Rationale and Design of the CREDENCE Trial: computed TomogRaphic evaluation of atherosclerotic DEtermiNants of myocardial IsChEmia.

BACKGROUND: Coronary computed tomography angiography (CCTA) allows for non-invasive assessment of obstructive coronary artery disease (CAD) beyond measures of stenosis severity alone. This assessment includes atherosclerotic plaque characteristics (APCs) and calculation of fractional flow reserve (FFR) from CCTA (FFRCT). Similarly, stress imaging by myocardial perfusion scintigraphy (MPS) provides vital information. To date, the diagnostic performance of integrated CCTA assessment versus integrated MPS assessment for diagnosis of vessel-specific ischemia remains underexplored. METHODS: CREDENCE will enroll adult individuals with symptoms suspicious of CAD referred for non-emergent invasive coronary angiography (ICA), but without known CAD. All participants will undergo CCTA, MPS, ICA and FFR. FFR will be performed for lesions identified at the time of ICA to be ≥40 and <90 % stenosis, or those clinically indicated for evaluation. Study analyses will focus on diagnostic performance of CCTA versus MPS against invasive FFR reference standard. An integrated stenosis-APC-FFRCT metric by CCTA for vessel-specific ischemia will be developed from derivation cohort and tested against a validation cohort. Similarly, integrated metric by MPS for vessel-specific ischemia will be developed, validated and compared. An FFR value of ≤0.80 will be considered as ischemia causing. The primary endpoint will be the diagnostic accuracy of vessel territory-specific ischemia of integrated stenosis-APC-FFRCT measure by CCTA, compared with perfusion or perfusion-myocardial blood flow stress imaging testing, against invasive FFR. DISCUSSION: CREDENCE will determine the performance of integrated CCTA metric compared to integrated MPS measure for diagnosis of vessel-specific ischemia. If proven successful, this study may reduce the number of missed diagnoses and help to optimally predict ischemia-causing lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02173275 . Registered on June 23, 2014.

Homoarginine in the renal and cardiovascular systems.

Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.

Semaglutide 2.4 mg clinical outcomes in patients with obesity or overweight in a real-world setting: A 6-month retrospective study in the United States (SCOPE).

Background: Management guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long-term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real-world setting is limited. Objective: To assess changes in body weight and other clinical outcomes at 6-month follow-up among adults on semaglutide 2.4 mg in a real-world setting in the United States (US). Methods: Observational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims-linked electronic health record database. Results: Mean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m2. After 6 months, mean body weight change was -10.5 ± 6.8 kg (95% CI: -11.2; -9.8, p < 0.001) and mean percentage body weight change was -10.0% ± 6.6% (95% CI: -10.7; -9.3, p < 0.001). Most (79.0%) patients had ≥5% body weight reduction, 48.1% had ≥10% body weight reduction, and 19.0% had ≥15% body weight reduction. Among patients with available data, the mean change in HbA1c (n = 30) was -0.6% ± 1.2% (95% CI: -1.0; -0.1, p = 0.016) and nearly two-thirds of patients with prediabetes or diabetes at baseline reverted to normoglycemia. Mean reductions of -4.4 ± 12.3 mmHg (95% CI: -5.7; -3.0, p < 0.001) and -1.7 ± 8.4 mmHg (95% CI: -2.6; -0.7, p < 0.001) were observed in systolic and diastolic blood pressure, respectively (n = 307). Statistically significant reductions in mean total cholesterol (-12.2 ± 38.8 mg/dl [95% CI: -24.3 to -0.06, p < 0.049]) and triglycerides (-18.3 ± 43.6 mg/dl [95% CI: -4.7; -31.9, p < 0.009]) were also observed (n = 42). Conclusions: This study demonstrated the effectiveness of semaglutide 2.4 mg in reducing body weight and improving cardiometabolic parameters in adults with overweight or obesity in a real-world clinical practice setting, showing a significant mean body weight reduction and improvements in biomarkers like blood pressure and HbA1c over a 6-month period. These findings, aligning with previous clinical trials at comparable time points, highlight the clinical relevance of semaglutide as an effective therapeutic option for obesity.

Costs and Healthcare Resource Utilization Associated with Idarucizumab or Andexanet Alfa Oral Anticoagulant Reversal in Patients Hospitalized with Life-Threatening Bleeds.

