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Background: The domino-donor operation occurs when a “conditioned” heart from the heart-lung transplant (HLT) recipient is transplanted into a separate heart transplant (HT) recipient. The purpose of this systematic review was to investigate the indications and outcomes associated with the domino procedure. Methods: An electronic search was performed to identify all prospective and retrospective studies on the domino procedure in the English literature. Eight studies reported 183 HLT recipients and 263 HT recipients who were included in the final analysis. Results: HLT indications included cystic fibrosis in 58% (95% CI: 27–84%) of recipients, primary pulmonary hypertension (PPH) in 17% (95% CI: 12–24%), bronchiectasis in 5% (95% CI: 3–10%), emphysema in 5% (95% CI: 0–45%), and Eisenmenger’s syndrome in 4% (95% CI: 2–8%). HT indications included ischemic heart disease in 40% (95% CI: 33–47%), non-ischemic disease in 39% (95% CI: 25–56%), and re-transplantation in 10% (95% CI: 1–59%). The pooled mean pulmonary vascular resistance (PVR) in HT recipients was 3.05 Woods units (95% CI: 0.14–5.95). The overall mortality in the HLT group was 28% (95% CI: 18–41%) at an average follow-up of 15.68 months (95% CI: 0.82–30.54), and 35% (95% CI: 17–58%) in the HT group at an average follow-up of 37.26 months (95% CI: 6.68–67.84). Freedom from rejection in HT was 94% (95% CI: 75–99%) at 1 month, 77% (95% CI: 30–96%) at 6 months, and 41% (95% CI: 33–50%) at 1 year. Conclusions: The domino procedure appears to be a viable option in properly selected patients that can be performed safely with acceptable outcomes.

[first paragraph of article]This year marks the 51st anniversary of the first human heart transplant operation by Christiaan Barnard at the Groote Schuur Hospital in Cape Town. This event has had a profound effect on Science, Medicine and Humanity, almost beyond expectations. The anniversary calls for celebrations, and evaluation, as with maturity comes accountability. We here attempt to summarise the reasons for celebrations, and highlight the remaining many challenges and expectations. Regarding the celebrations, this anniversary exemplifies and calls for celebration of at least four human attributes; courage, innovation, compassion, and human spirit.

OBJECTIVES Pulmonary hypertension (PHT) is associated with tricuspid annular dilatation, but the effect of acute increase of pulmonary pressure on three-dimensional (3D) tricuspid annular dynamics and shape is unknown. Better understanding of tricuspid annular dynamics may lead to improved and more durable surgical reparative techniques. METHODS In nine open-chest anaesthetized sheep nine sonomicrometry crystals were implanted on the right ventricle while on cardiopulmonary bypass. Additional nine crystals were implanted around the tricuspid annulus (TA) with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Two additional equidistant crystals were implanted between each commissure, creating three segments for every region. Pressure transducers were placed in the left ventricular (LV), right ventricular (RV) and right atrium. PHT was induced by acute pulmonary artery constriction with a pneumatic occluder. Sonomicrometry and echocardiographic data were collected before and after induction of PHT. TA area, regional and total perimeter, and 3D annular geometry were calculated from 3D crystal coordinates. Regional annular contraction was defined as the percentage difference between maximal and minimal region length during the cardiac cycle. RESULTS PHT increased RV pressure from 31 ± 9 mmHg to 46 ± 13 mmHg (P = 0.001) and decreased left ventricular (LV) pressure from 111 ± 24 mmHg to 78 ± 36 mmHg (P = 0.018). There was no significant tricuspid regurgitation observed with PHT. During PHT, the TA area increased by 12 ± 13% from 641 ± 139 mm(2) to 721 ± 177 mm(2) (P = 0.037). The total perimeter increased from 103 ± 11 mm to 109 ± 13 mm (P = 0.02). All annular regions dilated significantly with PHT with 8 ± 10, 5 ± 5 and 5 ± 5% increase in anterior, posterior and septal annular length, respectively (P < 0.05). PHT reduced regional annular contraction in the anterior region only (17 ± 7 vs 14 ± 8%; P = 0.02). The TA had a complex 3D saddle geometry and the shape of the annulus was altered during PHT only in the antero-posterior region. CONCLUSIONS The changes in tricuspid annular conformation, contractility and its 3D geometry observed during acute ovine PHT may help in the design of new pathology-specific tricuspid annular rings.

We report a rare case of a 59-year-old male who presented with a pulsating pseudoaneurysm 15 months after placement of a HeartMate II left ventricular assist device (Thoratec Corporation, Pleasanton, CA, USA). Computed tomography and echocardiogram imaging and surgical exploration revealed that bend relief spontaneously detached from the outflow conduit, and the sharp edges of the snap ring component of the bend relief caused perforation to the outflow graft. Learning objective: Left ventricular assist devices (LVADs) are of growing popularity within the field of cardiology as a means of bridge to transplant and as a destination therapy. This case highlights a rare, but potentially fatal complication of a popular LVAD, the HeartMate II. Since this case report, the US Food and Drug Administration has released a statement of this particular complication, and Thoratec has made changes to the design. However, many patients still have the older model in place, and are at risk of this rare but potentially fatal complication.>

Functional tricuspid regurgitation is a significant source of morbidity and mortality in the US. Furthermore, treatment of functional tricuspid regurgitation is suboptimal with significant recurrence rates, which may, at least in part, be due to our limited knowledge of the relationship between valvular shape and function. Here we study the dynamics of the healthy in vivo ovine tricuspid annulus to improve our understanding of normal annular deformations throughout the cardiac cycle. To this end, we determine both clinical as well as engineering metrics of in vivo annular dynamics based on sonomicrometry crystals surgically attached to the annulus. We confirm that the tricuspid annulus undergoes large dynamic changes in area, perimeter, height, and eccentricity throughout the cardiac cycle. This deformation may be described as asymmetric in-plane motion of the annulus with minor out-of-plane motion. In addition, we employ strain and curvature to provide mechanistic insight into the origin of this deformation. Specifically, we find that strain and curvature vary considerable across the annulus with highly localized minima and maxima resulting in aforementioned configurational changes throughout the cardiac cycle. It is our hope that these data provide valuable information for clinicians and engineers alike and ultimately help us improve treatment of functional tricuspid regurgitation.

