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Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be useful. We used regression discontinuity design (RDD), a technique well-established in economics, on the Get With The Guidelines-Stroke (GWTG-Stroke) data set. RDD, based on regression, measures the occurrence of a discontinuity in an outcome (e.g., odds of home discharge) as a function of an intervention (e.g., alteplase) that becomes significantly more likely when crossing the threshold of a continuous variable that determines that intervention (e.g., time from symptom onset, since alteplase is only given if symptom onset is less than e.g., 3 h). The technique assumes that patients near either side of a threshold (e.g., 2.99 and 3.01 h from symptom onset) are indistinguishable other than the use of the treatment. We compared outcomes of patients whose estimated onset to treatment time fell on either side of the treatment threshold for three cohorts of patients in the GWTG-Stroke data set. This data set spanned three different treatment thresholds for alteplase (3 h, 2003-2007, N = 1,869; 3 h, 2009-2016, N = 13,086, and 4.5 h, 2009-2016, N = 6,550). Patient demographic characteristics were overall similar across the treatment thresholds. We did not find evidence of a discontinuity in clinical outcome at any treatment threshold attributable to alteplase. Potential reasons for failing to find an effect include violation of some RDD assumptions in clinical care, large sample sizes required, or already-well-chosen treatment threshold.

AimsThirty-day risk standardized readmission and mortality rates (RSRR, RSMR) are key determinants for hospital performance for cardiovascular conditions such as acute myocardial infarction (AMI) and heart failure (HF). We evaluated whether individual hospitals in the USA perform similarly for HF and AMI over time based on readmission and mortality metrics.Methods and resultsA total of 1950 hospitals in the USA with continuous participation in the Centers for Medicare and Medicaid Services (CMS) public reporting programme between 2010 and 2016 were identified. Latent mixture modelling was used to define performance trajectory groups. Overall, there were consistent declines in the RSMR (16.1-14.0%) and RSRR (20.3-16.6%) for AMI from 2010 to 2016. For HF, RSRR declined over time (25.1-21.7%), while there was a modest increase in RSMR (11.3-12.0%); parallel findings were observed across performance trajectory groups. The proportion of best performing centres for HF care that were also best performers for AMI care based on the 30-day RSMR and 30-day RSRR metric was 54% and 35%, respectively. Furthermore, the discordance rate between the best and worst performers for both conditions was low (

BackgroundAround 50% of hospital readmissions due to heart failure are preventable, with lack of adherence to prescribed self-care as a driving factor. Remote tracking and reminders issued by mobile health devices could help to promote self-care, which could potentially reduce these readmissions.ObjectiveWe sought to investigate two factors: (1) feasibility of enrolling heart failure patients in a remote monitoring regimen that uses wireless sensors and patient-reported outcome measures; and (2) their adherence to using the study devices and completing patient-reported outcome measures.MethodsTwenty heart failure patients participated in piloting a remote monitoring regimen. Data collection included: (1) physical activity using wrist-worn activity trackers; (2) body weight using bathroom scales; (3) medication adherence using smart pill bottles; and (4) patient -reported outcomes using patient-reported outcome measures.ResultsWe evaluated 150 hospitalized heart failure patients and enrolled 20 individuals. Two factors contributed to 50% (65/130) being excluded from the study: smartphone ownership and patient discharge. Over the course of the study, 60.0% of the subjects wore the activity tracker for at least 70% of the hours, and 45.0% used the scale for more than 70% of the days. The pill bottle was used less than 10% of the days by 55.0% of the subjects.ConclusionsOur method of recruiting heart failure patients prior to hospital discharge may not be feasible as the enrollment rate was low. Once enrolled, the majority of subjects maintained a high adherence to wearing the activity tracker but low adherence to using the pill bottle and completing the follow-up surveys. Scale usage was fair, but it received positive reviews from most subjects. Given the observed usage and feedback, we suggest mobile health-driven interventions consider including an activity tracker and bathroom scale. We also recommend administering a shorter survey more regularly and through an easier interface.

