Comparison of heart transplantation patients with ischemic and idiopathic dilated cardiomyopathy

ObjectiveWe retrospectively analyzed our data to compare preoperative demographic, laboratory, echocardiographic, hemodynamic findings mortality and survival rates of heart transplantation patients with ischemic (ICM) and idiopathic dilated (IDCM) cardiomyopathy.MethodsThe data of 144 patients transplanted from February 1998 to January 2011 were analyzed. 38 patients with ischemic ICM and 86 patients with IDCM were compared.ResultsRecipient age, preoperative creatinine, recipient body mass index, intraoperative cross-clamp time, donor male sex ratio, recipient male sex ratio, hyperlipidemia ratio, and previous nitrate use were significantly higher and left ventricular end systolic diameter significantly lower in patients with ICM. Major causes of death after heart transplantation were infections (31.9%), right ventricle failure (14.8%), and sudden cardiac death (14.8%). Causes of death were not different between the groups. Overall mortality in the entire population was 37.9% (47/124), and it was not different between the groups (39.5% vs 37.2%; P = .48). Early mortality (<30 days) rate was 11.2% (14/124), late mortality rate was 26.6% (33/124), and no statistically significant difference was observed between the groups. Survival analysis showed that ICM patients were not associated with worse survival compared with IDCM (71.1% vs 81.1% after 1 year, 68.1% vs 73.0% at 2 years, and 54.2% vs 62.3% at 5 years; log rank = 0.57). Multivariate analysis showed that the only predictor of mortality was preoperative urea level and that heart failure etiology was not a predictor of this end point.ConclusionsPatients with ICM had similar survival and mortality rate compared with IDCM.     

Smoking After Cardiac Transplantation

Although smoking cessation is a prerequisite prior to listing for cardiac transplantation, some patients return to smoking after recovery. We have covertly assessed the smoking habits of our cardiac transplant recipients (with ethical approval) since 1993 by measuring urinary cotinine: a level of >500 ng/mL signifying continued tobacco use. We retrospectively analyzed survival, causes of death and the development of graft coronary artery disease (GCAD) with respect to the number of positive and negative cotinine levels. One hundred four of 380 (27.4%) patients tested positive for active smoking at some point posttransplant, and 57 (15.0%) tested positive repeatedly. Smokers suffered significantly more deaths due to GCAD (21.2% vs. 12.3%, p < 0.05), and due to malignancy (16.3% vs. 5.8%, p < 0.001). In univariate analysis, smoking after heart transplantation shortened median survival from 16.28 years to 11.89 years. After correcting for the effects of pretransplant smoking in time-dependent multivariate analysis, posttransplant smoking remained the most significant determinant of overall mortality (p < 0.00001). We conclude that tobacco smoking after cardiac transplantation significantly impacts survival by accelerating the development of graft vasculopathy and malignancy. We hope that this information will deter cardiac transplant recipients from relapsing, and intensify efforts in improving cessation rates.     

Cyclosporine treatment of high dose and long duration reduces the severity of graft coronary artery disease in rodent cardiac allografts.

BACKGROUND: Graft coronary artery disease (GCAD) limits allograft survival after cardiac transplantation. The objective of this study was to correlate GCAD with the level of immunosuppression in an established allogeneic rodent cardiac chronic rejection model to better understand the mechanisms of GCAD in this system. METHODS: Donor PVG hearts were transplanted into the abdomen of ACI rats. Six recipient groups received either 10, 7.5 or 5 mg/kg/day of oral cyclosporine (CsA), for 90 (10 mg/90 d, 7.5 mg/90 d, 5 mg/90 d) or 10 days (10 mg/10 d, 7.5 mg/10 d, 5 mg/10 d; n = 10 all groups), and grafts procured on Day 90. GCAD was assessed by histology for percent luminal narrowing (%LN), percent affected vessels (%AV) and intima/media ratio (I/M ratio). Sections were stained for ED1-positive macrophages and MHC Class II-positive cells. RESULTS: The 10 mg/90 d treatment group showed significantly reduced GCAD compared with the 5mg/10d treatment group (%LN = 4.3 +/- 3.1% vs 39 +/- 11.9%, p < 0.05). The 7.5 mg/90 d group had a reduced %LN and I/M ratio compared with the 5 mg/10 d group (%LN = 8.0 +/- 3.5% vs 39 +/- 11.9%, p < 0.05; I/M ratio = 0.06 +/- 0.02 vs 0.41 +/- 0.14, p < 0.05). There was a trend toward reduction of GCAD with both increasing the dose of CsA as well as the duration of treatment. Continuous treatment with CsA reduced perivascular macrophage and MHC II cell infiltration. Macrophage infiltrates correlated strongly with GCAD (R(2) > 0.90, p < 0.01), and MHC II infiltrates showed a weak correlation, although not statistically significant (R(2) > 0.56, p = NS). CONCLUSIONS: This study further defines the effect of cyclosporine on GCAD in this cardiac transplantation model. In this system, higher dose and longer duration of treatment with CsA markedly reduces macrophage and MHC II infiltration, correlating with diminished GCAD. However, increasing dose and duration of CsA did not completely eliminate the development of GCAD. Non-immunologic factors could contribute to this occurrence.     

