Severe Aortic Stenosis With Low Transvalvular Gradient and Severe Left Ventricular Dysfunction
Result of Aortic Valve Replacement in 52 Patients
Background—The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known.
Methods and Results—Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) ≤35% and aortic stenosis with transvalvular mean gradient <30 mm Hg underwent aortic valve replacement. The mean (±SD) preoperative characteristics included EF, 26±8%; aortic valve mean gradient, 23±4 mm Hg; aortic valve area, 0.7±0.2 cm2; and cardiac output, 3.7±1.2 L/min. Simultaneous coronary artery bypass graft surgery was performed in 32 patients (62%). Perioperative (30-day) mortality was 21% (11 of 52 patients). Ten additional patients died during follow-up. Advanced age (P=0.048) and small aortic prosthesis size (P=0.03) were significant predictors of hospital mortality by univariate analysis. By multivariate analysis, the only predictor of surgical mortality was smaller prosthesis size. The only predictor of postoperative survival was improvement in postoperative functional class (P=0.04). Postoperative functional improvement occurred in most patients. Postoperative EF was assessed in 93% of survivors; 74% demonstrated improvement. Positive change in EF was related to smaller preoperative aortic valve area and female sex.
Conclusions—Despite severe left ventricular dysfunction, low transvalvular mean gradient, and increased operative mortality, aortic valve replacement was associated with improved functional status. Postoperative survival was related to younger patient age and larger aortic prosthesis size, and medium-term survival was related to improved postoperative functional class.
Severe aortic stenosis carries a dismal prognosis when associated with congestive heart failure, with an expected survival of <2 years when treated medically.1 Aortic valve replacement is the only effective treatment, but the operative risk2 increases with the development of left ventricular (LV) systolic dysfunction.3 4 5 6 7
The results of aortic valve replacement are uncertain among patients with severe aortic stenosis, reduced LV ejection fraction (LVEF), and low transvalvular mean gradient. Although these patients represent <5% of patients with aortic stenosis, they also represent the most controversial subset. Increased perioperative risk and reduced late outcome compared with controls have been reported in patients with reduced LVEF.7 LV dysfunction may be secondary to long-standing severe aortic stenosis with superimposed myocardial fibrosis, extensive coronary artery disease, or prior myocardial infarction, and in this situation, the LV dysfunction is not likely to improve after aortic valve replacement. Some have therefore suggested that aortic valve replacement should not be considered in this subgroup of patients.8
Few data are available on the clinical outcome of patients with aortic stenosis, decreased LVEF, and low transvalvular mean gradient who undergo aortic valve replacement. Therefore, we tested the hypothesis that aortic valve replacement in patients with aortic stenosis, LVEF ≤35%, and transvalvular mean gradient <30 mm Hg can be performed at an acceptable operative and medium-term risk and that clinical and EF improvement occur in the majority of surgical survivors.
From the Mayo Clinic surgical database, we identified all patients who had aortic valve replacement for native aortic stenosis in the presence of severe LV systolic dysfunction (EF ≤35%) and associated low transvalvular mean gradient (mean gradient <30 mm Hg) between 1985 and 1995. We previously reported the outcome of aortic valve replacement in patients with aortic stenosis and reduced LVEF.7 Twenty-nine of the patients included in the present series were included in our previous report. Patients were excluded if they had concomitant valvular operations other than aortic valve replacement, previous aortic valve replacement, or more than moderate aortic valve regurgitation or were <18 years old. Preoperative clinical, echocardiographic, cardiac catheterization, hemodynamic, coronary artery (Table 1⇓⇓), and operative (Table 2⇓) data were reviewed in 52 consecutive patients who fulfilled entry criteria.
Comprehensive 2D and Doppler echocardiographic assessment30 was performed at the Mayo Clinic in 50 patients (96%) ≤30 days before aortic valve replacement. The EF was calculated by 2D echocardiography with a modification of the method of Quinones et al10 11 in 17 patients, by the volumetric method12 in 25 patients, and by visual estimate13 14 in 10 patients.
