Amit Pursnani

Guideline-Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events

IMPORTANCE The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. However, it is unclear whether this approach improves identification of adults at higher risk of cardiovascular events. OBJECTIVE To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the National Cholesterol Education Programs 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines. DESIGN, SETTING, AND PARTICIPANTS Longitudinal community-based cohort study, with participants for this investigation drawn from the offspring and third-generation cohorts of the Framingham Heart Study. Participants underwent multidetector computed tomography for CAC between 2002 and 2005 and were followed up for a median of 9.4 years for incident CVD. EXPOSURES Statin eligibility was determined based on Framingham risk factors and low-density lipoprotein thresholds for ATP III, whereas the pooled cohort calculator was used for ACC/AHA. MAIN OUTCOMES AND MEASURES The primary outcome was incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke). Secondary outcomes were CHD and CAC (as measured by the Agatston score). RESULTS Among 2435 statin-naive participants (mean age, 51.3 [SD, 8.6] years; 56% female), 39% (941/2435) were statin eligible by ACC/AHA compared with 14% (348/2435) by ATP III (P < .001). There were 74 incident CVD events (40 nonfatal myocardial infarctions, 31 nonfatal ischemic strokes, and 3 fatal CHD events). Participants who were statin eligible by ACC/AHA had increased hazard ratios for incident CVD compared with those eligible by ATP III: 6.8 (95% CI, 3.8-11.9) vs 3.1 (95% CI, 1.9-5.0), respectively (P<.001). Similar results were seen for CVD in participants with intermediate Framingham Risk Scores and for CHD. Participants who were newly statin eligible (n = 593 [24%]) had an incident CVD rate of 5.7%, yielding a number needed to treat of 39 to 58. Participants with CAC were more likely to be statin eligible by ACC/AHA than by ATP III: CAC score >0 (n = 1015): 63% vs 23%; CAC score >100 (n = 376): 80% vs 32%; and CAC score >300 (n = 186): 85% vs 34% (all P < .001). A CAC score of 0 identified a low-risk group among ACC/AHA statin-eligible participants (306/941 [33%]) with a CVD rate of 1.6%. CONCLUSIONS AND RELEVANCE In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.

High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial

PURPOSE To determine the association between nonalcoholic fatty liver disease (NAFLD) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. MATERIALS AND METHODS This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT, II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (≥50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD, univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD, traditional risk factors, and extent of coronary atherosclerosis as independent variables. RESULTS Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD. High-risk plaque was more frequent in patients with NAFLD than in patients without NAFLD (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. CONCLUSION NAFLD is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease.

Use of Coronary Artery Calcium Scanning Beyond Coronary Computed Tomographic Angiography in the Emergency Department Evaluation for Acute Chest Pain The ROMICAT II Trial

Background—Whether a coronary artery calcium (CAC) scan provides added value to coronary computed tomographic angiography (CCTA) in emergency department patients with acute chest pain remains unsettled. We sought to determine the value of CAC scan in patients with acute chest pain undergoing CCTA. Methods and Results—In the multicenter Rule Out Myocardial Infarction using Computer-Assisted Tomography (ROMICAT) II trial, we enrolled low-intermediate risk emergency department patients with symptoms suggesting acute coronary syndrome (ACS). In this prespecified subanalysis of 473 patients (54±8 years, 53% men) who underwent both CAC scanning and CCTA, the ACS rate was 8%. Overall, 53% of patients had CAC=0 of whom 2 (0.8%) developed ACS, whereas 7% had CAC>400 with 49% whom developed ACS. C-statistic of CAC>0 was 0.76, whereas that using the optimal cut point of CAC≥22 was 0.81. Continuous CAC score had lower discriminatory capacity than CCTA (c-statistic, 0.86 versus 0.92; P=0.03). Compared with CCTA alone, there was no benefit combining CAC score with CCTA (c-statistic, 0.93; P=0.88) or with selective CCTA strategies after initial CAC>0 or optimal cut point CAC≥22 (P≥0.09). Mean radiation dose from CAC acquisition was 1.4±0.7 mSv. Higher CAC scores resulted in more nondiagnostic CCTA studies although the majority remained interpretable. Conclusions—In emergency department patients with acute chest pain, CAC score does not provide incremental value beyond CCTA for ACS diagnosis. CAC=0 does not exclude ACS, nor a high CAC score preclude interpretation of CCTA in most patients. Thus, CAC results should not influence the decision to proceed with CCTA, and the decision to perform a CAC scan should be balanced with the additional radiation exposure required. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01084239.

