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European Journal of Heart Failure 2005 7(4):662-670; doi:10.1016/j.ejheart.2005.01.014
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© 2005 European Society of Cardiology

Acute heart failure: Clinical presentation, one-year mortality and prognostic factors

Alain Rudigera,*,1, Veli-Pekka Harjolab,1, Andreas Müllera, Eero Mattilab, Petrus Säilab, Markku Nieminenb and Ferenc Follatha

a Department of Medicine, University Hospital Zürich Switzerland
b Department of Medicine, Helsinki University Central Hospital Finland

* Corresponding author. Present address: Wolfson Institute of Biomedical Research, University College London, The Cruciform Building, Gower Street, London WC 1E 6BT. Tel.: +44 207 679 6666; Fax: +44 207 691 3104. E-mail address: arudiger99{at}yahoo.de


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Aims: Acute heart failure (HF) is a common but ill-defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an unfavourable outcome.

Methods and results: We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty-eight percent had de-novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV-EF was <35%, 35–50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU-treatment was necessary in 39% of the patients. Thirty-day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve-month all-cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age.

Conclusions: This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high.

Key Words: Acute heart failure • Cardiogenic shock • Pulmonary oedema • Mortality

Received August 9, 2004; Revised November 25, 2004; Accepted January 27, 2005


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Numerous studies have addressed the problem of chronic heart failure (HF) but acute HF has widely been neglected in the past. However, the number of patients suffering from acute heart failure (HF) is increasing, and the prognosis of acute, decompensated HF seems to be poor with a high in-hospital and midterm mortality [1–9]. Only little is known about the long-term prognosis and possible risk factors for a fatal outcome in this population [10]. Furthermore, the lack of a generally accepted definition has led to only poorly comparable results. In view of new diagnostic and therapeutic options a reassessment of the problem is required [11,12]. The aim of our prospective observation study was to use the same diagnostic criteria for acute HF in two different European centers, and to describe patients with acute HF with regard to clinical presentation, mortality, and risk factors for an unfavourable outcome.


   2. Methods
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Study population
We conducted a prospective observational study using an identical evaluation protocol in the University Hospital of Zurich, Switzerland (named as center 1 in the following text ), between December 2001 and September 2002, and in the Helsinki University Central Hospital, Finland (center 2) between September 2002 and February 2003. Center 1 operates both as tertiary referral hospital and as primary care facility, and center 2 is a tertiary referral hospital. The reference population for the primary care and tertiary referrals for center 1 is 100,000 and 1.5 million inhabitants, and 1.4 million inhabitants for tertiary care in center 2, respectively.

2.2. Diagnosis of acute heart failure
Acute HF was diagnosed in the presence of:

  1. an underlying heart disease
  2. at least two of the following clinical symptoms or signs: dyspnea NYHA III or IV, orthopnea, rales, elevated jugular venous pressure or systolic blood pressure (BP) below 90 mmHg with decreased end-organ perfusion
  3. a characteristic chest X-ray (cardiomegaly, venous congestion and/or pulmonary oedema).

Importantly, there had to be a rapid onset or significant worsening of HF symptoms within 7 days before admission.

The diagnosis of acute HF was made by the physicians in charge of the patient either at the emergency room, at the medical intensive care unit (ICU), or on the ward. In both hospitals all patients admitted to any of the medical wards, including the ICU, the cardiac care unit, and the cardiology clinic, were screened for these diagnostic criteria. At discharge acute HF had to be listed as one of the major diagnoses. Each patient was enrolled only once, even if he/she was readmitted during the observation period. Patients were excluded from the survey if they were discharged directly from the emergency room and treated as out-patients. Other causes for exclusion were shortness of breath due to pulmonary disease, pulmonary embolism or primary pulmonary hypertension.

