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J Am Coll Cardiol, 2004; 44:1241-1247, doi:10.1016/j.jacc.2004.06.031 © 2004 by the American College of Cardiology Foundation |

* Duke University Medical Center, Durham, North Carolina, USA
Louisiana State University, New Orleans, Louisiana, USA
Manuscript received January 23, 2004; revised manuscript received April 20, 2004, accepted June 7, 2004.
* Reprint requests and correspondence: Dr. Eric D. Peterson, Duke Clinical Research Institute, P.O. Box 17969, Durham, North Carolina 27715 (Email: peter016{at}mc.duke.edu).
| Abstract |
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BACKGROUND: The decision to perform CABG or concomitant CABG and AVR (CABG/AVR) in asymptomatic patients who need CABG surgery but have mild to moderate aortic stenosis (AS) is not clear-cut.
METHODS: We performed Markov decision analysis comparing long-term, quality-adjusted life outcomes of patients with mild to moderate AS undergoing CABG versus CABG/AVR. Age-specific morbidity and mortality risks with CABG, CABG/AVR, and AVR after a prior CABG were based on the Society of Thoracic Surgeons national database (n = 1,344,100). Probabilities of progression to symptomatic AS, valve-related morbidity, and age-adjusted mortality rates were obtained from available published reports.
RESULTS: For average AS progression, the decision to replace the aortic valve at the time of elective CABG should be based on patient age and severity of AS measured by echocardiography. For patients under age 70 years, an AVR for mild AS is preferred if the peak valve gradient is >25 to 30 mm Hg. For older patients, the threshold increases by 1 to 2 mm Hg/year, so that an 85-year-old patient undergoing CABG should have AVR only if the gradient exceeds 50 mm Hg. The AS progression rate also influences outcomes. With slow progression (<3 mm Hg/year), CABG is favored for all patients with AS gradients <50 mm Hg; with rapid progression (>10 mm Hg/year), CABG/AVR is favored except for patients >80 years old with a valve gradient <25 mm Hg.
CONCLUSIONS: This study provides a decision aid for treating patients with mild to moderate AS requiring CABG surgery. Predictors of AS progression in individual patients need to be better defined.
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This study utilizes Markov decision analysis to assess the relative benefits of prophylactic AVR. Multiple sensitivity analyses were also performed to determine the variables that most profoundly affect outcome, and to recommend treatment thresholds.
| Methods |
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Assumptions. Several assumptions were made to simplify the decision analysis. The population was assumed to be free from non-cardiac life-threatening morbidity. There were neither explicit indications nor contraindications for warfarin anticoagulationtherapy. We also assumed all patients undergoing AVR would receive a mechanical prosthesis. In sensitivity analysis, the alternative strategyof using a bioprosthetic valve in patients over 70 years of age was assessed (13). With this strategy, the model was modified to eliminate valve-related complications, substituting the possibility of valve deterioration.
Input variables. All input variables and their sources are noted in Table 1. Age-specific mortality was obtained from the 1998 U.S. life tables (14). Excess mortality in patients with coronary artery disease and AS (15,16) as well as excess mortality in patients who develop morbidity (17) were added to these rates. Operative mortality was obtained from the Society of Thoracic Surgeons (STS) national database (18). Age- and procedure-specific mortality rates were grouped by decade as shown in Table 2, and linear interpolation was used to extrapolate an age-specific rate for a patient between the given age ranges. The rate of mortality among patients with symptomatic AS was abstracted from published reports (19), as were the likelihoods of complication or morbidity from a mechanical valve (20).
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In the sensitivity analysis of bioprosthetic valves, the probability of spontaneous valve deterioration was modeled after Birkmeyer et al. (21) and varies according to patient age and the time since valve implant, or 3.48 · exp[9.92 0.358 · (patient age 60/10) · (years since implant)2.48].Mortality and morbidity of a repeat AVR for valve deterioration were assumed to be equal to those of an AVR following CABG.
Quality-of-life adjustments. Absolute survival and quality-adjusted survival were calculated for each management strategy. Future years of life were discounted at a rate of 3% per year (22). The utility of a year of life with significant morbidity, including symptomatic AS (23), stroke (24), permanent renal failure (24), and long-term morbidity from hemorrhagic complications (25), was discounted at a rate of 0.50. The relative utility of a year of life on chronic warfarin anticoagulation therapy was 0.99 relative to no anticoagulation therapy (26).
Sensitivity analyses. Multiple sensitivity analyses were performed to test the stability of our model with variation of selected model input parameters within reasonable ranges (Table 1). The decision tree shown in Figure 1 was constructed, and all the analyses described above carried out using DATA (TreeAge Software Inc., Williamstown, Massachusetts).
| Results |
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Life expectancy from Markov modeling. A hypothetical 65-year-old patient with asymptomatic AS of varying severity demonstrates the model's major findings. The quality-adjusted life expectancy for such a patient undergoing CABG varies from 8.6 years with a baseline valve gradient of 50 mm Hg, to 9.1 years for a valve gradient of 10 mm Hg. Alternatively, the survival rate after initial CABG/AVR is 8.9 years. Therefore, CABG alone is superior at lower baseline valve gradients, and initial CABG/AVR is the best management if the gradient is over 30 mm Hg.
Absolute mathematical event rates for a 65-year-old patient with a baseline peak aortic gradient of 30 mm Hg and an average rate of AS progression (5 mm Hg/year) are shown in Table 3. Because of perioperative risks from combinedCABG/AVR, the immediate post-surgical outcome is superior for patients receiving CABG alone. Over time, patients who initially receive CABG develop symptoms due to AS and require reoperation. Subsequent morbidity and mortality eventually exceed the up-front surgical risk of a combined CABG/AVR.
