Predictors of first hospitalization due to disease activity and infections in systemic lupus erythematosus patients.

OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.

Using linked electronic medical record-pharmacy data to examine lupus medication adherence: A retrospective cohort study.

INTRODUCTION: Medication nonadherence is common in systemic lupus erythematosus (SLE) and associated with morbidity and mortality. We explored the reliability of pharmacy data within the electronic medical record (EMR) to examine factors associated with nonadherence to SLE medications. METHODS: We included patients with SLE who were prescribed ≥1 SLE medication for ≥90 days. We compared two datasets of pharmacy fill data, one within the EMR and another from the vendor who obtained this information from pharmacies and prescription benefit managers. Adherence was defined by medication possession ratio (MPR) ≥80%. In addition to MPR for each SLE medication, we evaluated the weighted-average MPR and the proportion of patients adherent to ≥1 SLE medication and to all SLE medications. We used logistic regression to examine factors associated with adherence. RESULTS: Among 181 patients (median age 36, 96% female, 58% Black), 98% were prescribed hydroxychloroquine, 34% azathioprine, 33% mycophenolate, 18% methotrexate, and 7% belimumab. Among 1276 pharmacy records, 74% overlapped between linked EMR-pharmacy data and data obtained directly from the vendor. Only 9% were available from the vendor but not through linked EMR-pharmacy data. The weighted-average MPR was 57%; 45% were adherent to hydroxychloroquine, 46% to ≥1 SLE medication, and 32% to all SLE medications. Older age was associated with adherence in univariable and multivariable analyses. DISCUSSION: Our study showed that obtaining linked EMR-pharmacy data is feasible with minimal missing data and can be leveraged in future adherence research. Younger patients were more likely to be nonadherent and may benefit from targeted intervention.

Antithrombotic Strategies in Atrial Fibrillation After ACS and/or PCI: A 4-Way Comparison From AUGUSTUS.

BACKGROUND: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known. OBJECTIVES: The authors sought to determine which antithrombotic regimen best balances safety and efficacy. METHODS: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint. RESULTS: A total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death. CONCLUSIONS: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400).

Failure to Rescue After Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry.

BACKGROUND: Failure to rescue (FTR) describes in-hospital mortality following a procedural complication and has been adopted as a quality metric in multiple specialties. However, FTR has not been studied for percutaneous coronary intervention (PCI) complications. METHODS: This is a retrospective study of patients undergoing PCI from the American College of Cardiology National Cardiovascular Data Registry's CathPCI Registry between April 1, 2018, and June 30, 2021. PCI complications evaluated were significant coronary dissection, coronary artery perforation, vascular complication, significant bleeding within 48 hours, new cardiogenic shock, and tamponade. Secular trends for FTR were evaluated with descriptive analysis, and hospital-level variation and clinical predictors were analyzed with logistic regression. RESULTS: Among 2 196 661 patients undergoing PCI at 1483 hospitals, 3.5% had at least 1 PCI complication. In-hospital mortality occurred more frequently following a complication compared with cases without a complication (19.7% versus 1.3%). FTR increased during the study period from 17.1% to 20.1% (P<0.001). The median odds ratio for FTR was 1.48 (95% CI, 1.44-1.53) indicating significant hospital-level variation. Spearman rank correlation demonstrated the modest correlation between FTR and in-hospital mortality, 0.525 (P<0.001). CONCLUSIONS: Major procedural complications during PCI are infrequent, but FTR occurs in roughly 1 in 5 patients following a PCI procedural complication with significant hospital-level variation. Improved understanding of practices associated with low FTR could meaningfully improve patient outcomes following a PCI complication.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Antithrombotic Strategies According to Age: Insights from the AUGUSTUS Trial.

OBJECTIVE: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. METHODS: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. RESULTS: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. CONCLUSIONS: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Adaptive Discretization for Event PredicTion (ADEPT).

Recently developed survival analysis methods improve upon existing approaches by predicting the probability of event occurrence in each of a number pre-specified (discrete) time intervals. By avoiding placing strong parametric assumptions on the event density, this approach tends to improve prediction performance, particularly when data are plentiful. However, in clinical settings with limited available data, it is often preferable to judiciously partition the event time space into a limited number of intervals well suited to the prediction task at hand. In this work, we develop Adaptive Discretization for Event PredicTion (ADEPT) to learn from data a set of cut points defining such a partition. We show that in two simulated datasets, we are able to recover intervals that match the underlying generative model. We then demonstrate improved prediction performance on three real-world observational datasets, including a large, newly harmonized stroke risk prediction dataset. Finally, we argue that our approach facilitates clinical decision-making by suggesting time intervals that are most appropriate for each task, in the sense that they facilitate more accurate risk prediction.

