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European Heart Journal Advance Access originally published online on March 19, 2008
European Heart Journal 2008 29(7):859-870; doi:10.1093/eurheartj/ehn096
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

The timing of development and subsequent clinical course of heart failure after a myocardial infarction

Azam Torabi, John G.F. Cleland*, Nasrin K. Khan, Puan H. Loh, Andrew L. Clark, Farqad Alamgir, John L. Caplin, Alan S. Rigby and Kevin Goode

Department of Cardiology, Hull Royal Infirmary, University of Hull Castle Hill Hospital, Kingston-upon-Hull, Castle Road, Cottingham, East Yorkshire HU16 5JQ, UK

Received 7 July 2007; revised 31 January 2008; accepted 8 February 2008; online publish-ahead-of-print 19 March 2008.

* Corresponding author. Tel: +44 1482 624 084, Fax: +44 1482 624 085, Email: g.m.porter{at}hull.ac.uk

See page 833 for the editorial comment on this article (doi:10.1093/eurheartj/ehn067)


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Aims: Myocardial infarction (MI) is a common cause of heart failure (HF), which may develop early and persist or resolve, or develop late. The cumulative incidence, persistence, and resolution of HF after MI are poorly described. The aim of this study is to describe the natural history and prognosis of HF after an MI.

Methods and results: Patients with a death or discharge diagnosis of MI in 1998 were identified from records of hospitals providing services to a local community of 600 000 people. Records were scrutinized to identify the development of HF, defined as signs and symptoms consistent with that diagnosis and treated with loop diuretics. HF was considered to have resolved if diuretics could be stopped without recurrent symptoms. Totally, 896 patients were identified of whom 54% had died by December 2005. During the index admission, 199 (22.2%) patients died, many with HF, and a further 182 (20.3%) patients developed HF that persisted until discharge, of whom 121 died subsequent to discharge. Of 74 patients with transient HF that resolved before discharge, 41 had recurrent HF and 38 died during follow-up. After discharge, 145 (33%) patients developed HF for the first time, of whom 76 died during follow-up. Overall, of 281 deaths occurring after discharge, 235 (83.6%) were amongst inpatients who first developed HF.

Conclusion: The development of HF precedes death in most patients who die in the short- or long-term following an MI. Prevention of HF, predominantly by reducing the extent of myocardial damage and recurrent MI, and subsequent management could have a substantial impact on prognosis.

Key Words: Myocardial infarction • Heart failure • Epidemiology


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Heart failure (HF) is a common complication of myocardial infarction (MI), which may develop early or late. Once it has developed it may persist or resolve, and if it resolves it may re-occur. The cumulative incidence and resolution or persistence of HF after an MI is poorly described.

Surveys suggest that one-third or more patients admitted with an acute coronary syndrome (ACS) will be treated with a diuretic and it is likely that this will often be for signs or symptoms of HF.1,2 Surveys also suggest that between 9 and 55% of patients have or will develop HF during admission for MI,2–5 which may be transient or persist. The incidence of HF developing for the first time after discharge from the index admission is poorly described, with incomplete data regarding numbers surviving until discharge and confusion about how best to present incidence rates and therefore comparison between studies is difficult. Despite differences in statistical presentation, these studies would seem to suggest that most new cases of HF in those hospitalized with an MI develop during admission or early after discharge.6–8 Studies also suggest that patients who develop HF are at much greater risk of dying, whether or not they also have left ventricular systolic dysfunction (LVSD).2,9 However, few reports exist about the outcome of HF that is either transient or develops only subsequent to discharge. Also, it is unclear what proportion of cases occurring late after the index infarction is because of recurrent MI.

We set out to identify the timing of onset, persistence, resolution, and outcome of HF developing after an MI.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Study population
One hospital group in Hull and the East Riding of Yorkshire (UK) provide all of the acute cardiac services for about 600 000 people living in a geographically distinct part of the United Kingdom. Patients with a discharge diagnosis of acute MI during 1998 were identified from the Hospitals Information Department and their case notes screened. Patients who were transferred from another region, those with missing case notes, or in whom acute MI could not be confirmed from their records were excluded.

This study was approved by the Local Research Ethics Committee.

Follow-up
This was a retrospective analysis designed in 2004. The case records of all patients were reviewed to identify use of loop diuretics and if so whether this was due to symptoms or signs of HF. Follow-up data were collected until 31 December 2005. If no recent hospital record existed, the family practitioners of patients or patients themselves were contacted to ascertain the patient's current therapy and HF status. The occurrence of major events, such as recurrent MI and stroke were recorded.

Definition of myocardial infarction
At least two of the following five criteria had to be identified during case note review to confirm a diagnosis of MI.

