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European Journal of Heart Failure 2001 3(1):91-96; doi:10.1016/S1388-9842(00)00121-5
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© 2001 European Society of Cardiology

In-hospital heart failure, first-year ventricular dilatation and 10-year survival after acute myocardial infarction

Niels Gadsbøll*, Christian Torp-Pedersen and Poul Flemming Høilund-Carlsen

Department of Internal Medicine C and the Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital 2600 Glostrup, University of Copenhagen Denmark

* Corresponding author. Department of Cardiovascular Medicine, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark. Tel.: +45-3531-3333; fax: +45-3531-3226. E-mail address: ng02{at}bbh.hosp.dk (N. Gadsbøll).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Background: Little is known about the factors that determine long-term prognosis in patients who have survived the first year after acute myocardial infarction (AMI).

Aims: To study the influence of left and right ventricular (LV and RV) dilatation during the first year after AMI on subsequent 10-year survival in comparison with in-hospital heart failure and other established prognostic indices.

Methods: Radionuclide ventriculography was performed before the era of thrombolysis and post-infarction ACE-inhibition in 57 patients with AMI at hospital discharge and again 1 year later, and compared with survival the ensuing 10 years.

Results: After 1 year significant LV-dilatation (> 20%) had occurred in 32 (56%) patients. One year after the re-investigation the mortality in these was 19% vs. 0% in patients without dilatation (P = 0.02); after 5 years the difference was 38 vs. 12% (P = 0.02), whereafter it declined and became insignificant at 10 years. Neither RV-dilatation, nor LVEF determined at discharge or at the 1-year reinvestigation influenced long-term survival. In contrast, clinical heart failure recorded during the hospital stay had a sustained negative influence on long-term survival.

Conclusion: Progressive LV dilatation after discharge and clinical heart failure during the hospital stay are both determinants of late survival after AMI, whereas LV ejection fraction at hospital discharge or 1 year later has little, if any, effect on survival beyond 1-year post-AMI.

Key Words: Myocardial infarction • Cardiac function • Prognosis

Received May 9, 2000; Accepted August 1, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Left ventricular (LV) ejection fraction and LV volume measured early after acute myocardial infarction (AMI) are recognized determinants of survival the first year after AMI [1–3]. However, LV dilatation may proceed or start after discharge and progress during the months and years to come, often with a modest impact on LV ejection fraction due to the proportional increase in end-diastolic and end-systolic volume [4–6]. The natural history of this process and its significance for the long-term survival after AMI is unclear, possibly because present-day treatment with ACE-inhibitors and other prophylactic measures have blurred the picture.

We have previously reported that spontaneous LV dilatation occurs in more than 50% of post-AMI patients during the first year after hospital discharge [7]. The purpose of the present study was to examine the prognostic significance of this ‘first-year’ increase in LV volume on long-term survival in comparison with in-hospital heart failure and established prognostic factors such as LV ejection fraction in a cohort of patients, who did not receive thrombolytic treatment or ACE-inhibition post AMI. Also, we report on ‘first-year’ right ventricular (RV) dilatation and its association to long-term survival.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1. Study protocol
The investigation was a follow-up of a previous report concerning the spontaneous change in LV volume during the first year after AMI [7]. In that study, 57 hospital survivors of AMI underwent radionuclide ventriculography at discharge (1984–1985) and again 1 year later (1985–1986). For the purpose of the present study, all 57 patients were followed-up with regard to death from the time of the 1-year reexamination in 1985–1986 to 1 October 1996. Patient survival was determined by interrogation of the Danish Central Personal Register, which records all deaths among Danish citizens within 14 days of death. The study was approved by the Local Ethics Committee and conforms with the principles outlined in the Declaration of Helsinki.

2.2. Patients
Ninety-seven patients were eligible for the study [7]. Between hospital discharge and the 1-year re-investigation 18 patients died, seven had a recurrent AMI, two underwent coronary artery bypass surgery, one developed malignant disease and four patients did not want to participate in the 1-year follow-up. Of the remaining 65 patients, 57 had complete discharge and 1-year radionuclide data. A detailed description of the patients has been given previously [7].

