Michiel A. de Graaf

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

Background—The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results—A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ⩽0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69–0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65–0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). Conclusions—In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population

AIMS Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

Matching, an Appealing Method to Avoid Confounding?

Matching is a technique used to avoid confounding in a study design. In a cohort study this is done by ensuring an equal distribution among exposed and unexposed of the variables believed to be confounding. In a matched case-control study, a case, affected by the disease, is matched with one or more individuals not affected by the disease, the controls. Because in a matched case-control study case and control group become too similar not only in the distribution of the confounder but also in the distribution of the exposure, one finds a lower effect estimate (odds ratio closer to 1). A matched case-control study requires statistical analysis to correct for this phenomenon. Nonetheless, a matched case-control study is suitable for confounders that are difficult to measure.

Influence of coronary vessel dominance on short-and long-term outcome in patients after ST-segment elevation myocardial infarction

AIMS Prognostic importance of coronary vessel dominance in patients with ST-elevation myocardial infarction (STEMI) remains uncertain. The aim of this study was to assess influence of coronary vessel dominance on the short- and long-term outcome after STEMI. METHODS AND RESULTS Coronary angiographic images of consecutive patients presenting with first STEMI were retrospectively reviewed to assess coronary vessel dominance. Patients were followed after STEMI during a median period of 48 (IQR38-61) months for the occurrence of all-cause mortality and the composite of reinfarction and cardiac death. The population comprised 1131 patients of which 971 (86%) patients had a right dominant, 102 (9%) a left dominant, and 58 (5%) a balanced system. After 5 years of follow-up, the cumulative incidence of all-cause mortality was significantly higher in patients with a left dominant system, compared with a right dominant and balanced system (log-rank P = 0.013). Moreover, a left dominant system was an independent predictor for 30-day mortality (OR 2.51, 95% CI 1.11-5.67, P = 0.027) and the composite of reinfarction and cardiac death within 30-days after STEMI (OR 2.25, 95% CI 1.09-4.61, P = 0.028). In patients surviving first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome. CONCLUSIONS A left dominant coronary artery system is associated with a significantly increased risk of 30-day mortality and early reinfarction after STEMI. After surviving the first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome.

Feasibility of an automated quantitative computed tomography angiography-derived risk score for risk stratification of patients with suspected coronary artery disease.

Coronary computed tomography angiography (CTA) has important prognostic value. Additionally, quantitative CTA (QCT) provides a more detailed accurate assessment of coronary artery disease (CAD) on CTA. Potentially, a risk score incorporating all quantitative stenosis parameters allows accurate risk stratification. Therefore, the purpose of this study was to determine if an automatic quantitative assessment of CAD using QCT combined into a CTA risk score allows risk stratification of patients. In 300 patients, QCT was performed to automatically detect and quantify all lesions in the coronary tree. Using QCT, a novel CTA risk score was calculated based on plaque extent, severity, composition, and location on a segment basis. During follow-up, the composite end point of all-cause mortality, revascularization, and nonfatal infarction was recorded. In total, 10% of patients experienced an event during a median follow-up of 2.14 years. The CTA risk score was significantly higher in patients with an event (12.5 [interquartile range 8.6 to 16.4] vs 1.7 [interquartile range 0 to 8.4], p <0.001). In 127 patients with obstructive CAD (≥50% stenosis), 27 events were recorded, all in patients with a high CTA risk score. In conclusion, the present study demonstrated that a fully automatic QCT analysis of CAD is feasible and can be applied for risk stratification of patients with suspected CAD. Furthermore, a novel CTA risk score incorporating location, severity, and composition of coronary lesion was developed. This score may improve risk stratification but needs to be confirmed in larger studies.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

Objective— Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. Approach and Results— Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25–75 percentiles) value of plasma hs-cTnT was 6.17 (4.2–9.1) ng/L and of NT-proBNP was 61.66 (31.2–132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). Conclusions— In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.

Additional Diagnostic Value of Integrated Analysis of Cardiac CTA and SPECT MPI Using the SMARTVis System in Patients with Suspected Coronary Artery Disease

