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Eur J Cardiothorac Surg 2004;26:621-627
© 2004 Elsevier Science NL


Perioperative myocardial infarction has negative impact on health-related quality of life following coronary artery bypass graft surgery

Otso Järvinena*, Juhani Julkunenb,c, Timo Saarinenb, Jari Laurikkaa, Heini Huhtalad, Matti R. Tarkkaa

a Heart Center, Department of Cardiac Surgery, Tampere University Hospital, 33521, Tampere, Finland
b Rehabilitation Foundation, Helsinki, Finland
c Department of Psychology, University of Helsinki, Helsinki, Finland
d School of Public Health, University of Tampere, Tampere, Finland

Received 8 January 2004; received in revised form 22 April 2004; accepted 5 May 2004.

* Corresponding author. Tel.: +358-3-346-4348; fax: +358-3-247-5756
e-mail: otsojarvinen{at}koti.soon.fi


    Abstract
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Objective: Perioperative myocardial infarction (PMI) is a well-described complication of coronary artery bypass grafting (CABG). Data on its effect on patients' subsequent health-related quality of life (QOL) and on other related consequences is deficient. The aim here was to evaluate in a prospective follow-up design the risk factors for and consequences of PMI and especially its possible impact on health-related QOL. Methods: Comprehensive data, including preoperative risk profile, perioperative variables and postoperative morbidity up to discharge were collected of 501 CABG patients in the Heart Center of Tampere University Hospital and in all eighteen postoperative care hospitals. Eighty patients (16%) fulfilled ECG or cardiac enzyme criteria for PMI and they were compared to patients with no PMI. The RAND-36 Health Survey (RAND-36) was used as an indicator of QOL. The primary outcomes were change in physical component summary (PCS), mental component summary (MCS) and the eight dimensions of health-related QOL from the RAND-36. Symptomatic status was estimated according to New York Heart Association (NYHA) class. Assessments were made preoperatively and repeated 12 months later. Results: Multivariate logistic regression analysis identified long cardiopulmonary bypass time (P=0.006) and high age (P=0.049) as independent predictors for PMI. Thirty-day mortality was adversely affected by PMI (6.3 vs 1.0%, P=0.001). In discharged patients, the occurrence of PMI did not affect 1-year survival adversely (98.7 vs 98.6%). The PMI patients showed significant (P<0.05) improvements in six of the eight dimensions of RAND-36, but they presented with a negative change in their ‘general health’ scores at the follow-up. All QOL scores improved significantly (P<0.001) among the patients without PMI. A highly significant (P<0.001) pattern of change was seen in the RAND-36 PCS and MCS scores in both groups although PMI patients showed significantly (P=0.002) smaller change in their PCS scores. Both groups showed similar freedom from anginal symptoms at 1 year (89.6 vs 90.1%) but in the PMI group later readmissions due to cardiac-related causes were more common (23 vs 10%, P=0.002). Conclusions: PMI increases 30-day mortality and affects also adversely on later health-related QOL following CABG.

Key Words: CABG • Perioperative myocardial infarction • Quality of life


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Perioperative myocardial infarction (PMI) is a prominent cause of mortality and morbidity after coronary artery bypass grafting (CABG) surgery. The reported incidence of PMI is dependent on the diagnostic criteria used and varies widely. Clinically, a diagnosis of PMI is most often based on the appearance of new Q waves on the postoperative electrocardiogram (ECG) and on biochemical markers of myocardial injury; creatine phosphokinase isoenzyme MB (CK-MB), and more recently troponin-I and troponin-T. Current myocardial protection techniques allow the coronary bypass patient to leave the operating room without significant perioperative decrement in myocardial performance. Progress in surgical technique, in anesthesia and in postoperative care has also improved the results of coronary artery bypass surgery. At the same time, however, the profile of patients undergoing CABG has altered towards higher age with frequent preoperative comorbid conditions and increased postoperative morbidity [14]. Since life expectancy in this group of patients is limited by natural factors, the gain in added life years achieved by operative treatment is likewise limited. Quality of life (QOL) thus becomes a pertinent issue as providers and consumers of health care debate on the benefits to be gained from expensive medical and surgical interventions. Although risk factors for PMI during CABG have been described [5], there are limited data on its clinical consequences [6,7] as also on the subsequent health-related QOL of patients with PMI.