Background The post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated registry established to collect post–CE Mark Trial clinical data on patients receiving a HeartWare ventricular assist device (HVAD) in the European Union and Australia. Methods The ReVOLVE is a multi-center, prospective, single-arm registry performed at seven centers in Europe and two in Australia. Herein we describe a total of 254 commercial HVAD implants according to labeled indications between February 2009 and November 2012. Summary statistics included patients’ demographics, adverse events, length of support and outcomes. Results Compared with the clinical trial supporting the CE Mark of the HeartWare system, patient selection differed in that patients were older, and there were higher proportions of females and patients with idiopathic cardiomyopathies in the ReVOLVE cohort. Duration of support ranged from 1 to 1,057 days, with a mean of 363 ± 280 days (median 299.5 days). Transplantation was done in 56 patients (22%), explant for recovery was performed in 3 patients (1%), 43 died while on support (17%), and 152 (60%) remain on the device. Success in patients with the HeartWare system was 87% at 6 months, 85% at 1 year, 79% at 2 years and 73% at 3 years. Adverse event rates were low, comparable or improved when compared to the CE Mark Trial. Conclusion Real-world use of the HeartWare system continues to demonstrate excellent clinical outcomes in patients supported with the device.

Aims Dilated cardiomyopathy (DCM) patients have abundant levels of norepinephrine secondary to failure of the norepinephrine transporter uptake mechanism. Little is known about the effects of an LV assist device (LVAD) on cardiac sympathetic innervations and norepinephrine transporter dysfunction. This study examines the effects of continuous-flow HeartMate II LVAD on cardiac sympathetic innervations using [123I]metaiodobenzylguanidine ([123I]MIBG) nuclear imaging. Methods and results After injecting 431 ± 21 MBq of [123I]MIBG, planar scintigraphy was performed at 15 min and 4 h in 14 consecutive non-diabetic non-ischaemic DCM patients. Scans were executed early post-LVAD implantation (T1) and prior to either device explantation for myocardial recovery or transplant listing (T2). [123I]MIBG measured parameters included early and delayed heart–mediastinum (H/M) ratios and washout rate (W/O). Catecholamine levels were measured using liquid chromatography–mass spectrometry. Following 208.4 ± 85.5 days of LVAD support, both early and delayed H/M ratios increased by 42.1% (P < 0.001) and 54.7% (P < 0.001), respectively. The W/O rate decreased by 46% (P = 0.003). Plasma norepinephrine, epinephrine, and dopamine decreased significantly in correlation with [123I]MIBG parameters. Ten patients had recovered and had their device explanted as they had demonstrated a higher percentage change in delayed H/M ratio, W/O rate, and norepinephrine levels. Linear regression analysis revealed a strong correlation between percentage changes in both norepinephrine and epinephrine and myocardial recovery. Conclusion Combination therapy with LVAD and drug resulted in enhancement of [123I]MIBG uptake in DCM patients.

Extracorporeal membrane oxygenation (ECMO) may be used safely as a bridge to lung transplantation in carefully selected elderly patients. We report the case of a 70-year–old patient bridged on ECMO before transplantation. A brief discussion on improving outcomes for the elderly and patients bridged on ECMO in general is presented.

Lung transplantation has grown considerably in recent years and its availability has spread to an expanding number of countries worldwide. Importantly, survival has also steadily improved, making this an increasingly viable procedure for patients with end-stage lung disease and limited life expectancy. In this first of a series of articles, recipient selection and type of transplant operation are reviewed. Pulmonary fibrotic disorders are now the most indication in the U.S., followed by chronic obstructive pulmonary disease and cystic fibrosis. Transplant centers have liberalized criteria to include older and more critically ill candidates. A careful, systematic, multi-disciplinary selection process is critical in identifying potential barriers that may increase risk and optimize long-term outcomes.

Background— We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. Methods and Results— We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, β-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the β 2 -agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2±12.6 years (16 male patients), patients were on 2.0±0.9 inotropes, 7 (35) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39±0.43 L · min −1 · m −2 , pulmonary capillary wedge pressure was 31.5±5.7 mm Hg, and heart failure history was 3.4±3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2) were explanted after 286±97 days. Eight had symptomatic heart failure for ≤6 months and 4 for >6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70±7, left ventricular end-diastolic diameter was 48.6±5.7 mm, left ventricular end-systolic diameter was 32.3±5.7 mm, mV̇ o 2 was 21.6±4 mL · kg −1 · min −1 , pulmonary capillary wedge pressure was 5.9±4.6 mm Hg, and cardiac index was 3.6±0.6 L · min −1 · m −2 . Estimated survival without heart failure recurrence was 83.3 at 1 and 3 years. After a 430.7±337.1-day follow-up, surviving explants had an ejection fraction of 58.1±13.8, left ventricular end-diastolic diameter of 59.0±9.3 mm, left ventricular end-systolic diameter of 42.0±10.7 mm, and mV̇ o 2 of 22.6±5.3 mL · kg −1 · min −1 . Conclusions— Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy.

Objective Optimum strategy for salvage in patients with acutely decompensated end-stage heart failure and severe multiorgan dysfunction is complex. We present our experience with prolonged CentriMag (Levitronix, Waltham, Mass) support for transitioning patients after successful salvage from bridge to decision directly to transplant. Methods Records of patients who underwent salvage with a CentriMag as bridge to decision and later to transplant were reviewed. Between June 2003 and June 2008, 4 patients in cardiogenic shock from acute decompensated end-stage heart failure and multiorgan dysfunction underwent salvage with biventricular CentriMag as bridge to decision. Three were male. Mean age was 39.3 years (range 24–52 years). Three had dilated cardiomyopathy; 1 had ischemic cardiomyopathy. All had preoperative mechanical ventilation, large doses of multiple inotropes, and intra-aortic balloon support. All also had acute liver and renal failure and metabolic acidosis. Results After mean postimplant period of 43 days (range 7–70 days), patients had reversal of end-organ dysfunction; after mean waiting time of 31 days (range 21–67 days), all were transplant listed. Mean mechanical circulatory support was 87.7 days (range 26–105 days). No thromboembolic or neurologic events or mechanical failures occurred. Posttransplant mean ventilation and intensive care unit stay were 2 and 4 days (ranges 1–4 and 3–7 days), respectively. All patients were discharged home and remain alive and well. Conclusion CentriMag use as long as 3 months appears to be safe and cost-effective for bridging selected patients directly to transplant after salvage. Further clinical experience is still needed.