Purpose: To assess costs and healthcare resource utilization (HCRU) associated with the use of idarucizumab for the reversal of dabigatran and andexanet alfa for the reversal of direct oral Factor Xa inhibitors. Methods: This retrospective study utilizing Premier Healthcare Database (PHD) included patients aged ≥18 years on direct oral anticoagulants (DOACs) who experienced life-threatening bleeds, discharged from the hospital during 5/1/2018-6/30/2019, and received idarucizumab or andexanet alfa. Inverse of treatment probability weighting (IPTW) method was used to balance patient and clinical characteristics between treatment cohorts. Results: Idarucizumab patients were older than andexanet alfa patients (median age 81 vs 77 years; p < 0.001), and less likely to experience intracranial hemorrhage (ICH) (37.1%vs 73.8%; p = 0.001). After IPTW adjustment, idarucizumab patients incurred lower mean total hospital costs ($30,413 ± $33,028 vs $44,477 ± $30,036; p < 0.001),and mean intensive care unit (ICU) cost ($25,114 ± $30,433 vs $43,484 ± $29,335; p < 0.001). Conclusions: Anticoagulant reversal therapy with idarucizumab was associated with significantly lower adjusted mean total hospital and ICU costs compared with andexanet alfa. However, a higher prevalence of ICH bleeds was noted in the andexanet alfa group. Trial Registration: Not applicable.

Healthcare Resource Utilization for Oral Anticoagulant Reversal Therapies in Non-Valvular Atrial Fibrillation/Venous Thromboembolism Patients.

BACKGROUND: The objective of the study was to describe the healthcare resource utilization (HCRU) and associated costs with hospitalized patients receiving specific versus non-specific oral anticoagulation reversal therapy for life-threatening bleeds and emergency surgeries or urgent procedures. METHODS: This retrospective observational study using the Premier Healthcare Database included adult patients aged ≥ 18 years treated with idarucizumab (IDA) or 3- or 4-factor prothrombin complex concentrates (PCC) to reverse the effects of dabigatran or warfarin, respectively, between October 2015 and February 2018. RESULTS: Median ages for IDA (n = 1,232) and PCC (n = 4,939) patients were 78 and 74 years (P < 0.001), respectively. IDA patients had lower bleeding and stroke risk assessment scores (HAS-BLED; P < 0.001 and CHA2DS2-VASc; P = 0.014) and lower prevalence of comorbidities compared with PCC patients. Median hospital length of stay was 6 and 7 days for patients who received IDA or PCC (P < 0.001), respectively. The percentage of patients with an intensive care unit (ICU) admission was lower for IDA patients compared with PCC patients (61.3% vs. 68.7%; P < 0.001). Median total costs per hospitalization were $19,357 for IDA patients and $26,920 for PCC patients (P < 0.001). Median costs per hospitalization for IDA and PCC treatment were $3,277 and $4,424, respectively. When HCRU and costs were examined by cause of reversal and type of bleed, similar trends in hospitalized costs emerged for IDA compared with PCC treatment. CONCLUSIONS: This analysis revealed lower HCRU and total hospital costs in patients administered IDA compared with PCC for reversal of oral anticoagulation, though differences in population characteristics and bleeding events were observed that may have contributed to these findings.

An approach to evaluate myocardial perfusion defect assessment for projection-based DECT: A phantom study.

INTRODUCTION: Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown. METHODS: Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions. RESULTS: Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p < 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p < 0.001). Specificity of all material pair modes remained 100%. CONCLUSIONS: Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography.