  1. History of prolonged cardiac chest pain.
  2. An increase in biomarkers consistent with MI, which in 1998 was usually creatinine kinase (CK) ratio or CK-MB mass. These were considered abnormal if they were twice the upper limit of normal values.
  3. Progressive electrocardiographic changes consistent with MI or new onset left bundle branch block (LBBB).
  4. Sudden unexpected death
  5. Autopsy evidence of MI

Definitions
HF was clinically defined either as signs and symptoms consistent with that diagnosis (principally breathlessness and signs of fluid retention) resulting in treatment with loop diuretics or patients who died shortly after developing evidence of major cardiac dysfunction, such as cases of cardiogenic shock or pulmonary oedema. The latter group of patients were identified as a special subset so that the contribution of this group of patients to overall outcome could be identified. Cardiogenic shock was defined as an arterial pressure <100 mmHg because of low cardiac output requiring inotropic therapy or an intra-aortic balloon pump. For patients with an un-recordable blood pressure, a systolic pressure of 50 mmHg was entered as a default value for statistical purposes. Use of loop diuretics for the treatment of hypertension or renal failure was not included in the definition of HF. Evidence of LVSD was not required for a diagnosis of HF. Criteria for LVSD were left ventricular ejection fraction (LVEF)<40% or a qualitative report of moderate or severe LVSD on echocardiography, first-pass radionuclide ventriculography, or contrast angiography.

Resolution of heart failure
Consistent with European Society of Cardiology Guidelines,10 resolution of HF was defined as the withdrawal of diuretics without the recurrence of symptoms.

Statistical analysis
Data were entered into a Microsoft Access database and analysed using SPSS inc, version 13 (UK, Ltd). Key outcomes were the proportion of patients who died and mortality rate. Continuously distributed data are presented as median and inter-quartile range (IQR). Categorical data are presented as percentages. Groups of patients with and without HF were compared by the Chi-squared test. Logistic regression was used to look at the relationship between HF and gender. The incidence rate of HF per person-year of follow-up was calculated for the first year and for subsequent years of follow-up.11 This was only calculated for those discharged without HF or in whom HF had resolved by the time of discharge. Values for 95% confidence intervals (CIs) were calculated using boot strapping with 1000 re-substitutions.12

Kaplan–Meier (K–M) curves were generated to illustrate patients' overall survival and in relevant subgroups. K–M curves were compared by the log-rank test. Cox regression was used to look at mortality, from which hazard ratios (HRs) and 95% CI were calculated. The Cox regression model is semi-parametric in the sense that no assumption concerning event-free survival times is necessary. The Cox regression model is based on the assumption that the effect of a risk factor, expressed as HR, is constant over time. The purpose of this model was not to develop a risk stratification tool, but rather to determine the extent to which a particular clinical pathway altered the outcome. We present age-adjusted models in the text rather than adopting a formal statistical approach to model building (i.e. taking an epidemiological stance).

The assumption of proportionality of the Cox model covariates was tested by plotting residuals.13,14 Linearity of continuous data was checked by including a squared term.

HF status was categorized into six groups: (i) No HF at any time (this was the reference group); (ii) patients with HF on the index admission and persisting at follow-up until death or end of follow-up; (iii) persistent HF (PHF) on the index admission that resolved subsequent to discharge; (iv) transient HF (THF) on the index admission that resolved prior to discharge but recurred during follow-up; (v) THF on the index admission that resolved prior to discharge and did not recur prior to death or end of follow-up; (vi) patients who did not develop HF on the index admission, but who later developed HF during follow-up.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 Acknowledgements
 References
 
Of 1012 patients with a death or discharge diagnosis of acute MI in 1998, 116 were excluded from further analysis (78 because they had been transferred for acute management from another region, 22 because of lack of relevant documents for the event, and in 16 cases because the diagnosis of MI could not be confirmed from the record). Of the 896 patients left for the main analysis, 661 had no prior history of MI (Figure 1B). Thirty patients (3.3%) were lost to follow-up after the index admission. Documentation of the index event was generally good with little in the way of missing key data.


Figure 1
Figure 1
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  		Figure 1 (A) Flow diagram showing the sequence of development of heart failure (HF) and relationship with recurrent ischaemic episodes and mortality over approximately 6 years in patients admitted with an acute myocardial infarction (MI) to the Hull and East Yorkshire Hospitals Group during 1998. Follow-up data were incomplete in 30 patients. See text for details. (B) Flow diagram showing the sequence of development of HF and relationship with recurrent ischaemic episodes and mortality over approximately 6 years in patients who had a first acute MI (without prior MI) in the Hull and East Yorkshire Hospitals Group during 1998. Follow-up data were incomplete in 20 patients [two with transient HF (THF), two with persistent HF (PHF) during the index admission, and 16 in patients with no HF during index admission, one of whom was reported to have died by the administrative system].