CT angiography (CTA) and SPECT myocardial perfusion imaging (MPI) are complementary imaging techniques to assess coronary artery disease (CAD). Spatial integration and combined visualization of SPECT MPI and CTA data may facilitate correlation of myocardial perfusion defects and subtending coronary arteries and thus offer additional diagnostic value over either stand-alone or side-by-side interpretation of the respective datasets from the 2 modalities. In this study, we investigated the additional diagnostic value of a software-based CTA/SPECT MPI image fusion system over conventional side-by-side analysis in patients with suspected CAD. Methods: Seventeen symptomatic patients who underwent both CTA and SPECT MPI within a 90-d period were included in our study; 7 of them also underwent invasive coronary angiography (ICA). The potential benefits of the synchronized multimodal heart visualization (SMARTVis) system in assessing CAD were investigated through a case study involving 4 experts from 2 medical centers, in which we performed, first, a side-by-side analysis using structured CTA and SPECT reports and, second, an integrated analysis using the SMARTVis system in addition to the reports. Results: The fused interpretation led to a more accurate diagnosis, reflected in an increase in the individual observers’ sensitivity and specificity to correctly refer for invasive angiography eventually followed by revascularization. For the first, second, third, and fourth observers, the respective sensitivities improved from 50%, 60%, 80%, and 80% to 70%, 80%, 100%, and 90% and the respective specificities from 100%, 94%, 83%, and 83% to 100%, 100%, 94%, and 83%. Additionally, the interobserver diagnosis agreement increased from 74% to 84%. The improvement was primarily found in patients presenting with CAD in more vessels than the number of reported perfusion defects. Conclusion: Integrated analysis of cardiac CTA and SPECT MPI using the SMARTVis system results in an improved diagnostic performance.

Surgical treatment of aberrant aortic origin of coronary arteries

OBJECTIVES Aberrant origin of the coronary arteries is rare but can be life threatening. It is an important cause of sudden death in athletes and other young adults, and may be treated surgically. Consensus exists that interarterial left coronary artery (LCA) should be surgically repaired. For interarterial right coronary artery (RCA), the discussion remains open. The purpose of this study was to analyse our surgical experience. METHODS From 2001 until 2014, 31 patients were operated for interarterial RCA, interarterial LCA or intraseptal course of the LCA. Twenty-six patients had interarterial RCA, 4 patients interarterial LCA and 1 patient an intraseptal course of the LCA. Median age at operation was 38 years (range 9-66 years). Twenty-eight patients had previous or current symptoms. The most important were a life-threatening event with resuscitation in 3 and myocardial infarction in 3 others. Surgical repair of interarterial RCA consisted of unroofing of the ostium with or without reimplantation in 25 patients and CABG on the RCA with a venous graft in 1 patient. Reconstruction of interarterial LCA consisted of ostium reconstruction of the LCA with a venous patch in 4 patients. The patient with an intraseptal course had a complete release of the LCA out of the septum and reimplantation in the correct coronary sinus. Follow-up was done by analysis of outpatient records, direct patient contact, echocardiography, electrocardiography, CT-angiography and an exercise test. RESULTS Median follow-up was 6 years (range 0-11 years). One patient was lost to follow-up. No early or late mortality occurred. Three patients had ischaemia with ventricular fibrillation or ventricular tachycardia shortly after surgery. Two were immediately reoperated, 1 had a stent implantation 1.5 months after release of intraseptal LCA. Two of these patients show a slight dysfunction of the left ventricle at follow-up. All other patients are asymptomatic. CONCLUSIONS Surgery for aberrant origin of coronary arteries is safe. There is a risk of cardiac ischaemia shortly after operation, especially in LCA reconstruction. We strongly believe that a slit-like coronary ostium and an intramural aortic course is an absolute indication for surgical repair, also in asymptomatic aberrant RCA.

Coronary anatomy as related to bicuspid aortic valve morphology

Objective Variable coronary anatomy has been described in patients with bicuspid aortic valves (BAVs). This was never specified to BAV morphology, and prognostic relevance of coronary vessel dominance in this patient group is unclear. The purpose of this study was to evaluate valve morphology in relation to coronary artery anatomy and outcome in patients with isolated BAV and with associated aortic coarctation (CoA). Methods Coronary anatomy was evaluated in 186 patients with BAV (141 men (79%), 51±14 years) by CT and invasive coronary angiography. Correlation of coronary anatomy was made with BAV morphology and coronary events. Results Strictly bicuspid valves (without raphe) with left-right cusp fusion (type 1B) had more left dominant coronary systems compared with BAVs with left-right cusp fusion with a raphe (type 1A) (48% vs. 26%, p=0.047) and showed more separate ostia (28% vs. 9%, p=0.016). Type 1B BAVs had more coronary artery disease than patients with type 1A BAV (36% vs. 19%, p=0.047). More left dominance was seen in BAV patients with CoA than in patients without (65% vs. 24%, p<0.05). Conclusions The incidence of a left dominant coronary artery system and separate ostia was significantly related to BAVs with left-right fusion without a raphe (type 1B). These patients more often had significant coronary artery disease. In patients with BAV and CoA, left dominancy is more common.

Position of Edwards SAPIEN transcatheter valve in the aortic root in relation with the coronary ostia: implications for percutaneous coronary interventions.

To determine the implications of stable coverage of the coronary ostia by the Edwards SAPIEN valve frame in terms of myocardial ischemia and subsequent percutaneous coronary intervention (PCI), following transcatheter aortic valve implantation (TAVI).