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Ann Thorac Surg 1997;64:1089-1095
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Late Survival After Valve Operation in Patients With Left Ventricular Dysfunction

Carlyle Fraser Heart Center, Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia

Accepted for publication April 17, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. Left ventricular dysfunction is a predictor of hospital mortality after cardiac valve operation. We evaluated late survival in a large cohort of these patients.

Methods. From 1980 to 1993, 257 patients with a preoperative ejection fraction of 0.40 or less underwent aortic (n = 177), mitral (n = 72), or combined (n = 8) valve operation, with or without concomitant coronary artery bypass grafting.

Results. Hospital mortality was 12.5%. Follow-up was 98% complete. Logistic regression analysis showed that an ejection fraction of less than 0.30, mitral regurgitation, concomitant coronary artery bypass grafting, emergency operation, and reoperation were independent correlates of hospital mortality (all at p < 0.05). Kaplan-Meier survival curves of the 220 hospital survivors showed a 65% 5-year survival. Multivariate analysis revealed preoperative use of diuretics, male sex, reoperation, age exceeding 60 years, and aortic regurgitation to be independent predictors of poor late outcome (all at p < 0.05).

Conclusions. The liability of left ventricular dysfunction with regard to diminished long-term survival is not completely reversed by valve operation. If operation is not performed before left ventricular dysfunction develops, postoperative medical treatment of these dilated, remodeled ventricles should be considered.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Surgical repair has become the standard of care for patients with cardiac valve disease. In one study comparing medical and surgical treatment in 157 patients with rheumatic mitral valve (MV) disease, operation was associated with a significant improvement in survival over the 52% 5-year survival seen in the medically managed patients [1]. A similar favorable result from surgical therapy was seen in a separate study in which the outcomes in 252 operated and 47 unoperated patients with isolated aortic valve (AV) disease were retrospectively evaluated [2]. Several variables, however, identify a subset of patients at increased risk of morbidity and mortality after surgical intervention for the treatment of valve disease. Hospital mortality in these patients has been associated with advanced age, female sex, left ventricular (LV) dysfunction, emergency procedure, reoperation, advanced functional classification, concomitant coronary artery disease, and nonsinus rhythms [3–12]. Reduced long-term survival after surgical intervention has been predicted by advanced age, concomitant coronary artery disease, advanced functional classification, renal or hepatic failure, and aortic regurgitation. In most of these studies, preoperative LV function has also emerged as an independent predictor of long-term survival after valve procedures [3, 10, 13–19]. However, most of these studies have contained a limited number of patients with LV dysfunction or lacked prolonged follow-up data.

Many individuals with valvular heart disease are managed medically until clinical symptoms develop. However, because the signs and symptoms of valvular stenosis or insufficiency may not develop until after extensive myocardial damage has occurred, a significant number of patients who undergo valve operation have advanced LV dysfunction at the time of operation. To assess the potential benefit of valve replacement in patients with advanced LV dysfunction, it is necessary to accumulate data on the survival expectation in these patients as well as data on preoperative predictors of diminished long-term survival. To this end, we studied the in-hospital and long-term survival of 257 patients with significant preoperative LV dysfunction (ejection fraction [EF], 0.40) who underwent repair or replacement of the AV, or MV, or both, with or without concomitant coronary artery bypass grafting (CABG), between 1980 and 1993. Preoperative, intraoperative, and postoperative variables were analyzed with respect to early and long-term survival.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Patient Population
The patient population was identified from the Emory Cardiac Data Bank, which includes patients from Emory University Hospital and Crawford Long Hospital of Emory University. The patients identified underwent valve operation, either repair or replacement, between 1980 and 1993, with or without concomitant CABG. All patients had undergone cardiac catheterization within 2 months before operation, with a documented right anterior oblique plane ventriculogram EF of 0.40 or less.

Variables Registered
PREOPERATIVE VARIABLES.
Routine patient demographics noted included sex, age, medications, history of rheumatic heart disease, previous cardiac operations, the New York Heart Association (NYHA) classification (I to IV) and the Canadian Cardiovascular Society functional classification of angina (I to IV), preoperative diuretic use, and the need for an intraaortic balloon pump before the operation [20, 21]. The EF, calculated from the right anterior oblique plane ventriculogram on cardiac catheterization, was documented. The valve lesion shown by the catheterization study was recorded as follows: AV versus mitral valve MV versus combined valve (AV/MV) and predominant stenosis versus predominant regurgitation. The severity of regurgitation, the transvalvular pressure gradient, the calculated orifice area, the pulmonary artery pressure, and the LV end-diastolic pressure were also determined from the cardiac catheterization study.

OPERATIVE VARIABLES.
The operation performed was identified as valve replacement, valve repair, or combination; AV, MV, or both; concomitant CABG; and any other associated procedures. The type and size of the prosthetic device used in patients who underwent valve replacement or annuloplasty ring inserted were also recorded, as were the total cardiopulmonary bypass time and the cross-clamp time, whether an intraaortic balloon pump was used, intraoperatively and whether the operation was an emergency procedure.

