Abstract
Background
Few published studies address survival of kidney transplant patients after valve surgery, and none address relative outcomes related to tissue versus nontissue prosthesis. This study aimed to assess survival of US kidney transplant patients after cardiac valve replacement, and to compare associations of valve selection.
Methods and Results
Of 1,698,706 patients in the United States Renal Data System database, we identified 1335 kidney transplant patients hospitalized in 1991–2004 for cardiac valve replacement. Survival was estimated by the Kaplan-Meier method; independent predictors of death were examined in a comorbidity-adjusted (by Charlson and propensity score) Cox model. Of the cohort, 17% were aged 0–44, 50% 45–64, 28% 65–74, and 5% ≥ 75 years; 78% were white, 63% were men, and 20% had kidney failure caused by diabetes. Of 369 patients (28%) who received tissue valves, 75% had aortic, 20% mitral valve replacement, 5% both. Use of tissue valves increased from 13% in 1991–1995 to 38% in 2000–2004. Age, diabetes, and combined aortic and mitral valve replacement were the strongest predictors of all-cause mortality. In-hospital mortality was 14.0% overall, 11.4% for tissue-valve patients, and 15.0% for nontissue-valve patients (P = 0.09). Two-year survival estimates were 61.5% for tissue-valve and 59.5% for nontissue-valve patients (P = 0.30). The adjusted hazard ratio of death for tissue-versus nontissue-valve patients was 0.83 (95% confidence interval, 0.70–0.99).
Conclusion
Renal transplant patients requiring valve replacement have high mortality rates (approximately 20% per year). These data suggest minimally reduced mortality risk for patients receiving tissue versus nontissue valves.
Keywords: Kidney, survival, valves
Introduction
Cardiovascular disease remains the leading cause of death among kidney transplant patients.1,2 Cardiac disease accounts for 43% of all-cause mortality among dialysis patients, and for about 38% of all-cause mortality posttransplant.1,3 The number of kidney transplants (including combined kidney/pancreas) performed annually increased gradually from 3784 in 19802 to a peak of 18,018 in 2006, with a small decline to 17,356 in 2008.4 Five-year survival for kidney transplant patients is 80.3% for deceased-donor recipients and 89.5% for living-donor recipients; survival has gradually improved over the past 3 decades.1,2 In 2008, 15% of kidney transplants were performed in patients aged 65 years or older, compared with 9% in 2000.1,2,4 With improved survival, and with increased numbers of older patients receiving transplants, the number of kidney transplant patients at risk for developing cardiac disease is likely to increase over time.
Valvular heart disease is common in patients undergoing renal replacement therapy.5,6 Incidence in dialysis patients from 1992–1997 was 3.37 per 1000 person-years, 5 times the incidence in the general population.6 Mortality among dialysis patients hospitalized for valvular heart disease is high compared with all other dialysis patients (adjusted hazard ratio by Cox regression, 1.35; 95% confidence interval [CI], 1.25–1.46).5,6 Increased calcification rate is an important aspect of left-sided valvular disease in end-stage renal disease (ESRD) patients7; the rate of aortic stenosis progression is approximately 3 times faster in dialysis patients than in the general population (0.23 versus 0.05-0.1 cm2 per year).8
Use of bioprosthetic heart valves in hemodialysis patients was proscribed in past American College of Cardiology/American Heart Association guidelines, reflecting a widely held (but poorly supported) perception of high incidence of bioprosthetic valve failure mandating implantation of mechanical prosthetic valves in these patients.9 In our 2002 paper on outcomes of dialysis patients following heart valve replacement surgery,10 we reported estimated 2-year mortality of 60%, with no difference in survival for tissue versus non-tissue valves. Reflecting these new data, revised 2006 practice guidelines rescinded the proscription of bioprosthetic valves in dialysis patients.9,11
No specific practice guidelines have been directed toward valve selection for ESRD patients who undergo kidney transplants. Because of our previous work with dialysis patients, we wondered about transplant patient survival after cardiac valvular surgery, and about the potential contribution of prosthesis type to outcome. As transplant patients receive ongoing immunosuppression, often including steroid therapy, their outcomes might be different with respect to prosthetic valve type.