 
The median age of the patients was 70 (IQR 61–78) years and 333 (37%) were women (Table 1). Of men, 141 (25%) and of women, 147 (44%) were aged >75 years. There was a prior history of hypertension in 300 (33%), MI in 235 (26%), HF in 134 (15%), and diabetes in 82 (9%). In addition, 33 (4%) patients were newly diagnosed with diabetes during the index admission. Sixty-two percent were managed, at least in part, by a cardiologist during their index admission. ST-segment elevation myocardial infarction (STEMI) was present in 518 (58%) and non-STEMI in 316 patients (35%). Forty-seven patients had LBBB, five patients were in a paced rhythm, and 10 had no ECG recording available from the time of admission. During the index admission, patients with HF were more often treated with ACE-inhibitors, nitrates, digoxin, and insulin. However, patients who developed HF on the index admission were less likely to receive beta-blockers (P < 0.0005) (Table 2).


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  		Table 1 Patient characteristics recorded during the overall index admission and classified according to the development of heart failure (HF) and mortality during index admission [data are median (inter-quartile range) and number occurring (%)]

 

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  		Table 2 Treatment during index admission and any time until 31 December 2005

 
Overall, 480 patients (54%) had died by December 2005. Figure 1A describes the sequence of events that led to the development of HF and/or death. Figure 2 shows the overall proportion of patients who developed HF at any time during follow-up and their categorization according to persistence, remission, and timing of development of HF. HF was present during the index admission in 417 (47%) patients and these patients were older [75 (67–81) vs. 66 (57–74) years; (P < 0.0001)] and more likely to be women [54% vs. 42% in men; (P = 0.001)]. The median age of women with HF was 77 (IQR 71–84) and in men with HF was 73 (IQR 64–79). In a logistic model, the relationship between HF and sex was no longer significant (P = 0.46) after adjustment for age. During the index hospitalization, 161 patients (39%) with HF died; 71 of them fulfilled the definition of cardiogenic shock. Only 38 (8%) patients who did not fulfil the criteria for HF died during the index admission. HF resolved in 74 patients (18%) and therefore only 182 patients (20%) were discharged with PHF of whom 70 had HF prior to admission.


Figure 2
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  		Figure 2 Pie chart showing the proportions of patients developing different categories of heart failure according to early mortality, timing of onset, and persistence. See methods for definitions of transient, persistent, remission, and recurrence.

 
In patients whose HF persisted until discharge, only 27 had their diuretics discontinued subsequently. Two of these patients developed renal failure and progressed to dialysis. Diuretics were stopped in three patients because of hypotension and electrolyte disturbances with a recurrence in symptoms and subsequent death. In the remaining 22 patients, diuretics were withdrawn without a recurrence of HF symptoms. Of the 182 patients with PHF at the time of discharge, 121 (66%) died within 6 years.

Of 74 patients with THF during the index admission, 41 (55%) had recurrence of HF (THF in eight), which occurred during admission for ACS or within 30 days of discharge in 18 patients. Thirty eight (51%) of these patients died during follow-up, of which 29 were after the recurrence of HF (five after THF).

Of 441 patients discharged without any occurrence of HF, follow-up data were available for 417, of whom 145 (35%) subsequently developed HF, 58 of these in the year after the index admission. HF was transient during follow-up in 26 patients (18%). Late-onset HF occurred in 46 (32%) cases during admission for ACS or within 30 days of discharge. Of the 145 patients who developed HF after discharge, 76 (52%) died (six after THF) compared with 46 (16%) among the 296 patients who never developed HF at any time.

Thus, of 278 deaths occurring subsequent to discharge following an MI, 235 (84%) occurred subsequent to the development of THF or PHF (Figures 3 and 4). In those patients who did not have HF at the time of discharge and in whom follow-up records were available (n = 489), the incidence of HF was 0.194 (95% CI 0.154–0.239) per person-year within the first year and 0.048 (95% CI 0.039–0.057) per person-year thereafter.


Figure 3
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  		Figure 3 Kaplan–Meier curves showing prognosis among patients discharged after the index myocardial infarction with and without persistent or transient heart failure. For statistical comparisons see Table 4.

 

Figure 4
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  		Figure 4 Pie chart showing the proportion of patients who died with or without preceding evidence of heart failure subsequent to discharge from index admission.

