Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Machine learning-based marker for coronary artery disease: derivation and validation in two longitudinal cohorts.

BACKGROUND: Binary diagnosis of coronary artery disease does not preserve the complexity of disease or quantify its severity or its associated risk with death; hence, a quantitative marker of coronary artery disease is warranted. We evaluated a quantitative marker of coronary artery disease derived from probabilities of a machine learning model. METHODS: In this cohort study, we developed and validated a coronary artery disease-predictive machine learning model using 95 935 electronic health records and assessed its probabilities as in-silico scores for coronary artery disease (ISCAD; range 0 [lowest probability] to 1 [highest probability]) in participants in two longitudinal biobank cohorts. We measured the association of ISCAD with clinical outcomes-namely, coronary artery stenosis, obstructive coronary artery disease, multivessel coronary artery disease, all-cause death, and coronary artery disease sequelae. FINDINGS: Among 95 935 participants, 35 749 were from the BioMe Biobank (median age 61 years [IQR 18]; 14 599 [41%] were male and 21 150 [59%] were female; 5130 [14%] were with diagnosed coronary artery disease) and 60 186 were from the UK Biobank (median age 62 [15] years; 25 031 [42%] male and 35 155 [58%] female; 8128 [14%] with diagnosed coronary artery disease). The model predicted coronary artery disease with an area under the receiver operating characteristic curve of 0·95 (95% CI 0·94-0·95; sensitivity of 0·94 [0·94-0·95] and specificity of 0·82 [0·81-0·83]) and 0·93 (0·92-0·93; sensitivity of 0·90 [0·89-0·90] and specificity of 0·88 [0·87-0·88]) in the BioMe validation and holdout sets, respectively, and 0·91 (0·91-0·91; sensitivity of 0·84 [0·83-0·84] and specificity of 0·83 [0·82-0·83]) in the UK Biobank external test set. ISCAD captured coronary artery disease risk from known risk factors, pooled cohort equations, and polygenic risk scores. Coronary artery stenosis increased quantitatively with ascending ISCAD quartiles (increase per quartile of 12 percentage points), including risk of obstructive coronary artery disease, multivessel coronary artery disease, and stenosis of major coronary arteries. Hazard ratios (HRs) and prevalence of all-cause death increased stepwise over ISCAD deciles (decile 1: HR 1·0 [95% CI 1·0-1·0], 0·2% prevalence; decile 6: 11 [3·9-31], 3·1% prevalence; and decile 10: 56 [20-158], 11% prevalence). A similar trend was observed for recurrent myocardial infarction. 12 (46%) undiagnosed individuals with high ISCAD (≥0·9) had clinical evidence of coronary artery disease according to the 2014 American College of Cardiology/American Heart Association Task Force guidelines. INTERPRETATION: Electronic health record-based machine learning was used to generate an in-silico marker for coronary artery disease that can non-invasively quantify atherosclerosis and risk of death on a continuous spectrum, and identify underdiagnosed individuals. FUNDING: National Institutes of Health.

Coronary computed tomography angiographic detection of in-stent restenosis via deep learning reconstruction: a feasibility study.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Implications of the Use of Artificial Intelligence Predictive Models in Health Care Settings : A Simulation Study.

BACKGROUND: Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models. OBJECTIVE: To estimate changes in predictive model performance with use through 3 common scenarios: model retraining, sequentially implementing 1 model after another, and intervening in response to a model when 2 are simultaneously implemented. DESIGN: Simulation of model implementation and use in critical care settings at various levels of intervention effectiveness and clinician adherence. Models were either trained or retrained after simulated implementation. SETTING: Admissions to the intensive care unit (ICU) at Mount Sinai Health System (New York, New York) and Beth Israel Deaconess Medical Center (Boston, Massachusetts). PATIENTS: 130 000 critical care admissions across both health systems. INTERVENTION: Across 3 scenarios, interventions were simulated at varying levels of clinician adherence and effectiveness. MEASUREMENTS: Statistical measures of performance, including threshold-independent (area under the curve) and threshold-dependent measures. RESULTS: At fixed 90% sensitivity, in scenario 1 a mortality prediction model lost 9% to 39% specificity after retraining once and in scenario 2 a mortality prediction model lost 8% to 15% specificity when created after the implementation of an acute kidney injury (AKI) prediction model; in scenario 3, models for AKI and mortality prediction implemented simultaneously, each led to reduced effective accuracy of the other by 1% to 28%. LIMITATIONS: In real-world practice, the effectiveness of and adherence to model-based recommendations are rarely known in advance. Only binary classifiers for tabular ICU admissions data were simulated. CONCLUSION: In simulated ICU settings, a universally effective model-updating approach for maintaining model performance does not seem to exist. Model use may have to be recorded to maintain viability of predictive modeling. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2-vaccinated and Nonvaccinated Patients.

