Utility of multimodal longitudinal imaging data for dynamic prediction of cardiovascular and renal disease: the CARDIA study.

Background: Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD). Methods: In a multi-centered cohort of 5,114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy x-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors. Results: Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors; best model's C-index = 0.80-0.83 up to 20 years from baseline) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction. Conclusions: Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.

United States Investigational Device Exemption study of the Revolution Peripheral Atherectomy System.

OBJECTIVE: Atherectomy has become commonplace as an adjunct to interventional treatments for peripheral arterial disease, but the procedures have been complicated by risks including distal embolization and arterial perforation. This study aimed to examine the safety and effectiveness of a novel atherectomy system to treat femoropopliteal and below-knee peripheral arterial disease. METHODS: The Revolution Peripheral Atherectomy System (Rex Medical LP, Conshohocken, Pa) was studied in 121 patients with 148 femoropopliteal and below-knee lesions, enrolled at 17 United States institutions. Technical success was defined when the post-atherectomy angiographic stenosis was ≤50%, as assessed by an independent core laboratory. Major adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Among 148 site-identified target lesions in 121 patients, 21.4% were in the superficial femoral artery, 13.7% involved the popliteal artery, and 67.9% were in tibial arteries; 3.1% involved more than one segment. Technical success was 90.2%, with stenoses decreasing from 73% ± 19% at baseline to 42% ± 14% after atherectomy. Adjunctive treatment after atherectomy included angioplasty with uncoated balloons in 91%, drug-coated balloons in 11%, bare stent deployment in 8%, and drug-eluting stent placement in 3%. Procedural success (<30% residual stenosis) was achieved in 93.7% of target lesions. Complications during the procedure included one target vessel perforation and two distal embolizations; each of which were adjudicated by the Clinical Events Committee as unrelated to the device and were not visualized angiographically by the core laboratory. Freedom from major adverse events was 97.3% through 30 days. The Kaplan-Meier estimates of primary, assisted primary, and secondary patency were 81.6%, 87.7%, and 91.6% at 6 months, respectively. CONCLUSIONS: The use of the Revolution Peripheral Atherectomy System was associated with few procedural complications and a high rate of success at the index procedure and through 6 months.

Preliminary Results of the Outpatient Endovascular and Interventional Society National Registry.

PURPOSE: To present a new outcomes-based registry to collect data on outpatient endovascular interventions, a relatively new site of service without adequate historical data to assess best clinical practices. Quality data collection with subsequent outcomes analysis, benchmarking, and direct feedback is necessary to achieve optimal care. MATERIALS AND METHODS: The Outpatient Endovascular and Interventional Society (OEIS) established the OEIS National Registry in 2017 to collect data on safety, efficacy, and quality of care for outpatient endovascular interventions. Since then, it has grown to include a peripheral artery disease (PAD) module with plans to expand to include cardiac, venous, dialysis access, and other procedures in future modules. As a Qualified Clinical Data Registry approved by the Centers for Medicare and Medicaid Services, this application also supports new quality measure development under the Quality Payment Program. All physicians operating in an office-based laboratory or ambulatory surgery center can use the Registry to analyze de-identified data and benchmark performance against national averages. Major adverse events were defined as death, stroke, myocardial infarction, acute onset of limb ischemia, index bypass graft or treated segment thrombosis, and/or need for urgent/emergent vascular surgery. RESULTS: Since Registry inception in 2017, 251 participating physicians from 64 centers located in 18 states have participated. The current database includes 18,134 peripheral endovascular interventions performed in 12,403 PAD patients (mean age 72.3±10.2 years; 60.1% men) between January 2017 and January 2020. Cases were performed primarily in an office-based laboratory (85.1%) or ambulatory surgery center setting (10.4%). Most frequently observed procedure indications from 16,086 preprocedure form submissions included claudication (59%), minor tissue loss (16%), rest pain (9%), acute limb ischemia (5%), and maintenance of patency (3%). Planned diagnostic procedures made up 12.2% of cases entered, with the remainder indicated as interventional procedures (87.6%). The hospital transfer rate was 0.62%, with 88 urgent/emergent transfers and 24 elective transfers. The overall complication rate for the Registry was 1.87% (n=338), and the rate of major adverse events was 0.51% (n=92). Thirty-day mortality was 0.03% (n=6). CONCLUSION: This report describes the current structure, methodology, and preliminary results of OEIS National Registry, an outcomes-based registry designed to collect quality performance data with subsequent outcome analysis, benchmarking, and direct feedback to aid clinicians in providing optimal care.

