Biomedical subjects

L S Czer

Publications and source records attributed to L S Czer.

At least 19 recordsLinked to original sources

PubMed2001

Heart transplantation in patients seventy years of age and older: A comparative analysis of outcome.

OBJECTIVE: Advanced age has traditionally been considered a contraindication for heart transplantation because of the reported adverse effect of increased age on long-term survival. However, as the field of transplantation continues to evolve, the criteria regarding the recipient's upper age limit have been expanded and older patients are being considered as potential candidates. We analyzed the outcome of heart transplantation in patients 70 years of age and older and compared these results with those in younger patients (<70 years) over a 4-year period. METHOD: We retrospectively analyzed the results of 15 patients 70 years of age and older who underwent heart transplantation between November 1994 and May 1999 and compared them with results in 98 younger patients undergoing transplantation during the same period RESULTS: The older age group had a higher preoperative left ventricular ejection fraction (P =.02), higher incidence of female donors (P =.02), and longer cardiac allograft ischemic time (P =.01). No differences were found regarding incidence of diabetes mellitus, donor age, donor/recipient weight ratio, and mismatch (<0.80). The 30-day or to-discharge operative mortality was similar in both groups (0% in the older vs 5.1% in younger patients). Actuarial survival at 1 year and 4 years was not statistically different between the older and younger patients (93.3% +/- 6.4% vs 88.3% +/- 3.3% and 73.5% +/- 13.6% vs 69.1% +/- 5.8%, respectively). The length of intensive care unit stay and total post-transplantation hospital stay, incidence of rejection, and incidence of cytomegalovirus infection were similar between the groups. CONCLUSIONS: Heart transplantation in selected patients 70 years of age and older can be performed as successfully as in younger patients (<70 years of age) with similar morbidity, mortality, and intermediate-term survival. Advanced age as defined (> or =70 years) should not be an exclusion criterion for heart transplantation. The risks and benefits of transplant surgery should be applied individually in a selective fashion.

Adolescent↗

PubMed2001

Twenty-year comparison of tissue and mechanical valve replacement.

OBJECTIVE: We sought to compare outcomes with tissue and St Jude Medical mechanical valves over a 20-year period. METHODS: Valve-related events and overall survival were analyzed in 2533 patients 18 years of age or older undergoing initial aortic, mitral, or combined aortic and mitral (double) valve replacement with a tissue valve (Hancock, Carpentier-Edwards porcine, or Carpentier-Edwards pericardial) or a St Jude Medical mechanical valve. Total follow-up was 13,390 patient-years. There were 666 St Jude Medical aortic valve replacements, 723 tissue aortic valve replacements, 513 St Jude Medical mitral valve replacements, 402 tissue mitral valve replacements, 161 St Jude Medical double valve replacements, and 68 tissue double valve replacements. The mean age was 68 +/- 13.3 years (St Jude Medical valve, 64.5 +/- 12.9; tissue valve, 72.0 +/- 12.6). RESULTS: There were no overall differences in survival between tissue and mechanical valves. Multivariable analysis indicated that the type of valve did not affect survival. Analysis by age less than 65 years or 65 years or older and presence or absence of coronary disease revealed similar long-term survival in all subgroups. The risk of hemorrhage was lower in patients receiving tissue aortic valve replacements but was not significantly different in patients receiving mitral valve or double valve replacements. Thromboembolism rates were similar for tissue and mechanical valve recipients. However, reoperation rates were significantly higher in patients receiving both aortic and mitral tissue valves. The reoperation hazard increased progressively with time both in patients receiving aortic and in those receiving mitral tissue valves. Overall valve complications were initially higher with mechanical aortic valves but not with mechanical mitral valves. However, valve complication rates later crossed over, with higher rates in tissue valve recipients after 7 years in patients undergoing mitral valve replacement and 10 years in those undergoing aortic valve replacement. CONCLUSIONS: Tissue and mechanical valve recipients have similar survival over 20 years of follow-up. The primary tradeoff is an increased risk of hemorrhage in patients receiving mechanical aortic valve replacements and an increased risk of late reoperation in all patients receiving tissue valve replacements. The risk of tissue valve reoperation increases progressively with time.

Adult↗

PubMed2001

Combined heart-kidney transplantation with single-donor allografts.