 
A report on LV function during or shortly after the index admission was available in 507 (77%) surviving patients and 71 patients who died during the index admission (Table 3). Of 255 (30%) patients reported to have LVSD during or within 90 days of admission, 46 (18%) died during the index admission, 82 (32%) developed PHF, 30 (12%) developed THF, 50 (20%) developed HF only after discharge, eight (3%) died after discharge without documented HF (one with no follow-up data), and 34 (14%) survived without documentation of HF (four with no follow-up data). A further 26 (3%) patients had a prior diagnosis of LVSD without any imaging during index or within 90 days of index admission of whom 16 (62%) died during the index admission and seven after discharge. Overall, 108 (49%) patients with documented LVSD died after discharge, 98 (91%) of whom also had HF. Of 297 patients documented not to have major LV systolic dysfunction, nine (3%) died during the index admission, 34 (11%) developed PHF, 25 (8%) developed THF, 54 (18%) developed HF only after discharge, 20 (7%) died after discharge but without developing HF (one with no follow-up data), and 142 (50%) survived without developing HF (12 no follow-up data). Overall, 67 (38%) patients who were documented not to have LVSD died after discharge, 46 (69%) of whom had HF.


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  		Table 3 Imaging evidence of left ventricular (LV) function during index admission or shortly thereaftera

 
Of 283 (33%) patients for whom no report of LV function was identified, 128 (45%) died during the index admission, 49 (17%) developed PHF, 13 (5%) developed THF, 29 (10%) developed HF only after discharge, 14 (5%) died after discharge without documented HF (one with no follow-up data), and 44 (16%) survived without documentation of HF (five with no follow-up data). Overall, 85 (49%) patients, who had no assessment of LV function reported in their records, died after discharge; 80 (94%) of them also had HF.

Mode of death
Of 199 patients who died during the index admission, the mode of death was considered to be sudden cardiac (SCD) in 55 cases (14 after arrhythmia), HF in 114, stroke in two, cardiac procedure-related in four, other cardiac in eight, infection in four, cancer in one, and other non-cardiac in 11 patients.

Of 281 patients who died after the index admission, 168 died during a re-admission to hospital and 113 died out of hospital. Out of hospital deaths were usually poorly documented but were probably sudden because of arrhythmias or vascular events. Two patients had severe HF, one died of self-poisoning, nine had advanced cancer, one had severe pulmonary hypertension, and two had stroke. Among patients who died out of hospital, 83 (73%) had either THF or PHF, 48 of whom had documented LVSD, 19 documented absence of important LVSD at last cardiac imaging prior to death. Sixteen had no assessment of LV function. 30 (27%) had no HF, seven of whom had asymptomatic LVSD, 13 had documented absence of LVSD at last cardiac imaging prior to death and also 10 had no assessment of LV function. Of those who died on re-admission, nine were attributed to SCD, 68 to HF of whom 39 fulfilled the definition of cardiogenic shock prior to death, 11 to stroke, two to cardiac procedures, four to other cardiac causes, 22 to infection, 24 to cancer, and 27 to other non-cardiac causes. One patient had missing notes.

Cox model
The age-adjusted models are presented in Table 4. Patients with PHF at follow-up had a high mortality when compared with those having no HF. Adjusting for other factors (data not shown but available on request) such as creatinine, anaemia, beta-blockers, smoking, diabetes, prior MI, history of HF, gender, ST-elevation and non-ST-elevation, SVT, PTCA, CABG, and Q wave in discharge did not alter the nature of these relationships (though obviously the HRs were different).


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  		Table 4 Cox regression models; for mortality in patients unadjusted and age-adjusted subsequent to discharge (n = 667)

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 Acknowledgements
 References
 
This report suggests that the prognosis of MI is much worse than many contemporary clinical trials suggest, and that death is usually preceded by the development of HF. Of 896 patients with a hospital diagnosis of acute MI in 1998, 562 (62.7%) had or developed HF in the following 6 years. The high proportion of patients who develop HF after an MI might seem surprising, as ischaemic heart disease is common and the prevalence of HF only about 1%. This reflects the poor prognosis of HF, often a short-lived illness usually terminated by death, and suggests that the burden of HF may be better described by its incidence rather than prevalence.15 HF is also often under-represented in health-care statistics, because events such as death or hospitalization are ascribed to the cause of HF rather than its presence. Death is usually a complex process and attributing death to only one reason is often inappropriate. For instance, a patient could die of a lethal arrhythmia in the setting of worsening HF induced by a recurrent ischaemic event. This patient died as a consequence of a constellation of events. What is important is to identify which interventions might produce worthwhile benefit for patients.

