Real-World Exploration of LDL-Cholesterol Management in Patients with Atherosclerotic Cardiovascular Disease.

BACKGROUND: Although guidelines recommend low-density lipoprotein cholesterol (LDL-C) to be <70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), the rate of achieving this goal remains suboptimal. We sought to understand real world contemporary practice patterns of LDL-C management in patients with ASCVD, and whether LDL-C testing influenced management across US health systems. METHODS: A retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance was performed on patients with an LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with achievement of guideline directed LDL-C target. Changes in lipid lowering therapy (LLT) after LDL-C testing were also described. RESULTS: Among 216,074 patients with ASCVD, 129,886 (60.1%) had uncontrolled LDL-C (i.e. ≥70 mg/dL). Compared with participants with controlled LDL-C (<70mg/dL), those with uncontrolled LDL-C were more frequently female (50.9% vs 35.1%), or Black (13.7% vs. 10.3%), and less commonly had coronary artery disease as the form of vascular disease (73.0% vs. 83.5% %), heart failure (21.3% vs. 29.1% %), diabetes (34.1% vs. 48.2%), atrial fibrillation (19.3% vs. 26.1%), or chronic kidney disease (25.1% vs. 32.2%). In multivariable analyses, the factors most strongly associated with failure to achieve LDL-C control were female sex (RR 1.13 [95% CI 1.12-1.14] p <0.001) and Black race (1.15 [1.14-1.17] p <0.001). Among the 53,957 (41.5%) of those with uncontrolled LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline, only 21% were initiated on any LLT within 6 months of the uncontrolled LDL-C value. CONCLUSIONS: Within five diverse large health systems in the CardioHealth Alliance, more than half of the patients with ASCVD had uncontrolled LDL-C with significant disparities based on sex and race at baseline. The vast majority were not initiated on any lipid lowering therapy within 6 months of an elevated test result indicating persistent gaps in care that will likely worsen health inequities in outcomes. This highlights the urgent need for implementation efforts to improve equitable care.

Long-term Outcomes of Percutaneous Coronary Intervention in Patients with Prior Coronary Artery Bypass Grafting.

BACKGROUND Patients with a prior coronary artery bypass graft (CABG) may have a need for repeat revascularization, which is typically attempted first via percutaneous coronary intervention (PCI) of either a bypass graft or native vessel. Long-term outcomes of native vessel compared to graft PCI after CABG have not yet been explored in a large institution study. METHODS Patients with history of prior CABG who underwent PCI at our institution during 2010-2018 were included. Baseline characteristics and long-term outcomes of up to 5 years were compared between native vessel and bypass graft PCI groups. Cox regression was used to adjust for significant covariates in estimation of risk and calculation of hazard ratios. RESULTS During the study, 4,251 patients with a prior CABG underwent PCI. Native vessel PCI represented 67.1% (n=2,851) of the cohort. After adjusting for significant covariates, bypass graft PCI compared to native vessel PCI had a higher risk of overall mortality (HR 1.15; 95% CI, 1.04-1.29; p<0.05), all-cause readmission (HR 1.16; 95% CI, 1.1-1.3; p<0.05), readmission for PCI (HR 1.25; 95% CI, 1.13-1.38; p<0.05), readmission for heart failure (HR 1.16; 95% CI, 1.06-1.26; p<0.05), and composite of myocardial infarction and revascularization (HR 1.23; 95% CI, 1.12-1.35; p<0.05). CONCLUSIONS Among patients with prior CABG, bypass graft PCI compared to native vessel PCI was associated with higher risk of adverse long-term outcomes.

