Midterm follow-up after computed tomography angiography planned left atrial appendage closure.

BACKGROUND: While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™ legacy and FLX devices, there has been no reported long-term data for this approach. OBJECTIVES: We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device. METHODS: A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively. RESULTS: From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively. CONCLUSIONS: CTA-based preprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years.

Coronary artery calcium scoring for cardiovascular risk assessment in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce. METHODS: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE). RESULTS: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001). CONCLUSION: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD.

Risk factors for cardiovascular events and mortality in patients diagnosed with diffuse large B-cell lymphoma and treated with anthracyclines.

There is an increased risk of congestive heart failure (CHF) following anthracycline-based chemotherapy in patients with Diffuse Large B-cell lymphoma (DLBCL). Little is known about risk factors of CHF, other cardiovascular events (CVE), and CVE effect on outcomes. We conducted a retrospective review of 463 newly diagnosed DLBCL patients treated between 2002 and 2016 with anthracycline containing regimens. At a median follow up of 71.3 months, 10.4% patients developed new CHF, 4.97% had new atrial fibrillation and 3.2% had new coronary artery disease. Age over 65, advanced stage DLBCL and diabetes were associated with increased cumulative incidence of CVE. Patients with prior diabetes had decreased progression-free survival and overall survival in comparison to non-diabetics. Patients who had a CVE in the first year had significant worse OS then patients who did not have a CVE (Hazard Ratio 10.0, 95% CI, 7.24-13.88). A risk score incorporating age at DLBCL diagnosis, baseline lymphocyte count, disease stage and diabetes stratified into groups with low, intermediate and high risk for CVE, with 1-year cumulative incidence of CVE of 5.3%, 7.9% and 13.4%. Diffuse large B-cell lymphoma patients treated with anthracycline containing regimens have high incidence of CVE, which are not limited to CHF. Clinical variables at the time of diagnosis can identify the group of DLBCL patients at highest risk of CVE, for whom preventive interventions should be considered.

Routine Use of the "Penumbra" Thrombectomy Device in Myocardial Infarction: A Real-World Experience-ROPUST Study.

Objectives: Evaluation of the safety and efficacy of the Penumbra device as an adjunct to percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and a large thrombus burden that requires thrombectomy. Background: For patients with acute MI, PCI is the primary reperfusion method. Large thrombus burden has always been a limitation of successful reperfusion. However, the use of current aspiration devices has been associated with an increased incidence of stroke. Methods: We performed a retrospective chart review at the University Hospitals Medical Center in Cleveland. Our study included data from patients who underwent PCI for ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) assisted by the Penumbra Cat RX device (a wide-lumen thrombus aspiration catheter) between May 2019 and February 2021. The primary outcome was the final thrombolysis in myocardial infarction (TIMI) flow. The secondary endpoints were a composite of adverse cardiac events at 6 months. About 50% of the patients did undergo transfemoral PCI as per preference of individual operators. The Penumbra thrombectomy device can be used both by radial and femoral approach and does not need any different guide catheter use. Results: TIMI flow 3 was achieved in 111 patients (90.2%). The secondary endpoint occurred in 11 patients (8.9%, 3 MI, 8 heart failure hospitalizations). There were no stroke events or device-related complications. The door-to-balloon time was not affected by usage of the Penumbra device. Failure in the restoration of TIMI 3 flow was associated with the use of balloon angioplasty prior to the application of the Penumbra device, leading to distal embolization. Conclusions: The Penumbra Cat RX provides safe and effective thrombus removal with better clinical outcomes, even in high-risk patients with acute coronary syndrome.

Impact of COVID-19 pandemic on ST-elevation myocardial infarction in a non-COVID-19 epicenter.

