Heart Transplantation Publications (63119)

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Heart Transplantation Publications

2017Jan
J. Am. Coll. Surg.
J Am Coll Surg 2017 Jan 11. Epub 2017 Jan 11.
Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, TX; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX.

The optimal management of patients with congenitally-corrected transposition of the great arteries (ccTGA) is unclear. The goal of this study was to compare the outcomes in patients with ccTGA undergoing different management strategies.
Patients with ccTGA believed suitable for biventricular circulation treated in 1995-2016 were included. Read More

The cohort was divided into four groups: systemic right ventricle (RV) (patients without surgical intervention or with a classic repair), anatomic repair, Fontan palliation, and patients only receiving a pulmonary artery band (PAB) or a shunt. Transplant-free survival from presentation was calculated for each group.
The cohort included 97 patients: 45(46%) systemic RV, 26(27%) anatomic repair, 9(9%) Fontan, 17(18%) PAB/shunt. Median age at presentation was 2 months (0 days-69 years) and median follow-up was 10y (1m-28y). At initial presentation, 10(11%) patients had any RV dysfunction (8 mild, 2 severe), and 16(18%) patients had moderate/severe tricuspid regurgitation (TR). During the study, 10(10%) patients died, and 3(3%) patients underwent transplantation. At last follow up, 11(11%) patients were in NYHA class III/IV, 5(5%) had moderate/severe systemic ventricle dysfunction and 16(16%) had moderate/severe systemic atrioventricular valve regurgitation. Transplant-free survival at 10 years was 93%, 86%, 100% and 79% for systemic RV, anatomic repair, Fontan palliation and PAB/shunt, respectively (p=0.33). On multivariate analysis, only systemic RV dysfunction was associated with a higher risk for death or transplant (p=0.001).
Transplant free survival in ccTGA appears to be similar between patients with a systemic RV, anatomic repair, and Fontan procedure. Systemic RV dysfunction is a risk factor for death and transplant.

2017Jan
Circ Heart Fail
Circ Heart Fail 2017 Jan;10(1)
From the Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Milan, Italy (G.W., D.D., F.A., M.K., C.J., P.S., F.D., A.Z., M.O., M.M.C., S.D.S., E.P.N.); Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany (G.W., D.D., C.J.); Institute of Cardiology, Catholic University, Rome, Italy (F.A.); Collegium Medicum in Bydgoszcz, University of Nicolaus Copernicus, Toruń, Poland (M.K.); Department of Emergency and Organ Transplantation, Section of Cardiovascular Diseases, School of Medicine, University of Bari, Italy (P.S., F.D., A.Z.); Department of Heart Science, Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy (M.O., B.C., G.C.); Department of Cardiosurgery, University of Zurich, Switzerland (F.M.); Department of Emergency and Organ Transplantation, Section of Cardiovascular Diseases, School of Medicine, University of Bari, Italy (M.M.C.); and Department of Cardiology, Multimedica IRCCS, Milan, Italy (S.D.S., E.P.N.).

Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment.
We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. Read More

The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001).
The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting.

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. Read More

In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

2017Jan
Eur. Heart J.
Eur Heart J 2017 Jan 12. Epub 2017 Jan 12.
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA

Heart transplantation results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation. Evidence of reinnervation is usually found during the second year after transplantation and involve the myocardial muscle, sinoatrial node, and coronary vessels, but remains incomplete and regionally limited many years post-transplant. Read More

Restoration of cardiac innervation can improve exercise capacity as well as blood flow regulation in the coronary arteries, and hence improve quality of life. As yet, there is no evidence that the reinnervation process is associated with the occurrence of allograft-related events or survival.

2017Jan
Blood
Blood 2017 Jan 13. Epub 2017 Jan 13.
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States

Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented very stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in four macaques followed for up to 49 months post-transplantation. Read More

A broad range of clonal behaviors characterized by contribution level and biases towards certain cell types were extremely stable over time. Correlations between granulocyte and monocyte clonalities were greatest, followed by correlations between these cell types and B cells. We also detected quantitative expansion of T cell biased clones consistent with an adaptive immune response. In contrast to recent data from a non-quantitative murine model, there was little evidence for clonal succession after initial hematopoietic reconstitution. These findings have important implications for human hematopoiesis, given the similarities between macaque and human physiology.

