Pinteraction<0.00001) and decreasing iFR ( Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( Pinteraction=0.849) or iFR ( Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( Pinteraction=0.693) nor iFR ( Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Cardiac shockwave therapy in patients with chronic refractory angina pectoris.

BACKGROUND: Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. METHODS: We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3-7 spots/session, 100 impulses/spot, 0.09 mJ/mm(2)) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. RESULTS: One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p < 0.01) and the angina symptoms diminished from CCS class III to CCS class II (p < 0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2 ± 7.7 % to 56.4 ± 9.4 %, p = 0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015). No clinically relevant side effects were observed. CONCLUSION: CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

Comparison of random forest and parametric imputation models for imputing missing data using MICE: a CALIBER study.

Multivariate imputation by chained equations (MICE) is commonly used for imputing missing data in epidemiologic research. The "true" imputation model may contain nonlinearities which are not included in default imputation models. Random forest imputation is a machine learning technique which can accommodate nonlinearities and interactions and does not require a particular regression model to be specified. We compared parametric MICE with a random forest-based MICE algorithm in 2 simulation studies. The first study used 1,000 random samples of 2,000 persons drawn from the 10,128 stable angina patients in the CALIBER database (Cardiovascular Disease Research using Linked Bespoke Studies and Electronic Records; 2001-2010) with complete data on all covariates. Variables were artificially made "missing at random," and the bias and efficiency of parameter estimates obtained using different imputation methods were compared. Both MICE methods produced unbiased estimates of (log) hazard ratios, but random forest was more efficient and produced narrower confidence intervals. The second study used simulated data in which the partially observed variable depended on the fully observed variables in a nonlinear way. Parameter estimates were less biased using random forest MICE, and confidence interval coverage was better. This suggests that random forest imputation may be useful for imputing complex epidemiologic data sets in which some patients have missing data.

Management of Stable Angina in the Older Adult Population.

As society ages, the number of older adults with stable ischemic heart disease continues to rise. Older adults exhibit the greatest morbidity and mortality from stable angina. Furthermore, they suffer a higher burden of comorbidity and adverse events from treatment than younger patients. Given that older adults were excluded or underrepresented in most randomized controlled trials of stable ischemic heart disease, evidence for management is limited and hinges on subgroup analyses of trials and observational studies. This review aims to elucidate the current definitions of aging, assess the overall burden and clinical presentations of stable ischemic heart disease in older patients, weigh the available evidence for guideline-recommended treatment options including medical therapy and revascularization, and propose a framework for synthesizing complex treatment decisions in older adults with stable angina. Due to evolving goals of care in older patients, it is paramount to readdress the patient's priorities and preferences when deciding on treatment. Ultimately, the management of stable angina in older adults will need to be informed by dedicated studies in representative populations emphasizing patient-centered end points and person-centered decision-making.

Effectiveness of Shenshu Guanxin recipe granules for improving exercise tolerance in patients with stable angina pectoris: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effectivess of Shenshu Guanxin recipe granules (, SGR) in improving exercise tolerance and the quality of life in patients with Stable Angina Pectoris (SAP). METHODS: A total of 189 patients were consecutively enrolled between December 2012 and December 2014. The included patients were randomly assigned to SGR and placebo groups. The primary endpoints included mainly the results of treadmill exercise test and Seattle Angina Questionnaire (SAQ) during 12 weeks of treatment. RESULTS: After 12 weeks of treatment, SGR extended the time of exercise-induced ST-segment depression of 0.1 MV, lowered the maximum ST-segment depression, and shortened the duration of ST-segment depression in patients with SAP in southern China. Besides, the study also proved that SGR could improve the quality of life and functional status of patients with SAP. CONCLUSIONS: SGR showed a positive effect on exercise tolerance compared with the placebo besides optimal medical therapy. Also, the study proved that SGR could improve the SAQ score of the patients.

