IJC Heart & Vasculature 26 (2020) 100444 Contents lists available at ScienceDirect IJC Heart & Vasculature journal homepage: www.journals.elsevier.com/ijc-heart-and-vasculature Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation? Agra Bermejo Rosa a,b,⇑, Pascual-Figal Domingo b,d, Gude Sampedro Francisco b,c, Delgado Jiménez Juan b,e, Vidal Pérez Rafael a,b, Gómez Otero Inés a,b, Ferrero-Gregori Andreu b,f, Álvarez-García Jesús b,f, Worner Diz Fernando g, Segovia Jesús b,h, Crespo-Leiro María Generosa b,i, Cinca Cuscullol Juan b,f, Fernández Avilés Francisco b,j,k, Gónzalez-Juanatey Jose Ramón a,b, Red Española de Insuficiencia Cardiaca researchers (REDINSCOR II) c a Cardiology Department, Complejo Hospital Universitario de Santiago, Santiago de Compostela, Spain b Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV CB16/11/00226 - CB16/11/00420), Spain c Clinical Epidemiology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain d Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, Facultad de Medicina, Universidad de Murcia, CIBERCV, Murcia, Spain e Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain f Servicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain g Servicio de Cardiologia, Hospital Arnau de Vilanova, Lleida, Spain h Servico de Cardiologia, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain i Complexo Hospitalario Universitario A Coruña (CHUAC), Instituto de Investigación Biomédica de A Coruña (INIBIC), Universidad de A Coruña (UDC), A Coruña, Spain j Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain k Cardiology Department, University Hospital Gregorio Marañón, Madrid, Spain a r t i c l e i n f o a b s t r a c t Article history: Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known Received 15 July 2019 especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission Received in revised form 16 October 2019 HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on Accepted 8 November 2019 long- term outcomes. Available online 4 December 2019 Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used Keywords: to estimate the association between admission HR, discharge HR and HR difference and one- year all- Heart rate Acute heart failure cause mortality and HF readmission. Sinus rhythm Results: The mean age of the study population was 72 ± 12 years. Of these, 594 (42.4%) were female, 655 Atrial fibrillation (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had Mortality sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR) = 1.182, confidence interval (CI) 95% 1.024–1.366, p = 0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR = 1.276, CI 95% 1.115–1.459, p  0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients. Ó 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction condition requiring urgent evaluation and treatment, typically leading to urgent hospital admission [1]. Despite improvements Acute heart failure (AHF) refers to the rapid onset or worsening in the treatment and outcome of chronic heart failure (HF), those of symptoms and/or signs of HF [1]. It is a life-threatening medical for AHF have remained relatively unchanged for the last 30 years [2,3]. Much of this lack of progress can be attributed to imperfect ⇑ Corresponding author at: Cardiology Department, Complejo Hospital Universi- characterization and understanding of the physiopathology of tario de Santiago, Santiago de Compostela, Spain. CIBERCV, Travesía da Choupana AHF [4,5]. s/n, Santiago de Compostela, 15706 A Coruña, Spain. E-mail address: rosinagra@msn.com (A.B. Rosa). https://doi.org/10.1016/j.ijcha.2019.100444 2352-9067/Ó 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2 A.B. Rosa et al. / IJC Heart & Vasculature 26 (2020) 100444 Elevated resting heart rate (HR) has been associated with nation, the rhythm at the time of admission, serum laboratory increased mortality in the general population [6] as well as in those tests, pharmacological and no pharmacologic interventions, in- with coronary artery disease [7,8]. Similar findings have been hospital outcomes, and discharge information. In addition, blood reported in patients with HF, although most of these studies exam- samples were obtained for local laboratory analysis and left ven- ined patients with chronic HF [9,10]. tricular ejection fraction (LVEF) was estimated using Simpson’s The prognostic impact of HR in AHF is less well studied and also method according to current international recommendations few studies have included AHF patients with atrial