The association between social determinants of health and patient-centred outcomes in adults with heart failure with reduced ejection fraction.

AIMS: To explore the associations between social determinants of health and patient-centred outcomes among adults with chronic heart failure with reduced ejection fraction. DESIGN: Cross-sectional online self-report survey. METHODS: A survey assessing social determinants of health (demographics, socio-economic position, affordability of care and social support) and patient-centred outcomes, including the Kansas City Cardiomyopathy Questionnaire-12 and validated measures of medication adherence, treatment satisfaction, treatment burden and mental health, was completed by 512 adults with chronic heart failure with a reduced ejection fraction between 06 March and 29 June 2020. Multivariable analyses included linear and logistic regression. RESULTS: Female gender, having a care partner, and being offered financial assistance with medications were associated with worse health status, while perceiving medication as affordable and being married were associated with better health status. Females and having Medicaid, dual Medicaid/Medicare or no medical insurance were associated with a higher likelihood of depression, and non-white race/ethnicity was associated with less depression. Medication adherence was lower in patients having a care partner and offered financial assistance. Patients being offered financial and medication management assistance were more likely to be overwhelmed by the treatment burden, whereas those having some college education were less so. CONCLUSIONS: Social determinants of health are associated with patients' disease-specific health status, mental health and treatment satisfaction and burden. These findings underscore the importance of assessing social determinants of health in clinical practice and the need for developing and testing novel strategies to determine whether they improve patients' health. IMPACT: The relationship between social determinants of health- and patient-centred outcomes was assessed; affordability of care and social support factors were most strongly associated with outcomes for patients with chronic heart failure and reduced ejection fraction, underscoring the importance of assessing social determinants of health in routine clinical care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Social determinants of health data could potentially inform care delivery for patients with heart failure and reduced ejection fraction by helping to identify those who require additional support to manage their symptoms, access care and adhere to treatment. Social support and affordability of treatment were associated with most patient-centred outcomes, suggesting these factors may provide clinicians with an indicator of a patient's level of general well-being that could be assessed during routine follow-up care. REPORTING METHOD: This research followed the STROBE checklist for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Adults who have heart failure with reduced ejection fraction that consented to participate in the study provided the data used for all analyses reported on in the manuscript. Service users, caregivers or members of the public had no involvement in the study.

Out-of-pocket payments for part d covered medications by medicare fee-for-service beneficiaries with heart failure with reduced ejection fraction.

BACKGROUND: Out-of-pocket (OOP) drug costs for Medicare Fee-for-Service (FFS) beneficiaries with heart failure with reduced ejection fraction (HFrEF) are not well characterized. This study evaluated Part D OOP spending by Medicare beneficiaries with chronic HFrEF, stratified by those with and without a worsening HF event (WHFE). METHODS: Medicare FFS 100% Part D claims were used to identify HFrEF patients with 12 months of continuous Part D enrollment in 2018. HFrEF was defined as 1 inpatient or 2 outpatient claims of systolic HF or 1 systolic HF plus 1 HF outpatient claim. WHFE was defined as having a HF hospitalization or intravenous diuretic use within 12 months of HFrEF index date. OOP costs by Medicare Part D coverage phase for all covered drugs were calculated for HFrEF patients, and those with and without WHFE. RESULTS: Of 305,373 Medicare patients with HFrEF, 26% had a WHFE. Total mean (SD) OOP drug costs among all HFrEF patients was $1,166 (1,205)/year. Patients with WHFE and patients without WHFE had respectively a mean (SD) annual OOP costs of $1,302 (1,273) and $1,117 (1,176). Over 39% of HFrEF patients entered the "donut hole" (44% and 37% of patients with WHFE and without WHFE, respectively), while 11% of HFrEF patients entered the catastrophic phase (13% and 10% of patients with and without WHFE, respectively). CONCLUSIONS: More than 1 in 10 patients with heart failure entered the catastrophic phase within Medicare-Fee-For-Service, whereas in 2018 only 10% of costs were attributable to heart failure medication and 90% to comorbidities.

