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• W4377013093 abstract "The economic burden of heart failure (HF) is enormous, but studies of HF costs typically consider the disease to be a single entity. We sought to distinguish the medical costs for patients with HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). We identified 16,516 adult patients with an incident HF diagnosis and an echocardiogram from 2005 to 2017 in the electronic medical record of Kaiser Permanente Northwest. Using the echocardiogram nearest to the first diagnosis date, we classified patients with HFrEF (ejection fraction [EF] ≤40%), HFmrEF (EF 41% to 49%), or HFpEF (EF ≥50%). We calculated annualized inpatient, outpatient, emergency, pharmaceutical medical utilization and costs and total costs in $2,020, adjusted for age and gender using generalized linear models, with further analysis of the effects of co-morbid chronic kidney disease (CKD) and type 2 diabetes (T2D). For all HF types, 1 in 5 patients were affected by both CKD and T2D, and costs were significantly higher when both co-morbidities were present. Total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than HFrEF ($27,669, $25,649 to $29,689) or HFmrEF ($29,484, $27,166 to $31,800), driven by in- and outpatient visits. Across HF types, visits approximately doubled with the presence of both co-morbidities. Due to greater prevalence, HFpEF accounted for the majority of total and resource-specific treatment costs of HF, regardless of the presence of CKD and/or T2D. In summary, the economic burden was greater per HFpEF patient and was further amplified by co-morbid CKD and T2D. HFpEF accounted for the large majority of total HF costs, underscoring the need to implement effective treatments. The economic burden of heart failure (HF) is enormous, but studies of HF costs typically consider the disease to be a single entity. We sought to distinguish the medical costs for patients with HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). We identified 16,516 adult patients with an incident HF diagnosis and an echocardiogram from 2005 to 2017 in the electronic medical record of Kaiser Permanente Northwest. Using the echocardiogram nearest to the first diagnosis date, we classified patients with HFrEF (ejection fraction [EF] ≤40%), HFmrEF (EF 41% to 49%), or HFpEF (EF ≥50%). We calculated annualized inpatient, outpatient, emergency, pharmaceutical medical utilization and costs and total costs in $2,020, adjusted for age and gender using generalized linear models, with further analysis of the effects of co-morbid chronic kidney disease (CKD) and type 2 diabetes (T2D). For all HF types, 1 in 5 patients were affected by both CKD and T2D, and costs were significantly higher when both co-morbidities were present. Total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than HFrEF ($27,669, $25,649 to $29,689) or HFmrEF ($29,484, $27,166 to $31,800), driven by in- and outpatient visits. Across HF types, visits approximately doubled with the presence of both co-morbidities. Due to greater prevalence, HFpEF accounted for the majority of total and resource-specific treatment costs of HF, regardless of the presence of CKD and/or T2D. In summary, the economic burden was greater per HFpEF patient and was further amplified by co-morbid CKD and T2D. HFpEF accounted for the large majority of total HF costs, underscoring the need to implement effective treatments. The global economic burden of heart failure (HF) is enormous, with direct costs estimated at $65 billion annually in 2012,1Cook C Cole G Asaria P Jabbour R Francis DP. The annual global economic burden of heart failure.Int J Cardiol. 2014; 171: 368-376Abstract Full Text Full Text PDF PubMed Scopus (547) Google Scholar and the growing prevalence of HF suggests that costs will increase precipitously over time.2Echouffo-Tcheugui JB Bishu KG Fonarow GC Egede LE. Trends in health care expenditure among US adults with heart failure: the Medical Expenditure Panel survey 2002–2011.Am Heart J. 2017; 186: 63-72Crossref PubMed Scopus (44) Google Scholar On a per-person basis, health care costs are approximately 4 times higher for patients with versus without HF.3Klein S Jiang S Morey JR Pai A Mancini DM Lala A Ferket BS. Estimated health care utilization and expenditures in individuals with heart failure from the medical expenditure panel survey.Circ Heart Fail. 2021; 14e007763Crossref Scopus (1) Google Scholar These increased costs are driven primarily by hospitalizations,2Echouffo-Tcheugui JB Bishu KG Fonarow GC Egede LE. Trends in health care expenditure among US adults with heart failure: the Medical Expenditure Panel survey 2002–2011.Am Heart J. 2017; 186: 63-72Crossref PubMed Scopus (44) Google Scholar,4Liao L Allen LA Whellan DJ. Economic burden of heart failure in the elderly.Pharmacoeconomics. 