OBJECTIVES: Combined heart-kidney transplantation with allografts from the same donor has been long proved to be a feasible approach for selected patients with coexisting end-stage cardiomyopathy and renal disease. The purpose of this retrospective study is to analyze our long-term results and compare these results with heart-only transplantation over a 7-year period. METHODS: Between June 1992 and April 1999, 10 patients underwent combined heart-kidney transplantation at Cedars-Sinai Medical Center. They were all men from 44 to 70 years old (mean age, 59 +/- 8.3 years) who had a mean left ventricular ejection fraction of 19.4% +/- 5.0% (range, 9%-25%) and a mean creatinine clearance of 25.4 mL/min (range, 10-39 mL/min). Four patients underwent pretransplantation dialysis. RESULTS: There was no operative mortality. The actuarial survival at 1, 2, and 5 years was 100%, 88% +/- 11.7%, and 55% +/- 20.1%, respectively. By comparison, the operative mortality of 169 patients who underwent heart-only transplantation during the same time interval was 2.4%, with an actuarial survival at 1, 2, and 5 years of 92% +/- 2.1%, 84% +/- 2.8%, and 71% +/- 3.9%, respectively (P =.37). Eight patients showed no evidence of significant (> or =1B) cardiac allograft rejection postoperatively, and the actuarial freedom from rejection at 30 days, 1 year, and 2 years was 90% +/- 9%, 80% +/- 13%, and 80% +/- 13%, respectively. Renal allograft survival was 90% at 1 and 2 years. CONCLUSIONS: Combined heart-kidney transplantation yields satisfactory long-term results similar to those for heart-only transplantation, with a low incidence of cardiac allograft rejection and renal allograft survival when both allografts are from the same donor. This approach effectively expands the selection criteria for heart-only and kidney-only transplantation in potential candidates with coexisting end-stage cardiac and renal disease.

Actuarial Analysis↗

PubMed1999

The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation.

BACKGROUND: Vascular endothelial cells are primary targets for injury during both cellular and humoral allograft rejection (AR). In cardiac transplantation, the role of humoral immunity in mediating AR has not been extensively characterized. METHODS: Antibodies against human vascular endothelial cells (AECA) were measured using a cellular ELISA developed from human umbilical vein endothelial cells in 80 consecutive patients after cardiac transplantation. The aim was to determine the incidence of AECA formation after transplantation and their association with different types of AR, graft survival, and development of cardiac allograft vasculopathy (CAV). At least eight serum samples obtained from each patient were examined for AECA and an endomyocardial biopsy was performed at regular intervals during the first year after transplantation. RESULTS: Of the 80 patients examined, 31 were AECA (+) and 49 patients were AECA (-). There were no significant differences between the AECA (+) and (-) groups when examined for age, sex, and pretransplantation ischemia time. A significant correlation was found between the presence of AECA and humoral AR (P<0.015). AECA positivity did not correlate with the presence of cellular AR or the number of rejection episodes. In addition, allograft survival at 2 years after transplantation was significantly better in the AECA (-) group compared with that in the AECA (+) group (89.8% vs. 71.0%, P<0.0004). The persistence of AECA positivity during the first year after transplantation was also associated with a significantly greater incidence of CAV when compared with the patients who were AECA (-) (25.8% vs. 14.3%, P<0.004). CONCLUSIONS: AECA may be important in the mediation of humoral AR, may decrease allograft survival, and may identify a high-risk group for CAV.

Adolescent↗

PubMed1998

Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action.

BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. METHODS: In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.

Adult↗

PubMed1997

Correlation of cytomegalovirus DNA levels with response to antiviral therapy in cardiac and renal allograft recipients.