The characterisation of the patients included age, gender, pre-existing conditions, symptoms and signs on clinical examination. These data were collected by the study team from the patient charts. The results of the following investigations were assessed if available: blood tests, electrocardiogram (ECG), chest X-ray, echocardiogram, coronary angiography. We also evaluated the underlying cardiac disease and possible triggers of acute HF and followed the hospital course. After 12 months the patients or their general physicians were contacted from center 1. In center 2 survival information was obtained from national mortality registry.

2.3. Case definition
Patients included in the study were classified in one of the following three categories according to the modified Killip and Kimball classification [13,14]:

Cardiogenic shock: Impaired end-organ perfusion with the clinical signs of cold skin, decreased mental performance or oliguria and a systolic BP below 90 mmHg despite adequate treatment with fluids, or need of inotropes or vasopressors.

Pulmonary oedema: Dyspnea at rest, rales over all lung fields and chest X-ray compatible with alveolar pulmonary oedema without cardiogenic shock.

Congestive HF: Symptoms and signs of HF exclusive of cardiogenic shock or pulmonary oedema.

The study population was subdivided into groups of new acute HF and decompensated chronic HF. New (de-novo) acute HF was defined as the first manifestation of HF in patients without any previous episode of HF. Decompensated chronic HF was defined as rapid worsening of HF symptoms and signs in patients with pre-existing chronic HF.

2.4. Statistical analysis
All data were collected from the patient charts and entered into a computerised database. Median (range), mean (±SD) or percentage were calculated for the overall sample and subgroups. Comparisons were made with the use of the Mann–Whitney U test, t-test, Fisher's exact test, or the chi-square test, as appropriate. Survival estimates for all cause mortality were calculated with the method of Kaplan and Meier. The Log Rank test was used to compare the mortality of subgroups. All analyses were performed with the use of SPSS 11.5 for Windows. p-Values below 0.05 were taken as significant and all hypothesis testing was two-tailed.


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Patient characteristics
During the enrolment period, 96 and 216 consecutive patients with acute HF were included into the survey in centers 1 and 2, respectively. Baseline characteristics of the patients are given in Table 1. Fifty-six percent of the patients were men, and they were significantly younger than women (70±12 vs 77±12 years, p below 0.001). Twenty-eight percent of all patients had de-novo acute HF, whereas 72% had decompensation of chronic HF. Seventy-six percent of all patients were admitted to hospital within 3 days from the onset of symptoms. Co-morbidities were common and are shown in Table 2.


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  		Table 1 Baseline characteristics of patients with acute heart failure on hospital admission

 


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  		Table 2 Co-morbidities in patients with acute heart failure

 
Coronary heart disease (CHD), valvular heart disease and dilated cardiomyopathy were the three most common underlying heart diseases. In patients with valvular heart disease mitral regurgitation was the most common valve dysfunction and usually mild to moderate. However, 28 patients presented with severe aortic valve dysfunction, 17 had a history of aortic valve replacement, and 5 patients had a tricuspid valve dysfunction. Elevated systolic BP above 150 mmHg, acute ischemia and new atrial fibrillation were the most important triggers for clinical deterioration. Some patients had more than one underlying cardiac disorder or more than one possible trigger (Table 3). In 25% of the patients acute ischemia was estimated to be the trigger of acute HF. Within this group of patients 29% of patients had a ST-elevation myocardial infarction (STEMI) and the other 71% had an acute coronary syndrome without ST-elevation.


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  		Table 3 Underlying heart disease and possible triggers of acute heart failure

 
Seventy-six percent of the patients had a measurement of the left ventricular ejection fraction (LV-EF) by either echocardiography or ventriculography (Fig. 1). Median LV-EF was lower in patients from center 1 compared to patients from center 2 (34 [11–72]% vs 40 [15–80]%, p=0.042). Patients with a systolic BP >150 mmHg on admission had a higher LV-EF than patients with a systolic BP below 150 mmHg (43 [20–80]% vs 36 [11–73]%, p=0.004). Similarly, LV-EF was higher in patients with a history of elevated BP compared to patients with no history of elevated BP (42 [11–80]% vs 35 [15–73]%, p=0.002).


