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European Journal of Heart Failure 2007 9(9):879-885; doi:10.1016/j.ejheart.2007.05.014
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© 2007 European Society of Cardiology

Temporal trends in the frequency and longer-term outcome of heart failure complicating myocardial infarction

Farid Najafia,*, Annette J. Dobsona, Michael Hobbsa and Konrad Jamrozika

a School of Population Health, University of Queensland Herston Road, Herston, Queensland 4006, Australia
b University of Western Australia Australia

* Corresponding author. Tel.: +61 7 33464696; fax: +61 7 33655540. E-mail address: s4048347{at}student.uq.edu.au


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Aims: To investigate trends in incidence and long-term outcome of heart failure (HF) developing within 28 days of first-ever acute myocardial infarction (AMI).

Methods and results: We identified all residents of Perth, Western Australia aged 25–64 years, with no history of HF, who experienced a non-fatal, first-ever AMI between 1984 and 1993, and followed them for ten years. All patients (N=4006) met the criteria for ‘definite AMI’ in WHO MONItoring trends and determinants of CArdiovascular disease (MONICA) Project and 897 (22.4%) had early-onset HF complicating the index event. After adjustment for age, current smoking, history of diabetes and hypertension, Q-wave and anterior wall AMI, the odds of developing HF declined by 9% (odds ratio for period 1989–1993 relative to 1984–1988=0.91, 95% confidence interval (957percnt;CI): 0.78 to 1.06). Over 10 years of follow-up, patients with early-onset HF had a cumulative average number of re-admissions of 28 per 100 as compared with 9 per 100 in patients without HF. After adjustment for age, history of diabetes and hypertension, the hazard of death in patients with early-onset HF declined by 26% (HR for the period 1989–1993 relative to 1984–1988=0.74, 95%CI: 0.57 to 0.96).

Conclusion: Our data suggest a decline in the incidence of, and show encouraging evidence of improvement in survival after, early-onset HF complicating AMI.

Key Words: Heart failure • Myocardial infarction • Trends • Incidence • Survival • Western Australia

Received February 23, 2007; Revised April 4, 2007; Accepted May 21, 2007


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Heart failure (HF) is a common health problem worldwide. It has a poor prognosis (5-year cumulative mortality of around 50%) [1,2], with a high frequency of re-admissions to hospital (35%-50% within 6 months) [3,4]. Despite the importance of HF, its epidemiological features are incompletely documented or understood.

HF is a heterogeneous condition with several underlying causes that affect its epidemiology. Over the last two decades, there have been remarkable changes in the factors that contribute to the incidence of HF. It is widely believed that coronary artery disease is the major underlying cause of HF, accounting for more than 70% of cases [5]. Recent improvements in treatment of acute myocardial infarction (AMI) may have increased the proportion of the population-wide burden of HF attributable to AMI [6]. Hence, understanding the epidemiology of HF requires investigation of HF in the setting of AMI.

There are few whole-of-community studies of trends in HF complicating AMI and the available studies have yielded contradictory evidence regarding trends [7-11]. In addition, most of these studies have been conducted in North America. Of particular interest is the extent to which HF as an early complication (developing within 28 days) of AMI goes on to become chronic HF.

The World Health Organization MONItoring trends and determinants of CArdiovascular disease (MONICA) Project was a population-based study of trends in mortality, morbidity and risk factors for AMI. Using MONICA data from Perth, Western Australia, we have investigated trends in the incidence and long-term outcome of HF developing within 28 days of first-ever AMI. Our focus was on patients who survived the initial AMI because it is only these individuals who can potentially contribute to the community-wide caseload of chronic HF. We hypothesized that the frequency and possibly the long-term outcome of HF complicating first AMI, changed during the decade covered by the MONICA Project.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
The MONICA register in Western Australia covered residents of the Perth Statistical Division, effectively the metropolitan area of Perth, the capital city, aged 25-64 years. It included all major coronary events from 1984 to 1993 using the ‘cold pursuit’ method to identify non-fatal potential cases through surveillance of hospital discharge codes [12]. For each hospital record indicating AMI or subacute coronary heart disease (ICD-9-CM codes 410 and 411, respectively), a research nurse abstracted data including demographic details, medical history, presenting symptoms and signs, complications occurring while the patient was in hospital, and information on medications before the event, in hospital and on discharge.