BACKGROUND: Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. A rapid, sensitive, specific, and reliable test is desirable for early detection of CMV infection and for monitoring the efficacy of antiviral therapy. METHODS: We examined the incidence of CMV infection in 95 cardiac and 25 renal allograft recipients followed for up to 3 years using qualitative and quantitative polymerase chain reaction (PCR) techniques. Results were subsequently correlated with clinical findings. Of the 236 samples analyzed by the CMV PCR, 84 and 20 were also analyzed by blood buffy coat culture and anti-CMV antibody IgM assays, respectively. RESULTS: The sensitivity of the CMV PCR was found to be superior to that of the other assays, although the specificity of the blood buffy coat culture is as good as that of the CMV PCR, which is higher than that of the anti-CMV antibody IgM assay. CMV infection was detected by the CMV PCR in 17 of 95 cardiac and 9 of 25 renal transplant recipients. Clinical symptoms were observed when > or =500 copies of CMV DNA/1 microg of total DNA were detected by a quantitative CMV PCR assay using an external control CMV plasmid; however, some patients had symptoms when 50-100 copies were present. The levels of CMV DNA detected varied (50-1000 copies) in patients who developed asymptomatic CMV infection. The CMV DNA levels decreased to 50-100 copies 1-2 weeks after antiviral therapy was initiated and correlated well with disappearance of clinical symptoms. CMV DNA levels decreased to < or =5 copies at 4-7 weeks after treatment. This contrasts with patients who were unresponsive to anti-CMV therapy, in whom high levels of CMV DNA (> or =500 copies) persisted for at least 5 weeks and significant levels of CMV DNA (50-100 copies) were detected for several months afterward, despite multiple courses of anti-CMV therapy. Clinical symptoms also did not disappear during this period of observation. CONCLUSIONS: (1) The CMV PCR represents a rapid, sensitive, specific, reliable test for detection of CMV infection, especially for detection of virus replication in an incipient phase. (2) The quantitative CMV PCR is useful for monitoring the efficacy of antiviral therapy to distinguish patients who respond to therapy from those who do not. (3) CMV DNA levels > or =500 copies/1 microg of total DNA analyzed by the quantitative CMV PCR can be used to differentiate CMV infection from other infections and rejection.

Cytomegalovirus↗

PubMed1997

Cytomegalovirus infection induces anti-endothelial cell antibodies in cardiac and renal allograft recipients.

Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. CMV infection has an association with the development of allograft rejection (AR) through graft endothelial cell (EC) damage, but the mechanisms are not yet clear. There are few reports addressing the role of humoral immunity in vascular EC injury mediated by CMV infection whereas many reports are available regarding the mechanism(s) of CMV-associated allograft EC injury mediated by cellular immunity. Here we examine the incidence of CMV infection in 40 cardiac and 25 renal allograft recipients using polymerase chain reaction (PCR) techniques. We also monitored sera for the development of anti-EC antibodies (AECA) using an ELISA with human umbilical vein ECs as targets, and IL-2 levels using an ELISA. AECA levels (immunoglobulin-G and immunoglobulin-M) were significantly elevated in allograft recipients who demonstrated CMV-PCR positivity when compared with the CMV-PCR negative group (IgG: 23.1 +/- 16.4 vs 4.7 +/- 4.5, p < 0.0001; IgM: 47.0 +/- 53.6 vs 7.0 +/- 11.2, p < 0.0001). Serum AECA (IgG and IgM) levels increased one to four weeks after CMV DNA was detected and elevated AECA levels persisted for at least one to two months, and sometimes for several months. Elevated AECA levels correlated well with serum IL-2 levels. These results suggest that CMV infection is associated with an increased humoral immune response to EC antigens, which may be a risk factor for vascular rejection, chronic rejection and decreased allograft survival.

Autoantibodies↗

PubMed1997

Resting hemodynamics after total versus standard orthotopic heart transplantation in patients with high preoperative pulmonary vascular resistance.

