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Original Articles: Adult Cardiac

Aortic Valve Replacement for Patients With Severe Aortic Stenosis: Risk Factors and Their Impact on 30-Month Mortality

^a University at Albany, State University of New York, Albany, New York
^b Maimonides Medical Center, New York, New York
^c Columbia-Presbyterian Medical Center, New York, New York
^d New York University Medical Center, New York, New York
^e Rush University Medical Center, Chicago, Illinois
^f Medical University of Ohio, Toledo, Ohio
^g Duke University Medical Center, Durham, North Carolina

Accepted for publication February 20, 2009.

^_* Address correspondence to Dr Hannan, School of Public Health, State University of New York, University at Albany, One University Place, Rensselaer, NY 12144-3456 (Email: elh03{at}health.state.ny.us).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background: Few studies have reported population-based outcomes for aortic valve replacement patients.

Methods: Patients with severe aortic valve stenosis who underwent aortic valve replacement with or without concomitant coronary artery bypass graft surgery from January 1, 2003, to December 31, 2005, were included in the study. Statistical models were developed to identify significant risk factors for mortality, to compare survival for patients with and without selected risk factors, and to compare survival to an age- and sex-matched group from US life tables.

Results: There was total of 6,369 patients in the study. The in-hospital and 30-day mortality rates were 3.97% for aortic valve replacement and 5.69% for aortic valve replacement with concomitant coronary artery bypass graft surgery. Significant risk factors for 30-month mortality included concomitant coronary artery bypass graft surgery, advancing age, lower body surface area, emergency status, low ejection fraction, congestive heart failure, previous heart surgery, and several comorbidities. The 64.3% of patients with isolated aortic valve replacement who had neither congestive heart failure, ejection fraction less than 0.40, acute myocardial infarction less than 24 hours, nor hemodynamic instability had a risk-adjusted survival of 89.9% compared with the 90.0% survival rate of the age- and sex-matched general population (p = 0.28).

Conclusions: For the large number of patients without high-risk conditions, the 30-month survival is essentially as high as that of an age- and sex-matched group of the US population.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Aortic valve stenosis is the most frequent heart valve disease in developed countries [1, 2]. The prognosis for patients with severe aortic stenosis who do not undergo aortic valve replacement (AVR) is very poor, and much worse than the risk for patients undergoing AVR [1–15].

There is a continuing need to examine the significant risk factors for adverse outcomes after AVR, and to assess the prognosis for patients with several clinical features that frequently accompany aortic valve stenosis. Although numerous studies of this nature have been conducted, many are more than 10 years old, and the vast majority are single-institution studies [16–20].

The purposes of this study are (1) to identify the significant risk factors for 30-month mortality for patients with severe aortic valve stenosis who undergo AVR and (2) to compare risk-adjusted mortality for patients with and without each of several important risk factors to an age- and sex-matched group based on US census data [21]. The study is population-based and contains results for all patients with severe aortic valve stenosis undergoing AVR in New York State between 2003 and 2005.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Database
The database used in the study was the New York State Department of Health's Cardiac Surgery Reporting System. This registry was created in 1989 for the purpose of collecting information on all New York patients undergoing cardiac surgery in nonfederal hospitals in the state to better understand risk factors for these procedures and to improve quality of care and outcomes. The registry contains information on type of procedure performed, demographics, comorbidities, left ventricular function, hemodynamic state, extent of coronary artery disease and attempted coronary vessels, hospital identifiers, and in-hospital adverse outcomes. Data are audited and cross-checked against the Department's acute care hospital discharge database, the Statewide Planning and Research Cooperative System to ensure accuracy and completeness. Definitions for these data elements are identical in the two systems.

Deaths occurring among New York State patients after discharge from the hospital were obtained by matching patients in the Cardiac Surgery Reporting System with New York's Vital Statistics Death file using patient identifiers.