Bcl-2-mediated inhibition of apoptosis in rat cardiac allografts worsens development of graft coronary artery disease.

BACKGROUND: We hypothesized that adenovirally mediated Bcl-2 transfection of donor hearts would reduce the apoptosis that occurs during acute rejection while worsening the development of chronic graft coronary artery disease (GCAD). METHODS: PVG donor hearts were treated with either AdvBcl-2 or AdvNull virus before heterotopic transplantation into ACI rats. Bcl-2 expression was assessed on post-operative day 4 (POD) 4 by western blot. Apoptosis was measured using (99m)Technetium-bound-annexin V imaging and caspase 3 activity assay. Allograft survival was determined in a separate cohort of animals. Long-term-treated animals were then assessed for measures of GCAD on POD 90. RESULTS: Western blot analysis showed upregulation of Bcl-2 expression in AdvBcl-2-treated hearts. (99m)Tc-annexin V images demonstrated decreased uptake in the AdvBcl-2 group (1.41 +/- 0.33% vs 1.94 +/- 0.37%, p = 0.026). Caspase 3 activity was also significantly lower in this treatment group (0.112 +/- 0.032 vs 0.204 +/- 0.096, p = 0.049). Allograft survival was similar in both groups, respectively (7.7 +/- 1.2 vs 6.8 +/- 1.5 days, p = 0.340). GCAD, as determined by percent luminal narrowing (5.9 +/- 6.1% vs 1.6 +/- 1.5%, p = 0.039), intima-to-media ratio (5.1 +/- 5.1% vs 1.5 +/- 1.7%, p = 0.040) and percent of affected vessels (15.1 +/- 9.9% vs 5.3 +/- 4.4%, p = 0.009), was higher for the AdvBcl-2 group. CONCLUSION: Treatment of cardiac allografts with AdvBcl-2 resulted in a reduction of apoptosis that did not significantly improve short-term graft survival, but worsened chronic GCAD.     

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

BACKGROUND: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. METHODS: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. RESULTS: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. CONCLUSION: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.     

Sudden death and tailored medical therapy in elective candidates for heart transplantation.