2008; 26: 447-462Crossref PubMed Scopus (146) Google Scholar but all types of resource utilization contribute to the difference.5Korves C Eldar-Lissai A McHale J Lafeuille MH Hwa Ong S Sheng Duh M Resource utilization and costs following hospitalization of patients with chronic heart failure in the US.J Med Econ. 2012; 15: 925-937Crossref PubMed Google Scholar Nearly all studies of HF costs have considered the disease to be a single entity. Clinically, however, HF is classified according to ejection fraction (EF) to reflect that the underlying pathophysiology and causes of HF are different. It is likely that medical care utilization and costs differ between these HF types. A relatively small study attempted to determine costs for HF with reduced EF (HFrEF) versus HF with preserved EF (HFpEF), but that study dichotomized EF at ≥ or <50% rather than using the clinically recognized EF cut points of ≤40% for HFrEF and ≥50% for HFpEF.6Liao L Jollis JG Anstrom KJ Whellan DJ Kitzman DW Aurigemma GP Mark DB Schulman KA Gottdiener JS. Costs for heart failure with normal vs reduced ejection fraction.Arch Intern Med. 2006; 166: 112-118Crossref PubMed Scopus (111) Google Scholar Another study used diagnoses to classify patients with HFrEF or HFpEF,7Lam CSP Wood R Vaduganathan M Bueno H Chin A Luporini Saraiva G Sörstadius E Tritton T Thomas J Qin L Contemporary economic burden in a real-world heart failure population with Commercial and Medicare supplemental plans.Clin Cardiol. 2021; 44: 646-655Crossref PubMed Scopus (6) Google Scholar and a third evaluated up to 18 months of costs after a HF hospitalization.8Olchanski N Vest AR Cohen JT DeNofrio D. Two-year outcomes and cost for heart failure patients following discharge from the hospital after an acute heart failure admission.Int J Cardiol. 2020; 307: 109-113Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar To the best of our knowledge, no study has examined long-term costs by EF type beginning with an incident HF diagnosis. Moreover, the proportion of total HF costs attributable to each HF type is not known. Clearly there is a need for a comprehensive study of HF costs using a contemporary classification comparing HFrEF, mildly reduced EF (HFmrEF, 41% to 49%), and HFpEF.9Bozkurt B Coats AJS Tsutsui H Abdelhamid CM Adamopoulos S Albert N Anker SD Atherton J Böhm M Butler J Drazner MH Michael Felker G Filippatos G Fiuzat M Fonarow GC Gomez-Mesa JE Heidenreich P Imamura T Jankowska EA Januzzi J Khazanie P Kinugawa K Lam CSP Matsue Y Metra M Ohtani T Francesco Piepoli M Ponikowski P Rosano GMC Sakata Y Seferović P Starling RC Teerlink JR Vardeny O Yamamoto K Yancy C Zhang J Zieroth S Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.Eur J Heart Fail. 2021; 23: 352-380Crossref PubMed Scopus (357) Google Scholar,10Rosano GMC Moura B Metra M Böhm M Bauersachs J Ben Gal T Adamopoulos S Abdelhamid M Bistola V Čelutkienė J Chioncel O Farmakis D Ferrari R Filippatos G Hill L Jankowska EA Jaarsma T Jhund P Lainscak M Lopatin Y Lund LH Milicic D Mullens W Pinto F Ponikowski P Savarese G Thum T Volterrani M Anker SD Seferovic PM Coats AJS Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology.Eur J Heart Fail. 2021; 23: 872-881Crossref PubMed Scopus (109) Google Scholar We constructed a longitudinal rolling cohort using the electronic medical records (EMRs) of Kaiser Permanente Northwest (KPNW), an integrated delivery system serving approximately 650,000 individuals in the 100-mile radius around Portland, Oregon. The EPIC-based EMR used by KPNW since 1996 includes both inpatient and outpatient contacts, with links to laboratory, radiology, and pharmaceutical databases, and out-of-plan services paid for by KPNW, allowing the assessment of nearly all medical care received by its members. The study was reviewed and approved by the KPNW Institutional Review Board with a waiver of written informed consent. We identified 37,773 patients with an International Classification of Diseases, Ninth Revision diagnosis of HF (428.x) recorded in the EMR between January 1, 2005 and September 30, 2015 or an International Classification of Diseases diagnosis, Tenth Revision code (I51.x) recorded