OBJECTIVES: We sought to study the impact of COVID-19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST-elevation myocardial infarction (STEMI) in a non-hot-spot region. BACKGROUND: COVID-19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain. METHODS: From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18-hospital system. Pre- and post-COVID-19 cohorts were based on March 23rd, 2020, whenstay-at-home orders were initiated in Ohio. We used presenting heart rate, blood pressure, troponin, new Q-wave, and left ventricle ejection fraction (LVEF) to assess severity. Duration of intensive care unit stay, total length of stay, door-to-balloon (D2B) time, and radial versus femoral access were used to assess patterns of care. RESULTS: Post-COVID-19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q-wave, and higher initial troponin; however, these did not reach statistical significance. Among post-COVID-19 patients, those with >12-hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs. 8.5 ng/ml, p = .03). Of these, 27% avoided the hospital due to fear of COVID-19, 18% believed symptoms were COVID-19 related, and 9% did not want to burden the hospital during the pandemic. CONCLUSIONS: COVID-19 has remarkably affected STEMI presentation and care. Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

Second-year results from CINEMA: A novel, patient-centered, team-based intervention for patients with Type 2 diabetes or prediabetes at high cardiovascular risk.

Background: The care for patients with type 2 diabetes mellitus (T2DM) necessitates a multidisciplinary team approach to reduce cardiovascular (CV) risk but implementation of effective integrated strategies has been limited. Methods and Results: We report 2-year results from a patient-centered, team-based intervention called CINEMA at University Hospitals Cleveland Medical Center. Patients with T2DM or prediabetes at high-risk for CV events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure with reduced ejection fraction, chronic kidney disease (CKD) stages 2-4, and/or prevalent metabolic syndrome were included. From May 2020 through September 2022, 426 patients were enrolled in the CINEMA program. A total of 227 (54%) completed ≥1 follow-up visit after an initial baseline visit with median (IQR) follow-up time 4 [3], [4], [5], [6], [7] months with maximum follow-up time 19 months. Mean age was 60 years, 47 % were women, and 37 % were Black and 85% had prevalent T2DM, 48 % had established ASCVD, 29% had chronic HF, 27% had CKD and mean baseline 10-year ASCVD risk estimate was 25.1 %; baseline use of a SGLT2i or GLP-1RA was 21 % and 18 %, respectively. Patients had significant reductions from baseline in body weight (-5.5 lbs), body mass index (-0.9 kg/m2), systolic (-3.6 mmHg) and diastolic (-1.2 mmHg) blood pressure, Hb A1c (-0.5 %), total (-10.7 mg/dL) and low-density lipoprotein (-9.0 mg/dL) cholesterol, and triglycerides (-13.5 mg/dL) (p<0.05 for all). Absolute 10-year predicted ASCVD risk decreased by ∼2.4 % (p<0.001) with the intervention. In addition, rates of guideline-directed cardiometabolic medication prescriptions significantly increased during follow-up with the most substantive changes seen in rates of SGLT2i and GLP-1RA use which approximately tripled from baseline (21 % to 57 % for SGLT2i and 18 % to 65 % for GLP-1RA, p<0.001 for both). Conclusions: The CINEMA program, an integrated, patient-centered, team-based intervention for patients with T2DM or prediabetes at high risk for cardiovascular disease has continued to demonstrate effectiveness with significant improvements in ASCVD risk factors and improved use of evidence-based therapies. Successful implementation and dissemination of this care delivery paradigm remains a key priority.

Coronary Artery Calcium Scoring for Risk Assessment in Patients With Severe Hypercholesterolemia.