BACKGROUND: Due to the shortage of donor organs there is a long waiting time for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored medical therapy optimized according to the individual patients demands was introduced to select responding HTx candidates for continued management without transplantation. The development of modes of death over time (heart failure, sudden arrhythmic) in this population is unknown. METHODS: In 434 elective candidates for heart transplantation, submitted to our institution in the years 1984-1997 (50% coronary artery disease, mean age 51.6 +/- 12 years, 86% males) medical therapy was adjusted according to the results of repeated right heart catherizations. Adjuncts to conventional therapy with ACE inhibitors, digitalis and diuretics were amiodarone, beta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. Only patients not responding to these measures were processed to HTx. Clinical events (death, mode of death, HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to patients characteristics by multivariance analysis. RESULTS: During the mean follow-up of 2.36 +/- 2.4 years only 113 patients (25%) received a donor heart. One hundred-sixteen patients (26%) died without transplantation. Eighty-three (72%) of the deaths were sudden, 24 (20%) due to progression of heart failure and 9 (8%) due to other reasons. A shift from heart failure to sudden death was observed. Including 8 successful resuscitations due to documented VT/VF, there is a 20% risk of having a major arrhythmic event during the first two years of observation. Long-term (>1 year) medical responders had better hemodynamics at entry. Patients who died suddenly had similar clinical and hemodynamic data at entry than patients who needed an early transplant, but were in a comparable NYHA stage before death than long-term medical responders (2.15 +/- 0.8 vs 1.82 +/- 0.6, NS). Patients dying suddenly had significant more ventricular premature beats (1.6 +/- 2.9%/24 hours vs 1.06 +/- 2.8%/24 hours, p < .01) and complex ventricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p < .01) than long-term responders. Seventy-five percent of all sudden death occurred during the first 2 observation years. CONCLUSIONS: The rate of heart failure death in elective candidates for heart transplantation under optimized medical therapy is low when patients are followed closely and transplant can be done rapidly after deterioration is recognized. Sudden death represents the highest risk for most patients. This event occurred predominantly in stable patients under tailored medical therapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic measures in this population.     

The incidence and significance of late acute cellular rejection (>1000 days) after liver transplantation

Acute cellular rejection (ACR) after liver transplantation occurs in as much as 70% of patients within the first year. There is very little known about ACR that occurs more than 1 yr after transplant, and it is generally believed that late occurring ACR may be more resistant to medical treatment and is associated with a higher rate of chronic ductopenic rejection and graft loss. A total of 532 recipients with more than 1000 d follow-up and who did not have hepatitis C were identified. Forty-three (8.1%) had biopsy proven late ACR at a mean of 1545 +/- 441 d post-transplant. Additionally, 38 of the 43 (88.4%) patients with late ACR had earlier episodes of ACR before 1000 d post-transplant vs. only 295 of the 488 patients (60.5%) that did not have late ACR (p < 0.01). The incidence of primary sclerosing cholangitis (PSC) was 32.6% among patients with late ACR and 11.1% among patients without late ACR (p < 0.01). The overall patient survival for patients who had late ACR (n = 43) is 81.4% while for patients without late ACR (n = 488) it is 82.0% (p = ns). Patients remain at risk for ACR even after 1000 d post-transplant, particularly those with PSC.     

Increased reduction in exsanguination rates leaves brain injury as the only major cause of death in blunt trauma

IntroductionCentral nervous system (CNS) related injuries and exsanguination have been the most common causes of death in trauma for decades. Despite improvements in haemorrhage control in recent years exsanguination is still a major cause of death. We conducted a prospective database study to investigate the current incidence of haemorrhage related mortality.Materials and methodsA prospective database study of all trauma patients admitted to an urban major trauma centre between January 2007 and December 2016 was conducted. All in-hospital trauma deaths were included. Cause of death was reviewed by a panel of trauma surgeons. Patients who were dead on arrival were excluded. Trends in demographics and outcome were analysed per year. Further, 2 time periods (2007–2012 and 2013–2016) were selected representing periods before and after implementation of haemostatic resuscitation and damage control procedures in our hospital to analyse cause of death into detail.Results11,553 trauma patients were admitted, 596 patients (5.2%) died. Mean age of deceased patients was 61 years and 61% were male. Mechanism of injury (MOI) was blunt in 98% of cases. Mean ISS was 28 with head injury the most predominant injury (mean AIS head 3.4). There was no statistically significant difference in sex and MOI over time. Even though deceased patients were older in 2016 compared to 2007 (67 vs. 46 years, p < 0.001), mortality was lower in later years (p = 0.02). CNS related injury was the main cause of death in the whole decade; 58% of patients died of CNS in 2007–2012 compared to 76% of patients in 2013–2016 (p = 0.001). In 2007–2012 9% died of exsanguination compared to 3% in 2013–2016 (p = 0.001).DiscussionIn this cohort in a major trauma centre death by exsanguination has decreased to 3% of trauma deaths. The proportion of traumatic brain injury has increased over time and has become the most common cause of death in blunt trauma. Besides on-going prevention of brain injury future studies should focus on treatment strategies preventing secondary damage of the brain once the injury has occurred     