Contemporary outpatient management of patients with worsening heart failure with reduced ejection fraction: Rationale and design of the CHART-HF study.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) represent a distinct subset of patients with a substantial comorbidity burden, greater potential for intolerance to medical therapy, and high risk of subsequent death, hospitalization and excessive healthcare costs. Although multiple therapies have been shown to be efficacious and safe in this high-risk population, there are limited real-world data regarding factors that impact clinical decision-making when initiating or modifying therapy. Likewise, prior analyses of US clinical practice support major gaps in medical therapy for HFrEF and few medication changes during longitudinal follow-up, yet granular data on reasons why clinicians do not initiate or up-titrate guideline-directed medication are lacking. METHODS: We designed the CHART-HF study, an observational study of approximately 1,500 patients comparing patients with and without WHFE (WHFE defined as receipt of intravenous diuretics in the inpatient, outpatient, or emergency department setting) who had an index outpatient visit in the US between 2017 and 2019. Patient-level data on clinical characteristics, clinical outcomes, and therapy will be collected from 2 data sources: a single integrated health system, and a national panel of cardiologists. Furthermore, clinician-reported rationale for treatment decisions and the factors prioritized with selection and optimization of therapies in real-world practice will be obtained. To characterize elements of clinician decision-making not documented in the medical record, the panel of cardiologists will review records of patients seen under their care to explicitly note their primary reason for initiating, discontinuing, and titrating medications specific medications, as well as the reason for not making changes to each medication during the outpatient visit. CONCLUSIONS: Results from CHART-HF have the potential to detail real-world US practice patterns regarding care of patients with HFrEF with versus without a recent WHFE, to examine clinician-reported reasons for use and non-use of guideline-directed medical therapy, and to characterize the magnitude and nature of clinical inertia toward evidence-based medication changes for HFrEF.

Prognostic Interplay Between COVID-19 and Heart Failure With Reduced Ejection Fraction.

BACKGROUND: COVID-19 may negatively impact the prognosis of patients with chronic HFrEF and vice versa. METHODS: This study included 2 parallel analyses of patients in the United States who were in the TriNetX health database and who underwent polymerase chain reaction testing for SARS-CoV-2 as an inpatient or outpatient between January and September of 2020. Analysis A included patients with positive tests for COVID-19 and compared patients with histories of worsening heart failure with reduced ejection fraction (HFrEF) (hospitalization due to heart failure (HF) or IV diuretic use during the prior 12 months), HFrEF without worsening, and no prior HF. Analysis B included patients with histories of HFrEF and compared patients with positive vs negative COVID-19 tests. Outcomes included mortality and worsening HF. In both analyses, prespecified subgroup analyses were stratified by inpatient vs outpatient settings of the COVID-19 tests. RESULTS: In Analysis A, of 99,052 patients with positive COVID-19 tests, 514 (0.5%) and 524 (0.5%) patients had histories of worsening HFrEF and HFrEF without worsening, respectively. After adjustment, compared to patients without HF, worsening HFrEF (risk ratio [RR] 1.42, 95% CI 1.10-1.83; P< 0.001) and HFrEF without worsening (RR 1.33, 95% CI 0.96-1.84; P= 0.06) were associated with higher 30-day mortality rates. Excess risk of mortality tended to be pronounced in patients initially diagnosed with COVID-19 as outpatients (P for interaction, 0.12 and 0.006, respectively). In Analysis B, of 14,838 patients with HFrEF tested for COVID-19, 1038 (7.0%) had positive tests. After adjustment, testing positive was associated with excess 30-day mortality risk (RR 1.67, 95% CI 1.38-2.02; P< 0.001) and worsening HF (RR 1.33, 95% CI 1.17-1.51; P< 0.001). Mortality risk was nominally more pronounced among patients presenting as outpatients (P for interaction 0.07). CONCLUSION: In this large cohort of patients tested for COVID-19, among patients testing positive, a history of HFrEF with or without worsening was associated with excess mortality rates, particularly among patients diagnosed with COVID-19 as outpatients. Among patients with established HFrEF, compared with testing negative, testing positive for COVID-19 was independently associated with higher risk of death and worsening HF.

