Eligibility and Projected Benefits of Rapid Initiation of Quadruple Medical Therapy for Newly Diagnosed Heart Failure.

BACKGROUND: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized. OBJECTIVES: This study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation. METHODS: Among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the AHA/ACC/HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers. RESULTS: Of 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no GDMT. CONCLUSIONS: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed HFrEF, >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality.

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage.

Importance: Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice. Objective: To evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions. Design, Setting, and Participants: This cohort study used data from the American Heart Association Get With The Guidelines-Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023. Exposures: Anticoagulation-associated ICH. Main Outcomes and Measures: DTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined. Results: Of 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non-vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity. Conclusions and Relevance: In US hospitals participating in Get With The Guidelines-Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

Trends in Stroke Thrombolysis Care Metrics and Outcomes by Race and Ethnicity, 2003-2021.

Importance: Understanding is needed of racial and ethnic-specific trends in care quality and outcomes associated with the US nationwide quality initiative Target: Stroke (TS) in targeting thrombolysis treatment for acute ischemic stroke. Objective: To examine whether the TS quality initiative was associated with improvement in thrombolysis metrics and outcomes across racial and ethnic groups. Design, Setting, and Participants: This retrospective cohort study included patients who presented within 4.5 hours of ischemic stroke onset at hospitals participating in the Get With The Guidelines-Stroke initiative from January 1, 2003, to December 31, 2021. The data analysis was performed between December 15, 2022, and November 27, 2023. Exposures: TS phases I (2010-2013), II (2014-2018), and III (2019-2021). Main Outcomes and Measures: The primary outcomes were thrombolysis rates and time metrics. Patient function and mortality were secondary outcomes. Results: Analyses included 1 189 234 patients, of whom 1 053 539 arrived to the hospital within 4.5 hours. The cohort included 50.4% female and 49.6% male patients and 2.8% Asian [median (IQR) age, 72 (61-82) years], 15.2% Black [median (IQR) age, 64 (54-75) years], 7.3% Hispanic [median (IQR) age, 68 (56-79) years], and 74.1% White [median (IQR) age, 75 (63-84) years] patients). Unadjusted thrombolysis rates increased in both the pre-TS (2003-2009) and TS periods in all racial and ethnic groups from 10% to 15% in 2003 to 43% to 46% in 2021, but disparities were observed in adjusted analyses and persisted in TS phase III, with Asian, Black, and Hispanic patients having significantly lower odds of receiving thrombolysis than White patients (adjusted odds ratio, 0.85 [95% CI, 0.81-0.90], 0.76 [95% CI, 0.74-0.78], and 0.86 [95% CI, 0.83-0.89], respectively). Door-to-needle (DTN) times improved in all racial and ethnic groups during TS, with DTN times of 60 minutes or less increasing from 26% to 28% in 2009 to 66% to 72% in 2021. However, in adjusted analyses, racial and ethnic disparities emerged. During TS phase III, compared with White patients, Asian, Black, and Hispanic patients had significantly lower odds of receiving thrombolysis with a DTN time of 60 minutes or less compared with White patients (risk-adjusted odds ratios, 0.91 [95% CI, 0.84-0.98], 0.78 [95% CI, 0.75-0.81], and 0.87 [95% CI, 0.83-0.92], respectively). During TS, clinical outcomes improved for all racial and ethnic groups from pre-TS, with TS phase III showing higher odds of ambulation at discharge among Asian, Black, Hispanic, and White patients. Asian, Black, and Hispanic patients were less likely to present within 4.5 hours. Conclusions and Relevance: In this cohort study of patients with ischemic stroke, the TS quality initiative was associated with improvement in thrombolysis frequency, timeliness, and outcomes for all racial and ethnic groups. However, disparities persisted, indicating a need for further interventions.

COVID-19 Infection Is Associated With Poor Outcomes in Patients With Intracerebral Hemorrhage.