Relationship between predicting bleeding complication in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score and mortality among patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: The predicting bleeding complication in patients undergoing stent implantation and subsequent dual antiplatelet therapy, PRECISE-DAPT (P-DAPT) score has been validated in large cohorts as an effective tool in predicting bleeding complication after dual antiplatelet therapy (DAPT) as well as in predicting in-hospital mortality. The implication of using this score to predict outcomes, including mortality in patients with atrial fibrillation (AF) undergoing PCI is unknown. OBJECTIVE: Role of P-DAPT score to study clinical outcomes, including mortality, hospitalization, and major bleeding, particularly among patients with AF. METHODS: This is a retrospective observational study of 18,850 consecutive patients who underwent percutaneous coronary intervention (PCI) across a large multihospital healthcare system from 2010 to 2019. Patients were stratified into four groups depending on the presence or absence of AF and P-DAPT score, with score ≥ 25 defined as high risk. The primary outcome was all-cause mortality. The secondary outcomes evaluated were hospitalization and major bleeding. RESULTS: In the unadjusted analyses, a P-DAPT score ≥ 25, in both AF and non-AF population, was associated with increased mortality, hospitalization, and bleeding. After adjusting for baseline covariates, no significant differences in major bleeding risk were found across the four groups. However, a P-DAPT score of ≥25 in AF patients was associated with a higher risk for hospitalizations related to cardiovascular causes (HR: 2.15 95% CI 2.00-2.3, p < .0001). Among AF patients, P-DAPT score ≥ 25 was found to be strongly associated with mortality (HR 3.5; 95% CI 2.95-4.25, p < .0001) as compared with AF patients with score < 25 (HR 1.18, 95% CI 0.88-1.54, p = .26). CONCLUSION: In this large cohort of patients undergoing PCI, the P-DAPT score can help to identify patients at high risk for long-term mortality, particularly among those with atrial fibrillation.

Cardiovascular Stress Reactivity and Carotid Intima-Media Thickness: The Buffering Role of Slow-Wave Sleep.

OBJECTIVE: Exaggerated cardiovascular reactivity to acute psychological stress has been associated with increased carotid intima-media thickness (IMT). However, interstudy variability in this relationship suggests the presence of moderating factors. The current study aimed to test the hypothesis that poor nocturnal sleep, defined as short total sleep time or low slow-wave sleep, would moderate the relationship between cardiovascular reactivity and IMT. METHODS: Participants (N = 99, 65.7% female, age = 59.3 ± 9.3 years) completed a two-night laboratory sleep study and cardiovascular examination where sleep and IMT were measured. The multisource interference task was used to induce acute psychological stress, while systolic and diastolic blood pressure and heart rate were monitored. Moderation was tested using the PROCESS framework in SPSS. RESULTS: Slow-wave sleep significantly moderated the relationship between all cardiovascular stress reactivity variables and IMT (all pinteraction ≤ .048, all ΔRinteraction ≥ .027). Greater stress reactivity was associated with higher IMT values in the low slow-wave sleep group and lower IMT values in the high slow-wave sleep group. No moderating effects of total sleep time were observed. CONCLUSIONS: The results provide evidence that nocturnal slow-wave sleep moderates the relationship between cardiovascular stress reactivity and IMT and may buffer the effect of daytime stress-related disease processes.

A quality framework for the role of invasive, non-interventional cardiologists in the present-day cardiac catheterization laboratory: A multidisciplinary SCAI/HFSA expert consensus statement.

The present-day cardiac catheterization laboratory (CCL) is home to varied practitioners who perform both diagnostic, interventional, and complex invasive procedures. Invasive, non-interventional cardiologists are performing a significant proportion of the work as the CCL environment has evolved. This not only includes those who perform diagnostic-only cardiac catheterization but also heart failure specialists who may be involved in hemodynamic assessment and in mechanical circulatory support and pulmonary hypertension specialists and transplant cardiologists. As such, the training background of those who work in the CCL is varied. While most quality metrics in the CCL are directed towards evaluation of patients who undergo traditional interventional procedures, there has not been a focus upon providing these invasive, noninterventional cardiologists, hospital/CCL administrators, and CCL directors a platform for quality metrics. This document focuses on benchmarking quality for the invasive, noninterventional practice, providing this physician community with guidance towards a patient-centered approach to care, and offering tools to the invasive, noninterventionalists to help their professional growth. This consensus statement aims to establish a foundation upon which the invasive, noninterventional cardiologists can thrive in the CCL environment and work collaboratively with their interventional colleagues while ensuring that the highest quality of care is being delivered to all patients.

Revascularization heart team recommendations as an adjunct to appropriate use criteria for coronary revascularization in patients with complex coronary artery disease.