Medication Trajectory and Treatment Patterns in Medicare Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Although a worsening heart failure event (WHFE) is associated with poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF), it is unclear how guideline-directed medical therapy (GDMT) is used in this population compared to those without WHFEs. This study evaluated treatment patterns in patients with HFrEF, both with and without WHFEs. METHODS: A retrospective study using 100% Medicare Fee-For-Service claims identified beneficiaries with HFrEF, stratified by those with and without WHFEs (defined as hospitalization due to HF or outpatient intravenous diuretic use). The use of GDMT for HFrEF before and after WHFEs and adherence were assessed in patients who were prescribed and initiated GDMT. Logistic regression identified patients' characteristics associated with medication nonadherence. RESULTS: Of 353,642 patients with HFrEF, 31.4% had a WHFE. Although there was no overall change in the treatment trajectory of patients without WHFEs, GDMT use in patients with WHFEs intensified within the first 3 months of a WHFE, but the intensification was not sustained in subsequent months. From 0-3 months pre-WHFE to 0-3 months post-WHFE, the proportion of patients receiving dual (41%-48%) and triple-therapy (4%-12%) increased, followed by a decline to pre-WHFE rates. The 1-year adherence rates for those with and without WHFEs were 67.9% vs 73.3% for beta-blockers; 59.1% vs 70.9% for angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists; 53.9% vs 61.3% for angiotensin receptor-neprilysin inhibitors; and 49.2% vs 59.3% for mineralocorticoid receptor antagonists. WHFE, age < 65 years, Black race, asthma, chronic kidney disease, and depression were associated with nonadherence to medications. Asians and Hispanics were less adherent to some medication classes. CONCLUSIONS: This study demonstrated underuse of GDMT for patients with HFrEF with or without WHFEs. Although there was a treatment escalation within 3 months following WHFE, it was not sustained thereafter.

Medication use by US patients with pulmonary hypertension associated with chronic obstructive pulmonary disease: a retrospective study of administrative data.

BACKGROUND: Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). While clinical guidelines recommend specific drug therapies for pulmonary arterial hypertension (PAH), these drug therapies are not recommended for PH due to lung disease. METHODS: This was a retrospective cohort study using the Optum® Clinformatics® Data Mart from January 2009-September 2019. An algorithm was designed to identify adults with ≥ 2 ICD-9-CM or ICD-10-CM diagnosis codes for PH and with ≥ 2 diagnosis codes for COPD. Sensitivity analyses were conducted among subgroups of patients with evidence of a right heart catheterization (RHC) or pulmonary function test (PFT). Patient characteristics, medications used, and durations of use of PAH and COPD medications were analyzed. RESULTS: A total of 25,975 patients met the study inclusion criteria. Their mean age was 73.5 (SD 10.0) years and 63.8% were female. Medications targeting PAH were prescribed to 643 (2.5%) patients, most frequently a phosphodiesterase-5 inhibitor (2.1%) or an endothelin receptor antagonist (0.75%). Medications for COPD were prescribed to 17,765 (68.4%) patients, most frequently an inhaled corticosteroid (57.4%) or short-acting beta agonist (50.4%). The median durations of use ranged from 4.9 to 12.8 months for PAH medications, and from 0.4 to 5.9 months for COPD medications. Of the subgroup of patients with RHC (N = 2325), 257 (11.1%) were prescribed a PAH medication and 1670 (71.8%) used a COPD medication. Of the subgroup with a PFT (N = 2995), 58 (1.9%) were prescribed a PAH medication and 2100 (70.1%) a COPD medication. CONCLUSIONS: Patients with PH associated with COPD were identified in a US administrative claims database. Very few of these patients received any of the medications recommended for PAH, and only about two thirds received medications for COPD.

Representativeness of the VICTORIA Trial Population in Clinical Practice: Analysis of the PINNACLE Registry.