OBJECTIVE: Pretransplant pulmonary vascular resistance > or = 4 Wood-units predisposes to right ventricular failure after heart transplantation. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers synchronous contractions of the atria and a normal ventricular filling pattern, but requires longer ischemic time than standard orthotopic heart transplantation. To test if total orthotopic heart transplantation improves resting hemodynamics in pts with high preoperative pulmonary vascular resistance, we analyzed 65 pts with standard and 65 with total orthotopic heart transplantation transplanted between 12/88 and 7/94. Of these, 18 with total and 15 with standard orthotopic heart transplantation had a preoperative pulmonary vascular resistance > or = 4 Wood-units. METHODS: Right heart catheterization data were obtained at each endomyocardial biopsy. All data from biopsies at both 2 weeks and 1 year posttransplant that were free from humoral or greater than 1A cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with postop pacemakers, atrial fib or beta-blocker therapy at the time of biopsy were excluded. RESULTS: Ischemic time was different (172 +/- 44 versus 142 +/- 28 min, P = 0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes were similar. Cardiac output and index were higher in the total orthotopic group at 2 weeks (6.5 +/- 1.7 versus 5.1 +/- 1.0 l/min; 3.4 +/- 0.9 versus 2.8 +/- 0.6 l/min per m2) and 1 year (7.1 +/- 2.0 versus 4.9 +/- 1.1 l/min, P = 0.002; 3.6 +/- 1.1 versus 2.6 +/- 0.5 l/min per m2, P = 0.009). Right atrial and pulmonary arterial mean pressure (mmHg) were lower with total orthotopic heart transplantation at 2 weeks (6 +/- 4 versus 9 +/- 5, P = 0.04; 22 +/- 3 versus 25 +/- 7, P = 0.1) and 1 year (5 +/- 2 versus 7 +/- 3, P = 0.02; 19 +/- 4 versus 25 +/- 7, P = 0.03). Pulmonary capillary wedge pressure (mmHg) was borderline nonsignificant (11 +/- 4 versus 13 +/- 7 at 2 weeks, 8 +/- 3 versus 14 +/- 5 at 1 year, P = 0.055), as well as pulmonary vascular resistance (1.9 +/- 1 versus 2.5 +/- 1 at 2 weeks, 1.5 +/- 0.6 versus 2.7 +/- 1.7 WU at 1 year, P = 0.051). CONCLUSIONS: Total orthotopic heart transplantation improves cardiac output and index in pts with high preoperative pulmonary vacular resistance. There is a lower mean RA and PA pressure perhaps due to less tricuspid and mitral regurgitation. In view of the frequently observed restrictive filling pattern after cardiac transplantation, total orthotopic heart transplantation can be beneficial until this pattern has subsided by preserving atrioventricular synchrony and offering better atrial transport.

Aged↗

PubMed1997

The duration of administration of monoclonal antibody OKT3 for induction immunosuppression after heart transplantation.

The effective treatment of refractory allograft rejection with murine antihuman monoclonal antibody muromonab-CD3 (OKT3) and of patients with renal dysfunction has led to its use as induction therapy. The optimal protocol for OKT3 prophylaxis remains to be established. We compared 59 patients consecutively transplanted with the total orthotopic technique between 1/92 and 5/94. The first 21 patients were treated with OKT3 for 14 days, the next 19 for 10 days, and the last 19 for 7 days. Patients operated with different surgical techniques or other induction treatment were excluded. We compared length of stay (total and ICU), time to first rejection, rejection incidence and infection incidence (cytomegalovirus separately), and survival. Preoperative characteristics were similar except for significantly younger age in the 10-day group (p = 0.04). Preoperative hemodynamic parameters were similar except for a significantly higher left-ventricular ejection fraction (21%) in the 7-day group. Length of stays in the ICU and hospital were similar for the three groups (p = NS). Freedom from cellular rejection was lower with the 7 days course (p = 0.02), but freedom from humoral rejection was slightly higher (p = 0.11). However, patients in the 7-day group required treatment for rejection less frequently than patients in the other two groups (95% untreated at 2 months vs. 43% in the 14-day and 53% in the 10-day group; p = 0.002). There were no differences in incidence of infections, including cytomegalovirus. Survival was similar between the groups. There was one death in the 14-day and 1 in the 10-day group, both due to rejection. In conclusion, OKT3 therapy can be reduced safely to 7 days with a higher overall incidence of rejection but no increased necessity to treat for rejection, and no difference in infection incidence.

Adult↗

PubMed1997

Absence of endocardial lymphoid infiltrates (Quilty lesions) in nonheart transplant recipients treated with cyclosporine.

The clinical records and autopsy material from 14 patients treated with cyclosporine who were not recipients of cardiac allografts were reviewed to further study the nature of endocardial lymphoid infiltrates (quilty lesions). Although there was well-documented exposure to cyclosporine, no endocardial lymphoid infiltrates were identified in these cases, providing evidence that the endocardial-based Quilty lesion is not the result of the direct effect of cyclosporine and may represent a localized form of heart rejection confined to the endocardium.

Adolescent↗

PubMed1997

The effect of chronic alcohol use on the heart before and after transplantation in an experimental model in the rat.