Background Patients who developed myocarditis following SARS-CoV-2 vaccination show abnormalities on cardiac MRI. However, whether myocardial changes occur in asymptomatic individuals following vaccination is not well established. Purpose To assess myocardial 18Fluorine-fluorodeoxyglucose (18F-FDG) uptake on PET/CT in asymptomatic SARS-CoV-2 vaccinated patients compared to nonvaccinated patients. Materials and Methods This retrospective study included patients who underwent 18F-FDG PET/CT for indications unrelated to myocarditis during the period before (11/1/2020 - 2/16/2021) and after (2/17/20121 - 3/31/2022) SARS-CoV-2 vaccines were available. Myocardial and axillary FDG uptake were quantitatively assessed using maximum standardized uptake value (SUVmax). SUVmax values in all patients and in patients stratified by sex (male/female), age (<40, 41-60, >60 years), and time interval between vaccination and PET/CT were compared using Mann-Whitney U test or Kruskal-Wallis test with post ad -hoc Dwass, Steel, Critchlow-Fligner multiple comparison analysis. Results The study included 303 nonvaccinated patients (mean age, 52.9 years ± 14.9 [SD]; 157 females) and 700 vaccinated patients (mean age, 56.8 years ± 13.7 [SD]; 344 females). Vaccinated patients had overall higher myocardial FDG uptake compared to nonvaccinated patients (median SUVmax, 4.8 [IQR: 3.0-8.5] vs median SUVmax, 3.3 [IQR: 2.5-6.2]; P < .0001). Myocardial SUVmax was higher in vaccinated patients regardless of sex (median range, 4.7-4.9 [IQR: 2.9-8.6]) or patient age (median range, 4.7-5.6 [IQR: 2.9-8.6]) compared to corresponding nonvaccinated groups (sex median range, 3.2-3.9 [IQR: 2.4-7.2]; age median range, 3.3-3.3 [IQR: 2.3-6.1]; P range, <.001-.015). Furthermore, increased myocardial FDG uptake was observed in patients imaged 1-30, 31-60, 61-120, and 121-180 days after their second vaccination (median SUVmax range, 4.6-5.1 [IQR: 2.9-8.6]) and increased ipsilateral axillary uptake was observed in patients imaged 1-30, 31-60, 61-120 days after their 2nd vaccination (median SUVmax range, 1.5-2.0 [IQR: 1.2-3.4]) compared to the nonvaccinated patients (P range, <.001-<.001). Conclusion Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT. See also the editorial by Bluemke in this issue.

Functional Effects of Cardiomyocyte Injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Relationship of Plaque Features at Coronary CT to Coronary Hemodynamics and Cardiovascular Events.

Background Plaque assessments with coronary CT angiography (CCTA) and coronary flow indexes have prognostic implications. Purpose To investigate the association and additive prognostic value of plaque burden and characteristics at CCTA with coronary pressure and flow. Materials and Methods Data of patients with coronary artery disease who underwent CCTA within 90 days before physiologic assessments at tertiary cardiovascular centers between January 2011 and December 2018 were retrospectively analyzed, which included fractional flow reserve (FFR), resting distal coronary artery pressure (Pd)-to-aortic pressure (Pa) ratio (hereafter, Pd/Pa), coronary flow reserve (CFR), hyperemic flow (1/hyperemic mean transit time [Tmn]), resting flow (1/resting Tmn), and index of microcirculatory resistance (IMR). Four high-risk plaque (HRP) attributes at CCTA defined high disease burden (plaque burden, ≥70%; minimum lumen area, <4 mm2) and adverse plaque (low-attenuation plaque, positive remodeling). Their lesion-specific relationships with coronary hemodynamic parameters and major adverse cardiovascular events (MACE) were investigated using a generalized estimating equation and marginal Cox model. Results Among 406 lesions from 335 patients (mean age, 67 years ± 10 [SD]; 259 men), high disease burden is predicted by FFR (odds ratio [OR], 0.55; P < .001), resting Pd/Pa (OR, 0.47; P < .001), CFR (OR, 0.85; P = .004), and hyperemic flow (OR, 0.91; P = .03), and adverse plaque by FFR (OR, 0.67; P < .001), resting Pd/Pa (OR, 0.69; P = .001), hyperemic flow (OR, 0.76; P = .006), resting flow (OR, 0.54; P = .001), and IMR (OR, 1.27; P = .008). High disease burden (hazard ratio [HR], 4.0; P = .004) and adverse plaque (HR, 2.7; P = .02) were associated with a higher risk of MACE (n = 27) over median 2.9-year follow-up. In six lesion subsets with normal flow or pressure, at least three HRP attributes predicted a higher MACE rate (HR range, 2.6-6.3). Conclusion High-risk plaque features and plaque burden at coronary CT angiography were associated with cardiovascular events independent of coronary hemodynamic parameters. Clinical trial registration no. NCT04037163 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