The American College of Cardiology and the American Heart Association guidelines recommend treatment of patients with severe hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] ≥190 mg/100 ml) with a high-intensity statin. However, atherosclerotic cardiovascular disease (ASCVD) risk, even among those with severe hypercholesterolemia, is heterogeneous, and coronary artery calcium (CAC) scoring may be used to clarify risk. We sought to evaluate CAC in patients with severe hypercholesterolemia and measure its impact on real-world statin prescriptions. We identified patients with at least 1 LDL-C ≥190 mg100 ml who had a CAC scoring in the Community Benefit of No-Charge Calcium Score Screening Program (CLARIFY) study (NCT04075162) between 2014 and 2020. We explored the CAC distribution, factors associated with CAC >0, and ASCVD risk (myocardial infarction, stroke, revascularization, death). A total of 1,904 patients (1.257 women, aged 57.8 ± 9.3 years) with severe hypercholesterolemia were included. LDL-C ranged from 190 to 524 mg100 ml (mean 215.5 ± 27 mg100 ml). A total of 864 patients (45.4%) had CAC = 0 and 1,561 (82%) had CAC <100. In patients with LDL-C ≥250 mg100 ml, 67 (36.6%) had CAC = 0. Age, male gender, smoking, diabetes, systolic blood pressure, and obesity (ps ≤0.001) were associated with CAC >0. In patients with LDL-C ≥190 mg100 ml, CAC was associated with a higher risk for ASCVD events (CAC ≥100 vs CAC <100, hazard ratio 3.57 [1.81 to 7.04], p <0.001). A higher CAC category was associated with increased statin use after CAC scoring (p <0.001). In patients with severe hypercholesterolemia, 45% had CAC = 0, which was associated with a significantly lower ASCVD risk. CAC was associated with statin prescription and cholesterol lowering. In conclusion, CAC scoring may be used to clarify ASCVD risk in this heterogeneous population with severe hypercholesterolemia.

Disparities in statin prescription among patients with severe hypercholesterolemia in an integrated healthcare system.

Background: Severe hypercholesterolemia (SH), defined as a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg/dl, is associated with an increased risk for premature atherosclerotic cardiovascular disease. Despite guideline recommendations, many patients with severe hypercholesterolemia remain untreated. We conducted an observational analysis of a large pool of SH patients, exploring demographic and social factors contributing to disparities in the prescription of statin and other lipid-lowering therapies. Methods: We included all adults (age 18 or older) in the University Hospitals Health Care System, with an LDL-C ≥ 190 mg/dl on a lipid profile drawn between January 2, 2014, and March 15, 2022. Variables were compared across relevant categories of age, gender, race and ethnicity, medical history, prescription medication status, insurance type, and provider referral type. We used the Fischer exact test and Pearson Chi-square (χ 2) for variable comparisons. Results: A total of 7,942 patients were included in the study. The median age was 57 [IQR 48-66] years with 64% female, and 17% Black patients. Only 58% of the total cohort was prescribed statin therapy. Higher age was independently associated with a higher likelihood of receiving a statin, with an odds ratio of 1.25 (95% CI [1.21 - 1.30] per 10 years, p<0.001). Additional factors that were associated with higher rates of statin prescription in patients with SH were Black race (OR 1.90, 95% CI [1.65 - 2.17], p<0.001), smoking (OR 2.42, 95% CI [2.17 -2.70], p<0.001), and presence of diabetes (OR 3.88, 95% CI [3.27 - 4.60], p<0.001). Similar trends were also seen with other lipid-lowering therapies such as ezetimibe and fibrates. Conclusions: In our Northeast Ohio healthcare system, less than two-thirds of patients with severe hypercholesterolemia are prescribed a statin. Statin prescription rates were highly dependent on age and the presence of additional ASCVD risk factors.

Left Atrial Appendage Closure Outcomes in Patients With Cancer at a Single Tertiary Center.