Recent experimental studies have suggested that galectin-3 has an interaction with aldosterone, and modifies its adverse effects. We therefore aimed to elucidate whether the relationship between plasma aldosterone concentrations (PACs) and long-term fatal cardiovascular (CV) events would depend on plasma galectin-3 levels. A total of 2,457 patients (median age: 63.5 [interquartile range (IQR) = 56.3 to 70.6] years, 30.1% women) from the LUdwigshafen RIsk and Cardiovascular Health study, with a median follow-up of 9.9 (IQR = 8.5 to 10.7) years, were included. We tested the interaction between aldosterone and galectin-3 for CV-mortality using a multivariate Cox proportional hazard model, reporting hazard ratios (HRs) with 95% confidence intervals (95%CIs). Adjustments for multiple CV risk factors as well as medication use were included. Mean PAC was 79.0 (IQR = 48.0 to 124.0) pg/ml and there were 558 (16.8%) CV deaths. There was a significant interaction between PAC and galectin-3 (p = 0.021). When stratifying patients by the median galectin-3, there was a significant association between aldosterone and CV-mortality for those above (HR per 1 standard deviation = 1.14; 95%CI [1.01 to 1.30], p = 0.023), but not below the cut-off value (HR per 1 standard deviation = 1.00; 95%CI [0.87 to 1.15], p = 0.185). In conclusion, the current study demonstrates for the first time a modifying effect of galectin-3 on the association between aldosterone and CV-mortality risk in humans. These findings indicate that galectin-3 is an intermediate between aldosterone and adverse outcomes.

Healthcare resource utilization and expenditures among newly-diagnosed elderly non-valvular atrial fibrillation patients initiating oral anticoagulants.

Aims: Non-valvular atrial fibrillation (NVAF) prevalence increases with age. Hence, evaluating the economic burden among older-aged patients is vital. This study aimed to compare healthcare resource utilization (HRU) and costs among newly-diagnosed older-aged NVAF patients treated with warfarin, rivaroxaban, or apixaban vs. dabigatran.Materials and Methods: Newly-diagnosed older-aged (aged ≥65 years) NVAF patients initiating dabigatran, warfarin, rivaroxaban, or apixaban (first prescription date = index date) from 01JAN2010-31DEC2015 and with continuous enrollment for ≥12 months pre-index date were included from 100% Medicare database. Patient data were assessed until drug discontinuation/switch/dose change/death/disenrollment/study end (up to 12 months). Dabigatran initiators were 1:1 propensity score-matched (PSM) with warfarin, rivaroxaban, or apixaban initiators. Generalized linear models were used to compare all-cause HRU and costs per-patient-per-month (PPPM) between the matched cohorts.Results: After PSM with dabigatran, 70,531 warfarin, 51,673 rivaroxaban, and 25,209 apixaban patients were identified. Dabigatran patients had significantly fewer generalized-linear-model-adjusted PPPM hospitalizations (0.114 vs. 0.123; 0.111 vs. 0.121), and outpatient visits (2.864 vs. 4.201; 2.839 vs. 2.949) than warfarin and rivaroxaban patients, respectively, but had significantly more PPPM hospitalizations (0.103 vs. 0.090) and outpatient visits (2.780 vs. 2.673) than apixaban patients (all p < .0001). Dabigatran patients incurred significantly lower adjusted total PPPM costs ($3,309 vs. $3,362; $3,285 vs. $3,474) than warfarin and rivaroxaban patients, respectively (all p < .01) but higher total PPPM costs ($3,192 vs. $2,986) than apixaban patients (all p < .0001).Limitations: This study is subject to the inherent limitations of any claims dataset, including potential bias from coding errors and identification of medical conditions using diagnosis codes as opposed to clinical evidence. Medications filled over-the-counter or provided as samples by the physician are never captured in claims data.Conclusions: Newly-diagnosed older-aged NVAF patients initiating dabigatran incurred significantly lower adjusted all-cause HRU and costs than warfarin and rivaroxaban patients but higher adjusted HRU and costs than apixaban patients.

Evaluating the cost-effectiveness of percutaneous closure of a patent foramen ovale versus medical management in patients with a cryptogenic stroke: from the UK payer perspective.