The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is associated with the development of graft coronary artery disease (GCAD) following cardiac transplantation. This study assessed whether technetium 99m ((99m)Tc)-labeled MCP-1 binds its receptors in chronic cardiac transplants and thereby provides a potential modality to assess GCAD. METHODS: Allogeneic (PVG-->ACI, n = 9) and syngeneic (ACI-->ACI, n = 9) rat heterotopic heart transplants were performed. Allograft recipients were treated with 7.5 mg/kg per day of Cyclosporin A for 10 days until tolerance was achieved. After 90 days, animals were injected intravenously with (99m)Tc-MCP-1 and killed after 1 hour. Radioactivity of heart tissues was measured and standardized to uptake in the overall blood pool. Two-dimensional (99m)Tc-MCP-1 uptake (autoradiographs) was imaged by exposing 50-microm sections on a phosphoimager overnight. ED-1 staining of monocyte/macrophages was performed on serial sections. Additional sections were stained with elastin von Gieson and hematoxylin. Hearts were scored for luminal narrowing and intima/media ratio (I/M) with computerized image analysis. RESULTS: Allografts exhibited significantly more luminal narrowing (22.5 +/- 10.7% vs 2.6 +/- 4.6, p = 0.0005) and higher I/M (0.173 +/- 0.151 vs 0.015 +/- 0.029, p = 0.0088) than isografts. The ratio of (99m)Tc-MCP-1 uptake in allografts (1.04 +/- 0.4) was greater than that of isograft controls (0.72 +/- 0.11, p = 0.03). Pixel counts of autoradiographs and ED-1-stained sections demonstrated a modest correlation between the two (R(2) = 0.50). No significant differences were seen in acute rejection scores. CONCLUSION: (99m)Tc-MCP-1 uptake was higher in allografts vs isografts and was consistent with a greater degree of GCAD. These data demonstrating increased radiopharmaceutical uptake in hearts with GCAD provide a foundation for the development of a potentially non-invasive imaging assay of this disease process in heart transplantation.     

Sudden and cardiac death rates in hemodialysis patients

BACKGROUND: Sudden and cardiac death (including death from congestive heart failure, myocardial infarction, and sudden death) are common occurrences in hemodialysis patients. The intermittent nature of hemodialysis may lead to an uneven distribution of sudden and cardiac death throughout the week. The purpose of this study was to assess the septadian rhythm of sudden and cardiac death in hemodialysis patients. METHODS: Data from the United States Renal Data System (USRDS) were obtained to examine the day of death for United States hemodialysis and peritoneal dialysis patients from 1977 through 1997. The days of death were also determined for patients in the Case Mix Adequacy Study of the USRDS. RESULTS: There was an even distribution of sudden and cardiac deaths for patients on peritoneal dialysis, and hemodialysis patients dying of noncardiac deaths also had an even distribution. For all hemodialysis patients, Monday and Tuesday were the most common days of sudden and cardiac death. For patients in the Case Mix Adequacy Study designated as Monday, Wednesday, and Friday dialysis patients, 20.8% of sudden deaths occurred on Monday compared with the 14.3% expected (P = 0.002). Similarly, 20.2% of cardiac deaths occurred on Monday compared with the 14.3% expected (P = 0.0005). Similar trends were found on Tuesday for Tuesday, Thursday, and Saturday dialysis patients. CONCLUSIONS: The intermittent nature of hemodialysis may contribute to an increased sudden and cardiac death rate on Monday and Tuesday for patients enrolled in the USRDS.     

Long-term outcome of Hepatitis B-positive renal allograft recipients after development of antiviral treatment

