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European Journal of Heart Failure 2005 7(5):780-783; doi:10.1016/j.ejheart.2005.03.009
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© 2005 European Society of Cardiology

Short to long term mortality of patients hospitalised with heart failure in the Czech Republic—a report from the EuroHeart Failure Survey

Hana Rosolovaa,*, Jakub Cecha, Jaroslav Simona, Jindrich Spinarb, Ruzena Jandovac, Jiri Widimsky senc, Lubomir Holubeca and Ondrej Topolcana

a Centre of Preventive Cardiology of the 2nd Medical Department University Hospital E. Benese 13, 305 99 Pilsen, Czech Republic
b 2nd Medical Department of St. Anna Hospital Brno Czech Republic
c Department of Cardiology of the Institute of Clinical and Experimental Medicine (IKEM) Prague Czech Republic

* Corresponding author. Tel.: +42 37 740 2384; fax: +42 37 740 26 50. E-mail address:rosolova{at}fnplzen.cz


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Acknowledgments
 References
 
Background and aim: The European Society of Cardiology initiated the EuroHeart Failure Survey to obtain more data about the quality of care in patients hospitalised with suspected heart failure (HF). The Czech Republic was 1 of the 24 European Society countries included in the survey. The aim of this report is to extend the original follow-up period of 12 weeks out to 4 years to assess mortality.

Methods: All admitted patients were screened according to the EuroHeart Survey Protocol, over a 6-week period in six hospitals in Pilsen, Prague and Brno in the year 2000. Annual mortality and cause of death were obtained from the Prague Institute for Health Statistical Information (UZIS Praha).

Results: A total of 2365 patients were screened and about 25% of all admitted patients fulfilled the criteria for HF. About 14% of patients died between admission and the 12-week follow-up, 36% of male and 42% of female patients died during the 4-year follow-up (2000–2003). Cardiovascular diseases were the main causes of death (92%). Deceased patients were significantly older, had lower haemoglobin and total plasma cholesterol level, and had renal insufficiency and higher levels of big endothelin and BNP than the survivors. Mortality risk was increased independently by positive history of previous myocardial infarction OR=2.39 (1.59–3.59), by age OR=1.03 (1.01–1.05) and by plasma creatinine level OR=1.04 (1.01–1.07). Treatment with diuretics and digoxin was associated with a higher risk of death; by contrast, a protective effect of beta-blockers and statins was found in these HF patients.

Conclusion: Patients with HF were older and had a poor prognosis; approximately one third of the patients will die within 3 years.

Key Words: Chronic heart failure • Mortality

Received December 15, 2004; Accepted March 3, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Acknowledgments
 References
 
Heart failure (HF) is a common and increasing cause of morbidity and mortality. However, little information exists outside of randomised controlled trials on international variation in patient characteristics, diagnostic tests and pharmacological and non-pharmacological management. Hospitalisation is a common event both at the onset and during the clinical course of HF. Such episodes provide a key opportunity to clarify the diagnosis and optimise therapy. The proportion of medical admissions due to or complicated by HF also provides a measure of disease burden and costs of management of this condition.

Accordingly, the European Society of Cardiology initiated the EuroHeart Failure Survey to obtain more data concerning the quality of care in patients hospitalised with suspected HF [1,2]. The Czech Republic was 1 of the 24 European Society countries included in the survey. The aim of this report is to extend the original follow-up period of 12 weeks out to 4 years to assess mortality.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 Acknowledgments
 References
 
The Czech part of the EuroHeart study was done in three cities—Pilsen, Prague and Brno. Two centres (hospitals) were included in each city: The 1st and The 2nd Medical Departments in Pilsen University Hospital, The 1st Medical Department of Thomayer's Hospital and Department of Cardiology of the Institute of Clinical and Experimental Medicine (IKEM) in Prague, and The 1st Department of Cardiology and Angiology and The 2nd Medical Department of St. Anna Hospital in Brno. A total of 2365 consecutive deaths and discharges were screened during a 6-week period in all six hospitals in the year 2000. About 25% of all admitted patients (n=588) fulfilled one or more of the following criteria for definite or suspected HF or left ventricular dysfunction:

  1. A clinical diagnosis of HF recorded during admission (regardless of the primary reason for admission)—66% of all enrolled patients.
  2. A diagnosis of HF recorded in the hospital notes at any time in the last 3 years—89% of all enrolled patients.
  3. Administration of a loop diuretic for any reason other than renal failure during the 24 h prior to death or discharge—75% of all enrolled patients.
  4. Administration of treatment for HF or major ventricular dysfunction within 24 h of death or discharge (any prescription of ACE inhibitor, beta-blocker, diuretics, digitalis or spironolactone to determine the reason for their administration)—90% of all enrolled patients.

Data on symptoms, laboratory and other tests, concomitant illnesses and therapy were obtained from the hospital records and discharge reports. 12 weeks after discharge from hospital, surviving patients were contacted and asked to attend the local out-patient clinic. Personal history, physical examination and a fasting blood sample were taken and the course of the disease was assessed.