SCAI position statement on the performance of percutaneous coronary intervention in ambulatory surgical centers.

The Centers for Medicare & Medicaid Services (CMS) began reimbursement for percutaneous coronary intervention (PCI) performed in ambulatory surgical centers (ASC) in January 2020. The ability to perform PCI in an ASC has been made possible due to the outcomes data from observational studies and randomized controlled trials supporting same day discharge (SDD) after PCI. In appropriately selected patients for outpatient PCI, clinical outcomes for SDD or routine overnight observation are comparable without any difference in short-term or long-term adverse events. Furthermore, a potential for lower cost of care without a compromise in clinical outcomes exists. These studies provide the framework and justification for performing PCI in an ASC. The Society for Cardiovascular Angiography and Interventions (SCAI) supported this coverage decision provided the quality and safety standards for PCI in an ASC were equivalent to the hospital setting. The current position paper is written to provide guidance for starting a PCI program in an ASC with an emphasis on maintaining quality standards. Regulatory requirements and appropriate standards for the facility, staff and physicians are delineated. The consensus document identified appropriate patients for consideration of PCI in an ASC. The key components of an ongoing quality assurance program are defined and the ethical issues relevant to PCI in an ASC are reviewed.

Long-term (5-year) clinical evaluation of the Resolute zotarolimus-eluting coronary stent: The RESOLUTE US clinical trial.

OBJECTIVES: To assess the long-term safety and efficacy of the Resolute zotarolimus-eluting stent (R-ZES). BACKGROUND: The R-ZES has been associated with low rates of adverse events over short-intermediate term follow-up. However, reliable assessment of the safety and efficacy of any implanted device requires long-term evaluation. METHODS: The RESOLUTE US trial was a prospective, observational study conducted at 116 U.S. sites and enrolled patients with de novo coronary lesions. Patients were followed clinically for 5 years with independent event adjudication and data monitoring. RESULTS: A total of 1,402 patients (1,573 lesions) were enrolled; 34% had diabetes mellitus and 75% had ACC type B2/C lesions. The 5-year rate of target lesion failure (TLF) was 12.3%, target lesion revascularization was 6.5%, target vessel myocardial infarction was 3.2%, and cardiac death was 4.1%. Dual antiplatelet therapy usage was 94% at 1 year and 47% at 5 years, with a 0.1% and 0.5% respective incidence of definite or probable stent thrombosis. The 5-year rate of TLF was 16.9% among patients with diabetes mellitus and 14.7% in patients with at least one small (≤2.5 mm) vessel treated. Covariates independently associated with 5-year TLF in multivariable analysis included diabetes mellitus (odds ratio [OR] 1.89, p < .001), prior coronary artery bypass grafting (OR 2.28, p < .001), prior myocardial infarction (OR 1.85, p = .002), and smaller reference vessel diameter (OR 1.75, p = .004). CONCLUSIONS: Results from the fully adjudicated and monitored RESOLUTE US trial demonstrate long-term 5-year safety and efficacy of the R-ZES stent among a relatively low-risk population of patients, including a 0.5% rate of stent thrombosis at 5 years.

Stochastic tissue window normalization of deep learning on computed tomography.

Tissue window filtering has been widely used in deep learning for computed tomography (CT) image analyses to improve training performance (e.g., soft tissue windows for abdominal CT). However, the effectiveness of tissue window normalization is questionable since the generalizability of the trained model might be further harmed, especially when such models are applied to new cohorts with different CT reconstruction kernels, contrast mechanisms, dynamic variations in the acquisition, and physiological changes. We evaluate the effectiveness of both with and without using soft tissue window normalization on multisite CT cohorts. Moreover, we propose a stochastic tissue window normalization (SWN) method to improve the generalizability of tissue window normalization. Different from the random sampling, the SWN method centers the randomization around the soft tissue window to maintain the specificity for abdominal organs. To evaluate the performance of different strategies, 80 training and 453 validation and testing scans from six datasets are employed to perform multiorgan segmentation using standard 2D U-Net. The six datasets cover the scenarios, where the training and testing scans are from (1) same scanner and same population, (2) same CT contrast but different pathology, and (3) different CT contrast and pathology. The traditional soft tissue window and nonwindowed approaches achieved better performance on (1). The proposed SWN achieved general superior performance on (2) and (3) with statistical analyses, which offers better generalizability for a trained model.

