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Aims: The aim of this study was to describe the prognostic importance of left ventricular ejection fraction (LVEF) versus right ventricular (RV) dilatation and dysfunction in patients with heart failure (HF) from countries of different income levels., Methods and Results: We enrolled 17 321 participants with HF from 40 countries. Participants were followed for a median (25th-75th percentile) of 2.1 (2.0-4.6) years. Cox proportional hazards models were performed with adjustment for age, sex, HF aetiology, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, tobacco and alcohol use, functional class, and the use of HF medications, blood pressure, serum creatinine and HF duration. During follow-up, 5738 (33%) participants died and 3569 (21%) were hospitalized for HF. Compared with LVEF ≥50%, the hazard ratios (HR) for death were 0.88 (95% confidence interval [CI] 0.80-0.97, p = 0.009) in patients with LVEF 40-49%, 0.96 (95% CI 0.88-1.05, p = 0.40) for LVEF 30-39%, and 1.18 (95% CI 1.08-1.29, p < 0.0001) for LVEF <30%. RV enlargement was associated with an increased risk of death (HR 1.35, 95% CI 1.26-1.44, p < 0.0001). The relationship between LVEF and death differed according to HF aetiology (interaction p = 0.0010). In ischaemic HF and idiopathic dilated cardiomyopathy, there was a continuous inverse association between LVEF and the risk of death, but in hypertensive, valvular and other HF types, there was no association between LVEF and the risk of mortality., Conclusion: Reduced LVEF was associated with worse prognosis in ischaemic and idiopathic dilated cardiomyopathy but not in HF of other causes. RV enlargement was associated with a more marked increase in the risk of death., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Causes for sudden circulatory arrest (SCA) can vary widely making early treatment and triage decisions challenging. Additionally, cardiopulmonary resuscitation (CPR), while a life-saving link in the chain of survival, can be associated with traumatic injuries. Computed tomography (CT) can identify many causes of SCA as well as its sequelae. However, the diagnostic and therapeutic impact of CT in survivors of SCA has not been reviewed to date. This general review outlines the rationale and potential applications of focused head, chest, and abdomen/pelvis CT as well as comprehensive head-to-pelvis CT imaging after SCA. CT has a diagnostic yield approaching 30% to identify causes of SCA while the addition of ECG-gated chest CT provides further information about coronary anatomy and cardiac function. Risks of CT include radiation exposure, contrast-induced kidney injury, and incidental findings. This review's findings suggest that routine head-to-pelvis CT can yield clinically actional findings with the potential to improve clinical outcome after SCA that merits further investigation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Kelley Branch reports a relationship with Bayer AG that includes: consulting or advisory, funding grants, and travel reimbursement. Kelley Branch reports a relationship with Sanofi that includes: funding grants. Kelley Branch reports a relationship with Eli Lilly and Company that includes: funding grants. Kelley Branch reports a relationship with Kestra Medical Technologies Inc that includes: funding grants. Kelley Branch reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory.’., (Copyright © 2023. Published by Elsevier B.V.)

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries., Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development., Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years., Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death., Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies., Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H 2 receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large-scale WHI (Women's Health Initiative) study. Methods and Results This study included postmenopausal women from the WHI without a history of HF at baseline. HF was defined as first incident hospitalization for HF and physician adjudicated. Multivariable Cox proportional hazards regression models evaluated the association of H2RA use as a time-varying exposure with HF risk, after adjustment for demographic, lifestyle, and medical history variables. Sensitivity analyses examined (1) risk of HF stratified by the ARIC (Atherosclerosis Risk in Communities) score, (2) propensity score matching on H2RA use, (3) use of proton pump inhibitors rather than H2RA nonuse as the referent, and (4) exclusion of those taking diuretics at baseline. The primary analysis included 158 854 women after exclusion criteria, of whom 9757 (6.1%) were H2RA users. During median 8.2 years of follow-up, 376 H2RA users (4.9 events/1000 person-years) and 3206 nonusers (2.7 events/1000 person-years) developed incident HF. After multivariable adjustment, there was no association between H2RA use and HF in the primary analysis (hazard ratio, 1.07; 95% CI, 0.94-1.22; P =0.31) or in any of the sensitivity analyses. Conclusions Clinical H2RA use was not associated with incident HF among postmenopausal women. Future studies are needed to evaluate potential effect modification by sex, HF severity, or patterns of use on H2RA exposure and HF risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000611.

Background: The REWIND trial demonstrated cardiovascular (CV) benefits to patients with type 2 diabetes and multiple CV risk factors or established CV disease. This exploratory analysis evaluated the degree to which the effect of dulaglutide on CV risk factors could statistically account for its effects on major adverse cardiovascular events (MACE) in the REWIND trial., Methods: Potential mediators of established CV risk factors that were significantly reduced by dulaglutide were assessed in a post hoc analysis using repeated measures mixed models and included glycated hemoglobin (HbA1c), body weight, waist-to-hip ratio, systolic blood pressure, low-density lipoprotein (LDL), and urine albumin/creatinine ratio (UACR). These factors, for which the change in level during follow-up was significantly associated with incident MACE, were identified using Cox regression modeling. Each identified variable was then included as a covariate in the Cox model assessing the effect of dulaglutide on MACE to estimate the degree to which the hazard ratio of dulaglutide vs placebo was attenuated. The combined effect of the variables associated with attenuation was assessed by including all variables in an additional Cox model., Results: Although all evaluated variables were significantly improved by treatment, only changes in HbA1c and UACR were associated with MACE and a reduction in the effect of dulaglutide on this outcome was observed. The observed hazard ratio for MACE for dulaglutide vs placebo reduced by 36.1% by the updated mean HbA1c, and by 28.5% by the updated mean UACR. A similar pattern was observed for change from baseline in HbA1c and UACR and a reduction of 16.7% and 25.4%, respectively in the hazard ratio for MACE with dulaglutide vs placebo was observed. When HbA1c and UACR were both included, the observed hazard ratio reduced by 65.4% for the updated mean and 41.7% for the change from baseline with no HbA1c-UACR interaction (P interaction = 0.75 and 0.15, respectively)., Conclusions: Treatment-induced improvement in HbA1c and UACR, but not changes in weight, systolic blood pressure, or LDL cholesterol, appear to partly mediate the beneficial effects of dulaglutide on MACE outcomes. These observations suggest that the proven effects of dulaglutide on cardiovascular disease benefit are partially related to changes in glycemic control and albuminuria, with residual unexplained benefit. Clinicaltrials.gov; Trial registration number: NCT01394952. URL: https://clinicaltrials.gov/ct2/show/NCT01394952., (© 2021. The Author(s).)

