Accuracy and Potential Benefit of Ultraselective Invasive Coronary Angiography Guided by Computed Tomographic Coronary Angiography.

OBJECTIVES: It is unknown whether computed tomographic coronary angiography (CTCA) can be used to perform ultraselective invasive coronary angiography (ICA) by only visualizing the abnormal coronary artery on CTCA and defer visualization of the normal contralateral coronary artery. This study assessed the accuracy of CTCA in patients with coronary artery disease (CAD) on CTCA limited to either the left (LCA) or right coronary artery (RCA) in predicting a contralateral coronary artery without abnormalities on CTCA determined to be normal by ICA. METHODS: This retrospective analysis included patients with CAD limited to the LCA or RCA on CTCA. Primary endpoint was the accuracy of CTCA to predict a contralateral coronary artery without abnormalities on CTCA to be normal by ICA. Secondary endpoints were potential reductions in procedure time and radiation exposure if an ultraselective ICA approach would be used compared to standard ICA. RESULTS: In total, 202 patients were included. CTCA was correct in predicting a normal contralateral coronary artery in 201 of the 202 patients (99.5%). Deferring ICA of the normal contralateral coronary artery on CTCA resulted in a potential reduction in procedure time and dose area product of 4.22 ± 2.67 minutes (61 ± 16% reduction) and 1501 ± 1304 mGy•cm² (29 ± 13% reduction). CONCLUSIONS: In this retrospective study, CTCA was extremely accurate in predicting a normal contralateral coronary artery in patients with LCA- or RCA-limited CAD on CTCA. A potential CTCA-guided ultraselective ICA approach was feasible and would have led to a considerable decrease in procedure time and radiation exposure.

Five-Year Results of the Bioflow-III Registry: Real-World Experience with a Biodegradable Polymer Sirolimus-Eluting Stent.

PURPOSE: We aimed to assess long-term safety and performance of the Orsiro sirolimus-eluting coronary stent with biodegradable polymer in a large unselected population and in pre-specified subgroups. METHODS: BIOFLOW-III is a prospective, multicenter, international, observational registry with follow-up visits scheduled at 6 and 12 months, and at 3 and 5 years (NCT01553526). RESULTS: 1356 patients with 1738 lesions were enrolled. Of those, 392 (28.9%) declined to participate in the study extension from 18 months to 5 years, 37 (2.7%) withdrew consent, and 89 (6.6%) were lost to follow-up. At 5-years, Kaplan-Meier estimates of target lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, coronary artery bypass grafting and clinically driven target lesion revascularization was 10.0% [95% confidence interval (CI): 8.4; 12.0] in the overall population, and 14.0% [95% CI: 10.5; 18.6], 10.3% [95% CI: 7.8; 13.5], 1.8% [95% CI: 0.3; 12.0], and 11.3% [95% CI: 8.5; 15.1] in the pre-defined risk groups of patients with diabetes mellitus, small vessels ≤2.75 mm, chronic total occlusion, and acute myocardial infarction. Definite stent thrombosis was observed in 0.3% [95% CI: 0.1; 0.9] of patients. CONCLUSION: These long-term outcomes provide further evidence on the safety and performance of a sirolimus-eluting biodegradable polymer stent within daily clinical practice. The very low definite stent thrombosis rate affirms biodegradable polymer safety and performance.

Real-world experience with a novel biodegradable polymer sirolimus-eluting stent: twelve-month results of the BIOFLOW-III registry.

AIMS: We aimed to assess the safety and performance of a novel sirolimus-eluting stent with biodegradable polymer under real-world conditions. METHODS AND RESULTS: This prospective, multicentre, observational, all-comers registry enrolled 1,356 patients. The primary endpoint was target lesion failure at 12 months: it occurred in 5.1% (95% CI: 4.0-6.4) of patients in the overall population and in 7.7% (95% CI: 5.5-10.9), 5.8% (95% CI: 4.2-8.1), 1.8% (95% CI: 0.2-11.8) and 7.2% (95% CI: 5.1-10.0) of patients with diabetes mellitus, small vessels, chronic total occlusion and acute myocardial infarction, respectively. CONCLUSIONS: This novel stent platform demonstrated good clinical outcomes in an all-comers population, even in predefined high-risk groups. ClinialTrials.gov identifier: NCT01553526

Combined use of exercise electrocardiography, coronary calcium score and cardiac CT angiography for the prediction of major cardiovascular events in patients presenting with stable chest pain.

