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J Thorac Cardiovasc Surg 2008;135:1270-1279
© 2008 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Survival after valve replacement for aortic stenosis: Implications for decision making

^a Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
^b Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
^c Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio

Received for publication May 2, 2007; revisions received November 29, 2007; accepted for publication December 18, 2007.

^_* Address for reprints: Tomislav Mihaljevic, MD, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Avenue/Desk F24, Cleveland, OH 44195. (Email: mihaljt{at}ccf.org).

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 
Objective: Recommendations for aortic valve replacement in severe aortic stenosis are based primarily on the presence of symptoms. However, the onset of symptoms is often insidious, potentially leading to delayed intervention and suboptimal results. Identifying factors that reduce the survival of patients undergoing aortic valve replacement could lead to revised treatment guidelines and improved outcomes.

Methods: We conducted a single-center observational clinical study of 3049 patients with aortic stenosis who underwent native aortic valve replacement with a single type of bioprosthesis. The primary end point was all-cause mortality from the date of operation. Multivariable analysis of risk factors for death was performed in the multiphase hazard function domain.

Results: The presence of severe left ventricular hypertrophy at operation, which preceded symptoms in 17% of patients, was associated with decreased survival. This effect was magnified by the severity of aortic stenosis (P = .02) and use of small prostheses (P = .01). The presence of left ventricular dysfunction reduced survival (P = .0003). Although older age was a risk factor for death (P < .0001), elderly patients had survival comparable to their age, race, and sex-matched cohorts, whereas younger patients had worse than expected survival that was further diminished with insertion of a small prosthesis (P = .01).

Conclusion: To optimize survival, earlier aortic valve replacement should be considered even in asymptomatic patients before severe left ventricular hypertrophy or dysfunction develops. In younger patients, the largest possible prosthesis should be implanted to minimize residual gradient; in elderly patients, complex operations just to insert larger prostheses should be avoided.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 
Aortic valve replacement (AVR) is recommended for symptomatic patients with severe aortic stenosis to improve symptoms and increase survival.¹ However, the onset of symptoms may be insidious, difficult to elicit,² and therefore unreliable in isolation for decision making. As a result, AVR may be delayed until the disease is in advanced stages, precluding optimal survival benefit. We postulate that survival after AVR is adversely influenced by preoperative severity of aortic stenosis and its resultant secondary effects on left ventricular (LV) structure and function.

Advances in prosthesis technology and improved operative and postoperative management have decreased the risks of valve replacement; thus, operation should be considered before the secondary effects on LV structure and function from severe aortic stenosis decrease the benefit of valve replacement. To optimize survival after AVR, we investigated these non-symptom factors, specifically, the detrimental effects on survival of the complex interplay of severity of aortic stenosis, LV hypertrophy and dysfunction, age, and small prosthesis size, all of which may play a role in decision making, including the timing of operation.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 
Patients
Between October of 1991 and January of 2004, 3049 patients underwent native AVR for aortic stenosis or mixed stenosis and regurgitation, with or without coronary artery bypass grafting. Excluded were patients with predominant aortic regurgitation rather than stenosis, infective endocarditis, and rheumatic or other causes of aortic valve (AV) disease, and those who underwent any other concomitant valvar or aortic surgery. To avoid confounding of results with prosthesis type and model, the study was limited to a single prosthesis: the Carpentier-Edwards Perimount stented bovine pericardial valve (Model 2700, Edwards Lifesciences Corp, Irvine, Calif), one of the most commonly implanted prosthetic AVs. These patients represent the most common spectrum of surgery for AV stenosis in developed countries.

Preoperative patient characteristics, detailed echocardiographic variables, and intraoperative data were retrieved from the Cardiovascular Information Registry, a database maintained concurrently with patient care, and the Echocardiography Database (Table E1). Both have been approved for use in research by the institutional review board, with patient consent waived. Of the 3049 patients, 2859 (94%) had moderately severe or severe aortic stenosis and 1980 (65%) had pure aortic stenosis (Table E2).