A systematic review suggested that the crude incidence of HF for any reason in the overall population is 1.3/1000/year.16 Extrapolating from our data, the population incidence of HF related to MI may be about 0.7/1000/year. As population studies suggest that only about half the cases of HF are preceded by an MI,17,18 our data appear consistent with the overall situation but provide a rather different perspective. New-onset HF after discharge was more common than in previous reports,6–8 perhaps reflecting the intensity of surveillance or the definition used in our study. However, effective treatment of MI is likely to reduce mortality to a greater extent in patients with large MIs who are then likely to survive to develop HF. Therefore, our study provides some support for the widely held suspicion that good post-infarction care will increase rather than decrease the incidence and prevalence of HF.2

Understanding the natural history of patients who have had an MI with and without HF may help inform therapeutic choices. Among patients who had HF, it was present in 23.1% prior to the index infarct, many of whom had had a previous MI, it developed for the first time during the index hospital admission in 51.1% and within 30 days of a further coronary event in 6.1%. Only 19.4% of patients developed HF more than 30 days after the index infarction without a further hospitalization for MI. Not all MIs present with typical symptoms and may manifest as worsening HF or sudden death.19–22 Thus, most cases of HF observed in this cohort occurred in close proximity to an acute coronary event. This has two important implications. First, it challenges the concept that HF is often because of progressive LV remodelling with a long prodrome. Most cases of HF may have a sudden and rather unpredictable onset because of MI or arrhythmias, which would account for why most first diagnosis of HF occurs in hospital.23 Secondly, it reinforces the view that treatment directed at reducing the extent of acute myocardial damage and prevention of re-infarction might have important effects on the development of HF.24–28,29 Trials of statins,30,31 ACE-inhibitors,32,33 aldosterone antagonists,34 and beta-blockers,35 although not aspirin,36 appear to reduce the risk of HF after MI, which is partly mediated by reducing further coronary events. It is widely believed that these treatments can also reduce the risk of recurrent MI in patients with HF, thereby improving survival.37 However, a recent large study suggested that rosuvastatin could reduce non-fatal vascular events but not mortality, perhaps because vascular events were not an important driver of outcome.38 Similarly, anti-thrombotic agents have failed, so far, to reduce mortality in HF.39 Other treatments, such as ACE-inhibitors, aldosterone antagonists, and beta-blockers, appear more effective at reducing mortality than coronary events in patients with established HF, although it has been argued that this reflects their ability to prevent some patients with MI from dying suddenly.37 Treatment directed solely at preventing progressive LV remodelling in the years after MI might have only a minor role in the prevention of HF in this population, as few patients who developed HF did so remote from an acute coronary event. However, treatments aimed predominantly at ventricular remodelling may have an important role in slowing the progression of HF once it has developed.

About 40% of the deaths that occur within approximately 6 years after an MI occur during the index admission and 35% during a subsequent re-admission. Most of these deaths were associated with severe HF. About one-quarter of patients died out of hospital. Most of these patients had developed HF prior to death, although only about 10% reported deteriorating symptoms in the month before death. Little information could be obtained on the mode of death in these patients but adjudication committees of clinical trials, that often obtain more detailed data, assign most of these to sudden death and assume that arrhythmias rather than recurrent vascular events are the cause.37 Accordingly, widespread implantation of a defibrillator theoretically might reduce mortality among discharged patients by about 30%. However, the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)40 showed that implantation of a defibrillator early after MI did not reduce mortality, perhaps because this intervention cannot reduce the commonest mode of death in these patients which is worsening HF. More aggressive pharmacological therapy41 may be the best way to manage the risk of both sudden death and worsening HF. Whether early implantation of a device that also provides bi-ventricular pacing could improve prognosis awaits the outcome of further trials.42

The prognosis of HF in this study was worse than suggested by either randomized controlled trials43,44 or many surveys of MI.1 However, using the GRACE registry score, the predicted in-hospital mortality for our patients was 22%.45 The lower mortality observed in other cohorts most likely represents case-selection, with preference being given to recruitment of younger patients, who tend to be managed by cardiologists, in trials and surveys and the exclusion of cardiogenic shock and severe HF. Age was a powerful determinant not only of prognosis but also of the likelihood of being referred to a cardiologist in our study.

As reported by others,3 LVSD and clinical evidence of HF carried independent prognostic information. Patients who had both did worse than those who had either alone. Potential markers of the metabolic stress of a large infarction and the development of HF, including renal dysfunction and hyponatraemia were also independent predictors of an adverse outcome and each a potential target for therapy.

Study limitations
Patients with THF developing either during or after the index admission that subsequently resolved permanently had a HR <1 which may seem surprising (Table 4). There were few such patients in these cohorts, the CIs around the HR were wide and overlapped that of patients who never developed HF. Patients with THF had to survive long enough to permit HF to resolve and this may have introduced methodological bias favouring outcome in patients with THF. A similar potential bias towards an over-optimistic assessment of survival exists for patients with late-onset HF who had a poor outcome when compared with those who never developed HF. Also, exclusion of patients with recurrent or late-onset HF and a poor prognosis from the groups with only THF will bias outcome favourably in the latter group. A less likely explanation for the lower mortality in patients with THF is that their intrinsic risk is similar to patients who never had HF, but that they received the prognostic benefits of treatment for HF. We also acknowledge a potential pessimistic bias in assessing outcome in patients with PHF, as patients who die early have less opportunity to recover and therefore less opportunity to be labelled as THF.46 Ultimately, this analysis is descriptive and not designed to show whether one group does better than another but rather the outcome in each individual clinical group of patients.

