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Hillel Laks

Publications and source records attributed to Hillel Laks.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.

Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.

Biological Transport↗
PubMed2006

Aortic valve-sparing repair with autologous pericardial leaflet extension has a greater early re-operation rate in congenital versus acquired valve disease.

OBJECTIVE: We sought to establish whether there was a difference in outcome after aortic valve repair with autologous pericardial leaflet extension in acquired versus congenital valvular disease. METHODS: One hundred and twenty-eight patients underwent reparative aortic valve surgery at our institution from 1997 through 2005 for acquired or congenital aortic valve disease. The acquired group (43/128) (34%) had a mean age of 56.4+/-20.3 years (range, 7.8-84.6 years) and the congenital group (85/128) (66%) had a mean age of 16.9+/-19.2 years (range, 0.3-82 years). The endpoints of the study were mortality and reoperation rates. RESULTS: Thirty-day mortality was 0/43 (0%) in the congenital group and 1/85 (1.1%) in the acquired group. Late mortality in the acquired group was 3/43 (7%) and 3/84 (3.5%) in the congenital group (neither early nor late proportion of mortality is significantly different between the two groups, according to the nonparametric Binomial test for proportions). There were 13 total reoperations among 11 patients: 1/43 (2.3%) in the acquired group and 10/85 (11.7%) in the congenital group (p=0.07). Two patients from the congenital group were reoperated on twice. The mean interval between original repair and reoperation was 3.6+/-5 years (range, 0-7 years) for acquired and 3.5+/-2.5 years (range, 0-7 years) for the congenital group (Wilcoxon 2-sample test, p=0.7). Total early reoperation rate (<30 days after first surgery) was 11/128 (8.5%); for the congenital group 9/85 (10.5%) and for the acquired group 2/43 (4.6%). Early reoperation rate was significantly higher among the congenital group (p=0.013). The remaining patients are well at mean follow-up of 2.8+/-2.4 years (range 0-7.9). In the acquired group, the mean postoperative aortic regurgitation and stenosis grade by echocardiography was 0.5+/-0.3 (scale, 0-4) and 0.3+/-0.1, respectively. In the congenital group, the follow-up, mean aortic regurgitation and stenosis were 0.9+/-0.8 and 0.5+/-0.3, respectively. CONCLUSIONS: There was no significant difference in early or late mortality and late reoperation rate between the two groups. Early reoperation rate was higher in the congenital versus the acquired aortic valvular disease group. This study supports the fact that the valve-sparing technique is safe and reproducible and repeatable in patients with acquired valve disease.

Adolescent↗
PubMed2006

Exogenous IL-10 overexpression reduces perforin production by activated allogenic CD8+ cells and prolongs cardiac allograft survival.

Perforin is a cytolytic mediator produced by cytotoxic T cells (CD8(+) cells) and natural killer cells. We previously reported that ex vivo IL-10 gene therapy induced apoptosis of allogenic infiltrative CD8(+) cells and significantly prolonged cardiac allograft survival. To further test the hypothesis that localized IL-10 overexpression in cardiac allografts may also effect the alloreactive CD8(+) T cell function by downregulating its perforin production, we used a rabbit functional heterotopic allograft heart transplant model. Human recombinant IL-10 gene complexed with liposome was intracoronary delivered into the cardiac allografts ex vivo. The percentage of apoptotic infiltrative CD8(+) cells in cardiac allografts was increased 6-fold in the gene therapy group vs. the control group, whereas the percentage of perforin-positive CD8(+) cells was decreased 2.9-fold (P < 0.01). Perforin expression level in the allograft myocardium of the gene therapy group was deceased 3.2-fold (P < 0.01). The amount of infiltrative perforin-positive CD8(+) cells and perforin expression level were inversely correlated with IL-10 transgene and protein expression level in the myocardium of cardiac allografts (P < 0.01), the percentage of apoptotic cardiac myocytes (P < 0.01), and the peak left ventricular systolic pressure of cardiac allografts (P < 0.01) but significantly correlated with the infiltrative T cell cytotoxicity (P < 0.01) and allograft rejection score (P < 0.01). These results suggest that localized IL-10 gene therapy prolongs cardiac allograft survival, at least in part, through downregulation of perforin production by activated allogenic CD8(+) T cells. Reduction of cytolytic function of cytotoxic effector cells prevents the apoptosis of cardiac myocytes.

