BACKGROUND:In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), amyloid can be deposited in the peripheral nerves, causing polyneuropathy (PN). We evaluated the rate of incident PN diagnosis among ATTR-CM patients. METHODS:This study utilized German claims data from January 2016-December 2023. We included adults newly diagnosed with ATTR-CM without a prior history of PN based upon International Classification of Diseases-Tenth Revision-German Modification (ICD-10-GM) diagnosis codes and coding for diagnostic testing. We identified incident PN using both a narrow (ATTR-PN-related) and broad (also including non-ATTR-specific polyneuropathies) set of ICD-10-GM codes. Incidence rates/100 person-years (PYs) with 95% confidence intervals (CIs) were calculated. RESULTS:We identified 309 newly diagnosed patients with ATTR-CM free of PN. During a median follow-up of 430 days (Q1 = 175, Q3 = 936) the rate of broadly defined incident PN was 10.8 cases/100PYs (7.9-14.3), declining to 2.4 cases/100PYs (1.2-4.1) when the narrow ATTR-related PN definition was used. CONCLUSIONS:In German routine care, the incidence of ATTR-related PN in patients with ATTR-CM was 2.4/100PYs, rising to 10.8/100PYs under a broad symptom-based definition. Although ATTR-related PN was infrequently identified in ATTR-CM, PN and ATTR-CM may coincide.

Vericiguat reduced clinical endpoints in patients experiencing worsening heart failure in clinical trials, but its implementation outside trials is unclear. This retrospective analysis of longitudinally collected data was based on the IQVIA™ LRx database, which includes 80

BACKGROUND:Data are limited regarding guideline-directed medical therapy (GDMT) treatment patterns in patients with worsening heart failure (HF).METHODS:We used administrative claims databases in Germany and the USA to conduct a retrospective cohort study of patients with worsening HF. Two cohorts of patients with prevalent HF and a HF hospitalization (HFH) from 2016 to 2019, alive at discharge (N = 75,140 USA; N = 47,003 Germany) were identified. Index date was the first HFH during the study period. One-year HF rehospitalization and mortality rates were calculated and a composite endpoint of both outcomes assessed using Kaplan-Meier estimation. We evaluated HF medication patterns in the 6 months before and after the index date. New users of a HF medication (at discharge/after index HFH) were followed for 1 year to evaluate persistence (no treatment gaps > 2 months) RESULTS: One-year HF rehospitalization rates were 36.2% (USA) and 47.7% (Germany). One year mortality rates were 30.0% (USA) and 23.0% (Germany), and the composite endpoint (mortality/HF rehospitalization) was reached in 55.1 % (USA) and 56.6% (Germany). Kaplan-Meier plots showed the risk for the composite endpoint was high in the early post discharge period. Comparison of patterns pre- and postindex HFH showed some increase in use of mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitor (ARNI), and triple therapy; use of angiotensin-converting enzyme (ACE) inhibitor/ angiotensin receptor blocker (ARB) plus beta-blockers remained constant/slightly declined; < 20% patients received triple therapy (ACE inhibitor/ARB plus beta-blocker plus MRA). A third of patients were new users; 1 year persistence rates were often low.CONCLUSIONS:Morbidity, mortality, and rehospitalization risk is high among patients with worsening HF; uptake and continuation of GDMT is suboptimal.

Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective cohort study evaluating the changes in HF drug utilization patterns in 6 months before and after hospitalizations for HF. The adherence to newly initiated HF medications was evaluated based on the proportion of days covered (PDC) and persistence as continuous treatment episodes among new users. The study included 9091 patients hospitalized for HF between January 2016 and September 2019, including 2735 (30.1%) patients who were newly prescribed at least one HF medication after hospitalization. Despite increases in the use of foundational HF therapy (beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, or mineralocorticoid receptor antagonists), 35.6% and 7.6% of patients were treated with the HF foundational monotherapy or diuretics alone after hospitalization, respectively. The mean PDC of newly initiated HF medications ranged from 0.57 for thiazide diuretics to 0.77 for sodium-glucose cotransporter-2 inhibitors. Continuous use of HF medications during the first year after initiation was observed in 30–60% of patients. The mean PDC and one-year continuous HF medication use were consistently lower in patients aged ≥ 75 years and in patients with a history of HF hospitalization for all HF medication classes except for tolvaptan and digoxin. Despite the guideline recommendations of HF pharmacotherapy, both treatment and adherence were suboptimal after HF hospitalization, especially in vulnerable populations such as older patients and those with prior HF hospitalizations.