Effect of the 2010 task force criteria on reclassification of cardiovascular magnetic resonance criteria for arrhythmogenic right ventricular cardiomyopathy

BackgroundWe sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation.Methods968 consecutive patients referred to our institution for CMR with clinical suspicion of ARVC from 1995 to 2010, were evaluated for the presence of major and minor CMR criteria per the 1994 and 2010 ARVC TFC. CMR criteria included right ventricle (RV) dilatation, reduced RV ejection fraction, RV aneurysm, or regional RV wall motion abnormalities. When quantitative measures of RV size and function were not available, and in whom abnormal size or function was reported, a repeat quantitative analysis by 2 qualified CMR physicians in consensus.ResultsOf 968 patients, 220 (22.7%) fulfilled either a major or a minor 1994 TFC, and 25 (2.6%) fulfilled any of the 2010 TFC criterion. Among patients meeting any 1994 criteria, only 25 (11.4%) met at least one 2010 criterion. All patients who fulfilled a 2010 criteria also satisfied at least one 1994 criterion. Per the 2010 TFC, 21 (2.2%) patients met major criteria and 4 (0.4%) patients fulfilled at least one minor criterion. Eight patients meeting 1994 minor criteria were reclassified as satisfying 2010 major criteria, while 4 patients fulfilling 1994 major criteria were reclassified to only minor or no criteria under the 2010 TFC.Eighty-nine (9.2%) patients had alternative cardiac diagnoses, including 43 (4.4%) with clinically significant potential ARVC mimics. These included cardiac sarcoidosis, RV volume overload conditions, and other cardiomyopathies.ConclusionsApplication of the 2010 TFC resulted in reduction of total patients meeting any diagnostic CMR criteria for ARVC from 22.7% to 2.6% versus the 1994 TFC. CMR identified alternative cardiac diagnoses in 9.2% of patients, and 4.4% of the diagnoses were potential mimics of ARVC.

Early Resting Myocardial Computed Tomography Perfusion for the Detection of Acute Coronary Syndrome in Patients With Coronary Artery Disease

Background—Acute rest single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has high predictive value for acute coronary syndrome (ACS) in emergency department patients. Prior studies have shown excellent agreement between rest/stress computed tomography perfusion (CTP) and SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains unclear. We sought to determine the diagnostic accuracy of early rCTP, incremental value beyond obstructive coronary artery disease (CAD; ≥50% stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD presenting with suspicion of ACS to the emergency department. Methods and Results—In this prespecified subanalysis of 183 patients (58.1±10.2 years; 33% women), we included patients with any CAD by coronary computed tomography angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted Tomography I. rCTP was assessed semiquantitatively, blinded to CAD interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%–67%) and 78% (95% CI, 71%–85%), respectively. rCTP predicted ACS (adjusted odds ratio, 3.40 [95% CI, 1.37–8.42]; P=0.008) independently of obstructive CAD, and sensitivity for ACS increased from 77% (95% CI, 59%–90%) for obstructive CAD to 90% (95% CI, 74%–98%) with addition of rCTP (P=0.05). In a subgroup undergoing late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P=0.64) using a noninferiority margin of 10%. Conclusions—Early rCTP provides incremental value beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI to discriminate ACS and presents an attractive alternative to triage patients presenting with acute chest pain. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990262.

The 2013 ACC/AHA cardiovascular prevention guidelines improve alignment of statin therapy with coronary atherosclerosis as detected by coronary computed tomography angiography