Preoperative Echocardiography
Mean and peak instantaneous AV gradients were determined by Doppler measurements, and native AV orifice area was calculated by the continuity method.³ LV mass was calculated from end-diastolic LV septal and posterior wall thicknesses, and internal dimension was calculated by the formula validated by Devereux and colleagues.⁴ LV function was graded qualitatively as follows: ejection fraction (EF) 50% or greater, none; EF 40% to 49%, mild; EF 35% to 39%, moderate; EF 26% to 34%, moderately severe; and EF 25% or less, severe. We previously demonstrated the prognostic sensitivity of this grading method.⁵

Operative Technique
AVR was performed on cardiopulmonary bypass at normothermia or mild hypothermia. Antegrade and retrograde cold blood cardioplegia for myocardial protection was routine. Intraoperative transesophageal echocardiography was used to confirm diagnoses and assess prosthesis function.

Prosthesis Size
Prosthesis size was defined in terms of the geometric internal orifice diameter (in millimeters) corresponding to the manufacturer's label size.⁶ Patient–prosthesis size was expressed as standardized orifice size (prosthesis–patient Z value), the number of standard deviations by which the internal orifice diameter deviated from the mean normal aortic anulus diameter for the patient's body surface area.^6,7 Because a single-valve model was studied, these Z values are comparable to projected orifice area estimates.

End Point
The study end point was all-cause mortality from the date of operation. Patients were routinely followed 2, 5, 10, and 15 years after AVR. These active follow-up data were supplemented by Social Security Death Index data with a common closing date of October 25, 2005.^8,9 In all, 29 patients (0.95%) were untraced beyond hospital discharge and 126 patients (4%) did not have a Social Security number for supplemental passive follow-up. Follow-up was 5.1 ± 3.2 years (median 4.5 years), and 15,481 patient-years of data were available for analysis; 25% of living patients were followed more than 7.6 years, and 10% were followed more than 10 years. Survival was estimated nonparametrically by the Kaplan-Meier method and parametrically by a multiphase hazard model.¹⁰ Parametric modeling was used to resolve the number of phases of instantaneous risk of death (hazard function) and to estimate shaping parameters. (For additional details, see http://www.clevelandclinic.org/heartcenter/hazard.)

Reference population survival estimates were generated from equations for the US Life Tables for each patient according to age, race, and sex. These were averaged overall and within subgroups of patients.

Data Analysis
To better understand the interplay of AV stenosis, LV structure and function, age, and prosthesis size, we performed an ordered sequence of analyses, with extensive exploration of interactions, to build a model of mortality (Tables E1 and E2 show the variables). Although we assumed that sporadic missing values for variables were missing at random and used mean value imputation, we incorporated missing-value indicator variables for these to adjust the analysis for possible systematic biases; we found none.

Variable selection
Multivariable analyses were performed in the multiphase hazard function domain. Variable selection, with a P value criterion for retention of variables in the model of .05, used bootstrap aggregation (bagging) from automated analysis of 500 bootstrap data sets.^11,12 Variables appearing in 50% or more of the models were retained as risk factors.

Additional analyses
Linear regression was used to identify correlates of native AV orifice area, LV mass index, and prosthesis–patient size, and logistic regression was used for LV function.

Presentation
Continuous variables are summarized as means ± standard deviations and as 15th, 50th (median), and 85th percentiles, and categoric data are summarized as frequencies and percentages. Analyses were performed using SAS version 9.1 (SAS, Inc, Cary, NC). Uncertainty is expressed by 68% confidence limits equivalent to ±1 standard error.

	Results

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 
Overall Survival
Non–risk-adjusted survival estimates for the entire group at 30 days, 6 months, and 1, 5, and 10 years were 97%, 93%, 91%, 75%, and 47%, respectively (Figure E1, A). Risk of death was highest immediately after operation (Figure E1, B), decreased to its nadir approximately 1 year postoperatively (early hazard phase), and then gradually increased (late hazard phase). From approximately 2 years after valve replacement, survival was similar to that of matched population estimates.