Following regulatory guidance set forth in 2008 by the US Food and Drug Administration for new drugs for type 2 diabetes mellitus, many large randomized, controlled trials have been conducted with the primary goal of assessing the safety of antihyperglycemic medications on the primary end point of major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Heart failure (HF) was not specifically mentioned in the US Food and Drug Administration guidance and therefore it was not a focus of these studies when planned. Several trials subsequently showed the impact of antihyperglycemic drugs on HF outcomes, which were not originally specified as the primary end point of the trials. The most impressive finding has been the substantial and consistent risk reduction in HF hospitalization seen across 4 trials of sodium glucose cotransporter 2 inhibitors. However, to date, these results have not led to regulatory approval of any of these drugs for a HF indication or a recommendation for use by US HF guidelines. It is therefore important to explore to what extent persuasive treatment effects on nonprimary end points can be used to support regulatory claims and guideline recommendations. This topic was discussed by researchers, clinicians, industry sponsors, regulators, and representatives from professional societies, who convened on the US Food and Drug Administration campus on March 6, 2019. This report summarizes these discussions and the key takeaway messages from this meeting.

Background Limited data exist to guide treatment for patients with heart failure with preserved ejection fraction and atrial fibrillation, including the important decision regarding rate versus rhythm control. Methods and Results We analyzed the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked to Medicare claims data from 2008 to 2014 to describe current treatments for rate versus rhythm control and subsequent outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation using inverse probability weighted analysis. Rhythm control was defined as use of an antiarrhythmic medication, cardioversion, or AF ablation or surgery. Rate control was defined as use of any combination of β-blocker, calcium channel blocker, and digoxin without evidence of rhythm control. Among 15 682 fee-for-service Medicare patients, at the time of discharge, 1857 were treated with rhythm control and 13 825 with rate control, with minimal differences in baseline characteristics between groups. There was higher all-cause death at 1 year in the rate control compared with the rhythm control group (37.5% and 30.8%, respectively, P

ObjectiveTo develop and validate a novel, machine learning-derived model to predict the risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM).Research design and methodsUsing data from 8,756 patients free at baseline of HF, with

BackgroundPost-stroke care delivery may be affected by provider participation in Medicare Shared Savings Program (MSSP) Accountable Care Organizations (ACOs) through systematic changes to discharge planning, care coordination, and transitional care.ObjectiveTo evaluate the association of MSSP with patient outcomes in the year following hospitalization for ischemic stroke.DesignRetrospective cohort SETTING: Get With The Guidelines (GWTG)-Stroke (2010-2014) PARTICIPANTS: Hospitalizations for mild to moderate incident ischemic stroke were linked with Medicare claims for fee-for-service beneficiaries ≥ 65 years (N = 251,605).Main measuresOutcomes included discharge to home, 30-day all-cause readmission, length of index hospital stay, days in the community (home-time) at 1 year, and 1-year recurrent stroke and mortality. A difference-in-differences design was used to compare outcomes before and after hospital MSSP implementation for patients (1) discharged from hospitals that chose to participate versus not participate in MSSP or (2) assigned to an MSSP ACO versus not or both. Unique estimates for 2013 and 2014 ACOs were generated.Key resultsFor hospitals joining MSSP in 2013 or 2014, the probability of discharge to home decreased by 2.57 (95% confidence intervals (CI) = - 4.43, - 0.71) percentage points (pp) and 1.84 pp (CI = - 3.31, - 0.37), respectively, among beneficiaries not assigned to an MSSP ACO. Among discharges from hospitals joining MSSP in 2013, beneficiary ACO alignment versus not was associated with increased home discharge, reduced length of stay, and increased home-time. For patients discharged from hospitals joining MSSP in 2014, ACO alignment was not associated with changes in utilization. No association between MSSP and recurrent stroke or mortality was observed.ConclusionsAmong patients with mild to moderate ischemic stroke, meaningful reductions in acute care utilization were observed only for ACO-aligned beneficiaries who were also discharged from a hospital initiating MSSP in 2013. Only 1 year of data was available for the 2014 MSSP cohort, and these early results suggest further study is warranted.RegistrationNone.

