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Eur J Cardiothorac Surg 2002;22:904-911
© 2002 Elsevier Science NL
a Department of Thoracic and Cardiovascular Surgery, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
b Department of Cardiology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
Received 15 February 2002; received in revised form 2 September 2002; accepted 6 September 2002.
* Corresponding author. Tel.: +46-18-611-0000; fax: +46-18-551526
e-mail: laila.hellgren{at}thorax.uas.lul.se
| Abstract |
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Key Words: Heart valve surgery Early mortality Morbidity Time trends
| 1. Introduction |
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| 2. Material and methods |
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2.2. Data collection and follow-up
All clinical data were collected at a preoperative interview with the patient and stored in a computer.
The following variables were entered into the analyses: demographic variables (age at operation, sex, year of surgery), history of the disease (previous myocardial infarction), symptoms and clinical status (dyspnea, left heart failure, NYHA functional class, preoperative heart rhythm (sinus rhythm, atrial fibrillation, or other)), preoperative haemodynamics (stable, stable with inotropic treatment or shock), priority of surgery (elective, urgent, or emergency), associated conditions (hypertension, diabetes, history of cerebrovascular disease, decreased renal function (dialysis-dependent or not dialysis-dependent (defined as preoperative S-creatinine above 150 µmol/l)) or any other serious diseases, e.g. malignancies), preoperative catheterization data (presence of significant coronary artery disease (i.e. with stenosis of 50% or more in at least one coronary artery)), and characteristics of the surgical procedure (aortic cross-clamp time and cardiopulmonary bypass time, concomitant CABG, concomitant MVR, perioperative myocardial injury [defined as a new Q wave on ECG, and/or an elevation of serum cardiac enzymes measured on the first postoperative day. A concentration of serum aspartate aminotransferase (S-ASAT, normal range <0.6 µkat/l) exceeding 2.5 µkat/l and/or a concentration of creatinine kinase isoenzyme (CK-MB, normal range <3 µkat/l) exceeding 50 µkat/l was considered elevated]).
NYHA classification [9] of congestive heart failure was made on the basis of the clinical status of the patient at the preoperative interview: patients who suffered slight discomfort in their normal activity were allocated to NYHA class IIIA. Patients who managed only the lightest of activity without discomfort were allocated to NYHA IIIB, and those confined to bed because of symptoms were assigned to NYHA IV.
Left ventricular (LV) function was classified as either normal, moderate dysfunction, or severe dysfunction, on the basis of ejection fraction. Ejection fraction values above 0.5 were considered to be represent normal LV-function, values between 0.50 and 0.35 moderate LV dysfunction, and values below 0.30 severe LV dysfunction.
By use of two national registers, namely the Swedish Cause of Death Register and a continuously updated population register, all patients were followed up in January 2000. All patients were assigned a date of death or identified as being alive within 30 days from surgery.
2.3. Outcome event
Early mortality was defined as death from any cause within 30 days from surgery.
2.4. Postoperative complications
Postoperative complications registered were: heart failure (defined as one of the following: death within the first postoperative day due to heart failure, postoperative requirement of two or more inotropic drugs, failure to wean from CPB after prolonged reperfusion (over 45 min), or inadequate circulation later in the postoperative period). Inadequate circulation was defined as: mean arterial pressure (MAP) below 60 mmHg, poor peripheral perfusion as indicated by oliguria (less than 400 ml/24 h), mixed venous oxygen saturation below 60%, or a cardiac index of less than 2 l/min per m2). Bleeding was defined as excessive postoperative bleeding requiring reoperation. Neurological complication was defined as any neurological deficit occurring postoperatively with a corresponding cerebral lesion on computed tomography.
2.5. Statistical methods
Risk factors for a poor outcome were identified by univariate and multivariate analysis, using the logistic regression model [10]. Estimates for all models were obtained with the maximum likelihood method. The explanatory variables were first considered one by one and then in a multivariate analysis, in order to select the set of variables that best predicted the outcome. The odds ratio (OR) computed from the logistic regression analysis was used as a measure of the relative risk [11]. ORs are given with 95% confidence intervals (CI) within parentheses.
Further, stratified logistic regression models were used for the analysis of the interaction between risk factors and type of lesion. Interaction was then tested for by introduction of an interaction term.
Continuous variables were first tested in their original continuous form and then with a set of dummy variables representing ranges, defined by commonly used, or standard cut-off points. This model was preferred since it could not be assumed that the relation between the continuous variables and the logarithmic odds of operative mortality was linear. The odds ratios and their 95% confidence intervals are in general given for the variable in categorized form; this way of presenting the results was considered the most informative. In the multivariate analyses, the variables were used in their optimal form i.e., the form with the best discriminatory power.