Pericoronary Adipose Tissue Attenuation in Patients With Acute Coronary Syndrome Versus Stable Coronary Artery Disease.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation has been associated with coronary inflammation and can be evaluated with coronary computed tomography angiography. The aims of this study were to compare the PCAT attenuation across precursors of culprit and nonculprit lesions of patients with acute coronary syndrome versus stable coronary artery disease (CAD). METHODS: In this case-control study, patients with suspected CAD who underwent coronary computed tomography angiography were included. Patients who developed an acute coronary syndrome within 2 years after the coronary computed tomography angiography scan were identified, and patients with stable CAD (defined as any coronary plaque ≥30% luminal diameter stenosis) were 1:2 propensity score matched for age, sex, and cardiac risk factors. The mean PCAT attenuation was analyzed at lesion level and compared between precursors of culprit lesions, nonculprit lesions, and stable coronary plaques. RESULTS: In total, 198 patients (age 62±10 years, 65% male) were selected, including 66 patients who developed an acute coronary syndrome and 132 propensity matched patients with stable CAD. Overall, 765 coronary lesions were analyzed (culprit lesion precursors: n=66; nonculprit lesion precursors: n=207; and stable lesions: n=492). Culprit lesion precursors had larger total plaque volume, fibro-fatty plaque volume, and low-attenuation plaque volume compared to nonculprit and stable lesions. The mean PCAT attenuation was significantly higher across culprit lesion precursors compared to nonculprit and stable lesions (-63.8±9.7 Hounsfield units versus -68.8±10.6 Hounsfield units versus -69.6±10.6 Hounsfield units, respectively; P<0.001), whereas the mean PCAT attenuation around nonculprit and stable lesions was not significantly different (P=0.99). CONCLUSIONS: The mean PCAT attenuation is significantly increased across culprit lesion precursors in patients with acute coronary syndrome, compared to nonculprit lesions of these patients and to lesions of patients with stable CAD, which may suggest a higher intensity of inflammation. PCAT attenuation on coronary computed tomography angiography may be a novel marker to identify high-risk plaques.

Effectiveness and safety of Xuefu Zhuyu oral liquid on -stagnation and blood-stasis pattern in patients with stable angina, tension-type headache and primary dysmenorrhea: rationale and design of a master protocol.

We present the rationale and design of a master protocol study that clarifies the effectiveness and safety of Chinese herbal formulas on -stagnation and blood-stasis pattern (QBP). Three randomized controlled trials (RCTs) and real-world observational studies. Based on three registry cohorts of stable angina, tension-type headache and primary dysmenorrhea, patients with QBP will be enrolled in RCTs to receive either Xuefu Zhuyu (, XFZY) oral liquid or a placebo, while patients with non-QBP will be enrolled in the observational studies and experience follow-up. 1414 patients (RCTs: 574; observational studies: 840) will be recruited at seven centers in China over a 3-year period. The primary outcome is the visual analog scale of pain intensity. Adverse events will also be reported. The analysis will be undertaken separately in each sub-study, and then an overall analysis combining multiple subgroups will be performed to comprehensively investigate the effect of XFZY oral liquid. This study will provide high-quality evidence of XFZY oral liquid for QBP patients and show a paradigm of post-marketing evaluation of the effectiveness and safety for Chinese medicine following the notion of the pattern dominating different disease research models.

The Clinical Impact of ß-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: The outcome benefits of ß-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of ß-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). METHODS: A total of 3,075 patients with chronic CAD were included from the Grand Drug-Eluting Stent registry. We analyzed ß-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (ß-blockers vs. no ß-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of ß-blockers. RESULTS: During a median (interquartile range) follow-up of 3.1 (3.0-3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, ß-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63-1.24), all-cause death (HR, 0.87; 95% CI, 0.60-1.25), and MI (HR, 1.25; 95% CI, 0.49-3.15). In subgroup analysis, ß-blockers were associated with a lower risk of all-cause death in patients with previous MI and/or revascularization (HR, 0.38; 95% CI, 0.14-0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of ß-blockers. CONCLUSIONS: Overall, ß-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of ß-blockers may exist for patients with previous MI and/or revascularization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03507205.

