European Journal of Internal Medicine 26 (2015) 357–362
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European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
New onset heart failure — Clinical characteristics and short-term mortality. A RICA (Spanish registry of acute heart failure) study Jonathan Franco a, Francesc Formiga a,⁎, David Chivite a, Luis Manzano b, Margarita Carrera c, José Carlos Arévalo-Lorido d, Francisco Epelde e, Jose Manuel Cerqueiro f, Ana Serrado g, Manuel Montero Pérez-Barquero h, for the RICA investigadors 1 a
Geriatric Unit, Internal Medicine Service, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain Heart Failure and Vascular Risk Unit, Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain c Internal Medicine Service, Complejo Hospitalario de Soria, Soria, Spain d Internal Medicine Service, Hospital Comarcal de Zafra, Zafra, Badajoz, Spain e Short stay Unit, Emergency Service, Hospital Universitari de Sabadell, Corporació Sanitaria Parc Tauli, Department of Medicine, UAB, Sabadell, Barcelona, Spain f Internal Medicine Service, Hospital Lucus Augusti, Lugo Spain g Internal Medicine Service, Hospital Municipal de Badalona, Badalona, Barcelona, Spain h Internal Medicine Service, IMIBIC/Hospital Reina Sofía, Universidad de Córdoba, Spain b
a r t i c l e
i n f o
Article history: Received 28 October 2014 Received in revised form 11 February 2015 Accepted 4 April 2015 Available online 1 May 2015 Keywords: New onset heart failure Chronic heart failure Mortality
a b s t r a c t Background: Heart failure (HF) is a growing global epidemic. The main study aims is to evaluate the differences between new-onset and chronic-decompensated HF patients. Secondary objectives related only to new-onset HF patients include the role of left ventricular ejection fraction (LVEF) and mid-term mortality related risk factors Methods: We analyzed 2190 patients hospitalized for acute HF. We compare the 683 patients with a new-onset HF episode with the rest. Restricting the analysis to the new-onset HF patients, we also compare patients with preserved LVEF (EF N 50%) with those with reduced LVEF, and analyze the factors associated with three-month mortality. Results: A total of 683 (31.2%) patients fulfill the criteria for “new-onset HF”. These patients are older, their HF is more often related to hypertension, show higher blood pressure and heart rate values upon admission, and present with less global and disease-specific comorbidity and better baseline overall functional status. New-onset HF is more often characterized by preserved LVEF, milder baseline NYHA class and lower plasma natriuretic peptide values. After 3 months; 33 (5.2%) new-onset HF patients had died (p b 0.001). Cox multivariate analysis showed a correlation between mortality and older age (hazard ratio – HR – 1.08), higher global comorbidity (HR 1.20) and lesser prescription of beta-blockers at discharge (HR 0.34). LVEF was unrelated to mortality. Conclusions: New-onset HF patients show a clinical profile different to that of chronic-decompensated patients. For this subset of acute HF patients older age, higher comorbidity and beta-blocker nonprescription predict a higher risk of mid-term post-discharge mortality. © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction Heart failure (HF) syndrome is a significant and growing global epidemic, due to the combination of aging of the population and more effective treatment of its major precursors, such as hypertension or coronary heart disease [1,2]. Current guidelines have started to realize
⁎ Corresponding author at: Unit of Internal Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, L'Hospitalet de Llobregat 08907, Barcelona, Spain. Tel.: +34 93 260 74 19; fax: +34 93 260 74 20. E-mail address: [email protected] (F. Formiga). 1 A full list of RICA investigators is provided in the Appendix.
the differential characteristics of HF patients whose symptoms and signs develop “fast”, requiring immediate medical attention, often leading to hospitalization, which is the definition of “acute HF”. Patients presenting with acute HF who have not shown symptoms of HF prior to the acute episode are tagged as “de novo” or new-onset HF and contribute to a significant proportion (between 12% and 63%) of all acute HF episodes patients [1,3]. It has already been described that the clinical characteristics of the acute HF episode among this subset of “new” patients more often include severe features such as acute pulmonary edema or cardiogenic shock, which result in a greater risk of morbidity and mortality [4–6]. HF is a progressive syndrome with high morbidity and mortality despite the remarkable advances in diagnosis and treatment during the last three decades. Admission
http://dx.doi.org/10.1016/j.ejim.2015.04.008 0953-6205/© 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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J. Franco et al. / European Journal of Internal Medicine 26 (2015) 357–362
mortality rates for acute HF patients are as high as 10.5%, and about 25% of these patients will die within the first year following hospital admission [7–9]. Factors associated with this poor short-term prognosis include advanced age, renal disease, low blood pressure or increased plasma natriuretic peptide levels [10,11]. Few studies, however, have focused only on new-onset acute HF patients' clinical presentation and data related to prognosis [12–16]. The main objective of this study is to compare the characteristics present among patients with new-onset acute HF with those present among patients already diagnosed with HF who present with an acute HF episode (chronic-decompensated HF). Secondary evaluations are restricted to the new-onset group of patients, and include: a) differential characteristics according to the type left ventricular (LV) dysfunction present, and b) factors associated with survival status at three months after discharge from the index admission. 2. Patients and methods Patient data were collected from the Spanish National Registry on HF (Registro Nacional de Insuficiencia Cardiaca — RICA) — supported by the Spanish Working Group on Heart Failure, of the Spanish Society of Internal Medicine. RICA is a multi-center, prospective cohort registry of patients experiencing admissions due to acute HF to the internal medicine services of 52 hospitals, mostly public but also some private, across Spain [17,18]. The ethics committee of the University Hospital “Reina Sofia”, Córdoba, Spain, approved on behalf of the others the overall protocol, and all patients signed an informed consent prior to being included in the registry. All patients aged 50 years or older admitted to these hospitals and presenting with HF symptoms and signs and fulfilling the current European Society of Cardiology criteria for the diagnosis of HF are considered candidates for inclusion in the registry — however, patients who die for any cause during the index admission are not included in the database. All patients discharged alive are followed after the index admission via scheduled outpatient clinic controls at 3 and 12 months, and phone contacts to assess vital status, data on new admissions and
basic clinical information at 1 and 6 months. Unscheduled additional visits are performed at the patients' attending physicians' discretion. Patient failing to show up is contacted to ascertain the causes, using relatives as proxy informers when the patient cannot be reached. Patients are only included once in the registry — subsequent admissions are coded as readmissions. RICA patients are thoroughly evaluated during the admission and all data are recorded in detail through a web site — https://www. registrorica.org/, which contains the main database, accessed by the investigators using a personal password. Confidentiality is preserved since no personal data are stored (except date of birth and name initials to avoid data duplication). Data in the registry include: sociodemographic data, past medical story related to HF, co-morbidities, functional and cognitive status, acute HF episode admission clinical data (blood pressure, heart rate, weight and height, acute HF characteristics), complications during admission and drug prescription and general advice at discharge. HF is characterized more in detail by the use of functional class using the New York Heart Association (NYHA) scale, the evaluation of left ventricular ejection fraction (LVEF) by means of 2-D echocardiography, cardiothoracic ratio through chest X-ray measurements and heart rhythm and rate by electrocardiogram (EKG). Blood chemistry values include kidney function, lipid and glucose profile, uric acid, troponin and natriuretic peptides (when available). Glomerular filtration is estimated with the MDRD equation, and chronic kidney disease (CKD) is considered when the estimated glomerular filtration rate (eGFR) is lower than 60 ml/min/1.73 m2 . Barthel Index (BI) and the Charlson Comorbidity Score (CCS) were used to measure overall functional status and comorbid burden respectively. For the purpose of the analysis the database was divided between patients who had never previously developed signs and symptoms of HF before the acute episode leading to the index admission (new-onset HF), and those already diagnosed with HF who were experiencing a decompensation of the disease (chronic-decompensated HF). As mentioned, no data regarding patients who died during the index admission was available. For patients who failed to show up at the
Fig. 1. Three-month survival rate after the acute HF episode according to new-onset HF versus chronic decompensated HF diagnosis.
