Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Although clinical studies have demonstrated the association between a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice. OBJECTIVES: The aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients. METHODS: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model. RESULTS: After adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events. CONCLUSIONS: Repeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840).

Electronic Health Record Embedded Strategies for Improving Care of Patients With Heart Failure.

PURPOSE: A majority of clinical decisions use the electronic health record (EHR) and there is an unmet need to use its capability to help providers to make evidence-based decisions that improve care for heart failure patients. These electronic nudges are rooted in the human psychology of decision-making and often target specific cognitive biases. This review outlines the development of novel EHR nudges and specific lessons learned from each experience to inform the development of future interventions. RECENT FINDINGS: There have been several randomized clinical trials examining the impact of EHR alerts on quality of care for heart failure patients. These interventions have targeted both clinicians and patients. There are features of each trial that inform best practices and future directions for EHR nudges. Recent clinical trials have demonstrated that some EHR alerts can improve care for heart failure patients. These trials utilized default options, involved clinicians in the alert design process, provided actionable recommendations, and aimed to minimize disruptions to typical workflow. Alerts aimed at improving care should be examined in a randomized fashion in order to evaluate their impact on clinician satisfaction and patient care.

Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial.

BACKGROUND AND AIMS: Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF. METHODS: Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge. RESULTS: Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on ß-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT. CONCLUSIONS: A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure.

Pragmatic trial of messaging to providers about treatment of acute heart failure: The PROMPT-AHF trial.

Acute Heart failure (AHF) is among the most frequent causes of hospitalization in the United States, contributing to substantial health care costs, morbidity, and mortality. Inpatient initiation of guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death or HF hospitalization. However, underutilization of GDMT prior to discharge is pervasive, representing a valuable missed opportunity to optimize evidence-based care. The PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failure tests the effectiveness of an electronic health record embedded clinical decision support system that informs providers during hospital management about indicated but not yet prescribed GDMT for eligible AHF patients with HFrEF. PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failureis an open-label, multicenter, pragmatic randomized controlled trial of 1,012 patients hospitalized with HFrEF. Eligible patients randomized to the intervention group are exposed to a tailored best practice advisory embedded within the electronic health record that alerts providers to prescribe omitted GDMT. The primary outcome is an increase in the proportion of additional GDMT medication classes prescribed at the time of discharge compared to those in the usual care arm.

Clinical implications of Type 2 diabetes on outcomes after cardiac transplantation.

BACKGROUND: T2D is an increasingly common disease that is associated with worse outcomes in patients with heart failure. Despite this, no contemporary study has assessed its impact on heart transplantation outcomes. This paper examines the demographics and outcomes of patients with type 2 diabetes (T2D) undergoing heart transplantation. METHODS: Using the United Network for Organ Sharing (UNOS) database, patients listed for transplant were separated into cohorts based on history of T2D. Demographics and comorbidities were compared, and cox regressions were used to examine outcomes. RESULTS: Between January 1st, 2011 and June 12th, 2020, we identified 9,086 patients with T2D and 23,676 without T2D listed for transplant. The proportion of patients with T2D increased from 25.2% to 27.9% between 2011 and 2020. Patients with T2D were older, more likely to be male, less likely to be White, and more likely to pay with public insurance (p<0.001, all). After adjustment, T2D patients had a lower likelihood of transplantation (Hazard Ratio [HR]: 0.93, CI: 0.90-0.96, p<0.001) and a higher likelihood of post-transplant mortality (HR: 1.30, CI: 1.20-1.40, p<0.001). Patients with T2D were more likely to be transplanted in the new allocation system compared to the old allocation system (all, p<0.001). CONCLUSIONS: Over the last ten years, the proportion of heart transplant recipients with T2D has increased. These patients are more likely to be from traditionally underserved populations. Patients with T2D have a lower likelihood of transplantation and a higher likelihood of post-transplant mortality. After the allocation system change, likelihood of transplantation has improved for patients with T2D.

Impact of left ventricular outflow tract calcium on valve geometry in self-expanding transcatheter aortic-valve replacement.

