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Current pharmacological therapies for heart failure with reduced ejection fraction are largely either repurposed anti-hypertensives that blunt overactivation of the neurohormonal system or diuretics that decrease congestion. However, they do not address the symptoms of heart failure that result from reductions in cardiac output and reserve. Over the last few decades, numerous attempts have been made to develop and test positive cardiac inotropes that improve cardiac haemodynamics. However, definitive clinical trials have failed to show a survival benefit. As a result, no positive inotrope is currently approved for long-term use in heart failure. The focus of this state-of-the-art review is to revisit prior clinical trials and to understand the causes for their findings. Using the learnings from those experiences, we propose a framework for future trials of such agents that maximizes their potential for success. This includes enriching the trials with patients who are most likely to derive benefit, using biomarkers and imaging in trial design and execution, evaluating efficacy based on a wider range of intermediate phenotypes, and collecting detailed data on functional status and quality of life. With a rapidly growing population of patients with advanced heart failure, the epidemiologic insignificance of heart transplantation as a therapeutic intervention, and both the cost and morbidity associated with ventricular assist devices, there is an enormous potential for positive inotropic therapies to impact the outcomes that matter most to patients.

Patients with heart failure (HF), particularly those with impaired renal function receiving renin–angiotensin–aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow‐up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one‐quarter to two‐fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55–93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow‐up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE‐HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes. [ABSTRACT FROM AUTHOR]

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 β-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. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient‐reported outcomes (PROs) aim to switch traditional care to a more patient‐centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care. [ABSTRACT FROM AUTHOR]

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Increasing patient and therapeutic complexity have created both challenges and opportunities for heart failure care. Within this background, the coronavirus disease-2019 pandemic has disrupted care as usual, accelerating the need for transition from volume-based to value-based care, and demanding a rapid expansion of telehealth and remote care for heart failure. Patients, clinicians, health systems, and payors have by necessity become more invested in these issues. Herein we review recent changes in health care policy related to the movement from volume to value-based payment and from in-person to remote care delivery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Background: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial demonstrated that higher-risk patients with atrial fibrillation had lower rates of stroke or systemic embolism and a similar rate of major bleeding, on average, when treated with dabigatran 150mg compared to warfarin. Since population-level averages may not apply to individual patients, estimating the heterogeneity of treatment effect can improve application of RE-LY in clinical practice. Methods and results: For 18040 patients randomized in RE-LY, we used patient-level data to develop multivariable models to predict the risk for stroke or systemic embolism and for major bleeding including all three treatment groups (dabigatran 110mg, dabigatran 150mg, and warfarin) over a median follow up of 2.0 years. The mean predicted absolute risk reduction (ARR) for stroke/systemic embolism with dabigatran 150mg compared to warfarin was 1.32% (range 11.6% lower to 3.30% higher risk). The mean predicted ARR for bleeding was 0.41% (range 8.93% lower to 63.4% higher risk). Patients with increased stroke/systemic embolism risk included those with prior stroke/TIA (OR 2.01), diabetics on warfarin (OR 2.00), and older patients on dabigatran 150mg (OR 1.68 for every 10-year increase). Major bleeding risk was higher in patients on aspirin (OR 1.25), with a history of diabetes (OR 1.34) or prior stroke/TIA (OR 1.22), those with heart failure on dabigatran 110mg (OR 1.52), older patients on either dabigatran 110mg or 150mg (OR 1.57 and 1.93, respectively, for each 10-year increase), and heavier patients on dabigatran 110mg or 150mg; patients in a region outside the United States and Canada and with better renal function had lower bleeding risk. Conclusions: There is substantial heterogeneity in the benefits and risks of dabigatran relative to warfarin among patients with atrial fibrillation. Using individualized estimates may enable shared decision making and facilitate more appropriate use of dabigatran; as such, it should be prospectively tested. Clinical trial registration: www.clinicaltrials.gov number, NCT00262600. [ABSTRACT FROM AUTHOR]