All variables found to be significant (P<0.05) in the univariate analysis were considered in the multivariate analysis. An alternative model based on the preoperatively available variables was defined.
On the basis of the final multivariate model, based on all available risk factors, a risk score for early mortality was computed for each patient. Patients were categorized according to that risk score into either a high- or a low-risk group. The predicted outcome was compared with the actual observed outcome using different cut-off points. Sensitivity and specificity obtained by the final model using different cut-off points are presented as a receiver operating characteristic (ROC) curve [12] for validation of the risk model. The area under the ROC curve was used to assess how well the models could discriminate between patients who survived and those who died within 30 days from surgery.
The Cochran-Armitage Trend Test was used to test for trends in the incidence of postoperative complications and to determine the distribution of risk factors over time.
All calculations were performed with the SAS 6.12 statistical procedure.
| 3. Results |
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3.2. Risk factors
Factors related to an increased risk for early mortality are listed in Tables 1 and 4. Age over 70 years increased the early risk, with an OR for early mortality of 2.1. Patients in an advanced NYHA class, especially NYHA class IV, were also at increased risk, with an OR of 2.2. The strongest predictor of early death was preoperative shock, with an OR of 3.5. Operative factors that increased the risk for early mortality were aortic cross-clamp time over 150 min and bypass time over 180 min, ORs of 3.2 and 2.7, respectively.
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There was a significant interaction effect between preoperative atrial fibrillation and type of valve procedure (P-value for interaction variable=0.0015). Atrial fibrillation was a significant risk factor for early mortality (OR=2.6 (1.64.1)) in patients who underwent aortic replacement (i.e. the AVR and DVR groups), but had no effect in the MVR group (OR=0.96 (0.72.8)). The incidence of atrial fibrillation was 10% in the AVR group, 44% in the MVR group, 44% in the DVR group and 35% in the mitral valve repair group.
There were no other significant interaction effects between types of valve interventions and risk factors.
3.3. Time trends
There was a consistent decrease in early mortality over the study period (OR=0.9 for every year after 1990 (95% CI 0.870.94)) (Fig. 1)
. This decrease remained after adjustment for risk factors (Table 1) and was seen in all valve groups. There were too few patients in the mitral valve repair group to permit separate analyses of time trends.
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The annual number of procedures was constant over the study period. There was an increase in the proportion of patients older than 70 years of age (P-value for trend <0.002, Fig. 2, upper) , and of patients with diabetic disease (P-value for trend <0.0442, Fig. 2, lower), but no other significant change in clinical characteristics over time was detected.
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| 4. Discussion |
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We found that the mortality rates in this study were comparable to those reported from other population-based studies. The STS National Database with 86 580 patients [13], and the CSCR study with 14 190 patients [14], report early mortality rates for AVR of 4.0 and 3.3% and for MVR of 6.0 and 6.2%, respectively. Concomitant CABG increased the early risk, giving rates of 6.8 and 7.1% for AVR/CABG and a rate of 13% for MVR/CABG. The early mortality in our study of 4.8% for AVR and 9.0% for MVR, included concomitant CABG in totally 41% of the cases. Thus, the early mortality rates in this study are in good agreement with the rates of the STS and CSCR databases.
In older studies, declining mortality rates among AVR patients were found in the mid 1980s [15]. Not many studies have been conducted in recent times and in population- based patient groups. The only recent population-based study, from Northern New England [16], showed a decrease in risk-adjusted early mortality from 9.3% (19921993) to 5.3% (19961997) in patients undergoing AVR without concomitant CABG. The corresponding decline in our study was from 5.6% (19901991) to 4.9% for AVR (19961999) including CABG, and from 5.6 to 2.5% for isolated AVR. In the Northern New England study a decrease in mortality rate for MVR was also found, from 13.6% in 19921993 to 8.2% in 19961997. This was confirmed in our study, with a decrease in early mortality from 13.4% in 19901991 to 5.0% in 19981999 in the combined MVR and CABG population. The corresponding decrease in patients undergoing MVR without concomitant CABG was from 15.8 to 2.4%.
While the number of patients undergoing mitral valve surgery has remained constant over the last decade, there has been a shift towards an increased proportion of mitral valve repairs. Moreover, the possibility of valvuloplasty has led to a trend towards earlier surgery in some patients with mitral valve disease. Both of these changes may have contributed to the improved early results.