Background Patient characteristics insufficiently explain disparities in cardiovascular outcomes among hospitalized patients, suggesting a role for community or hospital-level factors. Here, we evaluate the association of hospital racial composition and payer mix with all-cause inpatient mortality for patients hospitalized with acute coronary syndrome (ACS). Methods and Results Using the National Inpatient Sample, we identified adult hospitalizations from 2014 with a primary diagnosis of ACS (n=550 005). We divided National Inpatient Sample hospitals into quartiles based on percent of minority (black, Hispanic, Asian or Pacific Islander, Native American race/ethnicity) and low-income payer (Medicaid or uninsured) discharges in 2014. We utilized logistic regression to determine whether hospital minority or low-income payer makeup associated with all-cause inpatient mortality among those admitted for ACS . In adjusted models, ACS patients admitted to hospitals with >12.4% to 25.4% (Quartile 2), >25.4% to 44.3% (Q3), and >44.3% (Q4) minority discharges experienced a 14% (OR 1.14, 95% CI 1.06-1.23), 13% (OR 1.13, 95% CI 1.04-1.23), and 15% (OR 1.15, 95% CI 1.04-1.26) increased odds of all-cause inpatient mortality compared with hospitals with ≤12.4% (Q1) minority discharges. ACS patients admitted to hospitals with >18.7% to 25.7% (Q2) and >34.0% (Q4) low-income payer discharges experienced a 9% (OR 1.09, 1.01-1.17) and 9% (OR 1.09, 1.00-1.19) increased odds of all-cause inpatient mortality when compared with hospitals with ≤18.7% (Q1) low-income payer discharges. Conclusions Hospital minority and low-income payer makeup positively associate with odds of all-cause inpatient mortality among patients admitted for acute coronary syndrome.

Background Chest pain center (CPC) accreditation plays an important role in the management of acute myocardial infarction (AMI). However, no evidence shows whether the outcomes of AMI patients are improved with CPC accreditation in China. Methods and Results This retrospective analysis is based on a predesigned nationwide registry, CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome). The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, reinfarction, stent thrombosis, stroke, and heart failure. A total of 15 344 AMI patients, from 40 CPC-accredited hospitals, were enrolled, including 7544 admitted before and 7800 after accreditation. In propensity score matching, 6700 patients in each group were matched. The incidence of 7-day MACE (6.7% versus 8.0%; P=0.003) and all-cause death (1.1% versus 1.6%; P=0.021) was lower after accreditation. In multivariate adjusted mixed-effects Cox proportional hazards models, CPC accreditation was associated with significantly decreased risk of MACE (hazard ratio: 0.78; 95% CI, 0.68-0.91) and all-cause death (hazard ratio: 0.71; 95% CI, 0.51-0.99). The risk of MACE and all-cause death both followed a reverse J-shaped trend: the risk of MACE and all-cause death decreased gradually after achieving CPC accreditation, with minimal risk occurring in the first year, but increased in the second year and after. Conclusions Based on a large-scale national registry data set, CPC accreditation was associated with better in-hospital outcomes for AMI patients. However, the benefits seemed to attenuate over time, and reaccreditation may be essential for maintaining AMI care quality and outcomes.

ObjectivesThis study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).BackgroundAlthough therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown.MethodsHealth status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.ResultsMultivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p

ObjectivesThis study sought to determine the degree to which U.S. patients enrolled in a heart failure (HF) trial represent patients in routine U.S. clinical practice according to race and sex.BackgroundBlack patients and women are frequently under-represented in HF clinical trials. However, the degree to which black patients and women enrolled in trials represent such patients in routine practice is unclear.MethodsThe ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized patients hospitalized for HF to receive nesiritide or placebo from May 2007 to August 2010 and was neutral for clinical endpoints. This analysis compared non-Hispanic white (n = 1,494) and black (n = 1,012) patients enrolled in ASCEND-HF from the U.S. versus non-Hispanic white and black patients included in a U.S. hospitalized HF registry (i.e., Get With The Guidelines-Heart Failure [GWTG-HF]) during the ASCEND-HF enrollment period and meeting trial eligibility criteria.ResultsAmong 79,291 white and black registry patients, 49,063 (62%) met trial eligibility criteria (white, n = 37,883 [77.2%]; black, n = 11,180 [22.8%]). Women represented 35% and 49% of the ASCEND-HF and trial-eligible GWTG-HF cohorts, respectively. Compared with trial-enrolled patients, trial-eligible GWTG-HF patients tended to be older with higher blood pressure and higher ejection fraction. Trial-eligible patients had higher in-hospital mortality (2.3% vs. 1.3%), 30-day readmission (20.2% vs. 16.8%), and 180-day mortality (21.2% vs. 18.6%) than those enrolled in the trial (all p