Many predictive HF models exist, but most have used only a small number of important clinical predictors to compute risk score. While useful during individual patient-clinician encounters, these models have limited utility to inform and identify population-level interventions. This study aimed to develop and internally validate predictive models of high-risk HF patients to identify a potential target population for intensified interventions or management adjustment in a large United States (U.S.) managed care population.

Background: Patient-reported health related quality of life (HRQOL) is not routinely assessed in clinical practice. Little is known about health status outcomes reported by patients with heart failure with preserved ejection fraction (HFpEF) in non-clinical trial settings.Purpose: To better understand patient burden of HFpEF in terms of HF-specific functional and symptom status, HRQOL, healthcare resource utilization (HCRU) and costs in a US-based commercial and Medicare Advantage insured population.Patients and methods: We conducted a cross-sectional survey of patients with HFpEF and linked their survey and administrative claims data. Consenting, eligible patients completed a survey that included the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the PROMIS Global Health-10 (GH-10) questionnaire, as well as clinical and demographic questions. HF medication use, HCRU and costs during the 12-month baseline period before the survey were determined from claims data. Generalized linear regression was used to assess the associations between baseline characteristics and the KCCQ-23 overall summary score.Results: Of 598 survey respondents with survey and claims data, 54.7% were female with mean age 74.0 years. The KCCQ-23 overall summary and clinical summary scores were 64.8 and 63.0, respectively, and the GH-10 physical and mental health summary scores were 39.9 and 45.5. Factors related to lower KCCQ-23 overall summary scores were HF treatment and symptom changes during the past 4-weeks before the survey, hospital admission during the past year, low household income, high comorbidity index, and morbid obesity (BMI>40). Total all-cause healthcare costs were $38,243 during the year prior to the survey, of which 42% were HF-related.Conclusion: Patient-reported outcome measure scores indicated impairment due to HF symptoms and physical limitations in this real -world sample of patients with HFpEF, highlighting a need to assess patient-reported outcomes as well as the clinical and economic outcomes traditionally assessed by clinicians, health systems and payers.

Background Electronic health record (EHR)-based identification of heart failure with preserved ejection fraction (HF-pEF) in the clinical setting may facilitate screening for clinical trials by improving the understanding of its epidemiology and outcomes; yet, previous data have yielded variable results. We sought to characterize groups identified with HFpEF by different EHR screening strategies and their associated long-term outcomes across a large and diverse population.Methods We retrospectively analyzed 116,499 consecutive patients from an academic referral center who underwent echocardiography, and 9,263 patients who underwent echocardiography within 6 months of right heart catheterization (RHC), between 2008 and 2018. EHR-based screening strategies identified patients with HFpEF using 1) International Clas-sification of Diseases (ICD)-9/10 codes, 2) H2FpEF score >6 and ejection fraction (EF) >50%, or 3) RHC wedge pressure >15 mmHg and EF >50%, when available. Primary outcomes were 1) cumulative incident heart failure hospitalization (HFH), and 2) death, over 10 years.Results There were 33,461 (29%) patients who met either ICD or H2FpEF-HFpEF definition, of whom 5,310 (16%) met both criteria. Compared to ICD-HFpEF, patients with H2FpEF-HFpEF were more likely older (median age 72 vs 67), White (78% vs 64%), and had atrial fibrillation (97% vs 41%). Among those also with RHC, 6,353 (69%) patients met any HFpEF criteria, of whom only 783 (12%) satisfied all three criteria. Female sex was more common among RHC-HFpEF (55%) compared to other methods (H2FpEF-HFpEF, 47%; ICD-HFpEF, 43%). Atrial fibrillation was substantially higher among HFpEF identified by the H2FpEF score (97%) compared to other methods (49% for ICD and 47% for RHC). Across HFpEF screening methods, 10-year cumulative incidence rates for HFH was 32% to 45% for echocardiography only and 43% to 52% for echocardiography and RHC populations; 10-year risk of death was 54% to 56% for echocardiography only and 52% to 57% for echocardiography and RHC populations.Conclusions Different EHR-based HFpEF definitions identified cohorts with modest overlap and varying baseline char-acteristics. Yet, long-term risk for HFH and death were similarly high for cohorts identified among both populations undergoing echocardiography only or echocardiography and RHC. These data aid in identifying relevant subgroups in clinical trials of HFpEF.