Our study will have missed patients who died of MI before reaching hospital and patients who, if they had symptoms, were not recognized as having had an MI. Epidemiological studies suggest that about one-third of patients with MI die before they reach hospital,47 and that about one-quarter of patients who survive an MI do not have symptoms that lead to urgent hospital referral.48–50 It is likely that the hospital records system failed to code some infarcts, although false-positive coding was rare. For these reasons, this study substantially underestimates the true incidence of MI in the community. The survey was of patients managed in 1998. Significant changes in prevention and management have occurred and may have altered outcome. In 2005, 781 patients had a death or discharge diagnosis MI reported in our hospital of which 106 died (14% compared with 22% in 1998). We defined HF as HF symptoms that led to treatment with loop diuretics but some patients may have been managed with thiazides. Not all patients had LV function assessed. Also, as systematic attempts were not made to withdraw diuretics, we may have under-estimated the transitory nature of HF in some cases. A simple, robust definition of HF remains elusive. However, patients who receive loop diuretics and who have cardiovascular disease clearly have a poor prognosis whether or not they have a low EF.49 Ultimately, HF is a clinical syndrome that relies on a doctor's skill in assessing a patient in the light of appropriate investigations.

The prevalence of diabetes mellitus was similar to that reported in another large trial from the same county in England, but is towards the lower end of the spectrum reported in the literature.8,51 This may reflect under-reporting of milder cases of diabetes, as it was not routine practice to obtain fasting blood glucose in these patients. However, surveys reporting high levels of diabetes have generally included large numbers of patients from North America, where the prevalence of diabetes is probably, genuinely higher than in our region.

Another potential limitation of our analysis is that patients who died early had less opportunity to recover or to develop late-onset HF. It is unclear how useful attempts at adjusting for this problem would be. Ultimately, our study is not trying to build a risk model, but to establish the proportion of patients who develop HF after an MI, to describe its time of onset, whether it resolves and the consequences of each in terms of mortality.


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
Acknowledgements
 References
 
In conclusion, the development of THF or PHF precedes death in the great majority of patients who die within 6 years of an MI. Most patients who develop HF after an MI do so shortly after an initial or recurrent coronary event suggesting that reducing infarct size and recurrent events rather than ventricular remodelling may be a more successful strategy to prevent HF. Improved management of HF and its important co-morbidities such as renal dysfunction and diabetes may slow the rate of progression and improve quality of life and prognosis in such patients.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
References
 
This project was supported in part by the Hull and East Yorkshire Cardiac Trust fund. We thank George Britchford, the hospital records department, and the hospital staff for their assistance in collecting these data.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 