The main purpose of this follow-up study was to assess the impact of PMI on health-related QOL (RAND-36) following CABG. Furthermore, 1-year symptomatic status and hospital readmissions were evaluated and risk factors for PMI determined.


    2. Materials and methods
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Data were obtained from Tampere University Hospital between May 2, 1999 and November 30, 2000. The cohort comprised 501 patients who underwent isolated coronary artery bypass grafting (CABG). The study was approved by the institutional review board of Tampere University Hospital and each patient gave written informed consent to participate. There were 415 (83%) male patients in the sample. The age range was from 36 to 87 years (median 63). Three hundred and ninety-nine (80%) of the procedures were performed electively, 102 (20%) urgently or as emergencies. Four hundred and forty-seven (89%) patients underwent bypass grafting via sternotomy incision with cardiopulmonary bypass (CPB; on-pump) and 54 (11%) were operated without CPB (off-pump). The CPB was conducted with a membrane oxygenator and a roller pump generating non-pulsatile flow, and was instituted using ascending aortic and right atrium cannulation. Moderate hemodilution (hematocrit 20–25%) and moderate hypothermia (32 °C) were employed. Antegrade and retrograde cold blood cardioplegia were used for myocardial protection. In off-pump cases, commercially available retractor and stabilization systems (Octopus®, Medtronic Inc., Minneapolis, MN, USA and CTS®, Cardio-Thoracic Systems INC., Cupertino, CA, USA) were used during the construction of anastomoses.

2.1. Definition of perioperative myocardial infarction (PMI)
The criteria of PMI included significant new electrocardiographic (ECG) Q waves in at least two adjacent leads (greater than 0.04 s in duration with a depth of at least one third of the height of the R wave in the same QRS complex) or creatine phosphokinase isoenzyme MB (CK-MB) >75 IU/l in one of three serial postoperative samples. A cardiologist reviewed 12-lead electrocardiograms routinely on the day before surgery, 4 h postoperatively, on the first 2 postoperative mornings, on the fourth postoperative day, and at other times if clinically indicated, and they were reviewed by a cardiologist. Myocardial enzymes were measured postoperatively at 6 and 18 h (or more frequently if clinically indicated). PMI was defined as infarction occurring within 7 days after surgery.

2.2. Data collection
During the primary hospital stay a comprehensive pre-, peri- and postoperative medical data body was collected. Most patients were discharged on the sixth day (median) after the operation to the local district hospital. The data from these secondary discharge hospitals were collected by the referring physicians and sent to the first author (O.J.) for analysis. All outcome events, including thirty-day mortality and complications, were recorded for joint analysis with the primary hospital data. Major postoperative complications included stroke, mediastinitis, sepsis, low output syndrome, prolonged ventilatory support (>36 h), acute renal failure requiring dialysis, pulmonary embolism and severe cardiac failure or severe ventricular arrhythmia requiring an intensive care unit (ICU) or coronary care unit (CCU) stay in the primary or secondary referral hospital. Atrial fibrillation was recorded as a minor complication.

2.3. Assessment of health-related quality of life
All assessments were made preoperatively and repeated 12 months later. The baseline self-report questionnaire was given to the patients the day before surgery. The follow-up questionnaire covering the same measures was mailed to the participants one year after the by-pass operation. Sixteen (3.2%) had died during this period. Four hundred and fifty-eight (94.4%) of the 485 surviving patients returned the follow-up questionnaire, the mean time of follow-up being 12.6 (SD 1.2) months. Compared with the 458 patients who completed the form, those 27 patients who did not were younger (median age 54 vs 63 years, P=0.006). However, there were no significant differences in the majority of variables, including sex, Euroscore risk sum, priority of operation or NYHA class.