Data regarding survival of kidney transplant patients after cardiac valve replacement are few, and no data have been published on the association of tissue versus nontissue valve selection and outcome. The purpose of the present study was to assess survival of kidney transplant patients in the United States after cardiac valve replacement, and to compare valve selection and associated patient survival.
Materials and Methods
All data were derived from the United States Renal Data System (USRDS). The accuracy of these data has been validated previously.12 This was a retrospective cohort study of kidney transplant patients hospitalized for first heart valve replacement surgery after initiation of renal replacement therapy, from January 1991 through December 2004. Patients were identified from the USRDS database (n = 1,698,706) by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 35.2X for cardiac valve replacement (excluding pulmonic valve replacement [35.25, 35.26] and tricuspid valve replacement [35.27, 35.28] due to insufficient numbers of patients for analysis), and codes 35.21, 35.22 for aortic valve replacement and 35.23, 35.24 for mitral valve replacement. Prosthetic valve type (bioprosthetic or mechanical) was determined from ICD-9-CM codes 35.21, 35.23 for tissue valves and 35.22, 35.24 for nontissue valves. Concomitant coronary artery bypass surgery (CAB) was determined from ICD-9-CM code 36.1X. Patient demographic data included age, sex, race, year of valve surgery, primary renal diagnosis, and prior ESRD duration (ESRD duration is time from date of first dialysis, or transplant date if transplant was the first renal replacement therapy modality, to procedure date).
Associations of comorbid conditions were examined because patient survival is significantly affected by comorbidity.13,14 We used a previously developed comorbidity profiling methodology based on ICD-9-CM diagnosis and procedure codes in the Medicare Part A institutional inpatient claims.15 Comorbid conditions, identified by ICD-9-CM codes from hospitalizations that occurred before the valve surgery, include prior acute myocardial infarction, other atherosclerotic heart disease, congestive heart failure, other cardiac conditions (including valvular heart disease, arrhythmia, and arrhythmia requiring pacemaker), nonskin malignancies, peripheral vascular disease, cerebrovascular ischemia (cerebrovascular accident and transient ischemic attack), chronic obstructive pulmonary disease, gastrointestinal disease, gallbladder disease, and liver disease. We also calculated a version of the Charlson score adapted for use with administrative databases,16,17 which provides a means of assessing comorbidity and overall mortality by accounting for the presence or absence of nineteen different conditions that are scored and summed. Each condition is weighted according to its potential to influence mortality.16 We grouped patients according to Charlson scores of 0, 1, 2, or ≥ 3.16 As a preliminary analysis found no difference in outcomes using individual comorbid conditions compared with the Charlson score in the Cox model, we retained the Charlson score in the Cox model.
In-hospital mortality was determined, and survival time was calculated from time of valve surgery to censoring or study endpoint (all-cause death). Follow-up commenced at time of surgery and ended at the earliest of death or December 31, 2004. Patients were censored only if lost to follow-up. Cause of death was ascertained from the Centers for Medicare & Medicaid (CMS) ESRD Death Notification (form CMS-2746). Hospitalization rates for gastrointestinal hemorrhage and bacterial endocarditis were also calculated.
Patient characteristics were compared using the chi square test. Survival was estimated by the life-table method.18 The log-rank test was used to compare the difference in cumulative survival in different groups. Patients who received both tissue and nontissue valves (n = 6) were excluded from the survival comparison of tissue versus nontissue valves. Only patients who received aortic or mitral valve replacements were included in the survival analysis. A Cox proportional hazards model was used to evaluate the associations of independent predictors (demographics, comorbidity, duration of ESRD before valve surgery, concomitant CAB, and type of valve surgery by valve site and prosthesis) on patient survival.19 The reported probability values in the Cox model are based on the Wald test statistic. A propensity score approach was also investigated, using a logistic regression model to compute probability of receiving a tissue valve based on all patient characteristics and comorbid conditions. Two approaches were then used: entering the propensity scores in the final proportional hazards model, and running 4 separate models within quartiles of propensity score. All reported probability values are 2-sided. All statistical analyses were performed under the SAS system for Windows version 9.1 (SAS Institute, Inc).