fibrillation (AF) [19]. HF was defined as being ischemic in aetiology if any of the fol- or had sufficient power to evaluate potential time-dependent dif- lowing criteria were satisfied: prior admission because of an acute ferences in the relationship between HR and outcomes [11]. coronary event (acute myocardial infarction or unstable angina), A recent large retrospective study suggested that higher HR was prior surgical or percutaneous myocardial revascularization, the independently associated with higher in-hospital mortality in AHF presence of myocardial infarction on electrocardiogram or patients [12]. Higher HR in AHF patients presenting to the emer- echocardiogram, or significant coronary disease detected by gency department also predicted higher 7-day mortality [13]. angiography. These observations lead to the inclusion of admission HR in risk Heart rhythm was electrocardiographically determined. HR was scores for the assessment of short-term prognosis in AHF [14,15]. determined in conformance with the local protocol for obtaining Despite the importance of HR as a predictor of clinical outcomes vital signs. In all patients, heart rate was electrocardiographically for patients with sinus rhythm [16], limited information about the or telemetrically determined. Heart rate difference (HRD) was relationship of HR (or the change in HR) to post-discharge out- defined as the difference between admission HR less discharge HR. comes is known in patients with AF and AHF [15]. Also whether early HR reduction improves outcomes in patients 2.3. Follow-up hospitalized with AHF is not clear because a recent study sug- gested the change in HR during hospitalization was a stronger pre- In addition to clinical follow-up adjusted to the patient’s needs, dictor of the risk of future cardiac events in patients with AHF vital status and events were gathered by telephone interview at 1, compared with other markers, in patients receiving beta-blockers 3, and 6 months, and at 1 year, if there was no in-person visit at [17]. those time points. Patients who died during the hospitalization The aim of our study was to evaluate the prognostic value of HR index were excluded (Supplementary Fig. 1). The outcomes for this at admission, HR at discharge and heart rate difference (HRD) in analysis were all-cause mortality and HF readmission one-year AHF patients with sinus rhythm (SR) and AF on long-term after discharge. outcomes. 2.4. Statistical analysis 2. Material and methods Quantitative variables are expressed as mean ± SD and qualita- tive variables are expressed as frequency (percentage). Qualitative 2.1. Study population variables were compared using the chi-square test or the Fisher exact test, and quantitative variables were compared by the Stu- We included patients from a national multicentre, prospective dent t-test. registry (REDINSCORII), which includes input from as many as 20 Logistic regression models were used to evaluate the relation- Spanish hospitals of varying complexity. The registry was compiled ship between the outcomes (one-year mortality and one-year consecutively between October 2013 and December 2014 and heart failure readmission) with HR (at admission, post-discharge included a total of 1831 patients admitted with acute HF. The or difference). We fit unadjusted and adjusted models separately REDINSCORII registry did not include any participants from the in SR and AF patients. Adjusted models included age, gender, pre- previous REDINSCOR I study, which examined patients with vious HF, NT-proBNP levels, LVEF, history of diabetes, betablockers chronic HF recruited during cardiology consultations [18]. The at discharge, ischemic HF, creatinine levels at admission, sodium study complies with the Declaration of Helsinki, ethics committees levels at admission, haemoglobin levels at admission, body mass at the participating hospitals approved the study, and all patients index (BMI) and systolic blood pressure at admission. We studied gave written informed consent. the possible nonlinear effect of each predictor on the outcome, Patients in the registry were older than 18 years and were hos- by means of Generalized Additive Regression models (GAM) using pitalized in the cardiology unit for at least 24 h; the main reason penalized regression splines [20]. Crude and adjusted relative risks for admission was the presentation of symptoms compatible with (RR) and 95% confidence intervals (CI) for a 10-unit increment in AHF, both de novo and decompensated, and a chest X-ray