Background/Aims: Hepatitis B virus (HBV) infection can adversely affect the clinical outcome of kidney transplantation (KT). Short-term efficacy of lamivudine has been demonstrated for chronic hepatitis B in KT recipients (KTR). Methods: To clarify the long-term impact of antiviral treatment for HBV-positive KTR, we retrospectively reviewed 94 HBV-positive (male 73%) and 282 age/sex-matched HBV-negative patients who underwent KT from February 1997 to November 2009, after lamivudine had come into wide use. Results: Mean follow-up was 75.7 months. 56 patients received antiviral agent for prophylaxis, and other 18 for HBV reactivation. During follow-up, 15 died, with 5 deaths being HBV related. Although the patient survival rate was lower for HBVpositive than HBV-negative KTRs (89% vs. 94% at 5 years, 78% vs. 88% at 10 years, p = 0.031), graft survival was comparable (86% vs. 92% at 5 years, 73% vs. 81% at 10 years, p = 0.113). In multivariate analysis, HBsAg positivity was a significant risk factor for patient death (OR 2.19, 95% CI 1.14 - 4.20, p = 0.019), but not significant for graft loss (OR 1.64, 95% CI 0.94 - 2.86, p = 0.079). Of the 26 hepatitis B e antigen (HBeAg)-positive patients, 14 experienced HBV reactivations, but all survived with stable liver chemistry, except for one who died of hepatocellular carcinoma. Among 57 HBeAg-negative patients, 12 died, whereas the remaining 45 survived without hepatic dysfunction. Conclusion: Long-term outcomes of HBV-positive KTRs may be favorable after antiviral agents have been introduced.     

Patients with postoperative atrial fibrillation have a doubled cardiovascular mortality

Objectives. To investigate the impact of postoperative AF on late mortality and cause of death in CABG patients. Design. All CABG patients without preoperative AF surgically treated between January 1, 1997 and June 30, 2000 were included (N = 1419). Altogether, 419 patients (29.5%) developed postoperative AF. After a median follow-up of 8.0 years, survival data were obtained, causes of death were compared and Cox proportional hazard analysis was used to determine predictors of late mortality. Results. The total mortality was 140 deaths/419 patients (33.4%) in postoperative AF patients and 191 deaths/1 000 patients (19.1%) in patients without AF. Death due to cerebral ischemia (2.6% vs. 0.5%), myocardial infarction (7.4% vs. 3.0%), sudden death (2.6% vs. 0.9%), and heart failure (6.7% vs. 2.7%) was more common among postoperative AF patients. Postoperative AF was an age-independent risk indicator for late mortality with a hazard ratio (HR) of 1.56 (95% confidence interval 1.23–1.98). Conclusions. Postoperative AF is an age-independent risk factor for late mortality in CABG patients, explained by an increased risk of cardiovascular death.     

Risk factors for sudden death after repair of tetralogy of Fallot

BACKGROUND: Sudden cardiac death remains the most common cause of death after repair of tetralogy of Fallot. It has been suggested that sudden cardiac death is related to right ventricular hypertrophy or dilation. However, it is uncertain whether the preoperative patient status or operative techniques predispose for sudden cardiac death. METHODS: From 1958 to 1977, 658 patients underwent repair of tetralogy of Fallot at our institution at a median age of 12.2 +/- 8.6 years. One third had at least one previous palliative operation 4.6 +/- 2.5 years earlier. A total of 490 patients survived the first postoperative year and were analyzed for sudden cardiac death. During a follow-up period of 25.3 +/- 5.8 years (range, 1.0 to 35.5 years), 42 patients died, and 15 (36%) of those deaths were as a result of sudden cardiac death. RESULTS: Actuarial 10-year, 20-year, and 30-year survival rates were 97%, 94%, and 89%. Freedom from sudden cardiac death was 99%, 98%, and 95% after 10, 20, and 30 years. The risk of sudden cardiac death increased after 10 years from 0.06%/y to 0.20%/y. Univariate predictors (p < 0.1) of sudden cardiac death were use of an outflow tract patch (p = 0.068), male sex (p = 0.048), no previous palliation (p = 0.013), and higher preoperative New York Heart Association status (p = 0.014). Multivariate analysis confirmed these risk factors except use of an outflow tract patch. CONCLUSIONS: The most important risk factors for sudden cardiac death were higher preoperative New York Heart Association class and no previous palliation. Thus, early surgical intervention is recommended. The risk of sudden cardiac death increases with time, suggesting that long-term follow-up by specialized cardiologists or pediatricians should be intensified. However, all patients who died suddenly had at least two risk factors at the time of surgery.     