The present analyses concern all patients with events which met the following criteria: the patient had no history of previous AMI or history of HF in the hospital record; the event met the MONICA criteria for ‘definite AMI’ [12]; and the patient was still alive 28 days after the onset of the symptoms of AMI. The criteria for definite AMI remained stable over the period of the study.

2.1. Definition of heart failure
We regarded a patient as having HF when either the medical record showed that he or she had cardiogenic shock, pulmonary oedema and cardiac failure while in hospital or the electronic record for the admission included the ICD-9-CM code for HF (428) and the patient was given diuretics while in hospital. We refer to such cases as ‘early-onset HF’, as opposed to ‘late-onset HF’ developing more than 28 days after the index AMI. Cardiogenic shock referred to systolic blood pressure less than 90 mm Hg. A diagnosis of pulmonary oedema required dyspnoea, tachypnoea (>23 breaths/min) and widespread fine or coarse crepitations not due to asthma. Cardiac failure was defined by the presence of at least two of bilateral basal crepitations not cleared by coughing, peripheral oedema and persistently elevated venous pressure, or by an entry in the medical record indicating that left ventricular failure was established.

2.2. Definitions of covariates
To indicate the severity of AMI, we classified each patient's maximum pulse rate within the first 24 h into one of two categories: normal (60-100 beats/min) and either bradycardia or tachycardia (<60 or >100 beats/min). The first recorded systolic blood pressure after the onset of symptoms of AMI was categorized into two groups (<100 mm Hg, ≥100 mm Hg). We also classified length of hospital stay (LOS) into two categories: ≤10 days and >10 days. Diabetes mellitus (DM) was defined by treatment with insulin or oral hypoglycaemic agents immediately prior to admission; patients managed by diet alone were considered as diabetic if their diagnosis was confirmed by the referring doctor's letter or the hospital record. Similarly, hypertension was defined by treatment for this condition at the time the AMI occurred. Patients were categorized as current smokers or non-smokers. Peak creatine phosphokinase (CPK) was defined as the ratio of the maximum CPK value for the event to the relevant upper limit of normal. The MONICA database includes Minnesota codes for up to four electrocardiograms together with summary variables for any ST-elevation, new Q-wave or anterior wall AMI. Reperfusion therapy during the index hospital admission included either medical (use of streptokinase or recombinant tissue plasminogen activator) or invasive (coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA)) approaches. Angiotensin converting enzyme inhibitors (ACEi) were introduced during the period covered by the MONICA Project and were included in a category named ‘other anti-hypertensive agents’, which excluded diuretics, beta-blockers and calcium channel blockers (CCBs).

2.3. Ascertainment of death and subsequent hospital admissions
Using the Western Australia Linked Data System (WALDS) [13], we followed up all patients included in our study sample for subsequent hospital admissions with a diagnosis of HF (either as principal diagnosis or second diagnosis) and for death. Very few residents of Western Australia with AMI die in other parts of the country [14].

2.4. Statistical analysis
Using Stata 9 [15], we summarized the characteristics of patients using proportions or means and standard deviations. Using univariate logistic regression, we calculated crude odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) to compare patients with and without early-onset HF. To check trends in severity of AMI, changes in systolic blood pressure, pulse, LOS, and ECG presentation were analysed using the chi-squared test, as were changes in use of treatments. Secular changes in CPK ratio were assessed using the t-test.