2.3. Radionuclide ventriculography
The patients were examined in the second week after their AMI (1984–1985) and again approximately 1 year later. Cardiac volumes were determined by the count-based principle with correction for the individual loss of radiation dependent on the depth of the left ventricle in the chest as previously described [8]. All cardiac volumes were indexed to body surface area. Normal values were: LV end-diastolic volume-index, 45–90 ml/m2; LV end-systolic volume-index, 15–35 ml/m2; and LV stroke volume-index, 30–55 ml/m2 [3]. Normal values for LV ejection fraction were 0.53–0.74 and for RV ejection fraction 0.57–0.77 [9]. RV end-diastolic volume-index was calculated as: RV end-diastolic volume-index=LV stroke volume-index/RV ejection fraction, anticipating the absence of significant valvular insufficiencies or intracardiac shunts. LV dilatation was defined as a 1-year increase in LV end-diastolic volume >20% above baseline (i.e. discharge level) [7].

2.4. Chest X-ray
Posteroanterior and lateral chest films were taken in the upright position on the day of discharge and on the day of the 1-year radionuclide investigation. All films were described by the same senior radiologist, who was unaware of the clinical and the radionuclide results. Pulmonary congestion was graded according to Kostuk et al. [10].

2.5. Physical examination
All patients were examined for signs of congestive heart failure daily during the hospital stay and at the 1-year reexamination. This was done by the same cardiologist (NG). The definition of each sign (dyspnea, a displaced apex beat, S3 gallop and rales) has been given previously [11].

2.6. Statistical analysis
Values are given as medians with ranges. Between group comparisons were made by the Wilcoxon signed rank test for paired data and the median test for unpaired data. Long-term survival of ‘dilatators’ vs. ‘non-dilatators’ (Figs. 1 and 2) was analyzed using the log-rank test. The significance of radionuclide and clinical data for survival beyond 1-year post-AMI was analyzed using the Cox proportional hazard method.


Figure 1
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  		Fig. 1 Long-term survival (1–11 years) in patients with and without left ventricular dilatation the first year after acute myocardial infarction.

 


Figure 2
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  		Fig. 2 Long-term survival (1–11 years) in patients with and without clinical heart failure during hospital admission for acute myocardial infarction.

 

   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
3.1. First-year changes
In the total study population LV end-diastolic volume-index increased significantly from 92 (38–188) ml/m2 at discharge to 112 (41–343) ml/m2 at the 1-year follow-up investigation. Likewise, LV end-systolic volume-index increased from 51 (9–159) ml/m2 to 65 (14–254) ml/m2 and LV stroke volume-index from 39 (24–66) ml/m2 to 47 (24–89) ml/m2. During the same period no significant change was observed in LV ejection fraction: 41 (14–76)% vs. 43 (13–74)%; RV ejection fraction: 62 (32–83)% vs. 64 (25–77)%; RV end-diastolic volume-index: 66 (37–120) ml/m2 vs. 71 (35–270) ml/m2; or RV end-systolic volume-index: 24 (7–75) ml/m2 vs. 24 (11–202) ml/m2. In 32 patients (56%) there was an increase in LV end-diastolic volume-index >20%, and these were identified as dilatators.

The changes from discharge to 1-year follow-up in the ‘dilatators’ vs. the ‘non-dilatators’ are shown in Table 1. In the dilatators, the median increases were in LV end-diastolic volume-index 44%, in LV end-systolic volume-index 58%, and in LV stroke volume-index 31%. The LV dilatators had a median increase in RV end-diastolic volume-index of 23% and one of 17% in RV end-systolic volume-index. In the ‘non-dilatators’ there was minute, but statistically significant, improvement in LV variables and no change in RV variables (Table 1).


