[Show abstract][Hide abstract] ABSTRACT: Background:
This case-control study identified perioperative risk factors associated with postoperative stroke risk after all cardiac surgical procedures.
Among 5498 adults 18 to 90 years old who underwent cardiac surgical procedures from 2005 to 2010, we identified 180 patients who suffered a stroke within 10 days postoperatively. Controls were randomly selected and frequency matched for sex and age-band to cases. Univariate and multivariate logistic regression analyses were performed to ascertain risk factors for postoperative stroke.
Emergency surgical procedures (odds ratio [OR], 3.04; 95% confidence interval [CI], 1.80 to 5.10), current smoking (OR, 1.97; 95% CI, 1.29 to 3.00), peripheral vascular disease (OR, 2.80; 95% CI, 1.41 to 5.53), and previous stroke with residual paralysis (OR, 4.27; 95% CI ,1.18 to 15.38) were associated with increased stroke risk. Preoperative blood pressures were higher in patients with cases than in controls (p < 0.0001). Log of immediate postoperative blood urea nitrogen (BUN) was higher in patients with cases than in controls (p < 0.0001). In adjusted multivariable logistic regression, postoperative BUN was associated with increased odds of stroke (OR, 2.37 per 25% increase in BUN, p < 0.0001). Postoperative stroke risk was also predicted by emergency surgical procedures (OR, 2.70, p = 0.014), current smoking (OR, 2.82, p = 0.002), and preoperative diastolic blood pressure (DBP) (OR, 1.77 for every 10-point increase in DBP, p < 0.0001). Receiver operator characteristic curves indicated that postoperative BUN (area under the curve, 0.855) largely explained the increased postoperative stroke risk.
In these analyses, we identified BUN as a marker of heightened postoperative stroke risk after cardiac surgical procedures. Postoperative risk markers may improve assessment of delayed postoperative strokes.
The Annals of Thoracic Surgery 02/2015; 99(4). DOI:10.1016/j.athoracsur.2014.11.034 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypothermic circulatory arrest (HCA) can lead to neurological complications including stroke, seizures, neurocognitive dysfunction, and delayed neuropsychomotor development in many patients. Neuroinflammation and excitotoxicity have been identified as key factors leading to the brain injury after HCA. The treatment has remained a challenge, with no suitable therapeutic options. Valproic acid (VPA) has been explored in this model, and offers some neuroprotection against excitotoxicity with a large dose, but leads to systemic side effects. Similarly N-Acetylcysteine (NAC) is known to be effective in reducing neuroinflammation, but large doses are required due to poor blood-brain barrier (BBB) penetration and insufficient brain localization. To overcome these challenges, we are exploring systemic, combination therapies targeted to activated microglia and injured neurons, using dendrimers. We use a well-established, clinically relevant canine model.1 Using fluorescently labeled, hydroxyl-terminated polyamidoamine (PAMAM) dendrimers, we showed that systemically administered dendrimers can cross the impaired blood-brain-barrier, and target activated microglia and injured neurons, with minimal uptake in the healthy cells in the brain.1,2 Based on above mentioned findings, we developed glutathione-sensitive dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multi-gram quantities for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA produced improvement in 24-hour neurological deficit score comparable to combination therapy with VPA and NAC at 10-30 fold higher doses, while significantly reducing the adverse side effects. This study highlights the potential of dendrimer-drug therapies of two clinically approved drugs in HCA-indued large animal model.1These are the first dendrimer nanotherapy studies in a large animal brain injury model.
* Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.Mishra MK, Beaty CA, Lesniak WG, Kambhampati SP, Zhang F, Wilson MA, Blue ME, Troncoso JC, Kannan S, Johnston MV, Baumgartner WA, Kannan RM. ACS Nano. 2014 Mar 25;8(3):2134-47.
* Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Kannan S, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, Romero R, Kannan RM. Sci Transl Med. 2012 Apr 18;4(130):130ra46.
[Show abstract][Hide abstract] ABSTRACT: Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB.
Journal of Neuropathology and Experimental Neurology 11/2014; 73(12). DOI:10.1097/NEN.0000000000000134 · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, general surgery and surgical subspecialty residency interests have remained somewhat static among medical students, casting some doubt on recruitment of the best students. A summer research program was designed to introduce interested medical students to surgical careers.