BACKGROUND: Patients with ischemic stroke and concomitant COVID-19 infection have worse outcomes than those without this infection, but the impact of COVID-19 on hemorrhagic stroke remains unclear. We aimed to assess if COVID-19 worsens outcomes in intracerebral hemorrhage (ICH). METHODS AND RESULTS: We conducted an observational study of ICH outcomes using Get With The Guidelines Stroke data. We compared patients with ICH who were COVID-19 positive and negative during the pandemic (March 2020-February 2021) and prepandemic (March 2019-February 2020). Main outcomes were poor functional outcome (defined as a modified Rankin scale score of 4 to 6 at discharge), mortality, and discharge to a skilled nursing facility or hospice. The first stage included 60 091 patients with ICH who were COVID-19 negative and 1326 COVID-19 positive. In multivariable analyses, patients with ICH with versus without COVID-19 infection had 68% higher odds of poor outcome (odds ratio [OR], 1.68 [95% CI, 1.41-2.01]), 51% higher odds of mortality (OR, 1.51 [95% CI, 1.33-1.71]), and 66% higher odds of being discharged to a skilled nursing facility/hospice (OR, 1.66 [95% CI, 1.43-1.93]). The second stage included 62 743 prepandemic and 64 681 intrapandemic cases with ICH. In multivariable analyses, patients with ICH admitted during versus before the COVID-19 pandemic had 10% higher odds of poor outcomes (OR, 1.10 [95% CI, 1.07-1.14]), 5% higher mortality (OR, 1.05 [95% CI, 1.02-1.08]), and no significant difference in the risk of being discharged to a skilled nursing facility/hospice (OR, 0.93 [95% CI, 0.90-0.95]). CONCLUSIONS: The pathophysiology of the COVID-19 infection and changes in health care delivery during the pandemic played a role in worsening outcomes in the patient population with ICH.

Bundled Payments for Care Improvement and Quality of Care and Outcomes in Heart Failure.

Importance: The Centers for Medicare & Medicaid Services (CMS) Bundled Payments for Care Improvement (BPCI) program was launched in 2013 with a goal to improve care quality while lowering costs to Medicare. Objective: To compare changes in the quality and outcomes of care for patients hospitalized with heart failure according to hospital participation in the BPCI program. Design, Setting, and Participants: This cross-sectional study used a difference-in-difference approach to evaluate the BPCI program in 18 BPCI hospitals vs 211 same-state non-BPCI hospitals for various process-of-care measures and outcomes using American Heart Association Get With The Guidelines-Heart Failure registry and CMS Medicare claims data from November 1, 2008, to August 31, 2018. Data were analyzed from May 2022 to May 2023. Exposures: Hospital participation in CMS BPCI Model 2 Heart Failure, which paid hospitals in a fee-for-service process and then shared savings or required reimbursement depending on how the total cost of an episode of care compared with a target price. Main Outcomes and Measures: Primary end points included 7 quality-of-care measures. Secondary end points included 9 outcome measures, including in-hospital mortality and hospital-level risk-adjusted 30-day and 90-day all-cause readmission rate and mortality rate. Results: During the study period, 8721 patients were hospitalized in the 23 BPCI hospitals and 94 530 patients were hospitalized in the 224 same-state non-BPCI hospitals. Less than a third of patients (30 723 patients, 29.8%) were 75 years or younger; 54 629 (52.9%) were female, and 48 622 (47.1%) were male. Hospital participation in BPCI Model 2 was not associated with significant differential changes in the odds of various process-of-care measures, except for a decreased odds of evidence-based ß-blocker at discharge (adjusted odds ratio [aOR], 0.63; 95% CI, 0.41-0.98; P = .04). Participation in the BPCI was not associated with a significant differential change in the odds of receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors at discharge, receiving an aldosterone antagonist at discharge, having a cardiac resynchronization therapy (CRT)-defibrillator or CRT pacemaker placed or prescribed at discharge, having implantable cardioverter-defibrillator (ICD) counseling or an ICD placed or prescribed at discharge, heart failure education being provided among eligible patients, or having a follow-up visit within 7 days or less. Participation in the BPCI was associated with a significant decrease in odds of in-hospital mortality (aOR, 0.67; 95% CI, 0.51-0.86; P = .002). Participation was not associated with a significant differential change in hospital-level risk-adjusted 30-day or 90-day all-cause readmission rate and 30-day or 90-day all-cause mortality rate. Conclusion and Relevance: In this study, hospital participation in the BPCI Model 2 Heart Failure program was not associated with improvement in process-of-care quality measures or 30-day or 90-day risk-adjusted all-cause mortality and readmission rates.

