Risk tolerance to MS therapies: Survey results from the NARCOMS registry.

BACKGROUND: There is little information about risk acceptance of multiple sclerosis (MS) patients to various MS therapies. OBJECTIVE: To determine MS patients׳ tolerance to risky therapies and identify associated characteristics. METHODS: MS patients from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry׳s online cohort were invited to complete questionnaires on decision making and risk tolerance (RT) to two therapeutic scenarios: a theoretical cure for MS [CureMS], with permanent reversal of all MS symptoms but a risk of immediate painless death; and natalizumab [NAT], a real-life scenario with benefits and risks as defined by Phase III trial results. RESULTS: The median RT for both scenarios was 1:10,000; 15-23% of respondents were not willing to take any risk for their MS therapy. Participants with greater disability or not taking any MS therapy showed a greater RT, while females and those caring for dependents had a lower RT. Females and older age were predictors of lower RT, while increasing disability and greater blunting attitude with respect to information seeking behavior were predictors of higher RT. CONCLUSION: MS patients displayed a wide range of RT for MS therapies. Our study identified gender, age, disability and information seeking behavior to be associated with RT.

Renal transplantations in African Americans: a single-center experience of outcomes and innovations to improve access and results.

OBJECTIVE: To report a single-center 10-year experience of outcomes of kidney transplantation in African Americans (AAs) vs Caucasian Americans (CA) and to propose ways in which to improve kidney transplant outcomes in AAs, increased access to kidney transplantation, prevention of kidney disease, and acceptance of organ donor registration rates in AAs. METHODS: We compared outcomes of deceased donor (DD) and living donor (LD) renal transplantation in AAs vs CAs in 772 recipients of first allografts at our transplant center from January 1995 to March 2004. For DD and LD transplants, no significant differences in gender, age, body mass index, or transplant panel reactive antibody (PRA) existed between AA and CA recipients. RESULTS: Primary diagnosis of hypertension was more common in AA, DD, and LD recipients. Significant differences for DD transplants included Medicaid insurance in 23% AA compared with 7.0% CA (P<.0001) and more frequent diabetes mellitus type 2 in AAs (15% vs 4.1%, P=.0009). Eighty-three percent of AAs had received hemodialysis compared with 72% of CAs (P=.02). AAs endured significantly longer pretransplant dialysis (911±618 vs 682±526 days CA, P=.0006) and greater time on the waiting list (972±575 vs 637±466 days CA, P<0001). In DD renal transplants, AAs had more human leukocyte antigen (HLA) mismatches than CAs (4.1±1.4 vs 2.7±2.1, P<.0001). Mean follow-up for survivors was 7.1±2.5 years. Among LD transplants, graft survival and graft function were comparable for AAs and CAs; however, among DD transplants, graft function and survival were substantially worse for AAs (P=.0003). In both LD and DD transplants, patient survival was similar for AAs and CAs. CONCLUSION: Our data show that AAs receiving allografts from LDs have equivalent short- and long-term outcomes to CAs, but AAs have worse short- and long-term outcomes after DD transplantation. As such, we conclude that AAs should be educated about prevention of kidney disease, the importance of organ donor registration, the merits of LD over DD, and encouraged to seek LD options.

Prediction of intraoperative transfusion requirements during orthotopic liver transplantation and the influence on postoperative patient survival.

BACKGROUND: Predicting blood product transfusion requirements during orthotopic liver transplantation (OLT) remains difficult. Our primary aim in this study was to determine which patient variables best predict recipient risk for large blood transfusion requirements during OLT. The secondary aim was to determine whether the amount of blood products transfused during OLT impacted patient survival. METHODS: Eight hundred four primary adult OLTs performed during a 9-year period were retrospectively analyzed, and predictive models were developed for blood product usage, usage >20 and usage >30 units of red blood cells (RBCs) plus cell salvage (CS). For survival analysis, potential predictors included all blood products administered during OLT. RESULTS: For analyses of RBC + CS usage, we used several statistical techniques: regression analysis, logistic regression, and classification and regression tree analysis. Several preoperative factors were highly statistically significant predictors of intraoperative blood product usage in each of the analyses, namely lower platelet count and higher Model for End-Stage Liver Disease Score or one or more of its components (creatinine, total bilirubin, international normalized ratio). Despite these highly significant associations, the models were unable to predict reliably that patients might require the largest amount of blood products during OLT. For example, the classification and regression tree analyses were able to predict only 32% and 11% of patients requiring >20 and >30 units of RBC + CS, respectively. Survival analysis demonstrated poorer survival among patients receiving larger amounts of RBC + CS during OLT. CONCLUSION: Prediction of intraoperative blood product requirements based on preoperatively available variables is unreliable; however, there is a strong measurable association between transfusion and postoperative mortality.