J. Franco et al. / European Journal of Internal Medicine 26 (2015) 357–362
3-month scheduled control we ascertained mortality by medical record review and/or interviews with the patients' relatives. 2.1. Data analysis Results are shown as mean (standard deviation), number (%), and hazard ratio (HR) with 95% confidence intervals (CI). The relationship between new onset HF and potential confounders was examined using Chi-square or Fisher exact tests for categorical variables. The Kolmogorov–Smirnov test was used to determine whether quantitative variables were normally distributed. ANOVA tests for normally distributed variables or Wilcoxon rank sum tests for continuous variables for non-normally distributed. Kaplan–Meier survival curves and the log-rank test were calculated from baseline to time of 3-month all-cause mortality as a function of patients' baseline for patients with new onset and chronic decompensated HF. We created Cox regression model to evaluate hazard ratio (HR) of all-cause mortality over time. Covariates used for adjustment of baseline variables were also evaluated in a stepwise Cox multivariable regression analysis, incorporating all of them with p b 0.5 in the univariate analysis. These analyses were completed with the Statistical Package for Social Sciences (SPSS) program (version 21.0, SPSS Inc., Chicago. IL, USA). Tests were 2-sided and p-values b 0.05 were regarded as statistical significant.
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summarized in Table 1. New onset HF patients are predominantly older; more often related to hypertension and show higher blood pressure and heart rate values at the time of emergency room presentation. Compared to chronic-decompensated patients, new-onset HF patients show less comorbility, both globally (lower CCS scores) and by individual diseases such as diabetes, CKD, chronic obstructive pulmonary disease (COPD), atrial fibrillation (AF) or anemia. New onset patients present more often with preserved systolic function (LVEF ≥ 50%), milder baseline NYHA class, lower values of plasma natriuretic peptides (although the difference is only significant for NT-proBNP) and better overall functional status (higher BI values). No differences between both groups exist regarding HF-related medications prescribed at the time of discharge. 3.1. Differences within the new onset HF patients' subgroup according to EF A total of 44 new-onset HF patients did not undergo echocardiography to evaluate LVEF. Among the remaining 639 patients, around two thirds (401, 62.7%) had LVEF ≥ 50%. Table 2 shows the differences between the subgroups of patients according to this cutoff value; those with preserved EF were predominantly women, hypertension was more often the cause of HF, AF and anemia were more common and NT-proBNP plasma values were lower. In contrast, patients with reduced LVEF are predominantly males with ischemic etiology and were more often prescribed beta-blockers upon discharge.
3. Results At the time of performing this analysis a total of 2190 patients were included in the RICA registry. Of them, 683 (31.2%) fulfilled the criteria for new-onset acute HF. For the whole RICA cohort, the mean age was 78.6 ± 8 and 1.148 were women (52%). The baseline characteristics of these patients according to new-onset vs. chronic-decompensated HF status are
3.2. Mortality after 3 months of follow-up among new onset HF patients (Fig. 1) After 3 months of follow-up, 209 (10%) of the RICA registry patients had died, 33 (5.2%) in the group of new onset HF and 176 (13%) in the chronic-decompensated HF group (p b 0.001). Table 3 shows the differences according 3-month survival status restricted to the new-
Table 1 Characteristics of patients with HF “new-onset” vs decompensation HF chronic.
