Head-to-pelvis CT imaging after sudden cardiac arrest: Current status and future directions.

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.

Ventricular fibrillation due to pheochromocytoma crisis in a previously asymptomatic patient.

Pheochromocytomas are catecholamine-producing tumors and a rare cause of sudden cardiac death. We describe the case of a previously healthy 28-year-old man who presented after a ventricular fibrillation out-of-hospital cardiac arrest (OHCA). His clinical investigation, including a coronary evaluation, was unremarkable. A protocolized head-to-pelvis computed tomography (CT) scan was ordered and revealed a large right adrenal mass with subsequent laboratory studies showing markedly elevated urine and plasma catecholamines. This raised suspicion for a pheochromocytoma as the underlying etiology behind his OHCA. He received appropriate medical management, underwent adrenalectomy with subsequent normalization of his metanephrines, and fortunately did not have recurrent arrythmias. This case highlights the first documented case of a ventricular fibrillation arrest as the initial presentation of pheochromocytoma crisis in a previously healthy individual, and how the use of early protocolized sudden death CT scan allowed for the prompt diagnosis and management of a rare cause of OHCA. Learning objective: We review the typical cardiac manifestations of pheochromocytoma and describe the first case of a pheochromocytoma crisis presenting as sudden cardiac death (SCD) in a previously asymptomatic individual. In young patients with unexplained SCD, it is important to consider pheochromocytoma in the differential diagnosis. We also review why an early head-to-pelvis sudden death computed tomography scan protocol may be helpful in the evaluation of patients resuscitated from SCD without an obvious etiology.

Exploring potential mediators of the cardiovascular benefit of dulaglutide in type 2 diabetes patients in REWIND.

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.

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials.

BACKGROUND: GLP-1 receptor agonists reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, uncertainty regarding kidney outcomes persists and whether benefits extend to exendin-4-based GLP-1 receptor remains uncertain. We aimed to meta-analyse the most up-to-date evidence on the cardiovascular benefits and risks of GLP-1 receptor agonists from outcome trials in patients with type 2 diabetes. METHODS: We did a meta-analysis, including new data from AMPLITUDE-O, using a random effects model to estimate overall hazard ratio (HR) for MACE; its components; all-cause mortality; hospital admission for heart failure; a composite kidney outcome consisting of development of macroalbuminuria, doubling of serum creatinine, or at least 40% decline in estimated glomerular filtration rate (eGFR), kidney replacement therapy, or death due to kidney disease; worsening of kidney function, based on eGFR change; and odds ratios for key safety outcomes (severe hypoglycaemia, retinopathy, pancreatitis, and pancreatic cancer). We also examined MACE outcome in patient subgroups on the basis of MACE incidence rates in the placebo group, presence or absence of cardiovascular disease, HbA1c level, trial duration, treatment dosing interval, structural homology to human GLP-1 or exendin-4, BMI, age, and eGFR. We searched PubMed for eligible trials reporting MACE (ie, cardiovascular death, myocardial infarction, or stroke), up to June 9, 2021. We meta-analysed data from published randomised placebo-controlled trials testing either injectable or oral GLP-1 receptor agonists in patients with type 2 diabetes. We restricted the search to trials of more than 500 patients with a primary outcome that included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. This meta-analysis was registered on PROSPERO, CRD42021259711. FINDINGS: Of 98 articles screened, eight trials comprising 60 080 patients fulfilled the prespecified criteria and were included. Overall, GLP-1 receptor agonists reduced MACE by 14% (HR 0·86 [95% CI 0·80-0·93]; p<0·0001), with no significant heterogeneity across GLP-1 receptor agonist structural homology or eight other examined subgroups (all pinteraction≥0·14). GLP-1 receptor agonists reduced all-cause mortality by 12% (HR 0·88 [95% CI 0·82-0·94]; p=0·0001), hospital admission for heart failure by 11% (HR 0·89 [95% CI 0·82-0·98]; p=0·013), and the composite kidney outcome by 21% (HR 0·79 [95% CI 0·73-0·87]; p<0·0001), with no increase in risk of severe hypoglycaemia, retinopathy, or pancreatic adverse effects. In sensitivity analyses removing the only trial restricted to patients with an acute coronary syndrome (ELIXA), all benefits marginally increased, including the outcome of worsening of kidney function, based on eGFR change (HR 0·82 [95% CI 0·69-0·98]; p=0·030). INTERPRETATION: GLP-1 receptor agonists, regardless of structural homology, reduced the risk of individual MACE components, all-cause mortality, hospital admission for heart failure, and worsening kidney function in patients with type 2 diabetes. FUNDING: None.

Exploring Medication Adherence with P2Y12 Inhibitors Using Conditional and Unconditional Quantile Regression Approaches.

BACKGROUND: Previous research assessing medication adherence with P2Y12 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 P2Y12 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 P2Y12 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.

Coronary CT radiation dose reduction strategies at an Australian Tertiary Care Center - improvements in radiation exposure through an evidence-based approach.

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.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Gorilla endoscopic sinus surgery: a life-saving collaboration between human and veterinary medicine.

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.

Evaluation of aortic regurgitation with cardiac magnetic resonance imaging: a systematic review.

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.

Coronary artery disease reporting and data system (CAD-RADSTM): Inter-observer agreement for assessment categories and modifiers.