RESULTS
Our final cohort included 1335 kidney transplant patients hospitalized for aortic or mitral valve replacement, or both. Mean follow-up time was 34.4 ± 34.5 months (25th to 75th percentile range, 6.35–51.17 months); median follow-up time was 23.97 months. The cohort was 62.6 % men and 37.4 % women, and 78% white, 18% African American, and 4% other races (Table 1). Age distribution was ≤ 44 years, 16.5%; 45–64 years, 50.3%; 65–74 years, 28.3%; and 75 years, 4.8%. Causes of renal failure were diabetes for 20% of the cohort, hypertension for 23%, glomerulonephritis for 32%, and other conditions for 26%.
Table 1.
Patient Characteristics (n = 1335)
| Characteristics | Cohort |
|||||||
|---|---|---|---|---|---|---|---|---|
| Overall | 1991–1995 | 1996–1999 | 2000–2004 | |||||
| Tissue | Nontissue | Tissue | Nontissue | Tissue | Nontissue | Tissue | Nontissue | |
| n = 369 | n = 966 | n = 35 | n = 229 | n = 72 | n = 300 | n = 262 | n = 437 | |
| Sex | ||||||||
| Men | 65.6 | 61.5 | 54.3 | 61.6 | 73.6 | 61.0 | 64.9 | 61.8 |
| Women | 34.4 | 38.5 | 45.7 | 38.4 | 26.4 | 39.0 | 35.1 | 38.2 |
| Race* | ||||||||
| White | 85.6 | 75.3 | 82.9 | 79.0 | 88.9 | 73.7 | 85.1 | 74.4 |
| African American | 12.2 | 20.4 | 17.1 | 20.1 | 9.7 | 21.0 | 12.2 | 20.1 |
| Other | 2.2 | 4.4 | 0.0 | 0.9 | 1.4 | 5.3 | 2.7 | 5.5 |
| Age, yr* | ||||||||
| 0–20 | 0.5 | 0.5 | 2.9 | 0.4 | 0.0 | 0.7 | 0.4 | 0.5 |
| 21–44 | 10.3 | 18.2 | 17.1 | 19.7 | 20.8 | 19.0 | 6.5 | 16.9 |
| 45–64 | 38.8 | 54.8 | 40.0 | 60.3 | 37.5 | 53.3 | 38.9 | 52.9 |
| 65–74 | 42.3 | 23.0 | 34.3 | 18.3 | 33.3 | 23.0 | 45.8 | 25.4 |
| ≥ 75 | 8.1 | 3.5 | 5.7 | 1.3 | 8.3 | 4.0 | 8.4 | 4.4 |
| Cause of renal failure | ||||||||
| Diabetes | 21.7 | 19.6 | 20.0 | 12.7 | 20.8 | 18.3 | 22.1 | 24.0 |
| Hypertension | 24.1 | 22.2 | 22.9 | 24.5 | 20.8 | 23.0 | 25.2 | 20.4 |
| Glomerulonephritis | 29.5 | 32.3 | 34.3 | 31.9 | 27.8 | 33.7 | 29.4 | 31.6 |
| Other | 24.7 | 26.0 | 22.9 | 31.0 | 30.6 | 25.0 | 23.3 | 24.0 |
| ESRD duration, yr | ||||||||
| 0–< 4 | 14.9 | 18.8 | 25.7 | 27.1 | 19.4 | 16.3 | 12.2 | 16.3 |
| 4–< 6 | 17.3 | 17.3 | 25.7 | 18.3 | 18.1 | 22.3 | 16.0 | 13.3 |
| 6–< 9 | 23.9 | 22.6 | 20.0 | 22.7 | 25.0 | 26.3 | 24.0 | 19.9 |
| 9–< 15 | 25.2 | 27.9 | 14.3 | 21.8 | 23.6 | 22.7 | 27.1 | 34.6 |
| ≥ 15 | 18.7 | 13.5 | 14.3 | 10.0 | 13.9 | 12.3 | 20.6 | 16.0 |
| Charlson score | ||||||||
| 0 | 31.2 | 29.1 | 40.0 | 26.6 | 29.2 | 29.3 | 30.5 | 30.2 |
| 1 | 39.3 | 35.8 | 22.9 | 38.0 | 47.2 | 38.0 | 39.3 | 33.2 |
| 2 | 16.5 | 20.5 | 22.9 | 18.3 | 9.7 | 19.7 | 17.6 | 22.2 |
| ≥ 3 | 13.0 | 14.6 | 14.3 | 17.0 | 13.9 | 13.0 | 12.6 | 14.4 |
| Concomitant CAB | 39.6 | 37.4 | 28.6 | 34.5 | 38.9 | 39.3 | 41.2 | 37.5 |
| Valve type* | ||||||||
