VAD Use Research Articles

Investigation of OCTA Biomarkers in Fabry Disease: A Long Term Follow-Up of Macular Vessel Area Density and Foveal Avascular Zone Metrics.

Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Prospective study of 26 eyes with FD followed up to 48months (mean 24, range 8-48). OCT angiography (OCTA) images (2.9 × 2.9mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = - 0.6; p < 0.0001). This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.

#5282 ACUTE KIDNEY INJURY IN INFECTIOUS DISEASE BY CORONAVIRUS IN BRAZIL: A STUDY ON INCIDENCE, RISK FACTORS, AND PROGNOSIS

Abstract Background and Aims Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 disease in its severe form, renal involvement is frequent (4-37%). To assess the incidence of acute kidney injury (AKI) in Brazilian patients hospitalized with COVID-19 and to identify both the risk factors associated with its onset and those associated with its prognosis. Method This is a prospective cohort study of patients hospitalized with COVID-19 at a public and tertiary university hospital in São Paulo from March 2020 to May 2021, encompassing the first and second waves of the pandemic. Patients were followed up until the clinical outcome (discharge or death). The evaluation of renal function was performed by measuring serum creatinine and urinary output and the diagnosis of AKI was performed according to the KDIGO 2012 criteria. The occurrence of AKI was established as the dependent variable, using the Chi-Square Test for the comparison of categorical variables and the t Test for continuous variables. Afterwards, a multivariate analysis was performed using the logistic regression model, with calculations of the Odds Ratio (OR), including in the model all the variables that showed association with the outcome (p≤0.20). A similar procedure was performed after establishing death as the dependent variable. Results 887 patients with COVID-19 were analyzed, 54.6% were admitted to the intensive care unit (ICU) and 45.4% were admitted to the ward. The overall incidence of AKI was 48.1%, more frequent in the ICU (83.8 vs 17.1%, p&amp;lt;0.0001). Upon hospital admission, 487 patients were submitted to urine test I, of which 58.5% had hematuria and 51.5% had proteinuria. The overall mortality was 38.9%. The average time for the diagnosis of AKI was 6 days and AKI KDIGO 3 was the most frequent (60.2%). Acute renal support was indicated in 58.8% of patients. According to logistic regression, the risk factors for AKI were the use of diuretics (OR 2.2, CI 1.2-4.1, p&amp;lt;0.05), mechanical ventilation (OR 12.9, CI 4.3-38.2, p&amp;lt;0.05), VAD (OR 2.7, CI 0.9-7.7, p = 0.06), dyslipidemia (OR 0.54, CI 0.3-1.05, p = 0.07), proteinuria (OR 2, CI 1.1-3.4, p&amp;lt;0.05), hematuria (OR 2, CI 1.1-3.5, p&amp;lt;0.05), CKD (OR 2.6, CI 1.2-5.5, p&amp;lt;0.05), older age (OR 1.03, CI 1-1.07, p&amp;lt;0.05), CPK (OR 1.02, CI 1-1.07, p&amp;lt;0.05) and D-dimer (OR 1.02, CI 1.01-1.09, p&amp;lt;0.05). The risk factors for death were arterial hypertension (OR 1.7, CI 1-3, p = 0.05), use of mechanical ventilation (OR 12.9, CI 4.3-38.2, p&amp;lt;0.05), presence of proteinuria (OR 1.6, CI 0.9-2.7, p = 0.07), presence of AKI (OR 6, CI 2.9-12.2, p&amp;lt;0.05), mainly KDIGO 3 (OR 0.6, CI 0.2-1.3, p = 0.2), high D-dimer (OR 1, CI 1, p = 0.05), SOFA score (1.35, CI 1.1-1.6, p&amp;lt;0.05) and ATN-ISS score (OR 996.4, CI 4.8-203271, p&amp;lt;0.05). Finally, the variables that showed the difference in the profile of patients between the two waves of the pandemic were identified, being less frequent in the second wave male gender (OR 0.51, CI 0.35-0.74, p&amp;lt;0.05) and Caucasian ethnicity (OR 0.47, CI 0.2-0.8, p&amp;lt;0.05), and more frequent in the second wave the use of mechanical ventilation (OR 1.57, CI 1-2.3, p&amp;lt;0.05), proteinuria (OR 1.44, CI 1-2.1, p&amp;lt;0.05), higher D-dimer values (OR 1.09, CI 1-1.1, p&amp;lt;0.05) and ATN-ISS score (OR 40.9, CI 1.7-948.1, p&amp;lt;0.05). Conclusion AKI associated with severe COVID-19 in Brazil was more frequent than in the Chinese, European, and North American cohorts, and the risk factors associated with its development are the use of diuretics, mechanical ventilation, VAD, dyslipidemia, proteinuria, hematuria, CKD, older age, elevated CPK and D-dimer. Mortality was high and higher in patients with arterial hypertension, on mechanical ventilation, with proteinuria, with AKI, mainly KDIGO 3, high D-dimer, and higher SOFA and ATN-ISS. In the second wave, AKI severity was greater, but mortality was similar to that of the first wave, which may reflect both the effectiveness of vaccines against SARS-CoV-2, as well as the constant learning that frontline professionals have built throughout the pandemic, to provide greater support to its patients.