Animals↗
PubMed2006

Risk factors for early death and reoperation following biventricular repair of pulmonary atresia with intact ventricular septum.

OBJECTIVE: Since a functional right ventricle is desirable when repairing pulmonary atresia with intact ventricular septum, we sought to determine the factors that portend a successful biventricular repair in these children. METHODS: A review of operative records at UCLA between 1982 and 2001 revealed 56 patients diagnosed with pulmonary atresia with intact ventricular septum that underwent either a partial (n=26) or complete biventricular repair. Kaplan-Meier survival curves with log rank statistics were used to evaluate the influence of demographic, technical, and anatomic factors on survival and need for reoperation. RESULTS: Five-year actuarial survival following biventricular repair was 91.5%. Non-Caucasian race (p=0.011) and omission of palliative right ventricular outflow tract obstruction (RVOTO) relief (p=0.042) were risk factors for early death. All patients with adequate follow-up required reoperation with median duration of 6.9 years. The most common cause of early reoperation (<1 year) was wound infection (35.3%) while pulmonary valve replacement (58.8%) constituted the majority of late reoperations. Risk factors for wound infection included female sex (p=0.011) and use of a synthetic transannular patch (p=0.085). The most significant risk factor for early pulmonary valve replacement was the use of a monocusp pericardial valve in the pulmonary annular position (p=0.003). CONCLUSIONS: Excellent survival follows biventricular repair of pulmonary atresia with intact ventricular septum if RVOTO relief is performed in conjunction with initial palliation. Although most patients eventually require reoperation, avoidance of synthetic transannular patches and monocusp pericardial pulmonary valves may reduce the incidence of wound infection and delay need for pulmonary valve replacement.

Adolescent↗
PubMed2006

Successful management of patients with pulmonary atresia with intact ventricular septum using a three tier grading system for right ventricular hypoplasia.

BACKGROUND: We sought to validate a simple grading scheme for right ventricular hypoplasia in determining suitability for a biventricular repair. METHODS: We reviewed the medical records for 106 patients with pulmonary atresia-intact ventricular septum (PA-IVS) treated between 1982 and 2001. Over this period, children were assigned to mild (> 2/3 normal size, 23.7% of patients), moderate (1/3 to 2/3, 41.2%), or severe (1/3, 35.1%) right ventricular hypoplasia, and this grouping, along with severity of coronary anomalies (45% right ventricle to coronary fistulae, 16% with right ventricle dependent coronary circulation [RVDCC]), triaged children to eventual single ventricle (severe) or two-ventricle (mild or moderate) repair. RESULTS: Actuarial 10-year survival was 86.3% with mortality predicted by severe hypoplasia (odds ratio [OR] 12.9, p < 0.001), RVDCC (OR 15.0, p < 0.001), and non-Caucasian race (OR 10.7, p < 0.001). Multivariate analysis with a Cox proportional hazards model confirmed only RVDCC (risk ratio [RR] 10.9, p = 0.0009} and non-Caucasian race (RR 6.9, p = 0.007) as significant. Although not an independent risk factor for survival, the degree of hypoplasia was the most important determinant for definitive repair. Severe hypoplasia virtually precluded two-ventricle repair (OR 33.1, p < 0.001 by chi2 analysis) and was the strongest risk factor for a one-ventricle system (OR 78.7, p < 0.001). Actuarial survival after either repair was 91%, and no biventricular repair later converted to a Fontan system. CONCLUSIONS: Surgical management of patients based on this three tier grade for right ventricular hypoplasia results in excellent survival and correctly predicts patients destined for eventual Fontan and biventricular repair.

Cardiac Surgical Procedures↗
PubMed2006

Cardiac surgery in children with end-stage liver disease awaiting liver transplantation.