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The clinical concept of coronary artery disease (CAD) has seen a paradigm shift over the last decade. CAD is mostly a progressive disease, and patients with CAD can develop acute coronary syndromes at any point in disease progression. In this clinical context, a new term, "chronic coronary syndrome," was published in the 2019 European Society of Cardiology guidelines, reflecting the importance of early diagnosis and active management. Recent advances have been made in the evaluation of CAD using coronary CT angiography (CCTA). The clinical usefulness of CCTA in patients with stable angina or chronic coronary syndrome begins with the detection of early asymptomatic CAD. The characterization of atherosclerotic plaque and its role in determining treatment strategies for CAD have been demonstrated for all stages of the disease. This review describes the pathophysiology of stable angina to aid in the understanding of the clinical applications of CCTA.

Rates of Elective Percutaneous Coronary Intervention in England and Wales: Impact of COURAGE and ORBITA Trials.

Background There are limited data about how COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) and ORBITA (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trials have impacted percutaneous coronary intervention (PCI) practices at regional or national level. We evaluated temporal trends in elective PCI rates for stable angina and, specifically, examined the impact of the COURAGE and ORBITA trials on PCI practices in England and Wales. Methods and Results We used national PCI data comprising >1.2 million patients undergoing PCI between January 2006 and December 2019. Patient demographics, procedural details, and clinical outcomes were analyzed, and temporal trends in PCI rates for stable angina were compared before and after the publication of the COURAGE and ORBITA trials. Of 1 245 802 PCI procedures, 430 248 (34.5%) were performed for stable angina. Over the study period, the number of elective PCI procedures per year (30 823 in 2006 to 34 103 in 2019) and per 100 000 population estimates (50.7 in 2006 to 58.4 in 2019) remained stable. The proportion of patients undergoing elective PCI without angina symptoms almost doubled from 5.1% to 9.7%. The incidence rate of elective PCI volume after the COURAGE trial, published in 2007, was not different from before the trial was published (incidence rate ratio, 1.06 [95% CI, 0.69-1.62]). It also remained stable after the publication of the ORBITA trial in 2017 (incidence rate ratio, 0.96 [95% CI, 0.74-1.23]). Conclusions In this nationwide analysis, rates of elective PCI for stable angina remained stable over 14 years. Publication of the COURAGE and ORBITA trials had no impact on elective PCI activity.

Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris.

Background: Growth differentiation factor-15 (GDF-15), a member of transforming growth factors, is a stress-responsive marker whose levels may significantly increase in response to pathological stresses associated with inflammatory tissue injuries such as unstable angina pectoris (USAP). This study evaluated the diagnostic value of GDF-15 in patients with USAP. Methods: The present cross-sectional study recruited 39 patients with USAP criteria and 30 patients with stable angina pectoris (SAP), referred to Shahid Beheshti Hospital, Kashan, Iran. All the patients with USAP had at least 1 coronary artery stenosis (>50%) in angiography. The control group comprised 42 healthy individuals. The serum levels of GDF-15 were measured in all the participants by ELISA. Also analyzed were the relationship between GDF-15 levels and thrombolysis in myocardial infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores in the patients with USAP to determine the severity of the disease. Result: The study population consisted of 111 subjects, 62 women and 49 men, divided into 3 groups of USAP (n=39, mean age=60.07±14.10 y), SAP (n=30, mean age=67.56±9.88 y), and control (n=42, mean age=61.21±7.76 y). The mean serum level of GDF-15 in the USAP group was significantly different from the other 2 groups (P<0.001), while no significant difference was observed in this regard between the SAP and control groups (P=0.797). No correlation was found between the mean GDF-15 serum level and the GRACE (P=0.816) and TIMI (P=0.359) risk scores in the USAP group. Conclusion: The mean serum level of GDF-15 exhibited a rise in our patients with USAP. GDF-15 may be a diagnostic biomarker of USAP and its severity.

Polygenic Risk Score-Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.