indicat- HR were calculated. Interactions were also assessed to study the ing pulmonary congestion. relationship between post-discharge-HR and mortality (and HF Exclusion criteria included ST-elevation acute coronary syn- readmission) according to LVEF groups (lower or higher than 40%). drome, an end-stage disease with a life expectancy <1 year, and Single-variable Cox models were used to evaluate association in any condition likely to preclude follow-up. Patients with missing both groups (SR and AF) between the all-time risk of death and of baseline electrocardiograms or in paced rhythm were excluded. heart failure readmission and post-discharge HR. Taking data cen- HF diagnostic was made according to the 2012 European Society soring into account, the log hazard ratios of the unadjusted Cox of Cardiology HF guidelines [1]. The population was divided models were used as criterion variables X to construct time- according to the rhythm in two groups: sinus rhythm or atrial fib- dependent Receiver Operating Curves (ROCs) [21] via the corre- rillation. The flowchart of the patients of the study is shown in Sup- sponding sensitivity and specificity functions: for given time t plementary Figure 1. and criterion threshold c, sensitivity (c, t) = P(X > c|T  t); speci- ficity(c,t) = P(X  c|T > t), where T is survival time. For each time 2.2. Study variables t, the area under the time-dependent ROC [AUC(t)] was calculated. To deal with missing values, we performed a missing data anal- Data collected for each AHF patient include demographics, ysis [22]. After assuming that these values were missing at ran- medical/surgical history including any history of AF, admission dom, multiple imputations by chained equations were used. The medications, admission and discharge vital signs, physical exami- main reasons for missing data were the lack of NT-proBNP levels A.B. Rosa et al. / IJC Heart & Vasculature 26 (2020) 100444 3 (459 patients, 30.2%), LVEF (333, 21.9%), BMI (253, 16.6%), ischemic 4. Prognostic effect of admission HR, discharge HR and HRD on HF (193, 12.7%), and betablockers at discharge (43, 2.8%), or for one year outcomes in SR patients. other information (<1%). Statistical analyses and graphics were carried out in R using the Crude and adjusted models observed that according to regres- packages ‘‘mgcv”, ‘‘mice”, ‘‘survival”, ‘‘survivalRoc”, ‘‘voxel” and sion analysis only discharge HR was associated with all cause ‘‘ggplot2”. These packages are freely available at http://cran.r-pro- one- year mortality (RR = 1.182, CI: 1.024–1.366, p = 0.022) ject.org. Differences were considered statistically significant at (Table 1). However it did not have impact on HF readmission P < 0.05 (RR = 1.027, CI: 0.914–1.155, p = ns). It was also found that age, systolic blood pressure at admission; creatinine, sodium, and NT- 3. Results proBNP levels were predictors of one year all cause mortality (Sup- plementary Table 5). 3.1. Baseline characteristics A prognostic effect of admission HR or HRD on HF readmission was not found (Table 1). Previous HF was associated with one-year The final cohort of the population included 1398 patients and HF readmission (Supplementary Table 5). their characteristics are summarized in supplementary Table 1. The mean age of the analyzed study population was 72 ± 12 years. 5. Prognostic effect of admission HR, discharge HR and HRD on Of these, 591 (42.4%) were female. The most frequent risk factor one year outcomes in AF patients was hypertension, affecting 1081 patients (77.6%); 652 patients (46.8%) had diabetes. More than half the patients (776; 55.7%) In the same analysis we found that in AF patients discharge HR had a previous HF diagnosis and the mean LVEF was 45 ± 17%. was associated with all cause one-year mortality (RR = 1.276, CI Among all included patients, 742 (53.3%) had sinus rhythm and 1.115–1.459, p  0.001) (Table 2) with no effect on HF readmission 651 (46,7%) had atrial fibrillation. (RR = 0.938, CI 95%, 0.835–1.053, p = ns) (Table 2). In this group of The two groups differed significantly in sex, diabetes mellitus, patients also diabetes mellitus, age, betablockers prescribed at dis- ischemic aetiology, LVEF, body mass index and in admission HR, charge (OR = 0.51, CI 95% 0.320–0.800), creatinine, hemoglobine discharge HR and HRD. Overall patients with SR were more fre- and NT-proBNP levels were associated with one year all cause mor- quently prescribed angiotensin-converting enzyme inhibitors tality (Supplementary Table 