To investigate the adjusted trends in risk of occurrence of early-onset HF after first-ever AMI, we used multiple logistic regression of early-onset HF against period (1989-1993 relative to 1984-1988) and adjusted for other variables that were statistically significantly predictors of the development of this complication in univariate logistic regressions. We also used univariate and multiple proportional hazard regression models to investigate factors associated with re-admission to hospital with a diagnosis of HF and with all-cause-mortality. To ensure comparability of follow-up, we calculated hazards during the 10 years beginning 28 days after the index hospital admission. We summarized the findings as ORs and hazard ratios (HR) and corresponding 95%CIs as well as calculating an event-based 10-year cumulative average number of re-admissions for patients with or without HF. We also summarized the probability of death using adjusted Kaplan-Meier curves based on a corrected group prognosis method [16]. Figures for crude cumulative mortality at 1, 5 and 10 years were estimated. Age was added to the models as a categorical variable (24-54, 55-59, and 60-64 years). Because of collinearity between ST-elevation and reperfusion therapy, we used only development of a Q-wave and anterior wall AMI as summary ECG variables.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
After exclusion of patients who died within 28 days and those with a history of HF before their first AMI, a total of 4006 patients with first-ever AMI met the inclusion criteria between 1984 and 1993.

Of these 4006 patients, 897 (22.4%) developed HF within 28 days of initial admission to hospital with a definite AMI. Table 1 shows that, compared with those without HF, patients with early-onset HF were older, more likely to be women, to have diabetes and hypertension, and to be current smokers. Patients who developed early-onset HF were marginally more likely to receive thrombolytic therapy. Univariate logistic regression suggested a 12% decline in risk of early-onset HF in 1989-1993 compared with 1984-1988 (OR for period=0.88, 0.95%CI: 0.76 to 1.02).


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  		Table 1 Characteristics of patients aged 25-64 years with first-ever myocardial infarction, with or without early-onset heart failure, MONICA Project, Perth, Western Australia, 1984-1993

 
3.1. Severity of myocardial infarction and its secular trends
Patients with early-onset HF had a higher mean peak CPK ratio than those who did not develop HF within 28 days. They were also more likely to have a maximum pulse of less than 60 beats/min or more than 100 beats/min. They stayed longer in hospital and showed more abnormalities in their ECGs (Table 1).

Analysis of data from all patients (with and without early-onset HF) showed no significant changes, in 1989-1993 relative to 1984-1988, in proportions of patients with a pulse of less than 60 beats/min or more than 100 beats/min in the first 24 h (27.6% vs. 26.8%, p for trend=0.41), or in the proportion with an initial systolic blood pressure lower than 100 mm Hg (6.6% vs. 5.2%, p for trend=0.06). The mean peak CPK ratio for all patients increased from 8.4 in 1984-1988 to 9.2 in 1989-1993 (p=0.002). However the proportions of patients who had ST-elevation or Q-wave AMI declined from 64.6% to 59.0% (p=0.001) and from 49.9% to 44.6% (p<0.001), respectively. There was no significant change in the proportion of patients with anterior wall AMI from 1984-1988 to 1989-1993 (p=0.06).

3.2. Management of heart failure
Differences in treatment before admission, in patients who did or who did not develop early-onset HF reflect the prevalence of other cardiovascular conditions (Table 2). Once admitted, patients who developed early-onset HF were much more likely to receive digitalis and ‘other anti-hypertensive agents’. Unsurprisingly, they were 28 times more likely to be prescribed diuretics at discharge and greater proportions were also prescribed digitalis and ‘other anti-hypertensive agents’. On the other hand, fewer patients with early-onset HF received beta-blockers and anti-platelet treatment during the hospital admission or CCBs at discharge.


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  		Table 2 Treatments of patients aged 25-64 years with first-ever myocardial infarction, with or without early-onset heart failure, MONICA Project, Perth, Western Australia, 1984-1993

 
From 1984-1988 to 1989-1993, regardless of the development of HF, patients became 5 times more likely to be prescribed ‘other anti-hypertensive agents’ (19.2% vs. 3.9%) at discharge. Also greater proportions were discharged with anti-platelet agents (85.8% vs. 42.4%) and beta-blockers (77.0% vs. 60.6%). In addition, the use of streptokinase increased from 17.3% to 47.9%.