In 2003, the division of cardiac surgery instituted an 8-week structured summer research experience for second-year medical students. Three students were competitively chosen from a pool of 20 to 30 interested applicants every year. They were taught basic operative suturing and knot-tying techniques. Students participated in large animal research projects, witnessed clinical operations, and developed individual clinical projects with an attending cardiac surgeon. The summer experience culminated with oral presentations to the cardiac surgery division, with many students producing manuscripts for publication or presentation at national meetings.
From 2003 to 2012, 30 students participated in the program. Of 23 participants who had applied for residency, 12 (52.2%) matched into general surgery or a surgical subspecialty, including 3 into plastic surgery, 2 into cardiothoracic surgery, 1 into orthopedic surgery, and 1 into neurosurgery. These students produced 64 publications and presented at 51 national and regional meetings.
These results suggest that an 8-week, structured program introducing students to cardiothoracic surgery can successfully attract students into surgical careers. The percentage (52%) of these students entering a surgical career compares favorably with national residency match results (16%) and graduating Johns Hopkins medical students (22%). Increased effort for early exposure to surgery may be a key factor in generating and securing surgical interest among medical students.
The Annals of thoracic surgery 04/2014; 97(6). DOI:10.1016/j.athoracsur.2014.02.029 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated changes in physical functional performance after orthotopic heart transplantation (OHT) with particular attention to the impact of recipient age on functional outcomes.
Retrospective review of all first-time, single-organ adult OHTs in the United States between 2005 and 2010. Patients were primarily stratified by age. The validated Karnofsky performance scale, which ranges from 0 (death) to 100 (fully independent with no evidence of disease and no complaints), was used to measure functional status.
A total of 10,049 OHT recipients were identified, with 1,431 (14%) aged 65 years or greater. Mean Karnofsky score prior to OHT was comparable between cohorts (younger: 50.7 ± 25.2 versus older: 50.1 ± 25.0; p = 0.38). At a median follow-up of 2.1 years (interquartile range 0.7 to 3.3 years), 64% of OHT recipients had improved functional performance. The mean improvement in Karnofsky score was similar between younger and older patients (19.6 ± 42.0 vs 17.5 ± 41.8; p = 0.10). Twenty percent of younger patients were functionally independent prior to OHT, with 67% being functionally independent at last follow-up (p < 0.001). Similarly, in the older cohort, 20% were functionally independent prior to OHT, with 66% being functionally independent at last follow-up (p < 0.001). Multivariable analysis adjusting for potential confounders confirmed that age, both as a continuous and categoric variable, did not impact odds of functional improvement after OHT. Subanalysis using 70 years as the age cutoff produced similar results.
In the modern era, OHT is associated with improvements in functional performance in most recipients, and this beneficial effect is preserved across the age spectrum. These data provide a benchmark for functional outcomes after OHT and may have important implications in organ allocation.
The Annals of thoracic surgery 03/2014; 97(5). DOI:10.1016/j.athoracsur.2013.12.048 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically-relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection, but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals, and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multi-gram quantities, in which a glutathione-sensitive linker is used for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24-hour neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.
[Show abstract][Hide abstract] ABSTRACT: Left ventricular assist devices (LVADs) have become common as a bridge to heart transplant as well as destination therapy. Acute care surgical (ACS) problems in this population are prevalent but remain ill-defined. Therefore, we reviewed our experience with ACS interventions in LVAD patients.
A total of 173 patients who received HeartMate(®) XVE or HeartMate(®) II (HMII) LVADs between December 2001 and March 2010 were studied. Patient demographics, presentation of ACS problem, operative intervention, co-morbidities, transplantation, complications, and survival were analyzed.
A total of 47 (27 %) patients underwent 67 ACS procedures at a median of 38 days after device implant (interquartile range 15-110), with a peri-operative mortality rate of 5 % (N = 3). Demographics, device type, and acuity were comparable between the ACS and non-ACS groups. A total of 21 ACS procedures were performed emergently, eight were urgent, and 38 were elective. Of 29 urgent and emergent procedures, 28 were for abdominal pathology. In eight patients, the cause of the ACS problem was related to LVADs or anticoagulation. Cumulative survival estimates revealed no survival differences if patients underwent ACS procedures (p = 0.17). Among HMII patients, transplantation rates were unaffected by an ACS intervention (p = 0.2).
ACS problems occur frequently in LVAD patients and are not associated with adverse outcomes in HMII patients. The acute care surgeon is an integral member of a comprehensive approach to effective LVAD management.