Biochemical screening and blood count were measured by standard methods in the local routine hospital laboratories. Plasma values of cardiac markers: pro-atrial natriuretic peptide (ANP), amino terminal pro-brain natriuretic peptide (BNP) and big endothelin were assessed by ELISA (Biomedica company). The reference values for these cardiac markers are as follows: ANP-normal range up to 1945 fmol/mL, BNP-normal range up to 250 fmol/mL and big endothelin-normal range up to 0.7 fmol/mL. All included patients gave written informed consent to participate in the study.

Information concerning re-hospitalisation was assessed by postal-questionnaire either by the general practitioner or directly by the patients or their relatives. The annual mortality and cause of death were obtained from the Prague Institute for Health Statistical Information (UZIS Praha).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 Acknowledgments
 References
 
A total of 2365 consecutive deaths and discharges were screened. About 25% of the patients screened were enrolled as suspected cases of HF. Male sex (58%) and higher age (70±12 years) predominated in patients with HF. The patients were mostly overweight (30%) or obese (40%); 10% were smokers and 35% were ex-smokers. Coronary heart disease with or without hypertension (55%) and hypertension without CHD (24%) were the most frequent causes of HF. Cardiomyopathy occurred in 12% and other causes of HF such as valvular disease, arrhythmias, cor pulmonale, etc. in 9% of the sample. Diabetes occurred in about 50% and stroke (including brain transitory ischemic attack) in 20% patients with HF.

We analysed the association between mortality and the followed parameters using Wilcoxon unpaired test. Deceased patients with HF were significantly older, had significantly lower haemoglobin, higher urea and creatinine levels, but lower cholesterol levels. Significantly higher levels of big endothelin and brain natriuretic peptide (BNP) were also observed in deceased HF patients compared to the survivors. We analysed drug use in deceased and surviving patients using the {chi}2 test. Deceased patients used diuretics and digoxin more frequently than surviving ones, whereas surviving patients used beta-blockers and statins more frequently than deceased patients (Table 1).


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  		Table 1 Comparison of baseline parameters in deceased and surviving patients

 
There were 41 deaths (7%) during the hospital stay and another 44 deaths (7.4%) during the 12-week follow-up period; i.e. 85 deaths (14.4%) in total from admission to the follow-up examination. The yearly mortality is shown in Table 2. About 39% of all patients with HF (36% male and 42% female) died during the 4-year follow-up (2000–2003). Cardiovascular diseases were the main causes of death (92%). Non-cardiovascular deaths included six cancers, two injuries, four bronchopneumonia and six unspecified causes. About 25% of patients surviving at the beginning of 2003 did not respond to our questionnaires 6 months later.


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  		Table 2 Yearly mortality rates among patients with heart failure during 2000–2003

 
Calculation of age-adjusted odds ratio (ORs) showed the risk of death associated with various clinical parameters and drugs used for treatment. We found that cardiomyopathy was associated with lower mortality risk: ORs=0.49 (0.27–0.86) obviously due to frequent management by heart transplantation. The history of previous myocardial infarction (MI) among patients with HF was associated with significantly high risk of death: ORs=2.09 (1.45–3.02). Hypertension and diabetes were not found as significant factors for increased risk of death in our sample (Fig. 1). Treatment with digoxin and diuretics increased the mortality risk significantly: ORs=1.75 (1.24–2.49) and ORs=1.99 (.25–3.17), respectively. It was noted that patients receiving digoxin and diuretics had a higher mean NYHA class (III vs. II–III) and higher age (75±10 vs. 63±12 years, p<0.01) than patients who were not receiving these drugs; however, there was no difference in ejection fraction (36.5±17.6% vs. 37.7±15%). On the other hand, treatment with beta-blockers and statins significantly reduced the mortality risk: ORs=0.56 (0.35–0.90) and ORs=0.44 (0.26–0.74), respectively. Use of aspirin, any antagonists of the renin–angiotensin–aldosterone system (i.e. ACE inhibitors, spironolactone, angiotensin II antagonists) and fibrates did not influence the risk of death in our sample of patients with HF (Fig. 2).


Figure 1
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  		Fig. 1 Personal and clinical parameters and age-adjusted risk of death. CHD=coronary heart disease, CM=cardiomyopathy, HT=hypertension, MI=myocardial infarction, DM=diabetes mellitus, ORs=age-adjusted odds ratio. n=588.

 


Figure 2
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  		Fig. 2 Type of treatment and age-adjusted risk of death in patients with heart failure. AAT II=antagonists of AT1 receptors for angiotensin II, ORs=age-adjusted odds ratio. n=588.

 
Using a multifactorial logistic regression model, taking death as a dependent variable and personal, clinical, laboratory and therapeutic parameters as independent variables, we found that age, history of previous MI and higher plasma creatinine level were observed significant positive predictors of death in patients with HF. In contrast, therapy with statins was independently associated with a reduced risk of death (Table 3).