6). (ACEIs), mineralocorticoid receptor antagonists (MRAs), and sta- As in SR patients a prognostic effect of admission HR or HRD on tins; patients with AF received more frequently digoxin and cal- one year all cause mortality or HF readmission (Table 2) was not cium channel blockers. found. However, age, haemoglobin and creatinine, levels were pre- dictors of one year HF readmission in this group of patients (Sup- 3.2. Sinus rhythm group plementary Table 6). There were 745 patients in the SR group. The mean discharge 6. Relationship with left ventricular ejection fraction HR was 72 ± 13 beats per minute (range 40–127 bpm) and the patients were classified into four groups according to the discharge A significant linear relationship was found between discharge- HR (Q1 = 40–63 bpm, Q2 = 63–70 bpm, Q3 = 70–80 bpm, Q4 = 80– HR and mortality in both LVEF groups (LVEF < 40%, LVEF > 40%) 127 bpm). Patients with lower HR at discharge (Q1, Q2) had higher The prognostic value is not dependent on LVEF having the highest LVEF, higher doses of amiodarone prescription and lower doses of predictive value in AF patients (Figure 1). Discharge HR was not diuretics compared with patients with higher HR at discharge (Q3, found to be associated with one-year HF readmission neither in Q4). Also, patients with lower HR at discharge had lower HR at SR nor AF patients. admission (78 ± 22 vs 92 ± 18 bpm, p < 0.001) and higher HR differ- ence (21 ± 22 vs 1 ± 20 bpm, p < 0.001). We did not find differences 6.1. Time-dependent prognostic value in the betablockers or digoxin prescription (Supplementary Table 2). We also performed time- dependent AUC (area under curve) to determine the effect of discharge HR during the 12 months after dis- 3.3. Atrial fibrillation group charge. In both rhythms, the highest AUC is observed during the first month postdischarge (Figure 2). However during the follow up dis- There were 653 patients in the AF group. The mean discharge charge HR has higher predictive value in AF compared with SR. HR was 74 ± 15 bpm (range 38–140 bpm). The patients were divided into four groups according to the discharge HR (Q1 = 38– 7. Discussion 64 bpm, Q2 = 64–73 bpm, Q3 = 73–84 bpm, Q4 = 84–140 bpm). The main differences between were found in terms QRS duration In this analysis of patients with AHF enrolled in the REDIN- (Q1 = 117 ± 33 vs. Q4 = 102 ± 26 ms, p < 0.001) and HRD difference SCORII multicentre Registry, we observed that only discharge HR (Q1 = 37 ± 32 vs Q4 = 9 ± 24 bpm, p < 0.001). Patients in Q4 were is associated with one-year mortality in SR and AF patients but prescribed more frequently on digoxin and calcium channel block- not admission HR or HR difference. The magnitude of the associa- ers and less on ACEIs. These results are shown in Supplemenatary tion is greater in AF patients, especially in the first months post dis- Table 3. charge. This relationship is not dependent on LVEF. We demonstrated that there is a linear relationship between discharge 3.4. Long-term follow up HR and mortality in AHF patients with AF suggesting that the lower discharge HR the better outcomes. Indeed, we did not observe HR The one-year all cause mortality was 17.2% (153 patients) in the effect of one- year HF readmission. Our results suggest that in AHF SR group and 22.20% (145 patients) in the AF group (p = 0.285). The only discharge HR should be considered as a therapeutic target in one-year HF readmission was 32.1% (229 patients) in the SR group this population. Several measures aimed to optimize HR at hospital and 31.8% (199 patients) in the AF group (p = 0.910). The baseline discharge, including guideline recommended medications that characteristics are described in supplementary Table 4. need to be started during hospital stay especially, in AF patients. 4 A.B. Rosa et al. / IJC Heart & Vasculature 26 (2020) 100444 Table 1 Prognostic impact of admission HR, discharge HR and HRD on long -term outcomes in sinus rhythm patients. All cause one year mortality RR, CI 95% P RR, CI 95% p HR admission 1.005 (0.928–1.089) 0.896 1.064 (0.971–1.165) 0.182 HR discharge 1.155 (1.020–1.307) 0.022 1.182 (1.024–1.366) 0.022 HR difference 0.950 (0.860–1.050) 0.212 0.995 (0.911–1.088) 0.917 One year HF readmission RR, CI 95% p RR, CI 95% p HR admission 0.927 (0.862–0.997) 0.041 0.970 (0.895–1.050) 0.447 HR discharge 1.028 (0.922–1.146) 0.621 1.027 (0.914–1.155) 0.651 HR difference 0.924 (0.861–0.990) 0.025 0.962 (0.892–1.037) 0.311 CI: confidence interval; HF: heart failure; HR: heart rate; RR: relative