World Journal of Surgery 12/2013; 38(4). DOI:10.1007/s00268-013-2403-0 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients undergoing aortic operations with hypothermic circulatory arrest (HCA) may require prolonged rewarming, a maneuver associated with impaired cerebral blood flow (CBF) autoregulation. The purpose of this study was to determine the effects of HCA on CBF autoregulation with a validated method based on near-infrared spectroscopy.
Regional cerebral oxygen saturation (rSco2) was monitored in 25 patients undergoing aortic reconstructive operations. HCA was used in 13 patients. Autoregulation was measured continuously during the operation by calculating the linear correlation coefficient between low-frequency changes in rSco2 and mean arterial pressure (MAP), generating the variable cerebral oximetry index (COx). When CBF autoregulation is functional, COx is near 0, because CBF and MAP are not correlated, but approaches 1 when autoregulation is impaired (ie, CBF is pressure passive). On the basis of prior studies, impaired autoregulation was defined as COx exceeding 0.3.
COx did not differ between HCA and non-HCA groups before cardiopulmonary bypass or during the cooling phase of the operation, although the lower limit of autoregulation tended to be lower in patients before HCA (p = 0.053). During patient rewarming, COx was lower in the HCA group (p = 0.045), and abnormal COx was less frequent (31% vs 75%, p = 0.047) compared with the non-HCA group.
During aortic reconstructive operations, CBF autoregulation is preserved during the cooling phase of the procedure in patients undergoing HCA. Perfusion maneuvers associated with HCA may be protective against impaired autoregulation during rewarming compared with the non-HCA group.
The Annals of thoracic surgery 12/2013; 96(6):2045. DOI:10.1016/j.athoracsur.2013.07.086 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to examine interhospital variability in inpatient costs of coronary artery bypass grafting (CABG).
The Nationwide Inpatient Sample was used to identify isolated CABGs performed between 2005 and 2008 in the United States. Charges for inpatient care were supplied by the data set, and hospital charge-to-cost ratios were used to derive inpatient costs for each patient and aggregated at the hospital level. Mixed-effect linear regression models were created to evaluate variability in costs between hospitals adjusting for 34 patient, operative, complication, and hospital-related variables.
A total of 633 hospitals performed isolated CABG in 183,973 patients. In unadjusted analysis, there was significant baseline variability in average inpatient costs of CABG between hospitals (SD, $12,130; P < .001). This variability represented 30% of the overall unadjusted average cost of performing CABG per hospital ($40,424). After risk adjustment, significant variability in average costs between hospitals persisted (P < .001). Of the 34 additional variables included in the model, only hospital region, postoperative sepsis, in-hospital mortality, and need for ventricular assist device, extracorporeal membrane oxygenation, permanent pacemaker, or implantable cardioverter-defibrillator were stronger predictors of increased costs compared with the hospital effect.
There is a wide variation in the cost of performing CABG in the United States. We determined that individual hospital centers, independent of multiple patient- and outcome-specific factors, are drivers of these differences. Comparison of hospital-specific behavior with identification of the causes of cost discrepancies represents an opportunity for standardization of care and improvement in resource use.
The Journal of thoracic and cardiovascular surgery 10/2013; 147(1). DOI:10.1016/j.jtcvs.2013.08.024 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study was to evaluate nationwide outcomes of ventricular assist device (VAD) implantation in elderly patients in the United States.
Patients undergoing VAD implantation between 2003 and 2008 were identified in the Nationwide Inpatient Sample. The primary outcome was inpatient mortality following VAD implantation. Secondary outcomes included disposition following discharge and costs of care. After stratification based on primary versus postcardiotomy VAD support, outcomes were compared between controls aged 60-69 years and elderly patients aged ≥70 years.
A total of 2787 patients aged 60-69 years and 1472 patients aged ≥70 years underwent VAD implantation during the study period. Unadjusted mortality rates were comparable between elderly and control patients in both primary support (35.7% vs. 32.1%, p = 0.61) and postcardiotomy support (58.1% vs. 56.1%, p = 0.70). Similarly, in risk-adjusted multivariable logistic regression analysis incorporating clinically relevant variables, age ≥70 did not exert an independent effect on inpatient mortality for either indication. Inpatient costs in the elderly were lower than controls in the primary support cohort, although costs per day were similar, with comparable overall costs between age groups in the postcardiotomy cohort. Elderly survivors were discharged to a facility more frequently than control survivors (primary: 49.9% vs. 29.6%, p = 0.007; postcardiotomy: 67.4% vs. 45.7%, p = 0.03).