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  		Table 3 Independent predictors of mortality in patients with heart failure (multiple logistic regression model)

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 Acknowledgments
 References
 
During a period of just 6 weeks in six hospitals in the Czech Republic, 588 death and discharges related to HF were identified which constituted approximately 25% of all medical admissions. There was a high mortality in the first 12 weeks. Thereafter, mortality plateauxed at around 12% per annum. Mortality tended to be higher in women perhaps reflecting their greater age. Sex was not an independent predictor of mortality after adjustment for other factors. These data contrast with other reports [3,4].

Diabetes mellitus was not found to be predictive of outcome either on univariate or multivariate analysis. Diabetes has not been consistently associated with increased mortality in studies of HF [5–7].

Interestingly, left ventricular ejection fraction was not a predictor of outcome either on univariate or multivariate analysis. This may reflect the fact that the ejection fraction reported was that obtained from routine medical practice and not necessarily on the index hospital admission. The strongest independent predictor of death was a history of prior myocardial infarction, a group of patients who might be expected to have more severe left ventricular systolic dysfunction. However, other studies of elderly patients admitted to hospital with HF have suggested that long term mortality is similar in patients with or without left ventricular systolic dysfunction [8].

Observational studies are not an appropriate way to assess whether a treatment is effective or not, since the treatment may be associated with other factors which might drive prognosis. For instance, patients taking diuretics and digoxin had a worse prognosis, which may reflect the fact these were sicker patients. Similarly, patients taking beta-blockers had a better outcome, but beta-blocker use was associated with a younger age and male sex. Most patients were treated with ACE inhibitors and therefore it is perhaps not surprising that a lower mortality was not observed in this group of patients. It is also unclear how the lower mortality in patients taking statins should be interpreted. Again, this may reflect their use in younger patients. Two large randomised controlled trials are currently underway, comparing statins with placebo [9].


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
Acknowledgments
 References
 
Patients with HF enrolled in the EuroHeart Failure Study in the Czech Republic are generally investigated appropriately and the majority of patients with left ventricular systolic dysfunction are treated with ACE inhibitors and beta-blockers. Nevertheless, approximately one third of the patients will die within 3 years.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Acknowledgments
References
 
The authors are grateful to Prof. J. Cleland for the many helpful suggestions in the preparation of this report.

This study was supported by the research grant—Ministry of Health, Czech Republic: IGA 71 78-3 (2002–2004).


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 Acknowledgments
 References
 

  1. Cleland J, et alfor the Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of CardiologyMason J, et alfor the Medicines Evaluation Group Centre for Health Economics UoY. The EuroHeart Failure Survey of the EUROHEART Survey Programme: a survey on the quality of care among patients with heart failure in Europe. Eur J Heart Fail (2000) 2(2):123–132.[Abstract/Free Full Text]
  2. Cleland JGF, et al, for the Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure Survey Programme: Survey on the Quality of Care Among Patients with Heart Failure in Europe: Part 1Patient Characteristics and Diagnosis. Euro Heart J (2003) 24:442–63.[Abstract/Free Full Text]
  3. Gustafsson F., Torp-Pedersen C., Burchardt H., Buch P., Seibaek M., Kjoller E., et althe DIAMOND study group. Female sex is associated with better long-term survival in patients with congestive heart failure. Eur Heart J (2004) 25:129–135.[Abstract/Free Full Text]
  4. Cowburn P.J., Cleland J.G.F., Coats A.J.S., Komajda M. Risk stratification in chronic heart failure. Eur Heart J (1998) 19:696–710.[Free Full Text]
  5. De Groote P., Lamblin N., Mouquet F., Plichon D., McFadden E., Va Belle E., et al. Impact of diabetes mellitus on long term survival in patients with congestive heart failure. Eur Heart J (2004) 25:656–662.[Abstract/Free Full Text]
  6. Ryden L., Armstrong P.W., Cleland J.G., Horowitz J.D., Massie B.M., Packer M., et al. Efficacy and safety of high-dose lisinopril in chronic heart failure patients with high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J (2000) 21(23):1967–1978.[Abstract/Free Full Text]
  7. Erdmann E., Lechat P., Verkenne P., Wiemann H. Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in high-risk patient groups with chronic heart failure. Eur J Heart Fail (2001) 3:469–479.[Abstract/Free Full Text]
  8. Cleland J.G.F., Tendera M., Adamus J. on behalf of the PEP-CHF investigators. Perindopril for elderly people with chronic heart failure: the PEP-CHF study. Eur J Heart Fail (1999) 1:211–217.[Abstract/Free Full Text]
  9. Tavazzi L., Tognoni G., Franzosi M.G., Latini R., Maggioni A.P., Marchioli R., et al. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail (2004) 6:635–641.[Abstract/Free Full Text]

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