risk *Adjusted by sex, age, ischemic heart failure, previous HF, creatinine levels, haemoglobin levels, sodium levels, body mass index, left ventricular ejection fraction, NT-proBNP levels, betablockers at discharge, diabetes mellitus, systolic blood pressure at admission. Table 2 Prognostic impact of admission HR, discharge HR and HRD on long-term outcomes in atrial fibrillation patients. All cause one year RR, CI 95% p RR, CI 95% p mortality HR admission 0.909 (0.848–0.973) 0.006 1.003 (0.995–1.012) 0.460 HR discharge 1.214 (1.082–1.362) <0.001 1.276 (1.115–1.459) <0.001 HR difference 0.863 (0.806–0.924) <0.001 0.946 (0.874–1.024) 0.169 One year HF readmission RR, CI 95% p RR, CI 95% p HR admission 0.918 (0.865–0.975) <0.001 0.953 (0.888–1.024) 0.188 HR discharge 0.931 (0.836–1.036) 0.190 0.938 (0.835–1.053) 0.277 HR difference 0.946 (0.896–1.000) 0.0504 0.980 (0.919–1.046) 0.548 CI: confidence interval; HF: heart failure; HR: heart rate; RR: relative risk. *Adjusted by sex, age, ischemic heart failure, previous HF, creatinine levels, haemoglobin levels, sodium levels, body mass index, left ventricular ejection fraction, NT-proBNP levels, betablockers at discharge, diabetes mellitus, systolic blood pressure at admission. Fig. 1. Effect of post-discharge heart rate on one year all cause mortality, cardiovascular mortality and heart failure readmission in sinus rhythm (A) and atrial fibrillation (B) patients. The role of HR as a prognostic predictor in chronic and acute follow-up; and a 5 bpm increment in the first week post-discharge worsened HF patients has been evaluated in a number of studies was associated with an increase of overall mortality [24]; discharge summarized in a recent paper published by Oliva et al. [23]; even HR was also associated with higher mortality in the ASCEND-HF though there is a relative paucity of data on the role of HF at dis- trial, where no significant interaction effect was observed between charge after a phase of clinical instability both in patients with SR HR at discharge and mortality with beta-blocker therapy at dis- or AF. The EVEREST trial examined 1947 patients with SR and left charge [25]. ventricular systolic dysfunction who had been admitted for AHF, For the first time we described that in real life patients dis- in the early pre-discharge increases of HR > 70 bpm have been charge HR is associated with one year all cause mortality in SR shown to be an independent predictor of mortality during the early and AF patients. In SR every increase of 10 bpm increases 18% A.B. Rosa et al. / IJC Heart & Vasculature 26 (2020) 100444 5 As previous studies, we found that admission HR did not have predictive value with long-term events [24,28]. Such discrepancy could be explained by the fact that at admission HR represents a marker of the severity of temporary hemodynamic conditions and may be therefore a predictor of early, as compared to late, adverse events [23]. We could not observe the effect of HR on one-year HF readmis- sion. The prognostic impact of HR in early HF readmission has been described [26], however, the impact of HR in long term HF read- mission is not well known and unfortunately, our results could not clarify this question. We also found a beneficial effect of betablockers in SR and AF patients. The role of betablockers in SR patients has been well established [1], however, Mareev et al. [27] questioned the use of betablockers in AF and HF patients. Our results reinforced the ben- eficial effect of betablockers in AF patients and they should be pre- scribed according to guidelines recommendations [1] in order to achieve the lower discharge HR especially in AF patients where the benefices of lowering HR are higher than in SR patients. Several studies have evaluated the prognostic role of HR in chronic HF with reduced and preserved ejection fraction with Fig. 2. The area under the time-dependent ROC [AUC(t)] of discharge Heart rate in and without AF [22,23,29,30]. In our study, we described that the sinus rhythm and atrial fibrillation patients. effect of postdischarge HR is not dependent of the LVEF in both SR and AF patients suggesting that lower discharge HR should be acquired in reduced and preserved LVEF patients. Although some studies [23] suggested a J-shaped for HR in the risk of the one-year all cause mortality and in AF every chronic HF patients we studied the possible nonlinear effect of dis- increase of 10 bpm increases 27% the risk of the one year all cause charge HR on the outcome by using penalized