We used the Finnish adaptation of the RAND-36 generic health-related QOL scale, for which reference values are available for the Finnish population [8]. The RAND-36 is a widely used and validated scale which yields scores for eight dimensions of health-related QOL: (1) general health, (2) physical functioning, (3) role functioning/physical, (4) bodily pain, (5) emotional well-being, (6) role functioning/emotional, (7) social functioning, and (8) energy [9,10]. The scores for each domain range from 0 to 100, 0 being the poorest and 100 the best possible health status. To reduce the number of outcome variables two summary scores can also be used: the Physical Component Summary (PCS) corresponds to the mean value of the physical sub-scales (1–4) while the Mental Component Summary (MCS) equals the mean value of psychic sub-scales (5–8) [1113]. The RAND-36 first item for ‘general health’ can also be used separately [9].

Pre- and postoperative functional capacity was ranked according to the New York Heart Association (NYHA) classification. Statistics Finland provided causes and dates of death after discharge.

2.4. Statistical analysis
Patient and outcome variables are expressed mainly as a percentage of the total. Categorical variables between the PMI and no-PMI groups were compared using Pearson's {chi}2 test. Continuous variables were compared by independent samples t-test for variables with normal distributions and Mann–Whitney test for variables with non-normal distributions. Predictors exhibiting a statistically significant relationship with PMI in univariate analyses were taken for multivariate logistic regression analysis to investigate their independency as predictors. Baseline and follow-up variables were compared using paired-samples t-test and analysis of variance for repeated measures with age as a covariate. Intergroup differences were analyzed by independent samples t-tests. P values of 0.05 or less were considered statistically significant. Statistical analyses were performed using SPSS 9.0 for Windows.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
The total number of patients undergoing CABG in our institution during the study period was 1128. Of these, 620 patients were unable or unwilling to complete the preoperative survey, and 7 other patients were excluded from the study by reason of an acute myocardial infarction within the 7 days preceding surgery. Compared with the 501 included patients, excluded ones proved to be older (median age 68 vs 63 years, P<0.001), less often men (65 vs 83%, P<0.001), and had a higher Euroscore risk sum (median 4 vs 2, P<0.001); they were more often operated urgently (47 vs 20%, P<0.001), and more often had three-vessel disease (68 vs 60%, P=0.029) or diabetes mellitus (22 vs 17%, P=0.039).

Eighty patients (16%) were diagnosed as having PMI. The distribution of postoperative peak CK-MB values among patients with Q-wave and non-Q-wave PMI is shown in Fig. 1 . Preoperative patient characteristics and intraoperative data for PMI and no-PMI groups are shown in Table 1. Patients in the PMI group were an average 3.7 years' older (P=0.001), presented more often with a history of stroke (P=0.018), had more frequently suffered rest angina in the preceding week (P=0.034), and their Euroscore risk score mean was higher by one point (P<0.001). PMI and no-PMI groups were closely similar in terms of other preoperative characteristics. PMI patients were less likely to be diabetics, smokers, overweight or with chronic obstructive pulmonary disease. The number of distal anastomoses did not differ significantly between the groups, but PMI patients received sequential anastomoses more frequently (P=0.029). When compared to the initial preoperative coronary angiogram, main target vessel revascularization was achieved in 91.3% of PMI and 95.3% of no-PMI cases. The use of combined antegrade and retrograde cardioplegia vs antegrade cardioplegia alone did not differ significantly between the PMI (81 vs 19%) and no-PMI (77 vs 23%) groups. PMI patients had an average 16 min longer CPB time (P<0.001) and 11 min longer aortic cross-clamp time (P<0.001). When all the factors associated (P<0.05) with an increased incidence of PMI in a univariate analysis (Table 1, high age; high Euroscore risk score; unstable angina; history of stroke; use of sequential anastomosis technique; long aortic cross-clamp time; long CPB duration) were taken for multivariate logistic regression analysis, only long CPB time (OR 3.02 95% CI 1.38–6.60, P=0.006) and advanced age (OR 1.03 95% CI 1.00–1.07, P=0.049) proved to be independent predictors for PMI.