BACKGROUND: Alcohol has potential deleterious effects on donor heart function. This study was conducted in rats to determine whether long-term alcohol ingestion produces impaired hemodynamic performance while maintaining a normal left ventricular ejection fraction in donor hearts before transplantation and whether donor cardiac function is affected after heart transplantation. METHODS: Rats fed 30% alcohol in their drinking water for 12 weeks were compared with rats fed a normal diet. Left ventricular ejection fraction was measured by echocardiography with Simpson and single plane Dodge formulas in living sedated rats after 10 and 12 weeks of alcohol feeding. Explanted heart function was assessed before and 3 days after heterotopic heart transplantation (no immunosuppression) with a Langendorff preparation. RESULTS: Blood ethanol levels at 4 and 8 weeks were 0.08 +/- 0.04 and 0.08 +/- 0.09 gm/dl. Left ventricular ejection fraction was similar in the group fed an alcohol diet for 12 weeks when compared with the control group (65.4% +/- 1.6% vs. 66.5% +/- 2.9%, p = 0.33). Explanted alcohol-fed hearts before transplantation had significantly lower maximum and developed pressures and had a blunted response to 0.1 ml 10(-9) mol/L isoproterenol. After transplantation alcohol-fed hearts had significantly lower maximum and developed pressures and decreased maximum rates of pressure rise and pressure decline. Allografts (ACI to Lewis) exhibited decreased function in comparison with isografts (ACI to ACI). CONCLUSIONS: Alcohol feeding for 12 weeks in rats does not affect pretransplantation left ventricular ejection fraction, but it impairs explanted heart function, both before and after transplantation, resulting in a subclinical cardiomyopathy that is worsened by the presence of allograft rejection. Long-term alcohol exposure and rejection have independent, additive detrimental effects on left ventricular performance of the transplanted heart. Alcohol-exposed hearts may not be suitable donors.

Animals↗

PubMed1997

Heart transplantation with bicaval and pulmonary venous anastomoses. A hemodynamic analysis of the first 117 patients.

BACKGROUND: A new surgical technique for orthotopic heart transplantation has been introduced into clinical practice. It accomplishes total atrioventricular transplantation as the recipient's atria are completely excised and the allograft is implanted using bicaval and pulmonary venous anastomoses. MATERIALS AND METHODS: We retrospectively analyzed post-transplant hemodynamic and patient survival in our first 117 patients transplanted with this new operative approach and compared them with 64 patients transplanted with the standard biatrial technique. RESULTS: Patients transplanted with the bicaval technique had a significantly lower right atrial mean, pulmonary arterial systolic, pulmonary arterial mean, and pulmonary capillary wedge pressures. In addition, a significant reduction in post-transplant tricuspid regurgitation and a trend towards less severe mitral regurgitation was observed. The need for permanent pacemaker implantation due to sinus node dysfunction after transplantation was completely eliminated with this new technique. Thirty-day operative survival and actuarial survival at 1, 2, 3, and 4 years was significantly greater in patients transplanted with the bicaval technique. CONCLUSIONS: Orthotopic heart transplantation performed with bicaval and pulmonary venous anastomoses offers improved post-transplant hemodynamics, eliminates the need for permanent pacemaker, and has improved patient survival when compared with the standard biatrial technique. These differences can be related in part to improved hemodynamic function of the cardiac allograft due to preservation of the anatomic configuration and physiologic function of the atria.

Adult↗

PubMed1996

Heart transplantation in patients 65 years of age and older: a comparative analysis of 40 patients.

BACKGROUND: Advanced age has traditionally been considered a relative contraindication to heart transplantation because of the potential for increased morbidity and decreased long-term survival. METHODS: We analyzed the results in 40 patients 65 years of age and older who underwent heart transplantation and compared them with those in 138 patients younger than 65 years. RESULTS: The older age group had a higher incidence of diabetes mellitus (p = 0.01), donor-recipient weight mismatch (< 0.80) (p = 0.004), lower donor-recipient weight ratio (p = 0.02), and longer allograft ischemic time (p = 0.008), among other differences. However, the 30-day operative mortality was similar in both groups (2.5% in older versus 2.2% in younger patients). Actuarial survival at 12, 24, and 36 months was not statistically different between the older and younger patients (86% +/- 6% versus 93% +/- 2%, 78% +/- 8% versus 89% +/- 3%, and 72% +/- 9% versus 81% +/- 4%, respectively; p = 0.26). The posttransplantation intensive care unit stay, total hospital stay, and associated hospital costs were also similar. The incidence of rejection during the first posttransplantation year was similar in both groups. CONCLUSIONS: Heart transplantation in selected patients 65 years of age and older can be performed successfully, with a morbidity and mortality comparable with those seen in younger patients. Advanced age should not be an exclusion criterion for heart transplantation, but selective criteria should be applied that identify risks and benefits individually.