BACKGROUND: The Coronary Artery Disease Reporting and Data System (CAD-RADS) provides a lexicon and standardized reporting system for coronary CT angiography. OBJECTIVES: To evaluate inter-observer agreement of the CAD-RADS among an panel of early career and expert readers. METHODS: Four early career and four expert cardiac imaging readers prospectively and independently evaluated 50 coronary CT angiography cases using the CAD-RADS lexicon. All readers assessed image quality using a five-point Likert scale, with mean Likert score ≥4 designating high image quality, and <4 designating moderate/low image quality. All readers were blinded to medical history and invasive coronary angiography findings. Inter-observer agreement for CAD-RADS assessment categories and modifiers were assessed using intra-class correlation (ICC) and Fleiss' Kappa (κ).The impact of reader experience and image quality on inter-observer agreement was also examined. RESULTS: Inter-observer agreement for CAD-RADS assessment categories was excellent (ICC 0.958, 95% CI 0.938-0.974, p < 0.0001). Agreement among expert readers (ICC 0.925, 95% CI 0.884-0.954) was marginally stronger than for early career readers (ICC 0.904, 95% CI 0.852-0.941), both p < 0.0001. High image quality was associated with stronger agreement than moderate image quality (ICC 0.944, 95% CI 0.886-0.974 vs. ICC 0.887, 95% CI 0.775-0.95, both p < 0.0001). While excellent inter-observer agreement was observed for modifiers S (stent) and G (bypass graft) (both κ = 1.0), only fair agreement (κ = 0.40) was observed for modifier V (high risk plaque). CONCLUSION: Inter-observer reproducibility of CAD-RADS assessment categories and modifiers is excellent, except for high-risk plaque (modifier V) which demonstrates fair agreement. These results suggest CAD-RADS is feasible for clinical implementation.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING: Bayer AG.

Risk assessment of patients with clinical manifestations of cardiac sarcoidosis with positron emission tomography and magnetic resonance imaging.

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).

Wide-detector axial CT versus 4 cm detector helical CT for transcatheter aortic valve replacement: iodine dose, radiation, and image quality.

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.

Rest-Only Myocardial CT Perfusion in Acute Chest Pain.

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.

Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.

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.

Identification of coronary heart disease in asymptomatic individuals with diabetes mellitus: to screen or not to screen.

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.

La enfermedad de la arterias coronarias (EAC) es muy prevalente en pacientes con diabetes mellitus (DM), y continúa siendo la principal causa de muerte en estos pacientes. Desafortunadamente, muchos diabéticos pueden carecer de síntomas de alerta en la presencia de isquemia miocárdica, por lo cual el diagnóstico de EAC puede ocurrir de manera tardía. Estudios observacionales han sugerido que la prevalencia de isquemia miocárdica puede ser alta en diabéticos asintomáticos (10 al 62% según la serie) y la mortalidad es mayor en esos pacientes. Por esto, el uso de pruebas para detección de EAC en el paciente diabético asintomático parece atractivo y es recomendado en ciertas circunstancias. Sin embargo, no fue si no hasta hace poco que dos estudios investigaron el verdadero rol de estas pruebas de manera aleatoria. En conjunto, 2,023 pacientes diabéticos asintomáticos fueron aleatorizados a recibir o no una prueba para detección de EAC y fueron seguidos en promedio por 4.4 ± 1.4 años. Al final de seguimiento, ambos estudios mostraron menos eventos cardiovasculares de los esperados, y el uso de pruebas para detección de EAC no redujo la tasa de eventos cardiovasculares comparado al no uso de estas pruebas. Los resultados de estos ensayos clínicos no soportan actualmente el uso de estas pruebas en el paciente diabético asintomático. Sin embargo, estos estudios tienen limitaciones importantes, y posibles hipótesis para explicar los resultados que son discutidas en el artículo.

Identification of coronary heart disease in asymptomatic individuals with diabetes mellitus: to screen or not to screen / Identificación de enfermedad cardiaca coronaria en individuos asintomáticos con diabetes mellitus: Tamizar o no tamizar

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, raging 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 yrs. 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.

La enfermedad de la arterias coronarias (EAC) es muy prevalente en pacientes con diabetes mellitus (DM), y continúa siendo la principal causa de muerte en estos pacientes. Desafortunadamente, muchos diabéticos pueden carecer de síntomas de alerta en la presencia de isquemia miocárdica, por lo cual el diagnóstico de EAC puede ocurrir de manera tardía. Estudios observacionales han sugerido que la prevalencia de isquemia miocárdica puede ser alta en diabéticos asintomáticos (10 al 62% según la serie) y la mortalidad es mayor en esos pacientes. Por esto, el uso de pruebas para detección de EAC en el paciente diabético asintomático parece atractivo y es recomendado en ciertas circunstancias. Sin embargo, no fue si no hasta hace poco que dos estudios investigaron el verdadero rol de estas pruebas de manera randomizada. En conjunto, 2,023 pacientes diabéticos asintomáticos fueron aleatorizados a recibir o no una prueba para detección de EAC y fueron seguidos en promedio por 4.4 ±1.4 años. Al final de seguimiento, ambos estudios mostraron menos eventos cardiovasculares de los esperados, y el uso de pruebas para detección de EAC no redujo la tasa de eventos cardiovasculares comparado al no uso de estas pruebas. Los resultados de estos ensayos clínicos no soportan actualmente el uso de estas pruebas en el paciente diabético asintomático. Sin embargo, estos estudios tienen limitaciones importantes, y posibles hipótesis para explicar los resultados que son discutidas en el artículo.

Comparison of blood flow models and acquisitions for quantitative myocardial perfusion estimation from dynamic CT.

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.