between October 1, 2015 and December 31, 2017. To ensure we were studying incident cases, we used the first HF diagnosis as the index date and excluded 13,433 individuals with an indication of HF in the preceding 12 months. We then selected the echocardiogram result nearest to the index date to classify patients as HFrEF (EF ≤40%, n = 2,430, 10.0%), HFmrEF (EF 41% to 49%, n = 1,646, 6.8%), HFpEF (EF ≥50%, n = 12,440, 51.1%), or no echocardiogram available (n = 7,824, 32.1%). After exclusion of those without a classifiable echocardiogram, the final sample size was 16,516. We followed up patients from their first HF diagnosis (index date) until they died or left the health plan for other reasons or until December 31, 2019. Covariate data, including demographics (age, gender, race/ethnicity), risk factors (blood pressure, body mass index, smoking status), co-morbidities, pharmaceutical usage, and laboratory values were extracted from the EMR and linked datasets during the baseline data collection period of up to 12 months preceding the index date. The main outcomes were annualized inpatient, outpatient, emergency, pharmacy, and total healthcare utilization and costs for each EF group overall and by the presence of chronic kidney disease (CKD) and/or type 2 diabetes (T2D) during the entire follow-up period after the index date, adjusted for age and gender. We calculated the annual utilization and costs on a per-member per-month basis. To annualize these data, we divided a patient's summed utilization or costs by the number of months of eligibility and then multiplied by 12. The estimates were then weighted by the number of months of eligibility to mitigate the effect of high end-of-life utilization and costs. Our costing method was developed and validated for research and risk adjustment purposes by the KPNW Center for Health Research11Hornbrook MC Goodman MJ Fishman PA Meenan RT O'Keeffe-Rosetti M Bachman DJ. Building health plan databases to risk adjust outcomes and payments.Int J Qual Health Care. 1998; 10: 531-538Crossref PubMed Scopus (16) Google Scholar and has been recently described in detail elsewhere.12Nichols GA Philip S Reynolds K Granowitz CB O'Keeffe-Rosetti M Fazio S. Comparison of medical care utilization and costs among patients with statin-controlled low-density lipoprotein cholesterol with versus without hypertriglyceridemia.Am J Cardiol. 2018; 122: 1128-1132Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Briefly, this costing algorithm assigns an average cost per unit of service based on general ledger information. For outpatient costs, this method creates standard costs for office visits by specialty/department and type of provider (MD vs Physician Assistant/Nurse Practitioner). The number of visits per department per clinician type is multiplied by the appropriate unit cost. Pharmaceutical costs were based on retail prices within the respective service areas. Hospitalization costs were calculated by multiplying the average daily cost per assigned diagnosis-related groups by the length of stay. Costs include not only pharmaceutical dispenses but also procedures and devices. Costs for medical services incurred at facilities not owned by KPNW were based on the amount paid to the nonplan provider. All costs are reported in $2,020. Of the 16,516 study patients, 15% had HFrEF, 10% had HFmrEF, and 75% had HFpEF (Table 1). Compared with patients with HFrEF, those with HFpEF were older (72.2 vs 68.7 years), more obese (body mass index 32 vs 29 kg/m2), and more likely to be women (54.2% vs 34.9%). Patients wirg HFpEF were more likely to have hypertension (83.9% vs 70.4%) and to be treated with any HF-related medication (88.6% vs 81.9%). The values for nearly all data elements among patients with HFmrEF were between HFrEF and HFpEF.Table 1Baseline characteristics of the study sample by HF typeHF typeHFrEF:HFmrEF:HFpEF:Baseline assessmentEF ≤ 40%EF 41-49%EF ≥ 50%No. (%) of total2,430 (15%)1,646 (10.0%)12,440 (75%)Mean (SD) age, yars69 (14)70 (13)72 (12)Male1,592 (65%)1,037 (63%)5,697 (46%)Hispanic63 (3%)44 (3%)286 (2%)Non-Hispanic Black85 (4%)44 (3%)348 (3%)Current smoker364 (15%)189 (12%)1,070 (9%)CKD (<60ml/min/1.73m2)850 (35%)625 (38%)5,324 (43%)Any cardiovascular disease2,283 (93%)1,495 (91%)10,462 (84%)Type 2 diabetes955 (39%)640 (39%)5,100 (41%)Hypertension1,711 (70%)1,317 (80%)10,437 (84%)Mean (SD) systolic blood pressure, mmHg121 (21)125 (21)130 (21)Mean (SD) diastolic blood pressure, mmHg72 (15)71 (14)70 (13)Mean (SD) body