Hemodynamics during humoral rejection events with total versus standard orthotopic heart transplantation.
01 Oct 2004-Annals of Thoracic and Cardiovascular Surgery (Ann Thorac Cardiovasc Surg)-Vol. 10, Iss: 5, pp 285-289
TL;DR: ToHT offers improved hemodynamics during humoral rejection as evidenced by higher cardiac output and index with lower right atrial and pulmonary capillary wedge pressures.
Abstract: Purpose: We hypothesized that total orthotopic heart transplantation (TOHT) improves humoral rejection hemodynamics compared with biatrial transplantation or standard orthotopic heart transplantation (SOHT). Methods: We reviewed 1942 biopsies from 134 patients (pts) and right heart catheterization data obtained at endomyocardial biopsy. Biopsies that displayed humoral rejection by histological findings and positive immunofluorescence for immunoglobulins and complement were analyzed. Patients with pacemakers, atrial fibrillation or -blocker therapy at the time of biopsy were excluded. Thirty-two pts after TOHT and 22 after SOHT matching these criteria were identified. Results: Demographic data, underlying disease, pretransplant hemodynamics, and donor demographics were similar. Cardiac output and index were higher in the total orthotopic group (5.9±1.1 vs 5.1±1.4 L/min, p=0.027; 3.3±0.5 vs 2.8±0.6 L/min/m 2 , p=0.016). Right atrial and pulmonary capillary wedge pressure were lower after TOHT (7±3 vs 11±5 mmHg, p<0.001; 13±4 vs 16±5 mmHg, p=0.035). Pulmonary pressures, pulmonary vascular resistance and heart rate were similar. Conclusion: TOHT offers improved hemodynamics during humoral rejection as evidenced by higher cardiac output and index with lower right atrial and pulmonary capillary wedge pressures. Future studies must examine the potential benefits of TOHT during combined cellular and humoral rejection events. (Ann Thorac Cardiovasc Surg 2004; 10: 285‐9)
••01 Jul 2013
TL;DR: Patients with cardiac sarcoidosis undergoing heart transplantation have acceptable long-term outcomes without evidence of recurrence of sarcoideosis in the allograft when maintained on low-dose corticosteroids.
Abstract: Background Cardiac sarcoidosis with end-stage heart failure has a poor prognosis without transplantation The rates of sarcoid recurrence and rejection are not well established after heart transplantation Methods A total of 19 heart transplant recipients with sarcoid of the explanted heart were compared with a contemporaneous control group of 1,050 heart transplant recipients without cardiac sarcoidosis Assessed outcomes included 1st-year freedom from any treated rejection, 5-year actuarial survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from nonfatal major adverse cardiac events (NF-MACE), and recurrence of sarcoid in the allograft or other organs Patients with sarcoidosis were maintained on low-dose corticosteroids after transplantation Results There were no significant differences between the sarcoid and control groups in 1st-year freedom from any treated rejection (79% and 90%), 5-year posttransplantation survival (79% and 83%), 5-year freedom from CAV (68% and 78%), and 5-year freedom from NF-MACE (90% and 88%) Causes of death (n = 5) in the sarcoid group were coccidioidomycosis, pneumonia, rejection, hemorrhage, and CAV No patient had recurrence of sarcoidosis in the cardiac allograft Three of 19 patients (16%) experienced recurrence of extracardiac sarcoid, with no mortality Conclusions Patients with cardiac sarcoidosis undergoing heart transplantation have acceptable long-term outcomes without evidence of recurrence of sarcoidosis in the allograft when maintained on low-dose corticosteroids Progression of extracardiac sarcoid was uncommon, possibly related to immunosuppression In patients with cardiac sarcoidosis, heart transplantation is a viable treatment modality
TL;DR: The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.
Abstract: Background This retrospective single-center study compared lymphocyte depletion in 144 heart transplant recipients using 2 different induction protocols with Thymoglobulin (Genzyme Transplant, Cambridge, MA). Methods Thymoglobulin (1.5 mg/kg) was given to 105 patients for 7 days (Thymo7) and 39 patients for 5 days (Thymo5). Results Patient clinical characteristics were similar except that the Thymo7 group had a higher prevalence of women (33% vs 15%, p = 0.04), gender mismatch (35% vs 19%, p = 0.07), donor African American race (19% vs 2%, p = 0.008), older donor age (35 ± 13 vs 31 ± 12, p = 0.08), and higher pre-transplant creatinine (1.43 ± 0.67 vs 1.25 ± 0.48 mg/dl, p = 0.095). Seventy-five percent of the Thymo7 group reached target (absolute lymphocyte count ≤200) and 42% at 21 days ( p = 0.002). Thymo7 patients had significantly lower rejection rates (≥1B) within the first year (7% vs 22%, p = 0.02). No humoral rejection occurred. At 1 year, freedom from rejection was 93% in the Thymo7 group vs 80% in the Thymo5 group ( p = 0.007), and cytomegalovirus disease (9% and 5%, p = 0.5) and bacterial infection (26% vs 32%, p = 0.5) were similar. One-year actuarial survival was 92% ± 3% in the Thymo7 and 100% in the Thymo5 group ( p = 0.07), and at 3 years, 85 ± 4% and 90 ± 6%, respectively ( p = 0.4). Conclusions Both Thymoglobulin regimens were well tolerated. The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.