Figure 1
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  		Fig. 1 Distribution of left ventricular ejection fractions (LV-EF) in patients with acute heart failure.

 
Patients with renal dysfunction (creatinine clearance [Cr-Cl] below 50 ml/min) were older (79±11 vs 69±12, p below 0.001) and had a lower hemoglobin level (117 [58–165]g/l vs 136 [43–180]g/l, p below 0.001) than patients with normal renal function. Patients with diabetes had a higher creatinine level on admission (104 [48–641]µmol/l vs 89 [37–506]µmol/l, p=0.006) than non-diabetics.

3.2. Clinical presentation of acute HF
The clinical presentations differed remarkably little between the two centers. Congestive HF with clinical and radiological signs of decompensation was the predominant presentation of acute HF and occurred in 75 (78%) and 183 (85%) patients from center 1 and center 2, respectively. Pulmonary oedema was diagnosed in 13 (14%) and 28 (13%) patients from center 1 and center 2, respectively. Cardiogenic shock was present in 8 (8.3%) patients from center 1, whereas cardiogenic shock was found in only 5 (2.3%) patients from center 2. Patients with cardiogenic shock had higher troponin levels (0.28 [0–48.3]µg/l vs 0.03 [0–7.95]µg/l, p=0.001), higher creatinine levels (115 ([72–436]µmol/l vs 92 [37–641]µmol/l, p=0.04) and a lower LV-EF (27 [11–55]% vs 40 [15–80]%, p=0.005).

When patients with shock were excluded from the analysis the following differences between patients with pulmonary oedema and congestive HF were obvious: Patients with pulmonary oedema more often had a history of elevated BP (78% vs 52%, p=0.002) and a trend to higher systolic BP on admission (150 [99–227] mmHg vs 140 [70–230] mmHg, p=0.053). On the other hand patients with congestive HF had higher creatinine levels (109 [44–369]µmol/l vs 90 [37–64]µmol/l, p=0.017).

3.3. Hospital course
ICU-admission was required in 39% of all patients. The median length of ICU stay was 3 days in both centers (range 1–66 and 1–16 for center 1 and 2, respectively). Total length of stay was 11.5 (2–77) days and 8 (1–50) days in center 1 and 2, respectively (p<0.001). Eight percent of the patients died during the initial hospitalisation, 61% of the patients were discharged home, and 31% of the patients were transferred to another hospital or to another department (e.g. cardiac surgery).

3.4. Follow up
The all-cause mortality at 30 days, 12 weeks, and 1 year was 11%, 18%, and 29%, respectively (2 patients from center 1 were lost for 12-month follow up). Thirty-day mortality was influenced by the clinical presentation on admission and was 46% in patients with cardiogenic shock, 9.8% in patients with pulmonary oedema and 8.9% in patients with congestive HF (p=0.001 shock vs no-shock, p=0.774 pulmonary oedema vs congestive HF). Thirty-day mortality was higher in patients with an elevated (≥0.1µg/l) troponin T level (21% vs 7.0%; p=0.002). On the other hand, patients with a history of high BP had a lower 30-day mortality than the ones without a history of hypertension (6.5% vs 15%; p=0.016). There was a trend to a higher 30-day mortality in patients requiring ICU-treatment (14% vs 8.4%, p=0.132).

One-year survival tended to be better in center 2 with an one-year mortality of 26% vs 37% in center 1 (p=0.081). Cardiogenic shock (more frequent in center 1) was associated with a substantial all-cause mortality rate of 62% at 12 months, resulting in an odds ratio of 4.1 (95% confidence interval [CI] 1.3–12.9). Other risk factors for increased one-year mortality were impaired left ventricular systolic function, renal insufficiency, the presence of CHD, and older age (Figs. 2–5GoGoGo). Odds ratios (95% CI) for LV-EF<35%, Cr-Cl <50 ml/min, the presence of CHD, and age >75years were 2.6 (1.5–4.8), 2.5 (1.4–4.3), 1.7 (1.0–2.9) and 1.7 (1.1–2.8), respectively. Renal insufficiency and impaired LV-EF remained risk factors for death when patients with cardiogenic shock were excluded from the analysis. No significant differences in one-year survival were found with respect to gender, presence of pulmonary oedema, history of HF, history of elevated BP, underlying CHD, myocardial ischemia, positive troponin level on admission, diabetes, low hemoglobin level on admission or ICU-treatment.