Number (%) of patients Age, yearsa BMI, kg/m2a Cause of heart failure, n (%) • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, n (%) Hypertension, n (%) SBP, mm Hga Heart rate, bpma Hemoglobin, g/dla Creatinine, mg/dla MDRD b 60 ml/min, n (%) BNP, pg/ml NT-pro-BNP, pg/ml LVEF b 50%, n (%) NHYA I–II, n (%) NYHA III–IV, n (%) Barthel Indexa COPD, n (%) Atrial fibrillation, n (%) Treatment at discharge • ACEI and/or ARB, n (%) • Beta-blockers, n (%) • Statins, n (%) Dead patients 3 months after discharge, n (%)
Total
New-onset HF
Chronic-decompensated HF
2190 78.6 ± 8.7 28.9 ± 6.1
683 (31.2%) 77.8 ± 9.2 29.2 ± 5.7
1507 (68.8%) 79.0 ± 8.4 28.7 ± 6.3
p
595 (27%) 806 (37%) 410 (19%) 379 (17%) 1001 (46%) 1875 (86%) 139.3 ± 28.2 88.3 ± 23.4 12.1 ± 2.1 1.4 ± 2.0 1276 (58%) 1.383 ± 2.600 6.088 ± 7.179 853 (42%) 1288 (60%) 852 (40%) 83.3 ± 21.5 569 (26%) 1197 (55%)
155 (23%) 275 (40%) 86 (13%) 167 (25%) 253 (37%) 546 (80%) 142.2 ± 27.4 93.8 ± 25.1 12.6 ± 2.1 1.2 ± 0.5 332 (49%) 1.270 ± 2.340 4.995 ± 6.086 238 (34.8%) 488 (73%) 185 (28%) 88.4 ± 19.8 153 (22%) 283 (41%)
440 (29%) 531 (35%) 324 (22%) 212 (14%) 748 (50%) 1329 (88%) 138.0 ± 28.5 85.8 ± 22.2 11.9 ± 2.1 1.4 ± 2.3 944 (63%) 1.427 ± 2.699 6.619 ± 7.602 615 (44%) 800 (55%) 667 (46%) 81.1 ± 21.9 416 (28%) 914 (61%)
0.002 0.024 b0.001 b0.001 b0.001 b0.001 0.001 b0.001 b0.001 0.007 b0.001 0.632 0.001 0.007 b0.001 b0.001 b0.001 0.010 b0.001
1554 (71%) 1169 (53%) 891 (41%) 209 (10%)
493 (72%) 369 (54%) 263 (39%) 33 (5.2%)
1061 (70%) 800 (53%) 629 (42%) 176 (13%)
0.396 0.712 0.173 b0.001
0.004 0.098
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers. a Results expressed as median [standard deviation].
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Table 2 Baseline characteristics of new onset HF according to type of LVEF.
Age Men, % Cause of heart failure, % • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, % Hypertension, % SBP (mm Hg) Heart rate Hemoglobin (g/dl) Creatinine (mg/dl) MDRD b 60 ml/min, % BNP NT-pro-BNP NHYA I–II, % NYHA III–IV, % Charlson Index COPD, % Atrial fibrillation, % Treatment • ACEI and/or ARB • Beta-blockers • Statins Dead patients 3 months after discharge
Table 3 Baseline characteristics of new onset HF patients according to 3-month survival status.
Total N = 639
Preserved ≥50% N = 401
Systolic b50% N = 238
p-Value
77.6 ± 9.3 322 (20%)
78.2 ± 8.7 175 (44%)
76.7 ± 10.2 147 (62%)
0.057 b0.001
146 (23%) 253 (40%) 84 (13%) 156 (24%) 238 (37%) 506 (79%) 142.2 ± 27.8 94.0 ± 25.2 12.6 ± 2.1 1.2 ± 0.5 305 (48%) 1.361 ± 2.504 5.151 ± 6.190 455 (72%) 174 (28%) 2.2 ± 2.2 141 (22%) 261 (41%)
45 (11%) 209 (52%) 60 (15%) 87 (22%) 153 (38%) 333 (83%) 143.0 ± 28.0 92.6 ± 25.9 12.4 ± 2.0 1.2 ± 0.6 198 (49%) 667.5 ± 572.3 4.238 ± 5.072 290 (74%) 104 (26%) 2.1 ± 2.1 90 (22%) 179 (45%)
101 (42%) b0.001 44 (19%) b0.001 24 (10%) 0.090 69 (29%) 0.045 85 (36%) 0.554 173 (73%) 0.002 140.8 ± 27.4 0.342 96.4 ± 23.8 0.071 12.9 ± 2.3 0.007 1.2 ± 0.5 0.910 107 (45%) 0.288 1.789 ± 3.087 0.019 6.857 ± 7.603 0.003 165 (70%) 0.359 70 (30%) 0.359 2.3 ± 2.2 0.216 51 (21%) 0.844 82 (35%) 0.013
459 (72%) 347 (54%) 253 (40%) 33 (5.6%)
280 (70%) 175 (44%) 153 (38%) 22 (5.9%)
179 (75%) 172 (72%) 100 (42%) 11 (5.0%)
0.147 b0.001 0.358 0.713
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers.
onset HF patient subgroup. Univariate analysis shows that those who died were older, with a higher percentage of HF related to heart valve disease, worse admission renal function, and greater comorbidity. At the time of hospital discharge this group had been prescribed less often ACEI/ARB and beta blockers. Cox multivariate analysis show that older age (hazard ratio – HR – 1.08), higher global comorbidity (HR 1.20) and not taking beta blockers upon discharge (HR 0.34) remain significant predictors of death within the first three months after index admission discharge (Table 4).
4. Discussion Approximately one third of the patients in the RICA registry, based in Internal Medicine settings, were diagnosed of acute new-onset HF at inclusion. Compared to the group of patients who were already diagnosed with the syndrome, they were younger, with a significant predominance of suspected hypertensive over ischemic heart disease. This finding probably is a consequence of the common practice in Spain to admit patients with new-onset HF suspected to be related to coronary heart disease in Cardiology units. New-onset HF patients show a lesser burden of comorbid disease — we presume that patients with longer HF duration, besides being slightly older, have more chances to develop other diseases, especially those associated with HF progression such as CKD or anemia. Blood pressure and heart rate values are higher among new-onset HF patients, probably due to the more severe clinical features (acute pulmonary edema, AF) typical of a first HF decompensation episode — however, it could also be related to the fact that chronic HF patients are usually taking more drugs that control blood pressure and heart rate. Milder baseline NYHA class and higher BI scores are also more common among new-onset HF patients – that probably reflects their overall
Total N = 636
Dead N = 33
Alive N = 603
p-Value
Age Men, % Cause of heart failure, % • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, % Hypertension, % SBP (mm Hg) Heart rate Hemoglobin (g/dl) Creatinine (mg/dl) MDRD b 60 ml/min, % BNP NT-pro-BNP
77.7 ± 9.2 319 (50%)
83.2 ± 7.2 20 (61%)
77.4 ± 9.2 299 (50%)
b0.001 0.283
144 (23%) 262 (41%) 77 (12%) 153 (24%) 237 (37%) 508 (80%) 142.4 ± 27.4 93.9 ± 24.9 12.7 ± 2.1 1.2 ± 0.5 313 (49%) 1.289 ± 2.431 4.994 ± 6.118
10 (30%) 9 (27%) 8 (24%) 6 (18%) 11 (33%) 24 (73%) 135.0 ± 22.8 94.2 ± 24.7 12.4 ± 2.1 1.5 ± 0.7 20 (61%) 429.8 ± 261 10.605 ±
134 (22%) 253 (42%) 69 (11%) 147 (24%) 226 (36%) 484 (80%) 142.8 ± 27.6 939 ± 25.0 12.7 ± 2.1 1.2 ± 0.5 293 (49%) 1.346 ± 2.499 4.683 ± 5.506
0.288 0.105 0.048 0.532 0.631 0.293 0.112 0.942 0.485 0.042 0.179 0.418 0.075
LVEF b 50%, % NHYA I–II, % NYHA III–IV, % Charlson Index COPD, % Atrial fibrillation, % Treatment • ACEI and/or ARB • Beta-blockers • Statins
371 (63%) 459 (72%) 175 (28%) 2.2 ± 2.1 143 (23%) 271 (43%)
11.887,4 22 (67%) 19 (59%) 13 (41%) 3.1 ± 2.3 10 (30%) 16 (49%)
349 (62%) 440 (73%) 162 (27%) 2.1 ± 2.1 123 (22%) 255 (42%)
0.713 0.105 0.105 0.008 0.269 0.483
470 (74%) 349 (55%) 250 (39%)
17 (52%) 8 (24%) 10 (30%)
453 (75%) 341 (57%) 240 (40%)
0.007 b0.001 0.360
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers.