3.3. Predictors of early-onset heart failure
After adjustment for variables other than aspects of treatment that were significantly associated with the incidence of early-onset HF in univariate analyses, there was some evidence of a reduction in the odds of early-onset HF from 1984-1988 to 1989-1993 (OR for period=0.91, 95%CI: 0.78 to 1.06). Age, current smoking, history of hypertension and history of diabetes, Q-wave and anterior wall AMI were positively and statistically significantly associated with occurrence of HF (Table 3).


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  		Table 3 Predictors of early-onset heart failure after first-ever myocardial infarction, MONICA Project, Perth, Western Australia, 1984-1993, patients aged 25-64 years: multivariable analysis

 
3.4. Subsequent admissions to hospital with a diagnosis of heart failure
After 10 years of follow-up, from the total of 897 patients with early-onset HF after AMI, 12.4% (n=108) had at least one subsequent admission to hospital with a diagnosis of HF (recorded in either the first or the second diagnostic position). The corresponding proportion for those without early-onset HF was 4.4% (n=138). The cumulative 10-year average number of re-admissions with a diagnosis of HF was 28 per 100 and 9 per 100, for patients with and without early-onset HF, respectively (Fig. 1). In addition to early-onset HF, age, history of diabetes, hypertension and current smoking were positively associated with a subsequent admission to hospital with a diagnosis of HF in both univariate and multivariate analyses (Table 4). There were no significant changes in the hazard of first re-admission with a diagnosis of HF between 1984-1988 and 1989-1993.


Figure 01
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  		Fig. 1 Event-based cumulative average number of re-admissions with a diagnosis of heart failure during 10 years of follow-up, MONICA Project, Perth, Western Australia, 1984-1993, patients aged 25-64 years.

 


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  		Table 4 Predictors of subsequent hospital admission with a diagnosis of heart failure among patients aged 25-64 years with first-ever myocardial infarction, during 10 years of follow-up, MONICA Project, Perth, Western Australia, 1984-1993

 
3.5. Survival after early-onset heart failure: trends and correlates
After 10 years of follow-up, 44 (24.6%) of the women and 187 (26.0%) of the men with early-onset HF had died. The crude cumulative mortality from all causes was 25.8% (95%CI: 22.9% to 28.6) and 13.7% (95%CI: 12.5-14.9) for patients with and without early-onset HF (p<0.001), respectively. The 1-year and 5-year mortality figures among patients with early-onset HF were 4.0% (95%CI: 2.9 to 5.5) and 13.2% (95%CI: 11.1 to 15.5), respectively. There was no statistically significant difference between the crude 1-year (ratio=1.4, 95%CI: 0.73 to 2.7) and 5-year mortality figures (ratio=1.28, 95%CI: 0.88-1.89) for cases from 1984-1988 relative to 1989-1993. While the crude survival over 10 years of follow-up improved over time (p=0.03), after adjustment for age, sex, history of diabetes, history of hypertension and reperfusion, there was no statistically significant difference in 10-year mortality between 1984-1988 and 1989-1993 (Fig. 2 and Table 5).


Figure 02
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  		Fig. 2 Adjusted estimates for cumulative mortality among patients aged 25-64 years with early-onset heart failure complicating first-ever non-fatal definite myocardial infarction, MONICA Project, Perth, Western Australia, 1984-1993.

 


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  		Table 5 Hazard of all-cause mortality during 10 years of follow-up among patients aged 25-64 years with early-onset heart failure complicating first-ever non-fatal definite myocardial infarction, MONICA Project, Perth, Western Australia, 1984-1993

 
The risk of death increased with increasing initial age and history of diabetes (Table 5). Reperfusion therapy was associated with a significant protective effect, even in multivariable analysis. The adjusted hazard ratio of death declined from 1984-1988 to 1989-1993 by 26% (HR=0.74, 95%CI: 0.57 to 0.96) or 14% (HR=0.86, 95%CI=0.65 to 1.13) without or with inclusion of reperfusion therapy in the model.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
In this population-based cohort the estimated percent decline, from 1984-1988 to 1989-1993, in the odds of HF as an early complication of AMI was 9% (OR for period=0.91, 95%CI: 0.78 to 1.06). Over the same period, survival to 10 years after early-onset HF improved by 26% (HR for period=0.74, 95%CI: 0.57 to 0.96), with approximately half of this reduction being due to the use of reperfusion.