Risk Factors
Risk factors for death early after operation ( <1 year) included older age, LV dilatation, smaller prosthesis size, calcified ascending aorta, and earlier date of operation ( Table 1). Risk factors for late death ( >1 year) included similar factors, but specifically older age, greater degree of aortic stenosis, greater LV mass index, smaller standardized prothesis–patient size, interactions among these 4 factors, and, in addition, LV dysfunction and advanced symptoms (moderate to severe vs none or mild; Figure 1, A). Risk factors associated with advanced symptoms included calcific aortic stenosis and severe LV dysfunction (Table E3). More recent patients were less likely to have advanced symptoms.

View larger version (90K): [in this window] [in a new window]   Figure 1. Survival after AVR according to primary risk factors. Each symbol represents a death, vertical bars are 68% confidence limits equivalent to ±1 standard error, and numbers in parentheses are patients remaining at risk. Solid lines are parametric estimates. Dashed lines with corresponding color represent corresponding survival of an age, race, and sex-matched population. A, Severity of symptoms expressed as New York Heart Association classes I and II versus III and IV. Figure includes all patients in study. B, Severity of aortic stenosis expressed as native AV orifice area. For clarity, only patients with extreme values are depicted, with the remaining values between (15% had orifice area 0.85 cm2 and 9.3% had orifice area < 0.5 cm2). C, Severity of LV hypertrophy, expressed as LV mass index. For clarity, only patients with extreme values are depicted, with the remaining values between (15% had mass < 100 g/m2 and 15% had mass 185 g/m2). D, LV dysfunction. All patients are depicted. E, Age. All patients are depicted. F, Prosthesis size, expressed as prosthesis–patient size (Z value). For clarity, only patients with extreme values are depicted, with the remaining values between (15% had Z values > 0.5 and 13% had Z values –1.5). NYHA, New York Heart Association.

Severity of aortic stenosis
Greater degree of severity of aortic stenosis at operation was associated with increased risk of late mortality (Figure 1, B). Patients with larger valve area experienced better survival than their population counterparts; those with smaller valve area had poorer early survival that was less than that of their population counterparts. Patients with small valves were older and more likely to have bicuspid morphology with LV hypertrophy and had more severe LV dysfunction (Table E4).

Left ventricular hypertrophy
Patients with severe LV hypertrophy had higher late mortality that was distinctly worse than that of their population counterparts (Figure 1, C). They tended to be younger men with more severe aortic stenosis and advanced symptoms (Table E5). A large proportion of asymptomatic patients (145/303 [48%]) and mildly symptomatic patients (616/1262 [49%]) had an LV mass index greater than the upper limit of normal for men (135 g/m^–2). Even when LV mass index was 185 g/m^–2 or greater, 17% of patients were asymptomatic and 14% of patients were mildly symptomatic.

Left ventricular function
Patients with any LV dysfunction had considerably worse survival than those with normal LV function and their population counterparts (Figure 1, D). They had more severe aortic stenosis, but lower peak aortic gradient, larger LV volumes, and greater degree of atrioventricular valve regurgitation (Table E6). Further, some degree of LV dysfunction had already occurred in 67 of 352 asymptomatic patients (19%) and in 389 of 1507 mildly symptomatic patients (26%).

Age
Although older age was a risk factor for mortality, survival of younger patients was less than that expected of their population counterparts (Figure 1, E). In contrast, survival of elderly patients exceeded that of their counterparts after the initial year of higher mortality. Patients younger than age 65 years, however, constituted only 14% of cases.

Prosthesis–patient size
Patients with prostheses most disproportionally small for body size had early survival similar to those with the largest size, but slightly worse late survival (Figure 1, F). They were older and had more severe aortic stenosis, tricuspid morphology, and less hypertrophy (Table E7).

