Gary R. Small

Prognostic and Therapeutic Implications of Statin and Aspirin Therapy in Individuals With Nonobstructive Coronary Artery Disease Results From the CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter Registry) Registry

Objective— We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Approach and Results— Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%–49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%–12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28–0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19–0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30–1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. Conclusions— The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD. Clinical Trial Registration— URL: http://clinicaltrials.gov/. Unique identifier NCT01443637

Prognostic Value of Rubidium-82 Positron Emission Tomography in Patients After Heart Transplant

Background—Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. Methods and Results—Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. Conclusions—Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

The Prognostic Value of Rb-82 Positron Emission Tomography in Patients Following Heart Transplant

Background—Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. Methods and Results—Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. Conclusions—Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

Prognostic Value of CT Angiography in Coronary Bypass Patients

OBJECTIVES We sought the incremental prognostic value of coronary computed tomography angiography (CTA) in coronary artery bypass graft (CABG) patients. BACKGROUND Coronary CTA is a noninvasive and accurate tool for the detection of obstructive coronary artery disease, and coronary CTA appears to have prognostic value in patients without previous revascularization. However, the prognostic value of coronary CTA to predict major adverse cardiac events in CABG patients is unclear. METHODS Consecutive CABG patients were prospectively enrolled and cardiac risk was calculated using the National Cholesterol Evaluation Program/Adult Treatment Panel III. Using the severity of native coronary artery disease and graft disease, the number of unprotected coronary territories (UCTs) (0, 1, 2, or 3) was calculated. Patients were followed for cardiac death and nonfatal myocardial infarction. All events were confirmed with death certificates or medical records and reviewed by a clinical events committee. RESULTS Between February 2006 and March 2009, 250 consecutive patients were enrolled and followed for a mean of 20.8 ± 10.1 months. At follow-up, 23 patients (9.2%) had major adverse cardiac events (15 cardiac deaths and 8 nonfatal MI). The absence of UCTs conferred a good prognosis with an annual event rate of 2.4%. Conversely, patients with 1, 2, and 3 UCTs had annualized event rates of 5.8%, 11.1%, and 21.7%, respectively. Multivariable analysis showed that UCTs (hazard ratio: 2.08; 95% confidence interval: 1.40 to 3.10; p < 0.001) was a predictor of major adverse cardiac events when adjusted for clinical variables. Examining the receiver-operator characteristic curves, the area under the curve increased from 0.61 to 0.76 when UCTs was combined with clinical variables (p = 0.001). CONCLUSIONS Assessing UCTs with coronary CTA appears to have prognostic value in CABG patients and is incremental to clinical variables. Coronary CTA appears to be a promising tool for risk stratification of CABG patients. Further multicenter studies using large CABG cohorts are needed to confirm our findings.

Quantifying coronary artery calcification from a contrast-enhanced cardiac computed tomography angiography study

AIMS We sought to quantify coronary artery calcium (CAC) using a single contrast-enhanced cardiac computed tomography angiography (CCTA) study. CCTA has been successfully used for the assessment of coronary artery stenoses, whereas non-contrast ECG-gated computed tomography (Standard-CAC) is commonly performed to quantify CAC. Thus each scan individually contributes to the total radiation dose. METHODS RESULTS Patients who underwent both Standard-CAC and CCTA scans were identified. Standard-CAC images were scored using the Agatston method. CCTA scans were scored for CAC (CCTA-CAC), whereby CAC was defined as plaque with attenuation 2 SD above the mean attenuation value of the ascending aorta (HU(aorta)). The correlation between Standard-CAC and CCTA-CAC was determined with the slope used to derive a correction factor for the conversion of CCTA-CAC results to a Standard-CAC Agatston score (AS). To test applicability, the correction factor was assessed in a separate validation cohort of similar demographics. From April 2011 to June 2012, a derivation cohort of 92 patients was identified and analysed. An additional 47 patients were identified for the validation cohort. Correlation between Standard-CAC and CCTA-CAC was excellent (r = 0.96). The slope (y = 2.74 × CCTA-CAC score) derived correction factor from the derivation cohort was used to adjust CCTA-CAC derived scores to an AS (CCTA-CAC(corrected) = 2.74 × CCTA-CAC). The correction factor was applied to the validation cohort CCTA-CAC results with excellent agreement between CCTA-CAC(corrected) and Standard-CAC (kappa = 0.93). CONCLUSIONS Quantification of CAC from a single contrast-enhanced CCTA scan is feasible and correlates well with Standard-CAC. Larger, multicentre studies are needed to validate the universal applicability of CAC quantified using CCTA.

Prognostic Assessment of Coronary Artery Bypass Patients With 64-Slice Computed Tomography Angiography: Anatomical Information Is Incremental to Clinical Risk Prediction

OBJECTIVES We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass graft (CABG) patients. BACKGROUND Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency might provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown. METHODS Six hundred fifty-seven CABG patients with all-cause mortality follow-up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centers. Clinical risk was profiled with modified logistic and additive EuroSCOREs (European Systems for Cardiac Operative Risk Evaluations). The CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT) or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS). RESULTS Forty-four deaths occurred during a mean follow-up of 20 months. Left ventricular ejection fraction, creatinine, age, severity of native vessel disease, UCT, CAPS, and EuroSCOREs were univariate predictors of mortality (p < 0.001). In multivariate analysis with additive EuroSCORE, UCT (p = 0.004) and CAPS were predictive of events (p < 0.001). In comparison with additive EuroSCORE, CAPS score was associated with a 27% net reclassification index. CONCLUSIONS Coronary computed tomography angiography provides incremental anatomical data to clinical risk assessment to help determine the prognosis of patients after CABG. The CAPS evaluation with CCTA might help identify those patients at highest risk.

