Perioperative Complications and In-Hospital Mortality in Partial and Radical Nephrectomy Patients with Heart-Valve Replacement

Background In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown. Patients and Methods Relying on the National Inpatient Sample (2000–2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes. Results Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5). Conclusions History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-024-15228-6.

Partial nephrectomy and radical nephrectomy represent guideline-recommended standard treatments in kidney cancer patients. 1,2Some patients who might benefit from partial or radical nephrectomy have a history of heart-valve replacement, which may predispose them to adverse in-hospital outcomes and possibly even higher in-hospital mortality.However, actual in-hospital complication rates and mortality figures in patients with history of heart-valve replacement treated with either partial or radical nephrectomy are unknown.
We addressed this knowledge gap and hypothesized that in-hospital outcomes, namely length of stay, estimated hospital cost, intraoperative and postoperative complications, critical care therapy use, and in-hospital mortality of partial or radical nephrectomy patients do not differ according to presence versus absence of history of heart-valve replacement in patients with kidney cancer.To test this hypothesis, we relied on a large-scale population-based cohort of kidney cancer patients who underwent partial or radical nephrectomy within the United States of America over a period of 20 years (2000-2019).

Data Source
Relying on discharge data from the National Inpatient Sample (NIS 2000-2019), we assessed length of stay, estimated hospital cost, perioperative complications, and inhospital mortality of patients treated with partial or radical nephrectomy.NIS is a set of longitudinal hospital inpatient databases included in the Healthcare Cost and Utilization Project (HCUP) and formed by the Agency for Healthcare Research and Quality (AHRQ) through a Federal-State-Industry partnership. 3All diagnoses and procedures were coded using the International Classification of Disease (ICD) 9th revision Clinical Modification (ICD-9-CM), ICD 10th revision Clinical Modification (ICD-10-CM), as well as ICD 10th revision Procedure Coding System (ICD-10-PCS).

Definition of Variables for Analyses
0][11] All ICD-9 and ICD-10 codes used for the identification of intraoperative and postoperative complications are summarized in Supplementary Table 1.Additionally, estimated hospital cost were calculated relying on total hospital charges provided by NIS.Converting total hospital charges into estimated hospital cost was performed using HCUP Cost-to-Charge Ratios, which were based on hospital accounting reports, according to NIS methodological guidelines. 3,6All calculations were adjusted to 2019 US dollar ($USD) relying on the overall Consumer Price index. 12To account for comorbidities, the Deyo modification of Charlson comorbidity index (CCI) was used, 13 according to coding algorithms for defining comorbidities in ICD-9-CM and ICD-10-CM codes by Quan et al. 14 .Covariates consisted of patient characteristics including age at admission (years, continuously coded) and CCI (0 versus 1 versus 2 versus ≥ 3).

Statistical Analyses
First, descriptive characteristics and primary outcome rates were tabulated.For categorical variables, frequencies and proportions were reported.For continuously coded variables, medians and interquartile ranges (IQR) were reported.Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were applied.Second, estimated annual percentage changes (EAPC) were tested with the least squares linear regression.Third, univariable and multivariable Poisson regression models addressing length of stay and estimated hospital cost, as well as logistic regression models addressing perioperative complications and inhospital mortality were fitted after adjustment for clustering at the hospital level using generalized estimating equation methodology. 10,11Subgroup analyses addressed patients with Perioperative Complications and In-Hospital Mortality … versus without history of prosthetic heart-valve replacement.All analytical steps were separately performed in partial nephrectomy and radical nephrectomy patients.
Analyses and reporting followed NIS reporting guidelines. 3Due to NIS data reporting agreement, counts and associated proportions were reported as less than eleven for sample sizes of less than eleven patients.R software environment was used for statistical computing and graphics (R version 4.2.2;R Foundation for Statistical Computing, Vienna, Austria). 15All tests were two sided, with a significance level set at p < 0.05.