Association of histologic variants in FSGS clinical trial with presenting features and outcomes.

BACKGROUND AND OBJECTIVES: FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes. RESULTS: The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005). CONCLUSIONS: This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.

Impact of pulmonary hemodynamics on 6-min walk test in idiopathic pulmonary fibrosis.

OBJECTIVES: Pulmonary hypertension (PH) has been associated with decreased functional capacity in patients with advanced idiopathic pulmonary fibrosis (IPF). We aimed to evaluate the true impact of altered pulmonary hemodynamics on functional capacity in a cohort of patients with IPF. METHODS: Between January 1990 and December 2007, 124 patients [73M/51F; 111 Caucasians] with IPF underwent right heart catheterization and 6-min walk test (6MWT). Pulmonary arterial hypertension (PAH) was defined as mPAP≥25 and pulmonary artery occlusion pressure (PAOP)≤15mmHg, and Pre-PH as mPAP>20 and <25mmHg with PAOP<15mmHg. Demographic, hemodynamic, spirometric, and 6MWT data were collected. RESULTS: Fifty four (44%) patients had PH. There were no significant differences between the PH and the non-PH groups in measures of pulmonary function other than PaO(2). Patients with PH and PAH had significantly lower 6-min walk distance (6MWD) (p=0.008 and p=0.03 respectively) and distance saturation product (DSP) (p=0.002 and p=0.006 respectively) compared to non-PH patients. Mean pulmonary arterial pressure (mPAP) was the best predictor of 6MWD by multivariate analysis (p=0.0006). Increasing mPAP was associated with a statistically significant decline in 6MWD (p=0.02) and DSP (p=0.01). Patients with 'Pre-PH' had lower 6MWD compared to patients with mPAP≤20mmHg (p=0.07). CONCLUSIONS: Relative to measures of pulmonary function and hypoxia, altered pulmonary hemodynamics had a greater impact on 6MWD in patients with IPF. Higher mPAP was associated with more significant exercise impairment. Mild abnormalities in pulmonary hemodynamics (so called 'Pre-PH') were associated with reduced 6MWD.

Should lung transplantation be performed using donation after cardiac death? The United States experience.

OBJECTIVE: We compared 1) survival after lung transplantation of recipients of donation after cardiac death (DCD) versus brain death donor organs in the United States and 2) recipient characteristics. METHODS: Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to May 2007. Follow-up after DCD lung transplantation extended to 8.6 years, median 1 year. Differences among recipients of DCD versus brain death donor organs were expressed as a propensity score for use in comparing risk-adjusted survival. RESULTS: A total of 14,939 transplants were performed, 36 with DCD organs (9 single, 27 double). Among the 36 patients, 3 have died after 1 day, 11 days, and 1.5 years. Unadjusted survival at 1, 6, 12, and 24 months was 94%, 94%, 94%, and 87%, respectively, for DCD donors versus 92%, 84%, 78%, and 69%, respectively, for brain death donors (P = .04). DCD recipients were more likely to undergo double lung transplantation and have diabetes, lower forced 1-second expiratory volume, and longer cold ischemic times. Once these were accounted for and propensity adjusted, survival was still better for DCD recipients, although the P value equals .06. CONCLUSION: Concern about organ quality and ischemia-reperfusion injury has limited the application of lung DCD. However, DCD as practiced in the United States results in survival at least equivalent to that after brain death donation. It also demonstrates selection bias, particularly in performing double lung transplantation, making generalization regarding survival difficult. Nevertheless, the data support the expanded use of DCD.

Prognosis of patients removed from a transplant waiting list for medical improvement: implications for organ allocation and transplantation for status 2 patients.