Incidence and severity of thrombocytopenia associated with use of intravascular microaxial ventricular assist devices for treatment of cardiogenic shock.

The use of temporary mechanical circulatory support (MCS) for patients with refractory cardiogenic shock has increased over the past decade. Impella devices (intravascular microaxial ventricular assist devices [VADs]) have become common MCS options but reportedly cause thrombocytopenia. Limited published data regarding the incidence or severity of microaxial VAD-associated thrombocytopenia exists. The goal of this study was to determine the incidence, timing, and severity of thrombocytopenia in a microaxial VAD population. A retrospective multicenter review of electronic medical records identified all patients implanted with microaxial VAD at three US academic teaching hospitals between June 2015 and August 2017. Patients were excluded for short-term procedural microaxial VAD use during percutaneous coronary intervention. Sixty-four patients underwent microaxial VAD insertion (95% for left-sided support) during the observed time period. Support was in place for a median duration of 5.2 (interquartile range [IQR]: 2.4-10.0) days. Within 7 days postinsertion, 98.5% of patients developed thrombocytopenia (platelet count <150,000/μl) and 81.3% of patients experienced a>50% platelet decrease. Average platelet count nadir was 68,200/μl or 63.9% from baseline occurring on median day 3.8 (IQR: 2.4-5.4). Twenty-four patients (38.1%) were tested for heparin-induced thrombocytopeniaby the heparin-dependent antibody (HDA) test. All HDAs were either negative or had serotonin release assay negative confirmation. Postdevice removal, platelet counts returned to baseline or >150,000/μl in 63% of patients by Day 5. Microaxial VAD-associatedthrombocytopenia is common. Practitioners should consider this when evaluating supported patients for other causes of thrombocytopenia. Platelet counts return to preimplantation levels within days of device removal.

Impact of occurrence of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation.

The impact of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation has not been studied. The UNOS database was queried for primary pediatric heart transplantation (1999-2020). The cohort was divided into recipients who received a cardiac allograft from a donor who had a cardiac arrest (CA) versus a donor who did not (NCA). Univariable and multivariable analysis was done to compare recipient outcomes, followed by survival analysis using the Kaplan-Meier method. A total of 7300 patients underwent heart transplantation, of which 579 (7.9%) patients belonged to the CA group. The CA group was younger (median 3 vs. 5 years, p < .001), male (51% vs. 47%, p = .03), and smaller in weight (13 vs. 17 kg, p < .001) and height (101 vs. 109 cm, p < .001) than the NCA group. The groups were similar in recipient heart failure diagnosis and blood type. The CA donors were younger (3 vs. 6 years, p < .001) versus nonwhite (48% vs. 45%, p = .003) and died from drowning and asphyxiation compared to blunt injury and intracranial hemorrhage in the NCA group. The left-ventricular ejection fraction was similar between the groups. There was no difference in VAD and ECMO use before the transplant. The listing status, waitlist days, and allograft ischemic times were similar. Posttransplant morbidity such as stroke, dialysis, pacemaker implantation, and treated rejection were similar. Donor cardiac arrest (hazard ratio = 0.93, p = .5) was not an independent predictor of mortality on multivariable analysis. There was no survival difference even beyond 20 years of follow-up between the groups (p = .88). The occurrence of donor cardiac arrest has no impact on long-term survival in pediatric heart transplant recipients.

The ABBA project (Assess Better Before Access): A retrospective cohort study of neonatal intravascular device outcomes.