better health status preceding the first episode of acute HF leading to hospitalization – we actually reported previously a significant post-discharge decline in functional outcomes for this kind of HF patient [19]. The discharge prescription of diuretics (84%) and beta-blockers (54%) after hospitalization is virtually identical to that reported in a French register of HF experiencing a first hospital admission patients [20], whereas ACEI/ARB prescription was slightly higher in our cohort (71% vs. 67%). Regarding the type of ventricular dysfunction present among new onset HF patients, as reported elsewhere [21,22], two distinct patterns emerge: preserved EF patients are typically of female sex, hypertensive and more often HF is accompanied by AF and anemia. Systolic HF patients, in contrast, are likely to be males with preexisting ischemic heart disease — probably due to the fact they are more often prescribed beta blockers at the time of discharge. Finally, the mortality rate at three months after the index admission discharge for the new onset HF cohort was close to 5%, very similar to a 4.4% previously reported [20], but lower that 30-day mortality reported in very elderly patients. Interestingly, in our study 30-day mortality was significantly lower than that of patients admitted for worsening chronic HF (13%). Another interesting study clearly shows age- and gender differences in short- (28 days) and long-term risk of death after first hospitalization for HF, with men having poorer short- and long-term survival than women [23]. We found that age, comorbidity and betablocker-use (but not gender), are the variables independently associated with higher mortality. Age is a well-recognized factor associated with mortality in general population and also in HF subjects [6,17], so it seems logical also for new onset HF. The same reasoning would be valid for global comorbidity [24]. Finally our results confirm the importance of starting treatment with beta-blockers in patients with HF, and even after the first decompensation [25]. In RICA patients with new onset HF there was no difference in mortality at 3 months of follow-up according to the EF values, a result similar to those recently
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Table 4 Factors related to all-cause mortality at 3 month follow-up. Univariate analysis
Age Gender (Men) Valvular heart disease Creatinine (mg/dl) Charlson Index Treatment prescription at discharge ACEI/ARB Beta-blockers
Multivariable analysis
Hazard ratio
95% confidence interval
p-Value
Hazard ratio
95% confidence interval
p-Value
1.08 1.63 2.60 1.16 1.18
1.03–1.14 0.76–3.48 1.12–6.05 0.69–1.95 1.03–1.36
0.002 0.209 0.027 0.572 0.016
1.09
1.03–1.14
0.001
2.27
0.98–5.21
0.054
1.20
1.06–1.36
0.003
0.62 0.34
0.28–1.37 0.15–0.76
0.240 0.009
0.35
0.15–0.78
0.011
reported by Senni et al. regarding 1-year all cause and cardiovascular mortality [3].
R, Pérez Bocanegra C, Pérez Calvo JI, Quesada MA, Quirós R, Rodríguez Ávila EE, Ruiz R, Ruiz Laiglesia F, Salamanca P, Sánchez Marteles M, Satué JA, Serrado A, Suárez I, Trullàs JC.
4.1. Strengths and limitations The strength of our study is the large size of the cohort, which represents a “real word”, usual-care sample of elderly patients with acute HF. The present study does however have several limitations that should be acknowledged. First, as mentioned in the Patients and methods section, patients who die during the index admission are not included in the registry and therefore their characteristics cannot be subject to analysis — however, the number of new onset HF patients who did not survive a first hospitalization is likely to be very low. Second, among the subgroup of patients who presented with an episode of chronicdecompensated HF the time elapsed since the onset of HF was not evaluated — patients with a longer history of HF and repeated admissions are more likely to be older and more comorbid but those with shorter disease duration are probably similar to new-onset patients. Mortality is analyzed as a whole, regardless of cardiovascular or noncardiovascular causes. Finally, some clinical data such as BNP or NTpro-BNP analyses were limited to some but not all patients and that could bias their significance as prognostic markers. In conclusion, patients experiencing a first hospital admission because of new-onset HF show a clinical profile that is somehow different to that of patients already diagnosed with HF. Among this subgroup, mid-term survival is similar regardless of reduced or preserved LVEF, and relates not only to non-modifiable data (older age and comorbid burden) but also to clinical practices amenable to change such as the non-prescription of beta-blockers at the time of hospital discharge. Conflict of interest The authors declare that they have no conflicts of interest. Acknowledgments We gratefully acknowledge all investigators who form part of the RICA registry. We would like to thank RICA's Registry Coordinating Center “S&H Medical Science Service” for their quality control data, logistic support, and administrative work and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper. Appendix A. RICA registry member Anarte L, Aramburu O, Arévalo-Lorido JC, Bas F, Carrera M, Cerqueiro JM, Chivite D, Conde A, Dávila MF, Díez Manglano J, Epelde F, Formiga F, Franco J, Gallego J, González Franco A, Guisado ME, Herrero A, López Castellanos G, López Reboiro ML, Manzano L, Martínez Zapico A, Montero Pérez-Barquero M, Murado I, Oropesa
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Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
New onset heart failure — Clinical characteristics and short-term mortality. A RICA (Spanish registry of acute heart failure) study Jonathan Franco a, Francesc Formiga a,⁎, David Chivite a, Luis Manzano b, Margarita Carrera c, José Carlos Arévalo-Lorido d, Francisco Epelde e, Jose Manuel Cerqueiro f, Ana Serrado g, Manuel Montero Pérez-Barquero h, for the RICA investigadors 1 a
Geriatric Unit, Internal Medicine Service, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain Heart Failure and Vascular Risk Unit, Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain c Internal Medicine Service, Complejo Hospitalario de Soria, Soria, Spain d Internal Medicine Service, Hospital Comarcal de Zafra, Zafra, Badajoz, Spain e Short stay Unit, Emergency Service, Hospital Universitari de Sabadell, Corporació Sanitaria Parc Tauli, Department of Medicine, UAB, Sabadell, Barcelona, Spain f Internal Medicine Service, Hospital Lucus Augusti, Lugo Spain g Internal Medicine Service, Hospital Municipal de Badalona, Badalona, Barcelona, Spain h Internal Medicine Service, IMIBIC/Hospital Reina Sofía, Universidad de Córdoba, Spain b
a r t i c l e
i n f o
Article history: Received 28 October 2014 Received in revised form 11 February 2015 Accepted 4 April 2015 Available online 1 May 2015 Keywords: New onset heart failure Chronic heart failure Mortality