OBJECTIVES: Evaluate transcatheter heart valve (THV) geometry according to left ventricular outflow tract (LVOT) calcium degree and its impact on hemodynamics and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with a contemporary self-expanding THV. BACKGROUND: LVOT calcium remains challenging for contemporary THVs. LVOT calcium location and degree may affect THV deployment and impact flow patterns and shear stress, accelerating THV degeneration. METHODS: EPROMPT (CoreValve Evolut Pro Prospective Registry; NCT03423459) is a prospective, investigator-initiated, multicenter registry of patients undergoing TAVR using CoreValve Evolut PRO/PRO + THVs. A total of 107 patients were enrolled in EPROMPT's computed tomography (CT) cohort between January 2018 and October 2021. These patients underwent follow-up CT scan 30 days post-TAVR. We analyzed THV geometry and its interaction with the aortic root following deployment using 30-day post-TAVR CT in patients with none/mild versus moderate/severe LVOT calcium. RESULTS: Thirty-day THV inflows were less eccentric in the short axis in patients with none/mild versus moderate/severe LVOT calcium (1.16 ± 0.09 vs. 1.21 ± 0.12; p = 0.007). THV became more circular and was similar between both cohorts at the THV waist (1.08 ± 0.06 vs. 1.09 ± 0.11; p = 0.551), leaflet tips (1.03 ± 0.04 vs. 1.05 ± 0.09; p = 0.299), and THV outflow (1.04 ± 2.2 vs. 1.03 ± 2.7; p = 0.143). Thirty-day > mild paravalvular leak was low in both cohorts (1.5% vs. 2.4%; p = 0.724); mean gradients were similar (7.7 ± 3.6 vs. 7.7 ± 3.4 mmHg; p = 0.955). CONCLUSIONS: Despite inflow deformities observed in patients with moderate/severe LVOT calcium, Evolut PRO/PRO + conforms to elliptical aortic annuli, maintaining circularity and proper function at the leaflets and outflow, even in patients with moderate/severe LVOT calcium.

Relation of Ischemic Heart Disease to Outcomes in Patients With Acute Respiratory Distress Syndrome.

Patients with ischemic heart disease (IHD) are often excluded from acute respiratory distress syndrome (ARDS) clinical trials. As a result, little is known about the impact of IHD in this population. We sought to assess the association between IHD and clinical outcomes in patients with ARDS. Participants from 4 ARDS randomized controlled trials with shared study criteria, definitions, and end points were included. Using multivariable logistic regression, we assessed for the association between IHD and a primary outcome of 60-day mortality. Secondary outcomes included 90-day mortality, 28-day ventilator-free days, and 28-day organ failure. Among 1,909 patients, 102 had a history of IHD (5.4%). Patients with IHD were more likely to be older and male (p <0.05). Noncardiac co-morbidities, severity of illness, and other markers of ARDS severity were not statistically different (all, p >0.05). Patients with IHD had a higher 60-day (39.2% vs 23.3%, p <0.001) and 90-day (40.2% vs 24.0%, p <0.001) mortality, and experienced more frequent renal (45.1% vs 32.0%, p = 0.006) and hepatic (35.3% vs 25.2%, p = 0.023) failure. After multivariable adjustment, 60-day (odds ratio [OR] 1.76; 95% confidence interval [CI]: 1.07 to 2.89, p = 0.025) and 90-day (OR 1.74; 95% CI: 1.06 to 2.85, p = 0.028) mortality remained higher. IHD was associated with 10% fewer ventilator-free days (incidence rate ratio 0.90; 95% CI: 0.85 to 0.96, p = 0.001). In conclusion, co-morbid IHD was associated with higher mortality and fewer ventilator-free days in patients with ARDS. Future studies are needed to identify predictors of mortality and improve treatment paradigms in this critically ill subgroup of patients.

Trends in transcatheter and surgical aortic valve replacement in the United States, 2008-2018.