mass index, kg/m2,29 (7)30 (7)32 (9)Sacubitril/valsartan7 (0.3%)2 (0.1%)0 (0.0%)ACE/ARB1,406 (58%)1,036 (63%)7,427 (60%)ß-blockers1,453 (60%)1,142 (69%)8,198 (66%)Diuretics1,285 (53%)853 (52%)7,439 (60%)Aldosterone antagonist287 (12%)156 (10%)784 (6%)Any HF-related medication2,015 (82%)1,435 (87%)11,022 (89%)Statins1,339 (55%)1,049 (64%)7,551 (61%)Glucose lowering drugs685 (28%)471 (29%)3,595 (29%)Data are means (standard deviation) or number (percentages). Open table in a new tab Data are means (standard deviation) or number (percentages). The proportion of patients with neither CKD nor T2D, CKD alone, T2D alone, and both CKD and T2D is listed in Table 2. In addition, the total number with CKD and/or T2D are listed. Compared with HFrEF, patients with HFpEF were more likely to have CKD alone (22.1% vs 17.4%) or in combination with T2D (20.7% vs 17.6%), for a total difference in CKD of 42.8% versus 35.0%. The proportion with T2D was similar across EF types. Across HF types, 18% to 21% of patients were affected by both CKD and T2D.Table 2Number and percent of patients with chronic kidney disease (CKD) and/or type 2 diabetes (T2D) by heart failure typeHF typeHFrEF:HFmrEF:HFpEF:EF ≤ 40%EF 41-49%EF ≥ 50%Baseline assessment(n=2,430)(n=1,646)(n=12,440)Neither CKD nor T2D1,0456754,59043%41%37%CKD without T2D4233342,74917%20%22%T2D without CKD5273472,52522%21%20%Both CKD and T2D4282912,57518%18%21%Total with CKD8516255,32435%38%43%Total with T2D9556405,10039%39%41% Open table in a new tab Mean age- and gender-adjusted medical utilization of all types was highest among HFpEF patients and (generally) lowest among HFrEF patients (Table 3). In patients with HFpEF but no CKD or T2D co-morbidity, both inpatient days and outpatient visits were highest compared with HFmrEF and HFrEF. Among those with either or both co-morbidities, only outpatient visits and pharmaceutical dispense were particularly increased among HFpEF patients. In addition, the use of all types was the highest for all 3 EF groups when both T2D and CKD were present and the lowest when among those with neither condition. Furthermore, across EF groups, utilization was greater among those with T2D only than those with CKD only, most prominently for the pharmaceutical dispenses.Table 3Mean age- and sex-adjusted medical care utilization (95% confidence intervals) by presence of baseline chronic kidney disease (CKD) and/or type 2 diabetes (T2D), by heart failure typeAge- and sex-adjusted annual health care utilizationMean number per person (95% confidence intervals)HFrEFHFmrEFHFpEFInpatient admissions Neither CKD nor T2D0.460.480.52(0.40–0.53)(0.40–0.56)(0.49–0.55) CKD only0.670.640.70(0.56–0.79)(0.51–0.76)(0.66–0.75) T2D only0.730.720.73(0.63–0.84)(0.59–0.85)(0.68–0.78) Both CKD and T2D1.001.060.98(0.88–1.13)(0.92–1.21)(0.93–1.03) All patients0.640.650.69(0.60–0.69)(0.60–0.71)(0.67–0.71)Inpatient days Neither CKD nor T2D1.961.972.37(1.58–2.35)(1.49–2.44)(2.19–2.56) CKD only3.002.853.04(2.34–3.65)(2.10–3.59)(2.78–3.30) T2D only3.203.263.40(2.58–3.81)(2.47–4.05)(3.12–3.67) Both CKD and T2D4.564.724.57(3.79–5.34)(3.80–5.64)(4.26–4.88) All patients2.812.843.16(2.53–3.09)(2.50–3.18)(3.04–3.28)Outpatient visits Neither CKD nor T2D13.8013.7215.48(13.20–14.40)(12.98–14.47)(15.20–15.77) CKD only15.7316.8818.68(14.46–17.00)(15.44–18.33)(18.18–19.19) T2D only17.9619.8719.51(16.84–19.09)(18.43–21.32)(19.00–20.02) Both CKD and T2D23.0526.1228.06(20.90–25.19)(23.60–28.65)(27.20–28.92) All patients16.5217.6619.64(15.93–17.10)(16.95–18.37)(19.38–19.89)Pharmaceutical dispenses Neither CKD nor T2D40.7840.3141.50(39.35–42.21)(38.54–42.07)(40.82–42.19) CKD only44.0244.5748.24(41.62–46.42)(41.84–47.30)(47.29–49.20) T2D only56.0660.1060.05(53.50–58.62)(56.81–63.39)(58.89–61.22) Both CKD and T2D63.3464.2866.15(60.22–60.47)(60.60–67.97)(64.90–67.40) All patients48.0748.8951.59(46.94–49.19)(47.53–50.26)(51.09–52.08) Open table in a new tab Table 4 lists the mean age- and gender-adjusted annualized per-person medical costs by HF type, and the group costs (mean per-person costs multiplied by the number of individuals in the EF group). The total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than both HFrEF ($27,669, $25,649 to $29,689) and HFmrEF ($29,484, $27,166 to $31,800). Although the differences were driven by outpatient and inpatient costs, the HFpEF group had the highest costs for pharmacy and emergency services as well. Given the difference in prevalence, HFpEF accounted for the majority of the total and