a b s t r a c t Background: Heart failure (HF) is a growing global epidemic. The main study aims is to evaluate the differences between new-onset and chronic-decompensated HF patients. Secondary objectives related only to new-onset HF patients include the role of left ventricular ejection fraction (LVEF) and mid-term mortality related risk factors Methods: We analyzed 2190 patients hospitalized for acute HF. We compare the 683 patients with a new-onset HF episode with the rest. Restricting the analysis to the new-onset HF patients, we also compare patients with preserved LVEF (EF N 50%) with those with reduced LVEF, and analyze the factors associated with three-month mortality. Results: A total of 683 (31.2%) patients fulfill the criteria for “new-onset HF”. These patients are older, their HF is more often related to hypertension, show higher blood pressure and heart rate values upon admission, and present with less global and disease-specific comorbidity and better baseline overall functional status. New-onset HF is more often characterized by preserved LVEF, milder baseline NYHA class and lower plasma natriuretic peptide values. After 3 months; 33 (5.2%) new-onset HF patients had died (p b 0.001). Cox multivariate analysis showed a correlation between mortality and older age (hazard ratio – HR – 1.08), higher global comorbidity (HR 1.20) and lesser prescription of beta-blockers at discharge (HR 0.34). LVEF was unrelated to mortality. Conclusions: New-onset HF patients show a clinical profile different to that of chronic-decompensated patients. For this subset of acute HF patients older age, higher comorbidity and beta-blocker nonprescription predict a higher risk of mid-term post-discharge mortality. © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction Heart failure (HF) syndrome is a significant and growing global epidemic, due to the combination of aging of the population and more effective treatment of its major precursors, such as hypertension or coronary heart disease [1,2]. Current guidelines have started to realize
⁎ Corresponding author at: Unit of Internal Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, L'Hospitalet de Llobregat 08907, Barcelona, Spain. Tel.: +34 93 260 74 19; fax: +34 93 260 74 20. E-mail address: [email protected] (F. Formiga). 1 A full list of RICA investigators is provided in the Appendix.
the differential characteristics of HF patients whose symptoms and signs develop “fast”, requiring immediate medical attention, often leading to hospitalization, which is the definition of “acute HF”. Patients presenting with acute HF who have not shown symptoms of HF prior to the acute episode are tagged as “de novo” or new-onset HF and contribute to a significant proportion (between 12% and 63%) of all acute HF episodes patients [1,3]. It has already been described that the clinical characteristics of the acute HF episode among this subset of “new” patients more often include severe features such as acute pulmonary edema or cardiogenic shock, which result in a greater risk of morbidity and mortality [4–6]. HF is a progressive syndrome with high morbidity and mortality despite the remarkable advances in diagnosis and treatment during the last three decades. Admission
http://dx.doi.org/10.1016/j.ejim.2015.04.008 0953-6205/© 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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mortality rates for acute HF patients are as high as 10.5%, and about 25% of these patients will die within the first year following hospital admission [7–9]. Factors associated with this poor short-term prognosis include advanced age, renal disease, low blood pressure or increased plasma natriuretic peptide levels [10,11]. Few studies, however, have focused only on new-onset acute HF patients' clinical presentation and data related to prognosis [12–16]. The main objective of this study is to compare the characteristics present among patients with new-onset acute HF with those present among patients already diagnosed with HF who present with an acute HF episode (chronic-decompensated HF). Secondary evaluations are restricted to the new-onset group of patients, and include: a) differential characteristics according to the type left ventricular (LV) dysfunction present, and b) factors associated with survival status at three months after discharge from the index admission. 2. Patients and methods Patient data were collected from the Spanish National Registry on HF (Registro Nacional de Insuficiencia Cardiaca — RICA) — supported by the Spanish Working Group on Heart Failure, of the Spanish Society of Internal Medicine. RICA is a multi-center, prospective cohort registry of patients experiencing admissions due to acute HF to the internal medicine services of 52 hospitals, mostly public but also some private, across Spain [17,18]. The ethics committee of the University Hospital “Reina Sofia”, Córdoba, Spain, approved on behalf of the others the overall protocol, and all patients signed an informed consent prior to being included in the registry. All patients aged 50 years or older admitted to these hospitals and presenting with HF symptoms and signs and fulfilling the current European Society of Cardiology criteria for the diagnosis of HF are considered candidates for inclusion in the registry — however, patients who die for any cause during the index admission are not included in the database. All patients discharged alive are followed after the index admission via scheduled outpatient clinic controls at 3 and 12 months, and phone contacts to assess vital status, data on new admissions and
basic clinical information at 1 and 6 months. Unscheduled additional visits are performed at the patients' attending physicians' discretion. Patient failing to show up is contacted to ascertain the causes, using relatives as proxy informers when the patient cannot be reached. Patients are only included once in the registry — subsequent admissions are coded as readmissions. RICA patients are thoroughly evaluated during the admission and all data are recorded in detail through a web site — https://www. registrorica.org/, which contains the main database, accessed by the investigators using a personal password. Confidentiality is preserved since no personal data are stored (except date of birth and name initials to avoid data duplication). Data in the registry include: sociodemographic data, past medical story related to HF, co-morbidities, functional and cognitive status, acute HF episode admission clinical data (blood pressure, heart rate, weight and height, acute HF characteristics), complications during admission and drug prescription and general advice at discharge. HF is characterized more in detail by the use of functional class using the New York Heart Association (NYHA) scale, the evaluation of left ventricular ejection fraction (LVEF) by means of 2-D echocardiography, cardiothoracic ratio through chest X-ray measurements and heart rhythm and rate by electrocardiogram (EKG). Blood chemistry values include kidney function, lipid and glucose profile, uric acid, troponin and natriuretic peptides (when available). Glomerular filtration is estimated with the MDRD equation, and chronic kidney disease (CKD) is considered when the estimated glomerular filtration rate (eGFR) is lower than 60 ml/min/1.73 m2 . Barthel Index (BI) and the Charlson Comorbidity Score (CCS) were used to measure overall functional status and comorbid burden respectively. For the purpose of the analysis the database was divided between patients who had never previously developed signs and symptoms of HF before the acute episode leading to the index admission (new-onset HF), and those already diagnosed with HF who were experiencing a decompensation of the disease (chronic-decompensated HF). As mentioned, no data regarding patients who died during the index admission was available. For patients who failed to show up at the
Fig. 1. Three-month survival rate after the acute HF episode according to new-onset HF versus chronic decompensated HF diagnosis.
