Despite recent advances in medical and device therapies, heart failure (HF) remains a highly prevalent and fatal disease associated with significant morbidity and cost to the healthcare system [1–3]. It is estimated that over 6.5 million adults in the United States (US) currently have HF and with an aging population, and the prevalence is expected to continue to increase for the foreseeable future [1,2,4]. Although HF survival rates have improved, mortality rates remain high at approximately 50% within 5 years following initial diagnosis [2,3]. HF readmission rates are also high, with approximately 25% of patients requiring hospital readmission within 30 days of discharge [5–7]. In 2012, total direct medical costs for HF totaled $21 billion with projections of more than $53 billion by 2030 . As a consequence, there is increased interest in understanding which HF populations may be contributing most to these costs.
Patients with HF are a heterogeneous group with at least two distinct subtypes, namely, patients with reduced ejection fraction (HFrEF) and patients with preserved ejection fraction (HFpEF) [9,10]. Each subtype accounts for about half of all patients with HF, although these proportions vary by population [11,12]. Prior studies have shown HFpEF patients have a wider age range and higher comorbidity burden compared to HFrEF patients [10,13]. In the general population, patients with HFpEF are usually older, have a higher proportion of women, and with higher prevalence of comorbidities such as obesity, coronary artery disease, diabetes mellitus (DM), atrial fibrillation, hypertension, and hyperlipidemia [9,10]. Because of this heterogeneity, incurred hospital expenditures depend on the type of HF, making this information important to payers and other decision makers [13,14].
Having clinical DM markedly increases the likelihood of developing HF [15–17]. In addition, DM rates among patients admitted to the hospital with HF are as high as 42% . The number of US adults aged 18 years or older living with diagnosed DM has increased rapidly from 5.5 million in the 1980s to over 21.9 million in 2014 . In 2017, due to the increasing prevalence in US, DM resulted in an estimated cost of $327 billion ($237 billion in direct costs and $90 billion in reduced productivity) . On average, medical expenditures for patients with DM exceed corresponding expenditures for those without DM by a factor of 2.3. In addition to medical costs, patients with DM incur substantial costs due to reduced and lost productivity and DM-induced disabilities. Furthermore, population-wide economic costs for DM increased by 26% during the 5 years from 2012 to 2017 .
Although prior research has evaluated inpatient expenditures and cost drivers for patients with HF  and patients with DM  independently, few studies have evaluated expenditures, cost drivers, and the relationship between cost and length of hospital stay (LOS) for patients with HF by both subtype (HFrEF vs. HFpEF) and DM status. We therefore sought to evaluate inpatient expenditures and LOS for patients admitted to our hospital with acute decompensated HF.
Our prior article details the population and data collection methods . Briefly, we created a retrospective cohort of consecutively admitted (index hospitalization only) acutely decompensated HF patients [coded with HF-related diagnosis-related group codes 291 (HF and shock with major complication or comorbidity), 292 (HF and shock with a complication or comorbidity), or 293 (HF and shock without a complication or comorbidity)], who were discharged between 1st October 2010 and 30th November 2013 (both dates inclusive). Each patient included was unique and we excluded subsequent hospitalizations for the same patient. We also excluded patients with prior heart transplant or prior left ventricular assist device placement because their costs cannot be generalized to a typical HF population.
For the present analyses, we stratified the cohort by left ventricular ejection fraction (LVEF) into a preserved ejection fraction (HFpEF) group (LVEF >40%) and a reduced ejection fraction (HFrEF) group (LVEF ≤40%), and by their DM status at admission. The LVEF threshold of 40% is typically used to designate patients in US as either HFrEF or HFpEF . Since the European Society for Cardiology defines patients with LVEF between 41 and 49% as mid-range LVEF, we performed a sensitivity analysis that excluded these patients and instead defined HFpEF as LVEF >50% . Combined with the DM status at admission, we had four distinct patient populations – HFrEF with DM, HFrEF without DM, HFpEF with DM, and HFpEF without DM.
We extracted cost information from the Tufts Medical Center cost accounting system, linking patient and admission information to their electronic medical record using medical record numbers and date of admission. We reported total costs, costs by category , and total costs per day for the index hospitalization by type of HF (HFrEF vs. HFpEF) and DM status. Direct cost components included room and board (room and board medical/surgical, room and board ICU, and dietary/housekeeping services), diagnostics (core blood laboratory, radiation oncology, radiology, MRI, and other ancillary diagnostic testing), therapies (operating room, electrophysiology laboratory, and cardiac catheterization laboratory), pharmacy, and others (blood bank and emergency department). We used the medical care services component of the US Consumer Price Index to adjust all costs to 2015 US dollars. Data on reimbursements were not available through the cost accounting system.
