Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data.

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780.

Correction to: Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification: A Euro-CCAD study.

BACKGROUND AND AIMS: Although much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score. METHODS: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CT scanning for CAC scoring. RESULTS: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p<0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes.

Fifteen-year trends in the management of cardiogenic shock and associated 1-year mortality in elderly patients with acute myocardial infarction: the FAST-MI programme.

AIMS: Alhough cardiogenic shock (CS) after acute myocardial infarction (AMI) is more common in elderly patients, information on the epidemiology of these patients is scarce. This study aimed to assess the trends in prevalence, characteristics, management, and outcomes of elderly patients admitted with CS complicating AMI between 1995 and 2010, using data from the FAST-MI programme. METHODS AND RESULTS: We analysed the incidence and 1-year mortality of CS in four nationwide French surveys carried out 5 years apart from 1995 to 2010, including consecutive AMI patients over 1-month periods. Among the 10 610 patients, 3389 were aged ≥75 years, of whom 9.9% developed CS. The prevalence of CS decreased in elderly patients from 11.6% in 1995 to 6.7% in 2010 (P = 0.02). Over the 15-year period, the characteristics of elderly patients with CS changed, with more diabetes, hypertension, and hypercholesterolaemia. The use of PCI increased markedly in elderly patients with and without CS, reaching 51% and 59%, respectively, in 2010. In addition, medical therapy also evolved, with more patients receiving antithrombotic agents, beta-blockers, and statins. Over time, 1-year mortality decreased by 32% among elderly patients with CS but remained high (59% in 2010). ST-segmet elevation myocardial infarction and previous AMI were independent correlates of increased 1-year death, while study period was associated with decreased mortality (2010 vs, 1995: hazard ratio 0.40, 95% confidence interval 0.27-0.61, P < 0.001), along with early use of PCI. CONCLUSION: Cardiogenic shock in elderly patients with AMI remains a major clinical concern. However, 1-year mortality declined in these patients, a decrease potentially mediated by broader use of PCI and the improvement of global patient management.

2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases.

Full text available at: http://eurheartj.oxfordjournals.org/content/early/2015/08/28/eurheartj.ehv318.

[Non-invasive imaging tests for detecting coronary artery disease in symptomatic stable patients. Is diagnostic performance sufficient for guiding strategy?]. / Détection de la maladie coronaire par les examens non invasifs d'imagerie cardiaque chez le patient symptomatique stable: la seule performance diagnostique est-elle suffisante pour guider la stratégie?

Several non-invasive imaging techniques are currently available for coronary artery disease detection in stable patients with chest pain: exercise electrocardiogram, myocardial scintigraphy, stress echocardiography, stress MRI, positron emission tomography and computed tomography coronary angiography. According to recent guidelines from the European Society of Cardiology, the diagnosis process shall be guided by the coronary risk of the patient. The first recommended step is to clinically assess the probability of coronary artery disease. Thereafter, the choice of technique will be driven by usual parameters such as availability, local expertise and the contraindications of each test. Although detection of coronary artery disease by non-invasive tests follows different pathophysiological pathways, diagnostic value appears comparable. Therefore, choice of a diagnostic test must also take into consideration other factors such as the risks and hazards of imaging techniques as well as cost-efficiency parameters.

Cost-effectiveness of computed tomography coronary angiography versus conventional invasive coronary angiography.

OBJECTIVES: To determine the costs and cost-effectiveness of a diagnostic strategy including computed tomography coronary angiography (CTCA) in comparison with invasive conventional coronary angiography (CA) for the detection of significant coronary artery disease from the point of view of the healthcare provider. METHODS: The average cost per CTCA was determined via a micro-costing method in four French hospitals, and the cost of CA was taken from the 2011 French National Cost Study that collects data at the patient level from a sample of 51 public or not-for-profit hospitals. RESULTS: The average cost of CTCA was estimated to be 180 (95 % CI 162-206) based on the use of a 64-slice CT scanner active for 10 h per day. The average cost of CA was estimated to be 1,378 (95 % CI 1,126-1,670). The incremental cost-effectiveness ratio of CA for all patients over a strategy including CTCA triage in the intermediate risk group, no imaging test in the low risk group, and CA in the high risk group, was estimated to be 6,380 (95 % CI 4,714-8,965) for each additional correctly classified patient. This strategy correctly classifies 95.3 % (95 % CI 94.4-96.2) of all patients in the population studied. CONCLUSIONS: A strategy of CTCA triage in the intermediate-risk group, no imaging test in the low-risk group, and CA in the high-risk group, has good diagnostic accuracy and could significantly cut costs. Medium-term and long-term outcomes need to be evaluated in patients with coronary stenosis potentially misclassified by CTCA due to false negative examinations.