Figure 2
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  		Fig. 2 Kaplan Meier curves for three groups of patients with different presentation of acute heart failure (N=312, Log Rank 0.002).

 


Figure 3
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  		Fig. 3 Kaplan Meier curves for three groups of patients acute heart failure and different left ventricular ejection fractions (N=238, Log Rank 0.001).

 


Figure 4
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  		Fig. 4 Kaplan Meier curves for two groups of patients with acute heart failure and different renal functions (N=266, Log Rank 0.001).

 


Figure 5
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  		Fig. 5 Odds ratios for different risk factors influencing one-year mortality of patients with acute heart failure. The numbers in brackets indicate the number of patients in each group. LV-EF denotes left ventricular ejection fraction, Cr-Cl creatinine clearance, CHD coronary heart disease, HF heart failure and BP blood pressure.

 

   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Acute HF can be diagnosed in the presence of an underlying heart disease and the appearance of typical symptoms and signs within 7 days. By using this simple clinical definition, we performed a prospective survey in two European centers. Therewith important insights on presentation, outcome and risk factors for increased short and long-term mortality of patients hospitalised with acute HF have been obtained.

4.1. Clinical presentation of acute HF
In the present study 4% of the patients had cardiogenic shock, 13% suffered from pulmonary oedema, and the majority presented with congestive HF severe enough to require hospital admission. Nearly one third had a de-novo acute HF, whereas two thirds had a decompensation of chronic HF. CHD was the leading underlying disease and was present in more than half the patients. The next common etiologies were valvular heart disease and dilated cardiomyopathy. Other underlying cardiopathies, like myocarditis or alcoholic cardiopathy, were rare findings. Elevated BP >150 mmHg, acute myocardial ischemia, atrial fibrillation and severe valve dysfunction were the most frequent factors associated with acute HF in our study. In contrast, acute ischemia, new atrial fibrillation and correctable valve disorders are often exclusion criteria in randomised controlled trials investigating new drugs for acute HF [15–18]. In the previous literature, the term acute has been used quite imprecisely and interpreted differently by investigators. Thus, we limited our study population to those with a time span of 7 days or less between the onset or worsening of HF symptoms and admission. More than two thirds of our patients were admitted to hospital within 72 h.

About a fourth of our population had a LV-EF <35%, a frequent inclusion criterion in chronic HF trials [19]. Thus, the clinical trials have to be interpreted with respect to their often restricted selection of patients which would exclude the majority of acute HF patients. However, a quarter of all patients presented with a preserved LV systolic function ( LV-EF ≥50%), which corresponds to previous reports [20–22].

4.2. Outcome and risk factors
The prognostic significance of elevated troponin levels was confirmed in our study, as in a wide variety of studies, especially regarding acute coronary syndrome [23–25]. Interestingly, 30-days survival was improved if the patient had a history of elevated BP. This may be explained by the higher LV-EF in patients with hypertension, an assumption that is supported by recent observations from the EuroHeart Failure Survey [26]. Another explanation might be the use of cardioprotective antihypertensive drugs like ACE-inhibitors or beta blockers in this patient group. However, treatments were not evaluated in this study and further investigations are needed to prove this hypothesis.

