Confocal Scanning Microscopy in Assessment of Cardiac Allograft Rejection--A Pilot Study.

Cardiac allograft rejection is typically diagnosed on the basis of hematoxylin and eosin (H&E) histology of endomyocardial biopsies. This diagnosis is made based on the degree of immune cell infiltrate and associated myocyte damage. However, considerable variability in rejection grading between pathologists can occur. Confocal microscopy provides high contrast and high resolution imaging that has the potential to provide detailed views of pathological features of allograft rejection. In this pilot study we sought to determine if confocal microscopy could be used to detect features of cardiac rejection. This was achieved by collection of additional sample at 30 biopsy procedures from 15 heart transplant patients. Routine pathological grading of H&E histology identified 5 gradings of 0R, 21 gradings of 1R, and 3 gradings of 2R. From these gradings, 3 samples for 0R, 9 samples for 1R, and 3 samples for 2R were imaged by confocal microscopy. This was achieved by fluorescently labeling sections with DAPI, wheat germ agglutinin, and phalloidin, to visualize the cell nuclei, cell border and extracellular matrix, and muscle cell actin, respectively. Labeling with these fluorescent markers was of high contrast. However, we did note variability in DAPI and phalloidin labeling of tissue sections. Confocal imaging of these labels revealed the following features at high resolution: perivascular and/or interstitial infiltrate, myocyte damage, and Quilty lesions. In particular increased detail of damaged myocytes reveals distortion in myofilament organization that could be exploited to distinguish between 1R and 2R grades. In conclusion, confocal microscopy provided high contrast and resolution imaging of cardiac biopsies that could be explored further to aid assessment of cardiac allograft rejection.

The utility of a 'non-significant' coronary angiogram.

BACKGROUND: Coronary angiography is the gold standard for assessing coronary artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50% stenosis) is found. It is uncertain whether this 'non-significant' result influences management and outcomes. We reviewed characteristics and outcomes in a contemporary cohort of chest pain referrals who had mild or absent CAD on coronary angiography. METHOD: All patients undergoing coronary angiography at Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983). Of these, 12.3% (n = 366) underwent coronary angiography for evaluation of chest pain and were found to have absent or mild CAD. These patients were followed up for 2.3 ± 0.6 years. RESULTS: Mean age was 60.0 ± 12.3 years, 56.1% were female. The ECG was abnormal in 55.0% of patients. Stress testing for inducible ischaemia was undertaken in 40.7% of patients and was abnormal in 57.7%. Following angiography, 43.2% had no changes to cardiac medications. Additional drug therapy (aspirin, statin, beta-blockers, ACE-inhibitor) was commenced in around 14.2-22.1% of cases. These drugs were discontinued in 4.1-8.2% of patients. Rates of major adverse cardiovascular events and readmissions with chest pain were 0.3% (1) and 1.9% (7) respectively at 30 days, and 1.9% (7) and 6.0% (22) at 1 year. CONCLUSION: Although even non-obstructive atheroma may justify medical therapy to limit disease progression, our findings may suggest that in these cases, invasive coronary angiography, may not lead to the patient/physician reassurance justified by historical data.

Return to work after heart transplantation: the New Zealand experience.