BACKGROUND: The usual diagnostic work-up of chest pain patients includes clinical risk profiling and exercise-ECG, possibly followed by additional tests. Recently cardiac computed tomographic angiography (CCTA) has been employed. We evaluated the prognostic value of the combined use of exercise-ECG and CCTA for the development of cardiovascular endpoints. METHODS: In 283 patients (143 male, mean age 54 ± 10 years) with intermediate pre-test probability for coronary artery disease presenting with stable chest pain, exercise-ECG, CCTA and calcium score were performed. Patients were followed-up for combined endpoint of acute coronary syndrome (ACS) and revascularization. RESULTS: After a median follow-up of 769 days (interquartile range 644-1007), 6 ACS and 9 revascularizations were recorded. A positive exercise-ECG predicted for the combined endpoint, [hazard ratio (HR) 5.14 (95% confidence interval (CI) 1.64-16.13), p=0.005], as well as a positive calcium score [HR 4.59 (95% CI 1.30-16.28), p=0.02] and a ≥ 50% stenosis on CCTA [HR 45.82 (95% CI 6.02-348.54), p<0.001]. ROC-analysis showed an area under the curve (AUC) of 0.79 (95% CI 0.67-0.90) for exercise-ECG, which increased significantly when CCTA was added: 0.91 (95% CI; 0.86-0.97; p=0.006). Multivariable Cox regression showed exercise-ECG predicted independently [HR 3.6, (95% CI 1.1-11.2), p=0.03], as well as CCTA [HR 31.4 (95% CI 4.0-246.6), p=0.001], but not calcium score [HR 0.6 (95% CI 0.2-2.3), p=0.5]. CONCLUSIONS: The combined subsequent use of exercise-ECG for functional information and CCTA for anatomical information provides a high diagnostic yield in stable chest pain patients with an intermediate pre-test probability for coronary artery disease.

Relation between mild to moderate chronic kidney disease and coronary artery disease determined with coronary CT angiography.

BACKGROUND: Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors. METHODS: A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m(2)); mild CKD (eGFR 60-89 mL/min/1.73 m(2)); and moderate CKD (eGFR 30-59 mL/min/1.73 m(2)). RESULTS: Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52-2.21) and moderate CKD (OR 2.46, 95%CI 1.69-3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16-2.40) and moderate CKD (OR2.36, 95%CI 1.35-4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant. CONCLUSION: Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.

Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype.

BACKGROUND: Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/-) model of atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/-) mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1) (VK(1), 1.5 mg/g) or vitamin K(1) and warfarin (VK(1)&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. CONCLUSIONS/SIGNIFICANCE: VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/-) mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

High-sensitivity cardiac troponin T: risk stratification tool in patients with symptoms of chest discomfort.

BACKGROUND: Recent studies have demonstrated the association between increased concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and the incidence of myocardial infarction, heart failure, and mortality. However, most prognostic studies to date focus on the value of hs-cTnT in the elderly or general population. The value of hs-cTnT in symptomatic patients visiting the outpatient department remains unclear. The aim of this study was to investigate the prognostic value of hs-cTnT as a biomarker in patients with symptoms of chest discomfort suspected for coronary artery disease and to assess its additional value in combination with other risk stratification tools in predicting cardiac events. METHODS: We studied 1,088 patients (follow-up 2.2 ± 0.8 years) with chest discomfort who underwent coronary calcium scoring and coronary CT-angiography. Traditional cardiovascular risk factors and concentrations of hs-cTnT, N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were assessed. Study endpoint was the occurrence of late coronary revascularization (>90 days), acute coronary syndrome, and cardiac mortality. RESULTS: Hs-cTnT was a significant predictor for the composite endpoint (highest quartile [Q4]>6.7 ng/L, HR 3.55; 95%CI 1.88-6.70; P<0.001). Survival analysis showed that hs-cTnT had significant predictive value on top of current risk stratification tools (Chi-square change P<0.01). In patients with hs-cTnT in Q4 versus

Performance of angiographic, electrocardiographic and MRI methods to assess the area at risk in acute myocardial infarction.

Objective Validation of methods to assess the area at risk (AAR) in patients with ST elevation myocardial infarction is limited. A study was undertaken to test different AAR methods using established physiological concepts to provide a reference standard. Main outcome measured In 78 reperfused patients with first ST elevation myocardial infarction, AAR was measured by electrocardiographic (Aldrich), angiographic (Bypass Angioplasty Revascularization Investigation (BARI), APPROACH) and cardiovascular magnetic resonance methods (T2-weighted hyperintensity and delayed enhanced endocardial surface area (ESA)). The following established physiological concepts were used to evaluate the AAR METHODS: (1) AAR size is always ≥ infarct size (IS); (2) in transmural infarcts AAR size=IS; (3) correlation between AAR size and IS increases as infarct transmurality increases; and (4) myocardial salvage ((AAR-IS)/AAR×100) is inversely related to infarct transmurality. Results Overall, 65%, 87%, 76%, 87% and 97% of patients using the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods obeyed the concept that AAR size is ≥IS. In patients with transmural infarcts (n=22), Bland-Altman analysis showed poor agreement (wide 95% limits of agreement) between AAR size and IS for the BARI, Aldrich and APPROACH methods (95% CI -22.9 to 29.6, 95% CI -28.3 to 21.3 and 95% CI -16.9 to 20.0, respectively) and better agreement for T2-weighted hyperintensity and ESA (95% CI -6.9 to 16.6 and 95% CI -4.3 to 18.0, respectively). Increasing correlation between AAR size and IS with increasing infarct transmurality was observed for the APPROACH, T2-weighted hyperintensity and ESA methods, with ESA having the highest correlation (r=0.93, p<0.001). The percentage of patients within a narrow margin (±30%) of the inverse line of identity between salvage extent and infarct transmurality was 56%, 76%, 65%, 77% and 92% for the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods, respectively, where higher percentages represent better concordance with the concept that the extent of salvage should be inversely related to infarct transmurality. Conclusions For measuring AAR, cardiovascular magnetic resonance methods are better than angiographic methods, which are better than electrocardiographic methods. Overall, ESA performed best for measuring AAR in vivo.