Recruiting a Diverse Cardiology Physician Workforce.

Importance: Understanding trends in the representation of women and individuals from underrepresented racial and ethnic populations in cardiovascular disease and cardiovascular subspecialty fellowships is essential to improving the diversity of the cardiology workforce. Objective: To examine changes in the representation of women and underrepresented individuals in cardiovascular disease and cardiovascular subspecialty fellowships over time. Design, Setting, and Participants: This cross-sectional study of trainee sex and race and ethnicity in various training programs from 2008 to 2022 used data from the Accreditation Council for Graduate Medical Education's publicly available online source. Participants included all residents, internal medicine residents, general surgery residents, and fellows in cardiovascular disease and cardiovascular subspecialty fellowships. Main Outcomes and Measures: Percentages of women and Black and Hispanic trainees in these programs were calculated for each year. Mann-Kendall tests were used to determine if changes over the years represented a significant trend. Results: Among the 3320 cardiovascular disease trainees in 2022, 848 (25.5%) were women, and 459 (13.8%) were Black or Hispanic, less than the representation among internal medicine trainees at 43.8% and 15.6%, respectively. However, the percentage of women trainees in cardiovascular disease significantly increased from 17.6% in 2008 (P = .001 for time trend) and also increased for interventional cardiology fellowships (from 6.3% in 2008 to 20.1% in 2022; P = .002). Over the same period, the proportion of women in general surgery increased from 27.4% to 45.2% (P < .001). The percentage of Black and Hispanic trainees in internal medicine significantly increased from 8.6% in 2012 (P < .001) while increases in general surgery were not statistically significant (9.7% to 16.1%; P = .35). There were also important increases in the percentages of Black and Hispanic trainees in cardiovascular disease (from 8.3% in 2012; P = .09) and interventional cardiology (3.8% to 13.4%; P = .12). Conclusions and Relevance: In this study, the representation of women in cardiovascular fellowships, including interventional cardiology, increased over recent years. While representation of Black and Hispanic individuals is low in all residencies, including cardiovascular fellowships, recent positive trends are important to recognize and provide hope to drive future efforts.

Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Sex differences in long-term outcomes following acute heart failure hospitalization: Findings from the Get With The Guidelines-Heart Failure registry.

AIMS: Sex differences in long-term outcomes following hospitalization for heart failure (HF) across ejection fraction (EF) subtypes are not well described. In this study, we evaluated the risk of mortality and rehospitalization among males and females across the spectrum of EF over 5 years of follow-up following an index HF hospitalization event. METHODS AND RESULTS: Patients hospitalized with HF between 1 January 2006 and 31 December 2014 from the American Heart Association's Get With The Guidelines-Heart Failure registry with available 5-year follow-up using Medicare Part A claims data were included. The association between sex and risk of mortality and readmission over a 5-year follow-up period for each HF subtype (HF with reduced EF [HFrEF, EF ≤40%], HF with mildly reduced EF [HFmrEF, EF 41-49%], and HF with preserved EF [HFpEF, EF >50%]) was assessed using adjusted Cox models. The effect modification by the HF subtype for the association between sex and outcomes was assessed by including multiplicative interaction terms in the models. A total of 155 670 patients (median age: 81 years, 53.4% female) were included. Over 5-year follow-up, males and females had comparably poor survival post-discharge; however, females (vs. males) had greater years of survival lost to HF compared with the median age- and sex-matched US population (HFpEF: 17.0 vs. 14.6 years; HFrEF: 17.3 vs. 15.1 years; HFmrEF: 17.7 vs. 14.6 years for age group 65-69 years). In adjusted analysis, females (vs. males) had a lower risk of 5-year mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.87-0.90, p < 0.0001), and the risk difference was most pronounced among patients with HFrEF (aHR 0.87, 95% CI 0.85-0.89; pinteraction [sex*HF subtype] = 0.04). Females (vs. males) had a higher adjusted risk of HF readmission over 5-year follow-up (aHR 1.06, 95% CI 1.04-1.08, p < 0.0001), with the risk difference most pronounced among patients with HFpEF (aHR 1.11, 95% CI 1.07-1.14; pinteraction [sex*HF subtype] = 0.001). CONCLUSIONS: While females (vs. males) had lower adjusted mortality, females experienced a significantly greater loss in survival time than the median age- and sex-matched US population and had a greater risk of rehospitalization over 5 years following HF hospitalization.