INTRODUCTION: Return to work and social re-integration following heart transplantation is a significant challenge for patients. The aim of this study is to provide a snapshot of the current employment status and factors associated with return to work in New Zealand recipients over the past decade. METHODS: Consecutive surviving patients who underwent heart transplantation in the 10 years from June 2001 to June 2011, alive in July 2012, were retrospectively identified. Details on demographics, employment before and after transplantation were obtained and recorded. RESULTS: A total of 87 patients were included, out of a total of 111 patients who underwent heart transplantation in the 10 year period from June 2001 (24 patients had died prior to July 2012). The median age of the study cohort was 52 years (range 15-75 years) and 19 were female. A total of 51 (58.6%) patients were in paid employment at the time of review. Of the 36 (41.4%) patients not in paid employment, 5 were students, 12 were retired and 10 were homemakers or not working through lifestyle choice. Two patients were unable to work for health reasons. Seven (8%) patients considered able to work were on an unemployment or invalid's benefit. Of the patients working prior to heart transplantation, 88.9% returned to work after a median of 8.5 months, and 70.6% remained on paid employment at a median follow-up of 77 months after transplantation. There was a statistically significant correlation between the time of stopping work prior to transplant and return to work after transplant (r = 0.497, P < .01). CONCLUSION: The current rate of paid employment in patients who underwent heart transplantation was similar to the overall employment rate in New Zealand. The most important predictor of returning to work was employment status prior to transplantation. Discussions regarding return to work early in the transplantation assessment process and actively assisting patients to seek employment after transplantation may improve employment rates.

Bone density in heart or lung transplant recipients--a longitudinal study.

BACKGROUND: Osteoporosis is prevalent among heart or lung transplant (HLT) candidates. Bone loss is common posttransplant, with an associated increase in fracture risk. There is a lack of consensus regarding optimal management of bone health in HLT recipients. We report bone health data in a cohort of HLT recipients before and after transplantation and make recommendations for management. METHODS: Patients over the age of 20 who had a heart or lung transplant between 2000 and 2011 were identified from the New Zealand HLT Service database, and demographic data, immunosuppressive regimens, bisphosphonate use, and serial bone mineral density (BMD) data were extracted. RESULTS: Pretransplant BMD was available in 52 heart and 72 lung transplant recipients; 30 and 42, respectively, also had posttransplant BMD data. Pretransplant osteopenia or osteoporosis prevalence were 23% and 8% for heart candidates and 36% and 31% for lung candidates. Posttransplant, BMD decreased significantly at the femoral neck but not at the lumbar spine in the first year, with subsequent stabilization particularly in the presence of bisphosphonate use. Pretransplant BMD was the major predictor for developing osteopenia or osteoporosis after transplantation. CONCLUSION: A significant proportion of HLT recipients have osteopenia or osteoporosis pretransplant, and this persists posttransplant. Pretransplant BMD is an important predictor of subsequent osteopenia or osteoporosis development, allowing risk stratification and targeted intervention.

Exploring parenthood in the New Zealand Heart Transplant Program.

Heart transplantation is an established treatment for end-stage cardiac disease. This study describes parenthood after heart transplantation in the New Zealand population. An analysis was performed of all heart recipients from the New Zealand program. Exclusion criteria were death within 3 months of transplantation or age <18 years at the time of the survey. Recipients (or next of kin if recipients deceased) were surveyed regarding family status at the time of transplantation and new parenthood after transplantation. A total of 145 of 199 eligible recipients completed the survey ∼12.2 years after transplant (119 male, 26 female). Before transplantation, 81% were in a permanent relationship; 72% had children. After transplantation, 19/45 recipients had 27 children (2 female recipients had 3 children), of whom 15 were planned. Complications occurred in 7/27 pregnancies (including one atrial septal defect requiring surgery). Two recipients died after the birth of their children (children aged 2.6 and 14.1 years). This study provides unique data relevant to both female and male recipients regarding new parenthood after heart transplantation and will promote more informed discussion with transplant recipients.

Progressive pulmonary hypertension post atrial septal defect device closure-early symptomatic improvement may not predict outcome.