Atrial fibrillation is the most common arrhythmia in patients with underlying malignancy. Patients with cancer have a higher risk of bleeding, and at the same time, carry an elevated risk of thromboembolism related to the hypercoagulable state, type of cancer, and anticancer treatment, rendering safe anticoagulation challenging in this population. Left atrial appendage closure is an alternative treatment option in patients with atrial fibrillation and high bleeding risk; however, the data on patients with cancer are limited. Our study aimed to compare the long-term outcomes in patients with cancer receiving left atrial appendage closure using the WATCHMAN device. This is a prospective, single-center study comparing outcomes in 389 patients who underwent percutaneous left atrial appendage closure using the WATCHMAN device over 5 years in a single, large academic hospital in the United States. The postprocedural outcomes of mortality, stroke, and major bleeding were evaluated in patients with and without cancer. Our study included 57 patients with cancer and 332 without cancer. The baseline characteristics were similar between the 2 groups. Metastatic disease was present in 16.4% of patients, and 25% were receiving active treatment at the time of the procedure. The median follow-up time was 354 (interquartile range 85 to 790) days. There was no difference in mortality (hazard ratio [HR] 1.3, 95% confidence interval [CI] 0.72 to 2.35, p = 0.38), major bleeding episodes (HR 1.2, 95% CI 0.45 to 3.33, p = 0.68), and stroke (HR 0.64, 95% CI 0.19 to 2.21, p = 0.49) at 3 years after the procedure in patients with and without cancer. There was no difference in the composite outcome (postprocedural mortality, stroke, and major bleeding) between the 2 groups (HR 1.25, CI 0.75 to 2.07, p = 0.38). Percutaneous left atrial appendage closure in patients with cancer appears to be safe and has a similar long-term risk compared with patients without cancer.

Prognostic Value of Pulmonary Artery Oxygen Saturation in Pulmonary Embolism Requiring Endovascular Intervention.

This retrospective study evaluates the prognostic value of pulmonary artery oxygen saturation (PA O2) among patients who undergo mechanical intervention for pulmonary embolism (PE). Patients who died within 90 days had less PA O2, and a greater percentage of patients with a PA O2 of <50 died within 90 days of intervention. Regression analysis revealed an association of PA O2 with mortality that held true despite accounting for Pulmonary Embolism Severity Index (PESI) score and type of endovascular intervention. Receiver operator curve testing revealed PA O2 <50% to be inferior to PESI score but superior to Bova score in predicting mortality after mechanical PE intervention, with the combination of PA O2 <50% and PESI outperforming PESI and PA O2 in predicting mortality. Our pilot evaluation suggests preintervention PA O2 <50% to be associated with increased risk of all-cause mortality and may help identify patients at greatest risk of deterioration.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.

Background: Coronary artery calcium (CAC) is a powerful predictor of major adverse cardiovascular events (MACE). Traditional Agatston score simply sums the calcium, albeit in a non-linear way, leaving room for improved calcification assessments that will more fully capture the extent of disease. Objective: To determine if AI methods using detailed calcification features (i.e., calcium-omics) can improve MACE prediction. Methods: We investigated additional features of calcification including assessment of mass, volume, density, spatial distribution, territory, etc. We used a Cox model with elastic-net regularization on 2457 CT calcium score (CTCS) enriched for MACE events obtained from a large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). We employed sampling techniques to enhance model training. We also investigated Cox models with selected features to identify explainable high-risk characteristics. Results: Our proposed calcium-omics model with modified synthetic down sampling and up sampling gave C-index (80.5%/71.6%) and two-year AUC (82.4%/74.8%) for (80:20, training/testing), respectively (sampling was applied to the training set only). Results compared favorably to Agatston which gave C-index (71.3%/70.3%) and AUC (71.8%/68.8%), respectively. Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were important determinants of increased risk, with dense calcification (>1000HU) associated with lower risk. The calcium-omics model reclassified 63% of MACE patients to the high risk group in a held-out test. The categorical net-reclassification index was NRI=0.153. Conclusions: AI analysis of coronary calcification can lead to improved results as compared to Agatston scoring. Our findings suggest the utility of calcium-omics in improved prediction of risk.

Comparison of Large-Bore Thrombectomy With Catheter-Directed Thrombolysis for the Treatment of Pulmonary Embolism.