Today, optimal preoperative assessment and management of patients with heart valve disease include more frequent use of echocardiography [17,18]. Echocardiography provides readily available and more objective measures of, for example, the severity of the lesion and left heart function. However, there is a lack of correlation between hemodynamic severity and clinical outcome, and the importance of obtaining a careful history concerning any symptoms must therefore be emphasized. The onset of symptoms can be insidious, and patients may incorrectly ascribe a decrease in exercise tolerance to other causes. Today optimal timing of surgery is based on careful and recurrent echocardiographic examinations and interviews with patients. This may be compared with earlier eras when the decision-making was predominantly clinical, and might have been the main reason for somewhat late surgical correction in patients with already irreversible damage to the heart.
The incidence of postoperative complications tended to decrease over time. In the total population, there was a substantial decrease in the incidence of heart failure from 25 to 12%. In the AVR group there was a decrease from 20 to 12%, and in the MVR group from 42 to 22%. During the same time period the overall incidence of perioperative myocardial injury fell from 20 to 13%. These declines might partly be due to the improved preoperative clinical status of the patient undergoing valve surgery today. There has been a refinement of the medical treatment over the last decade, and medications preserving the functional status of the heart, such as ACE inhibitors and/or beta-blockers, are more frequently in use today. Again, the more optimal timing of surgical correction prevents preoperative deterioration of the systolic and diastolic properties of the heart, which might contribute to the reduction of postoperative heart failure.
In the case of both early mortality and morbidity, the improvement trend must also be attributed to general improvements in the surgical technique, myocardial protection, anesthesia and postoperative care.
In our study, the risk factor profile was comparable to that observed in other studies, with old age and an advanced NYHA class as the most important risk factors. However, preoperative atrial fibrillation is not a generally accepted risk factor for early death in patients undergoing AVR or DVR, but it is a known risk factor for long-term mortality [19]. It may be speculated whether atrial fibrillation in patients undergoing AVR and DVR reflects the presence of more compromised myocardial dysfunction as compared to atrial fibrillation in patients with isolated mitral valve disease.
We have taken into account the majority of the now commonly identified and available risk factors. However, we did not include data about chronic obstructive pulmonary disease and peripheral vascular disease. These variables have been shown to be risk factors for early mortality in risk score models such as the STS mortality score and the EuroSCORE [13,20]. In the present study, comprising only primary heart valve procedures, the included risk factors could discriminate patients at high risk fairly well. Seventy-three percent of the patients who died had a calculated risk of 10% or more. However, a risk model based on data not available prior to surgery has limited usefulness in preoperative risk assessment. In our study, the alternative risk model, based on preoperatively available risk factors, yielded somewhat inferior risk prediction (only 38% of the patients who died had been allocated to the high-risk group) as compared to the risk model based on all available risk factors (including operative risk factors). This finding emphasizes the importance of an optimal surgical technique. It is obvious that a more complicated procedure also results in longer aortic cross-clamp and bypass times. Nevertheless, the aortic cross clamp time and bypass time can at least partly be considered surrogate measures of the quality of the surgical procedure. Given the same preoperative risk factors, the outcome in a single patient will be highly dependent on the surgical quality.
The long-term outcome after heart valve surgery is improved if the operative procedure is carried out in an earlier stage of the disease process [68,2123]. To be able to recommend surgery to asymptomatic or virtually asymptomatic patients, a low operative risk is important. Our study shows that the risks of morbidity and mortality associated with the surgical procedure have been reduced and today are low for most groups of patients undergoing heart valve surgery. However, the decision to submit a patient to surgery must be based on many considerations and cannot be made solely on the grounds of the estimated operative risks.
| References |
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hle E., Bergström R., Malm T., Nyström S.O., Hansson H.E. Early results of mitral valve replacement. Scand J Thor Cardiovasc Surg 1991;25:179-184.[Medline]
hle E. Observed and relative survival after aortic valve replacement. J Am Coll Cardiol 2000;35:747-756.This article has been cited by other articles:
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B. J. Leavitt, Y. R. Baribeau, A. W. DiScipio, C. S. Ross, R. D. Quinn, E. M. Olmstead, D. Sisto, D. S. Likosky, R. P. Cochran, R. A. Clough, et al. Outcomes of Patients Undergoing Concomitant Aortic and Mitral Valve Surgery in Northern New England Circulation, September 15, 2009; 120(11_suppl_1): S155 - S162. [Abstract] [Full Text] [PDF] |
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