BACKGROUND: Cardiac repair for congenital heart disease in children awaiting liver transplantation presents unique therapeutic challenges and dilemmas. We tested the hypothesis that operations in these children requiring cardiopulmonary bypass (CPB) were not associated with prohibitive morbidity and mortality. METHODS: Over the last 10 years (1994-2004), five infants were identified in our database with end-stage liver disease and awaiting liver transplantation that required cardiac surgery. Primary end point for the study was mortality. Secondary end points included morbidity and time to liver transplantation. The new pediatric end-stage liver disease (PELD) model was used to score liver disease severity. RESULTS: Three boys and two girls with mean age of 8.6 months (range, 1.5-21 months) and mean PELD of 18.0 (range, 10-29) required CPB for repair. The only early mortality in the series occurred after cardiac arrest during creation of a central shunt. The child expired two days later despite extracorporeal membrane oxygenation support. The patient had important myocardial hypertrophy. All other patients survived and underwent successful liver transplantation. CONCLUSIONS: Children with significant congenital heart disease awaiting liver transplantation can undergo safe cardiac repair with judicious perioperative support thereby reducing the risks of subsequent liver transplantation.

Comorbidity↗
PubMed2006

Mechanical reliability of the Jarvik 2000 Heart.

BACKGROUND: Device failure is a limitation of permanent mechanical circulatory support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial flow pump with ceramic bearings designed to provide more than 10 years' durability. METHODS: The Jarvik 2000 Heart was implanted in 102 patients between April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were implanted as a bridge-to-transplantation, and 19 with postauricular power supply as lifetime therapy. Eighteen pumps were recovered intact after clinical use and run continuously on the bench to further assess durability. RESULTS: No implantable component failure occurred either in patients or during bench testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and 51 years in vitro. The mean support time for bridge-to-transplant recipients was 159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients were supported moer than 2 years, with the longest ongoing approaching 5 years. External cables caused three system failures, with a 95% freedom from system failure at 4 years. Device malfunctions, related to external cables (9) and lack of a backup battery (1), caused no adverse consequences. Before introduction of noncorrosive, gold-plated stainless steel connectors, corrosion was observed on three connectors to the retroauricular power supply. CONCLUSIONS: The Jarvik 2000 Heart has had no implantable component failure. Meaningful durability data and failure mode can only be established by real-time testing in patients. The reliability and dependability of this device, in addition to the exchangeability of external components, give promise for long-term circulatory support in critically ill heart failure patients.

Equipment Failure Analysis↗
PubMed2006

Peri-operative renal function and outcome after orthotopic heart transplantation.

BACKGROUND: Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT). METHODS: We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl) < 40 ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were defined by CrCl > or = 40 ml/min. The primary end points of the study were early and late mortality. The secondary end point included post-operative renal failure defined by the requirement of dialysis or renal allograft in the early post-operative period. The Kaplan-Meier method was used to determine actuarial survival. RESULTS: Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) (p < 0.001). Early mortality was 41% for patients requiring post-operative dialysis and 3% for those not requiring such intervention (p < 0.001). Early mortality after post-operative dialysis was 41% (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2). CONCLUSIONS: CrCl < 40 ml/min is a useful marker for increased post-operative renal failure and mortality. Recipients who require post-operative dialysis have greatly increased mortality regardless of pre-operative CrCl. Dialysis in patients after heart transplantation carries a prohibitive risk. Dialysis as a bridge to renal transplantation may reduce this high mortality rate.

Adult↗
PubMed2006

Post-transplant lymphoproliferative disorder following pediatric heart transplantation.

Immunosuppression after heart transplantation is implicated in development of post-transplant lymphoproliferative disorder (PTLD). Despite a higher prevalence of PTLD in children, there is scarce knowledge about incidence, pathophysiologic mechanisms and risk factors for PTLD in pediatric recipients of cardiac allografts. We examined retrospectively the medical records of all 143 pediatric patients (mean age 9.2 +/- 6.1 yr) who received donor allografts between 1984 and 2002 and survived over 30 days. Five children (3.5%) developed PTLD over a mean follow-up period of 41.1 +/- 46.0 months. Time from transplant to diagnosis of PTLD ranged from 3.9 to 112 months (mean 48.0 +/- 41.9 months). Excluding PTLD, no other malignancies were found in this population. Actuarial freedom from PTLD was 99.2%, 99.2% and 96.2% at 1, 2, and 5 yr, respectively. Children who developed PTLD were more likely (by univariate analysis) to have been Rh negative (p = 0.01), Rh mismatched (p = 0.003), Epstein-Barr virus (EBV) seronegative (p = 0.001) and transplanted for congenital heart disease (p < 0.02). PTLD was associated with significant morbidity and mortality with a mean survival following diagnosis of 21.2 months. PTLD is a serious complicating outcome of cardiac transplantation that occurs in approximately 3.5% of children. Aside of immunosuppression, risk factors in this series for developing PTLD include EBV seronegativity and Rh negative status and mismatch. Non-hematogenous malignancies are rare in light of short allograft half-life.