Background: There is significant debate on whether large-bore thrombectomy (LBT) or catheter-directed thrombolysis (CDT) is superior for the treatment of intermediate- and high-risk pulmonary embolism (PE) while employing an early invasive strategy through endovascular therapies. Methods: Between 2018 and 2021, 147 patients who presented to our institution with acute intermediate- or high-risk PE and had undergone PE Response Team-guided endovascular intervention with either LBT (Inari FlowTriever) or CDT (EKOSonic) were retrospectively reviewed. Data on the patients' clinical characteristics, comorbidities, serum biomarkers, hemodynamics, and imaging characteristics were obtained. The primary outcome was all-cause mortality; the secondary outcomes were all-cause readmission, readmission for PE, and length of stay in the intensive care unit and hospital. The safety outcome of procedure-related bleeding was evaluated. Kaplan-Meier curves were used to estimate the cumulative event rate. Multivariate Cox-proportional hazard regression and inverse propensity weighting were used to adjust for confounders. Results: The median age of the patients was 63 (IQR, 53-73) years, and 48.3% of the patients were women. Patients in the LBT group had a higher PE Severity Index score (LBT vs CDT: median, 132 vs 108; P = .015) and greater prevalence of malignancy (LBT vs CDT: median, 22.7% vs 6%; P = .011). After propensity matching for baseline characteristics, there was no significant difference in all-cause mortality (LBT vs CDT: median, 15.8% vs 9.1%; hazard ratio, 0.64; 95% CI, 0.21-1.98; P = .442) for up to 1 year. The secondary outcomes or safety end points were also similar between the 2 interventions. An exploratory analysis showed elevated PE Severity Index scores, lower systolic blood pressures, and higher lactic acid levels to be associated with an increased risk of early death at 30 days. Conclusions: In this retrospective cohort study, there was no significant difference in the cumulative event rate of all-cause mortality between LBT and CDT. Further studies are needed to evaluate the use of LBT versus CDT versus noninvasive therapy to understand outcomes and appropriate patient selection among those with intermediate- and high-risk PE.

Relation of coronary calcium scoring with cardiovascular events in patients with diabetes: The CLARIFY Registry.

INTRODUCTION: Coronary artery calcium (CAC) scoring is not routinely performed in patients with diabetes based on an existing class I indication for statin therapy in these patients. However, CAC scoring may improve risk classification and prediction of atherosclerotic cardiovascular disease (ASCVD) events beyond risk scores in asymptomatic individuals with prediabetes and diabetes, warranting CAC assessment in this population. The routine availability through provision of no-charge CAC as an alternative to routine probabilistic risk scores may improve utilization of preventive therapies especially in traditionally underserved populations. METHODS: Prospective observational study in a large health system offering no-charge CAC scoring for primary prevention risk prediction with available glycosylated hemoglobin (HbA1c) measurements between June 2015 and March 2019 were divided according to no diabetes (HbA1c <5.7 %), prediabetes (HbA1c 5.7 %-6.4 %), or diabetes (HbA1c ≥ 6.5 % or charted history) and followed for major adverse cardiovascular events [myocardial infarction, stroke, death (MACE) or coronary revascularization]. Patient characteristics, health history, laboratory data, and statin prescription rates were measured at baseline and at one year after CAC scoring. RESULTS: A total of 12,194 subjects with available HbA1c underwent CAC scoring during the study period (6462 diabetes, 2062 prediabetes, and 3670 without diabetes). At a median follow-up of 1.2 years, there were 458 MACE events (71 patients without diabetes, 66 patients with prediabetes, and 321 patients with diabetes). Among patients with diabetes or prediabetes, increased CAC was associated with MACE (HR 1.38 [1.26-1.51], p < 0.001) and MACE or revascularization (HR 1.70 [1.57-1.85], p < 0.001). In patients with diabetes, CAC category was associated with greater statin initiation (89.6 % for CAC≥400 vs 60.1 % for CAC = 0, p < 0.001) and high intensity statin initiation (42.2 % for CAC≥400 vs 16.8 % for CAC = 0, p < 0.001) at one year post CAC scoring. Patients with diabetes had greater reductions in systolic blood pressure, LDL-C, total cholesterol, and triglycerides from baseline with a CAC ≥400 compared to a lower CAC category (p = 0.007). CONCLUSIONS: CAC burden is associated with ASCVD risk in patients with diabetes. CAC scoring increases statin prescriptions and reduces ASCVD risk in patients with diabetes, potentially warranting routine CAC assessment in this population.