BACKGROUND: For patients with an atrial septal defect and pulmonary hypertension it can be difficult to determine whether it is safe to intervene. With newer treatments for pulmonary hypertension and transcatheter techniques avoiding surgical stressors, it has been hoped that we can occlude previously inoperable defects safely. METHODS: We undertook a subgroup analysis of outcomes for patients with mean pulmonary artery pressure (PAp) ≥30mmHg from within our database of patients undergoing transcatheter ASD closure from 1997 to 2004. RESULTS: Data for 11 patients were reviewed. Mean age of the patients at intervention was 38 years (5-69 years). Eight patients have had symptomatic improvement with no evidence of progressive pulmonary hypertension. There was one death due to unrelated causes. Two patients have developed progressive pulmonary vascular disease with one death. CONCLUSIONS: Despite early symptomatic improvement, adverse outcomes may occur in patients with elevated pulmonary vascular resistance undergoing transcatheter ASD closure. Careful haemodynamic evaluation is vital. Modest elevation of pulmonary vascular resistance and the presence of left to right shunt (Qp:Qs>1.5:1) are reassuring.

Percutaneous closure of patent foramen ovale.

AIM: To review the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) in symptomatic patients without the use of general anaesthesia or echocardiographic guidance. METHOD: All patients accepted for percutaneous PFO closure by our service from August 2002 to August 2004 were included. Patient demographics and clinical information were obtained from clinical records and by telephone interview. Follow-up outcomes recorded were recurrence of systemic thromboembolism, residual shunt, and change in pattern of migraines. RESULTS: Forty consecutive adult patients, of whom 19 (48%) had an atrial septal aneurysm (ASA), underwent PFO closure using the Amplatzer occluder device with fluoroscopic guidance alone. Their mean age was 45 +/- 10 years (range 23-63 years) and 24 (60%) were male. The indications for closure were ischaemic stroke (n = 26), transient ischaemic attack (TIA) (n = 8), both stroke and TIA (n = 2), refractory hypoxia (n = 2), platypnoea-orthodeoxia (n = 1) and severe migraine with seizures (n = 1). Twenty patients suffered a single neurological event and 16 suffered >1 event, including six with only radiographic evidence of >1 event. Mean procedure time was 17.7 +/- 9.6 min and fluoroscopy time was 6.7 +/- 7.3 min. Implanted device sizes were 18 mm (n = 1), 25 mm (n = 37) and 35 mm (n = 2). In 33 patients, the procedure was performed as a day-case. No complications were encountered. No further neurological events occurred in 39 patients at a mean follow-up time of 11 +/- 7 months (3-25 months) nor was a significant shunt detected in the 34 who underwent follow-up echocardiography. CONCLUSIONS: Percutaneous closure of PFO with or without ASA, under local anaesthesia and without echocardiographic guidance, is a safe and effective procedure which can be performed as a day-case. This has now become our standard clinical practice.

Transcatheter closure of a complex postmyocardial infarction ventricular septal defect after surgical patch dehiscence.

Ventricular septal defect (VSD) complicating acute myocardial infarction is a rare but serious event carrying a high mortality. Residual shunting after emergency surgical repair is common, adversely affects prognosis and can necessitate reoperation. We describe the successful transcatheter VSD closure with the Amplatzer occluder in a 75-year old man after earlier emergency surgical repair of a VSD complicating an acute myocardial infarction. The technique and positioning of the device in a tortuous infero-apical VSD are described.

Transplant "twins": the experience of sharing transplanted thoracic organs from the same donor.

BACKGROUND: Many thoracic transplant recipients who receive organs from the same donor share facilities for 3 months, and are aware that they have received organs from the same donor. METHODS: A confidential questionnaire including open and closed questions assessed relationships between "twins" and the experience of having a twin. The Significant Others Scale assessed social support. Of 141 heart and 58 lung transplants, 25 pairs of transplant twins were identified. Questionnaires were sent to the 32 surviving twins. RESULTS: Twenty-six twins responded; 17 had received a heart and nine a lung. The 17 men and 9 women had a mean age of 51 years. Eighteen respondent's "twins" remained alive at the time of participation and eight had died. Sixty-six percent of the both- twin alive group and 43% of one-twin alive group felt they had a special bond with their twin, different from the other relationships that they have experienced. Fifty-six percent of the both-twin alive group and 43% of one-twin alive group felt having a twin enriched their transplant experience. Transplant twins rated social support last behind: the transplant support personnel; close family members; other transplant recipients; and good friends and general practitioners, both in levels of ideal and actual support. Transplant twins showed the largest discrepancy between levels of ideal and actual support than any other individual ranked. CONCLUSIONS: Being a transplant twin is a special experience that generally enriches the overall transplant experience but having a transplant twin, does not appear to enhance the amount of social support.