BACKGROUND: A growing population of patients with end-stage heart failure (HF) with reduced ejection fraction has limited treatment options to improve their quality and quantity of life. Although positive inotropes have failed to show survival benefit, these agents may enhance patient-reported health status, that is, symptoms, functional status, and health-related quality of life. We sought to review the available clinical trial data on positive inotrope use in patients with end-stage HF and to summarize evidence supporting the use of these agents to improve health status of patients with end-stage HF. METHODS: A literature review of randomized controlled trials examining the use of positive inotropy in HF with reduced ejection fraction was conducted. We searched MEDLINE, SCOPUS, and Web of Science between January 1980 to December 2018 for randomized controlled trials that used as their main outcome measures the effects of inotrope therapy on (1) morbidity/ mortality, (2) symptoms, (3) functional status, or (4) health-related quality of life. Inotropes of interest included adrenergic agents, phosphodiesterase inhibitors, calcium sensitizers, myosin activators, and SERCA2a (sarcoplasmic reticulum Ca2+- ATPase) modulators. RESULTS: Twenty-two out of 26 inotrope randomized controlled trials measured the effect of inotropes on at least one patient-reported health status domain. Among the 22 studies with patient-related health status outcomes, 11 (50%) gauged symptom response, 15 (68%) reported functional capacity changes, and 12 (54%) reported health-related quality of life measures. Fourteen (64%) of these trials noted positive outcomes in at least one health status domain measured; 11 (79%) of these positive studies used agents that worked through phosphodiesterase inhibition. CONCLUSIONS: There has been a lack of standardization surrounding measurement of patient-centered outcomes in studies of inotropes for end-stage HF with reduced ejection fraction. The degree to which positive inotropes can improve patient-reported health status and the adverse risk they pose remains unknown. [ABSTRACT FROM AUTHOR]

Background: Although the use of extracorporeal membrane oxygenation (ECMO) continues to increase, very little is known about how age influences the transition to definitive advanced therapies.Methods: Using the National Inpatient Sample database from 2008 to 2017, we analyzed patients supported by ECMO for cardiogenic shock and separated patients into 2 age cohorts: < 65 years and ≥ 65 years. Primary outcomes of interest included the proportion of patients undergoing orthotopic cardiac transplantation (OHT) and left ventricular assist device (LVAD) implantation.Results: Over the study period, we identified 16,132 hospitalizations of people with cardiogenic shock requiring ECMO support. Significantly fewer patients in the older group underwent OHT compared to the younger group (0.4% vs 1.2%, P < 0.001). Compared to the younger group, a lower proportion of those ≥ 65 years received an LVAD (3.7% vs 5.8%, P < 0.001). LVAD implantation increased over the study period in both age cohorts, whereas OHT increased only in the < 65 group (P < 0.05, all). After multivariable adjustment, patients in the oldest age group were still less likely to receive an LVAD (odds ratio 0.54; confidence interval: 0.43-0.69, P < 0.001) and continued to have the highest odds of in-hospital mortality (odds ratio 1.53; confidence interval : 1.39-1.69, P < 0.001).Conclusions: Survival of patients ≥ 65 years requiring ECMO for cardiogenic shock is poor and less commonly includes transition to definitive advanced therapies. Although we must stress that no patient should be denied ECMO based solely on age, we believe our results may be helpful for providers when counseling patients and their families. [ABSTRACT FROM AUTHOR]