BACKGROUND: In the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, vericiguat reduced the risk of mortality due to cardiovascular problems and of hospitalization due to heart failure (HF) among patients with HF with reduced ejection fraction (HFrEF) and recent worsening HF events (WHFEs). The representativeness of the VICTORIA population of patients with WHFE in clinical practice is unknown. METHODS AND RESULTS: Patients with HF and ejection fraction <45% were identified in the Practice Innovation And Clinical Excellence (PINNACLE) registry and were stratified by the occurrence of WHFEs. Characteristics and outcomes of patients in the PINNACLE registry with and without WHFEs were compared to the VICTORIA population. Of the 14,180 PINNACLE patients identified with HFrEF, 26.5% had had a WHFE. The VICTORIA population was similar to PINNACLE patients with WHFEs in mean age (67.3 vs 66.7), ejection fraction (28.9% vs 28.3%), body mass index (26.8 vs 27.6), and comorbidity burden. The rate of hospitalization because of HF at 1 year was 29.6% in the placebo group of VICTORIA, compared to 35.8% in PINNACLE patients with WHFEs and 13.3% in patients without WHFEs. CONCLUSIONS: The PINNACLE patients with WHFEs meeting the VICTORIA definition resembled the VICTORIA population in characteristics and outcomes, suggesting that VICTORIA's population may be generalizable to patients with WHFEs in clinical practice.

Patient-centered Outcomes in HFrEF Following a Worsening Heart Failure Event: A Survey Analysis.

BACKGROUND: Heart failure is a chronic disease punctuated by intermittent exacerbations that require hospitalization or intravenous diuretic therapy. The association of worsening heart failure events (WHFEs) with patient-centered outcomes in heart failure with reduced ejection fraction (HFrEF) remains unexplored. METHODS AND RESULTS: Patients with HFrEF completed an online survey assessing health status, medication adherence, treatment satisfaction, treatment burden, and medication costs and affordability. Patients with and without WHFEs were compared on all study variables, with adjustment for patient characteristics using linear or logistic regression. Overall, 512 patients (52.0% WHFEs) were included. Patients with WHFEs more commonly had depression (55.3% vs 24.0%), anxiety (46.2% vs 17.9%), and insomnia (77.8% vs 44.7%; P < 0.001 for all). Patients with WHFEs had lower adjusted mean Kansas City Cardiomyopathy Questionnaire values (52.9 vs 56.0) and Satisfaction with Medications Questionnaire values (70.5 vs 72.6) and higher Treatment Burden Questionnaire scores (51.1 vs 45.1; P < 0.001). Medication-related beliefs and long-term concerns were independently associated with nonadherence in patients with WHFE (adjusted odds ratios: 4.2 and 5.2, respectively; P < 0.01 for both). Patients with WHFE incurred 50.0% higher median monthly out-of-pocket HF prescription medication costs and less often perceived HF medications to be affordable. CONCLUSIONS: WHFE is associated with several adverse impacts on patients with HFrEF. Additional support is warranted to manage symptoms, comorbidities, and HF treatments to improve adherence and outcomes.

Low-Density Lipoprotein Cholesterol Target Attainment in Patients Surviving an Acute Coronary Syndrome in Thailand: Results From the Dyslipidaemia International Study (DYSIS) II.

BACKGROUND: Patients suffering an acute coronary syndrome (ACS) are at increased risk for future cardiovascular events. Effective management of hyperlipidaemia in such patients is essential. We aimed to document the use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) target achievement in patients hospitalised with an ACS in Thailand. METHODS: The Dyslipidemia International Study (DYSIS) II was a multinational, observational study that enrolled patients over 18 years of age who were hospitalised with an ACS in 2013-2014 and survived until discharge. Patients were analysed according to whether or not they were treated with LLT prior to hospital admission. A lipid profile was carried forward from blood taken within the first 24 hours after admission, and attainment of the LDL-C target of <70 mg/dL (1.8 mmol/L) for very high-risk subjects was reported. Details of LLTs were collected. Lipid levels, LLT use and cardiovascular events since discharge were collected at a follow-up interview 4 months later. RESULTS: A total of 320 ACS patients were enrolled from seven sites across Thailand, 188 (58.8%) of whom were being treated with LLT prior to the acute event. The mean LDL-C levels of the LLT and no LLT patients were 106.2 ± 39.4 mg/dL (2.75 ± 1.02 mmol/L) and 139.8 ± 46.6 mg/dL (3.62 ± 1.21), respectively, with 15.4% and 4.5% having an LDL-C level below 70 mg/dL (1.8 mmol/L). Lipid-lowering therapy consisted mainly of statins, with an atorvastatin-equivalent daily dosage of 17 ± 13 mg/day. At the 4-month follow-up, LDL-C target attainment remained low at 26.7% for the initial LLT group and 24.1% for the no LLT group. Although most patients were being treated with LLT at this point, the dosage was still low (28 ± 16 mg/day) and there was little use of combination therapy. CONCLUSION: In this cohort of Thai ACS patients, LDL-C levels were highly elevated, placing them at extreme risk of recurrent adverse cardiovascular events. Lipid-lowering therapy was widely used after the ACS; however, treatment was rarely optimised. Huge improvements are required in the management of hyperlipidaemia in Thailand.