Progression of chronic kidney disease (CKD) is associated with increased risk of cardiovascular or renal events that contribute to increasing healthcare costs. The purpose of this study was to develop predictive models for rapid progression of CKD, days out of the home, and high costs for patients with both CKD and type 2 diabetes (T2D) . This retrospective observational cohort study used administrative claims data for patients with CKD (stage 3-4) and T2D aged 65-89 years enrolled in a Humana Medicare Advantage Prescription Drug plan 1/1/2012-12/31/2017. Patients were enrolled ≥1 year pre-index and followed up to one year post-index. Outcomes included rapid progression of CKD (>1 decrease in estimated glomerular filtration rate [eGFR] >5 mL/min/1.73m2 per year) , days out of the home (days spent out of their residence [e.g., hospital]; ≥2% days out of the home) and high costs (75-90th and >90th percentiles) post-index. Pre-index demographic and clinical characteristics, selected based on the LASSO technique, were included in logistic regression models to generate parameter estimates and model performance statistics. We identified 169,876 patients with CKD stage 3-4 and T2D. The C-statistics for the models ranged from 0.694 to 0.745. Lower initial eGFR led to incrementally higher risk for more days out of the home and high costs. Patients with urinary albumin to creatinine ratio (UACR) ≥300 mg/g had three times increased risk for rapid progression of CKD, 57% higher risk of more days out of the home, and, among those in the 75-90th cost percentile, had 38% higher costs than patients with UACR<30 mg/g. The presence of congestive heart failure, anemia, or higher pre-index utilization (≥5 physician visits) increased the risk for all outcomes. The predictive models developed in this study can be potentially used as decision support tools for clinicians and payers, and the risk scores from these models can be applied to future outcomes studies focused on patients with T2D and CKD. Disclosure R. Nair: None. M.K. Pasquale: Consultant; Bayer AG. T. Evers: Employee; Bayer AG. M.M. Cockrell: Employee; Humana. Stock/Shareholder; Humana. A. Gay: Employee; Bayer AG. R. Singh: None. N. Schmedt: Employee; Bayer AG. Funding This study was funded by Bayer.