Case Volumes and Outcomes Among Early-Career Interventional Cardiologists in the United States.

BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States. OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.

On-treatment analysis of torsemide versus furosemide for patients hospitalized for heart failure: A post-hoc analysis of TRANSFORM-HF.

AIM: The TRANSFORM-HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non-adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on-treatment analysis inclusive of all randomized patients except those confirmed non-adherent to study diuretic. METHODS AND RESULTS: TRANSFORM-HF was an open-label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator-selected dosage. This post-hoc on-treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non-adherent to study diuretic. This modified on-treatment definition was applied separately at time of hospital discharge and 30-day follow-up. All-cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on-treatment analyses at discharge and 30-day follow-up, respectively. There was no significant difference in all-cause mortality between torsemide and furosemide in patients on-treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83-1.22], p = 0.96) and at 30-day follow-up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81-1.27], p = 0.90). All-cause mortality or all-cause hospitalization was similar between torsemide and furosemide in patients who were on-treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82-1.03]) and 30-day follow-up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82-1.05]). In patients who were on-treatment at 30-day follow-up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86-1.14], p = 0.87). CONCLUSIONS: In TRANSFORM-HF, a post-hoc on-treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03296813.

Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF.

BACKGROUND: The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups. METHODS: We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score. RESULTS: Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59-1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70-1.17] for HF with preserved LVEF versus HF with reduced LVEF; P=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup. CONCLUSIONS: Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813.

Implementation of a Multidimensional Strategy to Reduce Post-PCI Bleeding Risk.

BACKGROUND: The American College of Cardiology Reduce the Risk: PCI Bleed Campaign was a hospital-based quality improvement campaign designed to reduce post-percutaneous coronary intervention (PCI) bleeding events. The aim of the campaign was to provide actionable evidence-based tools for participants to review, adapt, and adopt, depending upon hospital resources and engagement. METHODS: We used data from 8 757 737 procedures in the National Cardiovascular Data Registry between 2015 and 2021 to compare patient and hospital characteristics and bleeding outcomes among campaign participants (n=195 hospitals) and noncampaign participants (n=1384). Post-PCI bleeding risk was compared before and after campaign participation. Multivariable hierarchical logistic regression was used to determine the adjusted association between campaign participation and post-PCI bleeding events. Prespecified subgroups were examined. RESULTS: Campaign hospitals were more often higher volume teaching facilities located in urban or suburban locations. After adjustment, campaign participation was associated with a significant reduction in the rate of bleeding (bleeding: adjusted odds ratio, 0.61 [95% CI, 0.53-0.71]). Campaign hospitals had a greater decrease in bleeding events than noncampaign hospitals. In a subgroup analysis, the reduction in bleeding was noted in non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction patients, but no significant reduction was seen in patients without acute coronary syndrome. CONCLUSIONS: Participation in the American College of Cardiology Reduce the Risk: PCI Bleed Campaign was associated with a significant reduction in post-PCI bleeding. Our results underscore that national quality improvement efforts can be associated with a significant impact on PCI outcomes.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM.

BACKGROUND: Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy). METHODS: A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ2 tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, ß-blocker use, and ergometer type. RESULTS: At baseline, women (n=102) were older (62 years versus 56 years; P<0.0001), had lower peak oxygen consumption (16.7 mL·kg-1·min-1 versus 21.3 mL·kg-1·min-1; P<0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P<0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P<0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P=0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P=0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P=0.348), change in peak oxygen consumption (1.2 mL·kg-1·min-1 versus 1.6 mL·kg-1·min-1; P=0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P=0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P=0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P=0.0008). CONCLUSIONS: Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.

Trans-Balance: Reducing demographic disparity for prediction models in the presence of class imbalance.