Determinants of improved one-year survival in non-ST-segment elevation myocardial infarction patients: insights from the French FAST-MI program over 15 years.

BACKGROUND: Improved early outcome in non-ST elevation myocardial infarction (NSTEMI) patients has been mainly attributed to a broader use of invasive strategies. Little is known about the impact of other changes in early management. METHODS: We aimed to assess 15-year trends in one-year mortality and their determinants in NSTEMI patients. We used data from 4 one-month French registries, conducted 5 years apart from 1995 to 2010 including 3903 NSTEMI patients admitted to intensive care units. RESULTS: From 1995 to 2010, no major change was observed in patient characteristics, while therapeutic management evolved considerably. Early use of antiplatelet agents, ß-blockers, ACE-inhibitors and statins increased over time (P < 0.001); use of newer anticoagulants (low-molecular-weight heparin, bivalirudin or fondaparinux) increased from 40.8% in 2000 to 78.9% in 2010 (P < 0.001); percutaneous coronary intervention (PCI)≤ 3 days of admission rose from 7.6% to 48.1% (P < 0.001). One-year death decreased from 20% to 9.8% (HR adjusted for baseline parameters, 2010 vs. 1995 = 0.47, 95% CI: 0.35-0.62). Early PCI (HR = 0.67; 95% CI: 0.49-0.90), use of newer anticoagulants (HR = 0.62; 95% CI: 0.48-0.78) and early use of evidence based medical therapy (HR = 0.54; 95% CI: 0.40-0.72) were predictors of improved one year-survival. CONCLUSIONS: One-year mortality of NSTEMI patients decreased by 50% in the past 15years. Our data support current guidelines recommending early invasive strategies and use of newer anticoagulants for NSTEMI, and also show a strong positive association between early use of appropriate medical therapies and one-year survival, suggesting that these medications should be used from the start.

Epicardial adipose tissue thickness correlates with the presence and severity of angiographic coronary artery disease in stable patients with chest pain.

OBJECTIVE: Epicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD). METHODS: We measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis. RESULTS: Of 970 patients (age 60.9 years, 71% male), 75% (n = 731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; p = 0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was OR = 1.46 [1.03-2.08], p = 0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (p = 0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76. CONCLUSION: Although left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.

Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction.

BACKGROUND: Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia. METHODS: We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 ± 17 years, LVEF = 24 ± 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 γ/min], before and after Ivabradine [5mg per os]. In the validation population (54 ± 11 years, LVEF = 22 ± 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion. RESULTS: In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 ± 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 ± 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 ± 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 ± 4.7% vs. + 3.6 ± 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 ± 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 ± 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 ± 5 mmHg, P = 0.007), daily urine output (+ 0.7 ± 0.5L, P = 0.008), oxygen balance (ΔScv02 = + 13 ± 15%, P = 0.010), and NT-pro BNP (-2270 ± 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017). CONCLUSION: This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock.

Prevalence and clinical impact of QRS duration in patients with low-flow/low-gradient aortic stenosis due to left ventricular systolic dysfunction.

AIMS: To evaluate the prognostic impact of QRS width in patients with low-flow/low-gradient aortic stenosis (LF/LGAS). METHODS AND RESULTS: Among 88 consecutive patients referred to our institution for LF/LGAS from September 1994 to March 2007, baseline demographic, clinical, echocardiographic, and electrocardiographic data were collected. This population was divided into two groups according to baseline QRS duration (cut-off QRS ≥130 ms). Follow-up data, including electrocardiographic evolution and overall mortality, were analysed. The mean follow-up duration was 3.1 (2.2-6.2) years. In the whole group, 67 patients underwent surgical aortic valve replacement. Forty-nine patients (56%) had a QRS duration ≥130 ms. Among operated patients, there was no significant change in QRS duration between baseline and latest follow-up (126 ± 26 ms vs. 131 ± 25 ms; P = 0.82). In addition, wider QRS was a strong independent predictor of overall mortality (hazard ratio 2.20, 95% confidence interval 1.15-4.24; P = 0.027). CONCLUSION: Significant intraventricular conduction disturbances are common in patients with LF/LGAS and do not recover after aortic valve replacement. QRS duration is strongly associated with mortality in this selected population.