J. Franco et al. / European Journal of Internal Medicine 26 (2015) 357–362
3-month scheduled control we ascertained mortality by medical record review and/or interviews with the patients' relatives. 2.1. Data analysis Results are shown as mean (standard deviation), number (%), and hazard ratio (HR) with 95% confidence intervals (CI). The relationship between new onset HF and potential confounders was examined using Chi-square or Fisher exact tests for categorical variables. The Kolmogorov–Smirnov test was used to determine whether quantitative variables were normally distributed. ANOVA tests for normally distributed variables or Wilcoxon rank sum tests for continuous variables for non-normally distributed. Kaplan–Meier survival curves and the log-rank test were calculated from baseline to time of 3-month all-cause mortality as a function of patients' baseline for patients with new onset and chronic decompensated HF. We created Cox regression model to evaluate hazard ratio (HR) of all-cause mortality over time. Covariates used for adjustment of baseline variables were also evaluated in a stepwise Cox multivariable regression analysis, incorporating all of them with p b 0.5 in the univariate analysis. These analyses were completed with the Statistical Package for Social Sciences (SPSS) program (version 21.0, SPSS Inc., Chicago. IL, USA). Tests were 2-sided and p-values b 0.05 were regarded as statistical significant.
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summarized in Table 1. New onset HF patients are predominantly older; more often related to hypertension and show higher blood pressure and heart rate values at the time of emergency room presentation. Compared to chronic-decompensated patients, new-onset HF patients show less comorbility, both globally (lower CCS scores) and by individual diseases such as diabetes, CKD, chronic obstructive pulmonary disease (COPD), atrial fibrillation (AF) or anemia. New onset patients present more often with preserved systolic function (LVEF ≥ 50%), milder baseline NYHA class, lower values of plasma natriuretic peptides (although the difference is only significant for NT-proBNP) and better overall functional status (higher BI values). No differences between both groups exist regarding HF-related medications prescribed at the time of discharge. 3.1. Differences within the new onset HF patients' subgroup according to EF A total of 44 new-onset HF patients did not undergo echocardiography to evaluate LVEF. Among the remaining 639 patients, around two thirds (401, 62.7%) had LVEF ≥ 50%. Table 2 shows the differences between the subgroups of patients according to this cutoff value; those with preserved EF were predominantly women, hypertension was more often the cause of HF, AF and anemia were more common and NT-proBNP plasma values were lower. In contrast, patients with reduced LVEF are predominantly males with ischemic etiology and were more often prescribed beta-blockers upon discharge.
3. Results At the time of performing this analysis a total of 2190 patients were included in the RICA registry. Of them, 683 (31.2%) fulfilled the criteria for new-onset acute HF. For the whole RICA cohort, the mean age was 78.6 ± 8 and 1.148 were women (52%). The baseline characteristics of these patients according to new-onset vs. chronic-decompensated HF status are
3.2. Mortality after 3 months of follow-up among new onset HF patients (Fig. 1) After 3 months of follow-up, 209 (10%) of the RICA registry patients had died, 33 (5.2%) in the group of new onset HF and 176 (13%) in the chronic-decompensated HF group (p b 0.001). Table 3 shows the differences according 3-month survival status restricted to the new-
Table 1 Characteristics of patients with HF “new-onset” vs decompensation HF chronic.
Number (%) of patients Age, yearsa BMI, kg/m2a Cause of heart failure, n (%) • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, n (%) Hypertension, n (%) SBP, mm Hga Heart rate, bpma Hemoglobin, g/dla Creatinine, mg/dla MDRD b 60 ml/min, n (%) BNP, pg/ml NT-pro-BNP, pg/ml LVEF b 50%, n (%) NHYA I–II, n (%) NYHA III–IV, n (%) Barthel Indexa COPD, n (%) Atrial fibrillation, n (%) Treatment at discharge • ACEI and/or ARB, n (%) • Beta-blockers, n (%) • Statins, n (%) Dead patients 3 months after discharge, n (%)
Total
New-onset HF
Chronic-decompensated HF
2190 78.6 ± 8.7 28.9 ± 6.1
683 (31.2%) 77.8 ± 9.2 29.2 ± 5.7
1507 (68.8%) 79.0 ± 8.4 28.7 ± 6.3
p
595 (27%) 806 (37%) 410 (19%) 379 (17%) 1001 (46%) 1875 (86%) 139.3 ± 28.2 88.3 ± 23.4 12.1 ± 2.1 1.4 ± 2.0 1276 (58%) 1.383 ± 2.600 6.088 ± 7.179 853 (42%) 1288 (60%) 852 (40%) 83.3 ± 21.5 569 (26%) 1197 (55%)
155 (23%) 275 (40%) 86 (13%) 167 (25%) 253 (37%) 546 (80%) 142.2 ± 27.4 93.8 ± 25.1 12.6 ± 2.1 1.2 ± 0.5 332 (49%) 1.270 ± 2.340 4.995 ± 6.086 238 (34.8%) 488 (73%) 185 (28%) 88.4 ± 19.8 153 (22%) 283 (41%)
440 (29%) 531 (35%) 324 (22%) 212 (14%) 748 (50%) 1329 (88%) 138.0 ± 28.5 85.8 ± 22.2 11.9 ± 2.1 1.4 ± 2.3 944 (63%) 1.427 ± 2.699 6.619 ± 7.602 615 (44%) 800 (55%) 667 (46%) 81.1 ± 21.9 416 (28%) 914 (61%)
0.002 0.024 b0.001 b0.001 b0.001 b0.001 0.001 b0.001 b0.001 0.007 b0.001 0.632 0.001 0.007 b0.001 b0.001 b0.001 0.010 b0.001
1554 (71%) 1169 (53%) 891 (41%) 209 (10%)
493 (72%) 369 (54%) 263 (39%) 33 (5.2%)
1061 (70%) 800 (53%) 629 (42%) 176 (13%)
0.396 0.712 0.173 b0.001
0.004 0.098
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers. a Results expressed as median [standard deviation].