Assessment of myocardial recovery during left ventricular assist device (LVAD) support is difficult to perform both safely and effectively. We developed a test involving short-term interruption of LVAD support with measurements of several hemodynamic and echocardiographic parameters at rest and, whenever possible, after exercise, to investigate inotropic reserve.After full heparinization, the HeartMate I XVE device was switched off. MAP, heart rate (HR), ejection fraction (EF) and left ventricular dimensions were measured on switching off, after 5, 10 and 15 minutes, and after 6-minute walk (6MW).In total, 207 serial tests were performed on 22 patients. A total of 97.6% of the patients tolerated the tests. Of the 202 tolerated tests, 130 were performed on 16 patients who had their device explanted due to myocardial recovery (recovered group), and 72 on 6 patients who did not recover and were transplanted (non-recovered group). After device discontinuation there was an immediate drop in mean arterial blood pressure (MAP), a rise in HR, a reduction in EF and increases in ventricular dimensions. These changes tended to be more marked in the non-recovered group. After 6MW, the recovered group had a significant rise in HR and EF and a non-significant increase in MAP, whereas, the non-recovered group there was a significant drop in MAP compensated by a rise in HR. The distance walked in the recovered group was significantly higher (544 +/- 102 vs 418 +/- 109 meters, p0.05). MAP, pulse pressure and EF were strong predictive factors for recovery.Acute discontinuation of the device to assess recovery is safe and well tolerated and is followed by specific changes in hemodynamic and echocardiographic parameters. This helps in the assessment of recovery, particularly with regard to findings taken after exercise.

Background The UK Government funds ventricular assist device (VAD) implantation as bridge to transplantation (BTT) at three centers. Results from this program have not been published. Methods All 70 VAD implants for BTT, 71 inotrope-dependent and 179 non-VAD transplant candidates, accepted for transplantation between April 2002 and December 2004, were prospectively monitored for survival to transplantation, survival overall and quality of life. Results Of the 70 VAD patients, 31 (44%) survived to heart transplantation, 4 (6%) were bridged to recovery and 5 remained on support at the end of the study. Thirty patients (43%) died while on support. Overall survival from VAD implant was 52% at 1 year. Ten percent of non-VAD inotrope-dependent patients and 9% of routine transplant candidates died while on the waiting list. For transplant recipients, 12-month post-operative survival was 84%, 85% and 84%, respectively, for VAD, inotrope-dependent and routine transplant candidates. VAD and non-VAD patients had similar post-transplant adverse event rates. Conclusions There was a role for VAD bridge to transplant for selected patients in the UK, despite the availability of an effective urgent transplant list. VAD patients who underwent transplantation had survival rates similar to other transplant candidates.

Objectives Left ventricular assist device (LVAD) implantation may alter right ventricular shape and function and lead to tricuspid regurgitation. This in turn has been reported to be a determinant of right ventricular (RV) failure after LVAD implantation, but the effect of mechanical left ventricular (LV) unloading on the tricuspid annulus is unknown. The aim of the study was to provide insight into the effect of LVAD support on tricuspid annular geometry and dynamics that may help to optimize LV unloading with the least deleterious effect on the right-sided geometry. Methods In seven open-chest anaesthetized sheep, nine sonomicrometry crystals were implanted on the right ventricle. Additional nine crystals were implanted around the tricuspid annulus, with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Left ventricular unloading was achieved by connecting a cannula in the left atrium and the aorta to a continuous-flow pump. The pump was used for 15 min at a full flow of 3.8 ± 0.3 l/min. Epicardial echocardiography was used to assess the degree of tricuspid insufficiency. Haemodynamic, echocardiographic and sonomicrometry data were collected before and during full unloading. Tricuspid annular area, and the regional and total perimeter were calculated from crystal coordinates, while 3D annular geometry was expressed as the orthogonal distance of each annular crystal to the least squares plane of all annular crystals. Results There was no significant tricuspid regurgitation observed either before or during LV unloading. Right ventricular free wall to septum diameter increased significantly at end-diastole during unloading from 23.6 ± 5.8 to 26.3 ± 6.5 mm (P = 0.009), but the right ventricular volume, tricuspid annular area and total perimeter did not change from baseline. However, the septal part of the annulus significantly decreased its maximal length (38.6 ± 8.1 to 37.9 ± 8.2 mm, P = 0.03). Annular contraction was not altered. The tricuspid annulus had a complex 3D saddle-shaped geometry that was unaffected during experimental conditions. Conclusions In healthy sheep hearts, left ventricular unloading increased septal-free wall RV diameter and reduced the length of the septal annulus, without altering the motion or geometry of the tricuspid annulus. Acute left ventricular unloading alone in healthy sheep was not sufficient to significantly perturb tricuspid annular dynamics and result in tricuspid insufficiency.

Background We sought to evaluate the effect of center volume on patient survival. Methods We performed a retrospective analysis on nationwide data from the Scientific Registry of Transplant Recipients provided by United Network for Organ Sharing pertaining to lung transplantation (LT) recipients transplanted between 2005 and 2013. Centers were categorized into 4 groups based on their annual volume as follows: less than 20, 20 to 29, 30 to 39, and greater than or equal to 40 LTs. Baseline characteristics were compared and Kaplan–Meier analysis was used to estimate survival. Results A total of 13,506 adult recipients underwent LT during the study period. Of these, 2,491 (18.4%) patients were transplanted in centers with volume less than 20, 2,562 (19.0%) in centers with volume 20 to 29, 2,998 (22.2%) in centers with volume 30 to 39, and 5,455(40.4%) in centers with volume greater than or equal to 40. Survival was poorest in the lowest volume centers (1-year 81.4% vs 85.5% and 5-year 49.7% vs 56.5%, respectively). Conclusions Post-LT survival in low volume centers is significantly lower than in high volume centers but the explanatory power of volume as a predictor of survival is low.

Mechanisms underlying the rapid deterioration of heart failure patients who subsequently require left ventricular assist device (LVAD) support are poorly understood. Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play a key role in myocardial remodelling and heart failure. We hypothesized that MMP and TIMP expression would be altered in these patients.Quantitative polymerase chain reaction was used to measure myocardial messenger RNA levels of MMP1 to MMP14, TIMP1 to TIMP4, collagen I and collagen III in 24 dilated cardiomyopathy (DCM) patients with deteriorating clinical status who required LVAD support (LVAD Group) and in 7 stable DCM patients undergoing transplantation without need for LVAD support (Tx Group).Levels of MMP1, MMP8 and TIMP4 were higher in the LVAD Group compared with the Tx Group (188% +/- 141%, 646% +/- 432%, and 66% +/- 33% higher, respectively, p0.05) whereas MMP2, MMP9, MMP10, MMP11, and MMP14 levels were similar. MMP3, MMP7, MMP12, and MMP13 were undetectable. All TIMPs were generally higher in the LVAD group, but only TIMP4 reached significance. Collagen I and III were not altered. We tested for correlations between MMP and TIMP expression with myocardial cytokine levels. MMP8 correlated positively with interleukin-6 and interleukin-1beta, suggesting a link between cytokines and MMPs in these patients.The data show that high myocardial collagenase (MMP1 and MMP8) expression without compensatory changes in collagen or TIMP expression is a feature of patients requiring LVAD support. This may be linked in part to elevated cytokine expression and suggests collagenase activity may be an important therapeutic target in deteriorating heart failure.

