Long‐Term Mechanical Circulatory Support in Pediatric Patients

This retrospective study reviews our results regarding the long‐term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2–16.5], median weight 13 kg [IQR 4.2–67.2]). Twenty‐two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single‐ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2–17.9), and the median weight was 54.9 kg (IQR 27.7–66). In the Berlin Heart group, the median support time was 65 days (IQR 4–619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1–1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long‐term mechanical circulatory support in patients with two‐ and single‐ventricle physiology with a low rate of adverse events.     

Bridging to a Long‐Term Ventricular Assist Device With Short‐Term Mechanical Circulatory Support

Implanting short‐term mechanical circulatory support (MCS) devices as a bridge‐to‐decision is increasingly popular. However, outcomes have not been well studied in patients who receive short‐term MCS before receiving long‐term left ventricular assist device (LVAD) support. We analyzed outcomes in our single‐center experience with long‐term continuous‐flow (CF)‐LVAD recipients with pre‐implantation short‐term MCS. From November 2003 through March 2016, 526 patients (mean age, 54.7 ± 13.5 years) with chronic heart failure (mean ejection fraction, 21.7 ± 3.6%) underwent implantation of either the HeartMate II (n = 403) or the HeartWare device (n = 123). Before implantation, 269 patients received short‐term MCS with the TandemHeart, the Impella 2.5/5.0, an intra‐aortic balloon pump (IABP), venoarterial extracorporeal membrane oxygenation (VA‐ECMO), or the CentriMag. The short‐term MCS patients were compared with the CF‐LVAD–only patients regarding preoperative demographics, incidence of postoperative complications, and long‐term survival. The 269 patients received the following short‐term MCS devices: 57 TandemHeart, 27 Impella, 172 IABP, 12 VA‐ECMO, and 1 CentriMag. Survival at 30 days, 6 months, 1 year, and 2 years was 94.2, 87.2, 79.4, and 72.4%, respectively, for CF‐LVAD–only patients versus 91.0, 78.1, 73.4, and 65.6%, respectively, for short‐term MCS + CF‐LVAD patients (P = 0.17). Within the short‐term MCS group, survival at 24 months was poorest for patients supported with VA‐ECMO or the TandemHeart (P = 0.03 for both), and survival across all four time points was poorest for patients supported with VA‐ECMO (P = 0.02). Short‐term MCS was not an independent predictor of mortality in multivariate Cox regression models (hazard ratio = 1.12, 95% confidence interval = 0.84–1.49, P = 0.43). In conclusion, we found that using short‐term MCS therapy—except for VA‐ECMO—as a bridge to long‐term CF‐LVAD support was not associated with poorer survival.     

Cardiac Index Declines During Long‐Term Left Ventricular Device Support

To investigate longitudinal trends in valvular and ventricular function with long‐term left ventricular assist device (LVAD) therapy, we analyzed hemodynamic and echocardiographic data of patients with at least 2 years of continuous LVAD support. All 130 patients who underwent HeartMate II implantation at our institution between 2005 and 2012 were reviewed. Twenty patients had hemodynamic and echocardiographic evaluations in both the early (0–6 months) and late (2–3 years) postoperative period. Patients on inotropic therapy or temporary mechanical support were excluded. The average times of early and late hemodynamic evaluations were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m² (P = 0.04) with concomitant increase in pulmonary capillary wedge pressure (PCWP; P = 0.02). The right atrial pressure to PCWP (RAP:PCWP) ratio decreased during LVAD support suggesting improvement in right ventricular function. While there was an increase in degree of aortic insufficiency (AI) at the late follow‐up period (P = 0.008), dichotomization by median decline in CI (?0.4 L/min/m²) indicated no difference in prevalence of AI among the groups. CI declined in patients with HeartMate II after 2 years of continuous support. An increase in preload and afterload was observed in those with the greatest decline in CI.     

Sustained Posttransplantation Diabetes Is Associated With Long‐Term Major Cardiovascular Events Following Liver Transplantation

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular‐related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long‐term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow‐up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20–3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long‐term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.     

Long‐Term Lung Transplantation in Nonhuman Primates

Despite advances in surgical technique and clinical care, lung transplantation still remains a short‐term solution for the treatment of end‐stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long‐term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre‐existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple‐drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse‐derived anti‐thymocyte globulin and a monoclonal antibody to the IL‐6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days.     

Thoracic Endovascular Aortic Repair of an Aberrant Right Subclavian Artery: Technique and Long‐Term Outcome

Abstract Background: Aberrant right subclavian artery (ARSA) is the most common congenital arch anomaly, which can be complicated by aneursymal dilation at its ostium. We describe a successful repair of an ARSA with a three‐stage operative procedure using a left carotid to subclavian bypass, coiling of the ARSA, and thoracic endovascular aortic repair with long‐term clinical and radiographic follow‐up . (J Card Surg 2010;25:390‐393)     

Long‐Term Pathology of Ovine Lumbar Spine Degeneration Following Injury Via Percutaneous Minimally Invasive Partial Nucleotomy