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Table 2 Baseline characteristics of new onset HF according to type of LVEF.
Age Men, % Cause of heart failure, % • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, % Hypertension, % SBP (mm Hg) Heart rate Hemoglobin (g/dl) Creatinine (mg/dl) MDRD b 60 ml/min, % BNP NT-pro-BNP NHYA I–II, % NYHA III–IV, % Charlson Index COPD, % Atrial fibrillation, % Treatment • ACEI and/or ARB • Beta-blockers • Statins Dead patients 3 months after discharge
Table 3 Baseline characteristics of new onset HF patients according to 3-month survival status.
Total N = 639
Preserved ≥50% N = 401
Systolic b50% N = 238
p-Value
77.6 ± 9.3 322 (20%)
78.2 ± 8.7 175 (44%)
76.7 ± 10.2 147 (62%)
0.057 b0.001
146 (23%) 253 (40%) 84 (13%) 156 (24%) 238 (37%) 506 (79%) 142.2 ± 27.8 94.0 ± 25.2 12.6 ± 2.1 1.2 ± 0.5 305 (48%) 1.361 ± 2.504 5.151 ± 6.190 455 (72%) 174 (28%) 2.2 ± 2.2 141 (22%) 261 (41%)
45 (11%) 209 (52%) 60 (15%) 87 (22%) 153 (38%) 333 (83%) 143.0 ± 28.0 92.6 ± 25.9 12.4 ± 2.0 1.2 ± 0.6 198 (49%) 667.5 ± 572.3 4.238 ± 5.072 290 (74%) 104 (26%) 2.1 ± 2.1 90 (22%) 179 (45%)
101 (42%) b0.001 44 (19%) b0.001 24 (10%) 0.090 69 (29%) 0.045 85 (36%) 0.554 173 (73%) 0.002 140.8 ± 27.4 0.342 96.4 ± 23.8 0.071 12.9 ± 2.3 0.007 1.2 ± 0.5 0.910 107 (45%) 0.288 1.789 ± 3.087 0.019 6.857 ± 7.603 0.003 165 (70%) 0.359 70 (30%) 0.359 2.3 ± 2.2 0.216 51 (21%) 0.844 82 (35%) 0.013
459 (72%) 347 (54%) 253 (40%) 33 (5.6%)
280 (70%) 175 (44%) 153 (38%) 22 (5.9%)
179 (75%) 172 (72%) 100 (42%) 11 (5.0%)
0.147 b0.001 0.358 0.713
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers.
onset HF patient subgroup. Univariate analysis shows that those who died were older, with a higher percentage of HF related to heart valve disease, worse admission renal function, and greater comorbidity. At the time of hospital discharge this group had been prescribed less often ACEI/ARB and beta blockers. Cox multivariate analysis show that older age (hazard ratio – HR – 1.08), higher global comorbidity (HR 1.20) and not taking beta blockers upon discharge (HR 0.34) remain significant predictors of death within the first three months after index admission discharge (Table 4).
4. Discussion Approximately one third of the patients in the RICA registry, based in Internal Medicine settings, were diagnosed of acute new-onset HF at inclusion. Compared to the group of patients who were already diagnosed with the syndrome, they were younger, with a significant predominance of suspected hypertensive over ischemic heart disease. This finding probably is a consequence of the common practice in Spain to admit patients with new-onset HF suspected to be related to coronary heart disease in Cardiology units. New-onset HF patients show a lesser burden of comorbid disease — we presume that patients with longer HF duration, besides being slightly older, have more chances to develop other diseases, especially those associated with HF progression such as CKD or anemia. Blood pressure and heart rate values are higher among new-onset HF patients, probably due to the more severe clinical features (acute pulmonary edema, AF) typical of a first HF decompensation episode — however, it could also be related to the fact that chronic HF patients are usually taking more drugs that control blood pressure and heart rate. Milder baseline NYHA class and higher BI scores are also more common among new-onset HF patients – that probably reflects their overall
Total N = 636
Dead N = 33
Alive N = 603
p-Value
Age Men, % Cause of heart failure, % • Ischemic • Hypertensive • Valvular • Others Diabetes mellitus, % Hypertension, % SBP (mm Hg) Heart rate Hemoglobin (g/dl) Creatinine (mg/dl) MDRD b 60 ml/min, % BNP NT-pro-BNP
77.7 ± 9.2 319 (50%)
83.2 ± 7.2 20 (61%)
77.4 ± 9.2 299 (50%)
b0.001 0.283
144 (23%) 262 (41%) 77 (12%) 153 (24%) 237 (37%) 508 (80%) 142.4 ± 27.4 93.9 ± 24.9 12.7 ± 2.1 1.2 ± 0.5 313 (49%) 1.289 ± 2.431 4.994 ± 6.118
10 (30%) 9 (27%) 8 (24%) 6 (18%) 11 (33%) 24 (73%) 135.0 ± 22.8 94.2 ± 24.7 12.4 ± 2.1 1.5 ± 0.7 20 (61%) 429.8 ± 261 10.605 ±
134 (22%) 253 (42%) 69 (11%) 147 (24%) 226 (36%) 484 (80%) 142.8 ± 27.6 939 ± 25.0 12.7 ± 2.1 1.2 ± 0.5 293 (49%) 1.346 ± 2.499 4.683 ± 5.506
0.288 0.105 0.048 0.532 0.631 0.293 0.112 0.942 0.485 0.042 0.179 0.418 0.075
LVEF b 50%, % NHYA I–II, % NYHA III–IV, % Charlson Index COPD, % Atrial fibrillation, % Treatment • ACEI and/or ARB • Beta-blockers • Statins
371 (63%) 459 (72%) 175 (28%) 2.2 ± 2.1 143 (23%) 271 (43%)
11.887,4 22 (67%) 19 (59%) 13 (41%) 3.1 ± 2.3 10 (30%) 16 (49%)
349 (62%) 440 (73%) 162 (27%) 2.1 ± 2.1 123 (22%) 255 (42%)
0.713 0.105 0.105 0.008 0.269 0.483
470 (74%) 349 (55%) 250 (39%)
17 (52%) 8 (24%) 10 (30%)
453 (75%) 341 (57%) 240 (40%)
0.007 b0.001 0.360
Abbreviations: BMI: body-mass index; SBP: systolic blood pressure; MDRD: Modification of Diet in Renal Disease formula; BNP: brain natriuretic peptide; LVEF: left-ventricle ejection fraction; NHYA: New York Heart Association; COPD: chronic obstructive pulmonary disease. ACEI: angiotensin-converting-enzyme inhibitors; ARB: angiotensin receptor blockers.