Background: Previous research assessing medication adherence with P2Y 12 inhibitors has shown good adherence rates, ranging from 78% to 92%. Studies that used administrative claims data defined adherence using an arbitrary cut point of ≥ 80% medication possession ratio (MPR) or proportion of days covered (PDC). While this method is used frequently, it does not allow the researcher to observe how each factor impacts adherence along the entire distribution. The objective of the study was to use conditional quantile regression (CQR) and unconditional quantile regression (UQR) to assess heterogenous effects of adherence to P2Y 12 inhibitors and covariates of interest and compare these results to those from a traditional logistic regression framework., Methods and Results: This study used the commercial claims and encounters databases from IBM ® MarketScan ® from 2010 to 2017. We included patients who had an incident percutaneous coronary intervention, used a drug-eluting stent, and filled an incident prescription for a P2Y 12 inhibitor. Adherence was measured for 185 days using PDC. Adherence to branded clopidogrel, generic clopidogrel, branded prasugrel, and branded ticagrelor was assessed, along with factors that could impact adherence, using logistic regression, CQR, and UQR. We found that while adherence to the antiplatelets was generally high, prasugrel and ticagrelor had significantly lower PDC compared to branded clopidogrel, especially around the 30th percentile. Across all quantiles in both the CRQ and UQR frameworks, comorbidities such as diabetes and depression and living in the southern region had significant negative effects on adherence, although the relative impact differed across quantiles., Conclusions: Using CQR and UQR allowed for heterogenous assessment of covariates along the adherence distribution, which is not possible with the traditional logistic regression method. The UQR framework revealed patients who initiate prasugrel or ticagrelor generally have lower adherence compared to those treated with branded clopidogrel, especially around the 30th quantile. Using these methods in other types of data sets, such as electronic health records, could help strengthen our results to develop policies to improve antiplatelet adherence in a targeted population.

Aim: To test the diagnostic accuracy of ECG-gated coronary computed tomography angiography (CCTA) to detect coronary artery disease (CAD) among survivors of out-of-hospital circulatory arrest (OHCA)., Methods: We prospectively studied head-to-pelvis computed tomography (CT) scanning (<6 h from hospital arrival) in OHCA survivors. This sub-study tested the primary outcome of CCTA diagnostic accuracy to identify obstructive CAD (≥50% stenosis) compared to clinically-ordered invasive coronary angiography. Patients were not optimized with beta receptor blockade or nitroglycerin. Secondary analyses included CCTA accuracy for CAD in major coronary arteries, obstructive disease at ≥70% stenosis threshold, and where non-evaluable CCTA segments were considered either obstructive or non-obstructive., Results: Of the 104 enrolled OHCA survivors, 28 (27%) received both CT and invasive angiography in this sub study. All CCTA studies were evaluable although 49/346 (14%) individual coronary segments were unevaluable, primarily due to being too small to evaluate (65%). Patient-level diagnostic accuracy for the ≥50% stenosis threshold was high at 0.93 (95% CI 0.77-0.98) with a specificity of 1.0 (95% CI 0.8-1.0), sensitivity of 0.85 (95%CI 0.58-0.96), negative predictive value of 0.88 (95% CI 0.66-0.97) and positive predictive value of 1.0 (0.74-1.0). When non-evaluable segments were considered obstructive, the sensitivity rose to 0.92 (95% CI 0.67-0.99) with lower specificity of 0.27 (95% CI 0.11-0.52)., Conclusion: Early CCTA of OHCA survivors has high diagnostic accuracy to detect obstructive coronary artery disease. However, the number of non-diagnostic coronary segments is high suggesting further CCTA refinement is needed, such as the pre-CCTA use of nitroglycerin., Clinical Trial Registration: NCT03111043 https://clinicaltrials.gov/ct2/show/record/NCT03111043., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The COMPASS trial (Cardiovascular Outcomes for People using Anticoagulation Strategies) demonstrated that dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily reduced the primary major adverse cardiovascular event (MACE) outcome of cardiovascular death, myocardial infarction, or stroke, as well as, mortality, in patients with chronic coronary syndromes or peripheral arterial disease. Whether this remains true in patients with a history of percutaneous coronary intervention (PCI) is unknown., Methods: In a prespecified subgroup analysis from COMPASS, we examined the outcomes of patients with chronic coronary syndrome with or without a previous PCI treated with DPI versus aspirin alone. Among patients with a previous PCI, we studied the effects of treatment according to the timing of the previous PCI., Results: Of the 27 395 patients in COMPASS, 16 560 patients with a chronic coronary syndrome were randomly assigned to DPI or aspirin, and, of these, 9862 (59.6%) had previous PCI (mean age 68.2±7.8, female 19.4%, diabetes mellitus 35.7%, previous myocardial infarction 74.8%, multivessel PCI 38.0%). Average time from PCI to randomization was 5.4 years (SD, 4.4) and follow-up was 1.98 (SD, 0.72) years. Regardless of previous PCI, DPI versus aspirin produced consistent reductions in MACE (PCI: 4.0% versus 5.5%; hazard ratio [HR], 0.74 [95% CI, 0.61-0.88]; no PCI: 4.4% versus 5.7%; HR, 0.76 [95% CI, 0.61-0.94], P -interaction=0.85) and mortality (PCI: 2.5% versus 3.5%; HR, 0.73 [95% CI, 0.58-0.92]; no PCI: 4.1% versus 5.0%; HR, 0.80 [95% CI, 0.64-1.00], P -interaction=0.59), but increased major bleeding (PCI: 3.3% versus 2.0%; HR, 1.72 [95% CI, 1.34-2.21]; no PCI: 2.9% versus 1.8%; HR, 1.58 [95% CI, 1.15-2.17], P -interaction=0.68). In those with previous PCI, DPI compared with aspirin produced consistent (robust) reductions in MACE irrespective of time since previous PCI (as early as 1 year and as far as 10 years; P -interaction=0.65), irrespective of having a previous myocardial infarction ( P -interaction=0.64)., Conclusions: DPI compared with aspirin produced consistent reductions in MACE and mortality but with increased major bleeding with or without previous PCI. Among those with previous PCI 1 year and beyond, the effects on MACE and mortality were consistent irrespective of time since last PCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.