This large-cohort population-based analysis provides a useful framework for inpatient prognosis and resource utilization in elderly patients undergoing VAD implantation. Although mortality rates and costs were found to be comparable between elderly patients and those aged 60-69 years, these rates were nonetheless significant. This combined with more frequent discharge-to-facility in elderly survivors underscores the importance of careful patient selection in this population.
Journal of Cardiac Surgery 02/2013; 28(2). DOI:10.1111/jocs.12066 · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Computed tomography (CT) scans of the head without contrast are routinely obtained to evaluate neurologic deficits after cardiac surgery, but their utility is unknown. We evaluated our experience with this imaging modality to determine its value.
We retrospectively identified cardiac surgery patients with postoperative neurologic deficits occurring during the first week after surgery between January 2000 and December 2012. Stroke was defined by neurologist's determination, whereas a nonfocal deficit (NFD) was defined by the presence of seizure, delirium, or cognitive impairment. We defined early noncontrast head CT as occurring within 7 days of surgery. Outcomes included positive findings on CT, in-hospital mortality, and length of stay. Multivariate logistic regression identified predictors of positive findings on head CT.
Within the population of 11,070 postoperative patients, 451 had early noncontrast head CT scans (4%). Two hundred two (44.7%) were associated with stroke, and 249 (55.2%) were associated with NFD. Among stroke patients, 40 of 202 (20%) showed acute infarction, 17 of 202 (8%) showed subacute infarction, and 5 of 202 (2%) showed hemorrhage. Among NFD patients, 1 of 248 (0.4%) showed acute infarction, 4 of 248 (1.6%) showed subacute infarction, and 1 of 248 (0.4%) showed hemorrhage. There was no difference in in-hospital mortality (stroke, 42 of 201 [21%] versus NFD, 41 of 248 [16%]; p = 0.2) or length of stay (stroke, 24 d versus NFD, 22 d; p = 0.5). On multivariable logistic regression, only focal deficits and aortic procedures predicted a positive finding on CT scan.
This study reviewed the utility of early postoperative noncontrast head CT in cardiac surgery patients. With focal neurologic deficits, this imaging modality was positive for approximately one third of patients, but rarely positive for NFD. Its use in this setting has limited utility.
The Annals of thoracic surgery 12/2012; 95(2). DOI:10.1016/j.athoracsur.2012.11.006 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : To evaluate the contribution of institutional volume and other unmeasured institutional factors beyond volume to the between-center variability in outcomes after orthotopic heart transplantation (OHT).
: It is unclear if institutional factors beyond volume have a significant impact on OHT outcomes.
: The United Network for Organ Sharing registry was used to identify OHTs performed between 2000 and 2010. Separate mixed-effect logistic regression models were constructed, with the primary endpoint being post-OHT mortality. Model A included only individual centers, model B added validated recipient and donor risk indices as well as the year of transplantation, and model C added institutional volume as a continuous variable to model B. The reduction in between-center variability in mortality between models B and C was used to define the contribution of institutional volume. Kaplan-Meier survival curves were also compared after stratifying patients into equal-size tertiles based on center volume.
: A total of 119 centers performed OHT in 19,156 patients. After adjusting for transplantation year and differences in recipient and donor risk, decreasing center volume was associated with an increased risk of 1-year mortality (P < 0.001). However, procedural volume only accounted for 16.7% of the variability in mortality between centers, and significant between-center variability persisted after adjusting for institutional volume (P<0.001). In Kaplan-Meier analysis, there was significant variability in 1-year survival between centers within each volume category: low-volume (66.7%-96.6%), intermediate-volume (80.7%-97.3%), and high-volume (83.8%-93.9%). These trends were also observed with 5-year mortality.
: This large-cohort analysis demonstrates that although institutional volume is a significant predictor of post-OHT outcomes, there are other unmeasured institutional factors that contribute substantially to the between-center variability in outcomes. Institutional volume should therefore not be the sole indicator of "center quality" in OHT.
Annals of surgery 09/2012; 256(4):616-23. DOI:10.1097/SLA.0b013e31826b4bc9 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
We evaluated the combined effect of hospital and surgeon volume on operative outcomes of mitral valve surgery in the United States.