Background When patients require readmission after a recent myocardial infarction (MI), returning to the discharging (index) hospital may be associated with better outcomes as a result of greater continuity in care. However, little evidence exists to answer this frequent patient question. Methods and Results Among Medicare patients aged ≥65 years discharged home alive post-MI from 491 US hospitals in the ACTION (Acute Coronary Treatment Intervention Outcomes Network) Registry, we compared reason for readmission, duration of rehospitalization, and 30-day mortality between patients readmitted to the index versus nonindex hospital within 30 days of index MI discharge. Among 53 471 MI patients, 7715 (14%) were readmitted within 30 days, and most readmitted patients (73%) returned to the discharging hospital. Reason for readmission was not significantly associated with location of readmission. In multivariable modeling, the strongest factors associated with readmission to a nonindex hospital were distance from the discharging hospital, transfer-in during the index MI hospitalization, and frequency of nonindex hospital admissions in the year preceding to the index MI. Duration of rehospitalization did not differ significantly between patients readmitted to the index versus nonindex hospital (median, 4 versus 3 days; P=0.17). Mortality risk was also not significantly different between patients readmitted to the index versus nonindex hospital overall (7.4 versus 7.7%; adjusted odds ratio, 0.89; 95% CI, 0.73-1.10) and when stratified by reason for readmission (P for interaction=0.61). Conclusions Post-MI readmissions did not differ in reason for readmission, duration of rehospitalization, or associated mortality when compared between patients who returned to the discharging hospital and those who sought care elsewhere.

BACKGROUND:Patients with heart failure (HF) show abnormal autonomic activities, which may stem from altered functional connectivity (FC) between different brain sites. METHODS AND RESULTS:We evaluate insular and cerebellar FC with other brain areas, before, during, and after the Valsalva challenge, with functional magnetic resonance imaging in 35 HF and 35 control subjects. Significant insular FC emerged with striatum, thalamus, and anterior cingulate. While left and right cerebellar cortices showed significant FC with each other constituting the cerebellum network, the insula and cerebellum networks showed significant negative FC with each other at baseline, challenge, and recovery phases. The challenge induced increased FC within the insula and the cerebellum networks in both HF and controls. However, patients with HF showed more increased insular network FC, but less enhanced cerebellar FC. During the recovery phase, the negative FC between the insular network and cerebellum enhanced significantly in controls, but not in HF. Lower left ventricle ejection fraction was correlated with lower insula network FC, and impaired negative FC between cerebellum and the insula network in HF. CONCLUSIONS:Increased insular FC in patients with HF might contribute to exaggerated sympathetic tone. While impaired cerebellar FC and diminished negative interactions between cerebellum and insular systems may indicate impaired parasympathetic functions in HF.

ObjectiveTo determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment.MethodsWe conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models.ResultsSES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103).ConclusionsLonger driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.

Background Intravenous recombinant tissue-type plasminogen activator (rtPA) remains the only medical therapy to improve outcomes for acute ischemic stroke (AIS), but the safety of rtPA in AIS patients with a history of recent myocardial infarction (MI) remains controversial. Methods and Results We sought to determine whether the presence of recent MI would alter the risk of mortality and rtPA-related complications. Multivariate logistic regression models were used to compare in-hospital outcomes between rtPA-treated AIS patients with recent MI within 3 months and those with no history of MI from the Get With The Guidelines-Stroke hospitals between February 2009 and December 2015. Among 40 396 AIS patients aged ≥65 years treated with rtPA, 241 (0.6%) had recent MI, of which 19.5% were ST-segment-elevation myocardial infarction. Patients with recent MI had more severe stroke than those without (median National Institutes of Health Stroke Scale [interquartile range]: 13.0 [7.0-20.0] versus 11.0 [6.0-18.0]). Recent MI was associated with an increased risk of mortality compared with no history of MI (17.4% versus 9.0%; adjusted odds ratio 1.60 [95% CI, 1.10-2.33]; P=0.014), but no statistically significant differences in rtPA-related complications (13.5% versus 9.4%; adjusted odds ratio 1.28 [0.88-1.86]; P=0.19). Recent ST-segment-elevation myocardial infarction was associated with higher risk of death and rtPA-related complications, but non-ST-segment-elevation myocardial infarction was not. Conclusions Among older AIS patients treated with rtPA, recent MI was associated with an increased risk of in-hospital mortality. Further investigations are necessary to determine whether the benefit of rtPA outweighs its risk among AIS patients with recent MI.