BACKGROUND: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD. METHODS: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a suspected ≥50% stenosis also underwent invasive coronary angiography with fractional flow reserve. A combined end point of obstructive CAD was defined as a visual invasive coronary angiography stenosis >90%, fractional flow reserve <0.80, or a quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not feasible. RESULTS: The PRS was associated with obstructive CAD independent of CRFs (adjusted odds ratio, 1.8 [95% CI, 1.5-2.2] per SD). The PRS had an area under the curve of 0.63 (0.59-0.68), which was similar to that for age and sex. Combining the PRS with CRFs led to a CRF+PRS model with area under the curve of 0.75 (0.71-0.79), which was 0.04 more than the CRF model (P=0.0029). By using pretest probability (pretest probability) cutoffs at 5% and 15%, a net reclassification improvement of 15.8% (P=3.1×10-4) was obtained, with a down-classification of risk in 24% of patients (211 of 862) in whom the pretest probability was 5% to 15% based on CRFs alone. CONCLUSIONS: Adding a PRS improved risk stratification of obstructive CAD beyond CRFs, suggesting a modest clinical potential of using PRSs to guide diagnostic testing in the contemporary clinical setting. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02264717.

High-Sensitivity Cardiac Troponin I and the Diagnosis of Coronary Artery Disease in Patients With Suspected Angina Pectoris.

BACKGROUND: We determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina. METHODS AND RESULTS: In a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; P<0.001) independent of known cardiovascular risk factors (odds ratio, 1.35; 95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin concentrations improved the discrimination and calibration of the CAD Consortium model for identifying obstructive CAD (C statistic, 0.788-0.800; P=0.004; χ2=16.8 [P=0.032] to 14.3 [P=0.074]). The updated model also improved classification of the American College of Cardiology/American Heart Association pretest probability risk categories (net reclassification improvement, 0.062; 95% confidence interval, 0.035-0.089). The revised model achieved similar improvements in discrimination and calibration when applied in the external validation cohort. CONCLUSIONS: High-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01149590.

Dynamic Computed Tomography Myocardial Perfusion Imaging: Comparison of Clinical Analysis Methods for the Detection of Vessel-Specific Ischemia.

BACKGROUND: The clinical analysis of myocardial dynamic computed tomography myocardial perfusion imaging lacks standardization. The objective of this prospective study was to compare different analysis approaches to diagnose ischemia in patients with stable angina referred for invasive coronary angiography. METHODS AND RESULTS: Patients referred for evaluation of stable angina symptoms underwent adenosine-stress dynamic computed tomography myocardial perfusion imaging with a second-generation dual-source scanner. Quantitative perfusion parameters, such as blood flow, were calculated by parametric deconvolution for each myocardial voxel. Initially, perfusion parameters were extracted according to standard 17-segment model of the left ventricle (fully automatic analysis). These were then manually sampled by an operator (semiautomatic analysis). Areas under the receiver-operating characteristic curves of the 2 different approaches were compared. Invasive fractional flow reserve ≤0.80 or diameter stenosis ≥80% on quantitative coronary angiography was used as reference standard to define ischemia. We enrolled 115 patients (88 men; age 57±9 years). There were 72 of 286 (25%) vessels causing ischemia in 52 of 115 (45%) patients. The semiautomatic analysis method was better than the fully automatic method at predicting ischemia (areas under the receiver-operating characteristic curves, 0.87 versus 0.69; P<0.001) with readings obtained in the endocardial myocardium performing better than those in the epicardial myocardium (areas under the receiver-operating characteristic curves, 0.87 versus 0.72; P<0.001). The difference in performance between blood flow, expressed as relative to remote myocardium, and absolute blood flow was not statistically significant (areas under the receiver-operating characteristic curves, 0.90 versus 0.87; P=ns). CONCLUSIONS: Endocardial perfusion parameters obtained by semiautomatic analysis of dynamic computed tomography myocardial perfusion imaging may permit robust discrimination between coronary vessels causing ischemia versus not causing ischemia.