Adolescent↗
PubMed2006

Use of an apical suctioning device for placement of a posterior epicardial defibrillator patch: a case report.

We report a case of a 43-year-old man with dilated cardiomyopathy and intractable ventricular tachycardias who did not respond to percutaneous implantable cardioverter defibrillator therapy and required implantation of epicardial patches. An apical suctioning device was used to retract the apex of the heart outside the mediastinal domain. The device provided excellent exposure and hemodynamic stability to safely implant the posterior epicardial patch.

Adult↗
PubMed2005

Modified reperfusion in clinical lung transplantation: the results of 100 consecutive cases.

OBJECTIVE: Severe primary graft dysfunction occurs in 10% to 20% of lung transplant recipients and is the leading cause of early death after lung transplantation. We hypothesized that altering the content of the initial reperfusate and maintaining a low reperfusion pressure after surgical implantation would lead to a low incidence of primary graft dysfunction. METHODS: We analyzed the records of all patients who underwent lung transplantation at our institution from March 1, 2000, to August 30, 2004. The modified reperfusion technique involved the insertion of a catheter into the main or individual pulmonary artery after implantation. The recipient blood was depleted of leukocytes; supplemented with nitroglycerin; adjusted for pH and calcium level; enriched with aspartate, glutamate, and dextrose; and then administered into the pulmonary arteries of the newly transplanted lung(s) for the first 10 minutes of reperfusion. Severe primary graft dysfunction was defined as a PaO2/inspired oxygen fraction of less than 150 with diffuse infiltrate on the radiograph in absence of other causes. RESULTS: During this interval, 100 patients underwent lung transplantation with the modified reperfusion technique. Forty-two patients underwent single-lung transplantation, of which 5 patients required cardiopulmonary bypass for the procedure. Fifty-eight patients underwent double-lung transplantation; all double-lung transplantation procedures were performed with patients on cardiopulmonary bypass. There were no technical complications associated with the modified reperfusion. The mean PaO2/inspired oxygen fraction at 6 hours in this cohort was 252 +/- 123 mm Hg. The median number of days on the ventilator was 2. More importantly, the incidence of severe primary graft dysfunction in this cohort was 2.0%. The early survival (30-day or in-hospital mortality) of this group of patients was 97%. CONCLUSIONS: The technique of modified reperfusion in human lung transplantation is associated with a low incidence of severe primary graft dysfunction and favorable short-term outcomes.

Humans↗
PubMed2005

Modulation of gene expression in neonatal rat cardiomyocytes by surface modification of polylactide-co-glycolide substrates.

Myocardial tissue engineering presents a potential treatment option for heart disease. Cardiomyocytes isolated at various stages of development retain the ability to form contractile networks in vitro, which suggests that it should be possible to reconstitute viable myocardium given the appropriate architecture, stimuli, and cardiomyogenic cell source. This study investigates the effects of modifying substrate surface energy (by plasma etching) and protein coating (by fibronectin adsorption) on neonatal rat ventricular myocyte (NRVM) function. Primary NRVMs were cultured for 96 h on modified and control films of a common degradable polymer, polylactide-co-glycolide. Cultures were analyzed for cell spreading, protein content, and mRNA expression of atrial natriuretic factor and beta-myosin heavy chain. The results demonstrate that NRVMs cultured on etched films significantly increased in spreading, myofibril development, protein content, and gene expression of atrial natriuretic factor and beta-myosin heavy chain compared with unetched films, and that this surface energy effect is overwhelmed by the addition of fibronectin. Conclusions from this study are that surface energy and protein adsorption influence the gene expression of adherent NRVMs, and may be important for modulating the function of engineered myocardium.