Venous access devices (VADs) play a vital role within the neonatal intensive care unit. However, there are significant risks associated with the use of VADs, with complications such as infection, thrombosis, device occlusion, and infiltration/extravasation frequently contributing to device-related failures and increasing the risk of significant patient harm or injury. This study aimed to explore the relationships between risk factors and different venous access device complications in the neonatal setting, and then use that evidence to develop an algorithm based on observational data. This is a retrospective, single-center cohort study that was conducted in a large 112-bed neonatal intensive care unit in Qatar. We examined venous access device data from January 2016 to December 2018 for all term and preterm neonates. Descriptive statistics were used to summarize the outcomes, which included a mean and its standard deviation or median and an interquartile range for continuous variables regarding normal distribution, and absolute numbers with percentages for discrete variables. The authors recorded a total of 23,858 VADs inserted during the study period. Of these, 21,313 (89%) were peripheral intravenous catheters, 689 (3%) were extended dwell-peripheral intravenous catheters, 1,335 (6%) were epicutaneo-caval catheters, and 521 (2%) were umbilical venous catheters. In total, 51,179 catheter days were registered, with 2.17 catheter days reported per patient. Peripheral device dwell times were significantly shorter when compared with central venous catheter devices (P < 0.001), with mean dwell times of 22 days ± 23 h and 236 days ± 183 h, respectively. After insertion, a complication occurred in 11,177 (51%) of peripheral VADs and 221 (12%) of central VADs. The type of device inserted [P < 0.001, hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.50-0.54], reason/indication for intravenous therapy (P < 0.001, HR = 0.85, 95% CI: 0.82-0.87), and the side of insertion of the device (P < 0.001, HR = 1.25, 95% CI: 1.24-1.27) had a significant relationship with outcomes. Four subgroups of VADs were identified (peripheral intravenous catheters, extended dwell-peripheral intravenous devices, epicutaneo-caval catheters, and umbilical venous catheters) with outcome-related differences. Central venous access devices (epicutaneo-caval catheters and umbilical venous catheters) had lower complications compared with peripheral VADs. Proper venous access device selection, early insertion, and early removal approaches remain crucial to preventing venous access device complications. Peripheral intravenous devices should be used carefully and closely watched for early detection of complications.

Bedside Peripheral Ultrasound-Guided Vascular Access in 253 Patients Hospitalized With COVID-19 Pneumonia: A Retrospective Italian Study.

BackgroundSeveral studies have recommended the use of vascular access in the treatment of COVID-19 patients. However, little is known about the utility and safety of using a peripheral ultrasound-guided vascular access device (UGVAD) at the bedside of hospitalized COVID-19 patients. To examine this, a retrospective monocenter study was carried out at the oncology-hematology department of Azienda Sanitaria di Piacenza, Italy.MethodsWe retrospectively analyzed data from three general hospitals in a district in North Italy on the positioning of UGVADs used with hospitalized COVID-19 patients. The positioning of the VAD was performed by a dedicated team using ultrasound guidance. The primary endpoint was the duration of VAD until the patient’s recovery or death. The secondary endpoints were complications of the use of VADs, which included vein thrombosis, infections, device malfunction, and viral contamination of the operators.ResultsBetween February 21, 2020, and April 30, 2020, 253 consecutive hospitalized patients with COVID-19 pneumonia underwent UGVAD positioning. A midline was inserted in 88.53% of the patients, while peripheral central venous catheters and femoral central catheters were inserted in 9.88% and 1.59% of the patients, respectively. The mean lifespan of the VADs was 10.36±9.96 days (range: 1-73). Primary endpoint: The use of the VAD allowed the planned treatment in 92.88% of the patients; in the remaining 7.12%, the VAD was repositioned. Secondary endpoints: Complications of VAD were registered in 15.02% of the patients (dislocation, 9.49%; infection, 1.98%; thrombosis, 1.58%; occlusion, 1.19%; and malfunction, 0.79%). No contamination of the operators was registered.Discussion and conclusionWith the limitation of being a retrospective study, our report suggests that ultrasound-guided positioning of VAD may allow the safe clinical management (drug infusion, hydration, parenteral nutrition, and phlebotomy) of hospitalized COVID-19 patients. The observance of recommended procedures protected all operators from infection.