Background In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation. Methods We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the β 2 -adrenergic–receptor agonist clenbuterol was administered to prevent myocardial atrophy. Results Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (±SD) of 320±186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64±12%, the mean left ventricular end-diastolic diameter was 59.4±12.1 mm, the mean left ventricular end-systolic diameter was 42.5±13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3±6.0 ml per kilogram of body weight per minute. Conclusions In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.

Background Primary graft failure after heart transplantation is a well-recognized catastrophic complication with a high mortality rate. It is becoming more frequent due to the increasing use of marginal donors. In these difficult cases a ventricular assist device (VAD) as a bridge to recovery or as a bridge to re-transplantation can be used. The recently introduced Levitronix Centrimag centrifugal pump might be an ideal device for this purpose. Methods In this study we describe 2 patients with primary graft failure who received a Levitronix in the last 2 years, immediately after failure to wean from cardiopulmonary bypass. Biventricular support was necessary in both patients. Results One patient was successfully re-transplanted after 2 days of support, and subsequently discharged. After 16 months she has good ventricular function with no symptoms of cardiac failure. The second patient showed signs of ventricular recovery after a few days and was weaned from the device after 7 days, with good graft function. No device-related complications were recorded. After 14 days he was discharged from the intensive care unit (ICU), and a post-operative echocardiogram showed normal dimensions, good ejection fraction and no valvular regurgitation. He was discharged home 26 days after the transplant. Conclusions In our experience, the Levitronix Centrimag seems to be safe and effective in the treatment of primary graft failure, achieving effective circulatory support and ventricular off-loading. We propose its use in isolated or biventricular graft failure either as bridge to re-transplant or as a bridge to recovery.

Background The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. Methods Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 ± 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). Results Mean support time was 14.2 ± 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. Conclusions The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.

Background Transplantation for patients with a high pulmonary vascular resistance (PVR) carries an increased risk of mortality and right heart failure following heart transplantation and continues to be a major problem. We evaluated the use of hearts from patients who underwent heart and lung transplantation for primary pulmonary hypertension (PPH) as part of a domino procedure because these hearts have hypertrophied right ventricles used to increased pulmonary pressures, but could have a compromised left ventricle or irreversible damage of the right ventricle. Methods We reviewed 12 patients with PVR >4 Wood units who underwent orthotopic heart transplantation between 1989 and 1998 using hearts from donors with PPH as part of a domino procedure. Results We studied 10 men and 2 women, mean age 42.9 years. Mean PVR was 5.3 (range, 4–9) Wood units. Mean ischemia time was 85.3 minutes, and mean donor age was 32 years. Actuarial survival was 75% at 1 year and 75% at 5 years. In the early post-operative period, 3 patients had temporary arrhythmias, 2 required permanent pacemaker implantation, 1 had atrial fibrillation, and 1 had ventricular tachycardia that required defibrillator implantation. At a mean follow-up of 7.8 years, 2 patients had developed asymptomatic transplant coronary disease (both at 8.5 years after transplantation), 1 moderate and 1 very mild; the rest had none. Mean left ventricular ejection fraction at latest follow-up was 70.1% (range, 63%–78%). Right ventricular function assessed clinically and by echocardiography was adequate in the short and long term. Conclusions Our results suggest that heart and lung recipients with PPH can provide useful donor hearts to patients with increased PVR and that these hearts function well in the intermediate and long term.

A 24-year-old woman with cystic fibrosis underwent bilateral sequential lung transplantation and unintentionally received an ABO incompatible graft (blood type A(1) graft into a type O recipient). The recipient had a high titer of IgG anti-A antibody (256 by the indirect antiglobulin test). Emergency treatment included antibody removal by plasmapheresis and additional immunosuppression with mycophenolate, rabbit antithymocyte globulin and polyspecific intravenous immunoglobulin. Subsequently, immunoadsorption and the anti-CD20 antibody rituximab were used to remove anti-A antibody and inhibit its resynthesis. Early graft function was good; one episode of rejection at Day 46 responded promptly to treatment with methylprednisolone. Subsequently, graft function continued to improve and anti-A antibody titers remained low. No infectious or other complications were encountered. The treatment regimen that we adopted may prove useful in other cases of unplanned ABO-incompatible organ transplants. The successful outcome suggests that planned ABO-incompatible lung transplants may be possible.

Cytokine activation in the myocardium of deteriorating patients with heart failure who undergo left ventricular assist-device (LVAD) implantation has been documented, but the underlying mechanisms remain poorly understood. We hypothesized the innate immune system is activated with expression of Toll-like receptor 4 (TLR4), leading to cytokine activation in these patients.We used quantitative real-time reverse-transcriptase polymerase chain reaction to measure TLR4, interleukin-1 (IL-1) receptor, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in myocardial samples from 36 patients. We compared 18 patients who underwent LVAD implantation with 18 patients with less severe heart failure who underwent elective heart transplantation.Toll-like receptor 4 expression was 1.69-fold greater (p0.05) and IL-1 receptor expression was 3.64-fold greater (p0.0001) in the deteriorating patients who required LVADs. Myocardial TNF-alpha (1.71-fold, p0.05), IL-6 (2.57-fold, p0.005), and IL-1 beta (9.78-fold, p0.001) also were increased in the LVAD candidates. Toll-like receptor 4 expression correlated strongly with IL-1 receptor expression (r= 0.75, p0.0001) and with IL-1 beta expression in individual patients (r = 0.7, p0.0001). Interleukin-1 receptor expression also correlated with IL-1 beta expression (r = 0.78, p0.0001) within patients. We found no correlation between TLR4 and either TNF-alpha or IL-6 expression.Patients who required LVAD support showed evidence of innate immune system activation, indicated by an increase in the key effector molecule TLR4 associated with a specific pattern of cytokine expression in the myocardium.