Background: Concern has been raised about consequences of including patients with left ventricular assist device (LVAD) or heart transplantation in readmission and mortality measures. Methods: We calculated unadjusted and hospital-specific 30-day risk-standardized mortality (RSMR) and readmission (RSRR) rates for all Medicare fee-for-service beneficiaries with a primary diagnosis of AMI or HF discharged between July 2010 and June 2013. Hospitals were compared before and after excluding LVAD and heart transplantation patients. LVAD indication was measured. Results: In the AMI mortality (n = 506,543) and readmission (n = 526,309) cohorts, 1,166 and 1,016 patients received an LVAD while 3 and 2 had a heart transplantation, respectively. In the HF mortality (n = 1,015,335) and readmission (n = 1,254,124) cohorts, 789 and 931 received an LVAD, while 212 and 202 received a heart transplantation, respectively. Less than 2% of hospitals had either ≥6 patients who received an LVAD or, independently, had ≥1 heart transplantation. The AMI mortality and readmission cohorts used 1.8% and 2.8% of LVADs for semi-permanent/permanent indications, versus 73.8% and 78.0% for HF patients, respectively. The rest were for temporary/external indications. In the AMI cohort, RSMR for hospitals without LVAD patients versus hospitals with ≥6 LVADs was 14.8% and 14.3%, and RSRR was 17.8% and 18.3%, respectively; the HF cohort RSMR was 11.9% and 9.7% and RSRR was 22.6% and 23.4%, respectively. In the AMI cohort, RSMR for hospitals without versus with heart transplantation patients was 14.7% and 13.9% and RSRR was 17.8% and 17.7%, respectively; in the HF cohort, RSMR was 11.9% and 11.0%, and RSRR was 22.6% and 22.6%, respectively. Estimations changed ≤0.1% after excluding LVAD or heart transplantation patients. Conclusion: Hospitals caring for ≥6 patients with LVAD or ≥1 heart transplantation typically had a trend toward lower RSMRs but higher RSRRs. Rates were insignificantly changed when these patients were excluded. LVADs were primarily for acute-care in the AMI cohort and chronic support in the HF cohort. LVAD and heart transplantation patients are a distinct group with differential care requirements and outcomes, thus should be considered separately from the rest of the HF cohort. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hyperkalemia, defined as a serum potassium level >5 mEq/L that results from multiple mechanisms, is a serious medical condition that can lead to life-threatening arrhythmias and sudden cardiac death. The coexistence of cardiac and renal diseases (ie, cardiorenal syndrome) significantly increases the complexity of care, but its economic impact is not well-characterized in this understudied Medicaid managed care population with hyperkalemia. OBJECTIVE: To calculate the economic impact of hyperkalemia on patients with cardiorenal syndrome in a Medicaid managed care population in the United States using real-world data. METHODS: In this retrospective cohort study, we used a proprietary Medicaid managed care database from 1 southern state. The total study population included 3563 patients, including 973 patients with hyperkalemia and 2590 controls (without hyperkalemia), who were matched based on age, comorbidities, and Medicaid eligibility status and duration, during a 30-month period between 2013 and 2016. The inclusion criteria for the hyperkalemia cohort were age >18 years, Medicaid-only insurance status, coded cardiorenal diagnosis, and a claim for hyperkalemia during the study period. The cost was determined using paid claims data. RESULTS: The mean healthcare costs (medical and pharmacy per member per year [PMPY] for patients with hyperkalemia was higher than that for the control cohort without hyperkalemia ($56,002 vs $23,653, respectively). These cost differences were driven by medical costs accrued in the hyperkalemia and in the control cohorts ($49,648 and $18,399 PMPY, respectively). Two of the largest drivers of the medical cost variance were inpatient costs ($33,116 vs $10,629 PMPY for the hyperkalemia and control cohorts, respectively) and dialysis costs ($2716 vs $810 PMPY, respectively). The medical loss ratios were 552% for the hyperkalemia cohort and 260% for the control cohort. Both cohorts had revenue deficits to the health plan, but the hyperkalemia cohort had double the medical loss ratio compared with the control cohort. CONCLUSIONS: The findings from this Medicaid managed care population suggest that hyperkalemia increases healthcare utilization and costs, which were primarily driven by the costs associated with inpa-tient care and dialysis. Our findings demonstrate that the Medicaid beneficiaries who have cardiorenal comorbidities accrue high costs to the Medicaid health plan, and these costs are even higher if a hyper-kalemia diagnosis is present. The very high medical loss ratio for the hyperkalemia cohort in our analysis indicates that enhanced monitoring and management of patients with hyperkalemia should be considered. [ABSTRACT FROM AUTHOR]