DISCUSSION
In kidney cancer patients undergoing partial or radical nephrectomy, the association between history of heart-valve replacement and length of stay, estimated hospital cost, perioperative complications, as well as in-hospital mortality is unknown.To address this knowledge gap, we relied on a population-based cohort of partial and radical nephrectomy patients within NIS (2000-2019) and made several important observations.First, we identified important differences in descriptive characteristics between patients with versus without history of heart-valve replacement who underwent partial or radical nephrectomy.Specifically, partial and radical nephrectomy patients with history of heart-valve replacement were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years) and harbored higher comorbidity burden (CCI ≥ 3 partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%) than their respective counterparts.Considering these differences, it is essential to rely on multivariable adjustment for baseline patient characteristics in analyses focusing on adverse perioperative outcomes, as was done in the present study.
Second, we hypothesized that complication and in-hospital mortality rates following partial or radical nephrectomy in patients with versus without history of heart-valve replacement do not differ.Of those, in-hospital mortality is feared the most.Examination of in-hospital mortality revealed no statistically significant differences after either partial nephrectomy (< 4.4% versus 0.2%; p = 0.1) or radical nephrectomy (< 1.6% versus 0.9%; p = 0.6) and failed to achieve independent predictor status of higher in-hospital mortality in multivariable analyses (partial and radical nephrectomy p = 0.5).This finding is important in treatment decision-making regarding partial or radical nephrectomy in kidney cancer patients with history of heart-valve Third, we also assessed eleven other adverse in-hospital outcomes in history of heart-valve replacement versus other partial or radical nephrectomy patients.In separately fitted multivariable models, history of heart-valve replacement independently predicted four of eleven adverse in-hospital outcomes in partial nephrectomy patients, namely intraoperative (OR 1.5; p < 0.001) and cardiac complications (OR 4.3; p < 0.001), blood transfusions (OR 2.0; p < 0.001), and longer length of stay (RR 1.3; p < 0.001).In radical nephrectomy patients, history of heart-valve replacement independently predicted five of eleven adverse in-hospital outcomes, namely postoperative bleeding (OR 4.1; p < 0.001), intraoperative (OR 1.5; p < 0.001) and cardiac complications (OR 2.7; p < 0.001), blood transfusions (OR 1.3; p = 0.02), and longer length of stay (RR 1.1; p < 0.001).Partial (n = 39,619) and radical nephrectomy (n = 94,764) subgroups, addressing the effect of prosthetic heart-valve replacement, virtually perfectly mimicked the results recorded in the overall cohort.Taken together, these observations indicate a less favorable in-hospital stay profile in patients with history of heart-valve replacement.However, this unfavorable profile is not prohibitive based on the absence of the ultimately feared in-hospital complication, namely in-hospital mortality.
Taken together, partial nephrectomy and radical nephrectomy patients with history of heart-valve replacement exhibit less favorable patient characteristics.These consist of older age and higher comorbidity burden (CCI ≥ 3).Despite these baseline disadvantages, heart-valve replacement patients undergoing partial or radical nephrectomy are not at higher risk of the most feared in-hospital complication, namely in-hospital mortality.Nonetheless, cardiac complications, blood transfusions, and intraoperative complications are significantly higher in those individuals.These observations are essential in medical decision-making and counselling prior to definitive therapy assignment.They should not discourage clinicians from relying on partial or radical nephrectomy as respective standards of care according to clinical indications for those two procedures.
The current study has limitations.First, due to the retrospective nature of NIS, selection and reporting biases may have remained.7][18] Second, despite its very large size, NIS only provides a limited number of patients with history of heart-valve replacement, due to the rarity of this condition.Therefore, subgroup analyses could only be performed in prosthetic heart-valve replacement but not in xenogenic or other heart-valve replacement patients.Moreover, we were unable to perform further subgroup analyses according to surgical approach (robotic-assisted versus laparoscopic versus open surgery).Third, NIS as well as ICD codes only offer a limited amount of detail.For example, timing, duration, and dose of anticoagulation as well as timing and frequency of blood transfusions were not available.Additionally, detailed information regarding procedure-related characteristics, such as intraoperative blood loss, were unknown.Moreover, we were unable to adjust for tumor characteristics since NIS does not contain such information.Finally, NIS exclusively provides in-hospital data.In consequence, data regarding readmissions and complications after hospital discharge were not available.Indeed, it could be interesting to also assess readmission and long-term complications rates after partial and radical nephrectomy in future studies.

CONCLUSIONS
History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay.Conversely, no statistically significant differences were observed in in-hospital mortality.

TABLE 1
Descriptive characteristics of 134,563 kidney cancer patients, undergoing partial or radical nephrectomy, stratified according to history of heart-valve replacement Bold values indicate statistically significant p < 0.05 a Wilcoxon rank sum test; Pearson's chi-squared test Characteristic Partial nephrectomy, n = 39,673 Radical nephrectomy, n = 94,890

TABLE 3
Univariable and multivariable regression models addressing length of stay, perioperative complications, and in-hospital mortality according to history of heart-valve replacement in 134,563 kid-ney cancer patients undergoing partial or radical nephrectomy after adjustment for clustering at the hospital level using generalized estimating equation methodology Bold values indicate statistically significant p < 0.05 *Adjusted for age at admission, and comorbidities (Charlson comorbidity index) CI Confidence interval, RR rate ratio, OR odds ratio

TABLE 4
Univariable and multivariable regression models addressing length of stay, perioperative complications, and in-hospital mortality according to history of prosthetic heart-valve replacement in 134,383 kidney cancer patients undergoing partial or radical nephrectomy after adjustment for clustering at the hospital level using generalized estimating equation methodology Bold values indicate statistically significant p < 0.05 *Adjusted for age at admission and comorbidities (Charlson comorbidity index) CI Confidence interval, RR rate ratio, OR odds ratio Perioperative Complications and In-Hospital Mortality … replacement.Particularly, healthcare providers can reassure patients with a history of heart-valve replacement that the risk of in-hospital mortality should not dissuade them from considering partial or radical nephrectomy as curative treatment option for kidney cancer.