Background: Hearts transplanted from patients undergoing heart–lung transplantation (domino hearts) are unique because they have not been subjected to the deleterious effects of brain-stem death. This study examines the incidence and severity of transplant-associated coronary artery disease in recipients of domino hearts. Methods: We retrospectively reviewed angiographic and clinical data from 97 patients who survived more than 1 year after domino heart transplantation at our hospital. Duration of follow-up ranged from 1 to 11 years after transplantation. The diagnosis of coronary artery disease was based on angiographic criteria. Results: At 1 year, freedom from angiographic coronary artery disease was 99% (70% confidence interval [CI], 97–100), at 5 years it was 83% (70% CI, 78–89), and at 10 years it was 77% (70% CI, 70–84). Donor age, cystic fibrosis in the donor, organ ischemia time during transplantation, and acute rejection after transplantation did not influence risk for the disease. We found an increased incidence of coronary disease in hearts from male donors compared with those from female donors: freedom from disease at 5 years was 72% (70% CI, 63–81) in men vs 93% (87–99) in women. Thirteen patients experienced coronary artery disease at a median of 3 years after transplantation; 4 patients died but most patients remained asymptomatic with angiographically mild disease at their last follow-up examination. Conclusions: We found decreased incidence and severity of transplant-associated coronary artery disease in recipients of domino hearts compared with that reported in recipients of cadaveric hearts. This data supports the continued practice of domino heart transplantation and also supports the hypothesis that brain death may contribute to the development of transplant coronary artery disease in recipients of hearts transplanted from cadaveric organ donors.

Objective: We sought to examine our management and outcome of lung carcinoma occurring after thoracic organ transplantation. Methods: We performed a retrospective review of cases of primary lung carcinoma diagnosed between 1990 and 2000 in patients who have previously undergone thoracic transplantation at our institution. Results: Seventeen patients were identified (1 lung and 16 heart transplants). Median time from transplantation to diagnosis of lung carcinoma was 89 months (range, 46-138 months). Predominant presentation was as an incidental finding at chest radiography (13/17). All patients had smoked cigarettes before transplantation, with 5 continuing to smoke after transplantation. Histologic types were squamous (n = 11), adenocarcinoma (n = 3), small cell (n = 2), and undifferentiated (n = 1). Revised International Union Against Cancer (UICC) clinical stage at the time of diagnosis was stage I or II in 11 of 17 patients. Of these, 9 underwent surgical resection; 2 patients unfit for surgical intervention had radiotherapy. Surgical procedures were lobectomy (n = 5), wedge excision (n = 3), and no resection (n = 1). Median survival after diagnosis was 12 months for all patients and 24 months if the tumor was resected. Six patients who had surgical resection subsequently died (survival of 2, 9, 21, 21, 36, and 67 months); 2 remain alive after 12 and 54 months, respectively. Conclusions: When possible, surgical intervention should be undertaken for early stage lung cancer occurring after thoracic transplantation because medium-term survival is achievable. Sublobar excisions and definitive radiotherapy should be considered if comorbidity prevents optimal surgical treatment. J Thorac Cardiovasc Surg 2002;124:1190-7

Background Hearts explanted from the recipients of heart–lung transplants provide a unique source of transplants from live donors. This article presents long-term results with this procedure at our center. Methods We performed a retrospective chart review of domino transplantations performed in our institution between 1989 and 1998. Results We analyzed 131 domino transplants (123 orthotopic, 8 heterotopic). Domino hearts were from patients with cystic fibrosis (69%), primary pulmonary hypertension (15%), and other diagnoses (16%). The mean recipient pulmonary vascular resistance (PVR) was 3.1 Wood units, 25% of patients having values >4 Wood units. Thirty-day mortality was 13%. The 1-, 5-, and 10-year graft survival was 75% (70% confidence interval [CI], 65–74), 70% (70% CI, 65–74), and 58% (70% CI, 52–64), respectively. Patients with PVR >4 Wood units had 1-year survival (76%; 70% CI, 69–84) similar to that of patients with PVR of ≤4 units (74%; 70% CI, 69–80). Recipients of hearts from patients with cystic fibrosis survived longer (5-year survival, 76%; 70% CI, 71–82) vs 65% for non–cystic fibrosis hearts (70% CI, 57–74) p = 0.09). One-year survival was decreased after transplantation of hearts from female donors (66%; 70% CI, 60–72)) compared with hearts from male donors (85%; 70% CI, 79–90); p = 0.06). Late deaths caused by coronary artery disease and malignancy were uncommon. Conclusion Although the rate of early mortality after domino transplantation was slightly higher than after cadaveric transplantation, we noted a remarkably low long-term attrition rate in recipients of domino grafts, up to 10 years. In addition, successful transplantation of patients with high PVR supports the hypothesis that heart–lung recipients may provide superior donor hearts for this patient group, many of whom traditional listing criteria would exclude.

Here we report the treatment of native heart complications (aortic regurgitation, ventricular fibrillation and heart failure) following a heterotopic heart transplant by excision of native heart and relocation the heterotopic heart in the orthotopic position. The patient was a 24 year old woman who had received a heterotopic transplant at the age of 9 years from a 9 year old donor. The donor heart had grown sufficiently to allow it to support her adult circulation.

Background. Myocardial dysfunction is common after brain death, but the mechanisms remain unclear. Apoptosis is tightly regulated by enzymes termed the caspases. We have investigated the caspases involved in the terminal part of the apoptotic pathway in dysfunctional (nontransplanted) donor hearts and their relation to inflammatory markers and compared them to hearts with good ventricular function (transplanted donors). Methods. Thirty-one donor hearts assessed for transplantation were examined. Western blotting was used to measure pro-caspase-9, caspase-3, DFF45, the activated nuclease CPAN and poly (ADP-ribose) polymerase, a DNA repair enzyme inactivated by caspase-3. Caspase-3 activity was also measured. Histologic and immunocytochemical analysis for HLA Class II and Real Time polymerase chain reaction for tumor necrosis factor-a and interleukin 6 were performed to detect inflammatory activation. Results. Cleaved caspase-9 was higher (5.5360.6 vs. 3.6460.4 O.D. units, P

Background —Myocardial failure is an important problem after heart transplantation. Right ventricular (RV) failure is most common, although its mechanisms remain poorly understood. Inflammatory cytokines play an important role in heart failure. We studied the expression of tumor necrosis factor (TNF)-α and other cytokines in donor myocardium and their relationship to the subsequent development of RV failure early after transplantation. Methods and Results —Clinical details were obtained, and ventricular function was assessed by transesophageal echocardiography in 26 donors before heart retrieval. A donor RV biopsy was obtained immediately before transplantation, and each recipient was followed for the development of RV failure. Reverse transcriptase–polymerase chain reaction was performed to detect TNF-α, interleukin-2, interferon-γ, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-α, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-α ( P P Conclusions —TNF-α expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.

