Duwarakan K. Satchithananda

The incidence of end-stage renal failure in 17 years of heart transplantation: a single center experience

BACKGROUNDnPredictions of the incidence of renal failure within a heart transplant population are based on the early experiences of cyclosporine (CsA)-based immunosuppression. We report a single-center experience of end-stage renal failure (ESRF) during a 17-year period encompassing current lower dose CsA regimens.nnnMETHODnProspectively collected data were analyzed on all patients who underwent first heart transplants between April 1982 and February 1999 (n = 697). We further categorized patients by the date of transplantation into a higher and lower dosage maintenance CsA group.nnnRESULTSnEnd-stage renal failure developed in 44 patients. The median time to dialysis was 87 months after transplantation and was independent of the initial CsA regimens used (p = 0.798). In the ESRF group, 14 underwent hemodialysis, 28 underwent peritoneal dialysis, and 9 underwent renal transplantation. One- and 5-year survival rates after dialysis were 82% and 62% respectively. The incidence of ESRF at our institution was 5.8%. It increased with post-operative survival and was independent of the initial CsA regimen used. We found no difference in pre-transplant age, sex, diagnosis, immediate post-operative creatinine, or the development of diabetes between the ESRF group and controls. The ESRF group received higher dosages of CsA within the first post-transplant year, although this did not reach significance (CsA dosage, 5.9 microg/kg/day vs 5.1 microg/kg/day, respectively p = 0.075).nnnCONCLUSIONSnLower dosage CsA regimes have not altered the incidence of ESRF at our institution, suggesting an individual predisposition to nephropathy. Therefore, reduction in the future incidence of ESRF may rely on extremely low-dose or calcineurin-free immunosuppression regimes.

Heart-lung transplantation for Eisenmenger syndrome: early and long-term results.

BACKGROUNDnHeart-lung transplantation (HLT) for Eisenmenger syndrome (ES) provides superior early and intermediate survival when compared with other forms of transplantation. The early risk factors and long-term outcome of HLT for ES are less well defined.nnnMETHODSnWe analyzed 263 patients who had undergone HLT at our institution during more than 15 years. Fifty-one consecutive patients with ES who underwent HLT, 33 (65%) of which had simple anatomy, were compared with 212 cases having HLT for other indications (non-ES).nnnRESULTSnFemale sex and previous thoracotomy were more prevalent in the ES group. Patients with ES had greater postoperative blood loss and returned more frequently to the operating room for control of bleeding. There were 8 (16%) early deaths in the ES group compared with 27 (13%) in non-ES (p = 0.65). One-, 5-, and 10-year survival rates for ES were 72.6%, 51.3%, and 27.6%, respectively, compared with non-ES of 74.1%, 48.1%, and 26.0%, respectively, and there was no difference in survival overall (p = 0.54). Among ES patients, previous thoracotomy was a risk factor for hospital death. A subgroup analysis based on simple versus complex type of ES did not show statistically significant differences in terms of postoperative course or early or late survival.nnnCONCLUSIONSnHeart-lung transplantation is a successful procedure for ES. Despite a greater frequency of risk factors and a more difficult operative course, early and late outcome with HLT is comparable to non-ES recipients.

Swan-Ganz catheter assessment of donor hearts: outcome of organs with borderline hemodynamics

BACKGROUNDnHigh-dosage inotrope use or periods of hypotension may cause rejection of donor hearts for transplantation. At our institution, we do not refuse potential donor organs based on these criteria alone before Swan-Ganz catheter (SGC) assessment. In this study, we evaluate the role of the SGC in donor heart resuscitation and selection and assess the outcome of using borderline organs.nnnMETHODSnWe retrospectively analyzed 129 donors assessed between 1996 and 1999, all with complete hemodynamic data. Two sets of SGC measurements were analyzed: one set from the initial assessments, and one set from assessments made just before organ harvesting. The physiologic targets were mean blood pressure >60 mm Hg, central venous pressure <12 mm Hg, pulmonary capillary wedge pressure <12 mm Hg, left ventricular stroke work index >15 x g.m/m(2), and use of only one inotrope. A poorly functioning heart was defined as an organ failing on 2 or more of these criteria. Hemodynamic categories were defined as A, good function throughout assessment; B, sub-optimal function and then improvement; and C, decreasing or poor function throughout. We have a policy to avoid allocating sub-optimal organs to high-risk recipients.nnnRESULTSnOne hundred fourteen donor hearts went on to be transplanted: 75 as orthotopic hearts and 39 as heart-lungs (5 of these were heart, lung, and liver transplantations, not reported further here). Of the 75 donor hearts used for heart transplantations, 53 were from Category A, 9 were from Category B, and 13 were from Category C. Of the donor hearts used for the 34 heart-lung transplantations 16 were from Category A, 10 were from Category B, and 8 were from Category C. Three patients died of donor organ failure: 1 of the corresponding hearts was from Category B, and 2 were from Category C. When comparing separately the outcome of the 2 procedures, we found no significant difference in duration of stay in the intensive care unit, requirement for mechanical support, 30-day mortality, or 1-year survival among patients with hearts from Categories A, B, and C. Ischemic time was the only significant risk factor for death (p = 0.006).nnnCONCLUSIONSnUse of organs from Categories B and C permitted expansion of the donor pool without compromising short-term outcome. However, these organs should be used with caution in combination with other risk factors, in particular long ischemic time.

Two-decade analysis of cardiac storage for transplantation

OBJECTIVEnCardiac storage solutions and methods remain unstandardized. We have surveyed the literature to establish how the subject has progressed, addressing models of preservation and measures of outcome. Since a lot of the literature on cardiac storage is generated in the laboratory, we were particularly interested to evaluate to what extent bench work finds its way into and clinical practice. The discussion focuses in addition to new areas of research and introduces the concept of integrated organ preservation.nnnMETHODSnFive representative journals (J Thorac Cardiovasc Surg, Circulation, J Heart Lung Transplant, Eur J Cardio-thorac Surg and Ann Thorac Surg) were searched by hand for papers published between 1980-1999. All laboratory, animal experimental and clinical studies focused on prolonged cardiac preservation and storage were selected.nnnRESULTSnTwo hundred and forty-nine publications were identified using preset criteria. Of these, 196 (79%) were studies performed in animal models and 10 (4%) were experiments carried out on animal tissue. One hundred and five experiments (42% of all studies) were performed in small animals. The most common animal model was of ischemia followed by ex vivo reperfusion (121 studies, 49% of publications). The measures of outcome were classified as biochemical, functional, morphologic and endothelial; the majority of studies had one (48%) or two (40%) end-points. Twenty-five studies (10%) had endothelial measures of outcome, alone or in combination with other types of outcomes. Human clinical work was represented by 34 (14%) studies of clinical transplantation and nine (4%) experiments on human tissue only. There were five randomized clinical trials, representing 2% of all papers and 15% of all clinical research.nnnCONCLUSIONnIn conclusion, most of the surgical publications on prolonged cardiac preservation result from animal research. Small animal models of ex vivo ischemia and reperfusion are predominant.

The energy metabolism in the right and left ventricles of human donor hearts across transplantation.

OBJECTIVEnBrain death appears to predominantly affect the right ventricle (RV) and right ventricular failure is a common complication of clinical cardiac transplantation. It is not clear to what extent myocardial energy stores are affected in the operative sequence. We aimed to describe the time-dependent variation in high energy phosphate (HEP) metabolism of the two ventricles, and the relationship with endothelial activation and postoperative functional recovery.nnnMETHODSnFifty-two human donors had serial biopsies from the RV and the left ventricle (LV) at (1) initial evaluation, (2) after haemodynamic optimisation, (3) end of cold ischaemia, (4) end of warm ischaemia, (5) reperfusion, and (6) at 1 week postoperatively. HEP was measured by chemiluminescence in biopsies 1-5 and adhesion molecules (P-selectin, E-selectin, VCAM-1) and thrombomodulin were analysed by immunohistochemistry in biopsies 5-6. Seventeen donors and five recipients had RV intraoperative pressure-volume recordings by a conductance catheter. Six patients served as live controls.nnnRESULTSnBrain death did not affect HEP metabolism quantitatively. There was no difference between the RV and LV at any time point, but significant time-dependent changes were observed. The RV was prone to HEP depletion at retrieval, with ATP/ADP falling from 3.89 to 3.13, but recovered during cold ischaemia. During warm ischaemia the ATP/ADP ratio fell by approximately 50%, from 5.48 for the RV and 4.26 for the LV, with partial recovery at reperfusion (P<0.005). Hearts with impaired function in the recipient showed marked variations in HEP levels at reperfusion, and those organs with RV dysfunction failed to replenish their energy stores. However, these organs were not different from normally functioning allografts in terms of endothelial activation and clinical risk factors. There was poor correlation between pressure-volume and HEP data in either donor or recipient studies. Hearts followed-up with HEP and pressure-volume studies showed improvement in the recipient, despite functioning against a higher pulmonary vascular resistance.nnnCONCLUSIONSnHEP are preserved over a wide range of contractile performance in the donor heart, with no metabolic difference between the two ventricles. No correlation with endothelial activation was seen either. Preservation efforts should be directed to the vulnerable periods of implantation and reperfusion.

Comparison of central venous and inferior vena caval pressures

Inferior vena caval pressures were measured in 60 patients undergoing cardiac catheterization and compared with central venous pressure from within the right atrium. Mean pressures within the abdominal inferior vena cava were essentially the same as mean right atrial pressure, suggesting that the inferior vena cava provides a useful safe alternative for measuring central venous pressure.

Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation.

OBJECTIVEnSolid organ transplantation is associated with activation of apoptotic pathways and other stress markers. We aimed to describe the expression of Bax, Bcl-2, iNOs and Hsp-70 in the endothelium and myocytes of both ventricles and to see if there is any relationship with clinical donor organ failure.nnnMETHODSnTwelve patients undergoing heart or heart-lung transplantation (including three domino cases) were studied with transmural biopsies from the right (RV) and the left ventricles (LV) at the following points: after donor optimisation; at the end of ischaemic time; and after 10 min of reperfusion. The 1-week endomyocardial RV biopsy was also examined. Five donor hearts turned down purely on functional grounds were analysed also.nnnRESULTSnThere was no difference between the RV and the LV for any of the markers at intraoperative assessment. The pattern of expression was not predictive of allograft failure. Donor hearts, however, have a strong pro-apoptotic phenotype, which is largely unopposed by the protective factors Bcl-2 and Hsp-70. Furthermore, the intensity of myocyte staining increases over time for Bax (P<0.001) and iNOs (P=0.02). Domino hearts showed a similar pattern. Compared to usable organs, poorly functioning donor hearts have stronger myocardial staining for Bax (P=0.002) and iNOs (P=0.01).nnnCONCLUSIONSnClinical cardiac transplantation is associated with activation of the Bax and iNOs pathways in both ventricles. The myocardium is affected in time-dependent fashion but this is compatible, to a certain extent, with satisfactory allograft function. Donor hearts turned down on the basis of poor haemodynamic performance have significantly higher expression of Bax and iNOs.

Systolic right ventricular dysfunction in 'good' donor hearts- a normal finding?

Cardiac enlargement was present in 5% of donors, 60% subsequently returned to normal size. Age, cause of death, sex and time from admission to harvest were not significantly different between transplanted and non-transplanted groups. Bivariate analysis demonstrated edema (p50.01), number of initial and final abnormal diagnoses (p50.007 and p50.006) initial and final right lung densities (p50.04 and p50.002) and final left lung densities (p50.02) were greater in the non-transplanted group. Worsening of lung infiltrates was more prominent in the nontransplanted group (p50.02), however improvement in densities was not associated with transplantation (p50.6). Multivariate analysis determined that moderate and severe lung densities (OR 3.8, p50.03 and 7.7 p50.012) were independent predictors of rejection for transplantation. With measures of lung density removed from the model, the number of final film abnormal diagnoses was an independent predictor of rejection for transplantation (OR 3.1, p50.004). Conclusions Over one third of organ donors initially have lung infiltrates and 28% to 38% of these abnormalities improve during evaluation but this improvement does not impact on successful procurement. Multiple abnormal radiographic diagnoses also contribute to rejection for transplantation.

Expression of endothelial adhesion molecules and thrombomodulin in cardiac transplantation

Objective: To describe the pattern of endothelial cell activation (ECA) in the transplanted human heart. Methods: 39 donor hearts had trucut biopsies from the right (RV) and the left ventricles (LV) at: initial assessment of the donor, end of warm ischaemia and after 10 min. of reperfusion. In addition, heart transplant patients had follow up RV biopsies during rejection surveillance at 1 week, 1 month and 3 months postoperatively. Biopsies exhibiting rejection were excluded from the analysis. 6 of the patients were cystic fibrosis domino donors. Another 9 patients undergoing routine cardiac surgery served as controls. Psel, VCAM-1, Esel and thrombomodulin (Thr) were examined by immunohistology. Results: There was no difference between the RV and the LV at any of the intraoperative time points, but important time-dependent variations were seen. Psel, and VCAM-1 (but not Esel) are upregulated in brain-dead and in domino donors (p 0.01 for LV and p 0.005 for RV). Thr is reduced at the baseline in all hearts used for transplantation, and the depletion accentuates postoperatively (p 0.30 for LV and p 0.02 for RV). Psel is present in 85% of vessels throughout transplantation and decreases to cca. 60% post-transplant (p 0.001). VCAM-1 is present in 20% of vessels initially, decreases to 5% during storage (this fall is inversely correlated to the ischaemic time), increases to 47% at reperfusion and gradually decreases thereafter (p 0.001). Esel expression increases progressively from 15% initially to 45% at reperfusion and decreases postoperatively (p 0.001). Patients with donor organ failure did not have any specific pattern of ECA. However, there was a trend towards accumulation of clinical risk factors in this group. Recipients of aprotinin had reduced expression of Esel and VCAM-1 in the LV at reperfusion. Conclusion: Cardiac transplantation (including domino) is associated with marked ECA changes, with no difference between the two ventricles. The changes persist in the postoperative period even in the absence of rejection. Expression of ECA markers is influenced by aprotinin but is not predictive of donor organ failure.

Permanent pacemakers: should straightened atrial leads be repositioned?

The aim of this study was to assess if atrial leads whose “J” configuration has straightened significantly on the postprocedural chest X ray should be repositioned. Between January 1996 and December 1997, 445 patients underwent dual chamber pacemaker implantation at the Papworth Hospital. Postprocedural chest X rays were available in 410 of these. The degree of straightening of the tip of the atrial lead was assessed from the lateral chest X ray and was graded as mild (−10 to +10 degrees from the horizontal), moderate (+10 to +30 degrees), or severe (≥+30 degrees). Patients were followed with regard to atrial sensing and pacing characteristics, lead displacements, and lead revisions. Fifty‐two (12%) patients had some degree of straightening (graded mild, moderate, severe) of the atrial lead on the postprocedure chest X ray (passive fixation in 48, active 4). Of these, 12 patients underwent next day lead repositioning, 5 of whom had abnormalities of pacing and/or sensing parameters. Seven patients therefore underwent repositioning of the atrial lead despite normal pacing parameters in view of lead straightening alone. Of the 12 patients who underwent repositioning, 3 still had lead straightening after the second procedure. The cohort for follow‐up consisted of 43 patients (24 [56%] men, age 69 ± 11 years at the time of implant) who were left with significant atrial lead straightening but adequate atrial parameters. Straightening was mild in 26 patients, moderate in 10, and severe in 7 patients. At implant the P wave amplitude was 4.8 ± 2.4 mV. Follow‐up was for 4.8 ± 2.1 years, a total of 178 patient years. At final follow‐up, the P wave amplitude was 2.7 ± 1.3 (P < 0.05 vs implant). Censoring events occurred in 16 cases, comprising 11 deaths (none suspected to be pacemaker or lead related), 3 cases of persistent atrial fibrillation, 1 system extraction for infection, and 1 lead extraction for erosion. There were no cases of inadequate atrial lead sensing or pacing in the remaining patients. Irrespective of the degree of lead straightening on the postoperative lateral chest X ray, atrial leads should not be repositioned unless there are abnormalities of pacing or sensing parameters. (PACE 2003; 26:2142–2145)