01 Dec 2011
TL;DR: HKT offers excellent survival and similar renal function when compared with HT alone, and patients with end-stage cardiac and renal failure can be considered for HKT.
Abstract: Background The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. Methods We reviewed the clinical outcomes of patients undergoing HKT (n = 30) or HT (n = 440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. Results There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P .05 for all comparisons). Conclusions HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.
••01 Dec 2011
TL;DR: Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients, and should not be excluded from transplant consideration based solely on an age criterion.
Abstract: Objective Advanced age has been viewed as a contraindication to orthotopic heart transplantation (OHT). We analyzed the outcome of OHT in patients who were aged 70 years or older and compared the results with those in younger patients during a two-decade period. Methods A total of 519 patients underwent first-time single-organ OHT at our institution from 1988 to 2009. Patients were divided into three groups by age: ≥ 70-years old (group 1, n = 37), 60 to 69-years old (group 2, n = 206), and ≤60-years old (group 3, n = 276). Primary endpoints were 30-days, and 1-, 5-, and 10-years survival. Secondary outcomes included re-operation for bleeding, postoperative need for dialysis, and length of postoperative intubation. Results There was no significant difference in survival between the greater than or equal to 70-year-old group and the two younger age groups for the first 10 years after OHT. Survival rates at 30 days, and 1-, 5-, and 10-years, and median survival in group 1 recipients were 100%, 94.6%, 83.2%, 51.7%, and 10.9 years (CI 7.1–11.0), respectively; in group 2 those numbers were 97.6%, 92.7%, 73.8%, 47.7%, and 9.1 years (CI 6.7–10.9), respectively; and in group 3 those numbers were 96.4%, 92.0%, 74.7%, 57.1%, and 12.2 years (CI 10.7–15.4; P = NS), respectively. There was no significant difference in secondary outcomes of re-operation for bleeding, postoperative need for dialysis, and prolonged intubation among the three age groups. Conclusions Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients. Advanced heart failure patients who are aged 70 years and older should not be excluded from transplant consideration based solely on an age criterion. Stringent patient selection, however, is necessary.
01 Jan 2016
TL;DR: Patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery, and VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival.
Abstract: Purpose The impact of prior implantation of a ventricular assist device (VAD) on short- and long-term postoperative outcomes of adult heart transplantation (HTx) was investigated. Methods Of the 359 adults with prior cardiac surgery who underwent HTx from December 1988 to June 2012 at our institution, 90 had prior VAD and 269 had other (non-VAD) prior cardiac surgery. Results The VAD group had a lower 60-day survival when compared with the Non-VAD group (91.1% ± 3.0% vs 96.6% ± 1.1%; P = .03). However, the VAD and Non-VAD groups had similar survivals at 1 year (87.4% ± 3.6% vs 90.5% ± 1.8%; P = .33), 2 years (83.2% ± 4.2% vs 88.1% ± 2.0%; P = .21), 5 years (75.7% ± 5.6% vs 74.6% ± 2.9%; P = .63), 10 years (38.5% ± 10.8% vs 47.6% ± 3.9%; P = .33), and 12 years (28.9% ± 11.6% vs 39.0% ± 4.0%; P = .36). The VAD group had longer pump time and more intraoperative blood use when compared with the Non-VAD group (P 48-hour ventilation and in-hospital infections (P = .0007 and .002, respectively). In addition, more VAD patients had sternal wound infections when compared with Non-VAD patients (8/90 [8.9%] vs 5/269 [1.9%]; P = .005). Both groups had similar lengths of intensive care unit (ICU) and hospital stays and no differences in the frequencies of reoperation for chest bleeding, dialysis, and postdischarge infections (P = .19, .70, .34, .67, and .21, respectively). Postoperative creatinine levels at peak and at discharge did not differ between the 2 groups (P = .51 and P = .098, respectively). In a Cox model, only preoperative creatinine ≥1.5 mg/dL (P = .006) and intraoperative pump time ≥210 minutes (P = .022) were individually considered as significant predictors of mortality within 12 years post-HTx. Adjusting for both, pre-HTx VAD implantation was not a predictor of mortality within 12 years post-HTx (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.77–1.97; P = .38). However, pre-HTx VAD implantation was a risk factor for 60-day mortality (HR, 2.86; 95% CI, 1.07–7.62; P = .036) along with preoperative creatinine level ≥2 mg/dL (P = .0006). Conclusions HTx patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery. VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival following HTx. Long-term (1-, 2-, 5-, 10-, and 12-year) survival did not differ significantly in HTx patients with prior VAD or non-VAD cardiac surgery.
