Publications by authors named "Holger Buchholz"

46 Publications

Human Leukocyte Antigen Antibody Sampling in Ventricular Assist Device Recipients: Are We Talking?

Transplant Proc 2021 Sep 17;53(7):2377-2381. Epub 2021 Aug 17.

Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada; Alberta Transplant Institute (ATI), Edmonton, AB, Canada.

Background: Ventricular assist devices (VADs) are commonly used as a bridge to transplantation but may yield HLA sensitization. We evaluated the prevalence of HLA antibody (Ab) sampling pre- and post-VAD placement in pediatric and adult patients and notification of VAD status to the HLA laboratory.

Methods: All pediatric and adult patients who received a first-time VAD between 2005 and 2013 were included in this single-center retrospective review. Data were collected from the University of Alberta Hospital histocompatibility laboratory's information system and a local VAD database.

Results: In total, 106 patients were included (40 pediatric, median 3.0 years [interquartile range, 0.3-10.7]; 66 adult, 55.0 years [46.8-61.2]). HLA Ab sampling within 1-month pre-VAD occurred in 70% of pediatric and 79% of adult recipients (P = .215). Testing within 1 month of VAD placement occurred in 89% of pediatric and 67% of adult recipients (P = .012). For those with HLA Ab sampling within 30 days postimplant, notification to the HLA laboratory of VAD status occurred in 19 of 27 (70%) pediatric and 24 of 33 (73%) adult patients (P = .533). Of patients transplanted post VAD with HLA Ab samples collected, 12 of 28 (43%) and 13 of 38 (34%) adult recipients did not have notification of VAD status to the HLA laboratory (P = .322).

Conclusions: There were inconsistencies in HLA Ab sampling and communication to the HLA laboratory surrounding VAD placement. Standardization of both HLA Ab assessment frequency after VAD implantation and communication regarding changes in clinical status and the occurrence of key sensitizing events such as VAD placement are imperative as patients await transplantation.
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http://dx.doi.org/10.1016/j.transproceed.2021.07.025DOI Listing
September 2021

Paracorporeal Support in Pediatric Patients: The Role of the Patient-Device Interaction.

Ann Thorac Surg 2021 Jul 28. Epub 2021 Jul 28.

Department of Pediatric Cardiology University of Alberta, Edmonton AB, Canada; Division of Pediatric Cardiology, Stollery Children's Hospital, Edmonton AB, Canada. Electronic address:

Background: Ventricular assist devices (VADs) are important in the treatment of pediatric heart failure. While paracorporeal pulsatile (PP) devices have historically been used, there has been increased use of paracorporeal continuous (PC) devices. We sought to compare the outcomes of children supported with a PP, PC, or combination of devices.

Methods: Retrospective review (2005-19) of patients <19 years of age from a single center, who received a PC, PP or combination of devices. Patient characteristics were compared between device strategies and Kaplan-Meier survival analysis was performed.

Results: Sixty-six patients were included (62% male, 62% non-congenital heart disease, median age 0.9 years (IQR 0.2, 4.9), median weight 8.5 kg (IQR 4.3, 17.7). PC devices were used in 45% of patients, PP in 35% and a combination in 20%. Patients on PC devices had a lower median weight (p=.02), a higher proportion of CHD (p=.02) and more patients requiring pre-VAD dialysis (p=.01). There was no difference in pre-VAD ECMO (p=.15) use. There was a difference in survival between the three device strategies (p=.02) CONCLUSIONS: Differences in survival was evident, with those on PC support having worse outcomes. Transition from PC to a PP devices was associated with a survival advantage. These findings may be driven by differences in patient characteristics across device strategies. Further studies are required to confirm these findings and to better understand the interaction between patient characteristics and device options.
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http://dx.doi.org/10.1016/j.athoracsur.2021.06.062DOI Listing
July 2021

Pediatric ventricular assist device registries: update and perspectives in the era of miniaturized continuous-flow pumps.

Ann Cardiothorac Surg 2021 May;10(3):329-338

Division of Pediatric Cardiology, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.

The success of ventricular assist devices (VADs) in the treatment of end-stage heart failure in the adult population has led to industrial innovation in VAD design, focusing on miniaturization and the reduction of complications. A byproduct of these innovations was that newer generation devices could have clinical applications in the pediatric population. Over the last decade, VAD usage in the pediatric population has increased dramatically, and the newer generation continuous flow (CF) devices have begun to supplant the older, pulsatile flow (PF) devices, formerly the sole option for ventricular assist in the pediatric population. However, despite the increase in VAD implants in the pediatric population, patient numbers remain low, and the need to share data between pediatric VAD centers has become that much more important for the continued growth of VAD programs worldwide. The creation of pediatric VAD registries, such as the Pediatric Registry for Mechanical Circulatory Support (PediMACS), the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) and the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) has enabled the collection of aggregate data from VAD centers worldwide, and provides a valuable resource for clinicians and programs, as more and more pediatric heart failure patients are considered candidates for VAD therapy.
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http://dx.doi.org/10.21037/acs-2020-cfmcs-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185382PMC
May 2021

Draft Genome Sequences of Pelagimyophage Mosig EXVC030M and Pelagipodophage Lederberg EXVC029P, Isolated from Devil's Hole, Bermuda.