AIMS: Percutaneous closure of a patent foramen ovale (PFO) is known to lower the risk of recurrent stroke in patients with a cryptogenic stroke. However, the economic implications of transcatheter PFO closure are less well known. From a UK payer perspective, a detailed economic appraisal of PFO closure was performed for prevention of recurrent ischemic stroke in patients with a PFO who had experienced a cryptogenic stroke. MATERIALS AND METHODS: A Markov cohort model was constructed using a 5-year time-horizon with a patient mean age of 45.2 years, reflecting the characteristics reported in the REDUCE trial. Transition probabilities, clinical inputs, costs, and utility values were ascertained from published and national costing sources. Total costs, incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated, utilizing a discount rate of 3.5%. A range of univariate and probabilistic sensitivity analyses were also performed. RESULTS: When applying a willingness-to-pay (WTP) threshold of £20,000/QALY in accordance with NICE guidelines, PFO closure compared with antiplatelet therapy alone showed a beneficial cost/QALY of £18,584, attained at 4 years. Applying discount rates of 0% and 6% had a negligible effect on the base-case model findings. PFO closure demonstrated a 76.9% probability of being cost-effective at a WTP threshold of £20,000/QALY at a 5-year time-horizon. LIMITATIONS: This model focused specifically on UK stroke patients and typically enrolled young (mean age <65 years old) patients. Hence, caution should be taken when comparing data vs non-UK populations, and it remains unclear how older patients might have affected cost-effectiveness findings, as the risk of paradoxical embolism can persist as patients age. CONCLUSION: Percutaneous closure of a PFO is cost-effective compared with antiplatelet therapy alone, underlining the economic benefits potentially afforded by this treatment in selected patients.

The Predictive Value of Coronary Artery Calcium Scoring for Major Adverse Cardiac Events According to Renal Function (from the Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter [CONFIRM] Registry).

The prognostic performance of coronary artery calcium score (CACS) for predicting adverse outcomes in patients with decreased renal function remains unclear. We aimed to examine whether CACS improves risk stratification by demonstrating incremental value beyond a traditional risk score according to renal function status. 9,563 individuals without known coronary artery disease were enrolled. Estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) was ascertained using the modified Modification of Diet in Renal Disease formula, and was categorized as: ≥90, 60 to 89, and <60. CACS was categorized as 0, 1 to 100, 101 to 400, and >400. Multivariable Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, and late revascularization (>90 days). Mean age was 55.8 ± 11.5 years (52.8% male). In total, 261 (2.7%) patients experienced MACE over a median follow-up of 24.5 months (interquartile range: 16.9 to 41.1). Incident MACE increased with higher CACS across each eGFR category, with the highest rate observed among patients with CACS >400 and eGFR <60 (95.1 per 1,000 person-years). A CACS >400 increased MACE risk with HR 4.46 (95% CI 1.68 to 11.85), 6.63 (95% CI 4.03 to 10.92), and 6.14 (95% CI 2.85 to 13.21) for eGFR ≥90, 60 to 89, and <60, respectively, as compared with CACS 0. Further, CACS improved discrimination and reclassification beyond Framingham 10-year risk score (FRS) (AUC: 0.70 vs 0.64; category free-NRI: 0.51, all p <0.001) for predicting MACE in patients with impaired renal function (eGFR < 90). In conclusion, CACS improved risk stratification and provided incremental value beyond FRS for predicting MACE, irrespective of eGFR status.

Association between epicardial fat volume and fractional flow reserve: An analysis of the determination of fractional flow reserve (DeFACTO) study.

BACKGROUND: This study examines the relationship between epicardial fat volume (EFV) and lesion-specific ischemia by fractional flow reserve (FFR). METHODS: In a study of 173 patients (63.0 ±â€¯8.3 years) undergoing FFR, EFV was determined using cardiac computed tomography. Relationships between EFV and FFR were assessed using multivariable linear and logistic regression. RESULTS: Using multivariable linear and logistic regression, no association between EFV and FFR was observed (ß [SE] = -0.001 [0.003], P = 0.6, OR [95% CI]: 1.02 [0.94-1.11], P = 0.64, respectively). CONCLUSION: In patients with suspected or known coronary artery disease undergoing invasive angiography, EFV was not associated with FFR.

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals.

Aims: Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results: Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion: CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.

Usefulness of baseline statin therapy in non-obstructive coronary artery disease by coronary computed tomographic angiography: From the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) study.