Impact of Abdominal Obesity on Proximal and Distal Aorta Wall Thickness in African Americans: The Jackson Heart Study.

OBJECTIVE: Abdominal obesity and wall thickness of the central arteries have been associated with higher risk of cardiovascular disease. Despite the higher burden of overweight and cardiovascular disease among African Americans, limited data are available on the association of abdominal obesity with aortic wall thickness in African Americans. We assessed the cross-sectional and the longitudinal associations of abdominal obesity with aortic intima-media thickness (aIMT) in a cohort of African Americans from the Jackson Heart Study. METHODS: Data on aIMT and repeated measures of waist circumference (WC) and waist to height ratio from 1,572 participants, as well as on abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and aIMT from 1,223 participants, were analyzed. aIMT was measured at proximal ascending aorta (PA-aIMT), proximal descending aorta (PD-aIMT), and distal aorta (bifurcation) using cardiac magnetic resonance. SAT and VAT were measured using computerized tomography. RESULTS: WC and WHtR were longitudinally associated with PA-aIMT and PD-aIMT; SAT and VAT were associated with PA-aIMT only. Only WC was associated with distal aIMT. CONCLUSIONS: Abdominal obesity measures are associated with increased proximal aIMT in adult African Americans. Only WC is associated with wall thickness in all three segments of the aorta.

Body Composition and Diabetes Risk in South Asians: Findings From the MASALA and MESA Studies.

OBJECTIVE: South Asians have a higher prevalence of type 2 diabetes compared with other race/ethnic groups. Body composition is associated with the risk for type 2 diabetes. Differences in body composition between South Asians and other race/ethnic groups are one hypothesized mechanism to explain the disproportionate prevalence of type 2 diabetes in this population. RESEARCH DESIGN AND METHODS: This study used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) cohorts to determine whether body composition mediated the elevated prevalence of impaired fasting glucose and type 2 diabetes in South Asians. Participants (n = 2,615) with complete body composition data were included. Ordinal logistic regression models were calculated to determine the odds for glycemic impairment in South Asians compared with the MESA cohort. RESULTS: In multivariate models, South Asians had a significantly higher prevalence of glycemic impairment and type 2 diabetes compared with all four race/ethnic groups included in the MESA (P < 0.001 for all). In unadjusted and multivariate adjusted models, South Asians had higher odds for impaired fasting glucose and type 2 diabetes compared with all other race/ethnic groups (P < 0.001 for all). The addition of body composition measures did not significantly mitigate this relationship. CONCLUSIONS: We did not identify strong evidence that accounting for body composition explains differences in the risk for type 2 diabetes. Future prospective studies of the MESA and MASALA cohorts are needed to understand how adipose tissue impacts the risk for type 2 diabetes and how to best assess this risk.

LumenRECON Guidewire: Pilot Study of a Novel, Nonimaging Technology for Accurate Vessel Sizing and Delivery of Therapy in Femoropopliteal Disease.

BACKGROUND: Proper vessel sizing during endovascular interventions is crucial to avoid adverse procedural and clinical outcomes. LumenRECON (LR) is a novel, nonimaging, 0.035-inch wire-based technology that uses the physics-based principle of Ohm's law to provide a simple, real-time luminal size while also providing a platform for therapy delivery. This study evaluated the accuracy, reliability, and safety of the LR system in patients presenting for a femoropopliteal artery intervention. METHODS AND RESULTS: This multicenter, prospective pilot study of 24 patients presenting for peripheral intervention compared LR measurements of femoropopliteal artery size to angiographic visual estimation, duplex ultrasound, quantitative angiography, and intravascular ultrasound. The primary effectiveness and safety end point was comparison against core laboratory adjudicated intravascular ultrasound values and major adverse events, respectively. Additional preclinical studies were also performed in vitro and in vivo in swine to determine the accuracy of the LR guidewire system. No intra- or postprocedure device-related adverse events occurred. A balloon or stent was successfully delivered in 12 patients (50%) over the LR wire. Differences in repeatability between successive LR measurements was 2.5±0.40% (R2=0.96) with no significant bias. Differences in measurements of LR to other modalities were 0.5±1.7%, 5.0±1.8%, -1.5±2.0%, and 6.8±3.4% for intravascular ultrasound core laboratory, quantitative angiography, angiographic, and duplex ultrasound, respectively. CONCLUSIONS: This study demonstrates that through a physics-based principle, LR provides a real-time, safe, reproducible, and accurate vessel size of the femoropopliteal artery during intervention and can additionally serve as a conduit for therapy delivery over its wire-based platform.