Study Group and End Points
The study includes patients with severe aortic valve stenosis (regarded as aortic valve area < 1 cm² and jet velocity > 4.0 m/s) who underwent AVR from January 1, 2003, to December 31, 2005. Patients who underwent AVR with and without concomitant coronary artery bypass graft (CABG) surgery were included in the study. All patients were included except 620 patients from out of state and 30 patients with missing Social Security numbers. These two groups were excluded because they could not be followed for longer-term outcomes using New York Vital Statistics data. A total of 6,359 patients were included in the study. The end points of interest were in-hospital or 30-day mortality (death in the index admission at any time or death within 30 days after discharge after the index admission) and 30-month mortality.

Statistical Analysis
The main purposes of the study were to identify significant risk factors for medium-term (30-month) mortality and to compare age- and sex-adjusted 30-month mortality for patients with and without certain risk factors (Canadian Cardiovascular Society class III or IV angina, congestive heart failure [CHF], concomitant CABG surgery, age 75 and older, and left ventricular ejection fraction [EF] < 0.40) with the age- and sex-matched population from the US life tables in 2004, which is based on 2004 final mortality statistics and US population estimates from the 2000 census [21].

Frequencies for a wide variety of risk factors (demographic, ventricular function, vessels diseased, previous myocardial infarction, previous interventions, and a large number of comorbidities) were computed, and differences in prevalence for each of these risk factors between patients undergoing isolated AVR and AVR with CABG surgery were examined. Significant differences were identified using Wilcoxon rank sum tests for continuous variables and ² tests for categorical variables.

Significant independent risk factors for in-hospital or 30-day mortality of AVR patients were identified using logistic regression. The data were split in half, and a model was developed on the development sample using the variables in Table 1 as independent variables and mortality as the binary dependent variable. Stepwise selection was used with a significance criterion of 0.05 for entry and removal. The resulting model was applied to the validation sample to test for discrimination and calibration, and then a new model was developed for the entire data set using the variables that were significant in the development sample.

Thirty-month risk-adjusted survival curves were then constructed for patients with and without each of several important risk factors (concomitant CABG surgery, age > 75 years, CHF, EF < 0.40, acute myocardial infarction [AMI] < 24 hours, or hemodynamic instability) using Cox proportional hazards models and methods for calculating adjusted survival [23]. The risk-adjusted survival rates for patients with and without the risk factor of interest were then compared with the survival of the age- and sex-matched general population in the years 2003 to 2005 [21].

All tests were conducted at the 0.05 level, all confidence limits were two-sided, and all analyses were conducted in SAS 9.1 (SAS Institute Inc, Cary, NC).

	Results

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
There was total of 6,369 patients in the study. A total of 3,327 patients (52.2%) were isolated aortic valve patients and the remainder underwent AVR with CABG surgery. As noted in Table 1, patients with combined AVR and CABG surgery were younger (64.2 years versus 68.9 years; p < 0.0001), less likely to be female (40.3% versus 49.3%; p < 0.0001), less likely to be Hispanic (3.9% versus 6.3%; p < 0.0001), and less likely to have severe aortic valve incompetence (5.0% versus 7.4%; p < 0.0001). Also, they were more likely to have left main disease (15.9% versus 1.3%; p < 0.0001), had more vessels diseased (eg, 21.5% with three-vessel disease versus 3.0% with fewer than three vessels diseased), had significantly lower ejection fractions, had more severe angina (eg, 15.8% versus 6.8% for Canadian Cardiovascular Society class IV), were more likely to have had a previous myocardial infarction (71.6% with no previous myocardial infarction versus 85.9%; p < 0.001). Furthermore, AVR with concomitant CABG patients had significantly higher prevalence of several comorbidities (cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, extensive aortic atherosclerosis, diabetes, cardiomegaly, and renal failure), had a significantly lower rate of endocarditis (0.2% versus 0.9%; p = 0.03), and were more likely to have had previous percutaneous coronary intervention (12.6% versus 9.1%; p < 0.0001), but were less likely to have undergone previous open heart surgery (7.8% versus 16.4%; p < 0.0001).

Table 2 indicates that significant risk factors for in-hospital or 30-day mortality were advancing age greater than 60 years, EF (adjusted odd ratio for each year EF < 0.55, 1.02; p = 0.0001), CHF (adjusted odd ratio, 1.67; p < 0.0001), AMI less than 24 hours or hemodynamically unstable (including shock cases, adjusted odd ratio, 3.37; p = 0.0002), lower body surface area, previous cardiac operations (adjusted odd ratio, 0.49 for each unit increase; p = 0.001), and several comorbidities (cerebrovascular disease, extensive aortic stenosis, diabetes, and renal failure).