The present report is one of the few population-based studies of the trends in the incidence and long-term survival of early-onset HF after AMI anywhere in the world. For an earlier period, 1950-1989, the Framingham investigators did not detect a temporal decline in early-onset HF after Q-wave AMI [8]. Despite a recent finding from the Worcester Heart Attack Study [10] of an increase in adjusted risk of early-onset HF after AMI since 1975-1978, an older report from the Worcester Study [9] showed a modest decline in the proportion of patients with AMI developing HF in hospital from 1975-1978 to 1993-1995. Investigators from Olmsted County [7] have also reported a 2% annual decline in incidence of HF after AMI (early- and late-onset HF combined) from 1979 to 1994.

While these latter two results are similar to our findings, the absolute incidence of HF varies between these studies: 37.8% in Worcester (1993-1995) [9], 24.2% in Olmsted County [7], 14.6% in Framingham (1980-1989) [8] and 22.4% in our study, which involves a younger group of patients than the other reports. At least in part such variation arises because the different investigations have employed different definitions of HF. However, comparisons of temporal trends over equivalent periods should be valid. In our sample the proportion of out-of-hospital deaths for patients with AMI remained stable over time, indicating that trends in early-onset HF have not been distorted by changes in the proportion of patients with AMI who reached hospital alive [17]. In addition, definite AMI was defined using the MONICA criteria, which also remained stable over the study period.

Consistent with reports of a progressive decline in the severity of AMI [18], the proportions of our patients with first-ever definite AMI who had ST-elevation or developed a Q-wave fell over the decade from 1984. However, there were no significant changes in systolic blood pressure and pulse. The observed increase in the mean peak CPK ratio in our data is confounded by a tripling in the proportion of patients receiving thrombolytic therapy.

The medical management of both AMI and HF evolved significantly from the mid-1980s to the early 1990s, but our findings of lower use of beta-blockers and anti-platelet agents, and higher use of calcium channel blockers in patients with early-onset HF are similar to patterns observed in a population-based study of medical records in Worcester [9]. The lower use of beta-blockers appears to exceed any caution of physicians in prescribing such treatments in patients with cardiogenic shock or pulmonary oedema.

We found that patients with early-onset HF were re-admitted more frequently with a diagnosis of HF (Fig. 1 and Table 4). Given the longer survival among patients without HF the apparent difference in risk of re-admission with HF probably under-estimates the true difference. In a minority of patients with signs and symptoms of HF after AMI, cardiac dysfunction may be a transient problem resulting from arrhythmia, papillary muscle dysfunction or myocardial stunning. However, in our data, early-onset HF was an important risk factor for a subsequent hospital admission with HF.

There are few population-based studies of trends in long-term survival following hospital discharge for patients with early-onset HF after first-ever AMI [9,19]. Because we studied only non-fatal cases of AMI in relatively young patients, the absolute long-term cumulative mortality was lower in our series compared with many previous reports. Nevertheless, as in the Worcester study [9], we did not find an improvement in one-year survival over time. However, we showed that survival over 10 years of follow-up after a diagnosis of HF complicating first-ever AMI did improve over time. This contrasts with the Rochester Epidemiology Project in which there was no detectable improvement in survival of patients with HF after AMI between 1979 and 1998 [19]. Even so, other studies have shown that long-term survival among patients with HF (regardless of the underlying aetiology) has improved over the time [1,20].

Several factors may affect trends in survival after a diagnosis of HF. Improvement in the treatment of HF is one possibility. Consistent with the growing evidence regarding the effectiveness of ACE inhibitors, the proportion of our patients who received ‘other anti-hypertensive agents’, which included ACE inhibitors, after discharge increased from 3.9% in 1984-1988 to 19.2% in 1989-1993. Because our data do not provide information on withdrawal of drugs, we could not adjust our statistical model of survival for changes in medication.