2017Jan
Acta Biomater
Acta Biomater 2017 Jan 10. Epub 2017 Jan 10.
Bioengineering Department, Clemson University, Clemson, SC 29634, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an unlimited cell source to treat cardiovascular diseases, the leading cause of death worldwide. However, current hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. Read More

Our previous results showed addition of e-SiNWs effectively enhanced the functions of the cardiac spheroids and improved the cellular maturation of hiPSC-CMs. Here, we examined two important factors that can affect functions of the nanowired hiPSC cardiac spheroids: (1) cell number per spheroid (i.e., size of the spheroids), and (2) the electrical conductivity of the e-SiNWs. To examine the first factor, we prepared hiPSC cardiac spheroids with four different sizes by varying cell number per spheroid (∼0.5k, ∼1k, ∼3k, ∼7k cells/spheroid). Spheroids with ∼3k cells/spheroid was found to maximize the beneficial effects of the 3D spheroid microenvironment. This result was explained with a semi-quantitative theory that considers two competing factors: 1) the improved 3D cell-cell adhesion, and 2) the reduced oxygen supply to the center of spheroids with the increase of cell number. Also, the critical role of electrical conductivity of silicon nanowires has been confirmed in improving tissue function of hiPSC cardiac spheroids. These results lay down a solid foundation to develop suitable nanowired hiPSC cardiac spheroids as an innovative cell delivery system to treat cardiovascular diseases.
Cardiovascular disease is the leading cause of death and disability worldwide. Due to the limited regenerative capacity of adult human hearts, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have received significant attention because they provide a patient specific cell source to regenerate damaged hearts. Despite the progress, current human hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. Our previous results showed addition of e-SiNWs effectively enhanced the functions of the cardiac spheroids and improved the cellular maturation of hiPSC-CMs. In this manuscript, we examined the effects of two important factors on the functions of nanowired hiPSC cardiac spheroids: (1) cell number per spheroid (i.e., size of the spheroids), and (2) the electrical conductivity of the e-SiNWs. The results from these studies will allow for the development of suitable nanowired hiPSC cardiac spheroids to effectively deliver hiPSC-CMs for heart repair.

2017Jan
Lancet Respir Med
Lancet Respir Med 2017 Jan 10. Epub 2017 Jan 10.
University Paris-Sud, Faculté de Médecine, Paris, F-94270, France; AP-HP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation (TORINO), Service de Pneumologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, Paris, France; UMR_S 999, Univ. Paris-Sud, INSERM, Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, Paris, France. Electronic address:

Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH.
We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. Read More

We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases). We sequenced the coding sequence and intronic junctions of the EIF2AK4 gene, and compared clinical characteristics and outcomes between EIF2AK4 mutation carriers and non-carriers. Medical therapies approved for pulmonary arterial hypertension (prostacyclin derivatives, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors) were given to patients according to the clinical judgment and discretion of treating physicians. The primary outcome was the event-free survival (death or transplantation). Secondary outcomes included response to therapies for pulmonary arterial hypertension and survival after lung transplantation. A satisfactory clinical response to specific therapy for pulmonary arterial hypertension was defined by achieving New York Heart Association functional class I or II, a 6-min walk distance of more than 440 m, and a cardiac index greater than 2·5 L/min per m(2) at the first reassessment after initiation of specific therapy for pulmonary arterial hypertension.
We obtained data from Jan 1, 2003, to June 1, 2016, and identified 94 patients with sporadic or heritable PVOD/PCH (confirmed or highly probable). 27 (29%) of these patients had bi-allelic EIF2AK4 mutations. PVOD/PCH due to EIF2AK4 mutations occurred from birth to age 50 years, and these patients were younger at presentation than non-carriers (median 26·0 years [range 0-50.3] vs 60·0 years [6·7-81·4] years; p<0·0001). At diagnosis, both mutations carriers and non-carriers had similarly severe precapillary pulmonary hypertension and functional impairment. 22 (81%) of mutations carriers and 63 (94%) of non-carriers received therapy approved for pulmonary arterial hypertension. Drug-induced pulmonary oedema occurred in five (23%) of treated EIF2AK4 mutations carriers and 13 (21%) of treated non-carriers. Follow-up assessment after initiation of treatment showed that only three (4%) patients with PVOD/PCH reached the predefined criteria for satisfactory clinical response. The probabilities of event-free survival (death or transplantation) at 1 and 3 years were 63% and 32% in EIF2AK4 mutations carriers, and 75% and 34% in non-carriers. No significant differences occurred in event-free survival between the 2 groups (p=0·38). Among the 33 patients who had lung transplantation, estimated post-transplantation survival rates at 1, 2, and 5 years were 84%, 81%, and 73%, respectively.
Heritable PVOD/PCH due to bi-allelic EIF2AK4 mutations is characterised by a younger age at diagnosis but these patients display similar disease severity compared with mutation non-carriers. Response to therapy approved for pulmonary arterial hypertension in PVOD/PCH is rare. PVOD/PCH is a devastating condition and lung transplantation should be considered for eligible patients.
None.