Use of Donor Hearts with Low Ejection Fraction in Pediatric Heart Transplantation: A PHTS Analysis

<h3>Purpose</h3> Despite a growing number of children awaiting heart transplant (HT), annual number of HT is relatively unchanged and waitlist mortality is high especially in infants. Donor heart discard rate is also high with ventricular dysfunction as a major reason. Use of donors with low ejection fraction (DLEF) is rare (<15%) in pediatric HT. We evaluated the use of DLEF in pediatric HT using the Pediatric Heart Transplant Society (PHTS) Database. <h3>Methods</h3> PHTS Database was queried from 1/1993 to 12/2020. DLEF was defined as: donor with left ventricular ejection fraction (LVEF) on pre-procurement echo <54% with wall motion abnormality or LVEF <50% irrespective of wall motion abnormality Donor and recipient characteristics, graft survival and trends of DLEF use across regions and eras were compared. <h3>Results</h3> Of 7520 pediatric HT, 7237 (96%) had a donor echo report but only 6332 (84%) had a LVEF reported. Of these, 143 (2.3%) were DLEF with median LVEF 47% [IQR 44-50%]. Focal or diffuse wall motion abnormality was seen in 35 (24%) and 23 (16%) had abnormal septal motion. Recipient characteristics between groups including age, diagnosis, end-organ function, use of VAD and/or ECMO at listing or transplant were similar. Mechanical ventilation at HT (p=.0082), earlier era (p<.0001), and regional variation (p<.0001) were associated with increased use of DLEF. Donor characteristics were similar with the exception that DLEF were more likely to be on epinephrine (20.7% vs 9.9%, p=<.0001) and/or vasopressin (73% vs 54%, p=.0018). DLEF use decreased over time (1993-2002: 4.26%; 2003-12: 2.18%; 2013-20: 1.6%). Differences were seen across UNOS regions (Region 4 vs 10: 0.9% vs 4.2%, p=<.0001). Graft survival at 3 months post-HT was similar for DLEF vs non-DLEF donors (91% vs. 94%, logrank p=0.1) (Fig 1). <h3>Conclusion</h3> Use of DLEF in pediatric HT is limited and lower than previously reported. Use of DLEF has decreased over time. DLEF had comparable graft survival at 3 months post-HT, supporting efforts to expand the use of DLEF in pediatric HT.

Impact of the 2018 Adult Heart Allocation Change on Pediatric Donor Offers and Waitlist Outcomes

<h3>Purpose</h3> On October 18, 2018, UNOS made important revisions to the adult allocation system for heart transplant (HT). Although the revisions primarily affect the prioritization of adult HT candidates, it could impact pediatric candidates indirectly as adult candidates listed Status 1 or 2 take priority over pediatric Status 1B and 2 candidates. We sought to determine if there was any effect on donor offers, declines and waitlist outcomes for pediatric candidates in light of the adult allocation change. <h3>Methods</h3> All children <18 listed for HT within a 2-year period before and after the adult allocation revision was implemented were identified using OPTN data. Match-run analysis was also performed to examine the offer and decline rates. The primary endpoints were candidate transplantation and mortality rates. <h3>Results</h3> A total of 2,397 children met the study inclusion criteria, including 1,295 children listed before and 1,102 children listed after the adult policy change. The two cohorts were similar with respect to age, weight, cardiac diagnosis, ECMO, ventilator, VAD use, and insurance status. Nationwide offers to pediatric 1A candidates increased 34% per day, though center rejection of offers also rose a similar amount (41%). Pediatric candidates listed Status 1B and 2 also received more offers with a similar rise in center rejections, though the increases were smaller than for 1A candidates. Transplantation and mortality within 30-, 60- and 90-days did not change for 1A/1B candidates perhaps owing to the concomitant rise in center rejections of offers. There was a modest but significant decline in the likelihood of 30- and 60-day transplantation for patients listed at Status 2 following the change, though the likelihood of 90-day transplantation was comparable. <h3>Conclusion</h3> The 2018 changes to the adult allocation system have, if anything, resulted in an increased flow of donor offers to pediatric candidates, however transplantation rates for children listed 1A and 1B appear similar before and after the change, partly because the rise in offers was associated with a rise in offer rejections. For pediatric Status 2 candidates, transplantation was slightly lower at 30- and 60-days, but comparable at 90 days. More work is needed to reduce offer rejections to increase the transplantation rate for pediatric HT candidates.