Microbiol Resour Announc 2021 Feb 18;10(7). Epub 2021 Feb 18.

School of Biosciences, University of Exeter, Exeter, United Kingdom

We present the genomes of two isolated bacteriophages infecting HTCC1062. phage Mosig EXVC030M () and phage Lederberg EXVC029P () were isolated by dilution-to-extinction culturing from the oxygen minimum zone at Devil's Hole (Harrington Sound, Bermuda).
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http://dx.doi.org/10.1128/MRA.01325-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892664PMC
February 2021

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

J Heart Lung Transplant 2021 04 19;40(4):251-259. Epub 2021 Jan 19.

Lucile Packard Children's Hospital Stanford, Stanford Children's Health, Palo Alto, California.

Background: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration.

Methods: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014).

Results: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group.

Conclusions: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.
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http://dx.doi.org/10.1016/j.healun.2021.01.010DOI Listing
April 2021

Efficient dilution-to-extinction isolation of novel virus-host model systems for fastidious heterotrophic bacteria.

ISME J 2021 06 25;15(6):1585-1598. Epub 2021 Jan 25.

School of Biosciences, University of Exeter, Exeter, UK.

Microbes and their associated viruses are key drivers of biogeochemical processes in marine and soil biomes. While viruses of phototrophic cyanobacteria are well-represented in model systems, challenges of isolating marine microbial heterotrophs and their viruses have hampered experimental approaches to quantify the importance of viruses in nutrient recycling. A resurgence in cultivation efforts has improved the availability of fastidious bacteria for hypothesis testing, but this has not been matched by similar efforts to cultivate their associated bacteriophages. Here, we describe a high-throughput method for isolating important virus-host systems for fastidious heterotrophic bacteria that couples advances in culturing of hosts with sequential enrichment and isolation of associated phages. Applied to six monthly samples from the Western English Channel, we first isolated one new member of the globally dominant bacterial SAR11 clade and three new members of the methylotrophic bacterial clade OM43. We used these as bait to isolate 117 new phages, including the first known siphophage-infecting SAR11, and the first isolated phage for OM43. Genomic analyses of 13 novel viruses revealed representatives of three new viral genera, and infection assays showed that the viruses infecting SAR11 have ecotype-specific host ranges. Similar to the abundant human-associated phage ɸCrAss001, infection dynamics within the majority of isolates suggested either prevalent lysogeny or chronic infection, despite a lack of associated genes, or host phenotypic bistability with lysis putatively maintained within a susceptible subpopulation. Broader representation of important virus-host systems in culture collections and genomic databases will improve both our understanding of virus-host interactions, and accuracy of computational approaches to evaluate ecological patterns from metagenomic data.
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http://dx.doi.org/10.1038/s41396-020-00872-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163748PMC
June 2021

Discharge and Readmission to the Pediatric Cardiac ICU in Pediatric Patients With Durable Ventricular Assist Devices.

Pediatr Crit Care Med 2020 09;21(9):e810-e818

Department of Pediatric Cardiology, University of Alberta, Edmonton, AB, Canada.

Objectives: Pediatric patients implanted with a durable ventricular assist device are initially managed in the pediatric cardiac ICU but are eligible for discharge to the ward. Our objectives were to characterize discharge and readmission of ventricular assist device patients to the pediatric cardiac ICU, identify risk factors for readmission, and determine whether discharge or readmission is associated with mortality.

Design: Retrospective study.

Setting: Stollery Children's Hospital.

Patients: Patients implanted with a durable ventricular assist device at less than 18 years old between 2005 and 2016.

Interventions: None.

Measurements And Main Results: There were 44 patients who underwent ventricular assist device implantation at a median age of 3.7 years (interquartile range, 0.6-9.0 yr), with the most common etiology being noncongenital heart disease (76.7%). Median time of total ventricular assist device support was 110.0 days (interquartile range, 42.3-212.3 d) with the median index pediatric cardiac ICU stay being 34.0 days (interquartile range, 19.8-81.0 d). Thirty patients (68.0%) were discharged to the ward with 18 (60.0%) having at least one readmission. The median time to first readmission was 18.0 days (interquartile range, 14.8-109.8 d) with a median of two readmissions per patient (interquartile range, 1.0-3.0). The most common reason for readmission was pump thrombosis (30.4%), followed by neurologic dysfunction (23.9%). There were no statistically significant pre- or post-implant factors associated with readmission, and readmission was not associated with mortality (p = 0.600). Univariate Kaplan-Meier survival analysis indicated that use of pre-implant extracorporeal membrane oxygenation, post-implant continuous renal replacement therapy, as well as failure to be discharged from the index pediatric cardiac ICU stay were associated with mortality.