Hemodynamic assessment of aortic stenosis was performed by 2D/Doppler methodology, and AVA was calculated by the continuity equation.15
Forty patients (77%) had preoperative hemodynamic assessment by cardiac catheterization. With fluid-filled catheters, LV and systemic arterial pressures were recorded simultaneously. Cardiac output and index were measured, and AVA was calculated from the Gorlin equation.16
Coronary angiography was performed in 50 patients (96%) (mean age±SD, 72±9 years). Coronary artery stenosis was defined as a luminal diameter narrowing of ≥70% in ≥1 of the major epicardial coronary arteries or ≥50% luminal diameter narrowing of the left main coronary artery.
When >1 method was used to define preoperative EF, mean pressure gradient, or AVA, the result of the echocardiographic Doppler method was used when it was performed up to 30 days before aortic valve replacement. The mean AVA (Table 1⇑) was obtained by echocardiographic Doppler technique in 42 patients and by cardiac catheterization in 10 patients.17
The surgical data are outlined in Table 2⇑.
The data are reported as mean±SD. The relationship, univariate and multivariate, of potential risk factors with operative mortality (ie, death within 30 days after operation) was assessed by logistic regression analysis. Overall survival was estimated by the Kaplan-Meier method, and the predictors were analyzed by the Cox proportional hazards model. The relationship of preoperative variables to postoperative EF was assessed by simple and multiple linear regression.
The 30-day mortality was 21% (11 of 52 patients). Univariate analysis for operative mortality identified 2 significant preoperative risk factors: a smaller prosthesis size (P=0.03) and advanced age at operation (P=0.048) (Table 3⇓). The mean aortic prosthesis size was 23.1±1.8 mm in survivors and 21.6±2.1 mm in patients who died perioperatively. The mean age was 70±11 years for survivors and 77±8 years for patients who died perioperatively. Multivariate analysis identified prosthesis size as the only predictor of hospital mortality. Body surface area was not significantly related to hospital mortality.
Ten patients (Table 4⇓) died during a median follow-up of 1.5 years (up to 3.9 years). Two patients were lost to follow-up. Two of the late deaths were from noncardiac causes. The survival of this patient group was 62% at 3 years (Figure 1⇓). The survival in the study group was significantly lower (P=0.04) than survival among the 128 patients who underwent aortic valve replacement for aortic stenosis, with mean gradient ≥30 mm Hg previously reported.7
The 3- and 5-year survival rates among patients without coronary artery disease were 71% compared with 58% and 29%, respectively, among patients with coronary artery disease (P=NS because of small sample size). This is in contrast to our previous report.7
The relationship between the number of perioperative and late deaths and the preoperative mean gradient is outlined in Table 5⇓.
Symptomatic improvement was noted in most of the survivors of surgery. Thirty patients had functional status noted before and after operation. Of these, 85% were severely symptomatic (NYHA class III or IV) before and only 23% were severely symptomatic after operation (Figure 2⇓): 77% of patients (23 of 30 patients) improved by ≥1 NYHA functional class at follow-up. Twenty-three patients (77%) were NYHA class I or II at follow-up.
The year and urgency of operation as well as a history of coronary artery bypass graft surgery or myocardial infarction did not significantly affect survival in this series. Additional factors, including age, sex, preoperative EF, aortic valve area (AVA), cardiac output, mean aortic gradient, prosthesis size, and aortic annular patch enlargement, were not related to survival.
EF was assessed echocardiographically in 93% of the 30-day survivors (38 of 41 patients) at a mean interval of 18 months after operation. Of the patients in whom LVEF was assessed after operation, 28 (74%) showed a positive change. The mean change was an increase of 10±14 EF units (P<0.001) (mean preoperative EF, 24±7%; mean postoperative EF, 32±14%) (Figure 3⇓). The postoperative EF ranged from 12% to 65%. AVA was significantly related to a change in EF after operation (P=0.03) (r=0.36). Sex was significantly related to postoperative EF (P=0.009); women had higher postoperative EF. There was no significant preoperative sex difference in EF.