Animals↗
PubMed2005

Liposome-mediated combinatorial cytokine gene therapy induces localized synergistic immunosuppression and promotes long-term survival of cardiac allografts.

Localized gene transfer has the potential to introduce immunosuppressive molecules only into the transplanted allograft, which would limit systemic side effects, and prolong allograft survival. However, an applicable gene transfer strategy is not available, and the feasible therapeutic gene(s) has not yet been determined. We developed an ex vivo liposome-mediated gene therapy strategy that is able to intracoronary deliver the combination of IL-4 and IL-10 cDNA expression vectors to the allograft simultaneously. We examined the efficiency, efficacy, and cardiac adverse effects of this combinatorial gene therapy protocol using a rabbit functional cervical heterotopic heart transplant model. Although the efficiency was moderate, the expression of both transgenes was long lasting and localized only in the target organ. The mean survival of cardiac allograft was prolonged from 7 to >100 days. Synergism of overexpressed IL-4 and IL-10 in the inhibition of T lymphocyte infiltration and cytoxicity, and modulation of Th1/Th2 cytokine production promote long-term survival of cardiac allografts.

Adjuvants, Immunologic↗
PubMed2005

Redo submammary incision for median sternotomy and cardiac repair.

BACKGROUND: Minimally invasive and cosmetically attractive approaches are fashionable in conducting cardiac operations. METHODS: We reviewed retrospectively our experience in patients undergoing cardiac operations by means of redo submammary incisions. RESULTS: Fifteen consecutive female patients with a mean age of 13.2 years (range, 0.7 to 44 years) underwent reoperation through a former submammary incision. Seventy-three percent (11 of 15) had median sternotomy, cardiopulmonary bypass, and cardiac repairs. The mean aortic cross-clamp and cardiopulmonary bypass times were 78 +/- 49.7 minutes (range, 16 to 182 minutes) and 114.4 +/- 66.4 minutes (range, 27 to 261 minutes), respectively. Twenty-seven percent (4 of 15) had off-pump procedures; 3 for pacemaker-related issues (1 a third time reentry) and 1 for removal of sternal wires. Mean time interval between the primary submammary incision and reoperation was 5.4 +/- 5.6 years (range, 0.01 to 20 years). Mean first 24 hours Hemovac drainage was 3.2 +/- 2.4 mL/kg (range, 0.4 to 8.5 mL/kg). Mean intensive care unit and hospital stays were 2.1 +/- 1.7 days (range, 0.0 to 5 days) and 5.5 +/- 3.6 days (range, 0.80 to 13 days), respectively. One patient exhibited a chylothorax requiring ligation of her thoracic duct. Another patient had an infected seroma requiring incision and drainage 2 months postoperatively. Skin necrosis and infection were absent in this group. Breast development and lactation were normal. The cosmetic results were satisfactory. There was no mortality. CONCLUSIONS: Redo sternotomies performed through redo transverse submammary incisions are safe for cardiac repair and result in acceptable cosmetic and functional results.

Adolescent↗
PubMed2005

Results of aortic valve-sparing and restoration with autologous pericardial leaflet extensions in congenital heart disease.