2017Jan

Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. We report on the long-term outcome after HTx at our centre and investigate trends in outcome over time.
During the period, between 1984 and 2014, a total of 610 HTx procedures were performed in 595 patients (median 48years; IQR 31-57years; range 24days-71years; mean 43years; 75% male) in our institution. Read More

Long-term outcome was investigated in the whole cohort, among children (n=76), bridged with mechanical circulatory support (MCS, n=131), re-transplanted (n=17), and concomitant kidney transplantation (n=12).
Long-term survival was at 1, 5, 10, 15 and 20years: 86% (95CI 0.83-0.89); 77% (95CI 0.73-0.80); 63% (95CI 0.59-0.68); 48% (95CI 0.43-0.54) and 30% (95CI 0.25-0.36), respectively. The median survival for the whole cohort was 14.1years. Patients transplanted during the most recent time period (2010-2014) had a better survival compared to previous eras, with a 1- and 3-year survival of 94% (95CI 0.89-0.97) and 93% (95CI 0.88-0.96), respectively (p<0.001). However, when survival was analysed for long-term MCS (n=80) versus short term MCS (n=35), there was a significantly poorer survival for the short-term MCS group (p=0.001). Independent predictors of long-term mortality included recipient age (p=0.041); previous smoking (p=0.034); ischemic heart disease (p=0.002); and preoperative ventilator therapy (p=0.004).
We have shown that continuous improvement in outcome after HTx still occurs. In the last time era, direct transplantation from short-term MCS was abandoned, which may have inflicted outcome during the last time era.

2016Dec
J. Heart Lung Transplant.
J Heart Lung Transplant 2016 Dec 16. Epub 2016 Dec 16.
Department of Cardiovascular Medicine, St. Vincent Heart Center of Indiana, Indianapolis, Indiana.

Axial configuration (AC) and centrifugal configuration (CC) left ventricular assist devices (LVAD) have different flow characteristics, and whether the interaction between device flow configuration and the pre-operative left ventricular internal diastolic diameter (LVIDD) mediates adverse events after LVAD implantation is unknown.
We queried 9,424 continuous-flow LVAD recipients who received LVADs from April 2008 to June of 2015 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The pre-operative LVIDD * flow configuration interaction term was tested in multivariable models to determine its relationship to adverse events. Read More


The pre-operative LVIDD * flow configuration interaction was a significant predictor of device thrombosis. As the LVIDD increased, the risk of AC device thrombosis increased compared with CC devices (p = 0.0099). At 7.0 cm, the hazard ratio (HR) for AC device thrombosis compared with the CC device was 1.61 (95% confidence interval [CI], 1.17-2.22; p = 0.004) and continued to rise as the LVIDD increased. The LVIDD * flow configuration interaction did not predict stroke, gastrointestinal bleeding, or patient survival. In multivariable models, the hazard of stroke was higher with the CC device regardless of the LVIDD (HR, 1.96; 95% CI, 1.64-2.36; p < 0.0001). Adjusted analyses showed LVAD implantation into a larger left ventricle was associated with a lower risk of death (HR, 0.90; 95% CI, 0.85-0.95; p = 0.0004) per centimeter of LVIDD.
Our study suggests that the pre-operative LVIDD, flow configuration, and interaction terms should be considered individually when choosing the appropriate LVAD to mitigate the rates of device thrombosis, stroke, and death.

2016Dec

Primary graft dysfunction (PGD) is one of the most common causes of early death after orthotopic heart transplantation. Mechanical circulatory support devices are required for severe forms of PGD. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) and temporary ventricular assist device (VAD) support have both been reported to be useful for severe PGD. Read More


Between January 2007 and December 2015, 597 patients received a heart transplant at our center. Of those, severe PGD developed in 44 patients (7.4%), and they received a continuous-flow external VAD (n = 17) or VA-ECMO (n = 27) support within 24 hours after transplant. We compared early and late outcomes between groups.
Baseline characteristics were similar between groups. Implantation of the temporary VAD required longer cardiopulmonary bypass time compared with VA-ECMO (323 ± 86 minutes vs 216 ± 65 minutes, p < 0.0001). Patients who received a VAD were more likely to have longer support time (14 ± 17 days vs 5.2 ± 3.9 days, p = 0.011), a higher incidence of major bleeding requiring chest reexploration (77% vs 30%, p = 0.0047), and a higher incidence of renal failure requiring renal replacement therapy (53% vs 11%, p = 0.0045) after surgery. Overall hospital mortality was 27%. In-hospital mortality for VAD and VA-ECMO patients were 41% and 19%, respectively (p = 0.16). Ten patients (59%) were weaned from VAD support, and 24 (89%) were weaned from VA-ECMO support after adequate graft function recovery (p = 0.03). The 3-year post-transplant survival was 41% in the VAD group and 66% in the VA-ECMO group (p = 0.13).
For severe PGD, support with VA-ECMO appears to result in better clinical outcomes compared with VAD.