| Aortic and mitral | 5.4 | 10.5 | 2.9 | 9.2 | 4.2 | 10.7 | 6.1 | 11.0 |
| Aortic only | 74.8 | 62.9 | 57.1 | 59.8 | 76.4 | 63.3 | 76.7 | 64.3 |
| Mitral only | 19.8 | 26.6 | 40.0 | 31.0 | 19.4 | 26.0 | 17.2 | 24.7 |
| Comorbid conditions | ||||||||
| AMI | 7.0 | 7.6 | 8.6 | 7.4 | 6.9 | 7.0 | 6.9 | 8.0 |
| CHF | 37.7 | 39.4 | 42.9 | 41.1 | 41.7 | 41.7 | 35.9 | 37.1 |
| PVD | 2.7 | 4.6 | 5.7 | 2.6 | 1.4 | 4.0 | 2.7 | 6.0 |
| Cerebrovascular disease | 5.7 | 3.9 | 2.9 | 5.7 | 4.2 | 5.3 | 6.5 | 2.1 |
| Dementia | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| COPD | 9.8 | 7.1 | 5.7 | 5.2 | 5.6 | 6.0 | 11.5 | 8.9 |
| Connective tissue disease | 3.3 | 4.1 | 0.0 | 6.6 | 2.8 | 2.3 | 3.8 | 4.1 |
| Ulcer disease | 0.3 | 1.4 | 0.0 | 2.2 | 0.0 | 1.3 | 0.4 | 1.1 |
| Mild liver disease | 0.3 | 0.4 | 0.0 | 0.4 | 0.0 | 0.7 | 0.4 | 0.2 |
| Moderate/severe liver disease | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | 0.3 | 0.0 | 0.2 |
| Diabetes | 13.3 | 15.4 | 5.7 | 11.8 | 11.1 | 14.7 | 14.9 | 17.9 |
| Diabetes with complications | 8.9 | 9.2 | 11.4 | 7.9 | 9.7 | 8.3 | 8.4 | 10.5 |
| Hemi- or paraplegia | 0.3 | 0.4 | 0.0 | 0.9 | 0.0 | 0.7 | 0.4 | 0.0 |
| Renal disease | 9.5 | 11.1 | 8.6 | 16.6 | 11.1 | 10.3 | 9.2 | 8.7 |
| Any malignancy | 1.1 | 0.5 | 0.0 | 0.4 | 1.4 | 0.3 | 1.2 | 0.7 |
| Metastatic tumor | 0.3 | 0.2 | 0.0 | 0.0 | 0.0 | 0.3 | 0.4 | 0.2 |
| AIDS | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
Note: Values are percents.
AMI, acute myocardial infarction; CAB, coronary artery bypass surgery; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; ESRD, end-stage renal disease; PVD, peripheral vascular disease.
P < 0.001, tissue versus nontissue prosthesis, using the chi square test (overall cohort).
Most valve surgeries were performed in 2000–2004: 264 patients (19.8%) in 1991–1995, 372 patients (27.9%) in 1996–1999, and 699 patients (52.4%) in 2000–2004. Use of tissue valves gradually increased from 13% in 1991–1995 to 38% in 2000–2004.
Aortic valve replacement was performed in 66% of patients, mitral valve replacement in 25%, and combined aortic and mitral valve replacement in 9%. Tissue valves were used in 31% of aortic, 22% of mitral, and 17% of combined aortic and mitral valve replacement surgeries. Concomitant CAB was performed in 38% of patients. Tissue valves were used in 369 patients (28%), and nontissue valve in 966 (72%). Median ESRD duration was 8.0 years for the overall cohort (25th percentile, 4.9 years; 75th percentile, 12.3 years), 8.4 years for patients receiving tissue valves (25th percentile, 5.2 years, 75th percentile, 12.7 years), and 7.8 years for patients receiving nontissue valves (25th percentile, 4.8 years, 75th percentile, 12.1 years). Charlson scores were 0 and 1 for most patients.