Introduction: Coronary CT Angiography (CCTA) is a rapidly increasing technique for coronary imaging; however, it exposes patients to ionising radiation. We examined the impact of dose reduction techniques using ECG-triggering, kVp/mAs reduction and high-pitch modes on radiation exposure in a large Australian tertiary CCTA service., Methods: Data on acquisition modes and dose exposure were prospectively collected on all CCTA scans from November 2009 to March 2014 at an Australian tertiary care centre. A dose reduction algorithm was developed using published techniques and implemented with education of medical staff, radiographers and referrers. Associations of CCTA acquisition to radiation over time were analysed with multivariate regression. Specificity in positive CCTA was assessed by correlation with invasive coronary angiography., Results: 3333 CCTAs were analysed. Mean radiation dose decreased from 8.4 mSv to 5.3, 4.4, 3.7, 2.9 and 2.8 mSv (P < 0.001) per year. Patient characteristics were unchanged. Dose reduction strategies using ECG-triggering, kVp/mAs reduction accounted for 91% of the decrease. High-pitch scanning reduced dose by an additional 9%. Lower dose was independently related to lower kVp, heart rate, tube current modulation, BMI, prospective triggering and high-pitch mode (P < 0.01). CCTA specificity remained unchanged despite dose reduction., Conclusion: Implementation of evidence-based CCTA dose reduction algorithm and staff education programme resulted in a 67% reduction in radiation exposure, while maintaining diagnostic specificity. This approach is widely applicable to clinical practice for the performance of CCTA., (© 2019 The Authors and State of Queensland Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Background: Patients with chronic coronary artery disease or peripheral artery disease and history of heart failure (HF) are at high risk for major adverse cardiovascular events. We explored the effects of rivaroxaban with or without aspirin in these patients., Methods: The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized 27 395 participants with chronic coronary artery disease or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with New York Heart Association functional class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary major adverse cardiovascular events outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified International Society of Thrombosis and Haemostasis criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on major adverse cardiovascular events and major bleeding in patients with or without a history of HF and an EF <40% or ≥40% at baseline., Results: Of the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline, and 12% had EF <40%. Rivaroxaban and aspirin had similar relative reduction in major adverse cardiovascular events compared with aspirin in participants with HF (5.5% versus 7.9%; hazard ratio [HR], 0.68; 95% CI, 0.53-0.86) and those without HF (3.8% versus 4.7%; HR, 0.79; 95% CI, 0.68-0.93; P for interaction 0.28) but larger absolute risk reduction in those with HF (HF absolute risk reduction 2.4%, number needed to treat=42; no HF absolute risk reduction 1.0%, number needed to treat=103). The primary major adverse cardiovascular events outcome was not statistically different between those with EF <40% (HR, 0.88; 95% CI, 0.55-1.42) and ≥40% (HR, 0.81; 95% CI, 0.67-0.98; P for interaction 0.36). The excess hazard for major bleeding was not different in participants with HF (2.5% versus 1.8%; HR, 1.36; 95% CI, 0.88-2.09) than in those without HF (3.3% versus 1.9%; HR, 1.79; 95% CI, 1.45-2.21; P for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone., Conclusions: In patients with chronic coronary artery disease or peripheral artery disease and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits than in those without HF., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Background The accuracy of absolute myocardial blood flow (MBF) from dynamic contrast-enhanced cardiac computed tomography acquisitions has not been fully characterized. We evaluate computed tomography (CT) compared with rubidium-82 positron emission tomography (PET) MBF estimates in a high-risk population. Methods In a prospective trial, patients receiving clinically indicated rubidium-82 PET exams were recruited to receive a dynamic contrast-enhanced cardiac computed tomography exam. The CT protocol included a rest and stress dynamic portion each acquiring 12 to 18 cardiac-gated frames. The global MBF was estimated from the PET and CT exam. Results Thirty-four patients referred for cardiac rest-stress PET were recruited. Of the 68 dynamic contrast-enhanced cardiac computed tomography scans, 5 were excluded because of injection errors or mismatched hemodynamics. The CT-derived global MBF was highly correlated with the PET MBF (r=0.92; P<0.001) with a mean difference of 0.7±26.4%. The CT MBF estimates were within 20% of PET estimates ( P<0.02) with a mean of (1) MBF for resting flow of PET versus CT of 0.9±0.3 versus 1.0±0.2 mL/min per gram and (2) MBF for stress flow of 2.1±0.7 versus 2.0±0.8 mL/min per gram. Myocardial flow reserve was -14±28% underestimated with CT (PET versus CT myocardial flow reserve, 2.5±0.6 versus 2.2±0.6). The proposed rest+stress+computed tomography angiography protocol had a dose length product of 598±76 mGy×cm resulting in an approximate effective dose of 8.4±1.1 mSv. Conclusions In a high-risk clinical population, a clinically practical dynamic contrast-enhanced cardiac computed tomography provided unbiased MBF estimates within 20% of rubidium-82 PET. Although unbiased, the CT estimates contain substantial variance with an standard error of the estimate of 0.44 mL/min per gram. Myocardial flow reserve estimation was not as accurate as individual MBF estimates.

Background: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need., Aims: The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI., Methods: COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study., Results: Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23-28)., Conclusions: The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.

Aim: To review data for non-invasive imaging in the diagnosis of non-traumatic out-of-hospital cardiac arrest (OHCA)., Data Sources: We searched MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov databases from inception to January 2017 for studies utilizing non-invasive imaging to identify potential causes of OHCA [computed tomography (CT), ultrasound including echocardiography, and magnetic resonance (MRI)]., Study Selection: Inclusion criteria were the following: (1) randomized control trials, cohort studies or observational studies; (2) contained a population ≥18 years old with non-traumatic OHCA who underwent diagnostic imaging with CT, MRI, echocardiography, or abdominal ultrasound; (3) imaging was obtained for diagnostic purposes; (4) patients were alive or were undergoing cardiopulmonary resuscitation at the time of imaging; (5) contained potential causes of OHCA. Endpoints studied were the number of potential OHCA causes identified, diagnostic accuracy measures (sensitivity, specificity, positive and negative predictive values), and diagnostic utility (number of imaging findings with reported changes in clinical management)., Results: Of the total 5722 studies identified, 17 (0.3%) met inclusion criteria. The majority of studies assessed the utility of CT in OHCA (n=10), and potential causes of OHCA were found in 8-54% of patients following head, abdominal and/or chest CT. Only 1/17 (6%) studies reported diagnostic accuracy measures, and 9/17 (53%) studies included a time to imaging criteria within 24h., Conclusion: Although non-invasive imaging is commonly performed in patients after OHCA, its diagnostic utility remains poorly characterized. Prospective studies are needed for appropriate imaging selection and their potential impact on treatment and outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Chronic rhinosinusitis is a common disease process in humans; however, in the primate population of gorillas, it has rarely been described. This case describes lifesaving sinus surgery on a critically ill gorilla performed by a human otolaryngology team in collaboration with the gorilla's veterinary medicine team., Methods: The 35-year-old western silverback gorilla was treated for 3 months with aggressive medical therapy for a worsening sinus infection. When his condition became severe, a computed tomography (CT) scan was performed showing advanced chronic rhinosinusitis with nasal polyps vs other masses and some bone erosion. As his condition deteriorated further, a tertiary otolaryngology team performed sinus surgery using the latest technology available, including image guidance, steroid-eluting sinus stents, and balloon sinus dilation. The postoperative course was complicated by subcutaneous infection and eventual fistulization. Fortunately, with culture-directed antibiotic therapy his condition gradually improved. One year later he required revision sinus surgery. At that point allergy testing was performed followed by appropriate allergy medical therapy. Now, 3 years out from his initial surgery, he continues to do well and has fathered a young female gorilla., Results: This case represents a unique collaboration between human physicians and veterinarians. The combined medical approach was critical to heal this ailing gorilla. This case discusses many of the challenges and offers recommendations for physicians who may be involved with similar care of animals in the future., Conclusion: The success of the surgical and medical treatment of this gorilla's life-threatening sinus infection required many experts, careful planning, and corporate generosity. The interaction between human and animal medicine would not have been successful without the close and trusting collaborations between human and veterinary health providers. We encourage human healthcare providers to seek volunteer opportunities through their local zoos by engaging in discussions with their local veterinarians., (© 2018 ARS-AAOA, LLC.)

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice 'bolus tracking' acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT's) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative perfusion imaging with an acquisition strategy offering substantial radiation dose and computational complexity savings over dynamic CT.