resource-specific treatment costs of HF. However, the proportion of costs attributable to HFpEF was disproportionately higher than the prevalence. For example, the HFpEF group represented 75.3% of the population but accounted for 78.4% of total HF treatment costs, 81.6% of pharmacy costs, 79.4% of outpatient costs, 78.1% of emergency costs, and 76.9% of inpatient costs.Table 4Mean age- and sex-adjusted annual per-person inpatient, outpatient, emergency, pharmaceutical and total medical care costs (95% confidence intervals) and total group costs by heart failure typeHFrEF (n=2,430)HFmrEF (n=1,646)HFpEF (n=12,440)Per-person costs (95% CI)Group costs% of costs, all groupsPer-person costs (95% CI)Group costs% of costs, all groupsPer-person costs (95% CI)Group costs% of costs, all groupsInpatient$15,008$36,469,44013%$15,877$26,133,54210%$16,750$208,370,00077%($13,440–$16,576)($14,077–$17,675)($16,132–$17,369)Outpatient$7,978$19,386,54012%$8,861$14,585,2069%$10,544$131,167,36079%($7,375–$8,581)($8,169–$9,552)($10,307–$10,782)Pharmacy$3,345$8,128,35011%$3,327$5,476,2427%$4,844$60,259,36082%($2,702–$3,988)($2,589–$4,085)($4,591–$5,098)Emergency$1,338$3,251,34013%$1,419$2,335,6749%$1,602$19,928,88078%($1,208–$1,468)($1,269–$1,568)($1,550–$1,653)Total$27,669$67,235,67013%$29,484$48,530,6649%$33,740$419,725,60078%($25,649–$29,689)($27,166–$31,800)($32,944–$34,536) Open table in a new tab Figure 1 displays the mean age- and gender-adjusted annualized per-person medical costs by HF type for patients with neither CKD nor T2D, CKD only, T2D only, and both CKD and T2D. Across all 4 of these co-morbidity categories, the total costs were highest for HFpEF compared with HFmrEF and HFrEF. However, because of relatively small sample sizes, the differences were not statistically significantly different. Not surprisingly, for all HF types, the costs were significantly higher when both conditions were present and significantly lower when neither were present. The costs among patients with T2D only were greater than among patients with CKD only, but the differences were not statistically significantly different. In this observational study of over 16,000 individuals with newly diagnosed HF, we found that the annualized total medical costs for up to 15 years after diagnosis ranged from approximately $28,000 to nearly $34,000 in $2,020. Higher per-person costs of all resource types were incurred by patients with HFpEF (relative to HFrEF and HFmrEF). Thus, coupled with the substantially greater prevalence of HFpEF (75.3%), we found that patients with HFpEF accounted for 78% to 82% of the costs incurred by all patients with HF. The high prevalence of HFpEF (75% of patients with an EF) relative to HFrEF (15%) is a somewhat surprising result because studies conducted in patients hospitalized with HF typically report a more balanced distribution of HFrEF and HFpEF. Although the ongoing Swedish Heart Failure Registry recently reported that about half of the population has HFrEF, with 1/4 each having HFmrEF or HFpEF13Savarese G Vasko P Jonsson Å Edner M Dahlström U Lund LH. The Swedish Heart Failure Registry: a living, ongoing quality assurance and research in heart failure.Ups J Med Sci. 2019; 124: 65-69Crossref PubMed Scopus (49) Google Scholar; it captures <10% of the incident cases,14Lund LH Carrero JJ Farahmand B Henriksson KM Jonsson Å Jernberg T Dahlström U. Association between enrolment in a heart failure quality registry and subsequent mortality-a nationwide cohort study.Eur J Heart Fail. 2017; 19: 1107-1116Crossref PubMed Scopus (69) Google Scholar making the comparison to our study of exclusively incident patients difficult. Several community-based studies using data through 2014 have suggested increasing trends in HFpEF, along with decreasing trends in HFrEF.15Steinberg BA Zhao X Heidenreich PA Peterson ED Bhatt DL Cannon CP Hernandez AF Fonarow GC Get With the Guidelines Scientific Advisory Committee and Investigators. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes.Circulation. 2012; 126: 65-75Crossref PubMed Scopus (611) Google Scholar, 16Chang PP Wruck LM Shahar E Rossi JS Loehr LR Russell SD Agarwal SK Konety SH Rodriguez CJ Rosamond WD. Trends in hospitalizations and survival of acute decompensated heart failure in four US communities (2005-2014): ARIC Study Community Surveillance.Circulation. 2018; 138: 12-24Crossref PubMed Scopus (118) Google Scholar, 17Tsao CW Lyass A Enserro D Larson MG Ho JE Kizer JR Gottdiener JS Psaty BM Vasan RS. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction.JACC Heart Fail. 2018; 6: 678-685Crossref PubMed Scopus (201) Google Scholar, 18Gerber Y Weston SA Redfield MM Chamberlain AM Manemann SM Jiang R Killian JM Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010.JAMA Intern Med. 2015; 175: 996-1004Crossref PubMed Scopus (459) Google Scholar These trends would affect the distribution of HF types over time and could help explain our findings. Nevertheless, it is possible that our observational methods have resulted in the inclusion of individuals in the HFpEF group who do not actually have HF. If so, our cost estimates for the HFpEF would likely be too low, suggesting that our per-person comparisons to HFrEF are conservative. The adjusted mean annualized costs we report ($27,669 for patients with HFrEF, $29,484 for HFmrEF, and $33,740 for HFpEF) are modestly higher than the previously published estimates. For example, Klein et al3Klein S Jiang S Morey JR Pai A Mancini DM Lala A Ferket BS. Estimated health care utilization and expenditures in individuals with heart failure from the medical expenditure panel survey.Circ Heart Fail. 2021; 14e007763Crossref Scopus (1) Google Scholar used Medical Expenditure Panel Survey data from 2012 to 2017 and found a total health expenditures of $21,177 (2017 dollars) among patients with HF. However, another study using Medical Expenditure Panel Survey data from 2002 to 2011 reported a total expenditures of $27,162 in 2010/2011.2Echouffo-Tcheugui JB Bishu KG Fonarow GC Egede LE. Trends in health care expenditure among US adults with heart failure: the Medical Expenditure Panel survey 2002–2011.Am Heart J. 2017; 186: 63-72Crossref PubMed Scopus (44) Google Scholar The discrepancy between these 2 studies using the same data, albeit from different years, illustrates the difficulty in comparing the cost estimates across published studies. Furthermore, our study was limited to newly diagnosed HF, and previous studies have found greater costs among incident versus prevalent cases.5Korves C Eldar-Lissai A McHale J Lafeuille MH Hwa Ong S Sheng Duh M Resource utilization and costs following hospitalization of patients with chronic heart failure in the US.J Med Econ. 2012; 15: 925-937Crossref PubMed Google Scholar,6Liao L Jollis JG Anstrom KJ Whellan DJ Kitzman DW Aurigemma GP Mark DB Schulman KA Gottdiener JS. Costs for heart failure with normal vs reduced ejection fraction.Arch Intern Med. 2006; 166: 112-118Crossref PubMed Scopus (111) Google Scholar Taken together, we conclude our findings are reasonable. A novel feature of our study is the comparison of costs and utilization among patients with HFrEF, HFmrEF, and HFpEF. A previous study directly compared the costs for patients with preserved versus reduced and mildly reduced EF (using a dichotomous EF cut point of 50%) and found no statistically significant difference between these 2 groups.6Liao L Jollis JG Anstrom KJ Whellan DJ Kitzman DW Aurigemma GP Mark DB Schulman KA Gottdiener JS. Costs for heart failure with normal vs reduced ejection fraction.Arch Intern Med. 2006; 166: 112-118Crossref PubMed Scopus (111) Google Scholar Another recent study examined the costs over a median 18 months after an HF hospitalization and reported monthly costs of $11,053 for HFrEF and $7,482 for HFpEF.7Lam CSP Wood R Vaduganathan M Bueno H Chin A Luporini Saraiva G Sörstadius E Tritton T Thomas J Qin L Contemporary economic burden in a real-world heart failure population with Commercial and Medicare supplemental plans.Clin Cardiol. 2021; 44: 646-655Crossref PubMed Scopus (6) Google Scholar These extremely high costs suggest a population that is not representative of all patients with HF. Still, another study of patients with HF found that in the 2-year period after an HF hospitalization, those with HFrEF incurred higher costs per month alive than HFpEF.8Olchanski N Vest AR Cohen JT DeNofrio D. Two-year outcomes and cost for heart failure patients following discharge from the hospital after an acute heart failure admission.Int J Cardiol. 2020; 307: 109-113Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar On the contrary, our data suggest that patients with HFpEF accrue greater resource utilization and medical costs than patients with either HFrEF or HFmrEF. Our study evaluated a more general HF population, which may account for the differences. Furthermore, our finding is consistent with a previous study in the current setting that focused on health care utilization and found significantly greater outpatient and emergency room visits among patients with HFpEF; although, the absolute differences were small.19Nichols GA Reynolds K Kimes TM Rosales AG Chan WW. Comparison of risk of re-hospitalization, all-cause mortality, and medical care resource utilization in patients with heart failure and preserved versus reduced ejection fraction.Am J Cardiol. 