OBJECTIVES: To evaluate how a comprehensive evidence-based clinical review by a multidisciplinary revascularization heart team on treatment decisions for revascularization in patients with complex coronary artery disease using SYNTAX scores combined with Society of Thoracic Surgeons-derived clinical variables can be additive to the utilization of Appropriate Use Criteria for coronary revascularization. BACKGROUND: Decision-making regarding the use of revascularization for coronary artery disease has come under major scrutiny due to inappropriate overuse of revascularization. There is little data in routine clinical practice evaluating how a structured, multidisciplinary heart team approach may be used in combination with the Appropriate Use Criteria for revascularization. METHODS: From May 1, 2012 to January 1, 2015, multidisciplinary revascularization heart team meetings were convened to discuss evidence-based management of 301 patients with complex coronary artery disease. Heart team recommendations were adjudicated with the Appropriate Use Criteria for coronary revascularization for each clinical scenario using the Society for Cardiovascular Angiography and Interventions' Quality Improvement Toolkit (SCAI-QIT) Appropriate Use Criteria App. RESULTS: Concordance of the Heart Team to Appropriate Use Criteria had a 99.3% appropriate primary indication for coronary revascularization. Among patients who underwent percutaneous revascularization, 34.9% had an inappropriate or uncertain indication as recommended by the Heart Team. Patients with uncertain or inappropriate percutaneous coronary interventions had significantly higher SYNTAX score (27.3 ± 6.6; 28.5 ± 5.5; 19.2 ± 6; P < 0.0001) and Society of Thoracic Surgeons-Predicted Risk of Mortality (6.1% ± 4.7%; 8.1% ± 6.3%; 3.7% ± 4.1%; P < 0.0081) compared to appropriate indications, frequently had concomitant forms of advanced comorbidities and frailty in the setting of symptomatic coronary artery disease. CONCLUSIONS: A formal, multidisciplinary revascularization heart team can provide proper validation for clinical decisions and should be considered in combination with the Appropriate Use Criteria for coronary revascularization to formulate revascularization strategies for individuals in a patient-centered fashion. © 2015 Wiley Periodicals, Inc.

Identification of Intrastent Pathology Associated With Late Stent Thrombosis Using Optical Coherence Tomography.

OBJECTIVE: To better characterize intrastent pathology using optical coherence tomography (OCT) in patients presenting with late and very late stent thrombosis (LST/VLST). BACKGROUND: The contribution of specific intrastent pathologies to the development of LST/VLST is not well understood. METHODS: In this single-center, retrospective, observational study of 796 consecutive patients treated for ST-segment elevation myocardial infarction (STEMI) with primary PCI we identified 57 patients (7.2%) in whom STEMI resulted from LST/VLST. Of the patients with LST/VLST, 21 patients (37%) had OCT performed at the discretion of the operator during PCI for LST/VLST. Independent reviewers performed qualitative offline analysis of OCT images to determine the cause of stent thrombosis defined as the specific intrastent pathology associated with thrombus deposition. RESULTS: The principal intrastent pathology causing LST/VLST was determined to be stent malapposition in 11 patients (55%), of which 5 (25% of all LST/VLST patents) had findings suggestive of positive vessel remodeling. Neoatherosclerosis was determined to be the cause of LST/VLST in 7 patients (35%). LST/VLST resulted from uncovered stent struts in 2 patients (10%). Among all LST/VLST patients, in-hospital mortality (12.3%) and post-hospital target vessel failure (TVF) or cardiac death (21.7%, median follow-up 1.6 years) remained high. There was a trend towards decreased TVF or cardiac death (7.7% vs. 27.3% P = 0.24) in patients who underwent OCT-guided therapy. CONCLUSIONS: LST/VLST remains a significant cause of STEMI and is associated with considerable morbidity and mortality. OCT use at the time of PCI consistently identifies significant intrastent pathology with potentially meaningful clinical impact.

Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission.

AIMS: Diabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure. METHODS AND RESULTS: We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models. CONCLUSION: Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

Outcomes of small coronary artery stenting with bare-metal stents versus drug-eluting stents: results from the NHLBI Dynamic Registry.