AimsThe relationship between resting stroke volume (SV) and prognostic markers in heart failure with preserved ejection fraction (HFpEF) is not well established. We evaluated the association of SV index (SVI) at rest with exercise capacity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in stable patients with HFpEF.Methods and resultsParticipants enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX) trial with available data on SVI by the Doppler method were included in this analysis (n = 185). A low-flow state defined by resting SVI

BackgroundThe necessity for rapid evaluation and treatment of acute ischemic stroke with intravenous tPA (tissue-type plasminogen activator) may increase the risk of administrating tPA to patients presenting with noncerebrovascular conditions that closely resemble stroke (stroke mimics). However, there are limited data on thrombolysis safety in stroke mimics.Methods and resultsUsing data from the Get With The Guidelines-Stroke Registry, we identified 72 582 patients with suspected ischemic stroke treated with tPA from 485 US hospitals between January 2010 and December 2017. We documented the use of tPA in stroke mimics, defined as patients who present with stroke-like symptoms, but after workup are determined not to have suffered from a stroke or transient ischemic attack, and compared characteristics and outcomes in stroke mimics versus those with ischemic stroke. Overall, 3.5% of tPA treatments were given to stroke mimics. Among them, 38.2% had a final nonstroke diagnoses of migraine, functional disorder, seizure, and electrolyte or metabolic imbalance. Compared with tPA-treated true ischemic strokes, tPA-treated mimics were younger (median 54 versus 71 years), had a less severe National Institute of Health Stroke Scale (median 6 versus 8), and a lower prevalence of cardiovascular risk factors, except for a higher prevalence of prior stroke/transient ischemic attack (31.3% versus 26.1%, all P

Background Current evidence on the association between serum urate and risk of atrial fibrillation ( AF ) is limited by cross-sectional designs and 1-time measurement of serum urate. The roles of serum urate, gout-related inflammation, and systemic inflammation in the etiology of AF are currently unknown. This gap is important, given that systemic inflammation is a recognized risk factor for AF . Methods and Results We conducted a prospective cohort study of 123 238 Chinese patients from 2006 to 2014. Serum urate concentrations were measured in 2006, 2008, 2010, and 2012. Incident AF cases were identified via biennial 12-lead ECG assessment. We used a Cox proportional hazards model to examine the sex-specific associations of cumulative average serum urate and changes in serum urate accounting for baseline level with risk of incident AF . We also assessed the joint associations of serum urate and high-sensitivity C-reactive protein levels. Comparing extreme categories, participants with the highest quintile of serum urate had 1.91-fold higher risk of AF (adjusted hazard ratio: 1.91; 95% CI, 1.32-2.76; P=0.001 for trend). Participants with both high serum urate and high-sensitivity C-reactive protein had 2.6-fold elevated risk of incident AF compared with those with normal levels of serum urate and high-sensitivity C-reactive protein (adjusted hazard ratio: 2.63; 95% CI, 1.63-4.23). Conclusions High serum urate levels and increases in serum urate over time were associated with increased risk of incident AF . Patients with high levels of both serum urate and high-sensitivity C-reactive protein had substantially higher risk of AF .

ObjectivesThe aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients' medications with changes in health status.BackgroundAlleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients' health status is unknown.MethodsThe association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression.ResultsAmong 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p

BackgroundHeart failure (HF) and cancer are a significant cause of morbidity and mortality in the US. Due to overlapping risk factors, these two conditions often coexist.MethodsWe sought to describe the national burden of HF for hospitalized patients with cancer. We identified adults admitted with a primary oncologic diagnosis in 2014 included in the National Inpatient Sample (NIS). Patient hospitalizations were divided based on presence or absence of comorbid HF. Primary outcomes included cost, length of stay (LOS), and inpatient mortality. Logistic regression analysis with cluster adjustment was performed to determine predictors of inpatient mortality.ResultsThere were 834,900 admissions for a primary oncologic diagnosis in patients without comorbid HF, and 64,740 (7.2%) admissions for patients with comorbid HF. Patients with HF were on average older and had more comorbidities. Patients with HF had significantly higher mean hospitalization cost ($22,571 vs $20,234, p-value

Background and Purpose- Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods- Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results- Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% ( P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions- Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2- VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