Conclusions: Readmissions to the pediatric cardiac ICU occurred in 60.0% of pediatric patients on durable ventricular assist devices with the first readmission occurring within a month of discharge from the index pediatric cardiac ICU stay. While readmission was not associated with mortality, lack of discharge from index pediatric cardiac ICU stay was likely due to a worse pre-implant clinical status.
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http://dx.doi.org/10.1097/PCC.0000000000002456DOI Listing
September 2020

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

ASAIO J 2020 08;66(8):939-945

Division of Cardiology, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta.

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.
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http://dx.doi.org/10.1097/MAT.0000000000001093DOI Listing
August 2020

End-Stage Liver Disease Models and Outcomes in Pediatric Patients Supported With Short-Term Continuous-Flow Ventricular Assist Devices.

ASAIO J 2020 08;66(8):933-938

Division of Pediatric Cardiology, University of Alberta, Alberta, Canada.

Short-term continuous-flow ventricular assist devices (STCF-VADs) are increasingly being utilized in pediatrics. End-stage liver disease (ELD) models have been associated with outcomes in adult patients on mechanical circulatory support. We sought to determine the relationship between outcomes in children on STCF-VADs and three ELD models: model for end-stage liver disease-excluding international normalized ratio (MELD-XI; all) and MELD-XI (> 1 year), PELD, and a novel score, PedMELD-XI. All patients (< 19 years) supported with STCF-VADs, between June 2009 and December 2016 were included. The MELD-XI, PELD, and PedMELD-XI scores were calculated and their association with adverse events and a composite measure of death, major bleeding, and neurologic dysfunction was analyzed. Of 32 patients, median age was 0.57 years (interquartile range [IQR], 0.10-4.43), median weight was 7.15 kg (IQR, 3.68-16.53), 53.1% had congenital heart disease, and 53.1% were male. In total, 78.1% patients experienced an adverse event (78.1% a major bleed, 25.0% neurologic dysfunction, and 15.6% death). The median MELD-XI score was 11.17 (IQR, 9.44-30.01), MELD-XI (>1 year) 9.44 (IQR, 9.44-24.33), PELD 6.00 (IQR, 4.00-13.75), and PedMELD-XI -14.91 (IQR, -18.85 to -12.25). A higher MELD-XI for all ages (13.80 vs. 9.44, p = 0.037) and less negative PedMELD-XI (-14.16 vs. -19.34, p = 0.028) scores were significantly associated with bleeding and the composite outcome. PedMELD-XI was significantly associated with death (-12.87 vs. -16.84, p = 0.041) while a trend was seen for increased MELD-XI in all ages being associated with death (31.52 vs. 10.11, p = 0.051). Last, there was no association with the models and neurologic events. MELD-XI and PedMELD-XI were significantly associated with major bleeding and the composite endpoints with PedMELD-XI also being associated with death. These results suggest that ELD models can be used to predict outcomes in this specific patient population, however, further analysis in a larger population is required.
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http://dx.doi.org/10.1097/MAT.0000000000001078DOI Listing
August 2020

Mechanical Circulatory Support in Pediatric and Adult Congenital Heart Disease.

Can J Cardiol 2020 02 14;36(2):223-233. Epub 2019 Oct 14.

Division of Pediatric Cardiology, Stollery Children's Hospital, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

The use of ventricular-assist device (VAD) support continues to increase and it is now considered part of the standard of care for most adult and children with end-stage heart failure unresponsive to medical management. However, the application of VAD therapy in both the pediatric and adult population with congenital heart disease (CHD) has been less extensive and continues to face significant challenges. Nevertheless, the experience is growing and the use of VADs in the CHD population is no longer limited to case reports, thereby increasing our understanding of how best to support this diverse patient population. The current body of literature provides a framework to understand the outcomes of this unique patient population with respect to mortality, risk factors, and associated morbidities in both adult and pediatric patients with CHD. This review will summarize that body of literature with focus on outcomes based on device type and anatomy. We also highlight efforts made by the community to improve outcomes of patients with CHD on VAD support.
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http://dx.doi.org/10.1016/j.cjca.2019.10.006DOI Listing
February 2020

HLA Alloimmunization Following Ventricular Assist Device Support Across the Age Spectrum.

Transplantation 2019 12;103(12):2715-2724

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

Background: Ventricular assist device (VAD) therapy has become an important tool for end-stage heart failure. VAD therapy has increased survival but is associated with complications including the development of human leukocyte antigen (HLA) antibodies. We sought to determine the incidence of HLA antibody development post-VAD insertion, across the age spectrum, in patients receiving leukocyte-reduced blood products, with standardized HLA antibody detection methods and to investigate factors associated with antibody development.

Methods: This was a retrospective analysis of all patients who underwent durable VAD placement between 2005 and 2014. Inclusion criteria included availability of pre- and post-VAD HLA antibody results. Associations between HLA antibody development in the first-year postimplant and patient factors were explored.

Results: Thirty-nine adult and 25 pediatric patients made up the study cohort. Following implant, 31% and 8% of patients developed new class I and class II antibodies. The proportion of newly sensitized patients was similar in adult and pediatric patients. The class I HLA panel reactive antibody only significantly increased in adults. Pre-VAD sensitization, age, sex (pediatrics), and transfusion were not associated with the development of HLA antibodies.

