Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial.

BACKGROUND: Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. OBJECTIVES: This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. METHODS: In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. RESULTS: A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. CONCLUSIONS: Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).

Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study.

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, ß-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the ß2-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, mV(O2) 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 mV(O2) 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.

Domino heart transplant following heart-lung transplantation: a systematic review and meta-analysis.

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.

Left ventricular assist device and drug therapy for the reversal of 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 beta2-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.

Engineering Analysis of Tricuspid Annular Dynamics in the Beating Ovine Heart.

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.

The Effect of Acute Pulmonary Hypertension on Tricuspid Annular Height, Strain, and Curvature in Sheep.

The tricuspid annulus shows significant alterations in patients with functional tricuspid regurgitation-tricuspid valve dysfunction that is secondary to other diseases such as pulmonary hypertension. Early changes in annular shape and dynamics may provide an understanding of disease mechanisms and could predict disease progression. To gain a mechanistic insight into these early changes we perform a spatially-resolved analysis of the effect of acute pulmonary hypertension on the tricuspid annulus in sheep. To this end, we suture sonomicrometry crystals to the annulus of nine sheep and record their locations in the beating heart, before and after inducing acute pulmonary hypertension. Using least-squares cubic splines, we derive mathematical representations of the annulus to describe pulmonary hypertension-induced annular shape changes via strain, relative curvature, and relative annular height between the control group and the acute pulmonary hypertension group. Moreover, we determine hypertension-induced alterations to annular dynamics as within-group strains, relative curvature, and relative height throughout the cardiac cycle for each group. We confirm that the annulus in acute pulmonary hypertension dilates significantly, becomes more circular, and flattens. Our regional analysis reveals that annular dilation, circularization, and flattening are driven by highly localized changes in annular strains, curvature, and height. Additionally, we find that acute pulmonary hypertension alters annular dynamics, albeit minimally. This regionally-resolved analysis of acute hypertension-induced changes of annular shape and dynamics provides insight into early disease mechanisms, and may inspire future generations of annuloplasty devices and techniques that address spatial annular heterogeneities.

Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support.

BACKGROUND: After left ventricular-assist device (LVAD) support, a proportion of patients recover sufficient ventricular function to enable explantation of the device. The exact molecular mechanisms involved in myocardial recovery remain unknown. Cytoskeletal proteins are essential for the structure and function of the cardiac myocyte and might play a major role. METHODS AND RESULTS: A total of 15 patients with nonischemic cardiomyopathy who required LVAD implantation were studied; 6 recovered sufficiently to allow explantation of the device compared with 9 who did not recover and required transplantation. LV myocardial samples were collected at implantation and explantation/transplantation. Affymetrix microarray analysis was performed on the paired samples and analyzed with reference to sarcomeric and nonsarcomeric cytoskeletal proteins. In the recovery group, of the nonsarcomeric proteins, lamin A/C increased 1.5-fold (P<0.05) and spectrin 1.6-fold (P<0.05) between the times of implantation and explantation. Integrins beta1, beta6, and alpha7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins alpha5 and beta5 increased 2.3-fold (P<0.01) and 1.2-fold (P<0.01) at explantation. The following sarcomeric proteins changed in the recovered group only: beta-actin increased 1.4-fold (P<0.05); alpha-tropomyosin, 1.3-fold (P<0.05); alpha1-actinin, 1.8-fold (P<0.01); and alpha-filamin A, 1.6-fold (P<0.05). Both troponin T3 and alpha2-actinin decreased by 1.6-fold at the time of explantation (P<0.05). Vinculin decreased 1.7-fold (P=0.001) in the recovered group but increased by 1.7-fold (P<0.05) in the nonrecovered group. Vinculin protein levels decreased 4.1-fold in the recovered group. CONCLUSIONS: Myocardial recovery was associated with a specific pattern of changes in sarcomeric, nonsarcomeric, and membrane-associated proteins, which could have important implications in understanding the mechanisms involved.

A global perspective of lung transplantation: Part 1 - Recipient selection and choice of procedure.

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.

Traumatic pseudoaneurysm resulting from ruptured outflow graft due to disconnection of HeartMate II LVAD Bend Relief.

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. .

Airway complications after lung transplantation: Contemporary survival and outcomes.