The focus of this work is to assess the long‐term progression of degeneration in the ovine lumbar spine following a minimally invasive model injury comparable to the damage of an intervertebral disc (IVD) herniation. A partial nucleotomy was performed on 18 sheep via the percutaneous dorsolateral approach. The animals were culled at 6 and 12 months to evaluate the damaged and neighboring functional spine units (FSUs) for degenerative characteristics via μ‐CT and histology. Both quantitative μ‐CT and histology investigations demonstrated statistically significant differences between the native and damaged FSUs investigated. Qualitative analysis of μ‐CT revealed numerous pathological markers consistent with intervertebral disc degeneration (IDD), with differences in frequency and severity between the native and damaged FSUs. The annulus fibrosus reforms a pressure seal within 6 weeks, but the extent of the trauma is significant enough to initiate IVD degeneration, which is already clearly visible at 6 months and especially so 12 months post‐op. IDD pathology consistent with signs of a herniation was seen in both the 6‐ and 12‐month groups. This technique provides a useful model injury for the preclinical evaluation of IDD in large animal models, especially in regards to simulating disc herniation as well as for testing the efficacy of associated therapies in the future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2376–2388, 2019     

Clinical Results and Pump Analysis of the Gyro Pump for Long‐Term Extracorporeal Life Support

Rescuing patients in severe cardiac failure with extracorporeal support remains challenging. The Gyro pump is a centrifugal blood pump and was now used for cardiopulmonary bypass, although it was originally developed for long‐term cardiac assist. Little is known about clinical experiences using this pump. Here, we report on the clinical results of long‐term extracorporeal life support for over 4 days using the Gyro pump with Excelung, a hollow fiber oxygenator coated with silicone and heparin. Seven patients underwent extracorporeal life support with 15 pump and oxygenator combinations. Gyro and Excelung were used for venoarterial extracorporeal support in six patients and for right ventricular support in one patient. Patient characteristics, pump driving conditions, and blood chemistry were obtained retrospectively. All pumps were subsequently disassembled and examined macroscopically, with 6 of 15 pumps also examined by scanning electron microscopy (SEM). The patient mortality rate was 57.1%. Mean duration of support was 10.5 ± 7.2 days per pump and oxygenator combination. Lactate dehydrogenase and aspartate aminotransferase were generally maintained below 1000 and 100 IU/L, respectively, after the first 4 days of pump driving. Thrombi were found in two pumps, one used without anticoagulation and the other driven at a very slow rotational speed. SEM revealed no wear in the male bearings and very low wear and deformation (0.02 ± 0.03 mm) in the female bearings. The combination of Gyro and Excelung may be applicable for long‐term biventricular and right ventricular support, although proper anticoagulation should be administrated to avoid thrombus formation inside the pump.     

Long‐Term Continuous Flow Left Ventricular Assist Device Support and End‐Organ Function: Prospects for Destination Therapy

Abstract Pulsatile flow left ventricular assist devices (PF‐LVADs) have successfully supported patients with severe heart failure for bridge‐to‐transplant (BTT) and destination therapy (DT). End‐organ dysfunction is often reversed, optimizing the patient's condition to enhance survival, and quality of life. Questions have been raised regarding the potential for continuous flow LVADs (CF‐LVADs) to provide the same quality of circulatory support. Prior research showing that PF is superior to continuous, non‐PF does not appear to be relevant with CF‐LVADs for BTT and DT. Under most clinical conditions, arterial pulsatility is present during CF‐LVAD support, and this type of support should not be termed “nonpulsatile.” Clinical studies have shown that renal, hepatic, and neurocognitive function is either maintained within a normal range, or is significantly improved, during CF‐LVAD support for durations up to 15 months. Results of the randomized clinical trial between the CF HeartMate II and the pulsatile HeartMate XVE (both by Thoratec Corp, Pleasanton, CA, USA) are pending final US Food and Drug Administration (FDA) review and are not yet published. Studies of microcirculation during CF‐LVAD support indicate that capillary blood flow is adequate to support cellular function. There are anecdotal cases of patients being supported with a CF‐LVAD for over seven years with preserved end‐organ function. Presently, there are no clinical reports indicating that end‐organ function is not well maintained. Current clinical evidence indicates that end‐organ perfusion and function can be well maintained for extended durations of support with a CF‐LVAD (J Card Surg 2010;25:490‐494)     

A Web‐Based Early Intervention Can Prevent Long‐Term PTS Reactions in Children With High Initial Distress Following Accidental Injury

The present study explored the targeting of a preventative information provision intervention delivered to children following accidental injury by assessing the impact of initial traumatic distress on response to treatment. Analyses were based on baseline and 6‐month outcome of child traumatic stress in a control (n = 28) and an intervention group (n = 31). Moderation of treatment outcome by initial levels of child traumatic stress was assessed through multiple hierarchical regression analyses. Results indicated the interaction between treatment provision and initial level of posttraumatic stress significantly predicted 6‐month outcome (β = ?.42, p = .019). When initial distress was high, children in the control group demonstrated an increase in trauma symptoms, and had significantly higher trauma symptoms at follow‐up than those in the treatment group (d = 0.94, p = .008). When initial distress was not elevated, no significant differences were noted between the groups. These results indicate that a preventative early intervention may be best targeted at children presenting with the specific risk factor of high initial distress.