Left ventricular ejection fraction (LVEF) is the single most used non-invasive measure of cardiac function in clinical practice and is an important prognostic factor for survival after myocardial infarction (MI), in stable coronary artery disease (CAD), and in heart failure 123. Health-related quality of life (HRQoL) has also been identified as a predictor of survival in patients with CAD and heart failure 4567.

However, the relationship between LVEF and HRQoL has not been settled and whether LVEF can predict HRQoL is still controversial. Some studies have observed an association 891011 while others have not 121314151617. Most of these studies reported on highly selected heart patients enrolled in clinical trials 91314, patients with known reduced LVEF 1314, and patients with chronic heart failure 1117. Only two previous studies included unselected MI patients, of which one observed an association between LVEF measured at the time of the MI and later HRQoL 1016. Better understanding of the relationship between cardiac function and quality of life might contribute to tailor treatment that would maintain or improve the patients' daily functioning. Evidently, more research on this subject is needed.

Accordingly, our aim was to assess the relationship between LVEF measured during hospitalization for acute MI and HRQoL 2.5 years later in an unselected MI patient population, using both a generic and a disease-specific HRQoL measure.

Respondents who had their LVEF measured (n = 256) during hospitalization for the index MI were younger than respondents who had not (n = 152), had less cardiovascular morbidity at admission, and a higher proportion were smokers. Further, a larger proportion of respondents who had their LVEF measured had ST-segment elevation MI, underwent acute revascularisation, and developed Q-wave MI, and a lower proportion had medication for angina pectoris at discharge (Table 1).

Among respondents who had their LVEF measured, those with reduced LVEF were older and had increased prevalence of heart failure at admission. There was an increased prevalence of previous MI, anterior wall infarction, and use of medication on the indication heart failure with falling LVEF. Further a smaller proportion of respondents with reduced LVEF underwent acute revascularization or had subsequent percutaneous coronary intervention (Table 1).

In this study LVEF measured during hospitalization for the index MI was a determinant of HRQoL 2.5 years later, with poorer HRQoL in patients with reduced LVEF. This relationship persisted after adjusting for comorbidities, sociodemographic variables, and variables related to the index MI. The summary score of the condition-specific KCCQ questionnaire, which has been validated in an earlier study 23, and the EQ-VAS showed a trend of falling scores with falling LVEF, while the EQ-5D Index only captured a difference between patients with normal and intermediate LVEF. A difference in score for the KCCQ clinical summary score between patients with normal LVEF and intermediate or reduced LVEF of 10 and17 points respectively, indicates a moderate to large clinical difference between the groups of patients with different LVEF 24.

The observed falling HRQoL scores with falling LVEF both for KCCQ clinical summary score and EQ-VAS indicate that the level of systolic heart function is a determinant for HRQoL. However, some influence from the mere fact that an MI has occurred cannot be ruled out since also patients with normal LVEF tend to have reduced EQ-5D scores compared to US norms 32. If so, it is possible that other cardiac pathophysiological mechanisms or psychological mechanisms are involved. An understanding of the way LVEF may influence HRQoL can be provided from a conceptual model outlined by Wilson and Cleary 33. In their model biological and physiological variables influence symptoms, that is, patients with reduced LVEF may experience symptoms such as fatigue, dyspnoea, and sleep disturbances. These symptoms can in turn affect the patients' functional status, general health, and overall quality of life. The impact on individual patients is further modified by psychological and socioeconomic variables 33. In our study the level of LVEF immediately after the index MI had a statistically significant impact on later HRQoL and in accordance with the usual interpretation of the KCCQ the clinical importance was moderate to large 24. However, the observed absolute change in R-square was small indicating that the amount of variation in HRQoL scores explained by LVEF was moderate. A moderate amount of variation in HRQoL score explained by a single clinical variable can be expected if Wilson and Cleary's model is valid, as other interrelated variables intervene between pathophysiology of the heart and quality of life 33.

Three previous studies have observed an association between LVEF and HRQoL in patients with CAD 8910. However, two of these studies reported on patients not comparable to those in the present study. One reported on patients admitted to hospital with acute chest pain, thus including patients with acute MI, unstable angina, and chest pain of other reasons 8. The second study presented results from patients enrolled in a clinical trial of thrombolysis, thus representing a highly selected group of MI patients 9. In the third study Ecochard et al. showed that LVEF < 46% measured by ventricular angiography within a month after the index MI was associated with reduced function on the Physical mobility dimension of the Nottingham Health Profile (NHP) assessed at one year 10. However, they did not observe any association between LVEF and the five other dimensions of the NHP (Energy level, Sleep, Pain, Emotional reactions, and Social isolation). By contrast, we found a relationship between LVEF and composite HRQoL scales covering physical, emotional, and social aspects of the HRQoL concept. Furthermore, we observed falling HRQoL scale scores with falling LVEF for the KCCQ clinical summary score and the EQ-VAS. Ecochard et al. did not find a similar fall by use of NHP, neither did we by use of the EQ-5D Index 10. The dissimilarities might be due to the fact that both NHP and EQ-5D Index are generic instruments and thus supposed to be less sensitive to smaller changes in health status and disease severity than the disease-specific KCCQ 34. Another reason why reduced LVEF was not independently associated with lower EQ-5D Index score in our study was the reduced statistical power due to low number of respondents with LVEF < 40%.