Conclusions: In a cohort of VAD patients receiving leukocyte-reduced blood products and standardized HLA antibody testing, roughly one-third developed new class I antibodies in the first-year postimplant. Adults showed significantly increased class I panel reactive antibody following VAD support. No patient-related factors were associated with HLA antibody development. Larger prospective studies are required to validate these findings and determine the clinical impact of these antibodies following VAD insertion.
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http://dx.doi.org/10.1097/TP.0000000000002798DOI Listing
December 2019

Bivalirudin Experience in a Heterogeneous Ventricular Assist Device Population.

ASAIO J 2020 06;66(6):677-682

Division of Pediatric Cardiology at the University of Alberta in Edmonton, Alberta, Canada.

Ventricular assist devices (VADs) are an increasingly common therapy for end-stage heart failure across all ages as a bridge to recovery or transplant and more recently as destination therapy. With increasing experience and difficulties with establishing therapeutic heparin levels, we have begun to explore the effectiveness of direct thrombin inhibitors in this patient population. This is a retrospective review of all long-term VAD patients, both adult and pediatric, who were anticoagulated with bivalirudin between January 2009 and January 2016. The starting dose was 0.3 mg/kg/hr, and dose was titrated for a goal partial thromboplastin time (PTT) of 70-100. There were 14 patients (13 males, 5 ≤18 years) with 17 episodes of bivalirudin therapy. The median age on initiation was 45 years (range, 15 days-67 years) with 10 episodes associated with a HeartWare HVAD, five a HeartMate II, and two with a Berlin Heart EXCOR. The predominant indication of bivalirudin therapy was suspected pump thrombosis (13/17). The median time from VAD insertion to initiation of bivalirudin was 116 days (range, 3-1,870) with the median duration of therapy being 21 days (range, 3-113). In patients with pump thrombosis, the mean baseline lactate dehydrogenase (LDH) was 229 ± 64 U/L, peak 690 ± 380 U/L, and decreased to 330 ± 243 U/L when bivalirudin was stopped. The outcomes following suspected pump thrombosis included: transitioned to warfarin (n = 7), death in two destination therapy patients who did not undergo pump exchange, transplantation (n = 2), and pump exchange (n = 2). A major bleeding complication occurred in only one patient. Our experience highlights the potential use of bivalirudin in a heterogenous VAD population. Although these initial results suggest some potential role for direct thrombin inhibitors for use in long-term VADs, larger prospective studies are required to support these preliminary observations and to determine who may benefit from direct thrombin inhibitors (DTIs) and the side effect profile in this patient population.
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http://dx.doi.org/10.1097/MAT.0000000000001062DOI Listing
June 2020

Host-hijacking and planktonic piracy: how phages command the microbial high seas.

Virol J 2019 02 1;16(1):15. Epub 2019 Feb 1.

University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD, UK.

Microbial communities living in the oceans are major drivers of global biogeochemical cycles. With nutrients limited across vast swathes of the ocean, marine microbes eke out a living under constant assault from predatory viruses. Viral concentrations exceed those of their bacterial prey by an order of magnitude in surface water, making these obligate parasites the most abundant biological entities in the ocean. Like the pirates of the 17th and 18th centuries that hounded ships plying major trade and exploration routes, viruses have evolved mechanisms to hijack microbial cells and repurpose their cargo and indeed the vessels themselves to maximise viral propagation. Phenotypic reconfiguration of the host is often achieved through Auxiliary Metabolic Genes - genes originally derived from host genomes but maintained and adapted in viral genomes to redirect energy and substrates towards viral synthesis. In this review, we critically evaluate the literature describing the mechanisms used by bacteriophages to reconfigure host metabolism and to plunder intracellular resources to optimise viral production. We also highlight the mechanisms used when, in challenging environments, a 'batten down the hatches' strategy supersedes that of 'plunder and pillage'. Here, the infecting virus increases host fitness through phenotypic augmentation in order to ride out the metaphorical storm, with a concomitant impact on host substrate uptake and metabolism, and ultimately, their interactions with their wider microbial community. Thus, the traditional view of the virus-host relationship as predator and prey does not fully characterise the variety or significance of the interactions observed. Recent advances in viral metagenomics have provided a tantalising glimpse of novel mechanisms of viral metabolic reprogramming in global oceans. Incorporation of these new findings into global biogeochemical models requires experimental evidence from model systems and major improvements in our ability to accurately predict protein function from sequence data.
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http://dx.doi.org/10.1186/s12985-019-1120-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359870PMC
February 2019

Preoperative Predictors of Mortality in Short-Term Continuous-Flow Ventricular Assist Devices.

ASAIO J 2019 Nov/Dec;65(8):769-774

Division of Cardiology, Division of Pediatric Cardiology, University of Alberta, Edmonton, Alberta, Canada.