Machine learning derived ECG risk score improves cardiovascular risk assessment in conjunction with coronary artery calcium scoring.

Background: Precision estimation of cardiovascular risk remains the cornerstone of atherosclerotic cardiovascular disease (ASCVD) prevention. While coronary artery calcium (CAC) scoring is the best available non-invasive quantitative modality to evaluate risk of ASCVD, it excludes risk related to prior myocardial infarction, cardiomyopathy, and arrhythmia which are implicated in ASCVD. The high-dimensional and inter-correlated nature of ECG data makes it a good candidate for analysis using machine learning techniques and may provide additional prognostic information not captured by CAC. In this study, we aimed to develop a quantitative ECG risk score (eRiS) to predict major adverse cardiovascular events (MACE) alone, or when added to CAC. Further, we aimed to construct and validate a novel nomogram incorporating ECG, CAC and clinical factors for ASCVD. Methods: We analyzed 5,864 patients with at least 1 cardiovascular risk factor who underwent CAC scoring and a standard ECG as part of the CLARIFY study (ClinicalTrials.gov Identifier: NCT04075162). Events were defined as myocardial infarction, coronary revascularization, stroke or death. A total of 649 ECG features, consisting of measurements such as amplitude and interval measurements from all deflections in the ECG waveform (53 per lead and 13 overall) were automatically extracted using a clinical software (GE Muse™ Cardiology Information System, GE Healthcare). The data was split into 4 training (Str) and internal validation (Sv) sets [Str (1): Sv (1): 50:50; Str (2): Sv (2): 60:40; Str (3): Sv (3): 70:30; Str (4): Sv (4): 80:20], and the results were compared across all the subsets. We used the ECG features derived from Str to develop eRiS. A least absolute shrinkage and selection operator-Cox (LASSO-Cox) regularization model was used for data dimension reduction, feature selection, and eRiS construction. A Cox-proportional hazards model was used to assess the benefit of using an eRiS alone (Mecg), CAC alone (Mcac) and a combination of eRiS and CAC (Mecg+cac) for MACE prediction. A nomogram (Mnom) was further constructed by integrating eRiS with CAC and demographics (age and sex). The primary endpoint of the study was the assessment of the performance of Mecg, Mcac, Mecg+cac and Mnom in predicting CV disease-free survival in ASCVD. Findings: Over a median follow-up of 14 months, 494 patients had MACE. The feature selection strategy preserved only about 18% of the features that were consistent across the various strata (Str). The Mecg model, comprising of eRiS alone was found to be significantly associated with MACE and had good discrimination of MACE (C-Index: 0.7, p = <2e-16). eRiS could predict time-to MACE (C-Index: 0.6, p = <2e-16 across all Sv). The Mecg+cac model was associated with MACE (C-index: 0.71). Model comparison showed that Mecg+cac was superior to Mecg (p = 1.8e-10) or Mcac (p < 2.2e-16) alone. The Mnom, comprising of eRiS, CAC, age and sex was associated with MACE (C-index 0.71). eRiS had the most significant contribution, followed by CAC score and other clinical variables. Further, Mnom was able to identify unique patient risk-groups based on eRiS, CAC and clinical variables. Conclusion: The use of ECG features in conjunction with CAC may allow for improved prognostication and identification of populations at risk. Future directions will involve prospective validation of the risk score and the nomogram across diverse populations with a heterogeneity of treatment effects.

Prevalence of thoracic aortic aneurysm in patients referred for no/low-charge coronary artery calcium scoring: Insights from the CLARIFY registry.