In severe aortic stenosis, the left ventricle compensates for chronic pressure overload by hypertrophy in an attempt to normalize wall stress. Initially, EF and cardiac output are maintained. When wall stress exceeds the compensating mechanism, LV systolic function declines secondary to afterload mismatch, and the mean pressure gradient generated by the LV may be low despite the presence of severe aortic stenosis. Thus, when LV dysfunction is due to afterload mismatch,4 as seen in severe aortic stenosis, aortic valve replacement results in improvement in EF symptoms and survival.7
LV function and mean aortic valve gradient are prognostic indicators of outcome among patients undergoing aortic valve replacement for aortic stenosis.18 However, the outcome of aortic valve replacement among patients with LV dysfunction and low transvalvular mean gradient has not been well characterized. These patients represent the most controversial and clinically challenging patients with aortic stenosis. Two series reported the outcome of aortic valve replacement in patients with low transvalvular pressure gradient.19 20 However, these 2 series combined described only 22 patients with transvalvular mean gradient <30 mm Hg, and no EF data were reported for 14 of them. When our present series was compared with the 125 patients with aortic stenosis and reduced LVEF but mean gradient >30 mm Hg previously reported,7 there was a significant difference in survival (P=0.04) (Figure 1B⇑). Thus, we undertook to define the outcome and to further stratify risk in this group of patients.
The paucity of data on the outcome of aortic valve replacement in patients with aortic stenosis and LV dysfunction with low mean gradient led us to review 52 such patients in an attempt to determine perioperative mortality, overall survival, and predictors of outcome. By multivariate analysis, we found that 30-day mortality was related to aortic prosthesis size. All patients had LV dysfunction and low mean gradient; therefore, further EF and mean gradient analysis alone were not related to survival. Improved postoperative EF was related to preoperative AVA and female sex.
In the present study, smaller aortic prosthesis size was associated with increased surgical mortality, as previously reported.18 This remained an important predictor of perioperative survival even though 17% had undergone simultaneous aortic root enlargement to allow placement of a larger prosthesis. Of the 11 patients who died perioperatively, 5 received an aortic prosthesis <23 mm. There was no relationship between body surface area and perioperative mortality, but small prosthesis size reflects small annulus dimension. The body surface area of the patient who received the 17-mm aortic prosthesis was 1.32 m2, and the mean±SD of body surface area of the 3 patients who received 19-mm prostheses was 1.52±0.03 m2. Small valve prostheses have higher transvalvular gradients than larger prostheses.21 22 The failure to decrease afterload effectively with smaller aortic prostheses in these patients with low preoperative mean transvalvular gradient may influence surgical outcome.
The problem of valve-prosthesis–patient mismatch is also potentially important regarding this series of patients. The effective orifice area of a prosthesis is less than that of a normal human valve. Occasionally, the reduced prosthetic valve area further confounds the clinical situation, resulting in symptomatic and hemodynamic deterioration. This occurs when the decrease in afterload is less than expected because of small prosthesis size. This may account, in part, for the increased mortality noted among patients with the smallest prostheses.23 24
Small aortic prostheses have also been associated with increased late mortality among patients undergoing simultaneous coronary artery bypass graft surgery.25 This association was not appreciated among the patients we report.
It remains uncertain whether annular enlargement26 to accommodate a prosthesis 1 or 2 sizes larger will improve mortality.
Effect of Aortic Valve Replacement on Postoperative EF
Aortic valve replacement for aortic stenosis decreases ventricular afterload.27 EF is expected to improve after aortic valve replacement among patients with severe aortic stenosis and decreased preoperative EF.5 6 27 28 Those who do not improve probably have permanent myocardial fibrosis. Previous studies showed that decreased preoperative EF, previous myocardial infarction, and low preoperative aortic valve gradient are associated with decreased postoperative EF.29
An improvement in postoperative LVEF of 10 EF units (Figure 3⇑) was noted in our study. The relationship of sex differences in LV adaptation to aortic stenosis has been described.30 31 32 A substantial sex-associated difference in regression of LV adaptation to chronic pressure and volume overload has also been reported.18 The factors accounting for these sex differences have not been characterized. The sex difference in our series (improved postoperative EF in women) was an isolated sex-related finding (ie, preoperative EF and mean gradient were not significantly different between men and women). Excessive hypertrophy has been reported in some patients with aortic stenosis.31 32 This finding was not noted among the 52 patients reported in this series.