BACKGROUND: Airway complications are rare and cause increased morbidity and mortality after lung transplantation (LT). We sought to examine risk factors associated with this complication and its impact on survival. METHODS: We retrospectively evaluated United Network for Organ Sharing data from 2000 to 2012. A backward stepwise logistic regression was performed on recipient-, donor-, and transplant-related variables to select independent risk factors associated with airway complications and mortality. Survival was evaluated using the Kaplan-Meier method. RESULTS: We evaluated 16,156 consecutive adult LT recipients, among whom 233 (1.4%) developed airway complications. Predictors of increased risk of airway complications included male gender (odds ratio [OR] 1.61, p = 0.001), advancing recipient age (OR 1.02, p < 0.001) and pre-transplantation admission to the intensive care unit (ICU) (OR 2.13, p < 0.001). The 30-day (89.6% vs 96.2%, p = 0.001), 90-day (69.9% vs 93.1%, p < 0.001), 1-year (54.6% vs 84.4%, p < 0.001), 3-year (38.7% vs 67.4%, p < 0.001) and 5-year (33.2% vs 54.2%, p < 0.001) survival rates were each significantly reduced in recipients with airway complications. Factors associated with an increased risk of 1-year mortality included recipient age (hazard ratio [HR] 1.01, p < 0.001), use of extracorporeal mechanical support (HR 1.5, p = 0.01), diagnosis of cystic fibrosis (HR 1.22, p = 0.01), glomerular filtration rate (GFR) 60 to 90 ml/min/1.73 m2 (HR 1.61, p < 0.001), GFR <60 ml/min/1.73 m2 (HR 1.13, p = 0.01), non-ICU hospitalization (HR 1.32, p < 0.001), pre-transplantation ICU hospitalization (HR 2.54, p < 0.001), donor with positive serology for cytomegalovirus (HR 1.16, p < 0.001) and donor with a smoking history (HR 1.19, p < 0.001). Double LT (HR 0.83, p < 0.001) was associated with a decreased risk of death. Chronic obstructive pulmonary disease/emphysema was protective compared with idiopathic pulmonary fibrosis (HR 0.85, p = 0.008). CONCLUSION: Airway complications are associated with a significant mortality burden.

Procedural volume and survival after lung transplantation in the United States: the need to look beyond volume in the establishment of quality metrics.

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.

The effect of acute mechanical left ventricular unloading on ovine tricuspid annular size and geometry.

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.

The effect of pulmonary hypertension on ovine tricuspid annular dynamics.

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.

Ten year survival after paediatric heart transplantation: a single centre experience.

OBJECTIVE: To report 10 years survival in children under the age of 16 years undergoing heart transplantation in a single institution. METHODS: One hundred and thirty nine/one hundred and ninety three patients (73%) survived more than 1 year after transplant. Seventy four (53%) of these survived more than 10 (10.0-20.1) years. Age at operation was 10 days-15.5 (mean 8.1) years. Patients were maintained on ciclosporin and azathiaprine alone. Routine steroids only given to 4 patients for either persistent rejection or deteriorating renal function. Rejection diagnosed on clinical or echocardiographic grounds. No routine biopsies were performed. Bi-annual coronary angiography was used to diagnose graft coronary disease. RESULTS: Graft coronary disease was found in 8 patients (11%), 2 were re-transplanted and have survived 4.3-7.2 years since. Two patients are alive without intervention 2.0-13.0 years from initial diagnosis. Two patients have undergone interventional procedures 11 and 16 years after transplantation and are alive 3 and 4 years, respectively, later. Seven patients have had post transplant lymphoproliferative disease (PTLD) and 6 have had no recurrence for 3-13 years after treatment. Impaired renal function with abnormal serum creatinine levels is increasingly common-11 patients have developed end stage renal failure, 7 requiring renal transplantation, hypertension occurred in only 3 patients other than those in renal failure. Late rejection episodes associated with probable non-adherence occurred in 7 patients. There were 10 late deaths; 2 from graft coronary disease; 1 from PTLD; 3 from renal failure; 3 from acute rejection and 1 from infection. Conditional actuarial survival from 1 year post transplant was 76 and 67% at 10 and 15 years, respectively. CONCLUSIONS: Survival for more than 10 years is increasingly realistic. In this age group adherence and deteriorating renal function are major challenges.

Transplantation using hearts from primary pulmonary hypertensive donors for recipients with a high pulmonary vascular resistance.

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.

Long-term results of cardiac transplantation from live donors: the domino heart transplant.

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 < or =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.

Low incidence and severity of transplant-associated coronary artery disease in heart transplants from live donors.

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.

Increased toll-like receptor 4 in the myocardium of patients requiring left ventricular assist devices.

BACKGROUND: 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. METHODS: 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. RESULTS: Toll-like receptor 4 expression was 1.69-fold greater (p < 0.05) and IL-1 receptor expression was 3.64-fold greater (p < 0.0001) in the deteriorating patients who required LVADs. Myocardial TNF-alpha (1.71-fold, p < 0.05), IL-6 (2.57-fold, p < 0.005), and IL-1 beta (9.78-fold, p < 0.001) also were increased in the LVAD candidates. Toll-like receptor 4 expression correlated strongly with IL-1 receptor expression (r= 0.75, p < 0.0001) and with IL-1 beta expression in individual patients (r = 0.7, p < 0.0001). Interleukin-1 receptor expression also correlated with IL-1 beta expression (r = 0.78, p < 0.0001) within patients. We found no correlation between TLR4 and either TNF-alpha or IL-6 expression. CONCLUSIONS: 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.

Successful repair of intraoperative aortic dissection detected by transesophageal echocardiography.

Aortic dissection is a rare but devastating complication of cardiac surgery. Early intraoperative diagnosis and management are essential for a favorable outcome. We describe the case of a 69-year-old man with worsening dyspnea who was admitted for mitral valve replacement having previously had a mitral valve repair. Precardiopulmonary bypass transesophageal echocardiography confirmed mitral regurgitation and showed mild atherosclerotic changes in the descending aorta. Following successful replacement of the mitral valve, an attempt to wean from cardiopulmonary bypass failed. This was characterized by acute onset hypovolemia. The transesophageal echocardiography showed the presence of features of acute aortic dissection involving only the descending aorta without identifying the entry point. The tear was successfully repaired by direct suture within the lumen.