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  		Table 1 Radionuclide data in dilatators vs. non-dilatators at hospital discharge and at the 1-year follow-up investigationa

 
Clinical characteristics in the dilatators and the non-dilatators are shown in Table 2. Dilatators were older, more frequently males and had typically anterior infarction and a history of heart failure during the hospital stay. In patients with heart failure, LV dilatation was particularly prominent. Thus, LV dilatation took place in 81% (17/21) of these compared to 42% (15/36) of patients without heart failure (P=0.008). The 1-year increase in LV end-diastolic volume-index in patients with in-hospital heart failure was from 94 ml/m2 to 132 ml/m2. In patients without heart failure the corresponding change was from 91 ml/m2 to 99 ml/m2.


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  		Table 2 Clinical data at hospital discharge in dilatators vs. non-dilatators

 
The number of patients with radiographic signs of pulmonary congestion (Kostuk class I–III) decreased in the dilatator-group from 11 at discharge to seven at the 1-year follow-up. In the non-dilatator group the corresponding figures were nine and two. The use of digoxin, diuretics, or antianginal therapy in the two groups did not change during the first year after discharge [7].

3.2. Prognosis beyond 1-year post-AMI
The follow-up time after the day of the 1-year reinvestigation ranged from 10.3 to 11.1 years (median 10.5 years). During that period 35 patients (61%) died.

Fig. 1 shows Kaplan–Meier estimates of survival in dilatators vs. non-dilatators. In the first 2 years after the 1-year reinvestigation, i.e. year 1–year 3 post-AMI the total mortality in the dilatators was 19% vs. 0% among the non-dilatators (P=0.02). Five years after the reinvestigation the corresponding figures were 38% vs. 12% (P=0.02). At the end of the follow-up period the difference in mortality had narrowed to 66% vs. 56% (P=0.13). To analyze whether LV dilatation was independently associated with survival beyond 1-year post-AMI, we entered all ‘discharge’ and ‘1-year’ radionuclide variables, together with heart failure during the hospital stay and patient age, into a Cox regression model using time to death within the first 5 years after the 1-year reinvestigation as the endpoint. In the univariate analysis LVEF at discharge and LVEF at the 1-year reinvestigation (P=0.32) were not significantly associated with survival beyond year 1 (P=0.53 and P=0.32, respectively). LV end-diastolic volume-index at discharge was not associated either (P=0.25), whereas the index at the 1-year reinvestigation was (P=0.03). LV end-systolic volume-index had an association of marginal statistical significance to late survival at both occasions (P=0.05 and P=0.05). LV dilatation within the first year after discharge, i.e. change in LV end-diastolic volume-index and in-hospital heart failure were both significantly associated with survival (P=0.04 and P=0.005). When all these variables together with age were entered into the Cox model at the same time, only heart failure during admission had an independent effect on late survival. When age, LV dilatation (ml/m2) and heart failure were entered, again, only heart failure had a significant association to late survival. Fig. 2 shows Kaplan–Meier estimates of survival in patients with and without signs of heart failure during admission.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
The present study was performed before the thrombolytic area, and several years before it was demonstrated that ACE-inhibitors may attenuate LV dilatation post-AMI. Accordingly, none of the patients received an ACE-inhibitor during admission (1984–1985) or between discharge and the 1-year follow-up (1985–1986). Moreover, at that time access to coronary revascularization at our hospital was restricted to the minority of patients with drug refractory angina. Thus, only two of the 97 eligible patients underwent bypass surgery in the first year after discharge. These and the seven patients with recurrent AMI were not restudied in 1985–1986.

In contrast to the echocardiographic SAVE substudy by St. John Sutton et al. [4] which also included patients with recurrent infarction, this historical situation yielded an unusual opportunity to study the natural course of unopposed ventricular dilatation during the first year after AMI, and to assess how this process may influence long-term survival.

Between hospital discharge and the 1-year reinvestigation more than half of the patients had a substantial, albeit clinically silent, increase in LV size that was not associated with a significant decrease in LVEF. Notably, of these dilatators 44% had a discharge LV ejection fraction >40% underscoring the problems of identifying patients from the ejection fraction alone, and questioning the rationale of using a single cut-off value below which ACE-inhibitor treatment should be started [12,13].

4.1. Heart failure and ventricular dilatation
We have previously reported that clinical heart failure during the hospital stay is the single most powerful determinant of the 1-year prognosis after AMI [3]. The present study suggests that clinical heart failure is associated with (or precipitates) a pronounced and progressive LV dilatation. Among the patients with in-hospital heart failure, 81% had significant LV dilatation the first year after discharge. The reason LV dilatation was so frequent in heart failure patients was probably because heart failure typically is seen in patients with anterior infarcts. The anterior LV wall and the thin-walled apical region have the greatest degree of curvature (shortest radius of curvature) and therefore are particularly sensitive to infarct-induced reduction in wall curvature, which according to the law of La Place increases wall tension by reducing the radius of curvature and promotes further LV dilatation [14]. Possibly, heart failure itself may have a causal relationship to LV dilatation. Although LV dilatation may precede and precipitate overt heart failure, it is also possible that once heart failure becomes manifest it further accelerates this dilatation [5,15]. Patients with overt heart failure have higher circulating levels of neurohormones than patients with subclinical LV dysfunction, and this neurohormonal activation also may exaggerate LV remodeling [16–18]. On the other hand, heart failure is not a prerequisite for LV dilatation as evidenced by the finding that 47% of the dilatators did not have any signs of heart failure during admission. Patency of the infarct related artery and the presence of collateral coronary vessels could be other important factors involved in the dilatatory process [19–21]. Unfortunately, we do not have data on the coronary anatomy of our patients, since coronary angiography at the time of the study was performed only in a minority of patients with AMI.

4.2. Dilatation, ejection fraction and prognosis
Neither discharge LV ejection fraction nor discharge LV end-diastolic volume-index were significantly associated with survival beyond 1-year post-AMI (end-systolic volume-index had a marginal statistical association). LVEF determined at the 1-year re-investigation was not significantly associated either. In contrast, the ‘updated’ larger LV end-diastolic volume-index and the degree of 1-year LV dilatation had a clear association to survival beyond 1-year post-AMI. One-year change in LV ejection fraction had no predictive prognostic power whatsoever. Despite the small size of our study, these results suggest that the prognostic power of LVEF or LV volumes determined at hospital discharge fades out with time and becomes increasingly useless with regard to evaluation of the prognosis in patients, who have survived the first year after AMI. This is supported by data from the TRACE study in which echocardiographic LV wall-motion scores determined 1–6 days after AMI had a strong relationship to 1-month and 1-year survival, but a weaker association to survival beyond 1-year post-AMI, and a much weaker relationship to survival beyond year 3 post-AMI [22].

In the dilatators, there was a concomitant 22% increase in RV end-diastolic volume-index (Table 1). We have previously suggested that this increase in RV size could be a trigger mechanism for fatal arrhythmias arising in the right ventricle by increasing RV wall stress [6]. However, the present study does not support this hypothesis. By univariate or multivariate analysis we could not demonstrate any association between early RV dilatation and late survival. Whether RV dilatation plays a role for the prognosis in the early phase of AMI could not be assessed in the present study [23].

4.3. Heart failure and prognosis
In contrast to radionuclide variables determined at discharge, a history of in-hospital heart failure had a clear association to survival beyond year 1 after AMI. In the light of the marked LV dilatation in patients with heart failure this was to be expected, and may explain why patients with clinical signs of heart failure have a particular benefit of ACE inhibition post-AMI as demonstrated in the AIRE and the AIRE extension studies [24]. However, in the multivariate analysis the presence of heart failure during the hospital stay had an association to late survival post-AMI stronger than that explained by the degree of progressive LV dilatation. This suggest that the dismal prognosis of patients with AMI who have clinical signs of heart failure is determined also by other mechanisms than those related to LV dilatation.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
Progressive LV dilatation after discharge and in particular clinical heart failure during the hospital stay are both determinants of late survival after AMI, whereas LVEF has little, if any prognostic significance in patients who have survived the first critical year after AMI.


   Acknowledgements
 
We are grateful to Professor Marc Pfeffer for fruitful comments in the preparation of the manuscript.


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

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