BACKGROUND: The purpose of this study is to evaluate the efficacy of aortic valve-sparing repair with glutaraldehyde-treated autologous pericardium in congenital valvular pathology. METHODS: Sixty-two patients underwent reparative aortic valve surgery from January 1997 through December 2003. The mean age was 25 +/- 20 years (+/- standard deviation) (range, 10 days to 81 years). Fifty percent (31 of 62) were less than 19 years old at operation. The diagnoses included bicuspid aortic valve (39 patients), ventricular septal defect (14 patients), severe aortic stenosis (6 patients), subaortic stenosis (7 patients), bacterial endocarditis (7 patients), neonatal truncus arteriosus (2 patients), Shone's complex (2 patients), transposition complex (1 patient), double-chambered right ventricle (1 patient), and Marfan's syndrome (1 patient). Twelve patients (19 %) had prior sternotomy and cardiac operations. Valve-sparing techniques included pericardial leaflet extensions in 62 patients, creation of one or more pericardial neoaortic sinuses in 8, subcommissuroplasty in 8, pericardial patch of perforated leaflets in 9, Dacron mesh wrap (Boston Scientific, Wayne, NJ) of dilated ascending aorta in 12, and concomitant tricuspid and mitral valve repairs in 3 and 4 patients, respectively. RESULTS: There was one early death (1.6%). There were no late deaths at a mean follow-up of 25 +/- 16 (range, 0.1 to 72.5 months). Six patients required reoperation and prosthetic or homograft replacement for aortic valve incompetence. One out of 6 reoperations required re-repair. The remaining patients are well with a mean aortic regurgitation grade by echocardiography of 1.3 +/- 0.9 (scale, 0 to 4). CONCLUSIONS: Aortic valve repair with pericardial leaflet extension is a promising technique for the growing child.

Adolescent↗
PubMed2005

Outcome of hearts with cold ischemic time greater than 300 minutes. A case-matched study.

OBJECTIVE: Expansion of potential donor pool may be facilitated by using cardiac allografts with long ischemic time. Early graft failure and potential relation to transplant coronary artery disease remains a concern. We sought to evaluate outcomes of heart transplantation in recipients of donor allografts with prolonged ischemia time. METHODS: The study group consisted of 46 (mean age, 52 years) consecutive patients at UCLA from 1994 to 2002 that underwent heart transplantation with ischemia time > 300 min. This group was compared to a case-matched control group of 46 (mean age, 51 years) patients identified from our database during this time frame for the following factors: UNOS status, congenital heart disease diagnosis, preop inotropes, pretransplantation creatinine > 1.5 and recipient age. Primary endpoint was mortality and secondary were rejection rate and transplant coronary artery disease. Allografts were perfused and stored in cold University of Wisconsin solution. RESULTS: Mean donor ages of the study and case-matched control group were 34+/-15 and 34+/-14 years, respectively. Mean ischemia times were 388 (range, 301-600 min) and 173 (range, 96-236 min), respectively. The death incidence rate per 100 transplants per year was 9% for the study group and 7.4% for the matched group (P = 0.50). Thirty-day mortality for the study and case-matched groups were 4.3 and 2.1%, respectively (P = 0.9). Late mortality was 16.5 and 18.5%, respectively (P = 0.9). The risk of death after 30 days was 7.5 and 5.8%, respectively (P = 0.5, log-rank). One-year incidence of acute cellular rejection in the study and case-matched groups were 2 and 4.5% (P = 0.36), respectively. One-year incidence of transplant coronary artery disease in the study and case-matched groups were 4.3 and 5.4%, respectively (P = 0.68). CONCLUSIONS: Donor hearts with ischemia time greater than 300 min provide comparable early and intermediate outcomes given judicious and careful donor and recipient matching and our current techniques of myocardial preservation and modified reperfusion.

Adolescent↗
PubMed2005

Ten-year follow-up of a randomized trial of pravastatin in heart transplant patients.

BACKGROUND: Outcomes from this trial's first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study. METHODS: Ninety-seven heart transplant recipients were randomized to pravastatin (n = 47) or no pravastatin (n = 50) within 2 weeks after surgery both in combination with cyclosporine and corticosteroids. Ten-year outcomes include survival, cholesterol levels, and development of cardiac allograft vasculopathy documented by coronary angiography. RESULTS: Forty-two percent of the control patients crossed over to pravastatin treatment during the second year of the study, and 81% of the control patients were eventually placed on statin therapy by the 10-year follow-up. The control group had subsequent low and comparable cholesterol levels in Years 2 to 10 of the study compared with the patients originally randomized to pravastatin. Intent-to-treat analysis demonstrated that the pravastatin group compared with control had increased 10-year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic cardiac allograft vasculopathy and/or death in the pravastatin group was significantly greater compared with the control group (43% vs 20%, p = 0.009). CONCLUSION: The 10-year follow-up of this study suggests that the use of pravastatin in heart transplant patients maintains survival benefit and appears to reduce the development of cardiac allograft vasculopathy.

Adult↗