We summarized patient demographics, clinical and laboratory characteristics, medications, and discharge disposition for both the total cohort and for each of the four HF subgroups separately. We reported mean and median values for continuous variables and counts with percentages for categorical data. We used Student’s t-test for continuous data and the χ2 test or Fisher’s exact test for categorical data to compare the HF subgroups. For highly skewed continuous data, we log-transformed the data and then used Student’s t-test. All tests were two-sided, with the a priori significance level set at 0.05.
Since costs tend to be skewed, we used generalized linear models with gamma distribution and log-link functions in our multivariable regressions, where costs were the outcome. We adjusted for patient demographics, prior HF history, HF etiology, and whether awaiting heart transplant to estimate adjusted total costs, costs by category, and total costs per day alive for each HF patient subgroup. We selected adjustment variables based on a priori clinical knowledge of what factors would likely affect medical costs, LOS, or both [24,25].
The Tufts Medical Center Institutional Review Board approved this study and waived the requirement for written patient consent because of the study’s retrospective nature. We used SAS version 9.4 software (SAS Institute Inc., Cary, North Carolina, USA) and STATA (Stata Statistical Software: Release 12, version College Station, Texas: StataCorp LP.) to perform all statistical analyses.
Our population had 544 people, of whom 285 (52.4%) were HFrEF patients (124 or 43.5% with DM) and 259 (47.6%) were HFpEF patients (113 or 43.6% with DM). HFpEF patients tended to be older and more likely to be female (Table 1). Among all patients with HF, patients with DM were more likely to have higher BMI and to have comorbidities (hypertension, hyperlipidemia, depression, and dialysis). Patients with DM were also more likely to have a prior history of HF at admission and ischemic etiology for HF. Patients with HFpEF had significantly higher SBP, with HFpEF with DM patients having the highest mean SBP values. A much higher proportion of HFrEF patients had defibrillator/pacemakers than did HFpEF patients, and were much more likely to be listed for heart transplant. BNP levels were much higher among HFrEF patients, with highest mean values seen among those without DM. Sensitivity analyses that omitted mid-range LVEF patients (i.e. LVEF from 41 to 49%) produced results similar to those reported for the main analyses.
Overall LOS was 4.31 ± 3.71 days, with the highest LOS seen among HFrEF patients with DM (5.10 ± 5.21 days) and the lowest LOS seen among HFpEF patients without DM (3.78 ± 3.27 days) (Table 2). Similar patterns were seen for LOS among ICU patients. Although total hospitalization costs were highest for HFrEF patients with DM ($11 576 ± 15 818), HFpEF patients with DM had the highest hospital cost per day alive ($2411 ± 794). Patients with DM tended to have longer LOS and hence higher total hospitalization costs. Furthermore, cost per day alive for patients with DM exceeded corresponding costs for patients without DM. Again, sensitivity analyses with and without mid-range LVEF patients produced results that were similar to the main analysis.
In our multivariable analyses adjusted for age, gender, race, BMI, previous history of HF, etiology of HF, and whether the patient was awaiting heart transplant, HFrEF patients had higher overall costs, with the highest costs seen among patients with DM (Table 3). When controlling for other factors, patients with DM had 20% or $2932 higher overall costs compared with patients without DM (P = 0.002). LVEF status was not a statistically significant predictor, with HFrEF patients having a 2% trend in higher cost compared to HFpEF patients (P = 0.7). In addition, costs per day alive for HFpEF patients exceeded corresponding costs for HFrEF patients, with the highest costs seen among those HFrEF patients with DM. When controlling for other factors, patients with HFrEF had 6% lower cost per day alive compared to those with HFpEF (P = 0.018), and a trend for longer LOS by 0.28 days (P = 0.4), while patients with DM had 7% higher cost per day alive compared with patients without DM (P = 0.007), and longer LOS by 0.88 days (P = 0.009). Room and board expenses were the major cost drivers, with costs for patients with DM exceeding costs for patients without DM. Similarly, patients with DM had higher diagnostic and pharmacy costs than patients without DM. HFpEF patients had higher therapy costs than did HFrEF patients, with costs highest among HFpEF patients with DM (Fig. 1).