The extent of coronary atherosclerosis is associated with increasing circulating levels of high sensitive cardiac troponin T.

OBJECTIVE: This study explored the relationship between coronary atherosclerotic plaque burden and quantifiable circulating levels of troponin measured with a recently introduced high sensitive cardiac troponin T (hs-cTnT) assay. METHODS AND RESULTS: Cardiac patients suspected of having coronary artery disease (CAD) but without acute coronary syndrome were studied. Cardiac troponin T levels were assessed using the fifth-generation hs-cTnT assay. All patients (n=615) underwent cardiac computed tomographic angiography (CCTA). On the basis of CCTA, patients were classified as having no CAD or mild (<50% lesion), moderate (50% to 70% lesion), severe (>70% lesion), or multivessel CAD (multiple >70% lesions). As a comparison, high-sensitivity C-reactive protein levels were measured. Progressively increasing hs-cTnT levels were found in patients with mild (median, 4.5 ng/L), moderate (median, 5.5 ng/L), severe (median, 5.7 ng/L), and multivessel (median, 8.6 ng/L) CAD compared with patients without CAD (median, 3.7 ng/L) (all P<0.01). For high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide, no such relationship was observed. In patients without CAD, 11% showed hs-cTnT levels in the highest quartile, compared with 62% in the multivessel disease group (P<0.05). Multivariance analysis identified hs-cTnT as an independent risk factor for the presence of CAD. CONCLUSIONS: In patients without acute coronary syndrome, even mild CAD is associated with quantifiable circulating levels of hs-cTnT.

Noninvasive assessment of arterial stiffness should discriminate between systolic and diastolic pressure ranges.

Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases. The intrinsically nonlinear (ie, pressure-dependent) elastic behavior of arteries may have serious consequences for the accuracy and interpretation of arterial stiffness measurements and, ultimately, for individual patient management. We determined aortic pressure and common carotid artery diameter waveforms in 21 patients undergoing cardiac catheterization. The individual pressure-area curves were described using a dual exponential analytic model facilitating noise-free calculation of incremental pulse wave velocity. In addition, compliance coefficients were calculated separately in the diastolic and systolic pressure ranges, only using diastolic, dicrotic notch, and systolic data points, which can be determined noninvasively. Pulse wave velocity at systolic pressure exhibited a much stronger positive correlation with pulse pressure (P<0.001) and age (P=0.012) than pulse wave velocity at diastolic pressure. Patients with an elevated systolic blood pressure (>140 mm Hg) had a 2.5-times lower compliance coefficient in the systolic pressure range than patients with systolic blood pressures <140 mm Hg (P=0.002). Most importantly, some individuals, with comparable age or pulse pressure, had similar diastolic but discriminately different systolic pulse wave velocities and compliance coefficients. We conclude that noninvasive assessment of arterial stiffness could and should discriminate between systolic and diastolic pressure ranges to more precisely characterize arterial function in individual patients.

Molecular imaging of macrophage cell death for the assessment of plaque vulnerability.

The ability to identify atherosclerotic plaques that are prone to rupture, also called vulnerable plaques, may provide a major step forward in the recognition of patients that have a high risk of developing acute myocardial infarction. Current clinical risk profiling algorithms, such as the Framingham and Procam risk scores, have reasonable predictive value in the assessment of the 10 year risk. These clinical risk profiling scores typically classify patients into low risk (10-year risk, less than 5%), intermediate risk (5% to 20% risk), and high risk (greater than 20%). The challenge to imagers is to identify the risk that is beyond 2% yearly risk. Molecular imaging may help identify plaque inflammation and apoptosis of inflammatory cells, which are obligatory components of the plaque instability. These processes offer specific biological targets that can potentially be exploited to obtain biological information on atherosclerosis development in the individual patient.