Studies that did not find an association between LVEF and later HRQoL also varied with regard to inclusion criteria and most of them reported on selective groups of patients and not on unselected acute MI patients as we did 1213141516. One reported on patients 65 years of age or older with CAD 12, two on clinical trials of post MI patients with reduced LVEF 1314, and one on patients with their first MI receiving thrombolysis 15. McBurney et al. did not detect any difference in HRQoL between patients with LVEF < 40% and patients with normal and sub-normal LVEF in a patient sample comparable to ours 16. However, they used a generic questionnaire, the short form 12 (SF-12) which probably is less sensitive to changes in health status and disease severity 34.

In our study on MI patients, age ≥ 70 years was associated with lower KCCQ clinical summary score. This contrasts with previous results on heart failure patients in which increased age independently correlated with higher KCCQ Quality of life scale score 35. One possible explanation for this discrepancy is that the KCCQ clinical summery score, which we used as an HRQoL measure in our study, is an overall scale including, in addition to the KCCQ Quality of life scale, scales on symptoms, physical limitations, and social limitations. Another possible explanation is that in our sample of patients with previous MI, increasing age is associated with more advanced CAD and age might act as a surrogate for disease severity 36. This might not be the case in a sample of patients with heart failure as the underlying cause in younger patients with heart failure more commonly is dilated cardiomyopathy or other cardiomyopathies rather than CAD 35. We did not observe an association of age with EQ-5D Index scores even though EQ-5D Index US norms report a small decrease in scores with increasing age 32.

We identified sex as an independent determinant of EQ-5D Index score, but not of KCCQ clinical summary score. A difference in score between men and women who are otherwise comparable might be less likely when applying a disease specific instrument than a generic instrument which has a broader perspective. Thus, the EQ-5D Index US norms have reported a small difference between men and women with poorer score in women 32. Our observations are in agreement with these observations.

Our study showed that the presence of COPD was associated with reduced HRQoL after MI. COPD and CAD share some causal risk factors, and might to some extent present with similar symptoms, for example dyspnoea. Therefore, it is not surprising that patients with COPD who suffer an MI are at increased risk of impaired HRQoL. Similarly, medication for angina pectoris was associated with reduced EQ-5D Index score, and presumably, the reason for this is the fact that such medication reflects enhanced disease severity. In our study the presence of peripheral vascular disease was associated with higher EQ-5D Index score. However, this finding is based on only 11 patients with peripheral vascular disease, and therefore should be interpreted with caution.

Due to the rather long time from the MI to measuring of HRQoL in our study, the association between LVEF and HRQoL could have been distorted. Although the patients reported on intervening major cardiac events, such as new MI or coronary revascularization procedures, other major life events, worsening or improvement of illness not reported in our study, might have had an effect on current HRQoL. We addressed this issue by entering the time between the index MI and HRQoL assessment as a variable in the multivariable analyses. This factor was not, however, independently associated with HRQoL.

In the context of study limitations the representativeness of the sample should be discussed. The eligible patients were representative of survivors of an unselected MI population. Three quarters of the patients responded to the survey, and LVEF was measured in two thirds of the respondents, thus we completed our analysis on approximately half of the eligible patients. This might have skewed the representativeness. However, results from a sub-group analysis of patients in one hospital in which all MI patients had their LVEF measured, were largely in line with the overall results, indicating that the main results pertains to unselected MI patients. Another limitation is the uncertainty of whether the clinicians categorizing the indications for drugs prescribed at discharge did assign the most important indication for each drug, as the protocol instructed. Cardiovascular drugs may have more than one indication for use, and we did not assess the reliability and validity of this classification. However, the classification was undertaken by experienced physicians, most of them cardiologists ensuring the best possible assessment.

LVEF measured during hospitalization for acute MI is an independent determinant for later HRQoL also after taking sociodemographic and clinical variables into account. The magnitude of the difference in HRQoL score between patients with normal, intermediate, and reduced LVEF was of clinical importance. As expected, in accordance with theoretical models, only a moderate amount of the observed variation in HRQoL score was explained by the level of LVEF.

Restoration of myocardial function after an MI is, in addition to being important for live expectancy, also crucial for long-term daily functioning after the event.

CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; EQ-VAS: EuroQol Visual Analogue Scale; HRQoL: health-related quality of life; KCCQ: Kansas City Cardiomyopathy Questionnaire; LVEF: left ventricular ejection fraction; MI: myocardial infarction; MUGA: multiple gated-acquisition radionuclide ventriculography; NHP: Nottingham Health Profile.

The authors declare that they have no competing interests. The work was performed at the Norwegian Knowledge Centre for the Health Services and at the Department of Pharmacotherapeutics, University of Oslo, Oslo, Norway. The project had no external funding or grants.

KIP: Had the idea to the study, organized the data collection and data preparation, performed statistical analysis, drafted the first version of the manuscript, revised the manuscript and approved the final version. EK: Participated in data collection and data preparation, participated in discussion of study findings, revision of the manuscript and approved the final version. AR: Participated in discussion of study findings, revision of the manuscript and approved the final version.

KS: Participated in study design, statistical analysis, manuscript preparation and revision, and approved the final version. AR: Participated in data collection, discussion of study findings, manuscript preparation and revision, and approved the final version.