OBJECTIVES: Examine 1-year outcomes of patients with small coronary arteries in the National Heart, Lung, and Blood Institute Dynamic Registry (NHLBI) undergoing drug-eluting stent (DES) vs. bare-metal stent (BMS) placement. BACKGROUND: While randomized trials of DES vs. BMS demonstrate reduced target vessel revascularization, it is unclear whether similar outcomes are seen in unselected patients after percutaneous coronary intervention (PCI) for small coronary arteries. METHODS: Utilizing patients from the NHLBI Registry Waves 1-3 for BMS (1997-2002) and Waves 4-5 for DES (2004 and 2006), demographic, angiographic, in-hospital, and 1-year outcome data of patients with small coronary arteries treated with BMS (n = 686) vs. DES (n = 669) were evaluated. Small coronary artery was defined as 2.50-3.00 mm in diameter. RESULTS: Compared to BMS-treated patients, the mean lesion length of treated lesions was longer in the DES treated group (16.7 vs. 13.1 mm, P < 0.001) and the mean reference vessel size of attempted lesions was smaller (2.6 vs. 2.7 mm, P < 0.001). Adjusted analyses of 1-year outcomes revealed that DES patients were at lower risk to undergo coronary artery bypass graft surgery (Hazard Ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), repeat PCI (HR 0.53, 95% CI 0.35-0.82, P = 0.004), and experience the combined major adverse cardiovascular event rate (HR 0.59, 95% CI 0.42-0.83, P = 0.002). There was no difference in the risk of death and myocardial infarction (MI) (HR 0.78, 95% CI 0.46-1.35, P = 0.38). CONCLUSIONS: In this real-world registry, patients with small coronary arteries treated with DES had significantly lower rates of repeat revascularization and major adverse cardiovascular events at 1 year compared to patients treated with BMS, with no increase in the risk of death and MI. These data confirm the efficacy and safety of DES over BMS in the treatment of small coronary arteries in routine clinical practice.

Comparison of drug-eluting and bare metal stents in large coronary arteries: findings from the NHLBI dynamic registry.

OBJECTIVES: This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. BACKGROUND: Randomized trials have demonstrated that DES reduce the risk of target vessel revascularization (TVR) compared to BMS. This benefit is less pronounced as artery diameter increases. Whether DES are superior to BMS for larger coronary arteries in the setting of routine clinical practice is unknown. METHODS: We analyzed data from 869 patients undergoing de novo lesion PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI Dynamic Registry according to whether they were treated with DES or BMS. Patients were followed for 3 years for the occurrence of cardiovascular events. RESULTS: At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI 0.93-3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52-2.49, P = 0.75) and for mortality 0.89 (95%CI 0.49-1.62, P = 0.71). CONCLUSIONS: In our study of the unrestricted use of DES for patients with lesions in larger diameter coronary arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do not support the preferred use of DES over BMS for patients with lesions located in arteries >3.5 mm. It is unknown whether secondary generation DES can offer better outcome compared to BMS in large coronary vessels. Further study on this issue is warranted.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

BACKGROUND: The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. OBJECTIVES: In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. METHODS: This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30 days, 1 year, and 3 years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). RESULTS: BB showed lower all-cause mortality at 30 days, 1 year, and 3 years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3 years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). CONCLUSION: In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Impact of Guideline-Directed Statin Prescriptions on Cardiovascular Outcomes by Race in a Real-World Primary Prevention Cohort.

Background: Data on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. Objectives: The purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. Methods: Statin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least "moderate" for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. Results: Among 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with "no statin" prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. Conclusions: Statins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in 5 Large US Health Systems.