Genome-first recall of healthy individuals by polygenic risk score reveals differences in coronary artery calcium.

Genetic risk for coronary artery disease (CAD) is commonly measured with polygenic risk scores (PRS); yet, the relationship of atherosclerotic burden with PRS in healthy individuals not at high clinical risk for CAD (ie, without a high pooled cohort equations [PCE] score) is unknown. Here, we implemented a novel recall-by-PRS strategy to measure coronary artery calcium (CAC) scores prospectively in 53 healthy individuals with extreme high PRS (median [IQR] PRS = 94% [83-98]) and low PRS (median [IQR] PRS = 3.6% [1.2-10]). The high PRS group was associated with a 2.8-fold greater CAC than the low PRS group, adjusted for age, sex, BMI, smoking, and statin use, and had a 6.7-fold greater proportion of individuals with CAC exceeding 300 HU. These findings reveal that extreme PRS tracks with CAD risk even in those without high clinical risk and demonstrate proof of principle for recall-by-PRS approaches that should be assessed prospectively in larger trials.

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

BACKGROUND: Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery. METHODS: The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. CONCLUSIONS: The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

F-18 meta-fluorobenzylguanidine PET imaging of myocardial sympathetic innervation.

BACKGROUND: I-123 meta-iodobenzylguanidine (MIBG) imaging has long been employed to noninvasively assess the integrity of human norepinephrine transporter-1 and, hence, myocardial sympathetic innervation. Positron-emitting F-18 meta-fluorobenzylguanidine (MFBG) has recently been developed for potentially superior quantitative characterization. We assessed the feasibility of MFBG imaging of myocardial sympathetic innervation. METHODS: 16 patients were imaged with MFBG PET (30-minute dynamic imaging of chest, followed by 3 whole-body acquisitions between 30 minutes and 4-hour post-injection). Blood kinetics were assessed from multiple samples. Pharmacokinetic modeling with reversible 1- and 2-compartment models was performed. Kinetic rate constants were re-calculated from truncated datasets. All patients underwent concurrent MIBG SPECT. RESULTS: MFBG myocardial uptake was rapid and sustained; the mean standardized uptake value (SUV (mean ± standard deviation)) was 5.1 ± 2.2 and 3.4 ± 1.9 at 1 hour and 3-4-hour post-injection, respectively. The mean K1 and distribution volume (VT) were 1.1 ± 0.6 mL/min/g and 34 ± 22 mL/cm3, respectively. Both were reproducible when re-calculated from truncated 1-hour datasets (Intraclass Correlation Coefficient of 0.99 and 0.91, respectively). Spearman's ϱ = 0.86 between MFBG SUV and VT and 0.80 between MFBG PET-derived VT and MIBG SPECT-derived heart-to-mediastinum activity concentration ratio. CONCLUSION: MFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation.

SUBRETINAL DRUSENOID DEPOSITS AND SOFT DRUSEN: Are They Markers for Distinct Retinal Diseases?

PURPOSE: Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases. METHODS: One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. RESULTS: There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 ± 18 vs. 69 ± 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038). CONCLUSION: Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.

AKI in Hospitalized Patients with COVID-19.

BACKGROUND: Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. METHODS: This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. RESULTS: Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.

High-sugar feeding and increasing cholesterol levels in infants.

Hypercholesterolaemia is an important risk factor for cardiovascular disease. Both total and LDL cholesterol levels are three-fold higher at the end of the first year of life and about four-fold higher in adulthood compared with the neonatal period. In the USA, only 25% of infants are exclusively breastfed and simple carbohydrate-rich formulas are preferentially consumed. Spikes in fasting glucose and insulin have been reported in formula-fed infants and are associated with higher levels of proprotein convertase subtilisin/kexin type 9, suggesting a potential link between high simple sugar intake and consequent increase in LDL cholesterol in early childhood.