2015; 116: 1088-1092Abstract Full Text Full Text PDF PubMed Google Scholar The present results are important because of the rising prevalence of HFpEF relative to HFrEF,15Steinberg BA Zhao X Heidenreich PA Peterson ED Bhatt DL Cannon CP Hernandez AF Fonarow GC Get With the Guidelines Scientific Advisory Committee and Investigators. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes.Circulation. 2012; 126: 65-75Crossref PubMed Scopus (611) Google Scholar, 16Chang PP Wruck LM Shahar E Rossi JS Loehr LR Russell SD Agarwal SK Konety SH Rodriguez CJ Rosamond WD. Trends in hospitalizations and survival of acute decompensated heart failure in four US communities (2005-2014): ARIC Study Community Surveillance.Circulation. 2018; 138: 12-24Crossref PubMed Scopus (118) Google Scholar, 17Tsao CW Lyass A Enserro D Larson MG Ho JE Kizer JR Gottdiener JS Psaty BM Vasan RS. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction.JACC Heart Fail. 2018; 6: 678-685Crossref PubMed Scopus (201) Google Scholar, 18Gerber Y Weston SA Redfield MM Chamberlain AM Manemann SM Jiang R Killian JM Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010.JAMA Intern Med. 2015; 175: 996-1004Crossref PubMed Scopus (459) Google Scholar suggesting that the overall burden of HF may be greater than previous forecasts. The greater costs among HFpEF in this age-adjusted analysis were driven, in part, by a higher prevalence of T2D and CKD, both of which are common co-morbidities of HF and are known to drive substantial medical costs.20American Diabetes AssociationEconomic costs of diabetes in the U.S. in 2017.Diabetes Care. 2018; 41: 917-928Crossref PubMed Scopus (1349) Google Scholar,21US Renal Data SystemUS Renal Data System 2018 Annual Data Report: Chapter 7: Healthcare expenditures for persons with CKD.Am J Kidney Dis. 2019; 73: S133-S158Google Scholar Indeed, our data show that treatment for patients with CKD or T2D was more costly than for those with neither condition and substantially greater when both were present. However, CKD and T2D were only modestly more common in HFpEF, and HFpEF was more costly regardless of the presence of CKD and/or T2D. Thus, our finding that the medical costs were greater among HFpEF than HFrEF was robust across 2 of the most common and costly co-morbidities of HF. Based on the same database study, we have previously reported that the clinical outcomes, such as HF hospitalization, mortality, and CKD incidence, were greater in patients with HFrEF than in those with HFpEF, but the larger size of the HFpEF group generated 4.7 to 6.7 times as many total outcomes.22Nichols GA Qiao Q Déruaz-Luyet A Kraus BJ. The clinical burden of newly diagnosed Heart failure among patients with Reduced, mildly Reduced, and preserved ejection fraction.IJC Heart Vasc. 2023; (In press)101182https://doi.org/10.1016/j.ijcha.2023.101182Crossref Scopus (1) Google Scholar In this study, we now confirm that health care costs increase with the number of co-morbidities but show for the first time that the burden at the time of diagnosis was comparable across HF groups. Taken together, our data suggest that HFpEF and its co-morbidities, such as T2D and/or CKD, pose a significant health economic burden at both patient and societal levels because of the high prevalence and rising incidence of HFpEF. Recently, sodium-glucose cotransporter-2 inhibitors have been indicated by HF management guidelines for the treatment of HF across the range of EF to reduce HF hospitalizations and cardiovascular mortality.23Heidenreich PA Bozkurt B Aguilar D Allen LA Byun JJ Colvin MM Deswal A Drazner MH Dunlay SM Evers LR Fang JC Fedson SE Fonarow GC Hayek SS Hernandez AF Khazanie P Kittleson MM Lee CS Link MS Milano CA Nnacheta LC Sandhu AT Stevenson LW Vardeny O Vest AR Yancy CW. 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.Circulation. 