Actuarial Analysis↗

PubMed1996

Heart transplantation in patients 70 years of age and older: initial experience.

BACKGROUND: Heart transplantation has become a highly successful therapeutic option for patients with end-stage cardiomyopathy. Consequently, the criteria for patient selection, particularly regarding recipients' upper age limits, have been expanded, with an increasing number of people older than 60 years of age now undergoing transplantation. METHODS: A retrospective analysis of 6 patients 70 years of age and older who underwent heart transplantation was done; their clinical courses and outcomes were compared with those of younger patients, with a special emphasis on their posttransplantation quality of life. RESULTS: All 6 patients are alive and clinically well at a mean follow-up of 12 months. No age-related complications have been observed, and their quality of life is excellent. There has been a very low incidence of rejection, as well as few episodes of rejection. CONCLUSIONS: Heart transplantation in selected people 70 years of age and older can be performed successfully with a morbidity comparable to that seen in younger patients and excellent short-term survival. This initial experience is encouraging, but further studies and long-term follow-up are needed to validate the more routine application of this therapy.

Age Factors↗

PubMed1996

Clinical experience with one hundred consecutive patients undergoing orthotopic heart transplantation with bicaval and pulmonary venous anastomoses.

OBJECTIVE: Our objective was to assess survival, need for pacemaker insertion, and rejection frequency with a new surgical technique of orthotopic heart transplantation using bicaval and pulmonary venous anastomoses. METHODS: We retrospectively reviewed 100 consecutive patients who had orthotopic heart transplantation with this technique between July 1991 and September 1995. RESULTS: The mean age was 57.0 +/- 11.1 years, with 51 patients being 60 years or older. The mean donor/recipient weight ratio was 0.92, and in 28 patients the ratio was less than 0.8. The early (30-day) survival was 100% and the 1- and 2-year survivals were 98% +/- 2% and 96% +/- 2%, respectively. Survival was not affected by age or by the duration of the OKT3 therapy (p > 0.2 for each of these parameters). The seven late deaths were due to infection (n = 2), graft atherosclerosis (n = 3), acute rejection (n = 1), and nonspecific graft failure (n = 1). No permanent pacemaker was required in the first 6 months after the operation, and all the patients were discharged in normal sinus rhythm. Freedom from treated rejection was significantly greater in patients with 7 days of OKT3 therapy than in patients with 14 days of therapy (p < 0.0001). CONCLUSIONS: Orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers an improved alternative to the standard biatrial technique, with a 30-day mortality of 0,% in 100 consecutive patients, excellent intermediate-term survival, and elimination of the need for pacemaker insertion. More normal anatomic configuration and synchronous function of the atria may have contributed to these results.

Adolescent↗

PubMed1996

Liposome-mediated transfer of genes containing HLA-class II alpha chain into cultured embryonic chick cardiac myocytes and COS7 cells.

Rejection remains a major problem after cardiac transplantation. One hypothesis is that transfer of recipient HLA genes could lead to expression of the antigens on the surface of donor cells and so facilitate graft acceptance. This paper describes a pilot study for relevant gene-transfer (transfection) experiments on adult cardiac myocytes, investigating the feasibility of transfection using cationic liposomes. The plasmid pcDV1-pL2 vector containing HLA-DR-alpha chain gene was incubated with Lipofectin, a DOTMA and DOPE lipid mixture, for 10 minutes. Embryonic chick cardiac myocytes (ECCM) and COS7 monkey cells were incubated with DNA: Lipofectin ratios of 1:1, 1:2, 1:4, and 1:10 for 16 hours (hrs). Using a fixed ratio of 1:4, incubation periods of 4, 8, and 16 hrs were compared. Finally, cells were incubated for 16 hrs and consecutively cultured for 6 days. Expression of the HLA-DR-alpha chain antigen was detected by indirect immunohistochemical staining. Highest transfection rates were achieved with a DNA: Lipofectin ratio of 1:4 for ECCM and COS7 cells (2.7% +/- 0.6% and 2.4% +/- 0.3% after 16 hrs incubation) and a transfection time of 4 hrs (5.8% +/- 0.6% and 5.3% +/- 1.7%). Immunohistochemically positive cells were present after 6 days (2.0% +/- 1.2% and 2.1% +/- 0.3%). We found a low level of expression of HLA-DR-alpha chain gene, influenced by transfection time and DNA: Lipofectin ratio. To increase the efficiency of liposome-mediated gene transfer and assess potential applications in cardiac transplantation, further investigation of cell properties promoting transfection is necessary.