Aims: The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial., Methods and Results: The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001)., Conclusion: COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: The aim of this review is to highlight recent advancements, current trends, and the expanding role for cardiac CT (CCT) in the evaluation of ischemic heart disease, nonischemic cardiomyopathies, and some specific congenital myocardial disease states., Recent Findings: CCT is a highly versatile imaging modality for the assessment of numerous cardiovascular disease states. Coronary CT angiography (CCTA) is now a well-established first-line imaging modality for the exclusion of significant coronary artery disease (CAD); however, CCTA has modest positive predictive value and specificity for diagnosing obstructive CAD in addition to limited capability to evaluate myocardial tissue characteristics., Summary: CTP, when combined with CCTA, presents the potential for full functional and anatomic assessment with a single modality. CCT is a useful adjunct in select patients to both TTE and CMR in the evaluation of ventricular volumes and systolic function. Newer applications, such as dynamic CTP and DECT, are promising diagnostic tools offering the possibility of more quantitative assessment of ischemia. The superior spatial resolution and volumetric acquisition of CCT has an important role in the diagnosis of other nonischemic causes of cardiomyopathies., Competing Interests: Compliance with Ethical StandardsBC Ramsey, E Fentanes, AD Choi, and DM Thomas all declare no conflicts of interest. KR Branch reports grants from Astellas, outside of the submitted work.All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

This review summaries the utility, application and data supporting use of cardiac magnetic resonance imaging (CMR) to evaluate and quantitate aortic regurgitation. We systematically searched Medline and PubMed for original research articles published since 2000 that provided data on the quantitation of aortic regurgitation by CMR and identified 11 articles for review. Direct aortic measurements using phase contrast allow quantitation of volumetric flow across the aortic valve and are highly reproducible and accurate compared with echocardiography. However, this technique requires diligence in prescribing the correct imaging planes in the aorta. Volumetric analytic techniques using differences in ventricular volumes are also highly accurate but less than phase contrast techniques and only accurate when concomitant valvular disease is absent. Comparison of both aortic and ventricular data for internal data verification ensures fidelity of aortic regurgitant data. CMR data can be applied to many types of aortic valve regurgitation including combined aortic stenosis with regurgitation, congenital valve diseases and post-transcatheter valve placement. CMR also predicts those patients who progress to surgery with high overall sensitivity and specificity. Future studies of CMR in patients with aortic regurgitation to quantify the incremental benefit over echocardiography as well as prediction of cardiovascular events are warranted., Competing Interests: Competing interests: Dr CH-C has been an speaker for Siemens, Merck and Edwards. Dr KRB has received research support from Bayer, Astellas. Ad board and Jansen. Drs JCL and EVK have no conflicts to report., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Despite having excellent diagnostic accuracy to detect anatomical coronary stenosis, coronary CT angiography (CTA) has a limited specificity to detect myocardial ischemia. CT perfusion (CTP) can identify myocardial perfusion defects during vasodilator stress, and when added to coronary CTA, improves the specificity of detecting hemodynamically significant stenosis. A CTP protocol typically involves the acquisition of two separate data sets: (I) a rest scan that can be used as both a coronary CTA and for evaluating rest myocardial perfusion, and (II) a stress CTP scan acquired during vasodilator stress testing. This review summarizes some the techniques, strengths, and limitations of CTP, and provides an overview of the recent evidence supporting the potential use of CTP in clinical practice., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Prior studies have shown that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and fluorodeoxyglucose (FDG) positron emission tomography (PET) confer incremental risk assessment in patients with cardiac sarcoidosis (CS). However, the incremental prognostic value of the combined use of LGE and FDG compared to either test alone has not been investigated, and this is the aim of the present study., Methods: Retrospective observational study of 56 symptomatic patients with high clinical suspicion for CS who underwent LGE-CMR and FDG-PET and were followed for the occurrence of death and/or malignant ventricular arrhythmias (VA)., Results: The combination of PET and CMR yielded the following groups: 1) LGE-negative/normal-PET (n=20), 2) LGE-positive/abnormal-FDG (n=20), and 3) LGE-positive/normal FDG (n=16). After a median follow-up of 2.6years (IQR 1.2-4.1), 16 patients had events (7 deaths, 10 VA). All, but 1, events occurred in patients with LGE. LGE-positive/abnormal-FDG (7 events, HR 10.1 [95% CI 1.2-84]; P=0.03) and LGE-positive/normal-FDG (8 events, HR 13.3 [1.7-107]; P=0.015) patients had comparable risk of events compared to the reference LGE-negative/normal-PET group. In adjusted Cox-regression analysis, presence of LGE (HR 18.1 [1.8-178]; P=0.013) was the only independent predictor of events., Conclusion: CS patients with LGE alone or in association with FDG were at similar risk of future events, which suggests that outcomes may be driven by the presence of LGE (myocardial fibrosis) and not FDG (inflammation)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this review discuss the application of cardiac magnetic resonance (CMR) to the evaluation and quantification of mitral regurgitation and provide a systematic literature review for comparisons with echocardiography. Using the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we searched Medline and PubMed for original research articles published since 2000 that provided data on the quantification of mitral regurgitation by CMR. We identified 220 articles of which 33 were included. Four main techniques of mitral regurgitation quantification were identified. Reproducibility varied substantially between papers but was high overall for all techniques. However, quantification differed between the techniques studied. When compared with two-dimensional echocardiography, mitral regurgitation fraction and regurgitant volume measured by CMR were comparable but typically lower. CMR has high reproducibility for the quantification of mitral regurgitation in experienced centres, but further technological refinement is needed. An integrated and standardised approach that combines multiple techniques is recommended for optimal reproducibility and precise mitral regurgitation quantification. Definitive outcome studies using CMR as a basis for treatment are lacking but needed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: This study aims to compare transcatheter aortic valve replacement (TAVR) planning on 16 cm wide-detector computed tomography (CT) to TAVR planning on 4 cm detector CT., Materials and Methods: A total of 36 patients who had TAVR planning axial CT on a wide-detector scanner (protocol 1) were compared to 36 patients who had helical 4 cm detector CT (protocol 2)., Results: Vascular attenuation was greater for protocol 1, but image noise, contrast-to-noise ratio, and signal-to-noise ratio were the same. Radiation dose was lower and iodine dose was less for protocol 1., Conclusion: Protocol 1 had greater vascular attenuation and similar image quality but lower radiation and less iodine compared to protocol 2., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Coronary computed tomography angiography (CCTA) is a rapidly growing and powerful diagnostic test that offers a great deal of precision with respect to diagnosing coronary artery disease (CAD). Guideline statements for patients with stable ischemic heart disease have recommended CCTA for only a limited portion of intermediate-risk patients who have relative or absolute contraindications for exercise or vasodilator stress testing. The publication of two large, prospective randomized clinical trials, the Prospective Multicenter Imaging Study for Evaluation of Chest Pain and the Scottish Computed Tomography of the Heart Trial are likely to expand these indications. These new data from large trials, in addition to other studies, show that CCTA is highly sensitive for the detection of CAD, identifies high-risk patients for cardiac events based on extent or plaque morphology of CAD that would not be identified by other noninvasive means, and provides significantly greater diagnostic certainty for proper treatment, including referral for invasive coronary angiography with revascularization more appropriately. Superior diagnostic accuracy and prognostic data with CCTA, when compared with other functional stress tests, may result in a reduction in unnecessary downstream testing and cost savings. In addition, newer CCTA applications hold the promise of providing a complete evaluation of a patient's coronary anatomy as well as a per-vessel ischemic evaluation. This review focuses on the interval knowledge obtained from newer data on CCTA in patients with stable ischemic heart disease, primarily focusing on the contributions of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain and the Scottish Computed Tomography of the Heart Trial.