Interplay of Risk Factors
Native AV orifice area, LV mass index, age, and prosthesis–patient size were not found to be additive (incremental) risk factors but to interact with one another to modulate risk (Table 1). As the degree of both aortic stenosis and LV hypertrophy increased, survival was greatly reduced ( Figure 2, A). Survival was also diminished when a small prosthetic valve was used in patients with severe LV hypertrophy (Figure 2, B). This effect was more pronounced in younger than in older patients, particularly below prosthesis–patient Z values of approximately –1.5 (Figure 2, C). Figure E2 illustrates more fully the interplay of these 4 factors, with diminishing order of effect on survival by age, followed by LV mass, native AV size, and prosthesis–patient size. In contrast with these 4 factors, the presence of LV dysfunction was an incremental risk factor only and did not interact with any other factor.

View larger version (42K): [in this window] [in a new window]   Figure 2. Nomograms of 10-year survival after AVR from the multivariable analysis of death (Table 1). To produce these risk-adjusted depictions, values for the following variables were held constant (unless depicted in the graph): age, 73 years; no mitral regurgitation; AV orifice area, 0.7 cm2; New York Heart Association functional class I/II; date of operation, January 2004; LV mass index, 135 g/m–2; no ventricular arrhythmia; no previous cardiac operation; left main stenosis, 70%; left circumflex stenosis, >0%; smoker; peripheral arterial disease; hypertensive; nondiabetic; no renal disease; blood urea nitrogen, 19 mg/dL–1; creatinine clearance, 65 mL/min–1; hematocrit, 38%. Solid lines are parametric estimates, and dashed lines are asymmetric 68% confidence limits. Note the expanded vertical axes. A, LV mass index and AV orifice area. B, Prosthesis–patient Z value and LV mass index. C, Prosthesis–patient Z value and age.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

Severity of Aortic Stenosis
More severe degrees of aortic stenosis were associated with worse long-term survival, particularly when severe LV hypertrophy was present. Chronic pressure overload in patients with aortic stenosis results in concentric LV hypertrophy. Although this represents a physiologic compensatory mechanism, severe LV hypertrophy may have deleterious effects on the LV, including increased sensitivity to ischemia (even in the absence of coronary artery disease) with consequent systolic or diastolic dysfunction.^13,14

Left Ventricular Hypertrophy
Although large LV mass has been associated with increased in-hospital mortality of patients undergoing AVR for aortic stenosis,¹⁵ our study provides evidence that links severe LV hypertrophy to decreased long-term survival. This suboptimal result of AVR is likely the result of irreversible myocardial changes and fibrosis associated with severe LV hypertrophy.^16,17 LV reverse remodeling may be delayed by a small prosthesis with high residual pressure gradient, emphasizing the need for using the largest possible prosthesis in patients with severe LV hypertrophy.

Left Ventricular Dysfunction
In advanced stages of disease, the hypertrophic process may become inadequate to keep systolic wall stress within normal limits, causing a decrease in EF.¹⁸ LV dysfunction was a strong predictor of worse long-term survival in our study, correlating with findings from previous studies.¹⁹

Age
Worse survival of younger patients compared with their age, race, sex-matched counterparts likely reflects the nature of aortic stenosis in these adults. A large proportion had bicuspid aortic stenosis (Figure E3), a congenital anomaly of not only the valve but also the proximal arterial tree that causes a chronic, sustained systolic pressure load early in life, unlike senile aortic stenosis.²⁰ We speculate that the early onset of myocardial hypertrophy early in life and chronicity of myocardial changes are responsible for late myocardial dysfunction, even after successful AVR.

Many elderly patients with severe symptomatic aortic stenosis are not referred for surgery because of their age, although improvement in postoperative quality of life of octogenarians after AVR is of similar magnitude to that of younger patients.^21,22 Survival of elderly patients in our study was comparable to that of their age, race, and sex-matched cohorts, which is in accord with previous findings.^6,23,24 These results suggest that AVR should be strongly considered in all patients with severe aortic stenosis, irrespective of age.

Prosthesis Size
Numerous single-institution studies have identified prosthesis–patient mismatch as a risk factor affecting survival after AVR for aortic stenosis.^25–32 However, these studies were conducted on relatively few patients with various types of aortic prostheses, resulting in heterogeneous study populations. In this study, we used a single type of prosthesis to avoid confounding of prosthesis–patient size with prosthesis type and model. The deleterious effect of small prosthesis–patient size in younger patients was absent in elderly patients, although the majority of small prostheses are implanted in the elderly. This suggests that patient–prosthesis size has clinical relevance (Figure E4); however, the effect was mild.