POSTOPERATIVE.
Variables recorded included postoperative catecholamine use and intraaortic balloon pump requirement, the number of days in the intensive care unit, and the total number of days in the hospital. Postoperative complications noted were myocardial infarction (new Q wave on postoperative electrocardiogram), prolonged mechanical ventilation (more than 72 hours), cerebrovascular accident (neurologic deficit lasting more than 24 hours), sepsis, renal failure (need for dialysis), and arrhythmias (atrial or ventricular arrhythmias). Hospital mortality was defined as death occurring during the hospitalization for the operation. That is, a patient who survived for more than 30 days after operation but died before hospital discharge was counted as a hospital mortality.

Follow-up
Follow-up, conducted between October 1995 and December 1995, was complete for 220 of the 225 hospital survivors (97.8%). A physician contacted the patients by telephone. Current NYHA and Canadian Cardiovascular Society functional classifications, rehospitalization for cardiac disease, cardiac catheterization since the valve operation, and subsequent cardiac valve reoperation data were obtained. The number of days from the date of the operation to the date of follow-up or death was also recorded.

Statistical Analysis
Continuous data were displayed as a mean ± standard deviation. The ² or Fisher's exact test was used to determine the significance of differences for categorical variables and the t test or Wilcoxon two-sample test for continuous variables [22]. Univariate correlates of late survival were identified by the log-rank test, and univariate (unadjusted) Kaplan-Meier curves were derived utilizing S-Plus statistical software (MathSoft, Inc., Seattle, WA) [22]. The multivariate (adjusted) correlates of late survival were identified with the Cox proportional hazards regression, in which the hazard of death was modeled from all characteristics identified in Tables 1 through 3. The results were displayed in terms of hazard ratios (HR), that is, the ratios of the hazard of death for patients with and without a particular characteristic, with 95% confidence intervals displayed in adjacent brackets. Hospital mortality was analyzed multivariately with logistic regression, which models the odds of hospital death. The results were displayed in terms of odds ratios (OR), that is, the odds of death for patients with and without a particular characteristic. All tests were two-tailed, and a p value of 0.05 or less was considered to indicate statistical significance. All missing data were assumed to be missing at random [23].

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

Operative variables are given in Table 3, which also includes a description of the surgical procedures performed. One hundred twenty-five (48.6%) patients had concomitant CABG: 44.6% of AV patients, 59.7% of MV patients, and 37.5% of AV/MV patients (p = 0.076) (see Table 3). Surgical repair of the aortic root was concurrently performed in 7.4% of all patients and resection or plication of an LV aneurysm in 3.9%. Carpentier-Edwards bioprostheses (Baxter Healthcare Corp, Chicago, IL) were used in 63.1% of patients and St. Jude mechanical prostheses (St. Jude Medical, St. Paul, MN) in 14.1% (Table 4).

Thirty-two patients died in the perioperative period, resulting in an overall hospital mortality rate of 12.5%. Mortality was 19.4% for patients with MV disease and 9.0% for patients with AV disease. Univariate analysis results are depicted in Figure 1. Independent predictors of hospital mortality, shown by logistic regression analysis of preoperative variables, were EF of less than 0.30 (OR, 2.98 [1.26, 7.08]; p = 0.014), mitral regurgitation (OR, 2.40 [0.99, 5.77]; p = 0.05), emergency operation (OR, 6.62 [2.24, 19.57]; p < 0.001), concomitant CABG (OR, 3.82 [1.50, 9.74]; p = 0.005), and reoperation (OR, 3.74 [1.48, 9.44]; p = 0.006). Functional classification (NYHA), age, and sex were not found to be independent predictors of hospital mortality.

View larger version (23K): [in this window] [in a new window]   Fig 1. . Univariate odds ratio with 95% confidence interval for hospital mortality. Variables marked with an asterisk were statistically significant in a multivariate model (p < 0.05). (CABG = concomitant coronary artery bypass grafting; EF = ejection fraction.)

View larger version (24K): [in this window] [in a new window]   Fig 2. . New York Heart Association (NYHA) classification and Canadian Cardiovascular Society (CCS) functional classification of angina. (A) Before valve operation. (B) At follow-up.

View larger version (18K): [in this window] [in a new window]   Fig 3. . Kaplan-Meier actuarial survival curve for the group of 220 hospital survivors.

View larger version (29K): [in this window] [in a new window]   Fig 4. . Kaplan-Meier survival curves for hospital survivors. (A) Degree of left ventricular dysfunction. (B) Preoperative diuretic use. (EF = ejection fraction.)

View larger version (26K): [in this window] [in a new window]   Fig 5. . Aortic regurgitation was found to be a significant predictor of poor late survival (A), whereas patients with aortic stenosis had long-term outcomes similar to those of all other patients (B).