Patterns of Referral and Postdischarge Utilization of Cardiac Rehabilitation Among Patients Hospitalized With Heart Failure: An Analysis From the GWTG-HF Registry.

BACKGROUND: Coverage for cardiac rehabilitation (CR) for patients with heart failure with reduced ejection fraction was expanded in 2014, but contemporary referral and participation rates remain unknown. METHODS: Patients hospitalized for heart failure with reduced ejection fraction (≤35%) in the American Heart Association Get With The Guidelines-Heart Failure registry from 2010 to 2020 were included, and CR referral status was described as yes, no, or not captured. Temporal trends in CR referral were assessed in the overall cohort. Patient and hospital-level predictors of CR referral were assessed using multivariable-adjusted logistic regression models. Additionally, CR referral and proportional utilization of CR within 1-year of referral were evaluated among patients aged >65 years with available Medicare administrative claims data who were clinically stable for 6-weeks postdischarge. Finally, the association of CR referral with the risk of 1-year death and readmission was evaluated using multivariable-adjusted Cox models. RESULTS: Of 69,441 patients with heart failure with reduced ejection fraction who were eligible for CR (median age 67 years; 33% women; 30% Black), 17,076 (24.6%) were referred to CR, and referral rates increased from 8.1% in 2010 to 24.1% in 2020 (Ptrend<0.001). Of 8310 patients with Medicare who remained clinically stable 6-weeks after discharge, the CR referral rate was 25.8%, and utilization of CR among referred patients was 4.1% (mean sessions attended: 6.7). Patients not referred were more likely to be older, of Black race, and with a higher burden of comorbidities. In adjusted analysis, eligible patients with heart failure with reduced ejection fraction who were referred to CR (versus not referred) had a lower risk of 1-year death (hazard ratio, 0.84 [95% CI, 0.70-1.00]; P=0.049) without significant differences in 1-year readmission. CONCLUSIONS: CR referral rates have increased from 2010 to 2020. However, only 1 in 4 patients are referred to CR. Among eligible patients who received CR referral, participation was low, with <1 of 20 participating in CR.

Clinical Profile, Health Care Costs, and Outcomes of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction.

Background Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (ie, stage D HF). The clinical profile and health care costs associated with these patients in US practice is not well described. Methods and Results We examined patients hospitalized for worsening chronic heart failure with reduced ejection fraction ≤40% from 2014 to 2019 in the GWTG-HF (Get With The Guidelines-Heart Failure) registry, who did not receive advanced HF therapies or have end-stage kidney disease. Patients with severely reduced EF defined as EF ≤30% were compared with those with EF 31% to 40% in terms of clinical profile and guideline-directed medical therapy. Among Medicare beneficiaries, postdischarge outcomes and health care expenditure were compared. Among 113 348 patients with EF ≤40%, 69% (78 589) had an EF ≤30%. Patients with severely reduced EF ≤30% tended to be younger and were more likely to be Black. Patients with EF ≤30% also tended to have fewer comorbidities and were more likely to be prescribed guideline-directed medical therapy ("triple therapy" 28.3% versus 18.2%, P<0.001). At 12-months postdischarge, patients with EF ≤30% had significantly higher risk of death (HR, 1.13 [95% CI, 1.08-1.18]) and HF hospitalization (HR, 1.14 [95% CI, 1.09-1.19]), with similar risk of all-cause hospitalizations. Health care expenditures were numerically higher for patients with EF ≤30% (median US$22 648 versus $21 392, P=0.11). Conclusions Among patients hospitalized for worsening chronic heart failure with reduced ejection fraction in US clinical practice, most patients have severely reduced EF ≤30%. Despite younger age and modestly higher use of guideline-directed medical therapy at discharge, patients with severely reduced EF face heightened postdischarge risk of death and HF hospitalization.

Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes. CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States.

BACKGROUND: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. OBJECTIVES: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria. METHODS: The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort. RESULTS: Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m2 (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high. CONCLUSIONS: Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs.

Comparing New York Heart Association Class and Patient-Reported Outcomes Among Patients Hospitalized for Heart Failure.

BACKGROUND: Alignment between clinician-reported New York Heart Association (NYHA) class compared and patient-reported outcomes among patients hospitalized for heart failure is unclear. METHODS: ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was a global randomized trial comparing nesiritide versus placebo among patients hospitalized for heart failure, irrespective of ejection fraction. Among patients with complete baseline data for NYHA class and the patient-reported EuroQOL-5 dimensions ([EQ-5D], both utility index and visual analog scale), levels of each scale were mapped across 4 prespecified categories "best" to "worst." Minor and moderate-severe discordance were defined as NYHA class and EQ-5D differing by 1 level and ≥2 levels, respectively. Multivariable models assessed factors independently associated with moderate-severe discordance, and associations between discordance and clinical outcomes. RESULTS: Among 5741 patients, concordance, minor discordance, and moderate-severe discordance between NYHA class and EQ-5D utility index occurred in 22%, 40%, and 38% of patients, respectively. For NYHA class and EQ-5D visual analog scale, this categorization occurred in 29%, 48%, and 23%. Discordance was more often due to disproportionately higher EQ-5D score (78% of discordance cases with utility index, and 70% with visual analog scale). NYHA class IV, higher EQ-5D scores, race, and geographic region were among patient factors independently associated with moderate-severe discordance. Magnitude of discordance was not associated with clinical outcomes; however, EQ-5D utility index disproportionately worse than NYHA class was associated with increased 180-day mortality (adjusted hazard ratio 1.27 [95% CI, 1.01-1.60]; P=0.04). CONCLUSIONS: In a global trial cohort of patients hospitalized for heart failure, the majority of patients exhibited discordance between clinician-reported NYHA class and patient-reported health status. Multiple patient factors were independently associated with moderate-severe discordance, and patients who perceived their health status as worse than the clinician's perception had higher mortality. Registration: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT00475852.

Assessing Heuristic Bias During Care for Patients Hospitalized for Heart Failure: Get With The Guidelines-Heart Failure.

BACKGROUND: Heuristic biases are increasingly recognized, and potentially modifiable, contributors to patient care and outcomes. Left digit bias is a cognitive bias where continuous variables are categorized by their left-most digit. The impact of this heuristic bias applied to patient age on quality of care in heart failure has not been explored. METHODS: We examined participants admitted from 2005 to 2021 in the Get With The Guidelines-Heart Failure registry. To create 2 naturally randomized groups, isolating the effect of left digit bias, we dichotomized patients into those discharged within 60 days prior to their 80th birthday (N=4238) and those discharged within 60 days after their 80th birthday (N=4329). We performed multivariable logistic regression to assess the association between discharge date relative to 80th birthday and several in-hospital quality metrics and in-hospital outcomes. Among Medicare participants (N=2759), we performed adjusted Cox regression to analyze the relationship between discharge date and risk of 1-year mortality or readmission. RESULTS: Among 8567 patients, 50.4% were female, 73% were non-Hispanic White, and 42.9% had an ejection fraction ≤40%. Discharge date relative to 80th birthday was not associated with numerous in-hospital quality metrics or in-hospital outcomes on unadjusted or adjusted logistic regression. Among Medicare beneficiaries, there was no association between discharge date and risk of mortality or readmission at 1-year postdischarge (hazard ratio, 1.03 [95% CI, 0.95-1.12]; P=0.52). CONCLUSIONS: In a large registry of patients hospitalized for heart failure, we did not detect a left digit bias' with respect to age at discharge, which resulted in differential quality of care or outcomes.

