Optimal timing of staged percutaneous coronary intervention after subintimal tracking and re-entry: Rationale and design of the subintimal tracking and re-entry with deferred stenting study.

BACKGROUND: Ten to fifteen percent of chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) are unsuccessful in contemporary practice. Subintimal tracking and re-entry (STAR) (one form of "investment procedure") with staged reattempt and stenting may further increase the ultimate success and safety of CTO as a bailout strategy. The optimal timing for staged stenting after STAR is unknown. METHODS AND RESULTS: We designed a six-center, prospective randomized trial with a planned enrollment of 150 patients where STAR is utilized in case of impending failure. The primary aim is to evaluate the optimal timing of the staged PCI after STAR by randomizing the timing to earlier (5-7 weeks) versus later (12-14 weeks) staged PCI. The primary endpoint of the study is the technical success rate of the staged procedure. The secondary endpoints include: (1) the rate of thrombolysis in myocardial infarction 3 flow at the start of staged intervention, (2) rate of partial technical and procedural success of the staged procedure, (3) rate of in-hospital and 12-month major cardiac and cerebrovascular adverse events, and (4) change in patient-reported quality at 30 days, 6 months, and 12 months assessed by Seattle Angina Questionnaire. CONCLUSION: This study will ascertain the optimal timing of staged stenting after bail-out STAR approach in contemporary CTO PCI (ClinicalTrials.gov NCT05089864).

Cardiovascular disease and maternal mortality: perceptions in a Midwest birthing population.

BACKGROUND: Missouri has one of the highest rates of maternal mortality in the United States. To date, there are currently no studies describing birthing peoples' knowledge or perceptions of contributing causes of maternal mortality. An improved understanding of population-specific knowledge can help to define how best to design targeted interventions to reduce disease-specific causes of maternal mortality. OBJECTIVE: This study aimed to examine the knowledge and understanding of maternal mortality in a Missouri birthing population. STUDY DESIGN: A 46-question, cross-sectional survey to assess the familiarity with local maternal mortality rates, groups affected, and causality was developed by the Missouri Perinatal Quality Collaborative and the Maternal-Child Learning and Action Network and emailed to a random sample of birthing people across Missouri. Those who identified as someone with birthing potential with a Missouri zip code and who were ≥18 years of age were eligible for inclusion. Unadjusted descriptive statistics were generated and stratified by age, race, and region. RESULTS: Among 2196 surveys sent, 1738 people completed the survey. Of those who responded, 78.2% were aware of the risk of pregnancy-related death with 14.7% reporting that they intimately knew someone who died. When asked if a certain group is affected disproportionately more, 66.4% responded affirmatively. Black (58.7%), uninsured (61.8%), poor (71.0%), those with substance abuse disorders (57.4%), and Native American (28.8%) birthing people were identified as groups that were perceived as suffering higher rates of maternal death. When polled on etiology, severe bleeding (56.9%) was believed to be the leading cause of death, and the second stage of labor was thought to be the period of highest risk (42.3%). Beliefs about the timing of death differed by age (P=.042) but not race (P=.81) or region (P=.191). CONCLUSION: Missouri birthing people are cognizant of the social factors associated with increased maternal mortality but are unaware of the leading causes of death, namely cardiovascular disease and mental health conditions. Future Perinatal Quality Collaborative work should focus on campaigns that raise public awareness about cardiovascular disease and mental health-related birthing risks and the importance of monitoring early warning signs after delivery.

Early Longitudinal Change in Heart Failure Health Status Following Initiation of Canagliflozin.

BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy improves health status in heart failure (HF). There is insufficient description regarding the timing, rate, and extent of the health status changes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) after initiation of SGLT2is. OBJECTIVES: The authors sought to model the association of canagliflozin treatment with rates of change in HF symptom status in HFpEF and HFrEF. METHODS: Study participants with HFrEF and HFpEF were treated with either canagliflozin 100 mg or placebo for 12 weeks. The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) was assessed at baseline and at 2, 4, 6, and 12 weeks. Longitudinal modeling assessed slope of KCCQ change across the study. RESULTS: Among 448 individuals with HF (181 with HFrEF and 267 with HFpEF), participants with HFpEF had lower baseline KCCQ-TSS scores than those with HFrEF (54 ± 21 vs 64 ± 20). Modeling demonstrated initial rapid improvement in KCCQ-TSS in both HF groups, with deceleration over the next 4 to 6 weeks. The rate of change was greater among HFpEF participants (0.7 points/day; 95% CI: 0.3-1.1 points/day) than HFrEF participants (ΔKCCQ-TSS/day = 0.5; 95% CI: 0.1-1.0 points/day) randomized to canagliflozin, but these differences were not statistically significant (0.2 points/day; 95% CI: -0.4 to 0.7 points/day; P = 056). CONCLUSIONS: After canagliflozin therapy, regardless of EF, modeling shows the KCCQ-TSS improves rapidly with the greatest improvements occurring within the first weeks of treatment. These results have implications for clinical use of SGLT2is and may be useful in the design of trials examining impact of these agents on health status in HF. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287).

Validation of a noninvasive cardiac output monitor in maternal cardiac disease: comparison of NICOM and transthoracic echocardiogram.

BACKGROUND: The physiological changes to the cardiovascular system during pregnancy are considerable and are more pronounced in those with cardiac disease. In the general population, noninvasive hemodynamic monitoring is a valid alternative to pulmonary artery catheterization, which poses risk in the pregnant population. There is limited data on noninvasive cardiac output monitoring in pregnancy as an alternative to pulmonary artery catheterization. OBJECTIVE: We sought to compare transthoracic echocardiography with a noninvasive cardiac output monitor (NICOM, Cheetah Medical) in pregnant patients with and without cardiac disease. STUDY DESIGN: This was a prospective, open-label validation study that compared 2-dimensional transthoracic echocardiography with NICOM estimations of cardiac output in each trimester of pregnancy and the postpartum period. Participants with and without cardiac disease with a singleton gestation were included. NICOM estimations of cardiac output were derived from thoracic bioreactance and compared with 2-dimensional transthoracic echocardiography for both precision and accuracy. A mean percentage difference of ±30% between the 2 devices was considered acceptable agreement between the 2 measurement techniques. RESULTS: A total of 58 subjects were enrolled; 36 did not have cardiac disease and 22 had cardiac disease. Heart rate measurements between the 2 devices were strongly correlated in both groups, whereas stroke volume and cardiac output measurements showed weak correlation. When comparing the techniques, the NICOM device overestimated cardiac output in the control group in all trimesters and the postpartum period (mean percentage differences were 50.3%, 52.7%, 48.1%, and 51.0% in the first, second, and third trimesters and the postpartum period, respectively). In the group with cardiac disease, the mean percentage differences were 31.9%, 29.7%, 19.6%, and 35.2% for the respective timepoints. CONCLUSION: The NICOM device consistently overestimated cardiac output when compared with 2-dimensional transthoracic echocardiography at all timepoints in the control group and in the first trimester and postpartum period for the cardiovascular disease group. The physiological changes of pregnancy, specifically the mean chest circumference and total body water, may alter the accuracy of the cardiac output measurement by the NICOM device as they are currently estimated. Although NICOM has been validated for use in the critical care setting, there is insufficient data to support its use in pregnancy.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.

BACKGROUND: Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin. METHODS: We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure). RESULTS: A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P=0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant). CONCLUSIONS: Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030235.

Percutaneous ventricular assist device for higher-risk percutaneous coronary intervention in surgically ineligible patients: Indications and outcomes from the OPTIMUM study.