Background Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure. Materials and methods The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides. Results Total creatine levels (phosphocreatine + creatine) were significantly decreased (P

Objectives: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. Methods: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n=127). Maximum follow-up was 27.1 years. Results: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. Conclusions: Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation. (J Thorac Cardiovasc Surg 1999;117:77-91)

Background Availability of cadaveric organs continues to be the key factor limiting the number of transplants performed. Donor with bacterial meningitis is often considered to be controversial for organ retrieval. The purpose of this retrospective study was to review the long-term outcome of orthotopic heart and lung transplantation at our institution, from donors who died as a result of meningitis. Methods Between July 1986 and July 2006, 39 adult patients who underwent heart and lung transplantation performed with organs from cadaveric donors with bacterial meningitis were retrospectively studied. Donors and recipients were identified by a prospectively kept database. Bacterial meningitis was identified either with positive blood or cerebrospinal fluid culture and positive signs and symptoms. All patients had one or more of these criteria. There were 15 heart, 12 lung (4 bilateral), and 12 heart-lung transplants. Results All donors had identified pathogens: Neisseria meningitidis (n = 21; 53.8%), Streptococcus pneumoniae (n = 16; 41%), and Haemophilus influenzae (n = 2; 5.2%). Adequate antimicrobial therapy before organ retrieval and after transplant was administered. The hospital mortality was 10.2% (n = 4). There were no infectious complications caused by meningeal pathogens. Other causes of hospital mortality were rejection (n = 2), intracranial bleeding (n = 1), and staphylococcus sepsis (n = 1). The mean posttransplant follow-up was 5.35 ± 5.54 years (range, 1 month to 18.9 years). Conclusions Intrathoracic organ transplantation using donors with bacterial meningitis is an acceptable strategy. No organism ( Neisseria meningitides, Streptococcus pneumoniae , and Haemophilus influenzae ) could be identified as contraindication because no recipient died of infectious-related diseases.

Cardiac fibromas are benign tumours, often diagnosed in childhood, but rarely they may be diagnosed in adults or the elderly. We present an interesting case of a middle-aged lady presenting with exertional chest pain and breathlessness, who was found to have a heavily calcified mass within the myocardium. With a previous history of chest trauma, a calcified myocardial haematoma was initially suspected. Complete surgical excision led to a total resolution of symptoms. Histological examination confirmed the diagnosis of a cardiac fibroma. Complete excision of cardiac fibromas, where possible, is advised and is associated with excellent survival.

After Mustard or Senning procedures, transplantation remains the only option for some patients who present at late stage with severe systemic (right) ventricular failure. In some circumstances these patients may require urgent mechanical circulatory support to bridge them to transplantation. The use of mechanical support poses considerable potential and actual specific problems both in terms of insertion and management of the device. We report the case of a 17-year-old patient who had a left ventricular assist device implanted from the right ventricle to the aorta for "end-stage" heart failure 15 years after the Mustard procedure. The specific problems are discussed and a management scheme is proposed.

Background. Despite improving results in lung transplantation, a significant number of grafts fail early or late postoperatively. The pulmonary retransplant registry was founded in 1991 to determine the predictors of outcome after retransplantation. We hypothesized that ambulatory status of the recipient and center retransplant volume, which had been previously shown to predict survival after retransplantation, would also be associated with improved graft function postoperatively. Methods. Two hundred thirty patients underwent retransplantation in 47 centers from 1985 to 1996. Logistic regression methods were used to determine variables associated with, and predictive of, survival and lung function after retransplantation. Results. Kaplan-Meier survival was 47% +/- 3%, 40% +/- 3%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the predictors of survival included ambulatory status or lack of ventilator support preoperatively (p = 0.005; odds ratio, 1.62; 95% confidence interval, 1.15 to 2.27), followed by retransplantation after 1991 (p = 0.048; odds ratio, 1.41; 95% confidence interval, 1.003 to 1.99). Ambulatory, nonventilated patients undergoing retransplantation after 1991 had a 1-year survival of 64% +/- 5% versus 33% +/- 4% for nonambulatory, ventilated recipients. Eighty-one percent, 70%, 62%, and 56% of survivors were free of bronchiolitis obliterans syndrome at 1, 2, 3, and 4 years after retransplantation, respectively. Factors associated with freedom from stage 3 (severe) bronchiolitis obliterans syndrome at 2 years after retransplantation included an interval between transplants greater than 2 years (p = 0.01), the lack of ventilatory support before retransplantation (p = 0.03), increasing retransplant experience within each center (fifth and higher retransplant patient, p = 0.04), and total center volume of five or more retransplant operations (P = 0.05). Conclusions. Nonambulatory, ventilated patients should not be considered for retransplantation with the same priority as other candidates. The best intermediate-term functional results occurred in more experienced centers, in nonventilated patients, and in patients undergoing retransplantation more than 2 years after their first transplant. In view of the scarcity of lung donors, patient selection for retransplantation should remain strict and should be guided by the outcome data reviewed in this article. (C) 1998 by The Society of Thoracic Surgeons.

Aims To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. Methods and results Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81. min−1 of oxygen and administered in doses increasing from 15 to 50 ng. kg−1. min−1 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 ng.kg−1.min−1 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56±5 to 45±4 mmHg ( P =0·0001). The pulmonary vascular resistance decreased by 38% from 964±169 to 595±116 dyne s−1.cm−5 ( P =0·0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. Conclusion Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertension.

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.