TL;DR: Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.
Abstract: Background Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. Methods We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology (“swollen cells” distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). Results A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls ( p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. Conclusion Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.
TL;DR: It is concluded that immunofluorescence should be routinely done on all heart biopsies for the first month after transplantation, because patients with vascular (humoral) rejection cannot be reliably identified by any other means.
Abstract: We prospectively studied 551 sequential endomyocardial biopsies from 36 consecutive cardiac allografts. With the use of a combination of light microscopy (including careful evaluation of vascular changes) and immunofluorescence to detect the deposition of immunoglobulin and complement, we identified three patterns of allograft rejection, designated as cellular rejection, vascular (humoral) rejection, and mixed rejection. Cellular rejection was diagnosed with modified Billingham criteria. Vascular rejection was diagnosed by finding the combination of prominent endothelial cell swelling and/or vasculitis on light microscopy and the vascular deposition of immunoglobulin and complement by immunofluorescence. In such patients, cellular lymphoid infiltrates were uniformly absent at the time the vascular changes were detected. Mixed rejection consisted of findings of both cellular and vascular rejection occurring simultaneously. Twenty of 36 allografts exhibited cellular rejection; seven allografts showed vascular rejection, and nine allografts developed mixed rejection. The vascular (humoral) pattern of rejection was important to identify because the patients with this type of rejection had a significantly decreased survival compared with that of patients with cellular rejection (p less than 0.05). Survival in the mixed rejection category was intermediate. Positive donor-specific cross-match and/or panel-reactive antibody greater than or equal to 5% and systolic dysfunction were seen in three of the seven allografts with vascular (humoral) rejection but not in the other types. In the early period after transplant (up to 3 weeks after transplant), the only reliable identifying characteristics of patients with vascular (humoral) rejection were the presence of vascular immunoglobulin and complement assessed by immunofluorescence and endothelial cell swelling and interstitial edema as confirmed by histologic examination. We conclude that immunofluorescence should be routinely done on all heart biopsies for the first month after transplantation. Patients with vascular (humoral) rejection cannot be reliably identified by any other means.
"Hemodynamics during humoral rejecti..." refers background in this paper
...beta-blockers), and (3) absence of atrial fibrillation or other arrhythmias at the...
TL;DR: There is rapid resolution of moderately elevated pulmonary arterial pressures after cardiac transplantation, and echocardiographic analysis showed that transplant recipients had an enlarged right ventricle on day 1 after surgery, and a volume overload contraction pattern and tricuspid regurgitation was present in the majority.
Abstract: Most patients with severe congestive heart failure have secondary pulmonary hypertension (PHT). Elevation of pulmonary vascular resistance (PVR) to greater than 480 dynes.sec.cm-5 (6 Wood units) is currently the principle hemodynamic contraindication to orthotopic cardiac transplantation. We performed serial two-dimensional Doppler echocardiographic examinations and right heart catheterizations in 24 recipients (21 men, 14-58 years old) of orthotopic cardiac transplants to determine the time course of resolution of PHT and the concomitant remodeling of the donor right ventricle. Right and left heart filling pressures declined in parallel and reached the upper normal range at 2 weeks after the transplant procedure and remained unchanged at 1 year follow-up. Mean pulmonary arterial pressure (mm Hg) decreased from 38 +/- 9 preoperatively to 22 +/- 5 at 2 weeks and was 19 +/- 5 at 1 year after the transplantation procedure. At 1 year after surgery, PVR had decreased from 202 +/- 89 dynes.sec.cm-5 preoperatively to 99 +/- 36 dynes.sec.cm-5 (p less than .001), while cardiac output increased from 3.7 +/- 1.2 to 6.3 +/- 1.5 liters/min (p less than .001). Echocardiographic analysis showed that transplant recipients had an enlarged right ventricle on day 1 after surgery, and a volume overload contraction pattern and tricuspid regurgitation was present in the majority. This increase in right ventricular size was maintained at 1 year follow-up while the incidence of tricuspid regurgitation decreased. We conclude that there is rapid resolution of moderately elevated pulmonary arterial pressures after cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: An alternative technique of total orthotopic heart transplantation is described, where complete excision of the recipient's atria is undertaken.
Abstract: An alternative technique of total orthotopic heart transplantation is described. Complete excision of the recipient's atria is undertaken. Ventricular as well as atrial orthotopic transplantation is performed.