INTRODUCTION/OBJECTIVE:Predictive risk models identifying patients at high risk for specific outcomes may provide valuable insights to providers and payers regarding points of intervention and modifiable factors. The goal of our study was to build predictive risk models to identify patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) at high risk for progression to end stage kidney disease (ESKD), mortality, and hospitalization for cardiovascular disease (CVD), cerebrovascular disease (CeVD), and heart failure (HF).METHODS:This was a retrospective observational cohort study utilizing administrative claims data in patients with CKD (stage 3-4) and T2D aged 65 to 89 years enrolled in a Medicare Advantage Drug Prescription plan offered by Humana Inc. between 1/1/2012 and 12/31/2017. Patients were enrolled ≥1 year pre-index and followed for outcomes, including hospitalization for CVD, CeVD and HF, ESKD, and mortality, 2 years post-index. Pre-index characteristics comprising demographic, comorbidities, laboratory values, and treatment (T2D and cardiovascular) were evaluated and included in the models. LASSO technique was used to identify predictors to be retained in the final models followed by logistic regression to generate parameter estimates and model performance statistics. Inverse probability censoring weighting was used to account for varying follow-up time.RESULTS:We identified 169 876 patients for inclusion. Declining estimated glomerular filtration rate (eGFR) increased the risk of hospitalization for CVD (38.6%-61.8%) and HF (2-3 times) for patients with eGFR 15 to 29 mL/min/1.73 m2 compared to patients with eGFR 50 to 59 mL/min/1.73 m2. Patients with urine albumin-to-creatinine ratio (UACR) ≥300 mg/g had greater chance for hospitalization for CVD (2.0 times) and HF (4.9 times), progression to ESKD (2.9 times) and all-cause mortality (2.4 times) than patients with UACR <30 mg/g. Elevated hemoglobin A1c (≥8%) increased the chances for hospitalization for CVD (21.3%), CeVD (45.4%), and death (20.6%). Among comorbidities, history of HF increased the risk for ESKD, mortality, and hospitalization for CVD, CeVD, and HF.CONCLUSIONS:The predictive models developed in this study could potentially be used as decision support tools for physicians and payers, and the risk scores from these models can be applied to future outcomes studies focused on patients with T2D and CKD.

OBJECTIVES To assess the relationship between relative estimated glomerular filtration rate (eGFR) change and outcomes in patients with type 2 diabetes (T2D). STUDY DESIGN This retrospective cohort study utilized administrative claims (Humana Research Database) for patients with T2D aged 65 to 89 years, enrolled in a Medicare Advantage plan, with an initial eGFR of 25 to 89 mL/min/1.73m2 in 2008 to 2017, and a second eGFR measurement within 3 to 24 months after the identification date. METHODS The primary exposure was relative decline in eGFR of 40% or more in a 2-year period. Outcomes included end-stage kidney disease (ESKD) or kidney failure, a composite cardiovascular (CV) outcome, and all-cause mortality assessed with multivariable adjusted survival models. Days out of the home and all-cause total costs were assessed using multivariable adjusted generalized linear models. RESULTS A total of 288,170 patients were included. The adjusted HR for ESKD or kidney failure was 4.38 (95% CI, 3.99-4.81) in patients with 40% or greater decline versus those with a decline of less than 40%. The adjusted HR was 1.67 (95% CI, 1.53-1.82) for the composite CV outcome and 1.98 (95% CI, 1.87-2.10) for all-cause mortality. Patients with a 40% or greater relative decline had 2.23 times higher all-cause total per patient per month costs ($1910 difference) and 1.82 times higher odds of 7 or more days out of the home versus those with less than 40% relative eGFR decline. CONCLUSIONS Our results indicate that a relative eGFR decline of 40% or greater is associated with an increased risk of ESKD or kidney failure, CV outcomes and all-cause mortality, and increased health care resource utilization and costs.

OBJECTIVE:To examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims database.PATIENTS AND METHODS:This cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results.RESULTS:A total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 [43.3%]). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period.CONCLUSION:Physicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up.

A ≥40% relative decline in estimated glomerular filtration rate (eGFR) has been supported for use as a surrogate endpoint for clinical outcomes. However, the associations between this change and resulting days that a patient spends out of their primary ambulatory residence (e.g., during inpatient admissions and nursing facility stays) and cost outcomes are limited. The purpose of this analysis was to evaluate the associations of relative changes in eGFR with days out of the home and with cost outcomes in patients with type 2 diabetes mellitus (T2DM).

Research supporting the validity of changes in estimated glomerular filtration rate (eGFR) as a surrogate endpoint for end-stage kidney disease (ESKD) or other clinical outcomes in patients with type 2 diabetes mellitus (T2DM) is limited. The primary purpose of this study was to evaluate the association between relative changes in eGFR and clinical outcomes in patients with T2DM.