Study Objective: Survivors of sudden cardiac arrest may be exposed to iodinated contrast from invasive coronary angiography or contrast-enhanced computed tomography, although the effects on incident acute kidney injury are unknown. The study objective was to determine whether contrast administration within the first 24 hours was associated with acute kidney injury in survivors of sudden cardiac arrest., Methods: This cohort study, derived from a prospective clinical trial, included patients with sudden cardiac arrest who survived for 48 hours, had no history of end-stage renal disease, and had at least 2 serum creatinine measurements during hospitalization. The contrast group included patients with exposure to iodinated contrast within 24 hours of sudden cardiac arrest. Incident acute kidney injury and first-time dialysis were compared between contrast and no contrast groups and then controlled for known acute kidney injury risk factors., Results: Of the 199 survivors of sudden cardiac arrest, 94 received iodinated contrast. Mean baseline serum creatinine level was 1.3 mg/dL (95% confidence interval [CI] 1.4 to 1.5 mg/dL) for the contrast group and 1.6 mg/dL (95% CI 1.4 to 1.7 mg/dL) for the no contrast group. Incident acute kidney injury was lower in the contrast group (12.8%) than the no contrast group (17.1%; difference 4.4%; 95% CI -9.2% to 17.5%). Contrast administration was not associated with significant increases in incident acute kidney injury within quartiles of baseline serum creatinine level or after controlling for age, sex, race, congestive heart failure, diabetes, and admission serum creatinine level by regression analysis. Older age was independently associated with acute kidney injury., Conclusion: Despite elevated baseline serum creatinine level in most survivors of sudden cardiac arrest, iodinated contrast administration was not associated with incident acute kidney injury even when other acute kidney injury risk factors were controlled for. Thus, although acute kidney injury is not uncommon among survivors of sudden cardiac arrest, early (<24 hours) contrast administration from imaging procedures did not confer an increased risk for acute kidney injury., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Cardiac computed tomography (CT) acquisitions for perfusion assessment can be performed in a dynamic or static mode. Either method may be used for a variety of clinical tasks, including (1) stratifying patients into categories of ischemia and (2) using a quantitative myocardial blood flow (MBF) estimate to evaluate disease severity. In this simulation study, we compare method performance on these classification and quantification tasks for matched radiation dose levels and for different flow states, patient sizes, and injected contrast levels. Under conditions simulated, the dynamic method has low bias in MBF estimates (0 to [Formula: see text]) compared to linearly interpreted static assessment (0.45 to [Formula: see text]), making it more suitable for quantitative estimation. At matched radiation dose levels, receiver operating characteristic analysis demonstrated that the static method, with its high bias but generally lower variance, had superior performance ([Formula: see text]) in stratifying patients, especially for larger patients and lower contrast doses [area under the curve [Formula: see text] to 96 versus 0.86]. We also demonstrate that static assessment with a correctly tuned exponential relationship between the apparent CT number and MBF has superior quantification performance to static assessment with a linear relationship and to dynamic assessment. However, tuning the exponential relationship to the patient and scan characteristics will likely prove challenging. This study demonstrates that the selection and optimization of static or dynamic acquisition modes should depend on the specific clinical task.

Objectives: Cardiac computed tomography perfusion (CTP) using stress testing is an emerging application in the field of cardiac computed tomography. We evaluated patients with acute chest pain (CP) in the emergency department (ED) with evidence of obstructive coronary artery disease (CAD), defined as >70% stenosis on coronary computed tomography angiography (CCTA) and confirmed by invasive coronary angiography (ICA), to evaluate the applicability of resting CTP in the acute CP setting., Methods: From January to December 2013, 183 low-intermediate risk symptomatic patients with negative cardiac biomarkers and no known CAD underwent a rapid CCTA protocol in the ED. Of these, 4 patients (1.4%) had obstructive CAD (≥70% stenosis) on CCTA confirmed by ICA. All 183 CCTA studies were evaluated retrospectively with CTP software by a transmural perfusion ratio (TPR) method with a superimposed 17-segment model. A TPR value <0.99 was considered abnormal based on previously published data., Results: A total of four patients were included in this pilot analysis. The duration from resolution of CP to performance of CCTA ranged from 1.6 to 5.0 hours. Three patients underwent revascularization, two with percutaneous coronary intervention (PCI) and one with coronary artery bypass grafting. The fourth patient was managed with aggressive medical therapy. Two patients had multivessel obstructive CAD and two patients had single-vessel CAD. The first patient underwent CCTA 5 hours after resolution of CP symptoms. CCTA demonstrated noncalcified obstructive CAD in the mid-LAD and mid-right coronary artery. ICA showed good correlation by quantitative coronary assessment (QCA) in both vessels and the patient underwent PCI. CTP analysis demonstrated perfusion defects in the LAD and right coronary artery territories. The second patient underwent CCTA 1.6 hours after resolution of CP symptoms with findings of obstructive ostial left main CAD. ICA confirmed obstructive left main CAD by QCA and intravascular ultrasound. The patient underwent revascularization with coronary artery bypass grafting. CTP demonstrated perfusion defects in the anterior and lateral wall segments. The third patient was evaluated for CP in the ED with CCTA demonstrating single-vessel CAD 10 hours after resolution of symptoms with findings of a noncalcified obstructive stenosis in the mid-LAD. The patient subsequently underwent ICA demonstrating good correlation to the CCTA findings in the LAD by QCA. CTP analysis revealed perfusion defects in LAD territory. He was successful treated with PCI. The final patient underwent CCTA 5.4 hours following resolution of CP with the finding of an intermediate partially calcified stenosis in the distal LAD. ICA was performed, with fractional flow reserve demonstrating a hemodynamically insignificant distal LAD at 0.86. CTP detected a perfusion defect in the LAD territory., Conclusions: When positive, rest CTP may have value in the risk stratification of patients presenting to the ED with nontraumatic acute CP.