We conducted a retrospective study using the NIS database from 2008 to 2018 to examine the most contemporary national hospitalization trends of transcatheter (TAVR) and surgical (SAVR) aortic valve replacement regarding volume, patient and hospital demographics and economics, resource utilization, total cost of stay, and in-hospital mortality. We demonstrate that TAVR procedures have been performed on a slow by steadily diversifying patient population while volume has grown significantly, while in-hospital mortality, length of stay, discharge home, and costs have improved, whereas these metrics have generally remained stable for SAVR. These trends will likely drive continued TAVR adoption, greatly expanding the overall aortic stenosis patient population eligible for AVR.

Trends in Heart Failure Hospitalizations in the US from 2008 to 2018.

BACKGROUND: Heart failure (HF) is a major driver of health care costs in the United States and is increasing in prevalence. There is a paucity of contemporary data examining trends among hospitalizations for HF that specifically compare HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively). METHODS AND RESULTS: Using the National Inpatient Sample, we identified 11,692,995 hospitalizations due to HF. Hospitalizations increased from 1,060,540 in 2008 to 1,270,360 in 2018. Over time, the median age of patients hospitalized because of HF decreased from 76.0 to 73.0 years (P < 0.001). There were increases in the proportions of Black patients (18.4% in 2008 to 21.2% in 2018) and of Hispanic patients (7.1% in 2008 to 9.0% in 2018; P < 0.001, all). Over the study period, we saw an increase in comorbid diabetes, sleep apnea and obesity (P < 0.001, all) in the entire cohort with HF as well as in the HFrEF and HFpEF subgroups. Persons admitted because of HFpEF were more likely to be white and older compared to admissions because of HFrEF and also had lower costs. Inpatient mortality decreased from 2008 to 2018 for overall HF (3.3% to 2.6%) and HFpEF (2.4% to 2.1%; P < 0.001, all) but was stable for HFrEF (2.8%, both years). Hospital costs, adjusted for inflation, decreased in all 3 groups across the study period, whereas length of stay was relatively stable over time for all groups. CONCLUSIONS: The volume of patients hospitalized due to HF has increased over time and across subgroups of ejection fraction. The demographics of HF, HFrEF and HFpEF have become more diverse over time, and hospital inpatient costs have decreased, regardless of HF type. Inpatient mortality rates improved for overall HF and HFpEF admissions but remained stable for HFrEF admissions.

Impact of Obesity on Heart Transplantation Outcomes.

Background Patients with obesity and advanced heart failure face unique challenges on the path to heart transplantation. There are limited data on waitlist and transplantation outcomes in this population. We aimed to evaluate the impact of obesity on heart transplantation outcomes, and to investigate the effects of the new organ procurement and transplantation network allocation system in this population. Methods and Results This cohort study of adult patients listed for heart transplant used the United Network for Organ Sharing database from January 2006 to June 2020. Patients were stratified by body mass index (BMI) (18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40-55 kg/m2). Recipient characteristics and donor characteristics were analyzed. Outcomes analyzed included transplantation, waitlist death, and posttransplant death. BMI 18.5 to 24.9 kg/m2 was used as the reference compared with progressive BMI categories. There were 46 645 patients listed for transplantation. Patients in higher BMI categories were less likely to be transplanted. The lowest likelihood of transplantation was in the highest BMI category, 40 to 55 kg/m2 (hazard ratio [HR], 0.19 [0.05-0.76]; P=0.02). Patients within the 2 highest BMI categories had higher risk of posttransplantation death (HR, 1.29; P<0.001 and HR, 1.65; P<0.001, respectively). Left ventricular assist devices among patients in obese BMI categories decreased after the allocation system change (P<0.001, all). After the change, patients with obesity were more likely to undergo transplantation (BMI 30-35 kg/m2: HR, 1.31 [1.18-1.46], P<0.001; BMI 35-55 kg/m2: HR, 1.29 [1.06-1.58]; P=0.01). Conclusions There was an inverse relationship between BMI and likelihood of heart transplantation. Higher BMI was associated with increased risk of posttransplant mortality. Patients with obesity were more likely to undergo transplantation under the revised allocation system.

Trends and Outcomes of Cardiac Transplantation in the Lowest Urgency Candidates.