Lifetime marijuana use and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND AND AIMS: Unlike tobacco, the effect of marijuana smoke on subclinical atherosclerosis, a surrogate measure for cardiovascular disease, is not known. This study aimed to determine the association between lifetime exposure to marijuana and measures of subclinical atherosclerosis in mid-life. DESIGN, SETTING AND PARTICIPANTS: We used data from the US-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of black and white men and women aged 18-30 years at baseline in 1985-86, with up to seven follow-up examinations over 25 years. A total of 3498 participants in the CARDIA study were included in this study. MEASUREMENTS: Cumulative years of exposure to marijuana (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of use) using repeated assessments every 2-5 years for 25 years. Abdominal artery calcium (AAC) and coronary artery calcium (CAC) scores were measured by computed tomography at year 25 examination. RESULTS: Among 3117 participants with AAC and CAC measurements, 2627 (84%) reported past marijuana use and 1536 (49%) past daily tobacco smoking. Compared with tobacco smokers, 46% of whom reported 10 or more pack-years of use, only 12% of marijuana users reported 5 or more marijuana-years of use and only 6% reported having used marijuana daily. We found a significant interaction between never and ever tobacco users on the association between cumulative marijuana use and AAC (P = 0.05). Among those who never smoked tobacco, cumulative marijuana-years were not associated with AAC or CAC in models adjusted for demographics, cardiovascular risk factors, licit and illicit drug exposure and depression symptoms. However, among ever tobacco smokers, marijuana exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using AAC = 0 and CAC = 0 as a reference group, the odds ratio (OR) was 1.97 [95% confidence interval (CI) = 1.21-3.21, P = 0.007] for AAC > 0/CAC = 0 and 1.83 (95% CI = 1.02-3.31, P = 0.04) for CAC > 0), regardless of AAC. Tobacco smoking was associated strongly with both AAC and CAC. CONCLUSION: Marijuana use appears to be associated with subclinical atherosclerosis, but only among ever tobacco users.

A universal drug delivery catheter for the treatment of infrapopliteal arterial disease: Results from the multi-center first-in-human study.

OBJECTIVE: The objective of this study was to assess the feasibility, safety and initial efficacy of paclitaxel administration using a novel drug delivery catheter for the prevention of restenosis in infrapopliteal de novo and restenotic lesions. BACKGROUND: Restenosis continues to be a great challenge after percutaneous revascularization procedures for peripheral arterial disease, particularly for below-the-knee applications. METHODS: A prospective, multicenter first-in-human registry of a novel delivery catheter delivering liquid paclitaxel was conducted in 10 patients. The primary efficacy endpoint at 6 months was freedom from clinically driven target lesion revascularization (CD-TLR) and the primary safety endpoint at 1, 3, and 6 months were thrombosis, major amputation in the target limb and target limb related death. RESULTS: All patients tolerated the procedure well with no reports of adverse procedural events. Twelve (n = 12) lesions in ten patients were treated with a mean lesion length of 83.3 ± 49.2 mm, with the lesion length range of 30mm to 182 mm. At 6-month follow-up, the rate of CD-TLR was 30% (3 of 10 patients). Zero patients (0 out of 10) demonstrated thrombosis, major amputation in the target limb and target limb related death at the 1, 3, and 6 month follow-up intervals. CONCLUSIONS: This first in-human experience obtained in a multicenter study of real-world de novo and restenotic lesions demonstrates a favorable safety and efficacy profile at 6 months. Randomized comparison to current drug coated balloons should be performed to further validate this approach and positive experience.