BACKGROUND: Indications and outcomes for percutaneous ventricular assist device (pVAD) use in surgically ineligible patients undergoing percutaneous coronary intervention (PCI) remain poorly characterized. AIMS: We sought to describe the use and timing of pVAD and outcome in surgically ineligible patients. METHODS: Among 726 patients enrolled in the prospective OPTIMUM study, clinical and health status outcomes were assessed in patients who underwent pVAD-assisted PCI and those without pVAD. RESULTS: Compared with patients not receiving pVAD (N = 579), those treated with pVAD (N = 142) more likely had heart failure, lower left ventricular ejection fraction (30.7 ± 13.6 vs. 45.9 ± 15.5, p < 0.01), and higher STS 30-day predicted mortality (4.2 [2.1-8.0] vs. 3.3 [1.7-6.6], p = 0.01) and SYNTAX scores (36.1 ± 12.2, vs. 31.5 ± 12.1, p < 0.01). While the pVAD group had higher in-hospital (5.6% vs. 2.2%, p = 0.046), 30-day (9.0% vs. 4.0%, p = 0.01) and 6-month (20.4% vs. 11.7%, p < 0.01) mortality compared to patients without pVAD, this difference appeared to be largely driven by significantly higher mortality among the 20 (14%) patients with unplanned pVAD use (30% in-hospital mortality with unplanned PVAD vs. 1.6% with planned, p < 0.01; 30-day mortality, 38.1% vs. 4.5%, p < 0.01). The degree of 6-month health status improvement among survivors was similar between groups. CONCLUSION: Surgically ineligible patients with pVAD-assisted PCI had more complex baseline characteristics compared with those without pVAD. Higher mortality in the pVAD group appeared to be driven by very poor outcomes by patients with unplanned, rescue pVAD.

ACC/AHA Hypertension Guidelines and CHA2DS2-VASc Up-Scoring in Patients With Atrial Fibrillation.

This cohort study compares rates of hypertension among nonhypertensive patients with atrial fibrillation using JNC 8 vs ACC/AHA thresholds.

Patient knowledge and preferences for peripheral artery disease treatment.

BACKGROUND: Shared medical decision making requires patients' understanding of their disease and its treatment options. Peripheral artery disease (PAD) is a condition for which preference-sensitive treatments are available, but for which little is known about patients' knowledge and treatment preferences as it relates to specific treatment goals. METHODS: In a prospective, multicenter registry that involved patients with PAD experiencing claudication, the PORTRAIT Knowledge and Preferences Survey was administered at 1 year. It asks questions about PAD treatment choices, symptom relief options, disease management, and secondary prevention. PAD treatment preferences were also queried, and patients ranked 10 PAD treatment goals (1-10 Likert scale; 10 being most important). RESULTS: Among 281 participants completing the survey (44.8% women, mean age 69.6 ± 9.0 years), 54.1% knew that there was more than one way to treat PAD symptoms and 47.1% were offered more than one treatment option. Most (82.4%) acknowledged that they had to manage their PAD for the rest of their life. 'Avoid loss of toes or legs,' 'decreased risk of heart attack/stroke,' 'long-lasting treatment benefit,' 'living longer,' 'improved quality of life,' and 'doing what the doctor thinks I should do' had mean ratings > 9.0 (SD ranging between 1.21 and 2.00). More variability occurred for 'avoiding surgery.' 'cost of treatment,' 'timeline of pain relief,' and 'return to work' (SD ranging between 2.76 and 3.58). The single most important treatment goal was 'improving quality of life' (31.3%). CONCLUSIONS: Gaps exist in knowledge for patients with PAD who experience claudication, and there is a need for increased efforts to improve support for shared decision-making frameworks for symptomatic PAD.(ClinicalTrials.gov Identifier: NCT01419080).

Association Between Wearable Device Measured Activity and Patient-Reported Outcomes for Heart Failure.

BACKGROUND: Wearable devices are increasingly used in research and clinical care though the relevance of their data in the context of validated outcomes remains unknown. OBJECTIVES: The purpose of this study was to characterize the relationship between smartwatch activity and patient-centered outcomes in patients with heart failure. METHODS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) was a randomized-controlled clinical trial that enrolled participants with heart failure and a compatible smartphone. Participants were provided a Fitbit Versa 2 and completed serial Kansas City Cardiomyopathy Questionnaires (KCCQs) through a smartphone application. We evaluated the relationship between daily step count and floors climbed and KCCQ total symptom (TS) and physical limitation (PL) scores at baseline and their respective changes between 2 and 12 weeks using linear regression models, with restricted cubic splines for nonlinear associations. RESULTS: In total, 425 patients were included: 44.5% women, 40.9% with reduced ejection fraction. Baseline daily step count increased across categories of KCCQ-TS scores (2,437.6 ± 1,419.5 steps/d for scores 0 to 24 vs 4,870.9 ± 3,171.3 steps/d for scores 75 to 100; P < 0.001) with similar results for KCCQ-PL scores. This relationship remained significant for KCCQ-TS and KCCQ-PL scores after multivariable adjustment. Importantly, changes in daily step count were significantly associated with nonlinear changes in KCCQ-TS (P = 0.004) and KCCQ-PL (P = 0.003) scores. Floors climbed was associated with baseline KCCQ scores alone. CONCLUSIONS: Daily step count was nonlinearly associated with health status at baseline and over time in patients with heart failure. These results may inform interpretation of wearable device data in clinical and research contexts. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287).