The economics of heart failure (HF) touches all patients with HF, their families, and the physicians and health systems that care for them. HF is specifically targeted by cost-reduction and care quality initiatives from the Centers for Medicare and Medicaid Services (CMS). The changing quality assessment and payment landscape is, and will continue to be, challenging for hospitals and HF specialists as they provide care for patients with this debilitating disease. Quality-based payment systems with evolving performance metrics are replacing traditional volume-based fee-for-service models. A critical objective of quality-based models is to improve care and reduce cost, but there are few data to support decision-making on how to improve. CMS payment programs and their implications for health systems treating HF were reviewed at a symposium at the Heart Failure Society of America conference in Nashville, Tennessee on September 15, 2018. This article constitutes the proceedings from that symposium. [ABSTRACT FROM AUTHOR]

Importance: The Affordable Care Act has led to US national reductions in hospital 30-day readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. Whether readmission reductions have had the unintended consequence of increasing mortality after hospitalization is unknown.Objective: To examine the correlation of paired trends in hospital 30-day readmission rates and hospital 30-day mortality rates after discharge.Design, Setting, and Participants: Retrospective study of Medicare fee-for-service beneficiaries aged 65 years or older hospitalized with HF, AMI, or pneumonia from January 1, 2008, through December 31, 2014.Exposure: Thirty-day risk-adjusted readmission rate (RARR).Main Outcomes and Measures: Thirty-day RARRs and 30-day risk-adjusted mortality rates (RAMRs) after discharge were calculated for each condition in each month at each hospital in 2008 through 2014. Monthly trends in each hospital's 30-day RARRs and 30-day RAMRs after discharge were examined for each condition. The weighted Pearson correlation coefficient was calculated for hospitals' paired monthly trends in 30-day RARRs and 30-day RAMRs after discharge for each condition.Results: In 2008 through 2014, 2 962 554 hospitalizations for HF, 1 229 939 for AMI, and 2 544 530 for pneumonia were identified at 5016, 4772, and 5057 hospitals, respectively. In January 2008, mean hospital 30-day RARRs and 30-day RAMRs after discharge were 24.6% and 8.4% for HF, 19.3% and 7.6% for AMI, and 18.3% and 8.5% for pneumonia. Hospital 30-day RARRs declined in the aggregate across hospitals from 2008 through 2014; monthly changes in RARRs were -0.053% (95% CI, -0.055% to -0.051%) for HF, -0.044% (95% CI, -0.047% to -0.041%) for AMI, and -0.033% (95% CI, -0.035% to -0.031%) for pneumonia. In contrast, monthly aggregate changes across hospitals in hospital 30-day RAMRs after discharge varied by condition: HF, 0.008% (95% CI, 0.007% to 0.010%); AMI, -0.003% (95% CI, -0.005% to -0.001%); and pneumonia, 0.001% (95% CI, -0.001% to 0.003%). However, correlation coefficients in hospitals' paired monthly changes in 30-day RARRs and 30-day RAMRs after discharge were weakly positive: HF, 0.066 (95% CI, 0.036 to 0.096); AMI, 0.067 (95% CI, 0.027 to 0.106); and pneumonia, 0.108 (95% CI, 0.079 to 0.137). Findings were similar in secondary analyses, including with alternate definitions of hospital mortality.Conclusions and Relevance: Among Medicare fee-for-service beneficiaries hospitalized for heart failure, acute myocardial infarction, or pneumonia, reductions in hospital 30-day readmission rates were weakly but significantly correlated with reductions in hospital 30-day mortality rates after discharge. These findings do not support increasing postdischarge mortality related to reducing hospital readmissions. [ABSTRACT FROM AUTHOR]