Adult↗

PubMed1996

Resting hemodynamics after total versus standard orthotopic heart transplantation.

Total orthotopic heart transplantation (TOHT) requires longer surgery than standard orthotopic heart transplantation (SOHT), but offers normal anatomy and synchronous atrial contraction. We endeavored to test whether TOHT improves resting hemodynamics. We analyzed 60 patients with SOHT and 66 with TOHT transplanted between 12/89 and 7/94. Age, preoperative NYHA class, ejection fraction, and donor characteristics were similar. After applying exclusion criteria at 2 weeks postoperatively, 53 SOHT and 58 TOHT patients were accepted for further study. Right-heart hemodynamics were examined at 2 weeks and 6 months posttransplant. Despite a longer ischemic time (161 +/- 36 vs. 142 +/- 37 min, p = 0.004), cardiac output and index were higher in the TOHT group at 2 weeks (6.1 +/- 1.4 vs. 5.4 +/- 1.0 L/min, TOHT vs. SOHT, p = 0.01; and 3.3 +/- 0.7 vs. 2.9 +/- 0.6 L/min/m2, p = 0.005) but similar at 6 months (5.9 +/- 1.2 vs. 5.6 +/- 1.4 L/min; and 3.0 +/- 0.6 vs. 2.9 +/- 0.7 L/min/m2). Right-atrial pressure was lower with TOHT at both time points (7 +/- 4 vs. 9 +/- 4 mmHg, p = 0.02: and 5 +/- 2 vs. 7 +/- 3, p = 0.0006). Wedge pressure was similar at 2 weeks (12 +/- 5 vs. 13 +/- 5, p = 0.045). Heart rate (bpm) was higher at both time points with TOHT (84 +/- 10 vs. 75 +/- 12, p = 0.0003: and 90 +/- 12 vs. 82 +/- 9, p = 0.0006). Pulmonary vascular resistance was similar at both time points. Despite a longer ischemic time, total orthotopic heart transplantation does not impair postoperative cardiac function. There is an early improvement in cardiac output, a sustained higher heart rate reflecting preservation of donor sinus node function, and a lower right-atrial pressure.

Blood Pressure↗

PubMed1996

Heart transplantation in patients with diabetic end-organ damage before transplantation.

Diabetes mellitus with preexisting end-organ damage (EOD) is considered a contraindication for heart transplantation. The outcome of such patients has not been well characterized. Among 138 patients transplanted between 12/88 and 7/94, 29 were diabetic (11 insulin-dependent); of these, 12 had preexisting EOD, defined as a creatinine clearance < or = 50 ml/min, a 24-hour urine protein concentration > or = 500 mg/L or typical symptoms of peripheral or autonomic polyneuropathy, and 17 had no EOD. We compared diabetics with and without EOD and non-diabetics (n = 109) for operative mortality, length of stay, serum creatinine, fasting glucose levels, and postoperative prednisone doses at 1,6, and 12 months. Actuarial survival and freedom from rejection and infection were analyzed. Both diabetic groups were significantly older than nondiabetics, Ischemic time, operative mortality, surgical technique, ICU- and total length of stay were similar. Actuarial survival and freedom from rejection were similar among the three groups. Infection rates including CMV did not differ. Serum creatinine levels increased in all groups compared to pretransplant levels (p = 0.001), but without significant differences among the groups. Post-transplant glucose levels at 6 and 12 months were higher for diabetic patients with EOD than for those without or for nondiabetics (183, 153, and 94 mg/dl at 6 months, p = 0.01; 202, 161, and 102 mg/dl at 12 months, p = 0.0001). Prednisone dosage was lower in diabetics with EOD at 6 months, but did not differ among the three groups at 12 months. The incidence of angiographically proven transplant vasculopathy did not differ at 1 and 2 years. Diabetics with preexisting EOD undergoing heart transplantation experience similar short- and intermediate-term results when compared to diabetics without EOD and nondiabetics. Metabolic control is more difficult to achieve, as indicated by higher fasting glucose levels. Larger and longer-term prospective studies have to confirm our findings, since the shortage of donor organs would increase if such patients were transplanted routinely.

Actuarial Analysis↗