Predictors of Revascularization in Lower-Extremity Peripheral Artery Disease: Insights From the PORTRAIT Study.

BACKGROUND: Peripheral artery disease (PAD) guidelines recommend revascularization only for patients with lifestyle-limiting claudication that is refractory to goal-directed medical therapy (class IIA, level of evidence A). However, real-world invasive treatment patterns and predictors of revascularization in patients with symptomatic lower-extremity PAD are still largely unknown. AIM: We aimed to examine rates, patient-level predictors, and site variability of early revascularization in patients with new or worsening PAD symptoms. METHODS: Among patients with new-onset or recent exacerbation of PAD in the 10-center Patient-centered Outcomes Related to TReatment practices in peripheral Arterial disease: Investigating Trajectories (PORTRAIT) study enrolled between June 2011 and September 2015, we classified early revascularization (endovascular or surgical) as procedures being performed within 3 months of presentation. Hierarchical logistic regression was used to identify patient characteristics associated with early revascularization. Variability across sites was estimated using the median odds ratio (OR). RESULTS: Among 797 participants, early revascularization procedures were performed in 224 (28.1%). Rutherford class 3 (vs Rutherford class 1; OR=1.86, 95% confidence interval [CI] 1.04-3.33) and having lesions in both iliofemoral and below-the-knee arterial segments (vs below the knee only; OR=1.75, 95% CI: 1.15-2.67) were associated with a higher odds of revascularization. Longer PAD duration >12 months (vs 1-6 months; OR=0.50, 95% CI: 0.32-0.77), higher ankle-brachial index scores (per 0.1 unit increase; OR=0.86, 95% CI: 0.78-0.96), and higher Peripheral Artery Questionnaire Summary scores (per 10 unit increase; OR=0.89, 95% CI: 0.80-0.99) were associated with a lower odds of revascularization. The raw rates for revascularization in different sites ranged from 6.25% to 66.28%, and the median OR was 1.88, 95% CI: 1.38-3.57. CONCLUSIONS: About 1 in 3 patients with symptomatic PAD received early revascularization. A more extensive disease and symptom burden were the main predictors of receiving early revascularization in PAD. There was significant site variability in revascularization patterns, and further studies will better understand the source of this variability and optimal selection criteria for early revascularization. CLINICAL IMPACT: Real world patterns and predictors of early revascularization in peripheral artery disease are not well understood. In this retrospective analysis of the POTRAIT study, about 1 out of 3 patients with PAD symptoms received early revascularization, with significant site variability. A more extensive disease and symptom burden were the main predictors of receiving early revascularization in PAD.

Circumstances of Hospitalization Impact Outcomes of Pulmonary Embolism.

Clinical tools that stratify risk of acute pulmonary embolism (PE) are useful in guiding therapeutic decision making, although may neglect pragmatic and potentially impactful characteristics of hospitalization during care of venous thromboembolism (VTE). Using a retrospective cohort design, consecutive patients discharged after inpatient care for acute PE were retrospectively evaluated for features of hospitalization, including patient characteristics, treatment efficiency, and circumstances of hospitalization. A proportional hazards model incorporated nontraditional risk factors to assess their association with a primary composite endpoint of in-hospital bleeding or death after adjusting for conventional PE risk estimators, including the Pulmonary Artery Severity Index (PESI) and right ventricular/left ventricular (RV/LV) ratio. From January 2016 to December 2018, 822 patients were discharged after treatment for acute PE, including high-risk (5.0%), intermediate-risk (64.2%), and low-risk (30.8%) PE. In-hospital death was 10-fold higher among those with high-risk PE compared to intermediate risk PE (36.6% vs 3.0%, P < 0.001). Overall, 60.4% of hospitalizations were primarily attributed to presentation with VTE. High risk PE was observed more frequently as a secondary event during hospitalizations ostensibly unrelated to VTE (26.8%). After adjustment for PESI score and RV/LV ratio, hypoalbuminia, IVC filter, and non-VTE hospitalization had strong associations with the primary composite outcome. Along with known markers of risk associated with PE, hypoalbuminia, IVC filter placement, and PE complicating hospitalization for circumstances not primarily related to VTE had strong associations with bleeding and death. These findings highlight the complex circumstances of acute PE care and need to refine practical risks.

Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.

BACKGROUND: Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear. METHODS: Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (≤40%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (≥45%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression. RESULTS: Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was ≤40, >40-≤60, and >60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6-7.5]; P<0.001). This was consistent in participants with EF≤40 (4.6 points [95% CI, 1.0-8.1]; P=0.01), >40 to ≤60 (4.9 points [95% CI, 0.8-9.0]; P=0.02) and >60% (6.8 points [95% CI, 1.5-12.1]; P=0.01; Pinteraction=0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (Pinteraction=0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all Pinteractionvalues nonsignificant). CONCLUSIONS: In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT02653482 and NCT03030235.

Association Between Change in Ambulatory Pulmonary Artery Pressures and Natriuretic Peptides in Patients with Heart Failure: Results From the EMBRACE-HF Trial.

BACKGROUND: Remote monitoring of pulmonary artery (PA) pressures and serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements guide heart failure (HF) treatment, but their association has yet to be described. METHODS AND RESULTS: In the Empagliflozin Evaluation by Measuring the Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trial, patients with HF and a remote PA pressure monitoring device were randomized to empagliflozin vs placebo. PA diastolic pressures (PADP) and NT-proBNP levels were obtained at baseline and 6 and 12 weeks. We used linear mixed models to examine the association between change in PADP and change in NT-proBNP, adjusting for baseline covariates. Of 62 patients, the mean patient age was 66.2 years, and 63% were male. The mean baseline PADP was 21.8 ± 6.4 mm Hg, and the mean NT-proBNP was 1844.6 ± 2767.7 pg/mL. The mean change between baseline and averaged 6- and 12-week PADP was -0.4 ± 3.1 mm Hg, and the mean change between baseline and averaged 6- and 12-week NT-proBNP was -81.5 ± 878.6 pg/mL. In adjusted analyses, every 2-mm Hg decrease in PADP was associated with an NT-proBNP reduction of 108.9 pg/mL (95% confidence interval -4.3 to 222.0, P = .06). CONCLUSIONS: We observed that short-term decreases in ambulatory PADP seem to be associated with decreases in NT-proBNP. This finding may provide additional clinical context when tailoring treatment for patients with HF.

Contemporary use of cardiovascular risk reduction strategies in type 2 diabetes. Insights from the diabetes collaborative registry.

BACKGROUND: Cardiovascular disease remains the primary source of morbidity and mortality in type 2 diabetes (T2D). We characterized the change over time in the use of evidence-based therapies to reduce cardiovascular risk in US patients with T2D. METHODS: Data from a longitudinal outpatient diabetes registry were used to calculate the prescription of SGLT2i or GLP-1RA over time and among those with high-risk comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD]) and a diabetes cardiovascular composite score (DCCS; calculated as: #eligible medications prescribed/#eligible medications x 100 for SGLT2i, GLP-1RA, statin, antiplatelet/anticoagulant therapy, ACEi/ARB/ARNI). Scores ranged from 0% to 100% (higher=more optimal care). RESULTS: Among 1,001,542 outpatients from 391 US sites, 51.7% patients had ASVCD, 17.7% HF, and 23.0% CKD. The percentage of patients prescribed an SGLT2i or GLP-1RA increased over time (7.3% in 2013 to 28.8% in 2019), and 18.3% of patients with ASCVD, HF, or CKD were on at least one of these medications at last follow-up vs 25.5% of patients without any of these comorbidities. Mean DCCS was 54±36%; 54±25% in patients with ASCVD, HF, or CKD vs 52±50% in patients without any of these comorbidities (P<0.001 for both). In a hierarchical linear model, male sex, and a diagnosis of CKD were independently associated with higher DCCS whereas a diagnosis of HF or ASCVD was associated with a lower DCCS. CONCLUSIONS: In a large, contemporary cohort of patients with T2D, we found improvement in the use of SGLT2i and GLP-1RA but unexpectedly lower use in patients with ASCVD, heart failure, and CKD, highlighting a treatment-risk paradox. Further education is needed to shift the understanding of these medications as tools for glucose-lowering to cardiovascular risk reduction and to improve their implementation in clinical practice.