Body mass index impacts the choice of lipid-lowering treatment with no correlation to blood cholesterol - Findings from 52 916 patients in the Dyslipidemia International Study (DYSIS).

A high body mass index (BMI) is associated with increased cardiovascular risk. We sought to identify whether BMI influences the choice of lipid-lowering treatment in a large, real-world cohort of 52 916 patients treated with statins. The Dyslipidemia International Study (DYSIS) is a cross-sectional, observational, multicentre study in statin-treated patients ≥45 years of age from 30 countries; 1.1% were underweight (BMI < 18.5 kg/m2 ), 33.1% had normal weight (BMI 18.5-24.9 kg/m2 ), 41.5% were overweight (BMI 25-29.9 kg/m2 ), 17.1% had class I obesity (BMI 30.0-34.9 kg/m2 ), 5.0% had class II obesity (BMI 35-39.9 kg/m2 ), and 2.1% had class III obesity (≥40 kg/m2 ). BMI correlated with high-density lipoprotein cholesterol (HDL-C) and triglycerides (Spearman's ρ: -0.147 and 0.170, respectively; P < 0.0001 for both); however, there was no correlation with low-density lipoprotein cholesterol (LDL-C; ρ: 0.003; P = 0.51). Statin intensity increased with increasing BMI (ρ: 0.13; P < 0.001), an association that held after adjustment for comorbidities (OR: 2.4; 95% CI: 2.0-3.0) on BMI ≥ 30 kg/m2 for atorvastatin equivalent ≥40 mg/d.

Early diagnosis of acute coronary syndrome.

The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.

Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology.

AIMS: Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines. METHODS AND RESULTS: The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development. CONCLUSIONS: A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases.

N-terminal pro-B-type natriuretic peptide concentrations, testing and associations with worsening heart failure events.

AIMS: In patients with heart failure (HF), we aimed to assess (i) the time trends in N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing; (ii) patient characteristics associated with NT-proBNP testing; (iii) distribution of NT-proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT-proBNP levels over time. METHODS AND RESULTS: NT-proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT-proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT-proBNP testing and (ii) changes in NT-proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT-proBNP testing increased over time, up to 55% in 2018, and was almost two-fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT-proBNP was 3070 ng/L (Q1-Q3: 1220-7395), approximately three-fold higher in WHFE vs. NWHFE. Compared with stable low NT-proBNP levels, increased (OR 4.27, 95% CI 2.47-7.37) and stable high levels (OR 2.48, 95% CI 1.58-3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population. CONCLUSIONS: NT-proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT-proBNP testing in clinical practice.

Excess healthcare resource utilization and costs for commercially insured patients with pulmonary arterial hypertension: A real-world data analysis.