INTRODUCTION: Risk prediction, including early disease detection, prevention, and intervention, is essential to precision medicine. However, systematic bias in risk estimation caused by heterogeneity across different demographic groups can lead to inappropriate or misinformed treatment decisions. In addition, low incidence (class-imbalance) outcomes negatively impact the classification performance of many standard learning algorithms which further exacerbates the racial disparity issues. Therefore, it is crucial to improve the performance of statistical and machine learning models in underrepresented populations in the presence of heavy class imbalance. METHOD: To address demographic disparity in the presence of class imbalance, we develop a novel framework, Trans-Balance, by leveraging recent advances in imbalance learning, transfer learning, and federated learning. We consider a practical setting where data from multiple sites are stored locally under privacy constraints. RESULTS: We show that the proposed Trans-Balance framework improves upon existing approaches by explicitly accounting for heterogeneity across demographic subgroups and cohorts. We demonstrate the feasibility and validity of our methods through numerical experiments and a real application to a multi-cohort study with data from participants of four large, NIH-funded cohorts for stroke risk prediction. CONCLUSION: Our findings indicate that the Trans-Balance approach significantly improves predictive performance, especially in scenarios marked by severe class imbalance and demographic disparity. Given its versatility and effectiveness, Trans-Balance offers a valuable contribution to enhancing risk prediction in biomedical research and related fields.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial.

BACKGROUND: Hypertension (HTN) is common in patients with hypertrophic cardiomyopathy (HCM), but its effect on the treatment of left ventricular outflow tract (LVOT) obstruction is undefined. Although elevated systolic blood pressure (SBP) may impact dynamic LVOT gradients, its response to cardiac myosin inhibition is unknown. OBJECTIVES: In a post hoc exploratory analysis of the EXPLORER-HCM trial (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), the authors examined the characteristics of patients with obstructive HCM and HTN and the associations between HTN, SBP, and the response to mavacamten treatment of LVOT obstruction. METHODS: Patients were stratified by baseline history of HTN and mean SBP during 30-week treatment with mavacamten or placebo. The study estimated treatment differences and evaluated HTN and SBP groups by treatment interaction. Analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints. RESULTS: HTN was present in 119 of 251 patients (47.4%), including 60 receiving mavacamten and 59 receiving placebo. Patients with HTN vs no HTN were older (63.4 vs 54.0 years; P < 0.001), had higher SBP (134 ± 15.1 mm Hg vs 123 ± 13.8 mm Hg; P < 0.001), more comorbidities, and lower peak oxygen consumption (19 ± 3 vs 20 ± 4 mL/kg/min; P = 0.021). Patients with HTN had similar NYHA functional class (NYHA functional class II, 72% vs 73%), Valsalva LVOT gradients (72 ± 34 mm Hg vs 74 ± 30 mm Hg), Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores (70.6 ± 18.8 vs 68.9 ± 23.1), and NT pro-B-type natriuretic peptide levels (geometric mean 632 ± 129 pg/mL vs 745 ± 130 pg/mL). Mavacamten-treated patients had improvement in all primary, secondary, and exploratory endpoints regardless of HTN status or mean SBP. CONCLUSIONS: The clinical benefits of mavacamten in symptomatic, obstructive HCM were similar in patients with and without HTN, despite differences in baseline characteristics. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545).

Facilitating Harmonization of Variables in Framingham, MESA, ARIC, and REGARDS Studies Through a Metadata Repository.

BACKGROUND: High-quality research in cardiovascular prevention, as in other fields, requires inclusion of a broad range of data sets from different sources. Integrating and harmonizing different data sources are essential to increase generalizability, sample size, and representation of understudied populations-strengthening the evidence for the scientific questions being addressed. METHODS: Here, we describe an effort to build an open-access repository and interactive online portal for researchers to access the metadata and code harmonizing data from 4 well-known cohort studies-the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, FHS (Framingham Heart Study), MESA (Multi-Ethnic Study of Atherosclerosis), and ARIC (Atherosclerosis Risk in Communities) study. We introduce a methodology and a framework used for preprocessing and harmonizing variables from multiple studies. RESULTS: We provide a real-case study and step-by-step guidance to demonstrate the practical utility of our repository and interactive web page. In addition to our successful development of such an open-access repository and interactive web page, this exercise in harmonizing data from multiple cohort studies has revealed several key themes. These themes include the importance of careful preprocessing and harmonization of variables, the value of creating an open-access repository to facilitate collaboration and reproducibility, and the potential for using harmonized data to address important scientific questions and disparities in cardiovascular disease research. CONCLUSIONS: By integrating and harmonizing these large-scale cohort studies, such a repository may improve the statistical power and representation of understudied cohorts, enabling development and validation of risk prediction models, identification and investigation of risk factors, and creating a platform for racial disparities research. REGISTRATION: URL: https://precision.heart.org/duke-ninds.