BACKGROUND: The extent to which the presence and extent of subclinical atherosclerosis by coronary computed tomography angiography influences a potential mortality benefit of statin is unknown. We evaluated the relationship between statin therapy, mortality, and subclinical atherosclerosis. METHODS: In the CONFIRM study, patients with normal or non-obstructive plaque (<50% diameter stenosis) for whom data on baseline statin use was available were included. Coronary artery calcium (CAC) was quantified using the Agatston score. The extent of non-obstructive coronary atherosclerosis was quantified using the segment involvement score (SIS). 8,016 patients were followed for a median of 2.5 years with analysis of all-cause mortality and major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, unstable angina, target vessel revascularization, and coronary artery disease-related hospitalization. RESULTS: 1.2% of patients experienced all-cause mortality. Patients not on baseline statin therapy had a stepwise increased risk of all-cause mortality by CAC (relative to CAC = 0; CAC 1-99: hazard ratio [HR] 1.65, CAC 100-299: HR 2.19, and CAC≥300: HR 2.98) or SIS (relative to SIS = 0; SIS 1: HR 1.62, SIS 2-3: 2.48 and SIS≥4: 2.95). Conversely, in patients on baseline statin therapy, there was no significant increase in mortality risk with increasing CAC (p value for interaction = 0.049) or SIS (p value for interaction = 0.007). The incidence of MACE was 2.1%. Similar to the all-cause mortality, the risk of MACE was increased with CAC or SIS strata in patient not on baseline statin therapy. However, this relation was not observed in patient on baseline statin therapy. CONCLUSION: In individuals with non-obstructive coronary artery disease, increased risk of adverse events occurs with increasing CAC or SIS who are not on baseline statin therapy. Statin therapy is associated with a mitigation of risk of cardiac events in the presence of increasing atherosclerosis, with no particular threshold of disease burden.

Influence of symptom typicality for predicting MACE in patients without obstructive coronary artery disease: From the CONFIRM Registry (Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry).

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%-49%) and none (0%). Based upon the Diamond-Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 ±12.0 years (54.9% male). During a median follow-up of 5.3 years (interquartile range, 4.6-5.9 years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction = 0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06-2.48, P = 0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34-1.57, P = 0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD.

Comprehensive Modeling and Visualization of Cardiac Anatomy and Physiology from CT Imaging and Computer Simulations.

In clinical cardiology, both anatomy and physiology are needed to diagnose cardiac pathologies. CT imaging and computer simulations provide valuable and complementary data for this purpose. However, it remains challenging to gain useful information from the large amount of high-dimensional diverse data. The current tools are not adequately integrated to visualize anatomic and physiologic data from a complete yet focused perspective. We introduce a new computer-aided diagnosis framework, which allows for comprehensive modeling and visualization of cardiac anatomy and physiology from CT imaging data and computer simulations, with a primary focus on ischemic heart disease. The following visual information is presented: (1) Anatomy from CT imaging: geometric modeling and visualization of cardiac anatomy, including four heart chambers, left and right ventricular outflow tracts, and coronary arteries; (2) Function from CT imaging: motion modeling, strain calculation, and visualization of four heart chambers; (3) Physiology from CT imaging: quantification and visualization of myocardial perfusion and contextual integration with coronary artery anatomy; (4) Physiology from computer simulation: computation and visualization of hemodynamics (e.g., coronary blood velocity, pressure, shear stress, and fluid forces on the vessel wall). Substantially, feedback from cardiologists have confirmed the practical utility of integrating these features for the purpose of computer-aided diagnosis of ischemic heart disease.

Diffuse coronary artery disease among other atherosclerotic plaque characteristics by coronary computed tomography angiography for predicting coronary vessel-specific ischemia by fractional flow reserve.

BACKGROUND AND AIMS: Coronary computed tomography angiography (CCTA) permits effective identification of diffuse CAD and atherosclerotic plaque characteristics (APCs). We sought to examine the usefulness of diffuse CAD beyond luminal narrowing and APCs by CCTA to detect vessel-specific ischemia. METHODS: 407 vessels (n = 252 patients) from the DeFACTO diagnostic accuracy study were retrospectively analyzed for percent plaque diffuseness (PD). Percent plaque diffuseness (PD) was obtained on per-vessel level by summation of all contiguous lesion lengths and divided by total vessel length, and was logarithmically transformed (log percent PD). Additional CCTA measures of stenosis severity including minimal lumen diameter (MLD), and APCs, such as positive remodeling (PR) and low attenuation plaque (LAP), were also included. Vessel-specific ischemia was defined as fractional flow reserve (FFR) ≤0.80. Multivariable regression, discrimination by area under the receiver operating characteristic curve (AUC), and category-free net reclassification improvement (cNRI) were assessed. RESULTS: Backward stepwise logistic regression revealed that for every unit increase in log percent PD, there was a 58% (95% CI: 1.01-2.48, p = 0.048) rise in the odds of having an abnormal FFR, independent of stenosis severity and APCs. The AUC indicated no further improvement in discriminatory ability after adding log percent PD to the final parsimonious model of MLD, PR, and LAP (AUC difference: 0.003, 95% CI: -0.003-0.010, p = 0.33). Conversely, adding log percent PD to the base model of MLD, PR, and LAP improved cNRI by 0.21 (95% CI: 0.01-0.41, p < 0.001). CONCLUSIONS: Accounting for diffuse CAD may help improve the accuracy of CCTA for detecting vessel-specific ischemia.