Objectives:The relationship between prior glycemic status and outcomes in intracerebral hemorrhage (ICH) is not established. We hypothesized that higher hemoglobin (Hb) A1c is associated with worse outcomes in ICH. Patients and methods:Using the GWTG-Stroke registry, data on patients with ICH between April 1, 2003 and September 30, 2015 were harvested. Patients were divided into four ordinal groups based on HbA1c values of 8.0%. Outcomes (mortality, modified Rankin Scale (mRS), home discharge and independent ambulatory status) were analyzed for patients overall and separately for patients with or without history of diabetes using multivariable regression models. Results:Among 75,455 patients with ICH (with available HbA1c data), patients with lower HbA1c (8.0%), (15.0%; 205/1364) were associated with higher in-hospital mortality. Lower HbA1c was also associated with higher mRS, less chance of going home, and lower likelihood of having independent ambulatory status in patients with prior history of diabetes. Conclusions:Among patients with no reported history of diabetes, both very low and very high HbA1c were directly associated with higher in-hospital mortality. Only very low HbA1c was associated with higher mortality in known diabetic patients. Further studies are needed to better define the relationship between HbA1c and outcomes, for it may have important implications for care of ICH patients.

BackgroundGuidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown.ObjectivesThis study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes.MethodsAmong 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up.ResultsAt baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months,

BackgroundIn 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a revised guideline on statin therapy initiation. The guideline included a 10-year risk calculation based on regression modeling, which made hand calculation infeasible. Compliance to the guideline has been suboptimal, as many patients were recommended but not prescribed statin therapy. Clinical decision support (CDS) tools may improve statin guideline compliance. Few statin guideline CDS tools evaluated clinical outcome.ObjectivesWe determined if use of a CDS tool, the statin macro, was associated with increased 2013 ACC/AHA statin guideline compliance at the level of statin prescription versus no statin prescription. We did not determine if each patient's statin prescription met ACC/AHA 2013 therapy intensity recommendations (high vs. moderate vs. low).MethodsThe authors developed a clinician-initiated, EHR-embedded statin macro command ("statin macro") that displayed the 2013 ACC/AHA statin guideline recommendation in the electronic health record documentation. We included patients who had a primary care visit during the study period (January 1-June 30, 2016), were eligible for statin therapy based on the ACC/AHA guideline prior to the study period, and were not prescribed statin therapy prior to the study period. We tested the association of macro usage and statin therapy prescription during the study period using relative risk and mixed effect logistic regression.ResultsSubjects included 11,877 patients seen in primary care, who were retrospectively recommended statin therapy at study initiation based on the ACC/AHA guideline, but who had not received statin therapy. During the study period, 125 clinicians used the statin macro command for 389 of the 11,877 patients (3.2%). Of the 389 patients for whom that statin macro was used, 108 patients (28%) had a statin prescribed during the study period. Of the 11,488 for whom the statin macro was not used, 1,360 (13%) patients received a clinician-prescribed statin (relative risk 2.3, p

BackgroundDiabetes mellitus is an increasingly prevalent condition among heart failure (HF) patients. The long-term morbidity and mortality among patients with and without diabetes with HF with reduced (HFrEF), borderline (HFbEF), and preserved ejection fraction (HFpEF) are not well described.MethodsUsing the Get With The Guidelines (GWTG)-HF Registry linked to Centers for Medicare & Medicaid Services claims data, we evaluated differences between HF patients with and without diabetes. Adjusted Cox proportional-hazard models controlling for patient and hospital characteristics were used to evaluate mortality and readmission outcomes.ResultsA cohort of 86,659 HF patients aged ≥65 years was followed for 3 years from discharge. Unadjusted all-cause mortality was between 4.4% and 5.5% and all-cause hospitalization was between 19.4% and 22.6% for all groups at 30 days. For all-cause mortality at 3 years from hospital discharge, diabetes was associated with an adjusted hazard ratio of 1.27 (95% CI 1.07-1.49, P = .0051) for HFrEF, 0.95 (95% CI 0.55-1.65, P = .8536) for HFbEF, 1.02 (95% CI 0.87-1.19, P = .8551) for HFpEF. For all-cause readmission, diabetes was associated with an adjusted hazard ratio of 1.06 (95% CI 0.87-1.29, P = .5585) for HFrEF, 1.48 (95% CI 1.15-1.90, P = .0023) for HFbEF, and 1.06 (95% CI 0.91-1.22, P = .4747) for HFpEF.ConclusionsHFrEF and HFbEF patients with diabetes are at increased risk for mortality and rehospitalization after hospitalization for HF, independent of other patient and hospital characteristics. Among HFpEF patients, diabetes does not appear to be independently associated with significant additional risks.