Objective: Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested., Research Design and Methods: People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring., Results: At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups., Conclusions: FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Coronary heart disease (CHD) is highly prevalent in patients with diabetes mellitus (DM), and remains the single most common cause of death among this population. Regrettably, a significant percentage of diabetics fail to perceive the classic symptoms associated with myocardial ischemia. Among asymptomatic diabetics, the prevalence of abnormal cardiac testing appears to be high, ranging between 10% and 62%, and mortality is significantly higher in those with abnormal scans. Hence, the potential use of screening for CHD detection among asymptomatic DM individuals is appealing and has been recommended in certain circumstances. However, it was not until recently, that this question was addressed in clinical trials. Two studies randomized a total of 2,023 asymptomatic diabetics to screening or not using cardiac imaging with a mean follow up of 4.4 ± 1.4 years. In combination, both trials showed lower than expected annual event rates, and failed to reduce major cardiovascular events in the screened group compared to the standard of care alone. The results of these trials do not currently support the use of screening tools for CHD detection in asymptomatic DM individuals. However, these studies have important limitations, and potential explanations for their negative results that are discussed in this manuscript.

Background: Coronary CT angiography (CCTA) has high sensitivity, with 3 recent randomized trials favorably comparing CCTA to standard-of-care. Comparison to exercise stress ECG (ExECG), the most available and least expensive standard-of-care worldwide, has not been systematically tested., Methods: CT-COMPARE was a randomized, single-center trial of low-intermediate risk chest pain subjects undergoing CCTA or ExECG after the first negative troponin. From March 2010 to April 2011, 562 patients randomized to either dual-source CCTA (n=322) or ExECG (n=240). Primary endpoints were diagnostic performance for ACS, and hospital cost at 30 days. Secondary endpoints were time-to-discharge, admission rates, and downstream resource utilization., Results: ACS occurred in 24 (4%) patients. ExECG had 213 negative studies and 27 (26%) positive studies for ACS with sensitivity of 83% [95% CI: 36, 99.6%], specificity of 91% [CI: 86, 94%], and ROC AUC of 0.87 [CI: 0.70, 1]. CCTA (>50% stenosis considered positive) had 288 negative studies and 18/35 (51%) positive studies with a sensitivity of 100% [CI: 81.5, 100], specificity of 94% [CI: 91.2, 96.7%], and ROC of 0.97 [CI: 0.92, 1.0; p=0.2]. Despite CCTA having higher odds of downstream testing (OR 2.0), 30 day per-patient cost was significantly lower for CCTA ($2193 vs $2704, p<0.001). Length of stay for CCTA was significantly reduced (13.5h [95% CI: 11.2-15.7], ExECG 19.7h [95% CI: 17.4-22.1], p<0.0005), which drove the reduction in cost. No patient had post-discharge cardiovascular events at 30 days., Conclusions: CCTA had improved diagnostic performance compared to ExECG, combined with 35% relative reduction in length-of-stay, and 20% reduction in hospital costs. These data lend further evidence that CCTA is useful as a first line assessment in emergency department chest pain., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that there is no particular advantage between quantitative estimation methods nor to performing dose reduction via tube current reduction compared to temporal sampling reduction. These data are important for optimizing implementation of cardiac dynamic CT in clinical practice and in prospective CT MBF trials.

Contrast enhancement on cardiac CT provides valuable information about myocardial perfusion and methods have been proposed to assess perfusion with static and dynamic acquisitions. There is a lack of knowledge and consensus on the appropriate approach to ensure 1) sufficient diagnostic accuracy for clinical decisions and 2) low radiation doses for patient safety. This work developed a thorough dynamic CT simulation and several accepted blood flow estimation techniques to evaluate the performance of perfusion assessment across a range of acquisition and estimation scenarios. Cardiac CT acquisitions were simulated for a range of flow states (Flow = 0.5, 1, 2, 3 ml/g/min, cardiac output = 3,5,8 L/min). CT acquisitions were simulated with a validated CT simulator incorporating polyenergetic data acquisition and realistic x-ray flux levels for dynamic acquisitions with a range of scenarios including 1, 2, 3 sec sampling for 30 sec with 25, 70, 140 mAs. Images were generated using conventional image reconstruction with additional image-based beam hardening correction to account for iodine content. Time attenuation curves were extracted for multiple regions around the myocardium and used to estimate flow. In total, 2,700 independent realizations of dynamic sequences were generated and multiple MBF estimation methods were applied to each of these. Evaluation of quantitative kinetic modeling yielded blood flow estimates with an root mean square error (RMSE) of ∼0.6 ml/g/min averaged across multiple scenarios. Semi-quantitative modeling and qualitative static imaging resulted in significantly more error (RMSE = ∼1.2 and ∼1.2 ml/min/g respectively). For quantitative methods, dose reduction through reduced temporal sampling or reduced tube current had comparable impact on the MBF estimate fidelity. On average, half dose acquisitions increased the RMSE of estimates by only 18% suggesting that substantial dose reductions can be employed in the context of quantitative myocardial blood flow estimation. In conclusion, quantitative model-based dynamic cardiac CT perfusion assessment is capable of accurately estimating MBF across a range of cardiac outputs and tissue perfusion states, outperforms comparable static perfusion estimates, and is relatively robust to noise and temporal subsampling.

Objective: Coronary CT angiography has high sensitivity, but modest specificity, to detect acute coronary syndrome. We studied whether adding resting CT myocardial perfusion imaging improved the detection of acute coronary syndrome., Subjects and Methods: Patients with low-to-intermediate cardiac risk presenting with possible acute coronary syndrome received both the standard of care evaluation and a research thoracic 64-MDCT examination. Patients with an obstructive (> 50%) stenosis or a nonevaluable coronary segment on CT were diagnosed with possible acute coronary syndrome. CT perfusion was determined by applying gray and color Hounsfield unit maps to resting CT angiography images. Adjudicated patient diagnoses were based on the standard of care and 3-month follow-up. Patient-level diagnostic performance for acute coronary syndrome was calculated for coronary CT, CT perfusion, and combined techniques., Results: A total of 105 patients were enrolled. Of the nine (9%) patients with acute coronary syndrome, all had obstructive CT stenoses but only three had abnormal CT perfusion. CT perfusion was normal in all other patients. To detect acute coronary syndrome, CT angiography had 100% sensitivity, 89% specificity, and a positive predictive value of 45%. For CT perfusion, specificity and positive predictive value were each 100%, and sensitivity was 33%. Combined cardiac CT and CT perfusion had similar specificity but a higher positive predictive value (100%) than did CT angiography., Conclusion: Resting CT perfusion using CT angiographic images may have high specificity and may improve CT positive predictive value for acute coronary syndrome without added radiation and contrast. However, normal resting CT perfusion cannot exclude acute coronary syndrome.

Purpose: The purpose of this study was to assess the diagnostic accuracy and one year prognosis of whole chest, "multiple rule out" CT for coronary artery disease (CAD) in Emergency Department patients., Methods and Findings: One hundred and two Emergency Department patients at low to intermediate risk of acute coronary syndrome (ACS), pulmonary embolism and/or acute aortic syndrome underwent a research 64 channel ECG-gated, whole chest CT and a standard of care evaluation. Patients were classified with obstructive CAD with either a coronary CT stenosis greater than 50% or a non-evaluable coronary segment. SOC and 3 month follow up data were used to determine an adjudicated clinical diagnosis. The diagnostic ability of obstructive CAD on CT to identify clinical diagnoses was determined. Patients were followed up for 1 year for cardiac events. Seven (7%) patients were diagnosed with ACS. CT sensitivity to detect obstructive CAD in ACS patients was 100% (95% CI 65%, 100%), negative predictive value 100% (96%, 100%), specificity 88% (80%, 94%), and positive predictive value 39% (17%, 64%). Pulmonary embolism and acute aortic syndrome were not identified in any patients. No cardiac events occurred in patients without obstructive CAD over 1 year., Conclusions: Whole chest CT has high sensitivity and negative predictive value for ACS with excellent one year prognosis in patients without obstructive CAD on CT. The frequency of pulmonary embolism or acute aortic syndrome and the higher radiation dose suggest whole chest CT should be limited to select patients. ClinicalTrials.org #: NCT00855231.