Cardiac resynchronization therapy plus coupled pacing improves acutely myocardial function in heart failure patients.

BACKGROUND: Coupled pacing (CP), which consists of an additional beat delivered after ventricular refractory period, has been proposed to reduce ventricular rate and increase ventricular contractility. We hypothesized that CP may be added to cardiac resynchronization therapy (CRT) to improve CRT effect in heart failure (HF) patients. METHODS: The study included 20 consecutive HF patients in sinus rhythm referred for CRT-defibrillator (CRT-D) implantation (baseline left ventricular ejection fraction [LVEF] 27 ± 6%, baseline QRS duration 149 ± 33 ms, age = 63 ± 11 years). CP associated with CRT (CRT + CP) was delivered during CRT-D implantation from the right and left ventricular leads simultaneously. Echocardiography data were collected at baseline, during CRT and CRT + CP to assess changes in LVEF, cardiac output (CO), longitudinal global strain assessed by speckle tracking, and LV dyssynchrony (opposing wall delay using tissue Doppler imaging). RESULTS: Compared to the conventional CRT, heart rate (HR) markedly decreased during CRT + CP (79 ± 20 beats/min vs 51 ± 8 beats/min, P < 0.0001) and was associated with a significant increase in LVEF (30 ± 8% vs 35 ± 8%, P = 0.0002) and peak of longitudinal global strain (-6 ± 2% vs -8 ± 2%, P < 0.0001). Importantly, during CRT + CP, CO increased (3.8 ± 1.0 L/min vs 4.4 ± 1.4 L/min, P = 0.004) and cardiac synchronicity remained unchanged (38 ± 24 ms for CRT alone vs 27 ± 18 ms for CRT + CP, P = 0.1). CONCLUSION: In sinus rhythm HF patients, acute CP application in addition to CRT decreases HR and contributes to myocardial contractility and CO improvement without deleterious impact on ventricular synchronicity.

Changes in three-dimensional speckle-tracking-derived myocardial strain during percutaneous coronary intervention.

BACKGROUND: The aim of this study was to evaluate changes in three-dimensional (3D) speckle-tracking-derived myocardial strain during ischemia. METHODS: Twenty patients referred for percutaneous coronary intervention were studied (mean age, 65 ± 11 years; mean left ventricular ejection fraction, 56 ± 7%). Of the 20 study patients, 12 had severe left anterior descending coronary artery stenosis. A full-volume apical view using multibeat 3D modality and two-dimensional (2D) apical views (four chamber, two chamber, and three chamber) were recorded during coronary occlusion before wall motion abnormalities. After percutaneous coronary intervention, ultrasound contrast agent was selectively delivered through the target lesion to delineate ischemic and peri-ischemic segments (ischemia-adjacent segments). Strain values derived from 2D and 3D speckle-tracking echocardiography were compared in ischemic and nonischemic segments. RESULTS: Despite no changes in wall motion and 2D left ventricular ejection fraction (56 ± 7% vs 56 ± 7%), global longitudinal strain by 2D imaging was impaired during percutaneous coronary intervention (-16 ± 3% vs -14 ± 3%, P = .01). Similar changes were observed for all 3D strain components: -11 ± 16% for longitudinal (-15 ± 4% vs -13 ± 4%, P = .03), -13 ± 25% for circumferential (-15 ± 4% vs -12 ± 4%, P = .02), -12 ± 16% for area (-25 ± 5% vs -22 ± 6%, P = .009), and -12 ± 25% for radial global strain (39 ± 12% vs 33 ± 12%, P = .04). During coronary occlusion, 2D longitudinal peak strain and all 3D peak strain components decreased in ischemic segments, while no changes was observed in nonischemic segments. In peri-ischemic segments, only 3D longitudinal and area strain were impaired during ischemia. CONCLUSIONS: Changes in myocardial deformation related to ischemia can be characterized by 3D speckle-tracking echocardiography before the stage of wall motion abnormality.