Echocardiographic Pulmonary Artery Systolic Pressure in the Coronary Artery Risk Development in Young Adults (CARDIA) Study: Associations With Race and Metabolic Dysregulation.

BACKGROUND: The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle-aged, biracial community-based cohort. METHODS AND RESULTS: At the CARDIA year-25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (ß 0.94, 95% CI 0.24-1.64; P=0.009), but this association was no longer significant after further adjustment for lung volume (ß 0.42, 95% CI -0.68 to 0.96; P=0.74). Insulin resistance, inflammation (C-reactive protein and interleukin-6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e'] and left atrial volume index). CONCLUSIONS: In a large biracial cohort of middle-aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-sectional Analysis of Two Cohort Studies.

BACKGROUND: The relationship between body weight and cardiometabolic disease may vary substantially by race/ethnicity. OBJECTIVE: To determine the prevalence and correlates of the phenotype of metabolic abnormality but normal weight (MAN) for 5 racial/ethnic groups. DESIGN: Cross-sectional analysis. SETTING: 2 community-based cohorts. PARTICIPANTS: 2622 white, 803 Chinese American, 1893 African American, and 1496 Hispanic persons from MESA (Multi-Ethnic Study of Atherosclerosis) and 803 South Asian participants in the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study. MEASUREMENTS: Prevalence of 2 or more cardiometabolic abnormalities (high fasting glucose, low high-density lipoprotein cholesterol, and high triglyceride levels and hypertension) among normal-weight participants was estimated. Correlates of MAN were assessed by using log-binomial models. RESULTS: Among normal-weight participants (n = 846 whites, 323 Chinese Americans, 334 African Americans, 252 Hispanics, and 195 South Asians), the prevalence of MAN was 21.0% (95% CI, 18.4% to 23.9%) in whites, 32.2% (CI, 27.3% to 37.4%) in Chinese Americans, 31.1% (CI, 26.3% to 36.3%) in African Americans, 38.5% (CI, 32.6% to 44.6%) in Hispanics, and 43.6% (CI, 36.8% to 50.6%) in South Asians. Adjustment for demographic, behavioral, and ectopic body fat measures did not explain racial/ethnic differences. After adjustment for age, sex, and race/ethnicity-body mass index (BMI) interaction, for the equivalent MAN prevalence at a BMI of 25.0 kg/m2 in whites, the corresponding BMI values were 22.9 kg/m2 (CI, 19.5 to 26.3 kg/m2) in African Americans, 21.5 kg/m2 (CI, 18.5 to 24.5 kg/m2) in Hispanics, 20.9 kg/m2 (CI, 19.7 to 22.1 kg/m2) in Chinese Americans, and 19.6 kg/m2 (CI, 17.2 to 22.0 kg/m2) in South Asians. LIMITATION: Cross-sectional study design and lack of harmonized dietary data between studies. CONCLUSION: Compared with whites, all racial/ethnic minority groups had a statistically significantly higher prevalence of MAN, which was not explained by demographic, behavioral, or ectopic fat measures. Using a BMI criterion for overweight to screen for cardiometabolic risk may result in a large proportion of racial/ethnic minority groups being overlooked. PRIMARY FUNDING SOURCE: National Institutes of Health.

Optical coherence tomography: guided therapy of in-stent restenosis for peripheral arterial disease.

Approximately 27 million people in Europe and North America currently have peripheral arterial disease (PAD). The endovascular treatment of stenosis or blocked peripheral arteries in PAD include percutaneous transluminal angioplasty with or without a drug coated balloon (DCB), atherectomy (rotational, directional, orbital or laser), and stenting. The development of next generation peripheral stents and drug-coated stents have led to the improved treatment of complex superficial femoral artery (SFA) lesions, and consequently increased their usage. Additionally, the technologies developed for PAD intervention have further improved the overall adoption of endovascular procedures leading to increased utilization of stents to address procedural dissections (bailout stenting), as support scaffolding for complex lesions, and to prevent preventing elastic recoil post balloon angioplasty. For example, bail-out stenting after DCB angioplasty has been reported to be as high as 40% in long lesions and as high as 46% in chronic total occlusions lesions. In total, approximately 200,000 stents are placed annually in the femoral and popliteal arteries in PAD patients in the USA, with 30% to 40% of these stents expected to develop in-stent restenosis within 2-3 years of implantation. Accordingly, the treatment of in-stent restenosis (ISR) remains a substantial healthcare burden. Few technologies reported on improved ISR patency rates as compared to PTA treatment alone, including drug-eluting stents and balloons, laser atherectomy or covered stents. However, the reported longer-term patency for ISR remains suboptimal creating a cyclical treatment pattern that burdens patients and providers. In this review, we present the rational and clinical evidence for utilizing OCT-guided therapies for the treatment of ISR for PAD.