Short-term continuous-flow ventricular assist devices (STCF-VADs) are increasingly being utilized to support critically ill patients, despite limited information regarding overall outcomes. All adult patients supported with an STCF-VAD between June 2009 and December 2015 were included in this retrospective single-center study. Associations between preoperative characteristics and unsuccessful bridge (death on device or within 30 days postdecannulation) were assessed using logistic regression. A total of 61 patients (77% male) were identified with a median age at implant of 54.6 years. Left VADs were implanted in 51%, right VADs in 21%, and both VADs in 28%, and patients were supported for a median of 11 days. Overall, 23% were weaned to recovery, 13% underwent heart transplantation, 16% converted to long-term VADs, and 48% had an unsuccessful bridge. In multivariable analysis, only renal insufficiency or dialysis (odds ratio = 7.53; p = 0.002) remained a significant independent predictor of an unsuccessful bridge. Short-term continuous-flow VADs can successfully bridge adult patients with mortality around 50%. Preimplant renal insufficiency or dialysis is correlated with an unsuccessful bridge in our patient population, likely reflecting the severity of illness preimplant. Further studies are required to determine whether this factor remains significant in a larger patient population.
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http://dx.doi.org/10.1097/MAT.0000000000000902DOI Listing
June 2020

Left ventricular assist device for ventricular recovery of anabolic steroid-induced cardiomyopathy.

J Surg Case Rep 2018 Aug 15;2018(8):rjy221. Epub 2018 Aug 15.

Division of Cardiac Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Herein we report a case of a 26-year-old gentleman with severe cardiomyopathy likely secondary to anabolic-androgenic steroid (AAS) abuse who received a HeartMate II (Abbott Laboratories, Abbott Park, IL) left ventricular assist device (LVAD) for rapidly deteriorating heart failure with hemodynamic compromise. Following 18 months on LVAD support, excellent recovery of ventricular function was achieved to allow for LVAD discontinuation. Given that active substance abuse is a contraindication to heart transplantation, few options remain for patients with AAS induced heart failure. Our case demonstrates that LVAD therapy can be an important intervention for bridging to candidacy, recovery or destination therapy.
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http://dx.doi.org/10.1093/jscr/rjy221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101629PMC
August 2018

Driveline Site Is Not a Predictor of Infection After Ventricular Assist Device Implantation.

ASAIO J 2018 Sep/Oct;64(5):616-622

Department of Pediatrics, University of Alberta, Edmonton, Canada.

Driveline infections (DLIs) remain a major source of morbidity for patients requiring long-term ventricular assist device (VAD) support. We aimed to assess whether VAD driveline exit site (DLES) (abdomen versus chest wall) is associated with DLI. All adult patients who underwent insertion of a HeartWare HVAD or HeartMate II (HMII) between 2009 and 2016 were included. Driveline infection was defined as clinical evidence of DLI accompanied by a positive bacterial swab and need for antibiotics. Competing risks analysis was used to assess the association between patient characteristics and DLI. Ninety-two devices (59 HMII) were implanted in 85 patients (72 men; median age 57.4 years) for bridge to transplant or destination therapy. VAD DLES was chest in 28 (30.4%) devices. Median time on VAD support was 347.5 days (IQR 145.5, 757.5), with 28 transplants and 29 deaths (27 on device). DLI occurred in 24 patients (25 devices) at a median of 140 days (IQR 67, 314) from implant. Staphylococcus aureus accounted for 15 infections (60%). Freedom from infection was 72.8% (95% confidence interval [CI] 53.1-78.0%) at 1 year and 41.9% (95% CI 21.1-61.5%) at 3 years. In competing risks regression, abdominal DLES was not predictive of DLI (hazard ratio, HR 1.65 [95% CI 0.63, 4.29]), but body mass index (BMI) >30 kg/m was (HR 2.72 [95% CI 1.25, 5.92]). In conclusion, risk of DLI is high among patients on long-term VAD support, and a nonabdominal DLES does not reduce this risk. The only predictor of DLI in this series was an elevated BMI.
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http://dx.doi.org/10.1097/MAT.0000000000000690DOI Listing
March 2019

Talking with caregivers of children living in the community with ventricular assist devices.

Pediatr Transplant 2017 Nov 29;21(7). Epub 2017 Aug 29.

University of Alberta, Edmonton, Alberta, Canada.

A VAD is a mechanical pump used to support the functioning of a failing heart. As a pediatric therapy, a VAD is used as a temporary solution for poor heart function, a bridge to transplantation or recovery, or a destination therapy. The goal of this qualitative study was to explore the perspectives of family and professional caregivers of children who are supported by VADs in outpatient settings. Semi-structured interviews were conducted with 22 caregivers of school-aged children discharged home on VAD support. Interviews were transcribed, and data were analyzed using qualitative content analysis. Caregivers identified issues facing children on VAD support in the contexts of home, school, and other childhood places including being physically connected to a device; experiencing changes; living a medical life; negotiating restrictions; cost of care; family, kinship, and community; and, present and future living. While a child with a VAD may have much in common with other medically complex children, the technological complications and risks of living with a VAD are uniquely identified by caregivers as an issue, especially when considering the way that children with a VAD are connected to their device-implanted yet exterior, mobile yet restricted, and autonomous yet dependent.
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http://dx.doi.org/10.1111/petr.13049DOI Listing
November 2017

The Spectrum of General Surgery Interventions in Pediatric Patients with Ventricular Assist Devices.