regression splines. mortality. However a linear relationship between HR and mortality was Our results are similar to the AHA GWTG-HF prospective reg- found. We must acknowledge some limitations; the REDINSCORII istry that has involved 46,000 patients who have been discharged registry includes patients admitted to Spanish cardiology services after a phase of clinical deterioration, and had found a correlation with decompensated or de novo HF and who were monitored between HR at discharge and the likelihood of re-hospitalizations prospectively for 1 year. Our results are therefore limited to this for all-causes [11]. However in this study, only elderly patients patient category, which is underrepresented in the literature (>65 years) were included, our results are applied to the all AHF because most registries include outpatients with stable chronic population regardless of age. Similar findings were described in a HF or a mix of acute and chronic HF patients. Also given the obser- study performed in the context of the EFFECT-HF program with a vational nature, unobserved variables may exert a confounding significant correlation between HR and early mortality, particularly effect on the results. HR was measured in two time-points: admis- in the subgroup of patients with HR comprised between 81 and sion and discharge; so time until HR control was not taken into 90 bpm (hazard ratio: 1.59) and higher than 90 bpm (hazard ratio: consideration. The evaluated treatments are those prescribed at 1.56) [26]. hospital discharge, and we are therefore also unable to confirm Current European Society of Cardiology HF guidelines do not whether the therapeutic strategy was maintained throughout the have a clear recommendation for heart rate control in AHF with follow-up period, a factor that could influence prognosis. We did AF [1] and ventricular rates <70 bpm are associated with a worse not have information about how many patients who were admit- outcome [27]. We have demonstrated that the lower discharge ted with atrial fibrillation were cardioverted to sinus rhythm. How- HR the better all cause and cardiovascular mortality (Fig. 2) and ever our results showed the impact of HR in a real cohort of maybe the recommendation of HR between 60 and 100 bpm patients with AHF. should be modified. Our data suggest that post-discharge HR can offer an important contribution in terms of the determination of prognosis; nevertheless, it remains to be clarified whether early 8. Conclusions HR reduction could have a positive impact on clinical events in AHF patients. Also, we observed that the prognostic value is higher In a cohort of AHF patients, only high discharge HR is associated in the first months post-discharge so it is reasonable to believe that with worse outcomes in SR and AF patients. Our study suggests post-discharge HR could be an important contribution in the prog- that HR should be optimized with guideline recommended medi- nostic stratifications of patients with a recent episode of worsening cations in the transition from hospital to ambulatory care in the HF. community especially in AF patients. To our knowledge, only a small single center registry analyzed the prognostic impact of HR changes during hospital admission in patients with AHF. Takahama et al described in this single hos- Funding pital registry of 421 patients that HR reduction (27 bpm during in-hospital stay) was associated with a significantly lower cardiac Nothing to declare. event rate, isolated HR at discharge was not associated with the prognosis [17]. In our study we did not observe a relationship between HRD and outcomes between SR or AF patients hospi- Declaration of Competing Interest talised for worsening HF; suggesting that only discharge HR should be considered as a therapeutic target in this population. We declare that we have no conflict of interest. 6 A.B. Rosa et al. / IJC Heart & Vasculature 26 (2020) 100444 Appendix A. Supplementary material [13] D.S. Lee, A. Stitt, P.C. Austin, T.A. Stukel, M.J. Schull, A. Chong, G.E. Newton, J.S. Lee, J.V. Tu, Prediction of heart failure mortality in emergent care: a cohort study, Ann. Intern. Med. 156 (2012) 767–775. Supplementary data to this article can be found online at [14] W.T. Abraham, G.C. Fonarow, N.M. Albert, W.G. Stough, M. Gheorghiade, B.H. https://doi.org/10.1016/j.ijcha.2019.100444. Greenberg, C.M. O’Connor, J.L. Sun, C.W. Yancy, J.B. Young, OPTIMIZE-HF Investigators and Coordinators. 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