Advances in Cardiac SPECT and PET Imaging: Overcoming the Challenges to Reduce Radiation Exposure and Improve Accuracy

Nuclear cardiology came of age in the 1970s and subsequently has expanded so that more than 9 million single-photon emission computed tomography (SPECT) studies are performed annually in North America. Coronary artery disease management has demanded a reliable technique that will detect, risk stratify, and assist with revascularization decisions. Using cardiac SPECT and positron-emission tomography (PET), researchers and clinicians have sought to achieve excellence in coronary artery disease diagnosis and risk stratification, and strive to achieve higher standards in these areas. Developments in other cardiac imaging modalities, however, such as cardiac computed tomography, cardiac magnetic resonance, and echocardiography, have raised expectations in terms of diagnostic accuracy and achieving high quality images with little or no ionizing radiation exposure. The challenge facing nuclear cardiology as it embarks upon a fifth decade of clinical use is whether high quality images can be obtained at lower radiation exposures. In this review we consider current practice in SPECT and PET perfusion imaging. We discuss emerging advances in techniques, technologies, and radiotracers that focus specifically on improvements in image quality that enhance diagnostic accuracy while reducing radiation exposure. We provide a perspective as to the future roles of cardiac SPECT and PET in ischemic heart disease, and consider emerging novel applications beyond perfusion imaging. Although for a number of years nuclear cardiology has shone brightly as a leading light for the imaging of ischemic heart disease, its half-life has not yet been reached. Instead, even with the pressure to reduce radiation exposure, the future continues to look bright for cardiac SPECT and PET.

Established and emerging dose reduction methods in cardiac computed tomography

Cardiac computed tomography (CT) is a non-invasive modality that is commonly used as an alternative to invasive coronary angiography for the investigation of coronary artery disease. The enthusiasm for this technology has been tempered by a growing appreciation of the potential risks of malignancy associated with the use of ionising radiation. In the spirit of minimizing patient risk, the medical profession and industry have worked hard to developed methods and protocols to reduce patient radiation exposure while maintaining excellent diagnostic accuracy. A complete understanding of radiation reduction techniques will allow clinicians to reduce patient risk while providing an important diagnostic service. This review will consider the established and emerging techniques that may be adopted to reduce patient absorbed doses from x-ray CT. By modifying (1) x-ray tube output, (2) imaging time (scan duration), (3) imaging distance (scan length) and (4) the appropriate use of shielding, clinicians will be able to adhere to the ‘as low as reasonably achievable (ALARA)’ principle.

Low-dose cardiac imaging: reducing exposure but not accuracy.

Cardiac imaging techniques that use ionizing radiation have become an integral part of current cardiology practice. However, concern has arisen that ionizing radiation exposure, even at the low levels used for medical imaging, is associated with the risk of cancer. From a single diagnostic cardiac imaging procedure, such risks are low. On a population basis, however, malignancies become more likely on account of stochastic effects being more probable as the number of procedures performed increases. In light of this, and owing to professional and industrial commitment to the as low as reasonably achievable (ALARA) principle, over the last decade major strides have been made to reduce radiation dose in cardiac imaging. Dose-reduction strategies have been most pronounced in cardiac computed tomography. This was important since computed tomography has rapidly become a widely used diagnostic alternative to invasive coronary angiography, and initial protocols were associated with relatively high radiation exposures. Advances have also been made in nuclear cardiology and in invasive coronary angiography, and these reductions in patient exposure have all been achieved with maintenance of image quality and accuracy. Improvements in imaging camera technology, image acquisition protocols and image processing have lead to reductions in patient radiation exposure without compromising imaging diagnostic accuracy.

A single slice measure of epicardial adipose tissue can serve as an indirect measure of total epicardial adipose tissue burden and is associated with obstructive coronary artery disease.

AIMS To evaluate the practical use of the single slice measurement of epicardial adipose tissue (EAT) at the level of the left main coronary artery (EATLM) in predicting the presence of obstructive coronary artery disease (CAD). METHODS AND RESULTS Quantification of EATTotal and EATLM was performed on non-contrast CT scans of consecutive patients (without history of revascularization, cardiac transplantation, device implantation, and congenital heart disease) who underwent coronary artery calcium (CAC) scoring and computed tomographic coronary angiography (CTA) between May 2011 and July 2011. One hundred and ninety-two patients were evaluated, of which 47 had obstructive CAD (>50% stenosis). EATLM (3.8 ± 2.2 cm(3)) and EATTotal (126.2 ± 56.3 cm(3)) are highly correlated (r = 0.89, P < 0.001). Multivariate analysis revealed that both EATLM (OR: 1.204 per 1 cm(3), 95% CI: 1.028-1.411, P = 0.021) and EATTotal (OR: 1.007 per 10 cm(3), 95% CI: 1.000-1.013, P = 0.038) are associated with obstructive CAD. However, when the CAC score was added to multivariate analysis, both failed to show statistical significance. (EATTotal, OR 1.004 per 1 cm(3), 95% CI: 0.996-1.011, P = 0.328 and EATLM, OR: 1.136 per 10 cm(3), 95% CI: 0.948-1.362) ROC curve analysis revealed that both EATTotal and EATLM are of incremental value in detecting CAD, when compared with clinical risk scores (NCEP plus EATTotal plus BMI and NCEP plus EATLM plus BMI vs. NCEP alone; AUC 0.7090, P = 0.009 and 0.7167, P = 0.003 vs. 0.6069, respectively). CONCLUSION Measuring epicardial adipose tissue on a single slice at the level of the left main coronary artery may serve as an indirect measure of total epicardial adipose tissue burden. EATLM and EATTotal are independently associated with obstructive coronary artery disease and are incremental to traditional risk factors for predicting its presence.