Ectopic Fat Depots and Coronary Artery Calcium in South Asians Compared With Other Racial/Ethnic Groups.

BACKGROUND: South Asians have a low body mass index and high prevalence of cardiovascular disease (CVD) relative to other racial/ethnic groups. Radiographically detected ectopic fat distribution is better associated with CVD than body mass index. We assessed whether differences in ectopic fat depots explained differences in the prevalence/severity of coronary artery calcium (CAC), a predictor of incident CVD events, among South Asians compared with other racial/ethnic groups. METHODS AND RESULTS: We examined the associations of radiographically detected visceral, intermuscular, intrahepatic, and pericardial fat with CAC among adults without baseline CVD. We compared 803 South Asians in the Mediators of Atherosclerosis in South Asians Living in America to 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis: 2622 whites, 1893 blacks, 1496 Latinos, and 803 Chinese Americans. We adjusted for body mass index and known CVD risk factors. South Asians had the highest intrahepatic fat and lowest pericardial fat volume (PFV). There was a positive graded association between ectopic fat and higher CAC scores in all the groups with the strongest associations observed with PFV. PFV was independently associated with CAC severity in South Asians (P=0.01) and blacks (P=0.05) and borderline in whites (P=0.06). PFV partially explained the higher CAC burden in South Asians compared with blacks, but not the other racial/ethnic groups. CONCLUSIONS: Differences in PFV explain a small fraction of the higher CAC burden in South Asians. Our findings suggest that ectopic fat depots may not explain the elevated CAC risk in South Asians.

Structural and Substituent Group Effects on Multielectron Standard Reduction Potentials of Aromatic N-Heterocycles.

Aromatic N-heterocycles have been used in electrochemical CO2 reduction, but their precise role is not yet fully understood. We used first-principles quantum chemistry to determine how the molecular sizes and substituent groups of these molecules affect their standard redox potentials involving various proton and electron transfers. We then use that data to generate molecular Pourbaix diagrams to find the electrochemical conditions at which the aromatic N-heterocycle molecules could participate in multiproton and electron shuttling in accordance with the Sabatier principle. While one-electron standard redox potentials for aromatic N-heterocycles can vary significantly with molecule size and the presence of substituent groups, the two-electron and two-proton standard redox potentials depend much less on structural modifications and substituent groups. This indicates that a wide variety of aromatic N-heterocycles can participate in proton, electron, and/or hydride shuttling under suitable electrochemical conditions.

Cardiac CT: A system architecture study.

BACKGROUND: We are interested in exploring dedicated, high-performance cardiac CT systems optimized to provide the best tradeoff between system cost, image quality, and radiation dose. OBJECTIVE: We sought to identify and evaluate a broad range of CT architectures that could provide an optimal, dedicated cardiac CT solution. METHODS: We identified and evaluated thirty candidate architectures using consistent design choices. We defined specific evaluation metrics related to cost and performance. We then scored the candidates versus the defined metrics. Lastly, we applied a weighting system to combine scores for all metrics into a single overall score for each architecture. CT experts with backgrounds in cardiovascular radiology, x-ray physics, CT hardware and CT algorithms performed the scoring and weighting. RESULTS: We found nearly a twofold difference between the most and the least promising candidate architectures. Architectures employed by contemporary commercial diagnostic CT systems were among the highest-scoring candidates. We identified six architectures that show sufficient promise to merit further in-depth analysis and comparison. CONCLUSION: Our results suggest that contemporary diagnostic CT system architectures outperform most other candidates that we evaluated, but the results for a few alternatives were relatively close. We selected six representative high-scoring candidates for more detailed design and further comparative evaluation.