AIMS:Approximately 50% of patients with heart failure have preserved (≥50%) ejection fraction (HFpEF). Improved understanding of the phenotypic heterogeneity of HFpEF might facilitate development of targeted therapies and interventions. METHODS:This retrospective study characterized a cohort of patients with HFpEF based on similar clinical profiles and evaluated 1-year heart failure related hospitalization. Enrolment, medical and pharmacy data were used to identify patients newly diagnosed with heart failure enrolled in a Medicare Advantage Prescription Drug or commercial healthcare plan. To identify only those patients with HFpEF, we used natural language processing techniques of ejection fraction values abstracted from a linked free-text clinical notes data source. The study population comprised 1515 patients newly identified with HFpEF between 1 January 2011 and 31 December 2015. RESULTS:Using unsupervised machine learning, we identified three distinguishable patient clusters representing different phenotypes: cluster-1 patients had the lowest prevalence of heart failure comorbidities and highest mean age; cluster-2 patients had higher prevalence of metabolic syndrome and pulmonary disease, despite younger mean age; and cluster-3 patients had higher prevalence of cardiac arrhythmia and renal disease. Cluster-3 had the highest 1-year heart failure related hospitalization rates. Within-cluster analysis, prior use of diuretics (cluster-1 and cluster-2) and age (cluster-2 and cluster-3) was associated with 1-year heart failure related hospitalization. Combination therapy was associated with decreased 1-year heart failure related hospitalization in cluster-1. CONCLUSION:This study demonstrated that clustering can be used to characterize subgroups of patients with newly identified HFpEF, assess differences in heart failure related hospitalization rates at 1 year and suggest patient subtypes may respond differently to treatments or interventions.

Background Although the significant burden of heart failure (HF) is well recognized, the relative contributions of systolic HF versus diastolic HF are less defined. Objective To explore the differential burden between patients with systolic and diastolic HF in terms of treatment patterns, healthcare resource utilization (HCRU), costs, and mortality risk. Methods This retrospective cohort study used administrative claims data from a large US commercial health insurer integrated with mortality data. Patients newly diagnosed with HF between January 1, 2010, and June 30, 2016, were identified and grouped according to systolic HF or diastolic HF diagnosis and were followed up to 4 years after diagnosis. Treatment patterns, HCRU, costs, and mortality were compared between the 2 groups of patients. Results Overall, 46,885 patients with systolic HF and 21,854 with diastolic HF were identified and included in the study. Patients with systolic HF had less HCRU than those with diastolic HF during the first year after HF diagnosis, including hospital admissions (70.2% vs 82.4%, respectively; P <.001) and emergency department visits (30.5% vs 39.1%, respectively; P <.001). The average per-patient costs for patients with systolic HF during the 1-year follow-up were higher than for those with diastolic HF ($64,154 vs $59,652, respectively; P <.001), but lower during years 2 through 4 (approximately $23,000-$25,000 annually vs approximately $28,000-$29,000 annually; P <.001). Patients with diastolic HF had a higher adjusted hospitalization risk (odds ratio, 1.62; 95% confidence interval [CI], 1.55-1.69), but comparable adjusted costs (exponentiated estimate, 1.01; 95% CI, 0.99-1.02) and slightly lower mortality risk (hazard ratio, 0.96; 95% CI, 0.93-0.99) versus patients with systolic HF. The number of HF-related medication classes received for other diagnoses during the year preceding an HF diagnosis was associated with lower risks for hospitalization, mortality, and lower costs, with a trend in benefits toward patients with systolic HF. Of note, 21.9% of patients with systolic HF and 25% of patients with diastolic HF filled no HF-related prescriptions in the year after diagnosis. Conclusion This real-world analysis confirms a high disease burden associated with HF and provides insight across the systolic HF and diastolic HF phenotypes. HF-related medication use after diagnosis was suboptimal and underscores a gap in patient care.