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We also found that the model results changed little when surgical morbidity and mortality rates were varied 20% above or below the STS national average. Finally, altering the decision analysis model to allow for insertion of a bioprosthesis in patients over age 70 years was superior, yet CABG/AVR with bioprosthesis still impacts only a few additional patient scenarios.
In contrast, the value of one year of life on anticoagulation therapy did affect the model's conclusions. Specifically, if patient displeasure from anticoagulation therapy reduces the value of one year of life on warfarin by 10% or more, then essentially all patients with a baseline valve gradient below 50 mm Hg should receive CABG alone, on the basis of the model data.
| Discussion |
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Previous studies of AVR at the time of CABG. The American Heart Association/American College of Cardiology task force recommends valve replacement at the time of coronary surgery if asymptomatic patients have severe AS, but the task force acknowledges limited data to support a policy of replacing a valvethat exhibits only mild or moderate AS (4). Small case series of CABG versus CABG/AVR for mild to moderate AS patients exist and have had conflicting treatment recommendations. In one series, only 8 of 51 patients with mild AS (16%) who had CABG alone required subsequent AVR at a mean of 71 months (27). Additionally, no differences in overall or cardiac-related mortality were demonstrated among 476 patients with mild or moderate AS who underwentCABG/AVR (n = 414) or CABG but not AVR (n = 62), but the estimated need for AVR (based on Kaplan-Meier event-free survival curves) at 72 months of follow-up was 24% in patients who underwent CABG and only 3% in patients undergoing AVR (7). An analysis by Rahimtoola (28) used surgical mortality and post-operative survival rates for CABG or CABG/AVR from published reports to calculate that prophylactic AVR is contraindicated in most patients with mild or moderate AS. Unfortunately, this analysis used cohorts of patients with coronary disease only as the basis for the natural history after CABG surgery. Patients with any degree of AS are likely at higher risk, and comparing their outcomes with those of patients without AS biases this article in favor of CABG surgery alone.
Information from the current study. The decision model permits tailoring of recommendations on the basis of patient age and valve gradient as shown in Figure 2. Assuming an average rate of progression of AS (5 mm Hg/year [1,9,29]), patients under age 70 years with a valve gradient >30 mm Hg benefit from CABG/AVR. For older patients, competing mortalities gradually increase the gradient threshold at which an AVR should be performed by roughly 1 to 2 mm Hg/year. Although treatment decisions change, we should note that the absolute survival differences are generally small except at the extremes of age and valve gradient.
A major finding from our sensitivity analysis was that the rate of progression of AS greatly influences the model's treatment recommendations. Thus, this study emphasizes the need for tools to accurately assess AS progression for the individual patient. To date, case series have illustrated that the rate of progression may vary markedly among individuals (3033). If known (by serial echocardiography), an individual's rate of AS progression should replace our population averages (Fig. 3). In addition, this individual variability emphasizes the need to determine reliable clinical predictors of AS progression for those lacking serial echo measurements. Although age, valve calcification, progressive symptoms, and concomitant coronary disease (3033) have been cited as predictors of AS progression, no uniform, consistent risk factors for progression are currentlyin clinical use because of inconclusiveness of the above studies.
Roughly two-thirds of patients receive mechanical prostheses (34), but in patients over age 65 years a bioprosthesis is usually recommended. Altering the current model to reflect this practice had little effect because thromboembolic and anticoagulation-related complications were partially offset by the risk of valve failure. Although the favored valve did shift with age, other variables were more critical in determining whether to replace the valve.
Limitations of the current analysis. Our model had certain simplifying assumptions that should be noted. The risk of prosthetic-valve endocarditis was not included because of very low rates (<1% at year one) of prosthetic-valve endocarditis in recent series (35). Similarly, mechanical valve failure is uncommon in contemporary practice (36) and was not incorporated into the baseline model. Rates of mortality for redo CABG or redo AVR for valve failure were not considered because of the absence of reliable rates of these event occurrences, and because no reliable estimate of mortality and morbidity rates during a redo-redo operation exist. In addition, the possibility that a life-saving revascularization procedure (redo CABG) may be performed at the time of an AVR for progressive AS or valve malfunction was not modeled. Rates of CABG mortality and morbidity are from the general STS database population and do not reflect the fact that CABG patients with AS may actually have a higher mortalityrate at the time of the index operation (6). Last, we chose to use valve gradient as our marker for progression and AS severity (rather than calculated valve area) because of the strong outcome data available regarding the progression and prognosis of patients with AS of varying degrees of severity (9), as well as the difficulties in calculating an accurate aortic valve area.
In addition, although patient age was an important factor in the treatment decision, the valve replacement threshold was directly dependent on life expectancy rather than age per se. Comorbidities such as diabetes, lung disease, or permanent renal failure should be considered when determining appropriate treatment. In general, the trends illustrated in this manuscript (that younger patients with higher baseline gradients or rapidly progressive AS should undergo AVR) and individual patient characteristics should have more bearing on the decision to replace a stenotic valve rather than using an absolute valve gradient threshold for a given patient age.
Clinical recommendations. The current study provides guidance to physicians and patients who are faced with a difficult clinical decision regarding replacement of a stenotic aortic valve during coronary surgery. Three major factors affect the decision to perform CABG/AVR or CABG alone: age (or life expectancy), baseline peak aortic valve gradient by echocardiography, and rate of AS progression. Assuming an average rate of progression,CABG/AVR should be considered once the baseline gradient exceeds 30 mm Hg. Individual patient characteristics, including comorbidities, local expertise in performing operations, and patient preference are still important when making this difficult decision.
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