Background Because of discrepancies between donor supply and recipient demand, the cardiac transplantation process aims to prioritize the most medically urgent patients. It remains unknown how recipients with the lowest medical urgency compare to others in the allocation process. We aimed to examine differences in clinical characteristics, organ allocation patterns, and outcomes between cardiac transplantation candidates with the lowest and highest medical urgency. Methods and Results We performed a retrospective analysis of the United Network for Organ Sharing database. Patients listed for cardiac transplantation between January 2011 and May 2020 were stratified according to status at time of transplantation. Baseline recipient and donor characteristics, waitlist survival, and posttransplantation outcomes were compared in the years before and after the 2018 allocation system change. Lower urgency patients in the old system were older (58.5 versus 56 years) and more likely female (54.4% versus 23.8%) compared with the highest urgency patients, and these trends persisted in the new system (P<0.001, all). Donors for the lowest urgency patients were more likely older, female, or have a history of cytomegalovirus, hepatitis C, or diabetes (P<0.01, all). The lowest urgency patients had longer waitlist times and under the new allocation system received organs from shorter distances with decreased ischemic times (178 miles versus 269 miles, 3.1 versus 3.5 hours; P<0.001, all). There was no difference in posttransplantation survival (P<0.01, all). Conclusions Patients transplanted as lower urgency receive hearts from donors with additional comorbidities compared with higher urgency patients, but outcomes are similar at 1 year.

Brief report: Cannabis and opioid use disorder among heart failure admissions, 2008-2018.

BACKGROUND: In the United States, both cannabis use disorder (CUD) and opioid use disorder (OUD) have increased in prevalence. The prevalence, demographics, and costs of CUD and OUD are not well known in heart failure (HF) admissions. This study aimed to use a national database to examine the prevalence, demographics, and costs associated with CUD and OUD in HF. METHODS: This study used the National Inpatient Sample from 2008 to 2018 to identify all primary HF admissions with and without the co-diagnosis of OUD or CUD using International Classification for Diagnosis, diagnosis codes. Demographics, costs, and trends were examined. RESULTS: Between 2008 and 2018, we identified 11,692,995 admissions for HF of which 84,796 (0.8%) had a co-diagnosis of CUD only, and 67,137 (0.6%) had a co-diagnosis of OUD only. The proportion of HF admissions with CUD significantly increased from 0.3% in 2008 to 1.3% in 2018 (p<0.001). The proportion of HF admissions with OUD significantly increased from 0.2% in 2008 to 1.1% in 2018 (p<0.001). Patients admitted with HF and either CUD or OUD were younger, more likely to be Black, and from lower socioeconomic backgrounds (p<0.001, all). HF admissions with OUD or CUD had higher median costs compared to HF admissions without associated substance abuse diagnoses ($8,611 vs. $8,337 for CUD HF and $10,019 vs. $8,337 for OUD HF, p<0.001 for both). CONCLUSIONS: Among discharge records for HF, CUD and OUD are increasing in prevalence, significantly affect underserved populations and are associated with higher costs of stay. Future research is essential to better delineate the cause of these increased costs and create interventions, particularly in underserved populations.

Mechanical ventilation at the time of heart transplantation and associations with clinical outcomes.

AIMS: The impact of mechanical ventilation (MV) at the time of heart transplantation is not well understood. In addition, MV was recently removed as a criterion from the new US heart transplantation allocation system. We sought to assess for the association between MV at transplantation and 1-year mortality. METHODS AND RESULTS: We utilized the United Network for Organ Sharing database and included all adult, single organ heart transplantations from 1990 to 2019. We utilized multivariable logistic regression adjusting for demographics, comorbidities, and markers of clinical acuity. We identified 60 980 patients who underwent heart transplantation, 2.4% (n = 1431) of which required MV at transplantation. Ventilated patients were more likely to require temporary mechanical support, previous dialysis, and had a shorter median waitlist time (21 vs. 95 days, P < 0.001). At 1 year, the mortality was 33.7% (n = 484) for ventilated patients and 11.7% (n = 6967) for those not ventilated at the time of transplantation (log-rank P < 0.001). After multivariable adjustment, patients requiring MV continued to have a substantially higher 90-day [odds ratio (OR) 3.20, 95% confidence interval (CI): 2.79-3.66, P < 0.001] and 1-year mortality (OR 2.67, 95% CI: 2.36-3.03, P < 0.001). For those that survived to 90 days, the adjusted mortality at 1 year continued to be higher (OR 1.48, 95% CI: 1.16-1.89, P = 0.002). CONCLUSION: We found a strong association between the presence of MV at heart transplantation and 90-day and 1-year mortality. Future studies are needed to identify which patients requiring MV have reasonable outcomes, and which are associated with substantially poorer outcomes.