Limitations
This was a single-center observational clinical study on valve replacement for the spectrum of severe aortic stenosis. However, the experience is large, as is the number of variables available to analyze these insufficiently studied aspects of treating aortic stenosis. Although asymptomatic patients were a minority in this study, this is the largest cohort of asymptomatic patients with aortic stenosis studied to date.

Implications for Guidelines
Current guidelines for treating severe aortic stenosis identify the onset of symptoms as the critical point for AVR, although symptoms are often subtle and not apparent to the physician on routine examination.^1,33 Our study underscores this point in that approximately 50% of patients with mild or no symptoms by routine history had developed severe LV hypertrophy, and an important percentage of these had shown signs of LV dysfunction before AVR. These findings suggest that relying on symptoms alone in therapeutic decision making is inadequate. Thus, AVR should be performed before severe LV hypertrophy and dysfunction develop. In younger patients, the largest possible prosthesis should be implanted to minimize the residual gradient. In elderly patients, complex operations just to insert larger prostheses should be avoided.

	Figure E1

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Time -related survival after AVR. A, Survival. Each symbol represents a death, vertical bars 68% are confidence limits, and numbers in parentheses are patients remaining at risk. Solid line represents parametric estimates enclosed within 68% confidence limits. Dash-dot-dash line is survival for the age, race, and sex-matched population. B, Instantaneous risk of death (hazard function). Estimates are enclosed within 68% confidence limits. Dash-dot-dash line represents hazard function for the age, race, and sex-matched population.

	Figure E2

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Ten -year survival after aortic value replacement according to interplay of primary risk factors. The 9 panels represent solutions to the multivariable equation by the indicated values of age, LV mass index, native AV size, and prosthesis–patient size (Z value). Solid lines represent parametric estimates enclosed within 68% confidence limits.

	Figure E3

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Bicuspid AV morphology according to age at AV replacement. Closed circles represent percentage of patients with bicuspid valves in decile age ranges; solid line is a trend line.

	Figure E4

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Nomogram for converting prosthesis–patient Z value and body surface area to Perimount pericardial prosthesis (Edwards Lifesciences, Irvine, Calif) label size. When a patient with a critical combination of risk factors (eg, older age and large LV mass index) is identified, use body surface area and minimum desired prosthesis–patient Z value (–1.5, dashed horizontal line) to convert to prosthesis label size for implantation.

	Table E1

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Variables used in analyses

Demography Age (y), gender, weight (kg), height (cm), body surface area (m2), body mass index (kg/m–2) AV stenosis Stenosis grade, regurgitation grade, orifice area (cm2), mean gradient (mm Hg), peak gradient (mm Hg) AV morphology Cusps: number of cusps, calcification, thickening, prolapse, tear, perforation, restricted cusp motion. Commissures: fused. Anulus: dilated. Symptomatology NYHA functional class (I–IV), emergency operation LV geometry, function, and structure Geometry End-diastolic dimension (cm), end-diastolic volume (mL), end-diastolic volume index (mL/m–2), end-systolic dimension (cm), end-systolic volume (mL), end-systolic volume index (mL/m–2), dilated left ventricle Function Fractional shortening, EF (%), degree of LV dysfunction (1 = none, 2 = mild, 3 = moderate, 4 = severe) Structure Posterior wall thickness (cm), intraventricular septal wall thickness (cm), mass (g), mass index (g/m–2) Other cardiovascular comorbidity Ascending aorta: aneurysmal, calcified, dilated, arteriosclerosis; atrial fibrillation/flutter; ventricular arrhythmia; coronary artery disease (stenosis 50% in left main trunk, left anterior descending coronary artery system, left circumflex coronary artery system, right coronary artery system); previous myocardial infarction; other valve disease (tricuspid regurgitation, mitral regurgitation) Noncardiac comorbidity History of smoking, history of peripheral arterial disease, hypertension, insulin-treated diabetes, blood urea nitrogen (mg/dL–1), creatinine (mg/dL–1), creatinine clearance (mL/min–1), hematocrit (%) AV prosthesis Label size, index size (cm2/m–2), standardized size (prosthesis–patient Z value) Concomitant procedure Coronary artery bypass grafting, internal thoracic artery graft used Support Aortic clamp time (minutes), cardiopulmonary bypass time (minutes) Experience Date of operation (years since January 1, 1991)

AV, Aortic valve; NYHA, New York Heart Association; LV, left ventricular; EF, ejection fraction.

	Table E2

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient, procedure, and prosthesis characteristics

Characteristic n a No. (%) or Mean ± SD Demography  Age (y) 3049 73 ± 8.3  Female 3049 1062 (35)  BSA (m2) 3044 1.95 ± 0.24 AV stenosis  Lesion 3049    Pure stenosis 1980 (65)    Mixed stenosis 1069 (35)    Pure regurgitation 0 (0)  Orifice area (cm2) 2540 0.68 ± 0.18  Mean gradient (mm Hg) 2614 46 ± 17  Peak gradient (mm Hg) 2622 77 ± 27 AV morphology 3049  Unicuspid 3 (0.098)  Bicuspid 710 (23)  Tricuspid 2335 (77)  Quadricuspid 1 (0.033) Symptomatology  NYHA functional class 3049    I 408 (13)    II 1692 (56)    III 668 (22)    IV 281 (9.2)  Emergency operation 3049 17 (0.6) LV geometry, function, and structure Geometry    End-diastolic dimension (cm) 2354 4.8 ± 0.85    End-diastolic volume (mL) 2354 114 ± 48    End-diastolic volume index (mL/m–2) 2350 59 ± 24    End-systolic dimension (cm) 2321 3.2 ± 0.97    End-systolic volume (mL) 2321 46 ± 36    End-systolic volume index (mL/m–2) 2317 24 ± 18  Function    Fractional shortening 2321 0.35 ± 0.12    EF (%) 2175 50 ± 13    Relative wall thickness (cm) 2247 0.57 ± 0.16    LV dysfunction 2696      None 1898 (70)      Mild 232 (8.6)      Mild to moderate 76 (2.8)    Moderate 182 (6.8)      Moderately severe 149 (5.5)      Severe 159 (5.9) Structure  Posterior wall thickness (cm) 2270 1.3 ± 0.23  Intraventricular septal wall thickness (cm) 2315 1.4 ± 0.29  Mass (g) 2240 277 ± 92  Mass index (g/m–2) 2236 142 ± 44 Other cardiovascular comorbidity  Ascending aorta 3049    Calcified 854 (28)    Dilated 409 (13)    Arteriosclerosis 697 (23)  Atrial fibrillation/flutter 3049 201 (6.6)  Ventricular arrhythmia 3049 317 (10)  Complete heart block/pacer 3049 140 (4.6)  No. of previous non-valve cardiac operations 3049    0 2410 (79)    1 529 (17)    2 99 (3.2)    3 11 (0.4)  Presence of coronary artery disease b 3021 2022 (67)    LMT 3017 395 (13)    LAD system 3021 1618 (54)    LCx system 3018 1389 (46)    RCA system 3012 1462 (48)  Previous myocardial infarction 3049 933 (31) Noncardiac comorbidity  Smoking 3011 1721 (57)  Peripheral arterial disease 3049 1637 (54)  Hypertension 2997 2140 (71)  Insulin-treated diabetes 2962 604 (20)  Renal disease 3049 178 (5.8)  BUN (mg/dL–1) 2948 22 ± 12  Creatinine (mg/dL–1) 2953 1.2 ± 0.92  Creatinine clearance (mL/min–1) 2950 69 ± 32  GFR (mL/min–1) 2953 69 ± 33  Hematocrit (%) 2529 38 ± 5.2  Bilirubin (mg/dL–1) 2385 0.72 ± 0.64 AV prosthesis  Type    Carpentier-Edwards Perimount valve, model 2700 (Edwards Lifesciences, Irvine, Calif) 3049 3049 (100)  Label size    19 511 (17)    21 955 (31)    23 1076 (35)    25 421 (14)    27 78 (2.6)    29 8 (0.3)  Internal (geometric) orifice size    Area (cm2) 3049 1.6 ± 0.26    Area index (cm2/m–2) 3044 1.8 ± 0.33    Standardized (Z value) 3044 –0.48 ± 0.94 Concomitant procedure  CABG 3049 1698 (56) a Data available. b 50% stenosis.

