In this study, we found that impaired renal function before discharge was independently associated with poor clinical outcomes in Chinese patients with ADHF. However, WRF during hospitalization was not related to clinical outcomes in these patients.
Renal function impairment and outcomes in patients with ADHF
Renal function impairment, which is common in patients with ADHF, is associated with poor clinical outcomes in these patients.4, 22 In the CRIC study,4 focusing on a large US CKD population, the rate ratio for HF re-hospitalization within 30 days was 2.6- and 1.9-fold higher in eGFR 30–44 and <30 mL/min/1.73m2, respectively, compared with eGFR ≥45 mL/min/1.73m2. Heywood et al.22 reported that renal dysfunction at admission was associated with higher in-hospital mortality in 118,465 patients hospitalized with ADHF. In the present study, we found that impaired renal function before discharge, defined as eGFRpredischarge <60 mL/min/1.73m2, was associated with poor outcomes in patients with ADHF, which were mostly driven by nonfatal HF. Although patients with impaired renal function had more comorbidities than those with preserved renal function, the findings were still consistent after adjusting for baseline comorbidities, including HTN, DM, and IHD. Interestingly, cardiac biomarkers, including troponin-I and NT-pro-BNP, were similar in patients with preserved and impaired renal function. The findings suggest that renal function itself, rather than comorbidities or the severity of HF, is related to clinical outcomes in patients with ADHF.
Definitions of WRF
WRF is commonly observed in patients hospitalized for ADHF, either on admission or during hospitalization. The definitions of WRF vary among different studies. Some were defined by increased levels of creatinine;7, 9–12, 14–16 some were defined by an increased percentage of creatinine;8 and some were defined by both.5, 6, 13 Recently, eGFR (calculated using the CKD-EPI formula) has been used to define WRF.17, 18 In the present study, we used eGFR (calculated using the MDRD formula) to evaluate changes in renal function during hospitalization, which had better performance than creatinine and is commonly used in our clinical practice.21 Using this definition, WRF during hospitalization was noted in 41 (34.5%) of 119 patients, which meant that nearly two-thirds of the patients could have preserved or improved renal function after decongestion therapy. Interestingly, WRF was not associated with comorbidities in these patients. However, it was related to more diuretic use and less digitalis use before discharge in these patients.
Impacts of WRF on clinical outcomes in patients with ADHF
The impact of WRF during hospitalization for ADHF has been examined in numerous studies. Some studies have reported that WRF is associated with worse long-term outcomes. Gottlieb et al.5 reported that any WRF predicted increased in-hospital mortality and prolonged hospital stays in patients hospitalized for HF. In the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial,7 WRF was associated with a higher rate of 6-month mortality (37.9% vs. 18.8%, P<0.001) and length of hospitalization (11.8 ± 9.1 days vs. 8.3±7.1 days, P<0.001) in patients with HF. In the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) registry,9, 10 WRF was associated with a higher rate of 30-day readmission (21.8% vs. 20.6%; P=0.01), 30-day mortality (10.0% vs. 7.2%, P<0.001), and 1-year mortality (HR, 1.12; 95% CI, 1.04–1.20, P=0.003) after HF admission. A prospective study of ADHF showed that patients with WRF had a poorer outcome, defined as re-hospitalization and post-discharge death, compared with patients without WRF (HR, 1.12; 95% CI, 1.02–1.22; P=0.015).11 Berra et al.12 reported that WRF was strongly associated with a higher risk of death or readmission within 1 year after discharge in patients hospitalized for HF (HR, 1.24; 95% CI, 1.06–1.45, P=0.0059). Other related studies have also suggested that HF patients with WRF were likely to have a prolonged length of hospital stay, increased healthcare costs, increased in-hospital mortality, and higher rates of re-hospitalization and post-discharge death.6
In contrast, some studies have demonstrated that WRF is not necessarily associated with clinical outcomes in patients with HF. In a prospective multicenter study,14 patients with WRF had longer duration admissions, but a similar mortality and re-hospitalization rate to those without WRF. In the Diuretic Optimization Strategies Evaluation (DOSE) trial,15 when under high dose diuretic treatment, WRF was not associated with the composite endpoint of death, re-hospitalization, or emergency room visit within 60 days when compared with patients with stable renal function. In the PROTECT study (Placebo-controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function study),16 WRF was found to be associated with longer length of admission and a higher risk of death or readmission for CV or renal reason within 30 days, only in patients who at the time of creatinine measurement were significantly congested. Using data from the Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome and DOSE trials,17 an in-hospital decline in eGFR was not significantly associated with the composite outcome of death or rehospitalization within 60 days; however, a decline in eGFR may be associated with better outcomes when NT-proBNP declined. Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST),18 acute declines in kidney function were associated with an increased risk of mortality and CV outcomes only in those patients who had worsened markers of decongestion. In this study, we found that WRF itself was not associated with CV death, nonfatal MI, nonfatal stroke, nonfatal HF hospitalization, or the composite endpoint of 4P-MACE in patients admitted for ADHF. However, it remains unclear whether WRF results in impaired renal function before discharge, which is related to poor outcomes in these patients.
Race and ethnicity
Racial differences in HF outcomes have been reported in previous studies,25–27 which revealed that black and white patients had worse outcomes than other ethnicities. Data from the National Inpatient Sample (NIS) in the USA revealed that the age-standardized HF hospitalization rate was highest in Blacks, followed by Hispanics, Whites, and Asian/Pacific Islanders; the inpatient mortality was highest for Whites.25 Data from the ARIC Community Surveillance Study26 showed that white patients had a significantly higher mortality at 1 year compared with black patients, and worse renal function served as an independent predictor of mortality in white patients. In a retrospective study involving 53,640 hospitalized HF patients,27 every increase in creatinine of 0.5 mg/dL was associated with a 10% increased risk in adjusted mortality for Blacks, compared with 15% increased risk in Whites.
The prevalence and incidence of CKD in Taiwan are relatively high compared to those in other countries, and it is associated with all-cause mortality in Taiwan.23, 24 In this study, impaired renal function, either upon admission or before discharge, was commonly noted in our patients (84 [70.6%] and 68 [57.1%], respectively). We found that impaired renal function before discharge was associated with up to two times the risk of 4P-MACE (HR, 2.003; 95% CI, 1.072–3.744; P=0.029) in Chinese patients with ADHF. This finding is compatible with the risks reported in the CRIC study,4 which was mainly focused on non-Hispanic Whites and non-Hispanic Blacks. This suggests that the impact of renal dysfunction in Chinese patients is as important as that in white and black patients. Since the relationships between ADHF and renal dysfunction have rarely been reported in the Chinese population, our study provides important information about risk stratification in patients with ADHF.
This study has some limitations. First, this was a single-center study with a small study population. However, this is the first study to comprehensively investigate the association between renal function during hospitalization and clinical outcomes in Chinese patients with ADHF. Further studies with larger sample sizes are required. Second, we did not have information regarding baseline renal function before admission. Since most of the patients were newly diagnosed with HF and were experiencing their first hospitalization, they did not undergo any tests before admission. Furthermore, the study was designed to investigate renal function during hospitalization and clinical outcomes in patients with ADHF; only renal function tests during hospitalization were collected. The findings are more applicable to patients without previous hospital visits, experiencing their first HF hospitalization. Third, serum biomarkers, troponin-I, NT-pro-BNP, and hs-CRP, were only measured once in this study. Therefore, we did not have information regarding the change in NT-pro-BNP, which was used as a marker of decongestion in previous studies.18 Further studies are needed to clarify the impact of biomarkers and their changes on clinical outcomes in this population.