This retrospective study was conducted to evaluate all-cause healthcare resource utilization (HCRU) and costs in commercially insured patients living with pulmonary arterial hypertension (PAH) and explore end-of-life (EOL)-related HCRU and costs. Data from the IQVIA PharMetrics® Plus database (October 2014 to May 2020) were analyzed to identify adults (≥18 years) with PAH (PAH cohort) and those without PH (non-PH cohort). Patients were required to have data for ≥12 months before (baseline) and ≥6 months after (follow-up) the first observed PH diagnosis (index date) for PAH cohort or pseudo index date for non-PH cohort. A PAH EOL cohort was similarly constructed using a broader data window (October 2014 to March 2022) and ≥1 month of follow-up. Annualized all-cause HCRU and costs during follow-up were compared between PAH and non-PH cohorts after 1:1 matching on propensity scores derived from patient characteristics. EOL-related HCRU and costs were explored within 30 days and 6 months before the death date and estimated by a claims-based algorithm in PAH EOL cohort. The annual all-cause total ($183,616 vs. $20,212) and pharmacy ($115,926 vs. $7862; both p < 0.001) costs were 8 and 14 times higher, respectively, in the PAH cohort versus matched non-PH cohort (N = 386 for each). In PAH EOL cohort (N = 28), the mean EOL-related costs were $48,846 and $167,524 per patient within 30 days and 6 months before the estimated death, respectively. Hospitalizations contributed 58.8%-70.8% of the EOL-related costs. The study findings indicate substantial HCRU and costs for PAH. While pharmacy costs were one of the major sources, hospitalization was the primary driver for EOL-related costs.

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH).

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT. BGT was comprised of mono-, double-, or triple-PAH targeted therapy. Building on STELLAR findings, we employed a population health model to assess the potential long-term clinical impact of sotatercept. METHODS: Based on the well-established ESC/ERS 4-strata risk assessment approach, we developed a six-state Markov-type model (low risk, intermediate-low risk, intermediate-high risk, high risk, lung/heart-lung transplant, and death) to compare the clinical outcomes of sotatercept plus BGT versus BGT alone over a lifetime horizon. State-transition probabilities were obtained from STELLAR. Risk stratum-adjusted mortality and lung/heart-lung transplant probabilities were based on COMPERA PAH registry data, and the post-transplant mortality probability was obtained from existing literature. Model outcomes were discounted at 3% annually. Sensitivity analyses were conducted to examine model robustness. RESULTS: In the base case, sotatercept plus BGT was associated with longer life expectancy from model baseline (16.5 vs 5.1 years) versus BGT alone, leading to 11.5 years gained per patient. Compared with BGT alone, sotatercept plus BGT was further associated with a gain in infused prostacyclin-free life years per patient, along with 683 PAH hospitalizations and 4 lung/heart-lung transplant avoided per 1000 patients. CONCLUSIONS: According to this model, adding sotatercept to BGT increased life expectancy by roughly threefold among patients with PAH while reducing utilization of infused prostacyclin, PAH hospitalizations, and lung/heart-lung transplants. Real-world data are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04576988 (STELLAR).

Contemporary outpatient management of patients with worsening heart failure with reduced ejection fraction: Clinical outcome results from the CHART-HF study.

Background: Based on available data from randomized clinical trials, patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) have substantial disease burden and poor outcomes. WHFE clinical outcome data in non-clinical trial patients, more representative of the US clinical practice, has not been demonstrated. Methods and results: CHART-HF collected data from two complementary, non-clinical trial cohort with HFrEF (LVEF <45 %): 1) 1,000 patients from an integrated delivery network and 2) 458 patients from a nationwide physician panel. CHART-HF included patients with WHFE between 2017 and 2019 followed by an index outpatient cardiology visit ≤6 months, and patients without WHFE in a given year between 2017 and 2019, with the last outpatient cardiology visit in the same year as the index visit. Compared to patients without WHFE (after covariate adjustment, all p < 0.05), patients with WHFE had a greater risk of HF-related hospitalization (hazard ratio [HR]: 1.53-2.40) and next WHFE event (HR: 1.67-2.41) following index visits in both cohorts. Conclusion: HFrEF patients with recent WHFE consistently had worse clinical outcomes in these non-clinical trial cohorts. Despite advances in therapies, unmet need to improve clinical outcomes in HFrEF patients with WHFE remains.

Treatment patterns of patients with worsening heart failure with reduced ejection fraction.