Heart Transplant Outcomes with Donation After Cardiac Death: UNOS Registry Analysis

<h3>Purpose</h3> Limitations in organ donation have led to approaches to expand the existing donor pool. Donation after cardiac death (DCD) has continued to increase after efforts led by the United Kingdom and Australia. We sought to describe the United States experience. <h3>Methods</h3> 5153 heart transplant (HT) recipients were identified in the UNOS Registry between 1/2019 and 6/2021, of which 229 were DCD recipients. HT recipients were grouped by DCD status or donation after brain death (DBD). Comparisons between groups were assessed using standard statistical methods, survival analysis was censored at 12-months via the Kaplan-Meier method. Multivariate Cox proportional hazard regression analysis (adjusted for age, sex, diabetes, race, ischemic time, dialysis, life support, waiting time & HLA mismatch) were performed. <h3>Results</h3> Recipients of DCD donors were of lower UNOS status (p<0.001), increased VAD use (p=0.01), and less dialysis (p=0.011). Additionally, DCD donor recipients had longer wait times (46.0 vs 30.0d, p=0.007), longer ischemic times (p<0.001) but younger donors (29.8 vs 23.4y, p<0.001). There was no difference in 1-month or 1-year survival by donor type (p=0.720). Unadjusted analysis demonstrated HR 0.91 (0.52-1.57) and following adjustment HR 0.88 (0.48-1.61). <h3>Conclusion</h3> Short-term survival of DCD donors is similar to DBD donors in this UNOS Registry analysis. DCD donor use has potential to expand the donor pool. Further study is warranted to assess longer term outcomes as well as best strategies for donation.

Abstract 11786: Heart Transplant in Congenital Heart Disease: Trends in Mortality With Ventricular Assist Devices

Introduction: Patients with congenital heart disease (CHD) may require cardiac transplantation for either primary management or failed surgical palliation. This study describes 1-year mortality of patients with CHD listed for transplant, trends in 1-year mortality over three decades, and use of mechanical support in this population. Methods: The United Network for Organ Sharing database was queried to identify patients aged 0-30 years with CHD listed for transplant from 1990 to 2019. VAD status at listing and 1-year mortality after listing were examined using the Cochran-Armitage trend test. Results: Overall, 9327 patients with CHD aged 0-30 years were listed for transplant between 1990 and 2019 with a total 1-year mortality rate of 26% (n=2466). For non-survivors to 1-year after listing, 66% (n=1619) died before transplant and 34% (n=847) after transplant. Patients &lt;1 year of age were the most frequent age group listed for transplant (n=3678, 39%) and experienced the highest 1-year mortality after listing (n=1264, 34%). The 1-year overall mortality decreased over the study period (1990-1999: 33% vs 2000-2009: 30% vs 2010-2019: 19%, p&lt;0.0001), including in infants &lt;1 year of age (1990-1999: 41% vs 2000-2009: 37% vs 2010-2019: 26%, p&lt;0.0001). Overall, few patients were supported with VAD at listing (3.1%). However, VAD use increased (1990-1999: 1.0% vs 2000-2009: 2.8% vs 2010-2019: 5.0%, p&lt; 0.0001) and the 1-year mortality for patients with VAD at listing decreased over time (1990-1999: 57% vs 2000-2009: 35% vs 2010-2019: 20%, p&lt;0.0001). Conclusions: Survival after listing for heart transplant is improving, however mortality amongst infants remains high. While there has been &gt;50% improvement in survival in patients of all ages with CHD supported with a VAD at listing, VADs are used rarely in patients with CHD. Further study is needed to understand which patients may benefit from mechanical circulatory support, especially among infants.