Background: Children with advanced heart failure, particularly those with elevated pulmonary vascular resistance, pose a difficult management problem because the normal donor right ventricle cannot cope with the high pulmonary resistance and because of the relative shortage of donor organs of an appropriate size for this age group. Methods: In an attempt to address these issues and evaluate the role of heterotopic transplantation in this context, we operated on 12 children, six boys and six girls, in the period between January 1, 1991, and March 31, 1996. Their ages ranged from 11 months to 15.2 years (mean 81.6 ± 62.8 months) and their mean weight was 23.3 kg (range 7.6 to 56.8 kg). Eight patients (66.6%) had significant elevation of pulmonary artery pressure (pulmonary artery systolic pressure=66 ± 9.4 mm Hg, mean transpulmonary gradient=22.3 ± 3.4 mm Hg). In all patients the donor pulmonary artery was anastomosed to the recipient right atrium without the use of any prosthetic material. Ischemic times varied between 135 and 255 minutes (mean 182.1 ± 30.7 minutes). The immunosuppression regimen included cyclosporine and azathioprine. Steroids were not routinely used. Results: One patient died in the hospital of acute rejection on postoperative day 16. Three patients had lobe collapse within 1 week and all were treated successfully. Two late deaths (18.2%) occurred as a result of cardiac rejection 3 months and 2 years after the operations. Nine survivors (75%) are alive, active, and growing normally at a mean follow-up of 2.2 years (range 11 months to 4.75 years). Repeated cardiac catheterization performed in seven patients with preoperative pulmonary hypertension showed a slow progressive drop in mean pulmonary artery pressure. No significant change was observed in the function of the recipient hearts. Conclusion: We conclude that heterotopic heart transplantation is feasible for a selected group of children with good medium-term results, notably regression of pulmonary artery pressure, normal growth, and lack of long-term chest complications. (J Torac Cardiovasc Surg 1997;113:1042-9)

Objective: To describe a technique of direct revascularisation of the bronchial artery using the left IMA and assess its medium term results in patients undergoing left single lung transplant (SLT). Methods: Between March 1991 and September 1993, 22 patients who underwent direct bronchial revascularisation at the time of left SLT (20 pedicled IMA, one free IMA, and one direct anastomosis to the aorta) have been followed up for a minimum period of 1 year (mean 30 ± 12 months). Their mean age was 47.8 ± 9.6 and the original disease was emphysema in 19, lymphangioleiomyomatosis in two, and pulmonary fibrosis in one. The mean ischaemia time was 269.7 ± 23.4 min. Results: There was one early death (4.5%) and 3 patients were re-explored for bleeding. The actuarial survival at 1 and 3 years was 91 ± 0.4% and 82.6 ± 1%, respectively. Bronchial healing was excellent in all patients and angiographic studies showed patent vascular anastomosis in all 22 patients, with good run off in 20 and poor in two. One patient developed clinical obliterative bronchiolitis at 22 months (4.5%) during a period of follow up varying from 12 to 43 months (mean 30 S.D. 12). At last follow up the mean FEVI was 1.4 ± 0.4 and the mean FVC was 2.2 ± 0.6. On average, each patient developed 1.5 ± 0.6 infection episodes and 1 ± 0.2 acute lung rejection. Conclusion: It is concluded that the medium term results of direct bronchial revascularisation are good. However the influence of this procedure on long term results needs further investigation.

Ischemic airway complications are common after en bloc double-lung transplantation with tracheal anastomosis. The aim of this study was to evaluate the effects of a direct revascularization of the donor bronchial artery with the recipient internal thoracic artery on airway perfusion.Seven patients undergoing double-lung transplantation with tracheal anastomosis were investigated intraoperatively and postoperatively (12 to 36 hours) with endoscopic laser Doppler flowmetry. Sixteen patients undergoing coronary artery bypass grafting served as a control group.Two patients who had double-lung transplantation with tracheal anastomosis died of sepsis and multiorgan failure 1 week after transplantation. In the remaining 5 patients healing of the anastomosis was excellent during the observation period of 3 to 52 months. In 5 patients clamping of the attached internal thoracic artery induced a reduction of the laser Doppler flowmetry signal from 10% to 60%. In the 2 patients with the highest graft perfusion level, no clamping effect could be detected. Compared with the control group, perfusion was significantly higher in the transplanted airways intraoperatively, at 71 versus 55 arbitrary perfusion units (p0.01). Postoperative transplant airway perfusion values were not significantly different from the intraoperative value. The coefficient of variation of repeated measurements was higher in the transplanted airways, with a coefficient of variation of 0.22 versus 0.17 in the control group (p0.01), indicating heterogeneous transplant airway perfusion.This study has documented that revascularization with the internal thoracic artery supplies the transplanted airway with additional oxygenated blood.

Background— Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown. Methods and Results— We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed ≈50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca 2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca 2+ content was increased in the recovery compared with the nonrecovery group. Conclusions— These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca 2+ handling as a key functional determinant in patients with heart failure.

Two hundred seventy-five unprocessed, viable homograft ("homovital") aortic valves were used for aortic valve replacement in patients aged 1.5 to 79 years (mean 45.8 +/- 19 years) with maximum follow-up of a 14-year period (mean 4.8 years). Ninety-two percent (252 patients) had New York Heart Association class III or IV functional status before operation and 25 underwent emergency operation. Valves were harvested under sterile conditions and kept in nutrient medium 199. Freehand (subcoronary) technique was used in 147 patients and freestanding root replacement was used in 128. Cumulative survival rates for the whole group were 92% +/- 2% at 5 years and 85% +/- 3% at 10 years, as compared with 96% +/- 2% and 94% +/- 4%, respectively, for the 98 patients who underwent isolated root replacement. Multivariate analysis determined that root replacement with associated procedures and operation for prosthetic endocarditis were risk factors for death, whereas previous xenograft valve, operation for endocarditis, and operation for aortic regurgitation were risk factors for reoperation. Actuarial rates for freedom from degenerative valve failure diagnosed at operation, by postmortem examination, or by routine echocardiography were 94% +/- 2% at 5 years and 89% +/- 3% at 10 years. Recipient age younger than 30 years and previous xenograft valve were risk factors for late degeneration. We conclude that homovital valves demonstrate good durability, particularly in patients older than 30 years, who had a 10-year freedom from degeneration rate of 97%.

ObjectiveThe proportion of patients who can be bridged with left ventricular assist devices to myocardial recovery and the long-term outcome of these patients is unknown.MethodsWe investigated the outcomes of patients bridged to recovery compared with those bridged to transplantation. All left ventricular assist devices were implanted as a bridge to transplantation with a very proactive program of promoting myocardial recovery. A total of 40 patients were bridged to recovery and 52 to transplantation. Of the bridged to recovery (explanted) group, 33 were men (age, 32.8 ± 11.8 years), 37 had dilated cardiomyopathy (familial in 3, peripartum cardiomyopathy in 3) and 3 had myocarditis. Of the bridged to transplantation (transplanted) group, 42 were men (age, 42.3 ± 12.5 years; P

s S209 Methods: Of 7841patients (pts) enrolled in the registry with continuous flow LVAD, 13 were identified as HIV infected. Results: Of the 13 patients, median age was 54 years (range 40-73), with 11 males, 8 African Americans and 5 whites. Etiology was ischemic in 4, non-ischemic in 8 and unknown in 1. Indication was BTT in 3, DT in 9 and BTC in 1. INTERMACS profile at implant: 2 in 5 pts, 3 in 4 pts and 4 in 4 pts. Overall 12 and 24 month survival in HIVinfected pts was only 69 and 47% respectively and worse than non-HIV pts (p< 0.05). Of 6 deaths, 3 occurred during the implant hospitalization from multi-organ failure, cardiopulmonary arrest and withdrawal of LVAD/ventilator. Conclusion: In contrast to the positive cases reports in the published literature, HIV infected patients enrolled in INTERMACS with LVAD had statistically worse survival compared to non-HIV pts. This is despite higher INTERMACS profiles at implant with 4/13 as profile 4 and no profile 1. The results of this small cohort must be interpreted cautiously, but warrant consideration and further study.