Objective: The aim of this study was to compare the size of the calcifications measured on the different keV images to a histological standard., Methods: Five ex vivo carotid endarterectomy (CEA) specimens were imaged with a dual-energy CT. CT images were reconstructed at different monochromatic spectral energies (40, 60, 77, 80, 100, 120, 140 keV). Cross-sectional area of the plaque calcifications present on each CT image was measured. The histological calcium areas on each corresponding CEA specimen were traced manually on digitised images of Toluidine Blue/Basic Fuchsin stained plastic sections. The CT images and corresponding histology sections were matched. The CT-derived calcium areas on each keV image were compared to the calcified area measurements by histology., Results: A total of 107 histology sections were matched to corresponding CT images. The average calcified area per section by histology was 7.6 ± 7 mm(2) (range 0-26.4 mm(2)). There was no significant difference between the calcified areas measured by histology and those measured on CT-virtual monochromatic spectral (VMS) reconstructed images at 77 keV (P = 0.08), 80 keV (P = 0.20) and 100 keV (P = 0.14)., Conclusions: Calcium area measured on the 80 keV image set was most comparable to the amount of calcium measured by histology.

Rationale and Objectives: Cardiac computed tomography (CCT) in the emergency department may be cost saving for suspected acute coronary syndrome (ACS), but economic outcome data are limited. The objective of this study was to compare the cost of CCT-based evaluation versus standard of care (SOC) using the results of a clinical trial., Materials and Methods: We developed a decision analytic cost-minimization model to compare CCT-based and SOC evaluation costs to obtain a correct diagnosis. Model inputs, including Medicare-adjusted patient costs, were primarily obtained from a cohort study of 102 patients at low to intermediate risk for ACS who underwent an emergency department SOC clinical evaluation and a 64-channel CCT. SOC costs included stress testing in 77% of patients. Data from published literature completed the model inputs and expanded data ranges for sensitivity analyses., Results: Modeled mean patient costs for CCT-based evaluation were $750 (24%) lower than the SOC ($2384 and $3134, respectively). Sensitivity analyses indicated that CCT was less expensive over a wide range of estimates and was only more expensive with a CCT specificity below 67% or if more than 44% of very low risk patients had CCT. Probabilistic sensitivity analysis suggested that CCT-based evaluation had a 98.9% probability of being less expensive compared to SOC., Conclusion: Using a decision analytic model, CCT-based evaluation resulted in overall lower cost than the SOC for possible ACS patients over a wide range of cost and outcome assumptions, including computed tomography-related complications and downstream costs., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to test the diagnostic accuracy of myocardial CT perfusion (CTP) imaging using color and gray-scale image analysis., Background: Current myocardial CTP techniques have varying diagnostic accuracy and are prone to artifacts that impair detection. This study evaluated the diagnostic accuracy of color and/or gray-scale CTP and the application of artifact criteria to detect hypoperfusion., Methods: Fifty-nine prospectively enrolled patients with abnormal single-photon emission computed tomography (SPECT) studies were analyzed. True hypoperfusion was defined if SPECT hypoperfusion corresponded to obstructive coronary stenoses on CT angiography (CTA). CTP applied color and gray-scale myocardial perfusion maps to resting CTA images. Criteria for identifying artifacts were also applied during interpretation., Results: Using combined SPECT plus CTA as the diagnostic standard, abnormal myocardial CTP was present in 33 (56%) patients, 19 suggesting infarction and 14 suggesting ischemia. Patient-level color and gray-scale myocardial CTP sensitivity to detect infarction was 90%, with specificity 80%, and negative and positive predictive value of 94% and 68%. To detect ischemia or infarction, CTP specificity and positive predictive value were 92% whereas sensitivity was 70%. Gray-scale myocardial CTP had slightly lower specificity but similar sensitivity. Myocardial CTP artifacts were present in 88% of studies and were identified using our criteria., Conclusions: Color and gray-scale myocardial CTP using resting CTA images identified myocardial infarction with high sensitivity as well as infarction or ischemia with high specificity and positive predictive value without additional testing or radiation. Color and gray-scale CTP had slightly better specificity than gray-scale alone., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this article is to determine the frequency of adverse cardiac events during the year following a negative cardiac CT angiogram in a population of patients presenting to the emergency department with low-to-moderate risk chest pain., Subjects and Methods: Eighty-one consecutive patients who had standard of care evaluation for low-to-moderate risk chest pain in the emergency department were enrolled and consented to have a cardiac CT angiogram added to their workup and to have follow-up for 1 year. Eleven patients were excluded, six because their cardiac CT examinations were unsuccessful, four because of a positive cardiac CT angiogram result, and one was lost to follow-up. Seventy patients with negative cardiac CT angiographic results (< 50% stenosis) were included and were interviewed in detail at 3, 6, and 12 months about intervening cardiac events, diagnostic testing, and therapy. Electronic medical records were also reviewed at each time point., Results: None of the 70 patients reported an adverse cardiac event over the 12-month follow-up period. At 1 year, the cause of chest pain was unknown in 49 patients, gastrointestinal in nine patients, anxiety in seven patients, musculoskeletal in three patients, and other in two patients. Three of four patients with 50% or greater stenosis on their cardiac CT had subsequent cardiac catheterization and stent placement., Conclusion: In patients with low-to-moderate risk chest pain evaluated in the emergency department, adverse cardiac events may be rare during the 12 months following a negative cardiac CT angiogram.

Objective: The purpose of this study was to evaluate the use of a triphasic contrast bolus for ECG-gated CT in the assessment of chest pain by measuring vascular luminal attenuation and determining the degree of contrast-related streak artifact., Materials and Methods: We reviewed the images from 44 ECG-gated CT examinations performed with a coronary contrast bolus modified for imaging of the entire chest. Luminal attenuation achieved with the resulting triphasic bolus was measured at specified vascular locations in the right side of the heart, pulmonary arteries, coronary arteries, and thoracic aorta. The occurrence of contrast-related streak artifact was recorded, and artifact severity was scored on a subjective 4-point scale., Results: The mean attenuation values in the pulmonary arteries (345.3 +/- 136.7 HU), coronary arteries (340.8 +/- 82.5 HU), and thoracic aorta (386.4 +/- 67.2 HU) were above a diagnostic threshold of 200 HU. Although there was no significant difference between the mean arterial values, the right-heart attenuation (281.6 +/- 121.8 HU) was significantly lower than the attenuation in the other two locations. On a location basis, 92.2% of the 1,972 arterial measurements were above the 200-HU threshold. Streak artifacts were found in 21 examinations (47.7%), and none was scored as severe. Statistical analysis revealed that the occurrence of streak artifact increased with higher right-heart attenuation., Conclusion: In this series, a triphasic contrast bolus for ECG-gated whole-chest CT consistently achieved arterial attenuation above a diagnostic threshold in the pulmonary arteries, coronary arteries, and aorta. Right-heart attenuation was simultaneously reduced, which is important for decreasing the prevalence and severity of streak artifacts.