  1. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, Boersma E, Fioretti PM, Simoons ML, Battler A. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin: the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J (2002) 23:1190–1201.[Abstract/Free Full Text]
  2. Cleland JG, Torabi A, Khan NK. Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction. Heart (2005) 91(Suppl. 2):ii7–ii13.[Abstract/Free Full Text]
  3. Kober L, Torp-Pedersen C, Jorgensen S, Eliasen P, Camm AJ. Changes in absolute and relative importance in the prognostic value of left ventricular systolic function and congestive heart failure after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Am J Cardiol (1998) 81:1292–1297.[CrossRef][Web of Science][Medline]
  4. Kober L, Torp-Pedersen C. Clinical characteristics and mortality of patients screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. Am J Cardiol (1995) 76:1–5.[CrossRef][Web of Science][Medline]
  5. Guidry UC, Evans JC, Larson MG, Wilson PW, Murabito JM, Levy D. Temporal trends in event rates after Q-wave myocardial infarction: the Framingham Heart Study. Circulation (1999) 100:2054–2059.[Abstract/Free Full Text]
  6. Hellermann JP, Goraya TY, Jacobsen SJ, Weston SA, Reeder GS, Gersh BJ, Redfield MM, Rodeheffer RJ, Yawn BP, Roger VL. Incidence of heart failure after myocardial infarction: is it changing over time? Am J Epidemiol (2003) 157:1101–1107.[Abstract/Free Full Text]
  7. Hellermann JP, Jacobsen SJ, Redfield MM, Reeder GS, Weston SA, Roger VL. Heart failure after myocardial infarction: clinical presentation and survival. Eur J Heart Fail (2005) 7:119–125.[Abstract/Free Full Text]
  8. Spencer FA, Meyer TE, Gore JM, Goldberg RJ. Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure: the National Registry of Myocardial Infarction. Circulation (2002) 105:2605–2610.[Abstract/Free Full Text]
  9. Kober L, Torp-Pedersen C, Pedersen OD, Hoiberg S, Camm AJ. Importance of congestive heart failure and interaction of congestive heart failure and left ventricular systolic function on prognosis in patients with acute myocardial infarction. Am J Cardiol (1996) 78:1124–1128.[Web of Science][Medline]
  10. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, Remme WJ. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J (2005) 26:1115–1140.[Free Full Text]
  11. Glynn RJ, Buring JE. Ways of measuring rates of recurrent events. BMJ (1996) 312:364–367.[Free Full Text]
  12. Efron B, Tibshirani R. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci (1986) 1:54–77.[CrossRef]
  13. Schoenfeld D. Partial residual estimation for the proportional hazards regression model. Biometrika (1982) 69:239–241.[Abstract/Free Full Text]
  14. Grambsch M, Therneau T. Proportional hazards tests and diagnostics based on weight residuals. Biometrika (1994) 81:515–526.[Abstract/Free Full Text]
  15. Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D'Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation (2002) 106:3068–3072.[Abstract/Free Full Text]
  16. Cowie MR, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Suresh V, Sutton GC. Incidence and aetiology of heart failure: a population-based study. Eur Heart J (1999) 20:421–428.[Abstract/Free Full Text]
  17. Cleland JG, Cohen-Solal A, Aguilar JC, Dietz R, Eastaugh J, Follath F, Freemantle N, Gavazzi A, van Gilst WH, Hobbs FD, Korewicki J, Madeira HC, Preda I, Swedberg K, Widimsky J. Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey. Lancet (2002) 360:1631–1639.[CrossRef][Web of Science][Medline]
  18. Cleland JG, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar JC, Dietz R, Gavazzi A, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, van Gilst WH, Widimsky J, Freemantle N, Eastaugh J, Mason J. The EuroHeart Failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J (2003) 24:442–463.[Abstract/Free Full Text]
  19. Cleland JG, Coletta AP, Nikitin NP, Clark AL. Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND. Eur J Heart Fail (2006) 8:326–329.[Abstract/Free Full Text]
  20. Stokes J III, Dawber TR. The silent coronary: the frequency and clinical characteristics of unrecognized myocardial infarction in the Framingham study. Ann Intern Med (1959) 50:1359–1369.[Abstract/Free Full Text]
  21. Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Packer M, Poole-Wilson PA, Ryden L. Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. Circulation (2000) 102:611–616.[Abstract/Free Full Text]
  22. Orn S, Cleland JG, Romo M, Kjekshus J, Dickstein K. Recurrent infarction causes the most deaths following myocardial infarction with left ventricular dysfunction. Am J Med (2005) 118:752–758.[CrossRef][Web of Science][Medline]
  23. Cleland JG, Clark AL, Caplin JL. Taking heart failure seriously. Diagnosis and initiation of treatment are the aspects to concentrate on. BMJ (2000) 3321:1095–1096.
  24. Wijeysundera HC, Vijayaraghavan R, Nallamothu BK, Foody JM, Krumholz HM, Phillips CO, Kashani A, You JJ, Tu JV, Ko DT. Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials. J Am Coll Cardiol (2007) 49:422–430.[Abstract/Free Full Text]
  25. Sutton AG, Campbell PG, Graham R, Price DJ, Gray JC, Grech ED, Hall JA, Harcombe AA, Wright RA, Smith RH, Murphy JJ, Shyam-Sundar A, Stewart MJ, Davies A, Linker NJ, de Belder MA. One year results of the Middlesbrough early revascularisation to limit infarction (MERLIN) trial. Heart (2005) 91:1330–1337.[Abstract/Free Full Text]