The association of independent predictors of all-cause mortality was examined in the Cox proportional hazards model (reported hazard ratios are adjusted for other factors in the model). The most powerful predictors of death were age > 75 years (hazard ratio [HR] 3.76, 95% CI 2.62–5.39), age 65–74 years (HR 2.11, 95% CI 1.65–2.68), combined aortic and mitral valve replacement (HR 1.71, 95% CI 1.35–2.16), and ESRD due to diabetes (HR 1.59, 95% CI 1.28–1.98; Table 2). ESRD duration was associated with increased mortality; patients with ESRD for 9–15 years had a 60% increased risk of death (HR 1.60, CI 1.28–1.99). Charlson scores > 0 were associated with a 25%–28% increased risk of death, and mitral valve replacement alone was associated with 37% increased mortality versus aortic valve replacement alone (HR 1.37, 95% CI 1.16–1.62).
Table 2.
Results from Cox Proportional Hazards Model
| Characteristics | Hazard Ratio (95% CI) |
|---|---|
| Valve type (reference, aortic only) | |
| Aortic and mitral | 1.71 (1.35–2.16) |
| Mitral only | 1.37 (1.16–1.62) |
| CAB (yes vs. no) | 1.09 (0.94–1.27) |
| Women (vs. men) | 1.03 (0.89–1.19) |
| Race (reference, white) | |
| African American | 1.21 (1.00–1.46) |
| Other | 1.38 (0.96–1.99) |
| Age, yrs (reference, 21–44) | |
| 0–20 | 0.54 (0.13–2.19) |
| 45–64 | 1.61 (1.30–2.00) |
| 65–74 | 2.11 (1.65–2.68) |
| ≥ 75 | 3.76 (2.62–5.39) |
| Year of surgery (reference, 1991–1995) | |
| 1996–1999 | 0.95 (0.79–1.14) |
| 2000–2004 | 0.84 (0.69–1.03) |
| Cause of renal failure (reference, other) | |
| Diabetes | 1.59 (1.28–1.98) |
| Hypertension | 1.22 (0.99–1.51) |
| Glomerulonephritis | 1.03 (0.85–1.25) |
| ESRD duration, yrs (reference, 0–< 4) | |
| 4–< 6 | 1.33 (1.05–1.69) |
| 6–< 9 | 1.39 (1.12–1.74) |
| 9–< 15 | 1.60 (1.28–1.99) |
| ≥ 15 | 1.47 (1.13–1.90) |
| Charlson score (reference, 0) | |
| 1 | 1.28 (1.07–1.53) |
| 2 | 1.25 (1.01–1.55) |
| ≥ 3 | 1.28 (1.01–1.61) |
| Tissue valve (vs. nontissue valve) | 0.83 (0.70–0.99) |
Sex was not predictive of all-cause death. Patients who received concomitant CAB had a 9% increased risk of death, but this association was not statistically significant (HR 1.09, 95% CI 0.94–1.27). Outcomes were better for kidney transplant patients who underwent valve replacement in 2000–2004 than for those who underwent valve replacement in 1991–1999. Mortality was 17% lower for patients who received tissue valves compared with those who received nontissue valves (HR 0.83, 95% CI 0.70–0.99). A Cox model without adjustment for other factors found similar results (HR 0.87, 95% CI 0.74–1.02). We also calculated the hazard ratio based on individual comorbid conditions, and found essentially no difference in the Cox model between individual comorbid conditions and calculated Charlson score (using individual comorbid conditions, the adjusted hazard ratio for tissue valves was 0.84 (95% CI 0.70–0.99). Overall, in-hospital death was 14%; in-hospital death was 11.4% for patients who received tissue valves, and 15.0% for those who received nontissue valves (P = 0.09).