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Fig. 1. Postoperative peak CK-MB values in patients with Q-wave and non-Q wave PMI.

 

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Table 1. Pre-operative characteristics and operative factors in patients with PMI and with no PMI

 
Thirty-day mortality was statistically significantly associated with PMI; five (6.3%) deaths occurred in the PMI group and four (1.0%) in no-PMI group (P=0.001). In a multivariate analysis, PMI (OR 5.3, 95% CI 1.2–22.6, P<0.05), redo surgery (OR 13.1, 95% CI 1.7–103.0, P<0.05) and subnormal (less than 50%) ejection fraction (OR 7.3, 95% CI 1.3–41.1, P<0.05) were identified as being independent predictors of 30-day mortality while female gender, non-elective operation, higher age, high Euroscore risk score sum (≥6) and diabetes were not. During the later follow-up period up to 12 months, only one additional death occurred in the PMI group (1.3%) as against six (1.4%) in the no-PMI group. The total 1 year mortality rates were 7.5% for PMI and 2.4% for no-PMI (P=0.017) groups, respectively. Fifty-seven per cent of the deaths in the PMI group and 50% in the no-PMI group were directly attributable to cardiac-related factors.

There was a slight and in most instances non-significant tendency to more adverse events among the PMI patients, as shown in Table 2. Supported ventilation time (median 15.9 vs 14.1 h, P<0.003) and the median length of ICU stay (2.0 vs 1.0 days, P<0.001) were significantly longer in the case of PMI patients. The occurrence of stroke, on the other hand, was lower in these patients. In general, a great majority of both PMI patients (86%) and those without PMI (92.6%) had a favorable outcome without other major complications (P=0.059).


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Table 2. Early adverse events in patients with PMI and with no PMI

 
Both PMI and no-PMI patients evidenced depressed preoperative health status in all eight dimensions of the RAND-36 as compared to the general Finnish population (Table 3.). In general, the baseline scores between the groups were closely similar, being in the PMI group slightly higher in four and slightly lower in the other four RAND-36 dimensions. All health scores improved significantly (P<0.001) among the patients without PMI. In PMI patients, significant changes were seen in all but two RAND-36 dimensions (general health and emotional well-being). Group differences were statistically significant in general health (P=0.010), physical functioning (P=0.036) and role functioning/physical (P=0.011) indicating less steep improvement of these QOL dimensions in the PMI patients. Thirty PMI patients (38%) in fact showed a small negative change in their general health scores at follow-up. As shown in Table 4, multivariate regression analysis revealed PMI to be an independent predictor of this adverse change in the general health scores at one year after CABG.


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Table 3. Mean quality of life scores (RAND-36) for study patients and general population

 

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Table 4. Multivariate logistic regression analysis of putative predictors of decreased General Health scores (RAND-36) 1 year after CABG

 
A highly significant (P<0.001) improvement was seen in the RAND-36 MCS and PCS scores in both patient groups (Fig. 2) . However, the magnitude of change in the PMI as compared to no-PMI patients was lower in both score categories, and repeated measures analysis of variance revealed a significant (P=0.002) group by change interaction for the PCS score indicating a more pronounced improvement for the no-PMI group. The possible confounding role of age was investigated using age as a covariate, and the results showed no age by change interaction for MCS (P=0.47) and PCS (P=0.89) scores. In all, 67% of the PMI patients and 75% of those without PMI (P=0.15) had a positive change in their MCS scores, while the corresponding figures for PCS scores were 81 and 87% (P=0.18), respectively.



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Fig. 2. Preoperative and one-year postoperative RAND-36 Mental Component Summary (MCS) and Physical Component Summary (PCS) scores of patients with PMI and with no PMI.