Sensitivity analyses that redefined HFpEF to include only those patients with LVEF >50% (rather than all patients with LVEF >40%, as in the main analysis) found no differences in patient demographics, clinical and laboratory characteristics, medications, and discharge disposition (Sensitivity Table 1, Supplemental digital content 1, http://links.lww.com/CAEN/A20) nor did the alternative HFpEF definition substantially influence the trends observed in the main analysis (Sensitivity Table 2, Supplemental digital content 1, http://links.lww.com/CAEN/A20).
Our present study aimed to describe the costs associated with an index acute HF hospitalization stratified by DM and HFrEF vs. HFpEF status. We found that overall costs were higher for patients with DM regardless of HFrEF vs. HFpEF status at admission. As we previously observed, LOS was a major driver for overall index admission cost . Interestingly, cost per day alive (i.e. cost adjusted for LOS) for patients with DM exceeded corresponding costs for patients without DM, with the highest cost per day observed for HFpEF patients with DM. These results extend our prior findings and suggest comorbidities like DM may increase costs for patients with HF.
Patients with HF have been broadly divided into two distinct groups based on their LVEF. The ACC/AHA Guidelines define HFrEF patients to include those individuals with LVEF of ≤40% and HFpEF patients to include those individuals with LVEF ≥50% . Approximately half the patients with HF have HFpEF, although evidence-based treatment strategies for this group are limited when compared to the treatment strategies for HFrEF patients [9–12]. The cutoff of ≤40% has traditionally been used for the definition of HFrEF, for instance, in recent clinical trials examining HF patients .
Patients with HF with a LVEF from 41 to 49% fall into a borderline or intermediate group and appear to have characteristics, treatment patterns, and outcomes similar to those of patients with HFpEF [7,23]. Based on this information, we defined our HFrEF group as having a LVEF ≤40% and our HFpEF group as having a LVEF >40%. To better understand the behavior of the intermediate ejection fraction group in our study, we also performed several sensitivity analyses defining HFpEF to include patients with LVEF ≥50% and HFrEF, but this alternative definition did not substantially influence our results.
DM is a major comorbidity and risk factor for the development of HF [15–17]. In the Framingham Study, DM was an independent risk factor for HF with men with DM having a 2.4-fold and women with DM a five-fold higher risk of HF . In addition, 42% of patients admitted to the hospital in the OPTIMIZE-HF Registry were found to have DM as a significant comorbidity . Our study had similar findings with an observed prevalence for DM in our acute HF population of 44% in both the HFrEF and HFpEF groups. In addition, HF patients with DM have been shown to have a higher mortality and readmission rates when compared to patients without DM [27,28]. These data taken together suggest a potential increased cost and economic burden for patients with HF and DM consistent with our study findings, demonstrating increased cost associated with the diabetic subgroup. In a recent study, the choice of blood glucose-lowering medication also appears to play a major role in the development of HF in patients with DM . Some diabetic drugs (i.e. saxagliptin and rosiglitazone) have been associated with an increased risk of developing HF and HF hospitalizations, whereas others (i.e. dapagliflozin, ertugliflozin, empagliflozin, and canagliflozin) have decreased these events . The sodium glucose cotransporter-2 inhibitors like empagliflozin and canagliflozin provide a new therapeutic strategy that may have an impact on cardiovascular outcomes for patients with HF in addition to the currently approved HF medications [29,30]. Whether these newer diabetic agents will have an impact on decreasing the cost of caring for patients with HF and DM is still to be determined.
This study is subject to the methodological limitations typical of any retrospective cohort study. The cohort and costs are from Tufts Medical Center, an academic teaching hospital, and may not be representative of other healthcare settings, especially community-based hospitals. This is also a relatively small single-center study. Despite this size limitation, the analysis incorporated detailed data on both clinical factors and costs by hospitalization component. Although this study’s cost data comprehensively account for care provided during an inpatient hospitalization at Tufts Medical Center, no attending physician reimbursement were available as part of this study. Inclusion of professional (physician) fees would be expected to add approximately 20% to inpatient costs .
We found that overall costs were higher for patients with DM, whether or not they were admitted with acute HF due to HFrEF or HFpEF. When we indexed admissions to account for LOS, we observed that cost per day alive for patients with DM continued to exceed corresponding costs for patients without DM, with the highest costs observed among HFpEF patients with DM. These findings extend our prior investigations and have implications on our understanding of the economic impact of certain HF comorbidities such as DM.
Conflicts of interest
There are no conflicts of interest.
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