View larger version (23K): [in this window] [in a new window]   Fig 1. Survival after isolated aortic valve replacement versus aortic valve replacement with concomitant coronary artery bypass grafting. Dashed lines are survival for age- and sex-matched US population. Solid and dash-dotted lines represent survival for aortic valve replacement patients with and without concomitant coronary artery bypass grafting, respectively. (A) Unadjusted Kaplan-Meier survival curves. (B) Adjusted Kaplan-Meier survival curves.

View larger version (10K): [in this window] [in a new window]   Fig 2. Survival after aortic valve replacement according to patient age. Dashed lines are survival for age- and sex-matched US population. Solid lines represent risk-adjusted survival in selected age and surgery subgroups. (A) Nonelderly patients (age < 75 years) with isolated aortic valve replacement. (B) Elderly patients (age > 75 years) with isolated aortic valve replacement. (C) Nonelderly patients undergoing aortic valve replacement with coronary artery bypass graft surgery. (D) Elderly patients undergoing aortic valve replacement with coronary artery bypass graft surgery.

View larger version (12K): [in this window] [in a new window]   Fig 3. Survival after isolated aortic valve replacement according to preoperative cardiac risk factors. Dashed lines are survival for age- and sex-matched US population. Solid and dash-dotted lines represent risk-adjusted survival for patients with and without each risk factor, respectively. (A) Acute myocardial infarction less than 24 hours or hemodynamically unstable. (B) Congestive heart failure. (C) Left ventricular ejection fraction less than 0.40. (D) Combination of congestive heart failure, left ventricular ejection fraction less than 0.40, and acute myocardial infarction less than 24 hours or hemodynamically unstable.

View larger version (12K): [in this window] [in a new window]   Fig 4. Survival after aortic valve replacement with concomitant coronary artery bypass graft surgery according to preoperative cardiac risk factors. Dashed lines are survival for age- and sex-matched US population. Solid and dash-dotted lines represent risk-adjusted survival for patients with and without each risk factor, respectively. (A) Acute myocardial infarction less than 24 hours or hemodynamically unstable. (B) Congestive heart failure. (C) Left ventricular ejection fraction less than 0.40. (D) Combination of congestive heart failure, left ventricular ejection fraction less than 0.40, and acute myocardial infarction less than 24 hours or hemodynamically unstable.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

The purposes of our study were to use population-based data from New York to (1) identify significant short-term and medium-term risk factors for patients undergoing AVR and (2) compare risk-adjusted mortality for patients with and without each of several important risk factors and to contrast this mortality with an age- and sex-matched group based on census data.

There were numerous significant risk factors for in-hospital or 30-day mortality, including advanced age, lower body surface area, compromised hemodynamic state, low ventricular function, previous myocardial infarction, previous heart surgery, and several comorbidities. Significant risk factors for 30-month mortality included concomitant CABG surgery, advancing age, lower body surface area, emergency status, low EF, CHF, previous heart surgery, and several comorbidities (cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, extensive aortic stenosis, diabetes, immunodeficiency, organ transplant, and renal failure).

Concomitant CABG surgery has been identified in some studies to be a significant risk factor for patients undergoing AVR [2], whereas other studies have not found CABG surgery to be an independent predictor of mortality [16, 18]. We found concomitant CABG surgery to be highly significant, with AVR with concomitant CABG surgery procedures having an adjusted 30-month mortality hazard ratio of 1.26 (p = 0.002) in comparison with isolated AVR.

Many earlier studies have identified age as a significant medium-term risk factor for AVR [3, 4, 7, 8, 14, 17–19]. A few have also identified low ventricular function as a risk [4, 7, 8, 12, 14]. Renal failure or insufficiency was also found to be a risk factor for mortality [4], as was diabetes [8] and extensive aortic atherosclerosis [14, 18]. Although we were unable to find any studies that identified lower body surface area as a risk factor for medium-term mortality, two studies did identify female sex, which may or may not be a proxy for lower body surface area [4, 7]. The inability of other studies to identify as many comorbidities as our study did may be related to most other studies having lower statistical power resulting from smaller sample sizes.