2022; 145: e876-e894PubMed Google Scholar Implementation of these guidelines in clinical practice may translate the benefits shown in large HF outcomes trials into relevant per-person and health economic value. Because sodium-glucose cotransporter-2 inhibitors not only reduce HF outcomes but also slow the progression of CKD and are indicated to treat T2D, they may help improve clinical outcomes and reduce the cost of care in the individual and population level, regardless of EF and/or the presence of co-morbidities. Due to the observational design, our study has unavoidable limitations. We intentionally adjusted our models for age and gender only. Although other variables could account for some of the results, the risk factor and co-morbidity differences between EF groups are characteristics of the HF type so it would be inappropriate to adjust for them. Furthermore, as noted previously, our findings were consistent in the presence or absence of CKD and T2D. Nevertheless, differential levels of other co-morbidities could impact our findings. We cannot rule out residual confounding from variables beyond age and gender, especially given the high level of co-morbidity in patients with HF. Because this was a retrospective study, we could not include the many data elements that a clinical trial would collect. As previously mentioned, we excluded patients without an available echocardiogram, which could have affected the relative differences between HF types. The excluded patients may have had other measures of EF that were not included in our data. EF cutoffs for categorization vary between guidelines, and we followed the recommendations of the new universal definition of HF.9Bozkurt B Coats AJS Tsutsui H Abdelhamid CM Adamopoulos S Albert N Anker SD Atherton J Böhm M Butler J Drazner MH Michael Felker G Filippatos G Fiuzat M Fonarow GC Gomez-Mesa JE Heidenreich P Imamura T Jankowska EA Januzzi J Khazanie P Kinugawa K Lam CSP Matsue Y Metra M Ohtani T Francesco Piepoli M Ponikowski P Rosano GMC Sakata Y Seferović P Starling RC Teerlink JR Vardeny O Yamamoto K Yancy C Zhang J Zieroth S Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.Eur J Heart Fail. 2021; 23: 352-380Crossref PubMed Scopus (357) Google Scholar Because we do not account for previous EF at inclusion to differentiate between patients with HFpEF progressing to HFrEF and patients with previous HFrEF who have recovered, the group with HFmrEF is not very well characterized. This may, at least, partially explain the intermediate phenotype of this mildly reduced EF group in (some but not all) population-based studies and hampers interpretation. Nevertheless, the results for the HFmrEF typically were between the HFrEF and HFpEF groups. Another limitation is that some misclassification may have occurred because estimating the EF assessed from echocardiograms is imprecise. Finally, the study site is an integrated delivery system located in Portland, Oregon, with enrollees that are predominantly White and have lower minority representation than in other parts of the country. However, the characteristics of the KPNW membership are representative of the service area.24Sukumaran L McCarthy NL Li R Weintraub ES Jacobsen SJ Hambidge SJ Jackson LA Naleway AL Chan B Tao B Gee J. Demographic characteristics of members of the Vaccine Safety Datalink (VSD): a comparison with the United States population.Vaccine. 2015; 33: 4446-4450Crossref PubMed Scopus (54) Google Scholar In conclusion, we found that health care utilization in patients with HF was the highest for all EF groups when both T2D and CKD were present. Interestingly, patients with HFpEF incurred significantly greater inpatient, outpatient, emergency, pharmaceutical, and total medical care costs than patients with HFrEF or HFmrEF, regardless of whether a patient was affected by common co-morbidities, such as CKD or T2D. Not only was the mean economic burden greater per HFpEF patient, but the substantially greater prevalence of HFpEF resulted in this group accounting for the large majority of the total HF costs. These findings underscore the urgency to implement guideline-recommended treatments targeting HF and its co-morbidities. Dr. Nichols has received research funding from Boehringer Ingelheim and Bristol-Myers Squibb. Qiao, Linden, and Kraus are employees of Boehringer Ingelheim. Dr. Nichols had the final say in all decisions regarding content and decision to publish. The remaining authors have no conflicts of interest to declare." @default.
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• W4377013093 title "Medical Costs of Chronic Kidney Disease and Type 2 Diabetes Among Newly Diagnosed Heart Failure Patients With Reduced, Mildly Reduced, and Preserved Ejection Fraction" @default.
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