Intersection of atrial fibrillation and heart failure with mildly reduced and preserved ejection fraction in >400 000 participants in the Get With The Guidelines-Heart Failure Registry.

AIMS: Although atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), few data are available evaluating AF-specific care patterns and post-discharge outcomes in patients hospitalized for HFpEF. We evaluated AF-specific medical therapies and post-discharge outcomes among patients hospitalized for heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF by AF history. METHODS AND RESULTS: Trends in AF prevalence were evaluated among patients hospitalized for HFmrEF or HFpEF in the Get With The Guidelines-Heart Failure Registry from 2014 to 2020. Among those with linked Centers for Medicare & Medicaid Services post-discharge data, we assessed associations of AF with 12-month outcomes and determined trends in post-discharge prescriptions. Among 429 464 patients (median age 76 years [interquartile range 65-85], 57% women), 216 486 (50%) had a history of AF. Over time, the proportion of patients with AF increased slightly. Among the 79 895 patients with post-discharge data, AF was independently associated with higher risk of mortality and all-cause readmissions at 12 months, with stronger associations in HFpEF than in HFmrEF (mortality hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.09-1.16 vs. HR 1.03, 95% CI 0.97-1.10; pinteraction  = 0.009). Anti-arrhythmic drug use after heart failure hospitalization was low (18%) and increased modestly over time. Amiodarone accounted for 71% of total anti-arrhythmic drug prescriptions. Overall use of anticoagulants after heart failure hospitalization has significantly increased from 52% in 2014 to 61% in 2019, but remained modest. CONCLUSION: Prevalence of AF is rising among patients hospitalized with HFpEF. Those with comorbid AF face elevated post-discharge risks of death and rehospitalization. Current use of pharmacological rhythm control is low.

The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD.

BACKGROUND: Guidelines for evaluating patients with suspected coronary artery disease (CAD) recommend pretest probability (PTP) estimation but provide no clear recommendations regarding diagnostic testing in patients with >5% to 15% risk of obstructive CAD. The diagnostic and prognostic value of PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS) calculation in this patient group is unknown. OBJECTIVES: This work aims to improve the evaluation of stable patients with suspected CAD by using the PMRS, which identifies patients at minimal risk of CAD and events in patients with >5% to 15% PTP of obstructive CAD. METHODS: Greater than 5% to 15% PTP patients from 2 large clinical trials were used for subcohort derivation: PROMISE (N = 10,003) and Dan-NICAD (Danish study of Non-Invasive Testing in Coronary Artery Disease) (N = 3,252). First, the PMRS cutoff associated with a prevalence of obstructive CAD ≤5% was determined in the >5% to 15% PTP PROMISE core lab computed tomographic angiography patients (discovery cohort: n = 2,191). This cutoff was validated for obstructive CAD in >5% to 15% PTP Dan-NICAD patients (CAD validation cohort: n = 1,386) and for prognostic impact on death and myocardial infarction in >5% to 15% PTP PROMISE non-core lab computed tomographic angiography patients (prognosis validation cohort: n = 2,753). RESULTS: In the discovery cohort, a CAD prevalence of ≤5% was found at a PMRS of ≥34%. In the CAD validation cohort, this cutoff down-classified 442 (31.9%) of >5% to 15% PTP patients into the low PTP group (CAD ≤5%); the prevalence of obstructive CAD in down-classified patients was 3.2% compared to 7.1% in non-down-classified patients. A PMRS ≥34% was nonsignificantly associated with a lower risk of myocardial infarction and death in the prognosis validation cohort (HR: 0.58 [95% CI: 0.29-1.18]; P = 0.13). CONCLUSIONS: For evaluating patients with suspected CAD, a combined use of traditional PTP and the PMRS correctly down-classified one-third of >5% to 15% PTP patients into a group with very low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.