Twelve-months all-cause mortality was increased by older age, impaired systolic left ventricular function and renal insufficiency. Moreover, the hemodynamic status on admission was the most important risk factor for mortality. Cardiogenic shock was associated with a substantial mortality. The 30-days and 12-month mortality of 46% and 62% in our study are only partly comparable with the ones published in the SHOCK trial which investigated patients with cardiogenic shock as a complication of myocardial infarction [27,28]. In both the control group and the intervention group with early revascularisation, mortality rates were high in SHOCK trial with 56% and 47% after 30 days and 76% and 53% after 1 year, respectively. In contrast to patients with shock, the short- and long-term outcome for hemodynamically stable patients were similar whether the patients had severe congestive HF or pulmonary oedema. This stands in contrast to data on patients with acute coronary syndromes and may be a result of the limited number of patients in our study [29]. Our high all-cause mortality rate at 12 months is comparable to the findings of a study including 150 patients with HF defined by the presence of rales and/or pulmonary vascular congestion on the chest X-ray [30]. In that single center study a mortality rate of 40% after 1 year was reported, and the presence of shock and a depressed LV-EF were negative predictors of in-hospital mortality but did, in contrast to our study, not influence one-year mortality.

4.3. Differences between the study centers
In the past, the lack of a uniform definition of acute HF had led to only poorly comparable results. Using identical inclusion criteria, we found very similar and comparable findings in the two study centers. Nevertheless, few differences were present. Cardiogenic shock was more common in center 1, which can be explained by different admission policies between the two centers. Additionally, renal dysfunction was more common in center 1. On the other hand, patients from center 2 had higher BP on admission and better LV-EF. Together, these findings probably explain the longer hospital stay and the trend to a higher 12-month mortality in center 1.

4.4. Limitations of the study
Some of the key clinical signs, that is, respiratory rate, examination of the jugular venous pressure and auscultation findings (third heart sound, rales) were not systematically documented by the physicians in charge of the patients. Some of this inconsistency of data most likely reflects that normal findings were not recorded. The incompleteness of routine medical records and patient charts at least partially illustrates that physicians probably underscore the importance of clinical signs for making the diagnosis and guiding the treatment of heart failure [31,32]. This lack of systematic evaluation of symptoms and signs at baseline is a limitation of our observational study, which, however, reflects real-life practice of performing clinical examination and writing medical reports. Hemodynamic monitoring with right heart catheterisation was performed only when indicated but the results were not collected for this study. B-type natriuretic peptide levels were not measured at the time of the study.

4.5. Comparison with acute HF trials and registries
It is often questioned whether randomised clinical trials represent real-life patient populations well enough. With respect to acute HF, this question has largely been unanswered. Thus, we compared the demographic findings of our study with OPTIME, VMAC and LIDO, three recent studies investigating milrinone, nesiritide and levosimendan, respectively, in patients with acute HF [33–35]. In all three studies, patients were explicitly younger and less women were included. All trials excluded patients with, among others, ongoing myocardial ischemia, uncontrolled atrial fibrillation, corrigible valve disorders or severe renal insufficiency. Therefore it—s not surprising that mortality was lower in all three trials, both in the treatment groups, as well as, in the control groups.

In the EuroHeart failure survey, 11,327 hospitalised patients with diagnosed or suspected acute or chronic HF were investigated in Europe. In comparison to that study, a similar distribution of age and gender was observed in our series. Furthermore, the prevalence of CHD and valvular heart disease, as well as important co-morbidities like diabetes, hypertension and atrial fibrillation were comparable [36]. Nevertheless, 12-week mortality was higher in our study than in the EuroHeart failure survey, i.e. 18% and 14%, respectively. This difference might have occurred by chance only. But importantly, patients with stable HF and even only suspicion of HF were included in EuroHeart failure survey which understandably may result in a lower mortality.

Only recently, guidelines for the diagnosis and classification of acute HF have been elaborated by the European Society of Cardiology and will be published later this year. These instructions will allow a uniform patient categorisation in upcoming epidemiological surveys and clinical trials.

In conclusion, this realistic assessment of acute HF in two large European hospitals with both central and regional function describes epidemiology, clinical presentation, short- and long-term outcome, and risk factors for increased mortality. These information allow a risk assessment of patients hospitalised with acute HF, and may serve as basis for future trials investigating new therapeutic options.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
1 A. Rudiger and V.-P. Harjola contributed equally to this survey. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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