OBJECTIVES: To address the present controversy regarding optimal management of status 2 heart transplant candidates, we studied the short- and long-term fate of medically improved patients removed from our transplant waiting list to assess return of heart failure and occurrence of sudden cardiac death, identify interventions to improve outcomes, and compare their survival with that of similar transplanted patients. METHODS: From January 1985 to February 2004, 100 status 2 patients were delisted for medical improvement (median on-list duration, 314 days). Return of heart failure, sudden cardiac death, and all-cause mortality were determined from follow-up (mean, 7.7 +/- 3.9 years among survivors; 10% followed >12 years). Hazard function modeling, competing-risks analyses, simulation, and propensity matching to equivalent patients undergoing transplantation were used to analyze and compare outcomes and predict benefit of interventions. RESULTS: Freedom from return of heart failure was 77% at 5 years. The most common mode of death was sudden cardiac death, with risk peaking at 2.5 years after delisting but remaining at 3.5% per year thereafter. Event-free survival at 1, 5, and 10 years was 94%, 55%, and 28%, respectively; simulation demonstrated that implantable cardioverter-defibrillators could have improved this to 45% at 10 years. Overall survival after delisting was better than that of matched status 2 patients who underwent transplantation, but was demonstrably worse after 30 months. CONCLUSIONS: Status 2 patients, including those delisted, require vigilant surveillance and optimal medical management, implantable cardioverter-defibrillators, and a revised approach to transplantation timing, such that overall salvage is maximized while allocation of scarce organs is optimized.

Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation.

Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (-0.02, 0.07) with P = 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (>12 ng/mL), P = 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT.

Atrial fibrillation after lung transplantation: timing, risk factors, and treatment.

BACKGROUND: Atrial fibrillation (AF) is common after lung transplantation and can be challenging to manage. Objectives of this study were to determine prevalence and timing of perioperative AF, identify its risk factors, evaluate treatment strategies, assess return to sinus rhythm by hospital discharge, and investigate its impact on outcomes. METHODS: From March 1995 to January 2005, 333 patients underwent primary lung transplantation (exclusive of heart and lung transplantation). Data on timing, prevalence, management, and outcome were extracted from the Unified Transplant Registry and Cardiothoracic Anesthesia databases, supplemented with medical record review. Risk factors for AF were identified by logistic regression analysis, and bootstrap bagging was used for variable selection. RESULTS: AF developed postoperatively in 68 patients (20%), with the peak incidence 2 days after operation. Risk factors were older age (p = 0.0004), primary pulmonary hypertension (5 of 12 [42%] versus 63 of 321 [20%] for others, p = 0.006), and extremes of weight (p = 0.04). Pharmacologic treatment consisted of rate control agents only in 18 patients (27%), antiarrhythmics only in 5 (7.5%), and both in 44 (66%). Cardioversion was required in 24 (36%). Rhythm was recorded for 59 patients, and 55 (93%) were in sinus rhythm at discharge. Postoperative AF had no short-term or long-term survival impact. CONCLUSIONS: AF after lung transplantation is common, with occurrence peaking 2 days postoperatively. Older patients and those with primary pulmonary hypertension are at elevated risk. Treatment requires a combination of multiple pharmacologic agents and electrical cardioversion. Almost all patients are discharged in sinus rhythm, and prognosis is unaffected.

Lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Outcomes of lung transplantation for idiopathic pulmonary fibrosis (IPF) are thought to be worse than those for other indications, although the reasons are unknown. In addition, the choice of single versus double lung transplantation is unclear. To guide decision-making, we (1) compared survival of patients receiving transplantation for IPF with survival of patients receiving transplantation for non-IPF diagnoses, (2) identified risk factors for mortality after transplantation for IPF, and (3) ascertained whether double lung transplantation for IPF confers a survival advantage. METHODS: From February 1990 to November 2005, 469 patients underwent lung transplantation, 82 for IPF. Multiphase hazard modeling was used to identify risk factors, and propensity matching was used to compare survival of IPF and non-IPF patients and to assess the effect of single versus double lung transplantation. RESULTS: Survival estimates after transplantation for IPF were 95%, 73%, 56%, and 44% at 30 days and 1, 3, and 5 years, somewhat worse than for matched non-IPF patients (p = 0.03). Risk factors for mortality were earlier date of transplantation (p = 0.07), single lung transplantation (p = 0.03), and higher wedge pressure (p = 0.003). Survival for double versus single lung transplantation was 81% versus 67% at 1 year and 55% versus 34% at 5 years; however, among matched non-IPF patients, corresponding survivals were 88% versus 71% at 1 year and 72% versus 48% at 5 years (p = 0.3). CONCLUSIONS: Survival after lung transplantation for IPF is worse than after other indications for transplantation when multiple clinical variables are accounted for. Survival may be improved by double lung transplant.