Beta-Blocker Use and Heart Failure Outcomes in Mildly Reduced and Preserved Ejection Fraction.

BACKGROUND: Although studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and suggest potential negative effects in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: The purpose of this study was to examine the association of beta-blockers with heart failure (HF) hospitalization and death in patients with HF and EF ≥40% METHODS: Beta-blocker use was assessed at first encounter in outpatients ≥65 years of age with HFmrEF and HFpEF in the U.S. PINNACLE Registry (2013-2017). The associations of beta-blockers with HF hospitalization, death, and the composite of HF hospitalization/death were assessed using propensity-score adjusted multivariable Cox regression models, including interactions of EF × beta-blocker use. RESULTS: Among 435,897 patients with HF and EF ≥40% (HFmrEF, n = 75,674; HFpEF = 360,223), 289,377 (66.4%) were using a beta-blocker at first encounter; more commonly in patients with HFmrEF vs HFpEF (77.7% vs 64.0%; P < 0.001). There were significant interactions between EF × beta-blocker use for HF hospitalization, death, and composite of HF hospitalization/death (P < 0.001 for all), with higher risk with beta-blocker use as EF increased. Beta-blockers were associated with decreased risk of HF hospitalization and death in patients with HFmrEF but a lack of survival benefit and a higher risk of HF hospitalization in patients with HFpEF, particularly when EF was >60%. CONCLUSIONS: In a large, real-world, propensity score-adjusted cohort of older outpatients with HF and EF ≥40%, beta-blocker use was associated with a higher risk of HF hospitalization as EF increased, with potential benefit in patients with HFmrEF and potential risk in patients with higher EF (particularly >60%). Further studies are needed to understand the appropriateness of beta-blocker use in patients with HFpEF in the absence of compelling indications.

Racial Differences in Quality of Life in Patients With Heart Failure Treated With Sodium-Glucose Cotransporter 2 Inhibitors: A Patient-Level Meta-Analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF Trials.

BACKGROUND: Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure. METHODS: We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States-based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request. RESULTS: Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7-6.3; P=0.0007) in White patients and +4.7 points (95% CI, 0.7-8.7; P=0.02) in Black patients, with no significant interaction by race and treatment (P=0.76). Other KCCQ scales showed similar results. CONCLUSIONS: Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure.

Outcomes of Medical Therapy Plus PCI for Multivessel or Left Main CAD Ineligible for Surgery.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used to revascularize patients ineligible for CABG, but few studies describe these patients and their outcomes. OBJECTIVES: This study sought to describe characteristics, utility of risk prediction, and outcomes of patients with left main or multivessel coronary artery disease ineligible for coronary bypass grafting (CABG). METHODS: Patients with complex coronary artery disease ineligible for CABG were enrolled in a prospective registry of medical therapy + PCI. Angiograms were evaluated by an independent core laboratory. Observed-to-expected 30-day mortality ratios were calculated using The Society for Thoracic Surgeons (STS) and EuroSCORE (European System for Cardiac Operative Risk Evaluation) II scores, surgeon-estimated 30-day mortality, and the National Cardiovascular Data Registry (NCDR) CathPCI model. Health status was assessed at baseline, 1 month, and 6 months. RESULTS: A total of 726 patients were enrolled from 22 programs. The mean SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score was 32.4 ± 12.2 before and 15.0 ± 11.7 after PCI. All-cause mortality was 5.6% at 30 days and 12.3% at 6 months. Observed-to-expected mortality ratios were 1.06 (95% CI: 0.71-1.36) with The Society for Thoracic Surgeons score, 0.99 (95% CI: 0.71-1.27) with the EuroSCORE II, 0.59 (95% CI: 0.42-0.77) using cardiac surgeons' estimates, and 4.46 (95% CI: 2.35-7.99) using the NCDR CathPCI score. Health status improved significantly from baseline to 6 months: SAQ summary score (65.9 ± 22.5 vs 86.5 ± 15.1; P < 0.0001), Kansas City Cardiomyopathy Questionnaire summary score (54.1 ± 27.2 vs 82.6 ± 19.7; P < 0.0001). CONCLUSIONS: Patients ineligible for CABG who undergo PCI have complex clinical profiles and high disease burden. Following PCI, short-term mortality is considerably lower than surgeons' estimates, similar to surgical risk model predictions but is over 4-fold higher than estimated by the NCDR CathPCI model. Patients' health status improved significantly through 6 months.