Objective: The current standard-of-care workup of low-risk patients with chest pain in an emergency department takes 12-36 hours and is expensive. We hypothesized that negative 64-MDCT coronary angiography early in the workup of such patients may enable a shorter length of stay and reduce charges., Materials and Methods: The standard-of-care evaluation consisted of serial cardiac enzyme tests, ECGs, and stress testing. After informed consent, we added cardiac CT early in the standard-of-care workup of 53 consecutive patients. Fifty patients had negative CT findings and were included in this series. The length of stay and charges were analyzed using actual patient data for all patients in the standard-of-care workup and for two earlier discharge scenarios based on negative cardiac CT results: First, CT plus serial enzyme tests and ECGs during an observation period followed by discharge if all were negative; and second, CT plus one set of enzyme tests and one ECG followed by discharge if all were negative. Comparisons were made using paired Student's t tests., Results: For standard of care and the two CT-based earlier discharge analyses, the mean lengths of stay were 25.4, 14.3, and 5.0 hours; mean charges were $7,597, $6,153, and $4,251. Length of stay and charges were both significantly less (p < 0.001) for the two CT-based analyses., Conclusion: In low-risk patients with chest pain, discharge from the emergency department based on negative cardiac CT, enzyme tests, and ECG may significantly decrease both length of stay and hospital charges compared with the standard of care.

Objective: The purpose of this study was to compare the patient radiation dose and coronary artery image quality of long-z-axis whole-chest 64-MDCT performed with retrospective ECG gating with those of CT performed with prospective ECG triggering in the evaluation of emergency department patients with nonspecific chest pain., Subjects and Methods: Consecutively registered emergency department patients with nonspecific low-to-moderate-risk chest pain underwent whole-chest CT with retrospective gating (n = 41) or prospective triggering (n = 31). Effective patient radiation doses were estimated and compared by use of unpaired Student's t tests. Two reviewers independently scored the quality of images of the coronary arteries, and the scores were compared by use of ordinal logistic regression., Results: Age, heart rate, body mass index, and z-axis coverage were not statistically different between the two groups. For retrospective gating, the mean effective radiation dose was 31.8 +/- 5.1 mSv; for prospective triggering, the mean effective radiation dose was 9.2 +/- 2.2 mSv (prospective triggering 71% lower, p < 0.001). Two of 512 segments imaged with retrospective gating were nonevaluable (0.4%), and two of 394 segments imaged with prospective triggering were nonevaluable (0.5%). Prospectively triggered images were 2.2 (95% CI, 1.1-4.5) times as likely as retrospectively gated images to receive a high image quality score for each segment after adjustment for segment differences (p < 0.05)., Conclusion: For long-z-axis whole-chest 64-MDCT of emergency department patients with nonspecific chest pain, use of prospective ECG triggering may result in substantially lower patient radiation doses and better coronary artery image quality than is achieved with retrospective ECG gating.

Purpose: To compare image quality and patient radiation dose in a group of patients who underwent 64-detector computed tomography (CT) coronary angiography performed with prospective electrocardiographic (ECG) gating with image quality and radiation dose in a group of patients matched for clinical features who underwent 64-detector CT coronary angiography performed with retrospective ECG gating., Materials and Methods: Institutional review board approval was obtained for this HIPAA-compliant study, and the informed consent requirement was waived due to the retrospective study design. Two independent reviewers separately scored coronary artery segment image quality and overall image quality for 100 cardiac CT studies (50 in each group). Interobserver variability was calculated. Patient radiation dose for the actual examination z-axis length was recorded, and a normalized dose was calculated for a 12-cm z-axis length of a typical heart., Results: The two groups matched well for clinical characteristics and CT parameters. There was good agreement for coronary artery segment image quality scores between the independent reviewers (kappa = 0.72). Of the 1253 coronary artery segments scored, the number of coronary artery segments that could not be evaluated in each group was similar (1.1% [seven of 614] in the prospective group vs 1.5% [10 of 647] in the retrospective group, P = .53). Image quality scores were not significantly different when matched for chest cross-sectional area (P > .05). Mean patient radiation dose was 77% lower for prospective gating (4.2 mSv) than for retrospective gating (18.1 mSv) (P < .01)., Conclusion: Use of 64-detector CT coronary angiography performed with prospective ECG gating has similar subjective image quality scores but 77% lower patient radiation dose when compared with use of retrospective ECG gating.

Unlabelled: Filtered backprojection (FBP) is the traditional method for 13N-NH3 PET studies. Ordered-subsets expectation maximization (OSEM) is popular for PET studies because of better noise properties. Scant data exist on the effect of reconstruction algorithms on quantitative myocardial blood flow (MBF) estimation., Methods: Twenty patients underwent dynamic acquisition rest/stress 13N-NH3 studies. In Part 1, 19 rest/stress image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets and 2 (OSEM2), 6 (OSEM6), or 8 iterations (OSEM8), and a 10-mm postreconstruction smoothing gaussian filter. In Part 2, 9 image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets, 8 iterations, and a gaussian 5-, 10-, or 15-mm postreconstruction smoothing filter. Average MBF (mL/min/mL of myocardium) was calculated using a 3-compartment model., Results: Part 1: For rest MBF, the correlations between FBP and each of the OSEM algorithms were r2 = 0.71, 0.73, and 0.77, respectively. MBF by OSEM6 (0.98 +/- 0.48 [mean +/- SD]) and OSEM8 (0.96 +/- 0.46) was not significantly different from FBP (1.02 +/- 0.39), but OSEM2 (0.80 +/- 0.37) was significantly lower (P < 0.0003). With stress, the correlations were high between FBP and OSEM6 and OSEM8 (r2 = 0.85 and 0.90), and MBF by OSEM6 and OSEM8 was not significantly different from FBP. Part 2: Resting MBF correlated well between FBP and all OSEM smoothing filters (r2 = 0.82, 0.85, and 0.88). Rest MBF using postsmoothing 5- or 10-mm filters was not different from FBP but was significantly lower with the 15-mm filter (P < 0.05). With stress, the correlations were good between FBP and OSEM regardless of smoothing (r2 = 0.76, 0.77, and 0.79). However, MBF with postsmoothing 10- and 15-mm filters was significantly lower than by FBP (P < 0.05)., Conclusion: Reconstruction algorithms significantly affect the estimation of quantitative blood flow data and should not be assumed to be interchangeable. Although aggressive smoothing may produce visually appealing images with reduced noise levels, it may cause an underestimation of absolute quantitative MBF. In selecting a reconstruction algorithm, an optimal balance between noise properties and diagnostic accuracy must be emphasized.