Surgical treatment of postinfarction left ventricular pseudoaneurysm.

BACKGROUND: Left ventricular pseudoaneurysm from myocardial infarction is rare and is associated with a high risk of rapid enlargement and rupture. The purposes of this study were to describe its clinical presentation, assess the accuracy of diagnostic imaging modalities, and determine operative and late surgical results. METHODS: From January 1986 through December 2001, 30 patients aged 50 to 85 years (mean, 68; 70% male) underwent left ventricular pseudoaneurysm repair. Two surgical approaches were used: primary repair (n = 5, 17%) and patch closure (n = 25, 83%). Twenty-one patients (70%) had concomitant procedures, including coronary revascularization (n = 17, 57%) and mitral valve surgery (n = 9, 30%); 8 patients (29%) underwent emergent surgery. Clinical presentation, preoperative imaging data, and surgical outcomes were abstracted from medical records or obtained by patient follow-up. RESULTS: The most common clinical presentations were heart failure (n = 22, 73%) and angina (n = 11, 41%). Pseudoaneurysm was rarely suspected at clinical presentation. Contrast ventriculography was diagnostic in 54% of patients in whom it was performed, as opposed to 97% for two-dimensional echocardiography (p = 0.2). Postoperative intra-aortic balloon pump was required in 7 patients (23%). Hospital mortality was 20%, and late survival was 73%, 59%, and 45% at 1, 5, and 8 years, respectively. CONCLUSIONS: Left ventricular pseudoaneurysm should be suspected in postinfarction patients with unexplained heart failure. Echocardiography is usually diagnostic and is superior to ventriculography. The surgical mortality rate is elevated in this complex patient population. Long-term survival is also poor, mainly because of underlying ischemic cardiomyopathy.

Characterization and importance of air leak after lobectomy.

BACKGROUND: Air leak after pulmonary resection is a common occurrence that is incompletely characterized. Our objectives were to determine prevalence of air leak and identify its risk factors, characterize its duration and discover its correlates, and evaluate its clinical importance. METHODS: Air leak was studied in 319 patients undergoing isolated anatomic lobectomy between January 1998 and July 2001. Risk factors for air leak were identified by logistic regression of patient characteristics, indications for lobectomy, lobe resected, and fissure management. Factors associated with air leak duration were sought by time-related analysis. Association of complications with air leak was evaluated by propensity-matched pairs analysis. RESULTS: Prevalence: Air leak prevalence was 58% (186 patients). It occurred less frequently after left lower lobectomy (p < 0.0001) and later in the series (p = 0.008). It was surgeon dependent (p = 0.007) but not associated with forced expiratory volume in 1 second. DURATION: The 10th, 50th, and 90th percentiles of air leak duration were 1.6, 3, and 7 days, respectively. No factors, including fissure management, were reliably associated with air leak duration. IMPORTANCE: Air leak was associated with more complications (30% vs 18%, p = 0.07) and protracted hospital course (p = 0.02). CONCLUSIONS: Postoperative air leak is a common occurrence after lobectomy, but fortunately it is self-limiting in most patients. Air leak is independently associated with longer hospital stay and other postoperative complications. Surgical technique is important and may be the only modifiable factor.

Elephant trunk procedure: newer indications and uses.