Changing patient characteristics in chronic hemodialysis

Patients accepted to chronic hemodialysis have changed. We analyzed these changes and survival, cause of death and other factors during 23 years at the Karolinska Hospital. Between 1965 and 1987, 274 patients were accepted: 60 are alive on dialysis, 75 died, 113 were transplanted, 25 sent to other units and one recovered renal function. The mean age increased from 44 to 55 years (p=0.001), the creatinine level at acceptance decreased from 1191 to 965 mumol/l (p = 0.001), the hemoglobin level rose from 70 to 85 g/l (p = 0.001) and the diastolic blood pressure decreased from 96 to 90 mmHg (p = 0.007). The number of co-morbid conditions increased from 1.2 to 1.4 (p less than 0.005). The diagnoses changed from over 90% primary renal disease to 20% systemic diseases such as nephrosclerosis and diabetes (p = 0.04). The chance of receiving a renal transplant decreased from 46 to 39% (p = 0.28). The transplanted patients were younger than the dialyzed patients 42 vs 47 years (p = 0.03) before 1980 and 49 vs. 56 years (p = 0.0001) after 1980. The cause of death changed. Withdrawal from dialysis increased from 5% of deaths before to 24% after 1980 (p = 0.047), cardiovascular deaths decreased from 85% to 55% (p = 0.01). Although the patients accepted for dialysis after 1980 had more serious renal disease and other degenerative diseases than those before, the mortality rate was reduced to only 1/4 to that before, in all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value and cost-effectiveness of different screening strategies for HLA antibodies prior to kidney transplantation

HLA antibody screening is conducted routinely prior to kidney transplantation, but the comparative prognostic value and cost-effectiveness of different methods are unclear. Pre-transplant sera of 141 patients transplanted between 1998 and 2000 were screened by ELISA and Luminex assays, and antibody specificities of reactive sera determined using bead array techniques. ELISA screening detected donor-specific antibodies (DSA) in 19 patients, who had a higher incidence of impaired graft function (60% vs. 20%, p = 0.04) and antibody-mediated rejection (AMR) within 90 d after transplantation (AMR, 35% vs. 5%, p = 0.02). Luminex screening detected eight additional patients with DSA, among those one with AMR. Six of eight patients with Luminex-only-DSA reported no prior immunizing events. Death-censored graft survival was shorter only in patients with DSA and AMR (median, 1.7 yr instead of between 9.5 and 11.0 yr for patients without DSA or patients with DSA but no AMR, p < 0.001). Material costs per detected clinically relevant DSA were about 57% higher for Luminex screening, but this increase could be avoided by modifying the cut-off recommended by the manufacturer. Conclusively, specification of antibodies only in sera reactive in screening tests was cost-effective to prevent shortened graft survival. Preformed DSA were only harmful if AMR was diagnosed within 90 d after transplantation.     

Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients

In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.     

Preventable complications and death from multiple organ failure among geriatric trauma victims.

We reviewed 374 consecutive trauma patients over age 65 years to determine (1) if the emergency room Trauma Score (TS) could predict mortality, thereby improving ICU triage, and (2) the frequency of preventable complications in patients who died (n = 31). Fifty-two percent of deaths (n = 16) occurred in patients with TS = 15 or 16. Multiple organ failure/sepsis (MOF/S) was the most common cause of death overall (42%) and was also the most frequent cause of death in patients with a TS = 15-16 (63%). Nonsurvivors in the TS = 15-16 subgroup were older (80.9 +/- 2.0 vs. 74.9 +/- 0.5 years, p less than 0.02) and had greater ISSs (15.8 +/- 3.7 vs. 8.0 +/- 0.4, p = 0.001) than survivors. Patients with a TS less than 15 suffered high overall mortality (45%). Preventable complications contributed to mortality in 32% of all deaths and in 62% of MOF/S deaths. Aggressive care to prevent avoidable complications may improve survival in elderly trauma victims.     