Importance: Readmission rates declined after announcement of the Hospital Readmission Reduction Program (HRRP), which penalizes hospitals for excess readmissions for acute myocardial infarction (AMI), heart failure (HF), and pneumonia.Objective: To compare trends in readmission rates for target and nontarget conditions, stratified by hospital penalty status.Design, Setting, and Participants: Retrospective cohort study of Medicare fee-for-service beneficiaries older than 64 years discharged between January 1, 2008, and June 30, 2015, from 2214 penalty hospitals and 1283 nonpenalty hospitals. Difference-interrupted time-series models were used to compare trends in readmission rates by condition and penalty status.Exposure: Hospital penalty status or target condition under the HRRP.Main Outcomes and Measures: Thirty-day risk adjusted, all-cause unplanned readmission rates for target and nontarget conditions.Results: The study included 48 137 102 hospitalizations of 20 351 161 Medicare beneficiaries. In January 2008, the mean readmission rates for AMI, HF, pneumonia, and nontarget conditions were 21.9%, 27.5%, 20.1%, and 18.4%, respectively, at hospitals later subject to financial penalties and 18.7%, 24.2%, 17.4%, and 15.7% at hospitals not subject to penalties. Between January 2008 and March 2010, prior to HRRP announcement, readmission rates were stable across hospitals (except AMI at nonpenalty hospitals). Following announcement of HRRP (March 2010), readmission rates for both target and nontarget conditions declined significantly faster for patients at hospitals later subject to financial penalties compared with those at nonpenalized hospitals (for AMI, additional decrease of -1.24 [95% CI, -1.84 to -0.65] percentage points per year relative to nonpenalty discharges; for HF, -1.25 [95% CI, -1.64 to -0.86]; for pneumonia, -1.37 [95% CI, -1.80 to -0.95]; and for nontarget conditions, -0.27 [95% CI, -0.38 to -0.17]; P < .001 for all). For penalty hospitals, readmission rates for target conditions declined significantly faster compared with nontarget conditions (for AMI, additional decline of -0.49 [95% CI, -0.81 to -0.16] percentage points per year relative to nontarget conditions [P = .004]; for HF, -0.90 [95% CI, -1.18 to -0.62; P < .001]; and for pneumonia, -0.57 [95% CI, -0.92 to -0.23; P < .001]). In contrast, among nonpenalty hospitals, readmissions for target conditions declined similarly or more slowly compared with nontarget conditions (for AMI, additional increase of 0.48 [95% CI, 0.01-0.95] percentage points per year [P = .05]; for HF, 0.08 [95% CI, -0.30 to 0.46; P = .67]; for pneumonia, 0.53 [95% CI, 0.13-0.93; P = .01]). After HRRP implementation in October 2012, the rate of change for readmission rates plateaued (P < .05 for all except pneumonia at nonpenalty hospitals), with the greatest relative change observed among hospitals subject to financial penalty.Conclusions and Relevance: Medicare fee-for-service patients at hospitals subject to penalties under the HRRP had greater reductions in readmission rates compared with those at nonpenalized hospitals. Changes were greater for target vs nontarget conditions for patients at the penalized hospitals but not at the other hospitals. [ABSTRACT FROM AUTHOR]

The article focuses on the mortality and the readmission rates in hospitals in patients with heart failure, acute myocardial infarction and pneumonia. It talks about the connection between the experience of the patient at the hospital with the readmission rate of patients to the hospital. It tells about the importance of providing quality medical care services by the hospitals to the patients.

Background: The risk of rehospitalization is elevated in the immediate post-discharge period and declines over time. It is not known if the extent and timing of risk vary across readmission diagnoses, suggesting that recovery and vulnerability after discharge differ by physiologic system. Objective: We compared risk trajectories for major readmission diagnoses in the year after discharge among all Medicare fee-for-service beneficiaries hospitalized with heart failure (HF), acute myocardial infarction (AMI), or pneumonia from 2008–2010. Methods: We estimated the daily risk of rehospitalization for 12 major readmission diagnostic categories after accounting for the competing risk of death after discharge. For each diagnostic category, we identified (1) the time required for readmission risk to peak and then decline 50% from maximum values after discharge; (2) the time required for readmission risk to approach plateau periods of minimal day-to-day change; and (3) the extent to which hospitalization risks are higher among patients recently discharged from the hospital compared with the general elderly population. Results: Among >3,000,000 hospitalizations, the yearly rate of rehospitalization was 67.0%, 49.5%, and 55.3% after hospitalization for HF, AMI, and pneumonia, respectively. The extent and timing of risk varied by readmission diagnosis and initial admitting condition. Risk of readmission for gastrointestinal bleeding/anemia peaked particularly late after hospital discharge, occurring 10, 6, and 7 days after hospitalization for HF, AMI, and pneumonia, respectively. Risk of readmission for trauma/injury declined particularly slowly, requiring 38, 20, and 38 days to decline by 50% after hospitalization for HF, AMI, and pneumonia, respectively. Conclusions: Patterns of vulnerability to different conditions that cause rehospitalization vary by time after hospital discharge. This finding suggests that recovery of various physiologic systems occurs at different rates and that post-discharge interventions to minimize vulnerability to specific conditions should be tailored to their underlying risks. [ABSTRACT FROM AUTHOR]