The recently released 2013 ACC/AHA guidelines for management of blood cholesterol have substantially increased the number of adults who are eligible for preventive statin therapy. We sought to determine whether eligibility for statin therapy as determined by the 2013 ACC/AHA guideline recommendation is better aligned with the actual presence of coronary artery disease (CAD) as detected by coronary CT angiography (CCTA) when compared to prior guidelines including the 2004 NCEP ATP III and 2011 ESC/EAS guidelines. In this secondary analysis of the prospective observational ROMICAT I (Rule Out Myocardial Infarction with Computer Assisted Tomography) cohort study, we included all men and women aged 40-79 years presenting with acute chest pain but not diagnosed with acute coronary syndrome nor on admission statin. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy by the 2013 ACC/AHA, the 2004 NCEP ATP III, and the 2011 ESC/EAS guidelines. We determined the presence and severity of CAD as detected by CCTA. The 2013 ACC/AHA algorithm identified nearly twice as many individuals as eligible for statins (n = 77/189; 41%) as compared to the 2004 ATP III criteria: (n = 41/189; 22%), (p < .0001) In addition, the 2013 ACC/AHA guidelines were more sensitive for treatment of CCTA-detected CAD than the 2004 ATP III guidelines [53.4% (42.5-64.1) vs 27.3% (18.3-37.8), p < .001] and the 2011 ESC/EAE guidelines [53.4% (42.5-64.1) vs 34.1% (24.3-45.0), p < .001]. However, the specificity of these guidelines was modestly reduced compared to the 2004 ATP III guidelines [70.3 (60.4-79.0) vs 83.2 (74.4-89.9), p < .001] and the 2011 ESC/EAE guidelines [70.3 (60.4-79.0) vs 86.1 (77.8-92.2), p < .001], suggesting increased treatment of subjects without CCTA-detected CAD. Overall, the 2013 ACC/AHA guidelines are more sensitive to identify patients who have CAD detected by CCTA eligible for statin therapy as compared with prior guidelines, with an acceptable trade-off in specificity for recommending statin therapy in those without CAD.

Potential for coronary CT angiography to tailor medical therapy beyond preventive guideline-based recommendations: Insights from the ROMICAT I trial

BACKGROUND Coronary CT angiography (CCTA) is used in the emergency department to rule out acute coronary syndrome in low-intermediate risk patients. OBJECTIVES We evaluated the potential of CCTA to tailor aspirin (ASA) and statin therapy in acute chest pain patients. METHODS We included all patients in the ROMICAT I trial who underwent CCTA before admission. Results of CCTA were blinded to caretakers. We documented ASA and statin therapy at admission and discharge and determined change in medications during hospitalization, agreement of discharge medications with contemporaneous guidelines, and agreement with the presence and severity of coronary artery disease (CAD) as determined by CCTA. RESULTS We included 368 patients (53 ± 12 years; 61% male). Baseline medical therapy at presentation included 27% on ASA and 24% on statin. Most patients who qualified for secondary prevention were on ASA and statin therapy at discharge (95% and 80%, respectively), whereas among those qualifying for primary prevention therapy, only 59% of patients were on aspirin and 33% were on statin at discharge. Excluding secondary prevention patients, among those with CCTA-detected CAD, only 66/131 (50%) were on ASA at discharge and only 53/131 (40%) were on statin. Conversely, in those without CCTA-detected CAD, 54/156 (35%) were on ASA and 20/151 (13%) were on statin at discharge. CONCLUSION There are significant discrepancies between discharge prescription of statin and ASA with the presence and extent of CAD. CCTA presents an efficient opportunity to tailor medical therapy to CAD in patients undergoing CCTA as part of their acute chest pain evaluation.

Detection of Cardiac Toxicity Due to Cancer Treatment: Role of Cardiac MRI

Opinion statementCommon cancer treatments including anthracycline-based chemotherapy, tyrosine kinase inhibitors, and thoracic radiation therapy can result in short- and long-term cardiovascular complications with a significant impact on morbidity and mortality. Anthracycline-based chemotherapy and tyrosine kinase inhibitors are associated with left ventricular systolic dysfunction and heart failure. Radiation therapy is associated with restrictive cardiomyopathy, coronary artery disease, as well as pericardial and valvular disease. The current standard surveillance of oncology patients for cardiotoxicity involves echocardiography, radionuclide cardiac blood pool imaging, and cardiac magnetic resonance (CMR) imaging. CMR can be used to evaluate ventricular structure and function, which is important for management decisions to prevent further cardiac injury. In patients for whom standard surveillance imaging demonstrates a drop in systolic function with or without symptoms, the use of CMR is an appropriate next step for further evaluation due to the accuracy and reproducibility of measurements of function and volumes combined with the additive information provided by tissue characterization through imaging of myocardial edema and myocardial fibrosis, although the clinical applications of these latter are as yet unclear. Overall, detection of early cardiotoxicity is important since therapeutic response is improved with prompt initiation of medical treatment.