Planned pregnancy in a heart transplant recipient.

Solid organ transplantation often leads to the return of fertility in recipients. In females of childbearing age this can be accompanied by a desire to have children. The present paper discusses a planned pregnancy in a heart transplant recipient and outlines important -management issues. These principles of management can be applied to most solid organ transplant recipients.

Rapamycin in cardiovascular medicine.

The cellular action of rapamycin (sirolimus), a natural fermentation product produced by Streptomyces hygroscopicus, is mediated by binding to the FK506 binding protein. By inhibiting a kinase known as the target of rapamycin, it restricts the proliferation of smooth-muscle cells by blocking cell-cycle progression at the G1/S transition. The finding that rapamycin possesses both anti-proliferative and antimigratory activity suggests that it could contribute to the control of arterial re-narrowing after percutaneous intervention and control the vascular manifestations of chronic rejection in transplanted hearts. The first clinical trials of implantation of rapamycin- coated stents in obstructive coronary artery lesions have been reported and, in selected patient groups, it appears that the restenosis process has been abolished. Studies are underway to establish the benefits of rapamycin-coated stents in day-to-day interventional practice, including small vessels, long lesions and patients with multivessel disease. With the addition of novel antiplatelet agents and delivery systems, it is possible that the two major limitations of percutaneous coronary intervention - restenosis and stent thrombosis - will be overcome. Cardiac graft loss due to intimal hyperplasia and accelerated atherosclerosis remains the major limitation to long-term survival following cardiac transplantation. Animal studies of rapamycin have suggested that this process can be reduced or abolished. Human studies of the efficacy of rapamycin in preventing both acute rejection and allograft arterial disease are in progress. Concerns regarding toxicity, carcinogenicity, delayed healing and endothelialization remain. As with any new agent or technology, we must remain vigilant to late adverse side-effects.

Clinical and angiographic factors associated with asymptomatic restenosis after percutaneous coronary intervention.

BACKGROUND: Angiographic restenosis after percutaneous coronary interventional procedures is more common than recurrent angina. Clinical and angiographic factors associated with asymptomatic versus symptomatic restenosis after percutaneous coronary intervention were compared. METHODS AND RESULTS: All patients with angiographic restenosis from the BENESTENT I, BENESTENT II pilot, BENESTENT II, MUSIC, WEST 1, DUET, FINESS 2, FLARE, SOPHOS, and ROSE studies were analyzed. Multivariate analysis evaluated 46 clinical and angiographic variables, comparing those with and without angina. The 10 studies recruited 2690 patients who underwent percutaneous revascularization and 6-month follow-up angiography (86% of those eligible). Restenosis (>/=50% diameter stenosis) occurred in 607 patients and was clinically silent in 335 (55%). Male sex (P=0.008), absence of antianginal therapy with nitrates (P=0.0002) and calcium channel blockers (P=0.02) at 6 months, greater reference diameter after the procedure (P=0.04), greater reference diameter at follow-up (P=0.004), and lesser lesion severity (percent stenosis) at 6 months (P=0.0004) were univariate predictors of asymptomatic restenosis. By multivariate analysis, only male sex (P=0.04), greater reference diameter at follow-up (P=0.002), and lesser lesion severity at 6 months (P=0.0001) were associated with restenosis without angina. CONCLUSIONS: Approximately half of patients with angiographic restenosis have no symptoms. The only multivariate predictors of silent restenosis at 6 months were male sex, greater reference diameter at follow-up, and lesser lesion severity on follow-up angiography.