Background . We have previously shown, by means of electron beam tomography, the pattern of calcification of the aortic root wall of homografts and porcine xenografts after aortic root replacement. However, application of similar methods for cusp calcification raises specific problems that have not been addressed before. Methods . A new method for localizing and quantifying calcification of the aortic valve cusps has been evolved. Intravenous contrast-enhanced electron beam tomography was introduced to visualize the aortic cusps. This technique was applied to quantify cusp calcification in 37 patients after aortic root replacement with a homograft (group H) or a Medtronic Freestyle valve (group F) at set intervals between 6 months and 2 years. A calcification score in Hounsfield units (HU) and a calcified volume score in cubic millimeters were calculated. Results . The aortic leaflets were clearly visualized in all patients. The mean calcium score in the cusps was 28.8 ± 64.4 HU in group F and 62.4 ± 66.9 HU in group H ( p = not significant). The mean calcified volume score was 327.0 ± 425.9 mm 3 in group F and 642.0 ± 443.0 mm 3 in group H ( p = not significant). Conclusions . Contrast enhancement electron beam tomography is a useful tool for quantification of calcium in the aortic valve leaflets. Our preliminary results show a tendency toward more calcification in the homografts. This needs to be studied further in a bigger cohort of patients followed up for longer periods.

Background : Heart transplantation (HTx), the gold standard therapy for advanced heart failure, is limited by donor availability; alternative therapies are now becoming available. Aim: We examined the outcome of HTx with current immunosuppressive and adjunctive therapy. Design and methods: We analysed the outcome of 399 consecutive patients who underwent transplantation at our centre (1995–2007). Prior to HTx 23% (98) required inotropic support, 8.5% (34) an intra-aortic balloon pump and 11% (43) a ventricular assist device. Results: Actuarial patient survival was 86% at 30 days, 79% at 1 year and 62% at 10 years. Survival was similar regardless of the heart failure severity, P = 0.22. The cumulative incidence of allograft vasculopathy, Costanzo grade ≥2, was 7% at 5 years and 23% by 10 years with an 11% cumulative probability of requiring a percutaneous coronary intervention by 10 years. Allograft function was preserved with a mean ± SD left ventricular ejection fraction of 73 ± 7% at 1 year and 74 ± 8% at 10 years. The cumulative incidence of malignancy by 10 years was 27% (skin malignancy 13% and post transplant lymphoproliferative diseases 10%). The cumulative incidence of developing chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤45 ml/min/1.73 m2 was 42% at 1 year, 62% at 5 years and 72% at 10 years and of requiring long-term renal replacement therapy was 10.6% at 10 years. Conclusion: HTx provided good medium-term survival for patients with advanced heart failure, independent of its severity. The incidence of allograft vasculopathy was lower than reported previously but malignancy and CKD remain cause for concern.

Objectives The aim of this study was to conduct an initial clinical evaluation of the new HeartWare Ventricular Assist System (HeartWare, Inc., Framingham, Massachusetts) in a multicenter, prospective, nonrandomized single-arm clinical trial. Background Heart failure is a worldwide epidemic. The effectiveness of heart transplantation and medical therapy is limited, resulting in the emergence of mechanical circulatory support as a primary treatment for end-stage heart disease. Left ventricular assist devices that use rotary pumps are small and durable, which might reduce morbidity and mortality during support. Methods Fifty heart transplant candidates with New York Heart Association functional class IV symptoms were supported at 5 international centers by the HeartWare System for 180 days, until heart transplant, myocardial recovery and device explant, or death. Patients who continue to be supported have been followed for a minimum of 2 years. Results Of the 50 patients, 20 (40%) received transplants, 4 (8%) had the pump explanted after myocardial recovery, and 17 (34%) continue support at 2 years. Nine (18%) patients died during support from sepsis (n = 3), multiple organ failure (n = 3), or hemorrhagic stroke (n = 3). The actual survival at 6, 12, and 24 months was 90%, 84%, and 79%, respectively. In the survivors, measures of quality of life showed a significant improvement over baseline values. Significant improvements were found for recognition memory at 3 months after implant (p = 0.006). The most frequent adverse events were infection and bleeding. Conclusions Patients with end-stage heart failure can be safely and effectively supported by the HeartWare Ventricular Assist System with improved quality of life and neurocognitive function.

Background Third-generation rotary blood pumps have magnetically levitated rotors that eliminate mechanical wear over the years. Together with their potential for miniaturization, these pumps seem suitable for long-term support of patients with a wide range of body surface areas (BSA). Recently, the novel HVAD pump (HeartWare Inc, Framingham, MA), a miniaturized centrifugal pump with a hydrodynamic, magnetically levitated rotor, became ready for clinical application. Methods In a multi-institutional trial in Europe and Australia, 23 patients (mean age, 47.9 ± 12 years) in end-stage heart failure were enrolled in 5 centers. The primary end point of the bridge-to-transplant study was survival to heart transplant or survival to 180 days on the device, whichever occurred first. Follow-up data at 1 year are presented. The small size of the device allows for intrapericardial placement of the pump. Results Implant procedures were generally fast and uneventful. Mean duration of support was 167 ± 143 days (range, 13–425 days), and mean blood flow provided by the pump was 6.1 ± 1.1 liters/min. At the 180-day end point, 2 patients had undergone successful transplant at 157 and 175 days, 2 patients died while on the device, and 19 patients continued pump support for more than 180 days. Actuarial survival after 6 months was 91% and was 86% at the 1-year follow-up. Conclusions The design of the HVAD pump enables a quick and less invasive implantation. The results to date demonstrate satisfactory long-term survival with excellent quality of life in this cohort of 23 patients of the initial multi-institutional Conformite Europeene (CE) mark trial.