Utility of the revised cardiac risk index for predicting postsurgical morbidity in Hb SC and Hb Sβ+‐thalassemia sickle cell disease
Authors: Ari Rosenberg, Vladimir Selounski, Hamid Wardak, Jin Han, Michel Gowhari, Joharah Hassan, Shivi Jain, Robert E. Molokie, Victor R. Gordeuk, Santosh L. Saraf
Journal: American Journal of Hematology (2016)

To the Editor: Sickle cell disease (SCD), caused by homozygous (Hb SS) or compound heterozygous (Hb SC or Hb Sβ+-thalassemia) mutations in the β-globin gene, leads to acute and chronic organ damage and patients frequently require surgical interventions to help manage these complications 1. While randomized studies in homozygous Hb SS patients have demonstrated improvements in the postoperative complication rate with preoperative red blood cell (RBC) transfusions 2, the preoperative management strategy for compound heterozygous SCD patients is less clear. The need for better preoperative assessment and care in compound heterozygous SCD is highlighted by the higher rates of non-SCD related postoperative complications in Hb SC (23%) versus Hb SS (11%) patients observed in the Cooperative Study of Sickle Cell Disease (CSSCD) cohort 1. Patients with compound heterozygous SCD have higher rates of overweight and diabetes mellitus than Hb SS patients 3 and utilizing presurgical evaluation tools commonly used in the general population may help identify patients at higher risk for postoperative complications. The Revised Cardiac Risk Index (RCRI) is a pre-operative risk assessment tool that predicts the Postsurgical Outcome Morbidity Survey (POMS) score and length of hospitalization in non-SCD patients 4, 5. The POMS score is a measure of short-term morbidity that evaluates nine different organ systems and is a commonly utilized core outcome measure in surgical trials 6. We performed a retrospective chart review of patients with Hb SC or Hb Sβ+-thalassemia at the University of Illinois at Chicago to evaluate outcomes according to pre-operative RBC transfusion and to determine whether the preoperative RCRI score is associated with the POMS score, length of hospitalization, and SCD-related postoperative complications. Of 133 patients screened, 36 underwent 52 surgical procedures between January 2001 and December 2014; each surgical procedure was analyzed as an independent event. The RCRI score was calculated by the sum of the number of risk factors present prior to each surgical procedure: (1) high-risk surgery defined as vascular, open intraperitoneal or intrathoracic procedures; (2) history of ischemic heart disease; (3) history of heart failure; (4) history of cerebrovascular disease; (5) diabetes mellitus; or (6) a preoperative serum creatinine greater than 2.0 mg/dL 5. The POMS score was determined at 3 days after the surgical procedure as previously described 6. If the patient had been discharged by the third day of hospitalization, the patient was assigned a POMS score of zero. The presence of postoperative morbidity was defined as a POMS score ≥1 and an SCD-related event was defined as a vaso-occlusive crisis (VOC) or acute chest syndrome. The Spearman correlation and the test for linear trend were used to identify variables associated with a higher POMS score and length of hospitalization, respectively. Length of hospitalization was not normally distributed and was log transformed for analyses. The Kruskal–Wallis and Pearson's Chi square test were used to compare continuous and categorical variables, respectively, based on preoperative RBC transfusion therapy and postoperative SCD-related events. Logistic and linear regression analyses were adjusted for age at the time of surgery. Systat 13 (Systat Software Corporation, Chicago, IL) was used for statistical analyses. Baseline characteristics of the patients undergoing surgery are provided in Table 1. The median age at the time of surgery was 47 years (range, 23–78 years), 73% had HbSC disease, and there were no episodes of mortality within the 30-day period after surgery. Four patients had five surgical procedures with cardiac disease as an RCRI risk factor: three had coronary artery disease determined by cardiac catheterization and one had heart failure determined by both clinical history and a low ejection fraction on transthoracic echocardiogram. Eight of the surgeries were considered high risk (open intraperitoneal: n = 7; intrathoracic, n = 1; vascular, n = 1). Preoperative RBC transfusions were performed in 13 (25%) of the 52 surgeries and a median of two RBC units (range, 1–5 units) was administered at a median of 1 day (range, 1–6 days) prior to the surgery. An RCRI score ≥1 was observed in 19 (37%) of the surgeries. On postoperative day three, 17 (33%) of the surgeries had postoperative morbidity as determined by the POMS score (Supporting Information Table 1). A higher RCRI score (r = 0.46, P = 0.0006) and preoperative RBC transfusion therapy (r = 0.36, P = 0.01) correlated with this day three POMS score. After adjusting for age, a higher RCRI score (OR 4.1, 95% CI: 1.4–12.1; P = 0.01) but not preoperative RBC transfusion therapy (OR 2.9, 95% CI: 0.7–11.8; P = 0.1) continued to be significantly predictive of POMS ≥1. The median length of hospitalization was 2 days (range, 1–13 days). A higher RCRI score (β = 0.59, 95% CI: 0.18–1.00; P = 0.006) and preoperative transfusion therapy (β = 0.68, 95% CI: 0.09–1.27; P = 0.03) were associated with length of hospitalization. After adjusting for age, a higher RCRI score (β = 0.51, 95% CI: 0.07–0.95; P = 0.02) but not preoperative transfusion therapy (β =0.53, 95% CI: −0.10 to 1.15; P = 0.1) continued to significantly associate with length of hospitalization. SCD-related events occurred in seven (13%) of the surgeries in the postoperative period (vaso-occlusive crises, n = 5; acute chest syndrome, n = 2). We did not observe significant associations of the RCRI score (P = 0.7) or preoperative RBC transfusion therapy (P = 0.8) with surgeries complicated by an SCD-related event. There are several limitations to our study. This was a retrospective analysis and our sample size was small and underpowered to detect anything but large effects of RBC transfusion therapy on postsurgical outcome. Our cohort also included several patients who had more than one surgical procedure. Future studies prospectively evaluating the RCRI and POMS scores in HbSC or HbSβ+-thalassemia and addressing these limitations are needed. In conclusion, the RCRI score was elevated in 37% of compound heterozygous SCD patients and was associated with postoperative morbidity defined by the POMS score and length of hospitalization. Future studies to tailor therapy based on the RCRI score in Hb SC and Hb Sβ+-thalassemia patients may help improve postsurgical morbidity in these patients. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Ari Rosenberg1, Vladimir Selounski1, Hamid Wardak2, Jin Han2,3, Michel Gowhari2, Joharah Hassan2, Shivi Jain2, Robert E. Molokie2,4, Victor R. Gordeuk2,Santosh L. Saraf2* 1Internal Medicine, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 2Comprehensive Sickle Cell Center, Division of Hematology & Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 3Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 4Jesse Brown VA Medical Center, Chicago, Illinois Additional Supporting Information may be found in the online version of this article. Contract grant sponsor: National Institutes of Health, National Heart, Lung, and Blood Institute; Contract grant number: K23HL125984. Additional Supporting Information may be found in the online version of this article. Supporting Information Table 1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.