Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

Background

Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored.

Methods

From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.

Results

Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06).

Conclusion

For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis.     

The complex biology and contribution of Staphylococcus aureus in atopic dermatitis,current and future therapies

Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of U.K. children and is a major cause of occupation‐related disability. A subset of patients, particularly those with severe AD, are persistently colonized with Staphylococcus aureus and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitization, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection. Staphylococcus aureus generates exoproteins that enable invasion and dissemination within the host skin but can also damage the skin and activate the host immune system. Antibiotics are often used by dermatologists to aid clearance of S. aureus; however, these are becoming less effective and chronic usage is discouraged with the emergence of multiple antibiotic‐resistant strains. New ways to target S. aureus using monoclonal antibodies and vaccines are now being developed. This review will attempt to evaluate the key biology of S. aureus, current treatment of S. aureus infections in AD and recent advances in developing new anti‐S. aureus therapies that have potential in severe AD.     

Pulmonary disorders and exercise

The respiratory system rarely limits exercise in the normal subject. In patients with chronic pulmonary processes or in the elite athlete, however, the respiratory system may indeed be the limiting factor. Common respiratory disorders include chest pain syndromes, cough, exercise-induced asthma, and vocal cord dysfunction. Chronic lung diseases such as asthma, COPD, and interstitial lung disease impact exercise capacity and endurance. Exercise testing can be useful to distinguish acute and chronic pulmonary causes of dyspnea during exercise, as well as to differentiate between cardiac and pulmonary causes.     

Rationale and design of the ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) trial

BackgroundCoronary CT angiography (CTA) has emerged as an effective noninvasive method for direct visualization of the coronary arteries, with high diagnostic performance compared with invasive coronary angiography (ICA). However, coronary CTA is prone to artifacts, including coronary motion, which may reduce its diagnostic performance. Intracycle motion compensation algorithms (MCAs) from a combination of software and hardware techniques now allow for correction of coronary motion, but the diagnostic performance of MCAs compared with traditional coronary CTA reconstruction methods remains unexplored.MethodsViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) is a prospective international multicenter trial of 218 patients which is designed to evaluate the performance of MCAs for the diagnosis of anatomically obstructive coronary artery disease (CAD) compared with an ICA reference standard, on a per-patient, per-vessel, and per-segment basis. Patients enrolled into ViCTORY will undergo investigational coronary CTA and clinically indicated ICA and will not receive heart rate-lowering medications before coronary CTA. Coronary CTA images will be reconstructed by conventional standard methods as well as by MCAs. Blinded core laboratory interpretation will be performed for coronary CTA and ICA in an intent-to-diagnose fashion.ResultsThe primary end point of ViCTORY is the per-patient diagnostic accuracy of MCAs for the diagnosis of anatomically obstructive CAD compared with ICA. Secondary end points will include other per-patient, per-vessel, and per-segment diagnostic performance characteristics, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Other key secondary end points will include diagnostic interpretability, image quality, the upper heart rate threshold of utility of MCAs, and the additive value of MCAs to traditionally reconstructed coronary CTA.ConclusionViCTORY will determine whether MCAs improve the diagnosis of obstructive CAD in patients undergoing coronary CTA who are not receiving heart rate-lowering medications.     

Submillisievert coronary computed tomography angiography using adaptive statistical iterative reconstruction �C a new reality

Coronary computed tomography angiography (CCTA) is becoming an increasingly robust tool in the assessment and exclusion of coronary artery disease. Multiple recent studies have raised concerns regarding the radiation dose exposure of CCTA. A novel approach to dose reduction in CCTA using adaptive statistical iterative reconstruction, resulting in a submillisievert CCTA examination, is described. To the authors’ knowledge, the present report describes the first submillisievert study performed in Canada. The ability to perform a diagnostic CCTA with such a low dose challenges the role of coronary calcium scoring and will likely have implications for the future use of this test.