BACKGROUND: Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease. However, lipoprotein (a) testing remains variable and it is unclear what factors influence testing and if testing changes clinical management. METHODS AND RESULTS: A retrospective study using electronic medical record data from 5 health systems identified an atherosclerotic cardiovascular disease cohort divided into those with and without a lipoprotein (a) test between 2019 and 2021. Baseline characteristics and lipid-lowering therapy patterns were assessed. Multivariable regression modeling was used to determine factors associated with lipoprotein (a) testing. Among 595 684 patients with atherosclerotic cardiovascular disease, only 2587 (0.4%) were tested for lipoprotein (a). Those who were older or Black individuals were less likely to have lipoprotein (a) testing, while those with familial hypercholesterolemia, ischemic stroke/transient ischemic attack, peripheral artery disease, prior lipid-lowering therapy, or low-density lipoprotein cholesterol ≥130 mg/dL were more likely to be tested. Those with a lipoprotein (a) test, regardless of the lipoprotein (a) value, were more frequently initiated on any statin therapy (30.3% versus 10.6%, P < 0.001), ezetimibe (7.65% versus 0.8%, P < 0.001), or proprotein convertase substilisin/kexin type 9 inhibitor (6.7% versus 0.3%, P < 0.001) compared with those without a test. Those with an elevated lipoprotein (a) level more frequently initiated ezetimibe (11.5% versus 5.9%, P < 0.001) or proprotein convertase substilisin/kexin type 9 inhibitor (10.9% versus 4.8%, P < 0.001). CONCLUSIONS: Lipoprotein (a) testing in patients with atherosclerotic cardiovascular disease is infrequent, with evidence of disparities among older or Black individuals. Testing for lipoprotein (a), regardless of level, is associated with greater initiation of any lipid-lowering therapy, while elevated lipoprotein (a) is associated with greater initiation of nonstatin lipid-lowering therapy. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for lipoprotein (a) testing, and its implications on management.

Machine Learning - Based Bleeding Risk Predictions in Atrial Fibrillation Patients on Direct Oral Anticoagulants.

Importance: Accurately predicting major bleeding events in non-valvular atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) is crucial for personalized treatment and improving patient outcomes, especially with emerging alternatives like left atrial appendage closure devices. The left atrial appendage closure devices reduce stroke risk comparably but with significantly fewer non-procedural bleeding events. Objective: To evaluate the performance of machine learning (ML) risk models in predicting clinically significant bleeding events requiring hospitalization and hemorrhagic stroke in non-valvular AF patients on DOACs compared to conventional bleeding risk scores (HAS-BLED, ORBIT, and ATRIA) at the index visit to a cardiologist for AF management. Design: Prognostic modeling with retrospective cohort study design using electronic health record (EHR) data, with clinical follow-up at one-, two-, and five-years. Setting: University of Pittsburgh Medical Center (UPMC) system. Participants: 24,468 non-valvular AF patients aged ≥18 years treated with DOACs, excluding those with prior history of significant bleeding, other indications for DOACs, on warfarin or contraindicated to DOACs. Exposures: DOAC therapy for non-valvular AF. Main Outcomes and Measures: The primary endpoint was clinically significant bleeding requiring hospitalization within one year of index visit. The models incorporated demographic, clinical, and laboratory variables available in the EHR at the index visit. Results: Among 24,468 patients, 553 (2.3%) had bleeding events within one year, 829 (3.5%) within two years, and 1,292 (5.8%) within five years of index visit. We evaluated multivariate logistic regression and ML models including random forest, classification trees, k-nearest neighbor, naive Bayes, and extreme gradient boosting (XGBoost) which modestly outperformed HAS-BLED, ATRIA, and ORBIT scores in predicting clinically significant bleeding at 1-year follow-up. The best performing model (random forest) showed area under the curve (AUC-ROC) 0.76 (0.70-0.81), G-Mean score of 0.67, net reclassification index 0.14 compared to 0.57 (0.50-0.63), G-Mean score of 0.57 for HASBLED score, p-value for difference <0.001. The ML models had improved performance compared to conventional risk across time-points of 2-year and 5-years and within the subgroup of hemorrhagic stroke. SHAP analysis identified novel risk factors including measures from body mass index, cholesterol profile, and insurance type beyond those used in conventional risk scores. Conclusions and Relevance: Our findings demonstrate the superior performance of ML models compared to conventional bleeding risk scores and identify novel risk factors highlighting the potential for personalized bleeding risk assessment in AF patients on DOACs.

Association between extracellular matrix expansion quantified by cardiovascular magnetic resonance and short-term mortality.