AV, Aortic valve; BSA, body surface area; BUN, blood urea nitrogen; CABG, coronary artery bypass grafting; EF, ejection fraction; GFR, glomerular filtration rate; LAD, left anterior descending; LCx, left circumflex; LMT, left main trunk; LV, left ventricular; NYHA, New York Heart Association; RCA, right coronary artery; SD, standard deviation.

	Table E3

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient variables associated with higher likelihood of NYHA class III or IV

Variable Coefficient ± SD P Reliability (%) a Calcified AV 0.69 ± 0.29 .02 72 Severe LV dysfunction b 0.39 ± 0.071 <.0001 100 Higher grade of mitral regurgitation c –0.64 ± 0.17 .0002 94 Female 0.35 ± 0.094 .0002 85 Larger body mass index 0.0303 ± 0.0072 <.0001 98 More previous cardiac operations 0.23 ± 0.082 .005 67 More coronary artery systems diseased d 0.30 ± 0.096 .002 97 Previous myocardial infarction 0.34 ± 0.095 .0004 100 History of renal disease 0.33 ± 0.16 .04 64 History of PAD 0.25 ± 0.089 .005 49 Lower hematocrit e –0.81 ± 0.203 <.0001 96 Earlier date of operation –0.069 ± 0.013 <.0001 99 a Percent of times factor appeared in 500 bootstrap analyses. b Ln(LV dysfunction), logarithmic transformation. c (1/mitral valve regurgitation+1), inverse transformation. d Number of coronary artery systems diseased: 0 or 1 versus 2 or 3. e (Hematocrit/40)2, squared transformation.

AV, Aortic valve; LV, left ventricular; PAD, peripheral arterial disease; SD, standard deviation.

	Table E4

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient variables associated with smaller native valve orifice area

Variable Coefficient ± SD P Reliability (%) a Older age b –0.028 ± 0.0054 <.0001 97 Lower weight c –0.082 ± 0.017 <.0001 99 Female –0.035 ± 0.0085 <.0001 67 Lower grade of AV regurgitation 0.014 ± 0.0032 <.0001 97 Bicuspid morphology –0.018 ± 0.008 .04 54 Larger LV mass index d 0.090 ± 0.0013 <.0001 100 Higher grade of LV dysfunction e –0.033 ± 0.0062 <.0001 100 No previous myocardial infarction –0.026 ± 0.0079 .001 100 No LCx system stenosis (70%) –0.045 ± 0.0078 <.0001 100 No history of hypertension –0.021 ± 0.0079 .008 88 No history of popliteal disease –0.022 ± 0.0104 .03 60 Earlier date of operation 0.0046 ± 0.0011 <.0001 100 a Percent of times factor appeared in 500 bootstrap analyses. b Exp(age/50), exponential transformation. c 80/weight, inverse transformation. d (125/LV mass index), inverse transformation. e Ln(LV dysfunction grade), logarithmic transformation.

AV, Aortic valve; LCx, left circumflex; LV, left ventricular; SD, standard deviation.