AIMS: Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease-modifying therapy. CHART-HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. METHODS AND RESULTS: CHART-HF collected retrospective electronic medical records of outpatients with HF and EF < 45% between 2017-2019 from a nationwide panel of 238 cardiologists (458 patients) and the Geisinger Health System (GHS) medical record (1000 patients). The index visit in the WHFE cohort was the first outpatient cardiologist visit ≤6 months following the WHFE, and in the reference cohort was the last visit in a calendar year without WHFE. Demographic characteristics were similar between patients with and without WHFE in both the nationwide panel and GHS. In the nationwide panel, the proportion of patients with versus without WHFE receiving ≥50% of guideline-recommended dose on index visit was 35% versus 40% for beta blocker, 74% versus 83% for ACEI/ARB/ARNI, and 48% versus 49% for MRA. The proportion of patients receiving ≥50% of guideline-recommended dose was lower in the GHS: 29% versus 34% for beta-blocker, 16% versus 31% for ACEI/ARB/ARNI, and 18% versus 22% for MRA. For patients with and without WHFE, triple therapy on index date was 42% and 44% of patients from the nationwide panel, and 14% and 17% in the GHS. Comparing end of index clinic visit with 12-month follow-up in the GHS, the proportion of patients on no GDMT increased from 14% to 28% in the WHFE cohort and from 14 to 21% in the non-WHFE group. CONCLUSIONS: Major gaps in use of GDMT, particularly combination therapy, remain among US HFrEF patients. These gaps persist during longitudinal follow-up and are particularly large among patients with recent WHFE.

Are there differences in LDL-C target value attainment in Austrian federal states? Yes!

UNLABELLED: Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences. DESIGN: Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).

Comparison of Machine Learning Algorithms for Predicting Hospital Readmissions and Worsening Heart Failure Events in Patients With Heart Failure With Reduced Ejection Fraction: Modeling Study.

BACKGROUND: Heart failure (HF) is highly prevalent in the United States. Approximately one-third to one-half of HF cases are categorized as HF with reduced ejection fraction (HFrEF). Patients with HFrEF are at risk of worsening HF, have a high risk of adverse outcomes, and experience higher health care use and costs. Therefore, it is crucial to identify patients with HFrEF who are at high risk of subsequent events after HF hospitalization. OBJECTIVE: Machine learning (ML) has been used to predict HF-related outcomes. The objective of this study was to compare different ML prediction models and feature construction methods to predict 30-, 90-, and 365-day hospital readmissions and worsening HF events (WHFEs). METHODS: We used the Veradigm PINNACLE outpatient registry linked to Symphony Health's Integrated Dataverse data from July 1, 2013, to September 30, 2017. Adults with a confirmed diagnosis of HFrEF and HF-related hospitalization were included. WHFEs were defined as HF-related hospitalizations or outpatient intravenous diuretic use within 1 year of the first HF hospitalization. We used different approaches to construct ML features from clinical codes, including frequencies of clinical classification software (CCS) categories, Bidirectional Encoder Representations From Transformers (BERT) trained with CCS sequences (BERT + CCS), BERT trained on raw clinical codes (BERT + raw), and prespecified features based on clinical knowledge. A multilayer perceptron neural network, extreme gradient boosting (XGBoost), random forest, and logistic regression prediction models were applied and compared. RESULTS: A total of 30,687 adult patients with HFrEF were included in the analysis; 11.41% (3184/27,917) of adults experienced a hospital readmission within 30 days of their first HF hospitalization, and nearly half (9231/21,562, 42.81%) of the patients experienced at least 1 WHFE within 1 year after HF hospitalization. The prediction models and feature combinations with the best area under the receiver operating characteristic curve (AUC) for each outcome were XGBoost with CCS frequency (AUC=0.595) for 30-day readmission, random forest with CCS frequency (AUC=0.630) for 90-day readmission, XGBoost with CCS frequency (AUC=0.649) for 365-day readmission, and XGBoost with CCS frequency (AUC=0.640) for WHFEs. Our ML models could discriminate between readmission and WHFE among patients with HFrEF. Our model performance was mediocre, especially for the 30-day readmission events, most likely owing to limitations of the data, including an imbalance between positive and negative cases and high missing rates of many clinical variables and outcome definitions. CONCLUSIONS: We predicted readmissions and WHFEs after HF hospitalizations in patients with HFrEF. Features identified by data-driven approaches may be comparable with those identified by clinical domain knowledge. Future work may be warranted to validate and improve the models using more longitudinal electronic health records that are complete, are comprehensive, and have a longer follow-up time.