Role of computed tomography screening for detection of coronary artery disease.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in Western populations, and the prediction and prevention of CAD is an inherent challenge facing current health care societies. Computed tomography (CT) has emerged as a noninvasive imaging tool in the field of cardiovascular disease. Notably, CT scanning for detection of coronary artery calcium (CAC) has proven useful in predicting adverse cardiovascular outcomes as well as early identification of CAD. In asymptomatic persons undergoing screening for CAD, CAC is well established as a surrogate of CAD risk and has demonstrated incremental benefit over and above traditional risk prediction tools. In addition, a zero CAC score has shown to reflect a substantially lower risk of CAD and may therefore be considered an important marker of CAD protection. Irrespective of screening in the asymptomatic population, CAC scanning has also displayed a beneficial role in the symptomatic population, specifically as gatekeeper in guiding further treatment decision making. Further still, the combination of alternative CT screening strategies such as CT screening for lung cancer with CAC scanning may hold particular promise as an effective screening approach by lowering overall health costs as well as limiting radiation exposure.

Multimodality Imaging in Coronary Artery Disease: Focus on Computed Tomography.

Coronary artery disease (CAD) is the leading cause of mortality worldwide, and various cardiovascular imaging modalities have been introduced for the purpose of diagnosing and determining the severity of CAD. More recently, advances in computed tomography (CT) technology have contributed to the widespread clinical application of cardiac CT for accurate and noninvasive evaluation of CAD. In this review, we focus on imaging assessment of CAD based upon CT, which includes coronary artery calcium screening, coronary CT angiography, myocardial CT perfusion, and fractional flow reserve CT. Further, we provide a discussion regarding the potential implications, benefits and limitations, as well as the possible future directions according to each modality.

Fractional Flow Reserve Measurement by Computed Tomography: An Alternative to the Stress Test.

Recent advances in computed tomographic technology have contributed towards improving coronary computed tomography angiography (CCTA) in determining the severity of coronary artery disease anatomically. Although the viability of CCTA has most often been confined to anatomical assessment, recent development has enabled evaluation of the haemodynamic significance of coronary artery disease. In light of this, CCTA-derived fractional flow reserve (FFRCT), a novel imaging modality, now permits the physiological assessment of coronary artery disease. To date, several studies have documented the diagnostic performance of FFRCT, and more trials are being performed that will further substantiate this technique. The present paper provides an overview and discussion of the available evidence for FFRCT in the clinical setting as well as potential future directions of FFRCT.

Vitamin D and Mortality.

In this narrative review, we aim to summarize and discuss the current evidence linking vitamin D and mortality. Low 25-hydroxyvitamin D [25(OH)D] concentrations are associated with an increased risk of mortality. This has been shown in different cohort studies including general populations, as well as various patient cohorts. Some single-study results and meta-analyses indicate that the shape of the relationship between 25(OH)D and mortality follows a U- or a reverse J-shaped curve. Interassay and laboratory differences are, however, a limitation of most previous surveys, and standardization of 25(OH)D measurements is needed for future investigations. Apart from observational data, it has been documented in meta-analyses of randomized controlled trials that vitamin D3 supplementation is associated with a moderate, yet statistically significant, reduction in mortality. This latter finding must be interpreted in light of some limitations such as incomplete follow-up data, but such a reduction of mortality with vitamin D3 supplementation as the finding of meta-analyses of randomized controlled trials strongly argues for the benefits and, importantly, also the safety of vitamin D.