BACKGROUND: Extracellular matrix expansion may be a fundamental feature of adverse myocardial remodeling, it appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and extracellular matrix is not clear because of difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance techniques to quantify the full spectrum of extracellular matrix expansion not readily detectable by conventional cardiovascular magnetic resonance. METHODS AND RESULTS: We recruited 793 consecutive patients at the time of cardiovascular magnetic resonance without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20-50 years). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction. ECV uses gadolinium contrast as an extracellular space marker based on T1 measures of blood and myocardium pre- and post-gadolinium contrast and hematocrit measurement. In volunteers, ECV ranged from 21.7% to 26.2%, but in patients it ranged from 21.0% to 45.8%, indicating considerable burden. There were 39 deaths over a median follow-up of 0.8 years (interquartile range 0.5-1.2 years), and 43 individuals who experienced the composite end point of death/cardiac transplant/left ventricular assist device implantation. In Cox regression models, ECV related to all-cause mortality and the composite end point (hazard ratio, 1.55; 95% confidence interval, 1.27-1.88 and hazard ratio, 1.48; 95% confidence interval, 1.23-1.78, respectively, for every 3% increase in ECV), adjusting for age, left ventricular ejection fraction, and myocardial infarction size. CONCLUSIONS: ECV measures of extracellular matrix expansion may predict mortality as well as other composite end points (death/cardiac transplant/left ventricular assist device implantation).

Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography.

BACKGROUND: Echocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources. METHODS AND RESULTS: We prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1-9), EF by echo (assessed visually) or CMR were modestly correlated (R(2) = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF. CONCLUSIONS: Among those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant.

Characteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes.

BACKGROUND: Adverse pregnancy outcomes (APOs), hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are associated with ischemic heart disease in later life. OBJECTIVES: The authors aimed to study the features of premature myocardial infarction (MI) among women with and without prior APOs. METHODS: We performed a retrospective analysis of women with premature MI (<65 years of age) referred for left heart catheterization matched with a database of abstracted pregnancy data. We compared MI characteristics and epicardial coronary anatomy between women with and without APOs during their index pregnancy and evaluated time from delivery to MI. RESULTS: Of 391 women with premature MI and associated coronary angiography (age: 49 ± 8 years), 154 (39%) had a prior APO (hypertensive disorders of pregnancy n = 78, preeclampsia n = 35, gestational diabetes mellitus n = 28, and preterm birth n = 48). Women with APO history had a higher prevalence of diabetes (33% vs 16% without APO; P = 0.001) and presented earlier with MI following delivery (19.6 [IQR: 14.3-23.5] years vs those without APO 21.5 [IQR: 17.0-25.4] years; P = 0.012), driven by preeclampsia (17.1 [IQR: 12.7-22.4] years, P = 0.010). Women with and without APOs had similar MI features including rates of ST-segment elevation MI, obstructive and multi-vessel coronary artery disease, percutaneous coronary intervention, and shock. CONCLUSIONS: Among women with premature MIs, 39% had a history of an APO. Women with APO history presented sooner after pregnancy but had similar MI characteristics vs those without APOs. Pregnancy history may identify women who warrant early, aggressive cardiovascular disease prevention.

Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Low prevalence of "ideal cardiovascular health" in a community-based population: the heart strategies concentrating on risk evaluation (Heart SCORE) study.

BACKGROUND: Cardiovascular health is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported. METHODS AND RESULTS: The AHA construct of cardiovascular health and the AHA ideal health behaviors index and ideal health factors index were evaluated among 1933 participants (mean age 59 years; 44% blacks; 66% women) in the community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. One of 1933 participants (0.1%) met all 7 components of the AHA's definition of ideal cardiovascular health. Less than 10% of participants met ≥ 5 components of ideal cardiovascular health in all subgroups (by race, sex, age, and income level). Thirty-nine subjects (2.0%) had all 4 components of the ideal health behaviors index and 27 (1.4%) had all 3 components of the ideal health factors index. Blacks had significantly fewer ideal cardiovascular health components than whites (2.0 ± 1.2 versus 2.6 ± 1.4; P < 0.001). After adjustment by sex, age, and income level, blacks had 82% lower odds of having ≥ 5 components of ideal cardiovascular health (odds ratio 0.18, 95% confidence interval, 0.10 to 0.34; P<0.001). No interaction was found between race and sex. CONCLUSION: The prevalence of ideal cardiovascular health is extremely low in a middle-aged community-based study population. Comprehensive individual and population-based interventions must be developed to support the attainment of the AHA's 2020 Impact Goal for cardiovascular health.