Background: Examining trends in cardiovascular events and mortality in US health systems can guide the design of targeted clinical and public health strategies to reduce cardiovascular events and mortality rates.Methods and Results: We conducted an observational cohort study from 2005 to 2011 among 1.25 million diabetic subjects and 1.25 million nondiabetic subjects from 11 health systems that participate in the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) DataLink. Annual rates (per 1000 person-years) of myocardial infarction/acute coronary syndrome (International Classification of Diseases-Ninth Revision, 410.0–410.91, 411.1–411.8), stroke (International Classification of Diseases-Ninth Revision, 430–432.9, 433–434.9), heart failure (International Classification of Diseases-Ninth Revision, 428–428.9), and all-cause mortality were monitored by diabetes mellitus (DM) status, age, sex, race/ethnicity, and a prior cardiovascular history. We observed significant declines in cardiovascular events and mortality rates in subjects with and without DM. However, there was substantial variation by age, sex, race/ethnicity, and prior cardiovascular history. Mortality declined from 44.7 to 27.1 (P<0.0001) for those with DM and cardiovascular disease (CVD), from 11.2 to 10.9 (P=0.03) for those with DM only, and from 18.9 to 13.0 (P<0.0001) for those with CVD only. Yet, in the [almost equal to]85% of subjects with neither DM nor CVD, overall mortality (7.0 to 6.8; P=0.10) and stroke rates (1.6–1.6; P=0.77) did not decline and heart failure rates increased (0.9–1.15; P=0.0005).Conclusions: To sustain improvements in myocardial infarction, stroke, heart failure, and mortality, health systems that have successfully focused on care improvement in high-risk adults with DM or CVD must broaden their improvement strategies to target lower risk adults who have not yet developed DM or CVD. [ABSTRACT FROM AUTHOR]

A previously healthy 22-year-old African American woman presented with bilateral vision loss associated with headache. Her ocular examination was significant for bilateral retinal arterial “boxcarring,” retinal whitening, retinal hemorrhages, and cherry red spots. She was diagnosed with bilateral central retinal artery occlusions and was hospitalized due to concomitant diagnosis of stroke and hypercoagulable state. She was also found to be in heart failure and kidney failure. Rheumatology was consulted and she was diagnosed with catastrophic antiphospholipid syndrome in association with systemic lupus erythematosus. Approximately 7 months after presentation, the patient’s vision improved and remained stable at 20/200 and 20/80. [ABSTRACT FROM AUTHOR]