For the entire cohort, the estimated all-cause survival at 0.5, 1, 2, 3, 5, and 10 years was 75.3%, 70.8%, 60.1%, 52.8%, 38.4%, and 16.0%, respectively. Corresponding values (95% CI), for patients who received tissue valves were 77.8% (73.2%–81.7%), 73.7% (68.9%–77.8%), 61.5% (56.1%–66.5%), 55.3% (49.6%–60.7%), 41.7% (35.2%–48.0%), and 19.5% (11.3%–29.4%); and for patients who received nontissue valves, 74.3% (71.5%–77.0%), 69.7% (66.7%–72.5%), 59.5% (56.3%–62.5%), 51.8% (48.5%–55.0%), 37.2% (33.8%–40.7%), and 15.1% (11.9%–18.8%). We found no significant difference (P = 0.09) in unadjusted survival for patients who received tissue valves compared with those who received nontissue valves (Figure 1).
Figure 1.
Estimated unadjusted all-cause survival for patients who received tissue and nontissue valves.
Inclusion of propensity scores in the Cox model did not appreciably change the hazard ratios of interest (HR for tissue versus nontissue valves 0.81, 95% CI 0.67–0.99 after inclusion of propensity scores). Hazard ratios from separate Cox models within quartiles of propensity score did not show significantly different associations of tissue versus nontissue valves across groups of patients with different probabilities of receiving tissue versus nontissue valves.
To further assess potential temporal trends in survival, a stratified analysis was performed grouping patients by valve surgery before 2000 and from 2000–2004 (censoring patients at 3 years of follow-up), as more recent surgery was associated with a nonsignificant trend toward better survival (HR 0.84, 95% CI 0.69–1.03 for surgery performed in 2000–2004 compared with 1991–1995). The hazard ratio for death for patients who received tissue versus nontissue valves before 2000 was 0.82 (95% CI 0.60–1.14), compared with 0.90 (95% CI 0.70–1.16) for surgery in 2000–2004, suggesting no significant difference in the relative survival of patients related to prosthetic valve type over time.
Cause-specific mortality was categorized as cardiovascular, infection, or other/unknown cause. For patients undergoing valve surgery before 2000 who subsequently died (n = 514), cause of death was 26.6% cardiovascular, 13.9% infection, and 59.5% other/unknown for those with tissue valves, and 29.4% cardiovascular, 14.3% infection, and 56.3% other/unknown for those with nontissue valves (P = 0.86 for tissue versus nontissue). Of patients undergoing valve surgery in 2000–2004, 315 died. Cause of death was 32.1% cardiovascular, 11.6% infection, and 56.3% other/unknown for those with tissue valves, and 28.1% cardiovascular, 14.8% infection, and 57.1% other/unknown for those with nontissue valves (P = 0.62 for tissue versus nontissue).
The estimated hospitalization rate for endocarditis was 5.0 per 100 patient-years for patients with tissue valves and 5.2 per 100 patient-years for patients with nontissue valves (P = 0.79). The rate for gastrointestinal hemorrhage was 4.4 per 100 patient-years for patients with tissue valves and 5.2 per 100 patient-years for patients with nontissue valves (P = 0.42).
Discussion
We previously reported that estimated 2-year mortality after cardiac valvular replacement surgery is approximately 60% among ESRD patients requiring dialysis.10 In the present study of another group of ESRD patients, those who undergo kidney transplant, 2-year mortality after cardiac valvular surgery was approximately 40%, and in-hospital death was about 14%, compared with our previously reported 19% among dialysis patients.10
Few prior studies provide meaningful data on valvular surgery in kidney transplant patients. Dresler et al20 reported on 45 kidney transplant patients, of whom 13 underwent isolated cardiac valve replacement and 1 underwent CAB and valve replacement. Valve replacements included 4 aortic, 3 mitral, 2 aortic and mitral, 2 aortic with replacement of ascending aorta, 1 aortic and mitral with ventricular myotomy, and 1 aortic and mitral with tricuspid reconstruction. In-hospital mortality was 28.6%, and 8 of 13 patients were alive at the end of 5 years. Bioprosthetic valves were used in 2 patients in the aortic position and in 1 patient in the mitral position. Our in-hospital mortality of 15.1% for patients who received nontissue valves is comparable to results shown by Musci et al,21 who retrospectively analyzed outcomes of heart valve operations done in solid organ transplant patients over an 18-year period. The study, done at a single hospital center in Germany, included cardiac valve operations in 16 kidney transplant patients (9 aortic, 3 mitral, 2 aortic and mitral, 1 mitral valve reconstruction, and 1 tricuspid valve reconstruction). Three patients died in hospital, an in-hospital mortality of 18.7%. Long-term survival was 81% at a mean follow-up time of 41.2 months. Mechanical valves were used in all the surgeries.