BACKGROUND: The elephant trunk procedure is used for extensive aortic aneurysms. We evaluated its safety, newer indications, and influence of second-stage completion on survival. METHODS: Records were reviewed for 94 consecutive patients (age 67 +/- 11 years, 47% men) who underwent the procedure between November 1990 and February 2003. The trunk was implanted as an extension of the ascending aorta and arch graft in 83 of 94 (88.3%) patients, distal arch graft in 8 of 94 (8.5%) patients, and in 3 distal to the left subclavian artery (3 of 94 patients [3.2%]). Aortic dissection was present in 37 (39.4%) patients and Marfan syndrome was present in 7 (7.4%). Twenty-three were reoperations (24.5%). In 9 patients, the trunk procedure was adjunctive in preparation for the second operation. In 15 patients, the anastomosis was completed between the left subclavian and common carotid arteries. Coronary artery bypass was performed in 36 (38.4%) and aortic valve operation in 55 (58.5%; 20 root sparing repairs, 16 composite grafts and 19 replacements) patients. RESULTS: There were two early 30-day in-hospital deaths (2.1%) and 5 permanent strokes (5.3%). Eleven died before the second-stage procedure. Forty-seven (57%) underwent second-stage procedures; 40 by thoracotomy and 7 by stent graft insertion, including 2 thoracoabdominal aneurysm repairs with visceral bypasses before stent grafting with 4 early deaths (8.5%). Five-year survival was 34% without a second-stage procedure versus 75% 3-year survival with it. CONCLUSIONS: With a current total of 142 elephant trunk procedures, we found it is safe and should be used more with initial cardiac surgery before descending or thoracoabdominal aorta repair.

Does preoperative atrial fibrillation reduce survival after coronary artery bypass grafting?

BACKGROUND: Preoperative atrial fibrillation has been identified as a risk factor for reduced long-term survival after coronary artery bypass grafting. This study sought to determine whether atrial fibrillation is merely a marker for high-risk patients or an independent risk factor for time-related mortality. METHODS: From 1972 to 2000, 46,984 patients underwent primary isolated coronary artery bypass grafting; 451 (0.96% prevalence) had electrocardiogram-documented preoperative atrial fibrillation (n = 411) or flutter (n = 40). Characteristics of patients with and without atrial fibrillation were contrasted by multivariable logistic regression to form a propensity score. With this, comparable groups with and without atrial fibrillation were formed by pairwise propensity-matching to assess survival. RESULTS: Patients with preoperative atrial fibrillation were older (67 +/- 9.0 versus 59 +/- 9.8 years, p < 0.0001), had more left ventricular dysfunction (66% versus 52%, p < 0.0001) and hypertension (73% versus 59%, p < 0.0001), but less severe angina (39% moderate or severe versus 49%, p < 0.0001). Many of these factors are themselves predictors of increased time-related mortality. In propensity-matched patients, survival at 30 days and at 5 and 10 years for patients with versus without atrial fibrillation was 97% versus 99%, 68% versus 85%, and 42% versus 66%, respectively, a survival difference at 10 years of 24%. Median survival in patients with atrial fibrillation was 8.7 years versus 14 years for those without it. CONCLUSIONS: Atrial fibrillation in patients undergoing coronary artery bypass grafting is a marker for high-risk patients; in addition, atrial fibrillation itself substantially reduces long-term survival. Thus, if patients in atrial fibrillation require surgical revascularization, it is appropriate to consider performing a concomitant surgical ablation procedure.

The Carbomedics Top Hat supraannular aortic valve: a multicenter study.

BACKGROUND: Introduced in 1993, the Carbomedics Top Hat (Sulzer, Carbomedics, Austin, TX) valve is a bileaflet mechanical aortic prosthesis designed to be placed in a supraannular position. Five institutions pooled their clinical experiences to evaluate early outcome in patients with this prosthesis. METHODS: From 1994 to 2000, 639 patients underwent aortic valve replacement with Top Hat (Sulzer Carbomedics) valves at 5 institutions. Mean age was 60 +/- 13 years. In this heterogeneous population, 28% of patients had previous cardiac operations and 64% had concomitant procedures, including procedures involving more than 1 heart valve in 32%. Implanted prostheses sizes included the 19 mm (15%), 21 mm (37%), 23 mm (33%), 25 mm (13%), and 27 mm (2%). Mean follow-up was 2.0 +/- 1.5 years, and there were 1,206 patient-years of follow-up available for analysis. RESULTS: Thirty-day mortality was 5.3%. Five-year survival was 74%. Risk factors for death included older age (p = 0.01), decreased ejection fraction (p = 0.007), and increased New York Heart Association functional class (p = 0.003). Five-year freedoms from thromboembolism and hemorrhage were 90% and 85%, respectively. Five-year freedoms from explant and endocarditis were both 99%. There were no structural valve failures. CONCLUSIONS: The Top Hat valve outcomes have been similar to those of the standard Carbomedics intraannular prostheses. The unique design of the Top Hat valve, with all its components in the aortic sinuses, has particular advantages in the small aortic root, in settings where leaflet entrapment may occur, and in multiple valve replacement.