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation

BACKGROUND: Successful bridging to transplantation (BTT) with ventricular assist devices (VAD) is an alternative to mitigate the effects of end-stage heart failure on organ function while awaiting a heart. The effects of long-term VAD BTT on patient outcomes following transplantation are poorly studied. METHODS: A retrospective chart review identified 145 patients BTT with a VAD between November of 1996 and June of 2005 at the Cleveland Clinic. Patients were divided into two groups and outcomes were compared: group 1 was supported for <100 days (median=44 days) and group 2 was supported for > or =100 days (median=161 days). RESULTS: Patients in group 1 were less likely to be blood type O (33% vs 68%, p<0.0001). BTT <100 days trended towards independently predicting improved survival by multivariate proportional hazards analysis (risk ratio=0.75, 95% CI=0.52-1.08, p=0.12), largely due to reduced in-hospital mortality in this group (2% vs 11%, p=0.055); however, no significant difference with respect to long-term survival was observed by Kaplan-Meier analysis (p=0.14). Furthermore, causes of death differed between groups: group 1 more commonly died of coronary artery vasculopathy (26% vs 0%, p=0.022) and group 2 more commonly died of sepsis (60% vs 26%, p=0.026). Ultimately, 21% of all group 2 patients died from sepsis (compared to 7% of group 1 patients, p=0.018). CONCLUSIONS: This study suggests that prolonged BTT with a VAD is a viable treatment strategy but may lead to significantly more post-transplant deaths from sepsis and higher in-hospital mortality. These data may inform management of this high-risk patient population.     

Selected patients listed for cardiac transplantation may benefit from defibrillator implantation regardless of an established indication.

BACKGROUND: End-stage heart failure (HF) patients are at high risk of sudden cardiac death. This study evaluates the role of implantable cardiac defibrillators (ICDs) in HF patients awaiting cardiac transplantation. METHODS: We identified 194 consecutive patients (age 51 +/- 12 years) with New York Heart Association Class 3 or 4 HF (ejection fraction 22 +/- 9%) listed for cardiac transplantation, 35 of whom underwent ICD implantation. Of the implanted patients, 16 (Group A) had an established indication for ICD implantation (cardiac arrest, n = 10; sustained ventricular tachycardia [VT], n = 3; and positive electrophysiology study, n = 3). Nineteen patients (Group B) underwent ICD implantation for non-established indications (syncope with non-ischemic cardiomyopathy, n = 4; non-sustained VT, n = 15). There were no procedural complications from ICD implantation. RESULTS: During follow-up of 9.2 +/- 10.1 months, there were 3 deaths in the ICD groups (A and B), and 40 in the control group (8.6% vs 25.2%, p = 0.032). Five patients in Group A and 6 in Group B (31%) received appropriate ICD therapy. The number of therapies per patient and the time to the first shock were similar between Groups A and B. Four of 6 Group B patients on outpatient inotropic therapy (67%) received appropriate ICD therapy. CONCLUSIONS: Selected end-stage heart failure patients awaiting heart transplantation, including those without established ICD indications, are at high risk for malignant arrhythmias and may benefit from ICD implantation. Patients with ICD seem to have improved survival compared to those without ICD. Randomized prospective studies are needed to confirm these findings.     

Increase in Malignancies as Cause of Death in Renal Transplant Patients

The Andalusian Kidney Transplant Registry is a Public Health Service Regional Registry of Andalusia, Spain. We have analyzed the causes of death among 5599 kidney transplantations performed between January 1, 1984 and December 31, 2007. The total number of patients who died after renal transplantation was 1106. Of these, 656 patients died with functioning renal grafts, which constituted the group analyzed in this study. No significant differences in the causes of death were observed as a function of age, sex, retransplant status, cause of end-stage renal disease, diabetes, and duration of the previous renal replacement therapy. Infections were the most frequent cause of death in the first year posttransplantation (early deaths). A significant difference was observed when these early deaths were compared with those that occurred after the first year posttransplantation (late deaths); there were fewer deaths due to infections (40.4% vs 15.9%, early vs late) and more deaths from cancer (4.9% vs 23.7%). The causes of death in the period 1984–1995 were compared with those in 1996–2007, excluding the deaths that occurred more than 12 years posttransplantation (not possible in the 1996–2007 periods n = 583). The causes of early death did not change. A significant difference was observed among late deaths with an increase in infections (14% vs 17%) and cancers (20% vs 29.7%). Thus, malignancies became the most frequent cause of late death in the 1996–2007 period. In conclusion, in our region, a long-term change in renal transplant patient mortality is taking place, with a significant increase in deaths due to cancer.