Despite the fact that cardiovascular disease (CVD) is the number 1 cause of death globally, investment in drug development and new drug approvals for CVD are precipitously declining. In contrast, the trajectory of both investment in development as well as new drug approvals for oncology have been increasing steadily over the same time frame. The factors that have spurred drug development in oncology may be applicable to new efforts to overcome barriers to drug development for CVD. Greater investment in basic research and application of expedited regulatory pathways have contributed to a lowering of development barriers in oncology. Barriers in implementation are also critical. More rapid adoption of guideline-based therapies and lower access barriers by payers have contributed to fewer implementation barriers for oncology therapeutics. There is substantially greater advocacy among patients and physicians for new oncology therapeutics, and such advocacy efforts are likely to have had a meaningful impact on lowering barriers to develop new oncology therapeutics. Broad support of patient and physician advocacy efforts directed towards CVD may help overcome existing development and implementation barriers to new drug development, thereby spurring more rapid progress in the fight to eradicate cardiovascular disease.

BackgroundSeveral cardiotoxic substances impact heart failure incidence. The burden of comorbid tobacco or substance use disorders among heart failure patients is under-characterized. We describe the burden of tobacco and substance use disorders among hospitalized heart failure patients in the United States.MethodsWe calculated the proportion of primary heart failure hospitalizations in the 2014 National Inpatient Sample with tobacco or substance use disorders accounting for demographic factors.ResultsOf 989,080 heart failure hospitalizations, 15.5% (n = 152,965) had documented tobacco (n = 119,285, 12.1%) or substance (n = 61,510, 6.2%) use disorder. Female sex was associated with lower rates of tobacco (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.70-0.74) and substance (OR 0.37; 95% CI, 0.36-0.39) use disorder. Tobacco and substance use disorder rates were highest for hospitalizations

ObjectivesThis study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories.BackgroundPatients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied.MethodsPatients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs.

BACKGROUND:The use of endovascular therapy (EVT) in patients with acute ischemic stroke who have large vessel occlusion has rapidly increased in the United States following pivotal trials demonstrating its benefit. Information about the contribution of interhospital transfer in improving access to EVT will help organize regional systems of stroke care. METHODS:We analyzed trends of transfer-in EVT from a cohort of 1 863 693 patients with ischemic stroke admitted to 2143 Get With The Guidelines-Stroke participating hospitals between January 2012 and December 2017. We further examined the association between arrival mode and in-hospital outcomes by using multivariable logistic regression models. RESULTS:Of the 37 260 patients who received EVT at 639 hospitals during the study period, 42.9% (15 975) arrived at the EVT-providing hospital after interhospital transfer. Transfer-in EVT cases increased from 256 in the first quarter 2012 to 1422 in the fourth quarter 2017, with sharply accelerated increases following the fourth quarter 2014 ( P

Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. However, with the increasing number of available therapies, clinicians face the challenge of simultaneously using several drugs, achieving target doses, and managing side effects that are often overlapping. Blood pressure, renal function, hyperkalaemia, and other factors may impede achieving target doses of all medications, leaving clinicians with dilemmas as to how to sequence and dose these various classes of drugs. The guideline-directed eligibility for certain drugs and devices requires stability on maximally tolerated doses of background therapies. However, significant variability exists in dosing achieved in clinical practice. We discuss the existing background data regarding the doses of heart failure medications in clinical trials and in practice, and provide recommendations on how to navigate this complex therapeutic decision-making.