View larger version (27K): [in this window] [in a new window]   Fig 6. . Univariate hazard ratio with 95% confidence interval for late mortality. Variables marked with an asterisk were found to be statistically significant in a multivariate model (p < 0.05). (CABG = coronary artery bypass grafting; CCS = Canadian Cardiovascular Society functional classification of angina; PAP = pulmonary artery pressure; NYHA = New York Heart Association classification.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

The predictors of poor hospital survival revealed in our analysis (see Fig 1) are compatible with the conclusions of the authors [3, 5, 6–9]. It is notable that univariate analysis revealed emergency operation to be associated with an approximately ninefold increase in hospital mortality in these very ill patients. This would make one tend to argue for the stabilization of patients with valve disease and poor LV function whenever possible. The concomitant performance of CABG is associated with a threefold increase in hospital mortality, indicating that the operative risk is greatly increased when the cause of the LV dysfunction is ischemic rather than valvular. The hospital mortality in patients with very low ejection fractions (EF, 0.1 to 0.3) is more than twofold greater than that in patients with less severe LV dysfunction (EF; 0.31 to 0.40). It should be emphasized, however, that the ORs shown in Figure 1 and the HRs shown in Figure 5 represent comparisons between patients in this series with the preoperative predictor compared with patients in this series without the preoperative predictor; the comparison is not made with the general population of patients undergoing valve procedures. In this regard it is important to note that mitral regurgitation also was associated with a greater than twofold increase in hospital mortality, as compared with the mortality in patients who had mitral stenosis, aortic regurgitation, or aortic stenosis.

The long-term operative results in these patients were certainly gratifying, with an excellent recovery of quality of life, as depicted in Figure 2, and with 90% of hospital survivors in functional class I or II at follow-up. Figure 3 depicts a relatively linear curve for long-term survival, with a 5-year survival rate of 65% and a 10-year survival rate of 40%. Of particular interest is the fact that, although mitral regurgitation was predictive of a poor hospital outcome, aortic regurgitation was predictive of a poor long-term outcome (HR of 1.58 as compared with the other valve lesions). The presence or absence of coronary artery disease in this series was not predictive of a poor long-term outcome. Perhaps this is related to the fact that in this series the mortality in patients with severe ischemic cardiomyopathy was relatively high at the time of operation and that long-term survival only applies to hospital survivors. Preoperative diuretic use as a marker of preoperative congestive heart failure was one of the strongest predictors of a poor long-term outcome. This finding reinforces the concept that valve operations should be performed before the clinical symptoms of congestive heart failure develop. Of particular note are those factors that were not predictive of poor long-term survival in this series (again noting that this series is confined to patients with poor LV function). Advanced congestive heart failure symptoms and advanced anginal symptoms, as well as elevated pulmonary artery pressures, were not predictive of poor long-term results in these patients with LV dysfunction.

One might question whether the survival liability of the LV dysfunction observed for valvular heart disease is equivalent to the survival liability observed for the LV remodeling that is consequent to ischemic heart disease. In the Survival and Ventricular Enlargement (SAVE) trial, more than 2,000 asymptomatic patients with an EF of 0.40 or less after a myocardial infarction who were prospectively randomized to receive placebo or captopril were followed up [24]. The 4-year cumulative survival rate was approximately 78% in the captopril group and 74% in the placebo group. The 4-year cumulative survival in the current series of patients with LV dysfunction who survived the valve operation was 72%. The mean age of the patients in the SAVE trial was approximately 59 years, whereas the mean patient age in the present series was 62 years. These data indicate that the survival liability of LV dysfunction related to valve disease may be approximately equivalent to the survival liability of LV dysfunction consequent to myocardial infarction. Once LV dysfunction has occurred, valve repair or replacement may improve the patient's survival expectations by eliminating the valvular dysfunction, but the survival liability of poor LV dysfunction persists.

In conclusion, one can predict a reasonable 5- and 10-year survival in patients with LV dysfunction who can survive cardiac valve operations. Emergency operations, concomitant CABG, reoperation, a very low EF, and mitral regurgitation as the predominant valve lesion have a negative effect on hospital survival in this group of patients with LV dysfunction who undergo a valve operation. Long-term survival in this series was surprisingly not influenced significantly by the presence of concomitant coronary artery disease requiring operation, by the presence of elevated pulmonary artery pressures, or by the preoperative presence of class III or IV symptoms. Preoperative diuretic use, male sex, and advanced age were associated with diminished long-term survival. Of the valvular lesions, aortic regurgitation was associated with a greater than 1.5 times increase in long-term mortality, as compared with predominant aortic stenosis, mitral regurgitation, and mitral stenosis.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Presented at the Sixty-ninth Scientific Session of the American Heart Association, New Orleans, LA, Nov 10–13, 1996.

Address reprint requests to Dr Guyton, Division of Cardiothoracic Surgery, Department of Surgery, Crawford Long Hospital, Emory University School of Medicine, 550 Peachtree St, NE, Atlanta, GA 30365-2225.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Charles O. Murphy Ellis L. Jones Joseph M. Craver John Parker Gott Robert A. Guyton Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duarte, I. G. Articles by Guyton, R. A. Search for Related Content PubMed PubMed Citation Articles by Duarte, I. G. Articles by Guyton, R. A.