Objective: Low-dose cardiac-gated chest CTs allow for simultaneous evaluation of coronary artery calcification and aortic size. We sought to evaluate the prevalence of thoracic aortic dilation (TAD) and thoracic aortic aneurysm (TAA) in a large cohort of patients undergoing coronary artery calcium (CAC) screening. Methods: We reviewed all patients from a large, prospective no-charge CAC screening program (CLARIFY, Clinicaltrials.gov NCT04075162) for whom measurements of the ascending aorta were available. TAD was defined as an ascending aortic diameter ≥4.0cm, while TAA was defined as ascending aortic diameter ≥ 4.5cm. We explored associations between patient characteristics, CAC, and the prevalence of TAD/TAA. Results: A total of 36,356 patients enrolled in the CLARIFY program underwent analysis for TAD/TAA. 3,130 patients (8.6%) had TAD and 237 (0.7%) had TAA. Patients with TAA were older (63±8 vs 59±10 years, p < 0.001), more likely to be male (87% vs 49%, p < 0.001), have higher BMI (32 vs 30 kg/m2, p < 0.001), and 10-year atherosclerotic cardiovascular disease estimated risk (18% vs 12%, p < 0.001). Similar differences were observed for individuals with TAD compared to individuals without TAD with respect to age (63 vs 59 years, p < 0.001), percent male (76% vs 46%, p < 0.001), BMI (32 vs 30 kg/m2, p < 0.001), and 10-year predicted risk (17% vs 11%, p < 0.001). CAC score was associated with prevalence of TAD (4.9% in those with CAC 0 to 16.5% in those with CAC≥400) and TAA (0.3% in those with CAC of 0 to 1.5% in those with CAC ≥400). Conclusion: In this large, prospective study of patients undergoing no-charge CAC screening, 8.6% had TAD (≥4.0cm) and 0.7% had TAA (≥4.5cm). Our results highlight a high yield of TAD/TAA diagnosis in this targeted cohort with cardiovascular risk factors and supports the role of no-charge CAC as a population-level strategy.

Lessons Learned From a Patient-Centered, Team-Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program.

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Effect of No-Charge Coronary Artery Calcium Scoring on Cardiovascular Prevention.

Prevention of cardiovascular disease is currently guided by probabilistic risk scores that may misclassify individual risk and commit many middle-aged patients to prolonged pharmacotherapy. The coronary artery calcium (CAC) score, although endorsed for intermediate-risk patients, is not widely adopted because of barriers in reimbursement. The impact of removing cost barrier on cardiovascular outcomes in real-world settings is not known. Within the University Hospitals Health System (Cleveland, Ohio), CAC was offered to patients with at least 1 cardiovascular risk factor at low charge between 2014 and 2017 ($99) and no charge from January 1, 2018 onward. CAC use and access, patient characteristics, reclassification of risk compared with the pooled cohort equations (PCEs) for atherosclerotic vascular disease, statin use, changes in parameters of cardiometabolic health, downstream cardiovascular testing, downstream coronary revascularization, and cardiovascular outcomes were evaluated. A total of 52,151 patients underwent CAC testing over the study period. Median 10-year PCE for atherosclerotic vascular disease, in the entire cohort was 8.3% (4.0% to 15.9%). Among patients with PCE >20%, 21% had CAC <100, whereas 37% of those with PCE <7.5% had CAC ≥100. Among patients who were not on statin before CAC testing, 1-year statin prescription was 24% and was significantly associated with higher CAC scores. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides all decreased significantly 1-year after CAC, and the degree of decrease was strongly linked with CAC scores. One year after CAC, 14% underwent noninvasive ischemic evaluation, 1.4% underwent invasive coronary angiography, and 0.9% underwent revascularization. The majority (74%) of revascularization procedures occurred in patients with CAC >400. In conclusion, reducing or removing the cost burden of CAC leads to significant test uptake by patients, which is followed by reclassification of statin eligibility, increases in the use of preventive medications, and improvement in risk factors, with very low rates of invasive downstream testing.