Background: Despite growing interest in value-based models, utilization patterns and costs for heart failure (HF) admissions are not well understood. We sought to characterize Medicare spending for patients with HF for 30- and 90-day episodes of care (which include an index hospitalization and 30 or 90 days following discharge) and to describe the patterns of post-acute care spending.Methods: Using Medicare fee-for-service administrative claims data from 2016 to 2018, we performed a retrospective analysis of patients discharged after hospitalization with primary discharge diagnoses of systolic HF, diastolic HF, hypertensive heart disease (HHD) with HF, and HHD with HF and chronic kidney disease. We analyzed coding patterns across these groups over time, median 30- and 90-day payments, and costs allocated to index hospitalization and postacute care.Results: The study included 935 962 patients discharged following hospitalization for HF (systolic HF: 178 603; diastolic HF: 165 156; HHD with HF: 226 929; HHD with HF and chronic kidney disease: 365 274). The proportion of HHD codes increased from 26% of HF hospitalizations in 2016 to 91% in 2018. There was substantial spending on 30-day (median $13 330, interquartile range $9912-$22 489) and 90-day episodes (median $21 658, interquartile range $12 423-$37 630) for HF with significant variation, such that the third quartile of patients incurred costs 3 times the amount of the first quartile. Across all codes, the index hospitalization accounted for ≈70% of 30-day and 45% of 90-day spending. Sixty-one percent of postacute care spending occurred 31 to 90 days following discharge, with readmissions and observation stays (36%) and skilled nursing facilities (27%) comprising the largest categories.Conclusions: This patient episode-level analysis of contemporary Medicare beneficiaries is the first to examine 90-day spending, which will become an increasingly important pasyment benchmark with the expansion of the Medicare Bundled Payments for Care Improvement Program. Further investigation into the drivers of costs will be essential to provide high-value HF care. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The number of patients treated for aortic valve disease in the United States is increasing rapidly. Transcatheter aortic valve replacement (TAVR) is supplanting surgical aortic valve replacement (SAVR) and medical therapy (MT). The economic implications of these trends are unknown. Therefore, we undertook to determine the costs, inpatient days, and number of admissions associated with treating aortic valve disease with SAVR, TAVR, or MT. Methods: Using the Nationwide Readmissions Database, we identified patients with aortic valve disease admitted 2012 to 2016 for SAVR, TAVR, and disease symptoms (congestive heart failure, unstable angina, non–ST-elevation myocardial infarction, syncope). Patients not undergoing SAVR or TAVR were classified as receiving MT. Beginning with the index admission, we estimated inpatient costs, days, and admissions over 6 months. Results: Among 190 563 patients with aortic valve disease, the average aggregate 6-month inpatient costs were $59 743 for SAVR, $64 395 for TAVR, and $23 460 for MT. Mean index admission was longer for SAVR (10.0 days) than for TAVR (7.0 day) or MT (5.3 days), but the average number of unplanned readmission inpatient days was 2.0 for SAVR, 3.0 for TAVR, and 4.3 for MT; the average number of total admissions was 1.3 for SAVR, 1.5 for TAVR, and 1.7 for MT (P <0.01 for all). TAVR index admission costs decreased over time to become similar to SAVR costs by 2016. Conclusions: Aggregate costs were higher for TAVR than SAVR and were significantly more expensive than MT alone. However, TAVR costs decreased over time while SAVR and MT costs remained unchanged. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The impact of respiratory failure on patients undergoing left ventricular assist device (LVAD) implantation is not well understood, especially since these patients were excluded from landmark clinical trials. We sought to evaluate the associations between immediate preimplant and postimplant respiratory failure on outcomes in advanced heart failure patients undergoing LVAD implantation. Methods and Results: We included all patients in the Interagency Registry for Mechanically Assisted Circulatory Support who were implanted with continuous-flow LVADs from 2008 to 2016. Of the 16 362 patients who underwent continuous-flow LVAD placement, 906 (5.5%) required preimplant intubation within 48 hours before implantation, and 1001 (6.1%) patients developed respiratory failure within 1 week after implantation. A higher proportion of patients requiring preimplant intubation were Interagency Registry for Mechanically Assisted Circulatory Support profile 1, required mechanical circulatory support, and presented with cardiac arrest or myocardial infarction (P <0.001, all). At 1 year, 54.3% of patients intubated preimplant were alive without transplant, 20.1% had been transplanted, and 24.2% died before transplant. Patients requiring preimplant intubation had higher rates of postimplant complications, including bleeding, stroke, and right ventricular assist device implantation (P <0.01 for all). Among Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients, preimplant intubation incurred additional risk of death at 1 year compared with Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients not intubated (hazard ratio, 1.37 [95% CI, 1.13–1.65]; P =0.001). After multivariable analysis, both preimplant intubation (hazard ratio, 1.20 [95% CI, 1.03–1.41]; P =0.021) and respiratory failure within 1 week (hazard ratio, 2.54 [95% CI, 2.26–2.85]; P <0.001) were associated with higher all-cause 1-year mortality. Conclusions: Respiratory failure both before and after LVAD implantation identifies an advanced heart failure population with significantly worse 1-year mortality. This data might be helpful in counseling patients and their families about expectations about life with an LVAD. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF. [Display omitted] • AF and HF commonly occur concurrently, and the combination is associated with worse prognosis than either condition alone. • GDMT for HF can reduce the incidence of AF. • Further research is needed to clarify the benefit of GDMT for HF in patients with concomitant AF across the range of left ventricular ejection fractions. [ABSTRACT FROM AUTHOR]