  26. Ellis SG, Da Silva ER, Spaulding CM, Nobuyoshi M, Weiner B, Talley JD. Review of immediate angioplasty after fibrinolytic therapy for acute myocardial infarction: insights from the RESCUE I, RESCUE II, and other contemporary clinical experiences. Am Heart J (2000) 139:1046–1053.[CrossRef][Web of Science][Medline]
  27. Rebuzzi AG, Niccoli G, Ferrante G. Acute myocardial infarction interventional procedures: primary percutaneous coronary intervention versus facilitated percutaneous coronary intervention, rescue angioplasty, rescue excimer laser. Minerva Cardioangiol (2007) 55:73–82.[Medline]
  28. Zeymer U, Schroder R, Machnig T, Neuhaus KL. Primary percutaneous transluminal coronary angioplasty accelerates early myocardial reperfusion compared to thrombolytic therapy in patients with acute myocardial infarction. Am Heart J (2003) 146:686–691.[CrossRef][Web of Science][Medline]
  29. Hochman JS, Lamas GA, Buller CE, Dzavik V, Reynolds HR, Abramsky SJ, Forman S, Ruzyllo W, Maggioni AP, White H, Sadowski Z, Carvalho AC, Rankin JM, Renkin JP, Steg PG, Mascette AM, Sopko G, Pfisterer ME, Leor J, Fridrich V, Mark DB, Knatterud GL. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med (2006) 355:2395–2407.[Abstract/Free Full Text]
  30. Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyorala K. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail (1997) 3:249–254.[CrossRef][Medline]
  31. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med (2005) 352:1425–1435.[Abstract/Free Full Text]
  32. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med (1992) 327:685–691.[Abstract]
  33. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med (1991) 325:293–302.[Abstract]
  34. Pitt B, Gheorghiade M, Zannad F, Anderson JL, van Veldhuisen DJ, Parkhomenko A, Corbalan R, Klug EQ, Mukherjee R, Solomon H. Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <or=30%. Eur J Heart Fail (2006) 8:295–301.[Abstract/Free Full Text]
  35. Houghton T, Freemantle N, Cleland JG. Are beta-blockers effective in patients who develop heart failure soon after myocardial infarction? A meta-regression analysis of randomised trials. Eur J Heart Fail (2000) 2:333–340.[Abstract/Free Full Text]
  36. Cleland JG. Is aspirin ‘the weakest link’ in cardiovascular prophylaxis? The surprising lack of evidence supporting the use of aspirin for cardiovascular disease. Prog Cardiovasc Dis (2002) 44:275–292.[CrossRef][Web of Science][Medline]
  37. Cleland JG, Massie BM, Packer M. Sudden death in heart failure: vascular or electrical? Eur J Heart Fail (1999) 1:41–45.[Free Full Text]
  38. Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J. Rosuvastatin in older patients with systolic heart failure. N Engl J Med (2007) 357:2248–2261.[Abstract/Free Full Text]
  39. Cleland JG, Findlay I, Jafri S, Sutton G, Falk R, Bulpitt C, Prentice C, Ford I, Trainer A, Poole-Wilson PA. The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J (2004) 148:157–164.[CrossRef][Web of Science][Medline]
  40. Gronefeld G, Connolly SJ, Hohnloser SH. The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT): rationale, design and specific aims. Card Electrophysiol Rev (2003) 7:447–451.[CrossRef][Medline]
  41. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med (2003) 348:1309–1321.[Abstract/Free Full Text]
  42. Yao G, Freemantle N, Calvert MJ, Bryan S, Daubert JC, Cleland JG. The long-term cost-effectiveness of cardiac resynchronization therapy with or without an implantable cardioverter-defibrillator. Eur Heart J (2007) 28:42–51.[Abstract/Free Full Text]
  43. Gerschutz GP, Bhatt DL. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study: to what extent should the results be generalizable? Am Heart J (2003) 145:595–601.[CrossRef][Web of Science][Medline]
  44. Scheen AJ. The CHARISMA study: in search of the best antiplatelet strategy for cardiovascular prevention. Rev Med Liege (2006) 61:656–661.[Medline]
  45. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van de WF, Avezum A, Goodman SG, Flather MD, Fox KA. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med (2003) 163:2345–2353.[Abstract/Free Full Text]
  46. Zhou Z, Rahme E, Abrahamowicz M, Pilote L. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol (2005) 162:1016–1023.[Abstract/Free Full Text]
  47. Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E, Amouyel P. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet (1999) 353:1547–1557.[CrossRef][Web of Science][Medline]
  48. Sigurdsson E, Thorgeirsson G, Sigvaldason H, Sigfusson N. Prevalence of coronary heart disease in Icelandic men, 1968–1986. The Reykjavik Study. Eur Heart J (1993) 14:584–591.[Abstract/Free Full Text]
  49. Cleland JG, Shelton R, Nikitin N, Ford S, Frison L, Grind M. Prevalence of markers of heart failure in patients with atrial fibrillation and the effects of ximelagatran compared to warfarin on the incidence of morbid and fatal events: a report from the SPORTIF III and V trials. Eur J Heart Fail (2007) 9:730–739.[Abstract/Free Full Text]
  50. Kannel WB, Abbott R. Incidence and prognosis of unrecognized myocardial infarction. N Engl J Med (1994) 311:1144–1147.
  51. Najafi F, Dobson AJ, Hobbs M, Jamrozik K. Temporal trends in the frequency and longer-term outcome of heart failure complicating myocardial infarction. Eur J Heart Fail (2007) 9:879–885.[Abstract/Free Full Text]

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