Evaluation of Racial and Ethnic Disparities in Cardiac Transplantation.

Background Racial and ethnic disparities contribute to differences in access and outcomes for patients undergoing heart transplantation. We evaluated contemporary outcomes for heart transplantation stratified by race and ethnicity as well as the new 2018 allocation system. Methods and Results Adult heart recipients from 2011 to 2020 were identified in the United Network for Organ Sharing database and stratified into 3 groups: Black, Hispanic, and White. We analyzed recipient and donor characteristics, and outcomes. Among 32 353 patients (25% Black, 9% Hispanic, 66% White), Black and Hispanic patients were younger, more likely to be women and have diabetes mellitus or renal disease (all, P<0.05). Over the study period, the proportion of Black and Hispanic patients listed for transplant increased: 21.7% to 28.2% (P=0.003) and 7.7% to 9.0% (P=0.002), respectively. Compared with White patients, Black patients were less likely to undergo transplantation (adjusted hazard ratio [aHR], 0.87; CI, 0.84-0.90; P<0.001), but had a higher risk of post-transplant death (aHR, 1.14; CI, 1.04-1.24; P=0.004). There were no differences in transplantation likelihood or post-transplant mortality between Hispanic and White patients. Following the allocation system change, transplantation rates increased for all groups (P<0.05). However, Black patients still had a lower likelihood of transplantation than White patients (aHR, 0.90; CI, 0.79-0.99; P=0.024). Conclusions Although the proportion of Black and Hispanic patients listed for cardiac transplantation have increased, significant disparities remain. Compared with White patients, Black patients were less likely to be transplanted, even with the new allocation system, and had a higher risk of post-transplantation death.

Comparison of Transcatheter and Open Mitral Valve Repair Among Patients With Mitral Regurgitation.

In 2013, the Food and Drug Administration approved the first transcatheter mitral valve repair (TMVr) device for degenerative mitral regurgitation for patients at prohibitive surgical risk. To better understand contemporary utilization trends and outcomes, we reviewed hospitalizations, identified using International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, in which the patient underwent TMVr or mitral valve repair (MVr) with a diagnosis of mitral regurgitation, without stenosis, from the National (Nationwide) Inpatient Sample from 2014 to 2017. We included 10,020 hospitalizations in which the patient underwent TMVr and 5845 in which the patient underwent MVr and assessed trends in demographic characteristics, patient comorbidities, total hospital charges, and outcomes. Transcatheter mitral valve repair experienced exponential growth, increasing from 150 to 5115 over the study period (P<.001 for trend), whereas MVr grew to a lesser degree. The median length of stay for TMVr decreased from 4 to 2 days; mortality declined from 3.3% to 1.6% (P<.001 for both). Both TMVr and MVr rates of discharge home increased over the study period. Total charges for TMVr increased from $149,582 to $178,109, whereas those for MVr increased to a lesser degree, from $149,426 to $157,146 (P<.001 for both). Discharge disposition, length of stay, and in-hospital mortality all exhibited favorable trends for both procedures. Caution must be exercised in direct comparisons between procedures as they target somewhat different populations. With expanded indications for TMVr, we anticipate further increases in procedural volume, although the effect on MVr remains unclear.

The Impact of Depression on Outcomes in Patients With Heart Failure and Reduced Ejection Fraction Treated in the GUIDE-IT Trial.