Smaller preoperative AVA was significantly related to a change in postoperative EF. The smaller preoperative AVA may suggest a more severe degree of aortic stenosis in these patients with low preoperative mean gradient. Preoperative identification of appropriate surgical candidates may be improved by the use of dobutamine infusion33 and/or transesophageal imaging.34 These modalities may aid in optimizing surgical and overall survival.
An important variable that we were unable to assess was the true degree of aortic valve stenosis. Estimation of AVA in patients with low cardiac output and low transvalvular gradient is difficult, and in several patients in this series, the surgeon noted less than severe aortic stenosis at operation. Thus, some patients may have had another cause for LV dysfunction in conjunction with aortic valve stenosis of moderate severity. In our current practice, we use dobutamine during hemodynamic assessment; however, this was not performed in a sufficient number to allow risk stratification in the current series.
Lack of Power
This series has limited power to stratify risk and identify statistical predictors of outcome. However, no larger series of such patients is available in the literature.
The postoperative EF was determined for 93% of survivors of surgery (38 of 41 patients). This should be considered in the interpretation of results, because the performance of echocardiography may have been an indicator for better outcome. Comparison of baseline characteristics between survivors with and without determination of postoperative EF indicated no differences in proportion of female patients, preoperative NYHA functional class, age, and percentage of patients with coronary artery disease in this assessment.
Echocardiographic estimates of LVEF may be a cause for concern; the use of echocardiography in this clinical setting, however, is standard clinical practice. Previous studies from our institution and others have documented acceptable correlations with angiography35 and have confirmed reproducibility.36 37 38
Other Causes of LV Dysfunction
Causes of LV dysfunction related to factors other than aortic stenosis and coronary artery disease cannot be excluded in this patient population.
Lack of Control Group
All of the patients included in this study underwent aortic valve replacement; thus, the clinical dilemma of differentiating LV systolic dysfunction due to aortic stenosis from moderate aortic stenosis with a coexistent cardiomyopathic process cannot be addressed.
Cardiac Output Determination
Cardiac output determination may be unreliable when measured by the thermodilution technique, particularly in low-output states. In our series, however, only 6 of the 50 patients in whom cardiac output was measured (12%) had measurement by thermodilution, so this technique should not have adversely affected our data.
Dobutamine Hemodynamic Assessment
Intravenous administration of dobutamine has been proposed as a method to determine surgical outcome in patients with low-output low-gradient aortic stenosis, when there is uncertainty about the severity of aortic stenosis.33 Hemodynamic evaluation during dobutamine infusion was not performed in enough patients to allow risk stratification in this series.
Patients with low-gradient aortic stenosis represent a small but controversial subset. In our patients with decreased LVEF, low mean gradient, advanced age, and high prevalence of coronary artery disease, surgical mortality was lower than previously reported and was related to aortic prosthesis size and patient age. The early and intermediate follow-up results are acceptable compared with those of age- and sex-matched controls. Marked improvement in symptoms and LVEF occurred in >70% of the survivors. Improved postoperative EF was influenced considerably by female sex and a small preoperative AVA. We submit that patients with severe aortic stenosis, reduced LV function, and low mean gradient, contrary to previous recommendations8 and despite increased operative mortality, should not be denied aortic valve replacement, given the substantial potential clinical benefit.
Reprint requests to Heidi M. Connolly, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
- Received September 9, 1999.
- Revision received November 19, 1999.
- Accepted December 2, 1999.
- Copyright © 2000 by American Heart Association
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