Our observed survival is poorer than reported in other studies,22–28 but the small sample size in these earlier studies, and inclusion of nonvalvular surgery, precludes any meaningful comparison. None of these studies compared the outcome of tissue versus nontissue valves. The major significance of the present study of 1335 patients is that it provides a point of national reference for survival outcome of kidney transplant patients after cardiac valve replacement.
In our study, in-hospital death was 11.4% for patients who received tissue valves and 15.0% for patients who received nontissue valves. The overall risk of mortality was reduced by 19% for patients who received tissue valves compared with those who received nontissue valves (HR 0.81, 95% CI 0.67–0.99) in a propensity-adjusted Cox model, but there was no significant difference in unadjusted survival.
Several potential explanations could account for the more favorable outcome for patients who receive tissue valves. Implantation of nontissue (mechanical) valves requires life-long therapy with oral anticoagulation. Thrombotic complications would be expected to occur more frequently with nontissue valves, and long-term oral anticoagulation is accompanied by increased risk of hemorrhage. Kidney transplant patients, who often receive immunosuppression with steroids, might be expected to be more susceptible to the additional (gastrointestinal) hemorrhagic risk posed by long-term anticoagulation. We found that the rate of hospitalizations due to gastrointestinal hemorrhage was about 20% higher among patients with nontissue versus tissue valves, but the difference was not statistically significant. We found a nonsignificant 16% reduction in mortality (HR 0.84, 95% CI 0.69–1.03) for patients who received surgery in 2000–2004 versus 1991–1995, possibly reflecting improvements in care, including less intense maintenance immunosuppression.
Our data indicate that kidney transplant patients with prosthetic heart valves are at increased risk for bacterial endocarditis. In a prior study of 47,899 kidney transplant patients, we found an incident rate of endocarditis of 2.72 per 1000 patient-years.29 In the present study of kidney transplant patients with prosthetic valves, endocarditis incidence was nearly twenty-fold higher than in our prior study, but there was no evidence for a difference in endocarditis risk related to valve selection.
Our study has several limitations. The USRDS database provides few clinical data. Important prognostic factors such as left-ventricular function and functional class are not identified in the database. Ascertainment of valve replacement type is based on claims data. Although published data exist regarding the accuracy of claims information compared with clinical data in patients with ischemic heart disease,30 we are unaware of any specific studies regarding validation of claims data accuracy for patients undergoing cardiac valve replacement. Our survival analysis is based on a retrospective study design; selection bias for a particular choice of valve could possibly have occurred, and our propensity model may not account for the contribution of all significant unknown confounders.
Our data suggest a minimal reduction in mortality risk associated with use of tissue valves in renal transplant patients requiring valve surgery. Although the proportion of tissue valves has increased over time, even in 2000–2004 they accounted for only 38% of valve implants. From the perspective of clinical management, even if survival outcomes were similar for tissue and nontissue valves (i.e., no difference in unadjusted survival or adjusted mortality risk), some clinicians and patients might favor tissue valves, as tissue valve implantation is not associated with the additional potential hazard of long-term anticoagulation (and the definite inconvenience of attendant monitoring of therapy).
We conclude that the overall 2-year mortality of renal transplant patients following left-sided cardiac valvular replacement is approximately 40% (irrespective of prosthetic valve type). The additional requirement for long-term anticoagulation with nontissue valves might support the preferential use of tissue valves by clinicians and their patients who wish to avoid warfarin therapy.
Acknowledgments
The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. The authors thank Nan Booth, MSW, MPH, and Shane Nygaard, BA, of the USRDS Coordinating Center, for manuscript editing and preparation, respectively.
Funding Source
The Cardiovascular Special Studies Center of the United States Renal Data System is supported by Contract No. HHSN2672007105003C (National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland). This study was performed as a deliverable.
Footnotes
Disclosure
The authors have no conflicts of interest with the subject matter of this manuscript.
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