BACKGROUND: It remains unclear why depression is associated with adverse outcomes in patients with heart failure (HF). We examine the relationship between depression and clinical outcomes among patients with HF with reduced ejection fraction managed with guideline-directed medical therapy (GDMT). METHODS AND RESULTS: Using the GUIDE-IT trial, 894 patients with HF with reduced ejection fraction were stratified according to a history of depression, and Cox proportional hazards regression modeling was used to examine the association with outcomes. There were 140 patients (16%) in the overall cohort who had depression. They tended to be female (29% vs 46%, P < .001) and White (67% vs 53%, P = .002). There were no differences in GDMT rates at baseline or at 90 days; nor were there differences in target doses of these therapies achieved at 90 days (NS, all). amino-terminal pro-B-type natriuretic peptide levels at all time points were similar between the cohorts (P > .05, all). After adjustment, depression was associated with all-cause hospitalizations (hazard ratio, 1.42, 95% confidence interval 1.11-1.81, P < .01), cardiovascular death (hazard ratio, 1.69, 95% confidence interval 1.07-2.68, P = .025), and all-cause mortality (hazard ratio, 1.54, 95% confidence interval 1.03-2.32, P = .039). CONCLUSIONS: Depression impacts clinical outcomes in HF regardless of GDMT intensity and amino-terminal pro-B-type natriuretic peptide levels. This finding underscores the need for a focus on mental health in parallel to achievement of optimal GDMT in these patients. TRIAL REGISTRATION: NCT01685840, https://clinicaltrials.gov/ct2/show/NCT01685840.

National Trends in the Burden of Atrial Fibrillation During Hospital Admissions for Heart Failure.

Background Heart failure (HF) and atrial fibrillation (AF) frequently coexist and may be associated with worse HF outcomes, but there is limited contemporary evidence describing their combined prevalence. We examined current trends in AF among hospitalizations for HF with preserved (HFpEF) ejection fraction or HF with reduced ejection fraction (HFrEF) in the United States, including outcomes and costs. Methods and Results Using the National Inpatient Sample, we identified 10 392 189 hospitalizations for HF between 2008 and 2017, including 4 250 698 with comorbid AF (40.9%). HF hospitalizations with AF involved patients who were older (average age, 76.9 versus 68.8 years) and more likely White individuals (77.8% versus 59.1%; P<0.001 for both). HF with preserved ejection fraction hospitalizations had more comorbid AF than HF with reduced ejection fraction (44.9% versus 40.8%). Over time, the proportion of comorbid AF increased from 35.4% in 2008 to 45.4% in 2017, and patients were younger, more commonly men, and Black or Hispanic individuals. Comorbid hypertension, diabetes mellitus, and vascular disease all increased over time. HF hospitalizations with AF had higher in-hospital mortality than those without AF (3.6% versus 2.6%); mortality decreased over time for all HF (from 3.6% to 3.4%) but increased for HF with reduced ejection fraction (from 3.0% to 3.7%; P<0.001 for all). Median hospital charges were higher for HF admissions with AF and increased 40% over time (from $22 204 to $31 145; P<0.001). Conclusions AF is increasingly common among hospitalizations for HF and is associated with higher costs and in-hospital mortality. Over time, patients with HF and AF were younger, less likely to be White individuals, and had more comorbidities; in-hospital mortality decreased. Future research will need to address unique aspects of changing patient demographics and rising costs.

Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure.

OBJECTIVES: The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada. BACKGROUND: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use. METHODS: A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared. RESULTS: U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of ß-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients. CONCLUSIONS: In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Effects of Atrial Fibrillation on Heart Failure Outcomes and NT-proBNP Levels in the GUIDE-IT Trial.

OBJECTIVE: To evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy. METHODS: We performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013-July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality. RESULTS: After adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; P=0.04) and HF hospitalization (hazard ratio, 1.31; 95% CI, 1.02 to 1.68; P=.03) but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF (89.4% vs 81.5%; P=.002) had an NT-proBNP level above 1000 pg/mL (to convert NT-proBNP values to pmol/L, multiply by 0.1182), and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up. CONCLUSION: Among patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy.