Serban C. Stoica

Octogenarians undergoing cardiac surgery outlive their peers: a case for early referral

Objective: To examine short and long term outcomes of octogenarians having heart operations and to analyse the interaction between patient and treatment factors. Methods: Multivariate analysis of prospectively collected data and a survival comparison with an age and sex matched national population. The outcomes were base in-hospital mortality, risk stratified by logistic EuroSCORE (European system for cardiac operative risk evaluation), and long term survival. Results: 12 461 consecutive patients (706 over 80 years) operated on between 1996 and 2003 in a regional UK unit were studied. Octogenarians more often had impaired ventricular function, pulmonary hypertension, and valve operations. They also included a higher proportion of women, had a higher serum creatinine concentration, and had a trend towards more unstable angina. Younger patients had a higher prevalence of previous cardiac operation, previous myocardial infarction, and diabetes. The in-hospital mortality rate was 3.9% for all patients (EuroSCORE predicted 6.1%, p < 0.001) and 9.8% for octogenarians (predicted 14.1%, p  =  0.002). Long bypass time and non-elective surgery increased the risk of death above EuroSCORE prediction in both groups. A greater proportion of octogenarians stayed in intensive care more than 24 hours (37% v 23%, p < 0.001). Long term survival was significantly better in the study patients than in a general population with the same age–sex distribution (survival rate at five years 82.1% v 55.9%, p < 0.001). Conclusions: Cardiac surgery in a UK population of octogenarians produced excellent results. Elective referrals should be encouraged in all age groups.

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

BACKGROUND Heart-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. METHODS We 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). RESULTS Female 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. CONCLUSIONS Heart-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

BACKGROUND High-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. METHODS We 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. RESULTS One 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). CONCLUSIONS Use 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.

The endothelium in clinical cardiac transplantation

Cardiac transplantation is the most successful therapy for refractory heart failure, but clinical transplantation is still confronted with the problems of acute rejection and acute pump failure. The limiting factor in achieving prolonged survival remains cardiac allograft vasculopathy. In recent years it has become apparent that from brain death onward, the cardiac endothelium plays a key role in these acute and chronic events. Brain death is associated with an inflammatory response that primes the endothelium for cumulative injury during the subsequent stages of ischemic cold storage, reperfusion and allorecognition. As a structural and functional interface, the endothelium is the site at which inflammatory cells move from the bloodstream through the vessel wall into the parenchyma. The endothelium interacts with the complement system, the coagulation and inflammatory cascades, circulating leukocytes, the immune system, the smooth muscle in the vessel wall, and the surrounding matrix and cardiomyocytes. A better understanding of its many roles may lead to expansion of our therapeutic possibilities and better outcomes overall. This article reviews the possible roles of the endothelium in relation to cardiac transplantation, and discusses the diagnostic and therapeutic modalities that are available to date.

Two-decade analysis of cardiac storage for transplantation

OBJECTIVE Cardiac 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. METHODS Five 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. RESULTS Two 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. CONCLUSION In 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.

OBJECTIVE Brain 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. METHODS Fifty-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. RESULTS Brain 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. CONCLUSIONS HEP 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.

Microsimulation and clinical outcomes analysis support a lower age threshold for use of biological valves

Objective To characterise contemporary results of aortic valve replacement in relation to type of prosthesis and subsequent competing hazards. Methods 5470 procedures in 5433 consecutive patients with aortic valve replacement ± coronary artery bypass grafting (CABG) were studied. Microsimulation of survival and valve-related outcomes was performed based on meta-analysis and patient data inputs, with separate models for age, gender and CABG. Survival was validated against the UK Heart Valve Registry. Results Patient survival at 1, 5 and 10 years was 90%, 78% and 57%, respectively. The crossover points at which bioprostheses and mechanical prostheses conferred similar life expectancy (LE) was 59 years for men and women (no significant difference between prosthesis types between the ages of 56 and 69 for men, and 58 an 63 for women). The improvement in event-free LE for mechanical valves was greater at younger ages with a crossover point of 66 years for men and 67 years for women. Long-term survival was independently influenced by age, male gender and concomitant CABG, but not by type of prosthesis. In bioprostheses the most common long-term occurrence was structural deterioration. For men aged 55, 65 and 75 at initial operation it had a lifetime incidence of 50%, 30% and 13%, respectively. The simulation output showed excellent agreement with registry data. Conclusion Bioprostheses can be implanted selectively in patients as young as 56 without significant adverse effects on life expectancy, although event-free life expectancy remains significantly lower with bioprostheses up to age of implant of 63.

Pulmonary Vein Augmentation for Single Lung Transplantation

We describe a simple method of augmenting pulmonary veins using the donor pericardium in lung grafts which have been procured without an adequate donor left atrial cuff. The method allows making use of lungs procured with suboptimal surgical technique, such as those with short atrial cuffs or completely separated superior and inferior pulmonary veins. We also have applied it equally successfully on the right lung.

Double aortic arch masquerading as asthma for thirty years.

A case of a 30-year-old woman with a double-barrelled aorta misdiagnosed as asthma is presented. The patient was significantly improved after surgical treatment but a degree of airway symptoms persisted. She was further investigated and diagnosed with tracheomalacia. The paediatric experience with managing tracheomalacia is briefly reviewed and recommendations for the treatment of the rare adult cases are made. Our report emphasises the importance of early diagnosis and treatment of aortic arch abnormalities.

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

OBJECTIVE Solid 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. METHODS Twelve 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. RESULTS There 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). CONCLUSIONS Clinical 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.