With regard to our findings on risk-adjusted 30-month survival, we found that most subgroups of patients undergoing AVR had lower survival rates than a group of people from the general population who were age and sex matched to the AVR group of interest. It is difficult to interpret these findings because in addition to healthy patients, the age- and sex-matched group of people from the general population includes people with severe aortic stenosis who did not undergo AVR as well as people with other serious health conditions. However, it is expected that the number in the former group is not very large because numerous studies have shown that patients with severe aortic stenosis fare better with AVR than without it [1, 3, 6–12]. Also, a reasonable assumption is that AVR patients are as likely to have other serious medical conditions as age- and sex-matched patients from the general population.

It was especially notable that patients with AVR with concomitant CABG surgery who were 75 or older had a risk-adjusted survival of 83.3%, not statistically different from the 84.0% survival for people from the general population who were age and sex matched to this group.

Also, the 64.3% of patients with isolated AVR who had neither CHF, EF less than 0.40, AMI less than 24 hours, nor hemodynamic instability had a risk-adjusted survival of 89.9%, statistically equivalent to the 90.0% survival rate of the age- and sex-matched general population. This is especially important because it means that this group of patients without major symptoms is very strongly indicated for AVR.

Of the different individual risk factors for 30-month mortality after isolated AVR, the one that was clearly the most dangerous was AMI less than 24 hours or hemodynamic instability. As indicated in Table 3, it had the highest adjusted hazard ratio (AHR, 3.11; p < 0.0001). Also, whereas patients without this risk factor fared nearly as well as patients from the age- and sex-matched general population on 30-month adjusted survival (88.4% versus 90.0%), patients with the risk factor had a much lower 30-month survival (69.8%). For patients with AVR with concomitant CABG surgery, patients with AMI less than 24 hours or who were hemodynamically unstable had an even lower risk-adjusted 30-month survival of 59.6%, compared with 83.6% for patients with neither AMI less than 24 hours nor hemodynamic instability, and a rate of 88.0% for the age- and sex-matched general population. However, less than 2% of patients in the isolated AVR group and in the AVR with concomitant CABG group had either an AMI within 24 hours or were hemodynamically unstable.

The 30-month survival for patients of age 75 and younger was 90.1% if they underwent an isolated AVR and 83.3% if they underwent AVR with concomitant CABG surgery. For patients older than 75, the 30-month survival was 86.2% for isolated AVR and 77.3% for AVR with concomitant CABG surgery. These percentages are similar to findings of other studies. For example, for isolated AVR, Mihaljevic and colleagues [15] reported a 1-year survival of 91%, and He and associates [20] and Morris and coworkers [19] reported respective 5-year survival rates of 74% and 81%.

In conclusion, we found that the medium-term mortality of AVR patients in a population-based study is excellent, and that for the large number of patients without high-risk conditions like CHF, low EFs, recent AMI, or hemodynamic instability, the 30-month survival is essentially as high as that of an age- and sex-matched group of the US population. Although we were not able to compare AVR patients with patients with aortic stenosis who did not undergo AVR, the fact that many AVR patients have been demonstrated to fare as well as an age- and sex-matched group of patients without aortic stenosis certainly indicates that AVR is an appropriate intervention for these patients.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
The authors would like to thank Paula Waselauskas, Kimberly S. Cozzens, Rosemary Lombardo, Cynthia Johnson, and the cardiac surgery departments and cardiac catheterization laboratories of the participating hospitals for their tireless efforts to ensure the timeliness, completeness, and accuracy of the registry data.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) 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): Stephen J. Lahey Craig R. Smith Alfred T. Culliford Robert S.D. Higgins Jeffrey P. Gold Robert H. Jones Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hannan, E. L. Articles by Jones, R. H. Search for Related Content PubMed PubMed Citation Articles by Hannan, E. L. Articles by Jones, R. H. Related Collections Valve disease Related Article