Validation of the new PROGRESS-CTO complication risk scores in the OPEN-CTO registry.

BACKGROUND: Risk stratification before chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is important to inform procedural planning as well as patients and their families. We sought to externally validate the PROGRESS-CTO complication risk scores in the OPEN-CTO registry. METHODS: OPEN-CTO is a prospective registry of 1000 consecutive CTO PCIs performed at 12 experienced US centers using the hybrid algorithm. Endpoints of interest were in-hospital all-cause mortality, need for pericardiocentesis, acute myocardial infarction (MI), and major adverse cardiovascular events (MACE) (a composite of all-cause mortality, stroke, periprocedural MI, urgent repeat revascularization, and tamponade requiring pericardiocentesis). Model discrimination was assessed with the area under the curve (AUC) method, and calibration with the observed-versus-predicted probability method. RESULTS: Mean age was 65.4 ± 10.3 year, and 36.5% of patients had prior coronary artery bypass graft. Overall, 41 patients (4.1%) suffered MACE, 9 (0.9%) mortality, 26 (2.6%) acute MI, and 11 (1.1%) required pericardiocentesis. Technical success was achieved in 86.3%. Patients who experienced MACE had higher anatomic complexity, and more often required antegrade dissection/reentry and the retrograde approach. Increasing PROGRESS-CTO MACE scores were associated with increasing MACE rates: 0.5% (score 0-1), 2.4% (score 2), 3.7% (score 3), 4.5% (score 4), 7.8% (score 5), 13.0% (score 6-7). The AUC were as follows: MACE 0.72 (95% confidence interval [CI]: 0.66-0.78), mortality 0.79 (95% CI: 0.66-0.95), pericardiocentesis 0.71 (95% CI: 0.60-0.82), and acute MI 0.57 (95% CI: 0.49-0.66). Calibration was adequate for MACE and mortality, while the models underestimated the risk of pericardiocentesis and acute MI. CONCLUSIONS: In a large external cohort of patients treated with the hybrid algorithm by experienced CTO operators, the PROGRESS-CTO MACE, mortality, and pericardiocentesis risk scores showed good discrimination, while the acute MI score had inferior performance.

Health Status Outcomes in Older Adults Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention.

Background Although chronic total occlusions (CTOs) are common in older adults, they are less likely to be offered CTO percutaneous coronary intervention for angina relief than younger adults. The health status impact of CTO percutaneous coronary intervention in adults aged ≥75 years has not been studied. We sought to compare technical success rates and angina-related health status outcomes at 12 months between adults aged ≥75 and <75 years in the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion) registry. Methods and Results Angina-related health status was assessed with the Seattle Angina Questionnaire (score range 0-100, higher scores denote less angina). Technical success rates were compared using hierarchical modified Poisson regression, and 12-month health status was compared using hierarchical multivariable linear regression between adults aged ≥75 and <75 years. Among 1000 participants, 19.8% were ≥75 years with a mean age of 79.5±4.1 years. Age ≥75 years was associated with a lower likelihood of technical success (adjusted risk ratio=0.92 [95% CI, 0.86-0.99; P=0.02]) and numerically higher rates of in-hospital major adverse cardiovascular events (9.1% versus 5.9%, P=0.10). There was no difference in Seattle Angina Questionnaire Summary Score at 12 months between adults aged ≥75 and <75 years (adjusted difference=0.9 [95% CI, -1.4 to 3.1; P=0.44]). Conclusions Despite modestly lower success rates and higher complication rates, adults aged ≥75 years experienced angina-related health status benefits after CTO-percutaneous coronary intervention that were similar in magnitude to adults aged <75 years. CTO percutaneous coronary intervention should not be withheld based on age alone in otherwise appropriate candidates.