Outcome following heart transplantation in Maori and Polynesian patients: a comparison with European New Zealanders.

AIM: To compare demographic, clinical and outcome data of Maori and Polynesian with New Zealand European heart transplant patients. METHODS: A retrospective analysis was made of data from the 104 patients who underwent heart transplantation at Green Lane Hospital over a period of twelve years, of whom 79 were European, 23 Maori/Polynesian, and two Asian. Clinical characteristics, blood group, HLA matching and outcomes of recipients were compared. RESULTS: There was no significant difference in age and gender between the two groups. Maori and Polynesian patients were heavier, had a greater body mass index and were more likely to have rheumatic heart disease than their European counterparts. Maori/Polynesian patients were predominantly blood group A, whilst European patients were mainly group O. The waiting time for a donor heart was similar in both groups. There was no significant difference in number of rejection episodes and survival. CONCLUSIONS: Green Lane Hospital has the largest international experience of heart transplantation in Maori and Polynesian patients. Although there are some differences in clinical profile, outcome in terms of rejection episodes and survival is similar in the two groups.

5 French guide catheters for percutaneous coronary intervention: a feasibility study in 100 consecutive patients.

Percutaneous coronary intervention using smaller-diameter guide catheters may have a favorable impact on groin complications, mobilization time, hospital stay, and contrast use. This prospective registry study assessed the feasibility of routine stent delivery through 5 Fr guide catheters. Of the 100 consecutive patients, 5 Fr guided intervention was attempted in 84 and was successful in all but 2 patients who had chronic complete occlusions. Reasons for not selecting a 5 Fr guide were planned kissing balloons (eight), directional coronary atherectomy (one), and no suitable 5 Fr guide in stock (seven). There was no stent dislodgment, need to change to a larger-caliber guide, or inadequate contrast opacification. When necessary, guide support was achieved by deep-vessel intubation, which was not associated with vascular damage. The only adverse sequelae were non-Q-wave myocardial infarctions in two patients. Coronary artery stenting using 5 Fr guide catheters is feasible and applicable to most patients.

Coronary angioplasty in New Zealand 1995-1998: a report from the National Coronary Angioplasty Registry.

AIMS: To report coronary angioplasty data collected by the New Zealand Coronary Angioplasty Registry from 1995-1998. METHOD: Information on all patients undergoing attempted coronary angioplasty in eight New Zealand institutions was recorded on datasheets at the time of, or soon after, the procedure. These were forwarded to the registry at Green Lane Hospital. RESULTS: Over the four-year period, 8395 angioplasty procedures were performed by 26 cardiologists in eight coronary interventional facilities, with a procedural success rate of 94%. Procedural numbers grew steadily, with 55% more coronary angioplasties performed in 1998 than in 1995 (p = 0.02). The New Zealand national angioplasty rate, which rose from 459/million population in 1995 to 684/million in 1998, remains lower than that of Australia and Western European countries. Excluding those that underwent angioplasty for acute myocardial infarction, the number of peri-procedural deaths was similar, with six in 1995 and four in 1998 (p = 0.30), and the requirement for emergency bypass surgery fell from 22 cases in 1995 to three in 1998 (p < 0.001). The use of stents increased dramatically, with 85% of patients receiving a stent in 1998, compared with 23% in 1995 (370% increase, p < 0.001). This was associated with a reduction in the number of patients requiring repeat percutaneous interventions for restenosis (10.7% in 1995 to 6.4% in 1998, p < 0.001). CONCLUSION: There has been a steady growth in the numbers of patients with coronary artery disease treated by coronary angioplasty, and in the number treated by intracoronary stents from 1995 to 1998. The need for urgent coronary bypass surgery has fallen. Continued submission of complete and accurate data to the coronary angioplasty registry is vital for ongoing audit.