Nonobstructive Coronary Artery Disease by Coronary CT Angiography Improves Risk Stratification and Allocation of Statin Therapy

OBJECTIVES This study sought to determine prognostic value of nonobstructive coronary artery disease (CAD) for atherosclerotic cardiovascular disease (ASCVD) events and to determine whether incorporation of this information into the pooled cohort equation reclassifies recommendations for statin therapy as defined by the 2013 guidelines for cholesterol management of the American College of Cardiology and American Heart Association (ACC/AHA). BACKGROUND Detection of nonobstructive CAD by coronary computed tomography angiography may improve risk stratification and permit individualized and more appropriate allocation of statin therapy. METHODS This study determined the pooled hazard ratio of nonobstructive CAD for ASCVD events from published studies and incorporated this information into the ACC/AHA pooled cohort equation. The study calculated revised sex- and ethnicity-based 10-year ASCVD risk and determined boundaries corresponding to the original 7.5% risk for ASCVD events. It also assessed reclassification for statin eligibility by incorporating the results from meta-analysis to individual patients from a separate cohort. RESULTS This study included 2 studies (2,295 subjects; 66% male; prevalence of nonobstructive CAD, 47%; median follow-up, 49 months; 67 ASCVD events). The hazard ratio of nonobstructive CAD for ASCVD events was 3.2 (95% confidence interval: 1.5 to 6.7). Incorporation of this information into the pooled cohort equation resulted in reclassification toward statin eligibility in individuals with nonobstructive CAD, with an original ASCVD score of 3.0% and 5.9% or higher in African-American women and men and a score of 4.4% and 4.6% or higher in Caucasian women and men, respectively. The absence of nonobstructive CAD resulted in reclassification toward statin ineligibility if the original ASCVD score was as 10.0% and 17.9% or lower in African-American women and men and 13.7% and 14.3% or lower in Caucasian women and men, respectively. Reclassification is observed in 14% of patients. CONCLUSIONS Detection of nonobstructive CAD by coronary computed tomography angiography improves risk stratification and permits individualized and more appropriate allocation of statin therapy across sex and ethnicity groups.

Feasibility of a radiation dose conserving CT protocol for myocardial function assessment

OBJECTIVE Assessment of myocardial function can be performed at higher noise levels than necessary for coronary arterial evaluation. We evaluated image quality and radiation exposure of a dose-conserving function-only acquisition vs retrospectively electrocardiogram(ECG)-gated coronary CTA with automatic tube current modulation. METHODS Of 26 patients who underwent clinically indicated coronary CTA for coronary and function evaluation, 13 (Group I) underwent prospectively ECG-triggered coronary CTA, followed by low-dose retrospectively ECG-gated scan for function (128-slice dual-source, 80 kVp; reference tube current, 100 mA; 8-mm-thick multiplanar reformatted reconstructions) performed either immediately (n = 6) or after 5- to 10-min delay for infarct assessment (n = 7). 13 corresponding controls (Group II) underwent retrospectively ECG-gated protocols (automatic tube potential selection with CARE kV/CARE Dose 4D; Siemens Healthcare, Forchheim, Germany) with aggressive dose modulation. Image quality assessment was performed on the six Group I subjects who underwent early post-contrast dedicated function scan and corresponding controls. Radiation exposure was based on dose-length product. RESULTS Contrast-to-noise ratio (CNR) was preserved throughout the cardiac cycle in Group I and varied according to dose modulation in Group II. Visual image quality indices were similar during end systole but were better in Group II at end diastole. Although the total radiation exposure was equivalent in Group I and Group II (284 vs 280 mGy cm), the median radiation exposure associated with only the dedicated function scan was 138 mGy cm (interquartile range, 116-203 mGy cm). CONCLUSION A low-dose retrospective ECG-gated protocol permits assessment of myocardial function at a median radiation exposure of 138 mGy cm and offers more consistent multiphase CNR vs traditional ECG-modulation protocols. This is useful for pure functional evaluation or as an adjunct to single-phase scan modes. ADVANCES IN KNOWLEDGE Radiation exposure can be limited with a tailored myocardial function CT protocol while maintaining preserved images.