In Perth, the use of reperfusion therapy during the admission to hospital for first-ever AMI increased from 20.8% in 1984-1988 to 57.6% in 1989-1993. Although there is some controversy about the effect of reperfusion (specifically fibrinolysis) on survival of patients with AMI complicated by HF [21], we found that reperfusion therapy was associated with better long-term survival, even after adjustment for multiple other factors. Indeed, it seems that a substantial fraction of the observed improvement in survival of patients with early-onset HF was due to reperfusion therapy; the temporal trend was not statistically significant after a term for reperfusion therapy was forced into the multivariate model presented in Table 5.

4.1. Limitations
Although the available data did not permit use of the Framingham criteria to define HF, all of our cases met the criteria defined by the Study of Men Born in 1913 [22]. In addition, the definitions of the clinical signs and symptoms that we used to identify HF were stable over the period of the MONICA study. Our exclusion of older people limits the generalizibility of the absolute values we report for the incidence and survival of patients with a first-ever AMI complicated by HF. Conversely, the selected nature of our initial cohort probably serves to reduce the variability associated with lack of specificity in the underlying cause of HF and therefore our results on trends in incidence of, and survival after, early-onset HF are not confounded by changes in prevalence and prognosis associated with different underlying causes for HF. While the management of AMI and HF has changed since the period in which our patients initially presented, the absolute incidence of early-onset HF we report is comparable with that from studies carried out more recently [7-9]. In any case, one needs to look at patterns of aetiological factors well into the past if we are to understand the epidemiology of chronic conditions such as HF as they appear today. Our series is twice the size of that investigated in Olmsted County, Minnesota [7] (1537 patients) and eight times that reported from the Framingham Heart Study [8] (589 patients), giving us greater power to show changes over time in the incidence and outcome of HF after AMI. However, because of smaller proportion of women (16.0%) in our sample compared with Framingham (29.0%) and Olmsted County (39.0%), our study has more limited power to examine the trends in events by sex.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
This population-based study suggests that the incidence of HF complicating first-ever AMI may have fallen (OR=0.91, 95%CI: 0.78-1.06) from 1984 to 1993 in the largest city in Western Australia. In keeping with previous studies, we found no change in one-year survival of such patients, but our data provide evidence of an improvement in longer-term survival of patients with early-onset HF (HR=0.74, 95%CI: 0.57-0.96).


   Acknowledgement
 
We are grateful to the School of Population Health at the University of Western Australia for providing us with a de-identified copy of MONICA data linked to Mortality and Hospital Morbidity Data. The Government of Iran has provided a scholarship to support Dr Najafi's studies in Australia.


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

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F. Najafi, K. Jamrozik, and A. J. Dobson
Understanding the 'epidemic of heart failure': a systematic review of trends in determinants of heart failure
Eur J Heart Fail, May 1, 2009; 11(5): 472 - 479.
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 Eur Heart JHome page
P. Abrahamsson, J. Dobson, C. B. Granger, J. J.V. McMurray, E. L. Michelson, M. Pfeffer, S. Pocock, S. D. Solomon, S. Yusuf, K. Swedberg, et al.
Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
Eur. Heart J., February 1, 2009; 30(3): 338 - 345.
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 J Am Coll CardiolHome page
J. A. Ezekowitz, P. Kaul, J. A. Bakal, P. W. Armstrong, R. C. Welsh, and F. A. McAlister
Declining in-hospital mortality and increasing heart failure incidence in elderly patients with first myocardial infarction.
J. Am. Coll. Cardiol., January 6, 2009; 53(1): 13 - 20.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
A. Torabi, J. G.F. Cleland, N. K. Khan, P. H. Loh, A. L. Clark, F. Alamgir, J. L. Caplin, A. S. Rigby, and K. Goode
The timing of development and subsequent clinical course of heart failure after a myocardial infarction
Eur. Heart J., April 1, 2008; 29(7): 859 - 870.
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