Machine learning to define phenotypes and outcomes of patients hospitalized for heart failure with preserved ejection fraction: Findings from ASCEND-HF.

BACKGROUND: Heart Failure with Preserved Ejection Fraction (HFpEF) is a heterogenous disease with few therapies proven to provide clinical benefit. Machine learning can characterize distinct phenotypes and compare outcomes among patients with HFpEF who are hospitalized for acute HF. METHODS: We applied hierarchical clustering using demographics, comorbidities, and clinical data on admission to identify distinct clusters in hospitalized HFpEF (ejection fraction >40%) in the ASCEND-HF trial. We separately applied a previously developed latent class analysis (LCA) clustering method and compared in-hospital and long-term outcomes across cluster groups. RESULTS: Of 7141 patients enrolled in the ASCEND-HF trial, 812 (11.4%) were hospitalized for HFpEF and met the criteria for complete case analysis. Hierarchical Cluster 1 included older women with atrial fibrillation (AF). Cluster 2 had elevated resting blood pressure. Cluster 3 had young men with obesity and diabetes. Cluster 4 had low resting blood pressure. Mortality at 180 days was lowest among Cluster 3 (KM event-rate 6.2 [95% CI: 3.5, 10.9]) and highest among Cluster 4 (18.8 [14.6, 24.0], P < .001). Twenty four-hour urine output was higher in Cluster 3 (2700 mL [1800, 3975]) than Cluster 4 (2100 mL [1400, 3055], P < .001). LCA also identified four clusters: A) older White or Asian women, B) younger men with few comorbidities, C) older individuals with AF and renal impairment, and D) patients with obesity and diabetes. Mortality at 180 days was lowest among LCA Cluster B (KM event-rate 5.5 [2.0, 10.3]) and highest among LCA Cluster C (26.3 [19.2, 35.4], P < .001). CONCLUSIONS: In patients hospitalized for HFpEF, cluster analysis demonstrated distinct phenotypes with differing clinical profiles and outcomes.

Patient-reported and Clinical Outcomes Among Patients Hospitalized for Heart Failure With Reduced Versus Preserved Ejection Fraction.

BACKGROUND: Differences between patients hospitalized for heart failure with reduced ejection fraction (HFrEF) vs HF with preserved EF (HFpEF) are not well-characterized, particularly as pertains to in-hospital decongestion and longitudinal patient-reported outcomes. The objective of this analysis was to compare patient-reported and clinical outcomes between patients hospitalized with HFrEF vs HFpEF. METHODS AND RESULTS: The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial enrolled 7141 patients hospitalized for HF with reduced or preserved EF. We assessed the association between an EF ≤ 40% vs an EF >40% with in-hospital decongestion, risk of rehospitalization and mortality, and quality of life as measured by the EuroQOL 5 Dimensions (EQ-5D). Among 5800 patients (81%) with complete EF data, 4782 (82%) had an EF ≤40% and 1018 (18%) had an EF >40%. Both groups demonstrated similar rates of decongestion by weight change and urine volume through 24 hours, a similar risk of 30-day mortality and HF rehospitalization, and a similar 180-day mortality. Patients with HFpEF had worse EQ-5D scores at hour 24 (median 0.76, [interquartile range (IQR) 0.51-0.84] vs 0.78 [IQR 0.57-0.84]; P = .01) that persisted through discharge (0.81 [IQR 0.69-0.86] vs 0.83 [IQR 0.71-1.00]; P < .001) and the 30-day follow-up (0.78 [IQR 0.60-0.85] vs 0.83 [IQR 0.71-1.00]; P < .001). After adjustment, these differences were attenuated and not statistically significant. CONCLUSIONS: In this large, multinational cohort of patients hospitalized for HF, patients with an EF ≤ 40% vs an EF >40% experienced similar in-hospital decongestion and postdischarge clinical outcomes. Patients with an EF >40% reported worse in-hospital and postdischarge patient-reported health status, but these measures were similar to HFrEF after accounting for other clinical factors.