Corresponding Author [ABSTRACT FROM AUTHOR]

Background: Beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i.Methods: This study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage.Results: Tier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR: $84-$100), including $47 (IQR: $40-$47) for ARNI and $45 (IQR: $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR: $1,956-$2,579) compared with $1,319 (IQR: $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR: $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR: $0-$9).Conclusions: Medicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced. [ABSTRACT FROM AUTHOR]

Background: The use of guideline-directed medical therapy (GDMT) is underprescribed in patients with heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to examine whether targeted and tailored electronic health record (EHR) alerts recommending GDMT in eligible patients with HFrEF improves GDMT use.Methods: PROMPT-HF (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure) was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. A total of 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days postrandomization. Providers were surveyed on knowledge of guidelines and user experience.Results: The study enrolled 1,310 ambulatory patients with HFrEF from April to October 2021. Median age was 72 years; 31% were female; 18% were Black; and median left ventricular ejection fraction was 32%. At baseline, 84% of participants were receiving β-blockers, 71% received a renin-angiotensin-aldosterone system inhibitor, 29% received a mineralocorticoid receptor antagonist, and 11% received a sodium-glucose cotransporter-2 inhibitor. The primary outcome occurred in 176 of 685 (26%) participants in the alert arm vs 117 of 625 (19%) in the usual care arm, thus increasing GDMT class prescription by >40% after alert exposure (adjusted relative risk: 1.41; 95% CI: 1.03-1.93; P = 0.03). The number of patients needed to alert to result in an increase in addition of GDMT classes was 14. A total of 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF.Conclusions: A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure. (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure [PROMPT-HF; NCT04514458]). [ABSTRACT FROM AUTHOR]

OBJECTIVES: To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF). STUDY DESIGN: Systematic literature review. METHODS: A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for β-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) with HFrEF. RESULTS: A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%). CONCLUSIONS: Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted. [ABSTRACT FROM AUTHOR]

Background: Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations for toxicity, and subsequent outcomes over this time period.Methods: To describe digoxin prescription trends, we conducted a population-level, cohort study using data from IQVIA, Inc.'s National Prescription Audit (2007-2014) for patients aged ≥65 years. Further, in a national cohort of Medicare fee-for-service beneficiaries aged ≥65 years in the United States, we assessed temporal trends of hospitalizations associated with digoxin toxicity and the outcomes of these hospitalizations between 1999 and 2013.Results: From 2007 through 2014, the number of digoxin prescriptions dispensed decreased by 46.4%; from 8,099,856 to 4,343,735. From 1999 through 2013, the rate of hospitalizations with a principal or secondary diagnosis of digoxin toxicity decreased from 15 to 2 per 100,000 person-years among Medicare fee-for-service beneficiaries. In-hospital and 30-day mortality rates associated with hospitalization for digoxin toxicity decreased significantly among Medicare fee-for-service beneficiaries; from 6.0% (95% confidence interval [CI], 5.2-6.8) to 3.7% (95% CI, 2.2-5.7) and from 14.0% (95% CI, 13.0-15.2) to 10.1% (95% CI, 7.6-13.0), respectively. Rates of 30-day readmission for digoxin toxicity decreased from 23.5% (95% CI, 22.1-24.9) in 1999 to 21.7% (95% CI, 18.0-25.4) in 2013 (P < .05).Conclusion: While digoxin prescriptions have decreased, it is still widely prescribed. However, the rate of hospitalizations for digoxin toxicity and adverse outcomes associated with these hospitalizations have decreased. These findings reflect the changing clinical practice of digoxin use, aligned with the changes in clinical guidelines. [ABSTRACT FROM AUTHOR]