 
Eighty-six percent and 87% of the PMI and no-PMI patients, respectively, had improved by at least 1 NYHA functional class one year after the operation, 10.4 and 9.9% of all patients in these groups, respectively, being in NYHA functional class III or IV. Also low preoperative ejection fraction was not associated with increase in one year angina severity; the proportion of individuals with preoperative low ejection fraction (<50%) was 18% among patients with postoperative NYHA class I-II and 24% in the group with NYHA III or IV (P=0.40). During the first postoperative year, 23% of the PMI and 10% of the no-PMI patients (P=0.002) were readmitted to the secondary referral or primary hospital for cardiac-related reasons such as recurrent chest pain, myocardial infarction, arrhythmia and congestive heart failure. A new coronary angiography was performed in 6 PMI (8.1%) and 12 no-PMI cases (2.9%), leading to coronary angioplasty in 1 (1.4%) and 3 cases (0.7%), and to a redo CABG in 2 (2.7%) and 1 (0.2%) patients in the PMI and in no-PMI groups, respectively.


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
The outcome of CABG is traditionally measured in terms of mortality or morbidity [1416], and PMI is a major adverse event. Postoperative mortality is easy to define, but there is lack of consensus regarding the definition and quantification of myocardial infarction in the perioperative and early postoperative period [17]. Myocardial infarction sustained during this period has been defined on three types of criteria: electrocardiographic changes, blood enzyme levels and new wall motion abnormalities evidenced by ventricular angiography or echocardiography. A persistent new Q-wave on the ECG has traditionally been accepted as a single indication of a definite myocardial infarction, but not all authors take it as a golden standard [18]. CK-MB isoenzyme has been most widely used for years, but recent studies have suggested that troponin I is the most sensitive and specific in depicting myocardial ishemic events [19,20]. In our institution, troponin I was not routinely measured at the beginning of this study period. We were also unable to include a standardized perioperative echocardiography in our study protocol. Our definition of PMI therefore included the ECG and/or CK-MB enzyme criteria and revealed a 16% occurrence of PMI, which is well within the limits of the wide range reported in the literature [21].

Our main interest was focused on the clinical significance of PMI and its impact on subsequent health-related QOL. However, this called for evaluating first the possible differences in patient characteristics and early postoperative adverse events between PMI and no-PMI patients. Although preoperative and intraoperative predictors of PMI in our data were many, most of these variables lost their significance in multivariate analysis. Long CPB time proved to be a relatively powerful independent predictor of PMI, whereas the effect of advanced age was less markedly associated with PMI. The influence of CPB time on outcome may reflect both problems encountered during revascularization and the time-related influence of CPB on the human body.

PMI was an independent predictor of 30-day mortality but showed no effect on subsequent mortality. This is in line with the earlier findings of groups under Brasch [6] and Chaitman [22], who showed no effect of new perioperative Q waves on long-term survival. PMI patients needed longer ventilatory support and longer ICU stay, but in other respects PMI was not significantly associated with early adverse events.

A variety of health measurement tools have been developed over the last decade for the purpose of quantifying and differentiating between different health states. We chose the Finnish version of the RAND-36 Health Survey questionnaire, as this has been carefully adapted to Finnish populations and yields population-based reference values derived from studies made of randomly selected Finns [8]. The selection was based on the Finnish Population Register and the sample consisted of 2060 persons aged 18–79 years, and the results were weighted against the age and gender distribution in the general Finnish population. The generic health-related QOL measure has also previously been used to evaluate health status in general population surveys, to determine the effectiveness of medical treatments in patients with angina [23], and also more recently to evaluate the impact of mitral valve [24] and CABG surgery [25] on patients' QOL.