Background The angiotensin-receptor/neprilysin inhibitor ( ARNI ) sacubitril/valsartan reduces hospitalization and mortality for patients with heart failure with reduced ejection fraction. However, adoption of ARNI into clinical practice has been slow. Factors influencing use of ARNI have not been fully elucidated. Using data from the Get With The Guidelines-Heart Failure registry, Hospital Compare, Dartmouth Atlas, and the American Hospital Association Survey, we sought to identify hospital characteristics associated with patient-level receipt of an ARNI prescription. Methods and Results We analyzed patients with heart failure with reduced ejection fraction who were eligible for ARNI prescription (ejection fraction≤40%, no contraindications) and hospitalized from October 1, 2015 through December 31, 2016. We used logistic regression to estimate the associations between hospital characteristics and patient ARNI prescription at hospital discharge, accounting for clustering of patients within hospitals using generalized estimating equation methods and adjusting for patient-level covariates. Of 16 674 eligible hospitalizations from 210 hospitals, 1020 patients (6.1%) were prescribed ARNI at discharge. The median hospital-level proportion of patients prescribed ARNI was 3.3% (Q1, Q3: 0%, 12.6%). After adjustment for patient-level covariates, for-profit hospitals had significantly higher odds of ARNI prescription compared with not-for-profit hospitals (odds ratio, 2.53; 95% CI , 1.05-6.10; P=0.04), and hospitals located in the Western United States had lower odds of ARNI prescription compared with those in the Northeast (odds ratio, 0.33; 95% CI , 0.13-0.84; P=0.02). Conclusions Relatively few hospital characteristics were associated with ARNI prescription at hospital discharge, in contrast to what has been observed in early adoption in other disease areas. Additional evaluation of barriers to implementing new evidence into heart failure practice is needed.

BackgroundWhen used in appropriately selected heart failure (HF) patients, cardiac resynchronization therapy (CRT) reduces mortality and hospitalization. It is not understood whether CRT implantation during hospitalization for HF is associated with similar benefits.HypothesisTiming of CRT implantation relative to hospitalization for HF is associated with clinical outcomes.MethodsThis analysis included patients eligible for CRT and discharged alive between January 2005 and December 2012 from 388 hospitals in Get With The Guidelines-HF. Participants were linked with Centers for Medicare and Medicaid Services data to evaluate outcomes of all-cause mortality and HF re-hospitalization based on CRT status (present on admission, placed during hospitalization, and prescribed at discharge; reference = no CRT).ResultsOf 15 619 CRT-eligible HF patients, 2408 (15%) had CRT on admission, 1269 (8%) underwent CRT implantation during hospitalization and 643 (4%) had CRT prescribed at discharge. Compared with patients without CRT, mortality was lower in those who received CRT implantation during HF hospitalization (adjusted hazard ratio [HR] 0.63; P < 0.0001) and those prescribed CRT at discharge (adjusted HR 0.78; P = 0.048). A reduction in HF re-hospitalization was observed in patients with CRT implanted during hospitalization (adjusted HR 0.64; P < 0.0001), but not in those who were prescribed CRT at discharge (adjusted HR 1.02; P = 0.77).ConclusionCRT implantation during HF hospitalization was associated with lower rates of mortality and HF re-hospitalization. These data suggest that a CRT utilization strategy that does not delay implantation to the post-discharge period may be appropriate. Randomized data are needed to definitively identify optimal timing of CRT implantation.

BackgroundReal-world data on the clinical outcomes of heart failure (HF) across the spectrum of ejection fraction (EF) and the prognostic value of B-type natriuretic peptide (BNP) have not been well examined.HypothesisThe real-world association between the clinical outcomes of HF and EF or BNP levels may differ across different EF or BNP values.MethodsThe Optum Integrated Claims-Clinical data (07/2009-09/2016) was used to identify adult patients with ≥1 HF diagnosis during hospitalization or emergency room visit. Three EF cohorts were formed: reduced (rEF; EF < 40%), mid-range (mrEF; EF 40%-49%), and preserved EF (pEF; EF ≥ 50%). Stratifications by BNP levels were performed using median BNP as cutoff between high vs low BNP (H-BNP vs L-BNP).ResultsIn total, 7005 HF patients with EF measurements (2456 patients with both HF and BNP measurements) were identified. rEF patients had higher risk of stroke (hazard ratio [HR] = 1.57, P = 0.010) and acute myocardial infarction (AMI) (HR = 2.42, P < 0.001) compared to pEF patients. H-BNP was associated with a significantly higher risk of mortality (P < 0.001). rEF patients with H-BNP had a significantly higher risk of stroke than those with L-BNP.ConclusionsPatients with rEF had a significantly higher rate of stroke and AMI vs pEF patients, as did patients with H-BNP vs L-BNP. The present study is the first to show the real-world association of EF and BNP (alone and in combination) with clinical outcomes, further supporting the recommendation to use these markers in clinical practice. These results may help to guide future recommendations and improve the clinical management of HF.