better health status preceding the first episode of acute HF leading to hospitalization – we actually reported previously a significant post-discharge decline in functional outcomes for this kind of HF patient [19]. The discharge prescription of diuretics (84%) and beta-blockers (54%) after hospitalization is virtually identical to that reported in a French register of HF experiencing a first hospital admission patients [20], whereas ACEI/ARB prescription was slightly higher in our cohort (71% vs. 67%). Regarding the type of ventricular dysfunction present among new onset HF patients, as reported elsewhere [21,22], two distinct patterns emerge: preserved EF patients are typically of female sex, hypertensive and more often HF is accompanied by AF and anemia. Systolic HF patients, in contrast, are likely to be males with preexisting ischemic heart disease — probably due to the fact they are more often prescribed beta blockers at the time of discharge. Finally, the mortality rate at three months after the index admission discharge for the new onset HF cohort was close to 5%, very similar to a 4.4% previously reported [20], but lower that 30-day mortality reported in very elderly patients. Interestingly, in our study 30-day mortality was significantly lower than that of patients admitted for worsening chronic HF (13%). Another interesting study clearly shows age- and gender differences in short- (28 days) and long-term risk of death after first hospitalization for HF, with men having poorer short- and long-term survival than women [23]. We found that age, comorbidity and betablocker-use (but not gender), are the variables independently associated with higher mortality. Age is a well-recognized factor associated with mortality in general population and also in HF subjects [6,17], so it seems logical also for new onset HF. The same reasoning would be valid for global comorbidity [24]. Finally our results confirm the importance of starting treatment with beta-blockers in patients with HF, and even after the first decompensation [25]. In RICA patients with new onset HF there was no difference in mortality at 3 months of follow-up according to the EF values, a result similar to those recently
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361
Table 4 Factors related to all-cause mortality at 3 month follow-up. Univariate analysis
Age Gender (Men) Valvular heart disease Creatinine (mg/dl) Charlson Index Treatment prescription at discharge ACEI/ARB Beta-blockers
Multivariable analysis
Hazard ratio
95% confidence interval
p-Value
Hazard ratio
95% confidence interval
p-Value
1.08 1.63 2.60 1.16 1.18
1.03–1.14 0.76–3.48 1.12–6.05 0.69–1.95 1.03–1.36
0.002 0.209 0.027 0.572 0.016
1.09
1.03–1.14
0.001
2.27
0.98–5.21
0.054
1.20
1.06–1.36
0.003
0.62 0.34
0.28–1.37 0.15–0.76
0.240 0.009
0.35
0.15–0.78
0.011
reported by Senni et al. regarding 1-year all cause and cardiovascular mortality [3].
R, Pérez Bocanegra C, Pérez Calvo JI, Quesada MA, Quirós R, Rodríguez Ávila EE, Ruiz R, Ruiz Laiglesia F, Salamanca P, Sánchez Marteles M, Satué JA, Serrado A, Suárez I, Trullàs JC.
4.1. Strengths and limitations The strength of our study is the large size of the cohort, which represents a “real word”, usual-care sample of elderly patients with acute HF. The present study does however have several limitations that should be acknowledged. First, as mentioned in the Patients and methods section, patients who die during the index admission are not included in the registry and therefore their characteristics cannot be subject to analysis — however, the number of new onset HF patients who did not survive a first hospitalization is likely to be very low. Second, among the subgroup of patients who presented with an episode of chronicdecompensated HF the time elapsed since the onset of HF was not evaluated — patients with a longer history of HF and repeated admissions are more likely to be older and more comorbid but those with shorter disease duration are probably similar to new-onset patients. Mortality is analyzed as a whole, regardless of cardiovascular or noncardiovascular causes. Finally, some clinical data such as BNP or NTpro-BNP analyses were limited to some but not all patients and that could bias their significance as prognostic markers. In conclusion, patients experiencing a first hospital admission because of new-onset HF show a clinical profile that is somehow different to that of patients already diagnosed with HF. Among this subgroup, mid-term survival is similar regardless of reduced or preserved LVEF, and relates not only to non-modifiable data (older age and comorbid burden) but also to clinical practices amenable to change such as the non-prescription of beta-blockers at the time of hospital discharge. Conflict of interest The authors declare that they have no conflicts of interest. Acknowledgments We gratefully acknowledge all investigators who form part of the RICA registry. We would like to thank RICA's Registry Coordinating Center “S&H Medical Science Service” for their quality control data, logistic support, and administrative work and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper. Appendix A. RICA registry member Anarte L, Aramburu O, Arévalo-Lorido JC, Bas F, Carrera M, Cerqueiro JM, Chivite D, Conde A, Dávila MF, Díez Manglano J, Epelde F, Formiga F, Franco J, Gallego J, González Franco A, Guisado ME, Herrero A, López Castellanos G, López Reboiro ML, Manzano L, Martínez Zapico A, Montero Pérez-Barquero M, Murado I, Oropesa
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