	Table E5

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient variables associated with larger preoperative left ventricular mass index

Variable Coefficient ± SD P Reliability (%) a Male –0.079 ± 0.083 .3 78 Interaction: Male/age b 0.21 ± 0.065 .002 97 Interaction: Female/age c –0.0602 ± 0.104 .6 — Higher AV mean gradient d 0.069 ± 0.0067 <.0001 100 Higher grade of aortic regurgitation 0.039 ± 0.0054 <.0001 100 NYHA functional class III/IV 0.032 ± 0.013 .02 70 Ventricular arrhythmia 0.066 ± 0.019 .0005 92 Complete heart block 0.14 ± 0.028 <.0001 100 History of hypertension 0.036 ± 0.013 .007 76 Higher grade of mitral regurgitation 0.038 ± 0.0065 <.0001 100 History of renal disease 0.063 ± 0.027 .02 100 Higher BUN e 0.046 ± 0.016 .004 100 Lower hematocrit f –0.075 ± 0.028 .008 69 Earlier date of operation –0.021 ± 0.0019 <.0001 100 a Percent of times factor appeared in 500 bootstrap analyses. b Male/(50/age), inverse transformation. c Female/(50/age), inverse transformation. d (AV mean gradient/45)2, squared transformation. e Ln(BUN), logarithmic transformation. f (Hematocrit/40)2, squared transformation.

AV, Aortic valve; BUN, blood urea nitrogen; NYHA, New York Heart Association; SD, standard deviation.

	Table E6

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient variables associated with left ventricular dysfunction

Variable Coefficient ± SD P Reliability (%) a Smaller native AV orifice area b –2.5 ± 0.28 <.0001 100 Lower AV peak gradient –0.031 ± 0.0032 <.0001 100 Larger LV end-systolic volume index 0.094 ± 0.0057 <.0001 100 Dilated LV 1.1 ± 0.202 <.0001 100 Higher grade of mitral regurgitation 0.32 ± 0.063 <.0001 99 Higher grade of tricuspid regurgitation c –0.76 ± 0.22 .0007 99 Previous myocardial infarction 0.87 ± 0.12 <.0001 99 LCx system stenosis (50%) 0.50 ± 0.12 <.0001 85 Complete heart block/pacer 0.86 ± 0.25 .0006 67 Higher BUN d 0.503 ± 0.14 .0005 84 a Percent of times factor appeared in 500 bootstrap analyses. b Ln(native AV area), logarithmic transformation. c (1/[TV regurgitation+1]), inverse transformation. d Ln(BUN), logarithmic transformation.

AV, Aortic valve; BUN, blood urea nitrogen; LCx, left circumflex; LV, left ventricular; SD, standard deviation.

	Table E7

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

Patient variables associated with smaller prosthesis–patient Z value

Variable Coefficient ± SD P Reliability (%) a Older b –1.4 ± 0.14 <.0001 100 Female –0.75 ± 0.032 <.0001 100 Smaller AV orifice area c 0.204 ± 0.056 .0003 85 Tricuspid morphology –0.46 ± 0.035 <.0001 100 Smaller LV mass index 0.0039 ± 0.00038 <.0001 100 Complete heart blocker/pacer –0.15 ± 0.067 .03 64 History of hypertension –0.084 ± 0.032 .01 52 RCA system stenosis (>0%) –0.11 ± 0.031 .0003 94 Treated diabetes –0.11 ± 0.036 .003 88 Lower GFR d 1.5 ± 0.073 <.0001 100 Higher creatinine clearance e –1.8 ± 0.073 <.0001 100 Earlier date of operation 0.020 ± 0.0044 <.0001 98 a Percent of times factor appeared in 500 bootstrap analyses. b Ln(age), logarithmic transformation. c AV orifice area2, squared transformation. d Ln(GFR), logarithmic transformation. e Ln(creatinine clearance), logarithmic transformation.

AV, Aortic valve; GFR, glomerular filtration rate; LV, left ventricular; RCA, right coronary artery; SD, standard deviation.

	Footnotes

 
This study was supported in part by the Kenneth Gee and Paula Shaw, PhD, Chair in Heart Research.

Presented at the 87th Annual Meeting of the American Association for Thoracic Surgery, Washington, DC, May 5 to 9, 2007.

	References

Top Abstract Introduction Patients and Methods Results Discussion Figure E1 Figure E2 Figure E3 Figure E4 Table E1 Table E2 Table E3 Table E4 Table E5 Table E6 Table E7 References

 

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