The Nationwide Inpatient Sample was used to identify adult patients undergoing isolated mitral valve surgery for mitral regurgitation from 2003 to 2008. Hospitals and surgeons were separately stratified into equal-size tertiles according to annual overall mitral valve operative volumes. Multivariate logistic regression analysis was conducted, adjusting for multiple patient, hospital, and operative data, to determine the separate and combined effects of hospital and surgeon volume on operative outcomes.
A total of 50,152 eligible patients were identified during the study period. Although both hospital and surgeon volume correlated significantly with operative mortality in separate risk-adjusted analyses, only lower surgeon volume persisted as a significant risk factor in the combined risk-adjusted analysis. Moreover, although hospital volume only accounted for 10.7% of the surgeon volume effect on increased mortality for low-volume surgeons, surgeon volume accounted for 74.5% of the hospital volume effect on increased mortality in low-volume hospitals. Surgeon, but not hospital, volume correlated with inpatient costs. Also, significant trends were seen with repair rates, with increasing surgeon volume demonstrating a relatively stronger correlation with the odds of repair (P < .001) than hospital volume (P = .01).
The effect of hospital volume on operative outcomes of mitral valve surgery was largely driven by the individual surgeon volumes within that hospital. Conversely, surgeon volume affected these outcomes independently of hospital volume. Identifying the processes by which higher volume surgeons attain better outcomes in mitral valve surgery would therefore be prudent.
The Journal of thoracic and cardiovascular surgery 08/2012; 146(3). DOI:10.1016/j.jtcvs.2012.07.070 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Impaired cerebral autoregulation may predispose patients to cerebral hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was to identify risk factors for impaired autoregulation during coronary artery bypass graft, valve surgery with CPB, or both and to evaluate whether near-infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify this condition.
Two hundred and thirty-four patients were monitored with transcranial Doppler and NIRS. A continuous, moving Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and cerebral blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional autoregulation is indicated by an Mx and COx that approach zero (no correlation between CBF and MAP); impaired autoregulation is indicated by an Mx and COx approaching 1. Impaired autoregulation was defined as an Mx ≥0.40 at all MAPs during CPB.
Twenty per cent of patients demonstrated impaired autoregulation during CPB. Based on multivariate logistic regression analysis, time-averaged COx during CPB, male gender, Pa(CO(2)), CBF velocity, and preoperative aspirin use were independently associated with impaired CBF autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with impaired autoregulation compared with five of 187 (2.7%) patients with preserved autoregulation (P=0.011).
Impaired CBF autoregulation occurs in 20% of patients during CPB. Patients with impaired autoregulation are more likely than those with functional autoregulation to have perioperative stroke. Non-invasive monitoring autoregulation may provide an accurate means to predict impaired autoregulation. Clinical trials registration. www.clinicaltrials.gov (NCT00769691).
BJA British Journal of Anaesthesia 06/2012; 109(3):391-8. DOI:10.1093/bja/aes148 · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to derive and validate a risk score for rejection after orthotopic heart transplantation.
The United Network for Organ Sharing registry was used to identify patients undergoing orthotopic heart transplantation between 1998 and 2008. A total of 14 265 eligible patients were randomly divided into derivation (80%; n=11 412) and validation (20%; n=2853) cohorts. The primary outcome was drug-treated rejection within 1 year of orthotopic heart transplantation. Covariates found to be associated (exploratory univariate P<0.2) with rejection were entered into a multivariable logistic regression model. Inclusion of each variable in the model was assessed by improvement in the McFadden pseudo-R(2), likelihood ratio test, and c index. A risk score was then generated through the use of relative magnitudes of the odds ratios from the derivation cohort, and its ability to predict rejection was tested independently in the validation cohort. A 13-point risk score incorporating 4 variables (age, race, sex, HLA matching) was created. The mean scores in the derivation and validation cohorts were 8.3±2.2 and 8.4±2.1, respectively. Predicted 1-year rejection rates based on the derivation cohort ranged from 16.2% (score=0) to 50.7% (score=13; P<0.001). In weighted regression analysis, there was a strong correlation between these predicted rates of rejection and actual, observed rejection rates in the validation cohort (r(2)=0.96, P<0.001). Logistic regression analysis also demonstrated a significant association (odds ratio, 1.13; P<0.001). The c index of the composite score was equivalent in both the derivation and validation cohorts (c=0.67).
This novel 13-point risk score is highly predictive of clinically significant rejection episodes within 1 year of orthotopic heart transplantation. It has potential utility in tailoring immunosuppressive regimens and in research stratification in orthotopic heart transplantation.