Importantly, the RAND-36 baseline scores were well comparable between the PMI and no-PMI groups. One year after CABG, patients in the PMI group showed a significant improvement in six of the eight dimensions of health-related QOL (i.e. all except general health and emotional well-being). All the patients in the no-PMI group, on the other hand, showed highly significant (P<0.001) improvement in all eight parameters. Furthermore, one third of the PMI patients had a negative change in their general health scores at follow up and multivariate logistic regression analysis revealed PMI to be (the only) independent predictor of lower score. A tendency toward less marked improvement among PMI patients was also seen in the psycho-social (MCS) and especially in the physical (PCS) components of the QOL, as this group showed a significantly lower magnitude of change in their PCS scores. Patients in the PMI group were a mean 3.7 years older, and our previous studies suggest that higher age predicts adverse outcome in general and also less marked improvement in health-related QOL following the CABG operation [4,25]. The possible confounding role of age was therefore investigated using repeated measures analysis of variance with age as a covariate, but the results showed no age by change interaction for PCS and MCS scores, indicating a less steep improvement for the PMI patients. No obvious explanation for this finding is to hand. We found only one previous study including a QOL analysis of patients sustaining PMI after cardiac surgery [7]. The study in question, however, included only 42 PMI patients, and the authors used an unvalidated QOL instrument with no baseline values for comparison with postoperative findings. They found no differences in 24 months postoperative QOL between those who suffered PMI and those who did not.

Freedom from anginal symptoms at one year was closely similar in both groups Incomplete revascularization, if involved, may reflect in recurrent ischaemia and pain, but the two groups in our study achieved almost equal main target vessel revascularization. NYHA class is based on patient interview and was also reported by the patients in our study; however, we were not able to confirm that symptoms experienced were attributable solely to myocardial ischemia.

The prevalence of hospital readmissions in the postdischarge period after cardiac operations has not been extensively studied, possibly because readmissions are difficult to track in that most of them take place in other hospitals. However, rehospitalization rates after surgical procedures can be used as an indicator of quality of care, since they affect QOL, and they also have financial implications. In our study, readmissions for cardiac-related reasons during the first postoperative year were more than twice as common among PMI patients as compared with those not suffering PMI after CABG. PMI patients also undervent invasive cardiac reprocedures more often, although the absolute numbers were small in both groups and no statistical handling of this is possible.

This is the first time that a comprehensive, properly validated QOL instrument has been used to evaluate the impact of PMI on subsequent health-related QOL following CABG. All assessments were made preoperatively and repeated 12 months later. The rate of response to our follow-up questionnaire was good (94.4% of the survivors), and except for younger age, no other differences were found between the non-responders and responders in preoperative clinical characteristics such as sex, Euroscore risk sum, priority of operation or NYHA class. All the relevant medical and clinical variables were carefully recorded for common analysis with QOL data, and our data also included events in the secondary referral hospitals, which is important, since only 2.4% of the patients were discharged directly home.

This study had several obvious limitations. First, there were a large number of patients who refused or were unable to complete the baseline survey prior to CABG and were thus excluded from this psycho-social and medical follow-up. Excluded patients were five years older and were more often acutely ill and were in many instances operated urgently or as emergency cases. This selection limits the interpretation of our results. Second, our institution lacked routine troponin measurement in the determination of PMI at the beginning of the study period. An increased concentration of CK-MB alone is a sensitive but not very specific criterion. The requirement of the presence of pathologic Q waves to indicate myocardial infarction increases specificity but has a lower sensitivity. In addition, we also lacked data on postoperative left ventricular ejection fraction because echocardiography was used only when clinically indicated. Finally, a 1-year follow-up is not more than ‘a mid-term period’ in evaluating outcomes and stability of QOL after CABG, but we intend a further follow-up of these patients.

To conclude, our results suggest that PMI is an important clinical event which has a negative impact on health-related quality of life following CABG. PMI increases 30-day mortality but, interestingly enough, is not significantly associated with other early adverse events and shows no effect on later mortality. Both intraoperative factors and preoperative characteristics (such as prolonged CPB time and advanced age) influence the risk of PMI after CABG.


    References
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

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