ASAIO J 2018 Jan/Feb;64(1):105-109

Ventricular assist devices (VADs) have positively impacted the management of heart failure. However, they come with a range of complications. Although general surgical complications have been assessed in adults with VADs, there is no study to date that has assessed general surgery intervention in the pediatric population. Fifty-two patients who received VADs from 2005 to 2015 at the Stollery Children's Hospital were assessed for general surgery intervention and anticoagulation status at the time of intervention. Eighteen patients (35%) had general surgery intervention; there were 21 nonemergency procedures and six emergency procedures performed. For nonemergency procedures, 89% of patients had anticoagulation held within 24 hours of surgery and 84% had anticoagulation resumed within 4 hours postoperatively. Antiplatelet therapy was not held perioperatively. In both emergency and nonemergency procedures, anticoagulation status was not a factor in the success of the procedure. This study shows that it is safe to have general surgery intervention on the same admission as a VAD implant provided an appropriate interdisciplinary healthcare team is involved with the perioperative management of the patient.
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http://dx.doi.org/10.1097/MAT.0000000000000609DOI Listing
July 2018

Successful Treatment of Pediatric Ventricular Assist Device Thrombosis.

ASAIO J 2018 Mar/Apr;64(2):e28-e32

Pump thrombosis represents a significant cause of morbidity and mortality in patients on continuous flow ventricular assist devices (CF-VAD). Pump thrombosis in the pediatric CF-VAD population has been reported between 11% and 44%, with the largest reported series from the PediMACS registry reporting a rate of approximately 15%. We report our early experience with four pediatric patients who developed pump thrombosis on a CF-VAD. Our limited experience suggests that the treatment of pediatric VAD thrombosis can be approached with similar principles to the adult population. Our current strategy includes:i. Initiating treatment with bivalirudin for an isolated rise in lactate dehydrogenase (LDH) with no corresponding rapid rise in plasma-free hemoglobin which may prevent further progression.ii. Treatment with a low-dose systemic tissue plasminogen activator (TPA) protocol as opposed to targeted therapy via catheter intervention if bivalirudin fails.iii. If there are concerns with respect to the impact of hemolysis on kidney function or the patient is close to a previous surgery, device exchange can be considered.The balance between achieving appropriate anticoagulation/antiplatelet therapy in the face of bleeding/hemorrhagic complications remains a challenge. There is a need for larger studies in the pediatric population to outline an algorithm for the definitive management of VAD thrombosis.
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http://dx.doi.org/10.1097/MAT.0000000000000606DOI Listing
February 2019

Neurologic, Neurocognitive, and Functional Outcomes in Children Under 6 Years Treated with the Berlin Heart Excor Ventricular Assist Device.

ASAIO J 2017 Mar/Apr;63(2):207-215

From the *Division of Pediatric Neurology, Department of Pediatrics, University of Alberta, Edmonton, Canada; †Division of Developmental Pediatrics, Department of Pediatrics, University of Alberta, Edmonton, Canada; ‡Pediatric Rehabilitation, Glenrose Rehabilitation Hospital, Edmonton, Canada; §Division of Pediatric Critical Care, Department of Pediatrics, University of Alberta and Stollery Children's Hospital, Edmonton, Canada; ¶Division of Pediatric Cardiology, Department of Pediatrics, University of Alberta and Stollery Children's Hospital, Edmonton, Canada; and ‖Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, Canada.

The objective of this study is to describe the neurologic, neurocognitive, and functional outcomes of children aged under 6 years supported on the Berlin Heart EXCOR ventricular assist device (VAD) followed in the Complex Pediatric Therapies Follow-up Program (CPTFP). Sixteen patients were prospectively followed through this longitudinal, developmental program. The patients were evaluated with neurologic physical examination. Intelligence quotients (IQ) and functional outcome scores (ABAS-II scores) were obtained. Neuroimaging reports from before, during, and after VAD implantation were retrospectively reviewed for reported brain injury (BI). Twelve patients (75%) had neuroimaging documented BI at some point in their life (i.e., before, during, or after VAD support). Five patients (31%) had neuroimaging evidence of acute BI incurred while on the VAD. The high overall number of patients with neuroimaging documented BI at any point in their life illustrates that the risk for BI also exists outside the window of VAD support. Patients with abnormal neurologic physical examination at follow-up had lower IQ and ABAS-II scores compared with patients with normal neurologic physical examination (mean full-scale IQ 66.9 vs. 95.0, p = 0.001; mean ABAS-II 66.3 vs. 94.2, p < 0.001).
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http://dx.doi.org/10.1097/MAT.0000000000000462DOI Listing
October 2017

Long-term use of low-molecular-weight heparin in a patient with Heartware BIVAD (HVAD) with underlying sustained ventricular fibrillation.

J Cardiol Cases 2016 Dec 7;14(6):171-173. Epub 2016 Sep 7.

Division of Cardiovascular Surgery, Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada.

We report the case of a 59-year-old patient with Heartware (Framingham, MA, USA) biventricular assist device (BIVAD) implantation who had long-term sustained ventricular fibrillation and was managed on low-molecular-weight heparin for up to two years without any adverse events. The successful outcome in this case provides a clue that the long-term management of Heartware BIVADs with low-molecular-weight heparins could be a viable option even in patients with underlying malignant arrhythmias. < Long-term management of Heartware biventricular assist devices (BIVADs) using low-molecular-weight heparin is possible. This treatment strategy can serve as an alternative to oral anticoagulants in a select group of patients. This case report also suggests that BIVADs can potentially serve as a useful alternative to total artificial heart.>.
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http://dx.doi.org/10.1016/j.jccase.2016.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283705PMC
December 2016

A Systematic Review of the Cost-Effectiveness of Long-Term Mechanical Circulatory Support.

Value Health 2016 06;19(4):494-504

Division of Nephrology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. Electronic address:

Background: Mechanical circulatory support (MCS) is an option for the treatment of medically intractable end-stage heart failure. MCS therapy, however, is resource intensive.

Objective: The purpose of this report was to systematically review the MCS cost-effectiveness literature as it pertains to the treatment of adult patients in end-stage heart failure.

Methods: We conducted a systematic search and narrative review of available cost- effectiveness and cost-utility analyses of MCS in adult patients with end-stage heart failure.

Results: Eleven studies analyzing the cost-effectiveness or cost-utility of MCS were identified. Seven studies focused on bridge to transplantation, three studies focused on destination therapy, and one study presented analyses of both strategies. Two articles evaluated the cost-effectiveness of the HeartMate II (Thoratec Corp., Pleasanton, CA). Incremental cost-effectiveness ratios between MCS and medical management ranged between $85,025 and $200,166 for bridge to transplantation and between $87,622 and $1,257,946 for destination therapy (2012 Canadian dollars per quality-adjusted life-year). Sensitivity analyses indicated that improvements in survival and quality of life and reductions in device and initial hospital-stay costs may improve the cost-effectiveness of MCS.

Conclusions: Current studies suggest that MCS is likely not cost-effective with reference to generally accepted or explicitly stated thresholds. Refined patient selection, complication rates, achieved quality of life, and device/surgical costs, however, could modify the cost-effectiveness of MCS.
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http://dx.doi.org/10.1016/j.jval.2014.12.020DOI Listing
June 2016

Supporting pediatric patients with short-term continuous-flow devices.

J Heart Lung Transplant 2016 05 8;35(5):603-9. Epub 2016 Feb 8.

Division of Pediatric Cardiac Surgery, Stollery Children's Hospital, Edmonton, Alberta, Canada.

Background: Short-term continuous-flow ventricular assist devices (STCF-VADs) are increasingly being used in the pediatric population. However, little is known about the outcomes in patients supported with these devices.

Methods: All pediatric patients supported with a STCF-VAD, including the Thoratec PediMag or CentriMag, or the Maquet RotaFlow, between January 2005 and May 2014, were included in this retrospective single-center study.

Results: Twenty-seven patients (15 girls [56%]) underwent 33 STCF-VAD runs in 28 separate hospital admissions. The STCF-VAD was implanted 1 time in 23 patients (85%), 2 times in 2 patients (7%), and 3 times in 2 patients (7%). Implantation occurred most commonly in the context of congenital heart disease in 14 runs (42.2%), cardiomyopathy in 11 (33%), and after transplant in 6 (18%). The median age at implantation was 1.7 (interquartile range [IQR] 0.1, 4.1) years, and median weight was 8.9 kg (IQR 3.7, 18 kg). Patients were supported for a median duration of 12 days (IQR 6, 23 days) per run; the longest duration was 75 days. Before implantation, 15 runs (45%) were supported by extracorporeal membrane oxygenation (ECMO). After implantation, an oxygenator was required in 20 runs (61%) and continuous renal replacement therapy in 21 (64%). Overall, 7 runs (21%) resulted in weaning for recovery, 14 (42%) converted to a long-term VAD, 4 (12%) resulted in direct transplantation, 3 (9%) were converted to ECMO, and 5 (15%) runs resulted in death on the device or within 1 month after decannulation. The most common complication was bleeding requiring reoperation in 24% of runs. In addition, 18% of runs were associated with neurologic events and 15% with a culture-positive infection. Hospital discharge occurred in 19 of 28 STCF-VAD admissions (67%). In follow-up, with a median duration of 9.2 months (IQR 2.3, 38.3 months), 17 patients (63%) survived.

Conclusions: STCF-VADs can successfully bridge most pediatric patients to recovery, long-term device, or transplant, with an acceptable complication profile. Although these devices are designed for short-term support, longer support is possible and may serve as an alternative approach to patients not suitable for the current long-term devices.
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http://dx.doi.org/10.1016/j.healun.2016.01.1224DOI Listing
May 2016

A multicenter study of the HeartWare ventricular assist device in small children.

J Heart Lung Transplant 2016 05 18;35(5):679-81. Epub 2016 Jan 18.

Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.

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http://dx.doi.org/10.1016/j.healun.2016.01.019DOI Listing
May 2016

Mechanical circulatory support in univentricular hearts: current management.

Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2015 ;18(1):17-24

Division of Cardiac Surgery, University of Alberta, Stollery Children׳s Hospital, Edmonton, Alberta, Canada.

Failing single-ventricle patients have now come into focus as the next cohort where improvement in outcomes for mechanical circulatory support can be realized. There is a paucity of published patient reports or management protocols in this patient population. Increased interest exists in finding answers of how to bridge these patients to transplant. We review the current literature and describe our approach to the patient with univentricular heart needing mechanical circulatory support.
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http://dx.doi.org/10.1053/j.pcsu.2015.02.002DOI Listing
February 2016

Refractory cardiogenic shock in a patient with β-thalassemia major requiring mechanical circulatory support: Case report and literature review.

Pediatr Transplant 2015 Jun 11;19(4):E93-6. Epub 2015 Mar 11.

Division of Cardiac Surgery, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.

Iron overload cardiomyopathy secondary to β-thalassemia major is a potentially reversible condition managed with chelation and medical hemodynamic support, as bridge-to-recovery or transplant. We describe our experience, and challenges faced, in a pediatric patient with iron overload cardiomyopathy secondary to β-thalassemia major, requiring biventricular MCS.
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http://dx.doi.org/10.1111/petr.12454DOI Listing
June 2015

Mechanical ventricular assist device as a bridge to recovery post-ABO-incompatible heart transplantation for failed Fontan circulation.

Transpl Int 2014 Jul 29;27(7):e54-7. Epub 2014 Mar 29.

Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada.

A girl received an ABO-incompatible heart transplantation (ABOiHTx) at the age of 3.5 years for failed univentricular palliation with protein-losing enteropathy (PLE). She was born with a hypoplastic left heart syndrome and underwent multistage palliation to a Fontan circulation at 2½ years of age. After the Fontan surgery, she developed PLE, necessitating a Fontan revision, followed by a Fontan takedown and eventually HTx, which was performed with a blood group B heart into an O recipient. Right ventricular (RV) failure secondary to increased pulmonary vascular resistance (PVR) evolved immediately after HTx. A temporary right ventricular assist device (RVAD) was implanted and later switched to a pneumatic pulsatile RVAD. With the adaption of PVR on the RVAD, the PLE resolved and the RVAD was explanted. In the following 12 months, she developed multiple relapses of PLE which eventually resolved after exchange of the calcineurin inhibitor.
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http://dx.doi.org/10.1111/tri.12294DOI Listing
July 2014

Right ventricular dysfunction in children supported with pulsatile ventricular assist devices.

J Thorac Cardiovasc Surg 2014 May 15;147(5):1691-1697.e1. Epub 2013 Dec 15.

Department of Pediatric Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.

Objectives: To describe the incidence and severity of right ventricular dysfunction (RVD) in pediatric ventricular assist device (VAD) recipients and to identify the preoperative characteristics associated with RVD and their effect on outcomes.

Methods: Children bridged to transplantation from 2004 to 2011 were included. RVD was defined as the use of a left VAD (LVAD) with an elevated central venous pressure of >16 mm Hg with inotropic therapy and/or inhaled nitric oxide for >96 hours or biventricular assist (BiVAD).

Results: A total of 57 children (median age, 2.97 years; range 35 days to 15.8 years) were supported. Of the 57, 43 (75%) had an LVAD, and of those, 10 developed RVD. The remaining 14 (25%) required BiVAD. Thus, RVD occurred in 24 of 57 patients (42%). Preoperative variables such as younger age (P = .01), use of extracorporeal mechanical support (P = .006), and elevated urea (P = .03), creatinine (P = .02), and bilirubin (P = .001) were associated with RVD. Multiple logistic regression analysis indicated that elevated urea and extracorporeal mechanical support (odds ratio, 26.4; 95% confidence interval, 2.3-307.3; and odds ratio, 27.8; 95% confidence interval, 2.5-312.3, respectively) were risk factors for BiVAD. The patients who developed RVD on LVAD had a complicated postoperative course but excellent survival (100%), comparable to those with preserved right ventricular function (91%). The survival for those requiring BiVAD was reduced (71%).

Conclusions: RVD occurred in approximately 40% of pediatric VAD recipients and affects their peri-implantation morbidity and bridging outcomes. Preoperative extracorporeal membrane oxygenation and elevated urea were risk factors for BiVAD. Additional studies of the management of RVD in children after VAD implantation are warranted.
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http://dx.doi.org/10.1016/j.jtcvs.2013.11.012DOI Listing
May 2014

Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines.

Can J Cardiol 2013 Dec;29(12):1535-52

The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.
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http://dx.doi.org/10.1016/j.cjca.2013.08.008DOI Listing
December 2013
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