Cardiac miRNAs were involved in the regulation of pathophysiological mechanisms underlying HF in pediatric patients after ventricular assist device implantation

Abstract Background VAD use in heart failure (HF) children have undergone rapid progress in the last three decades through pump technological innovation and improvement of perioperative care. Studies in HF adults showed that VAD put native heart at rest and lead to molecular changes in cardiac muscle, including at microRNA (miRNA) level. However, little is known on changes induced by VAD implant in cardiac miRNA expression and their putative targets in HF children. Purpose The aims of this study were to evaluate: 1) modification of miRNA expression in cardiac muscle from HF children after VAD support; 2) the putative targets of selected miRNAs by in silico analysis; 2) the role of the identify miRNAs on putative targets by in vitro study. Methods Cardiac biopsies were collected from HF children at the moment of VAD implant [n=8; 20 (7.5–64.5) months, 2 males; 19 (15.75–32.25) LVEF%] and at the time of heart transplant after VAD support [n=5; 32 (5–204) months; 4 males; 13.5 (10–18) LVEF%]. Cardiac miRNA expression was evaluated by NGS. The potential miRNA targets were identified by bioinformatics analyses and their cardiac expression by real-time PCR was evaluated. HL-1 cell line was used for testing the regulatory role of selected miRNA on predicted targets by miRNA mimic transfection study. Results At NGS, 465 miRNA were found on average in each sample and the cardiac expression levels of miR19a-3p, miR-1246 and miR-199b-5p decreased in HF children after VAD support compared to pre-implant (Fig. 1A-B). In silico analysis showed that more than 5000 potential gene targets regulated by miR-19a-3p, miR-1246 and miR-199b-5p. Among them, adiponectin receptors (AdipoR1, AdipoR2, T-CAD) were identified as common targets for 3 miRNAs. Real-time PCR data showed that levels of all adiponectin receptors increased significantly whilst the expression of 3 miRNAs decreased after VAD support (Fig. 1C). Moreover, AdipoR2 and T-CAD were inversely related to miRNA levels (Fig. 1D). In vitro studies confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2 (Fig. 1E-F), whilst only miR-199b-5p reduced the expression of T-CAD (Fig. 1G). Finally, AdipoR1 expression levels are not modified compared to control by miRNAs mimic transfection (data not shown). Conclusion In HF children the use of VAD could modify the expression of several miRNAs potentially involved in the regulation of several pathophysiological mechanisms underlying HF. Specifically, the reductions of miR-1246, mir-19a-3p, miR-199b-5p were associated with an increase of the adiponectin receptors AdipoR2 and T-CAD mRNA, suggesting the existence of a miRNAs related fine tuning of the adiponectin system at cardiac tissue level by VAD implant, able to favour the protective effect of adiponectin in HF cardiac muscle. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): FP7-ICT-2009 Project, Grant Agreement 24863 Figure 1

Waitlist Mortality for Children Listed for Heart Transplant in the United States: How are We Doing?

PurposeStudies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors like refinements to the heart allocation system, patient selection, greater ABO incompatible (ABO-I) HT and VAD support are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist.MethodsAll children <18 years listed for isolated HT from 1999-2020 were identified using OPTN data and grouped into 3 eras (Era 1: 1999-2006; Era 2: 2006-2016; Era 3: 2016-2020) based on when UNOS revised the heart allocation system. Cox proportional hazards modeling was used to identify factors associated with death or delisting due to deterioration.ResultsOverall 11,374 patients met inclusion criteria (3,248 in Era 1; 5,378 in Era 2; 2,748 in Era 3). Waitlist mortality declined significantly across eras (21%, 17%, 13%, P<0.001). The prevalence at listing of major risk factors for mortality declined across eras including a reduction by 47% in ECMO use (11% to 6%, P<0.001), 33% in ventilator use (27% to 18%, P<0.001), 26% in dialysis use (2.5% to 1.8%, P=0.08); in contrast VAD use at listing increased by 243% (6% to 15%, P<0.001). Infant mortality declined significantly (27% to 20%, P<0.001) with a 48% decline in mortality for blood group O patients (relative to the background decline for all blood groups) and a 69% decline in infant VAD mortality (P<0.01). In Era 3, RCM and re-transplant patients not eligible for status 1A without exception had higher mortality than 1A DCM patients on LVAD support (16% vs 5.3%, P<0.01).ConclusionPediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system suggesting opportunities for allocation improvement may still exist. Studies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors like refinements to the heart allocation system, patient selection, greater ABO incompatible (ABO-I) HT and VAD support are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist. All children <18 years listed for isolated HT from 1999-2020 were identified using OPTN data and grouped into 3 eras (Era 1: 1999-2006; Era 2: 2006-2016; Era 3: 2016-2020) based on when UNOS revised the heart allocation system. Cox proportional hazards modeling was used to identify factors associated with death or delisting due to deterioration. Overall 11,374 patients met inclusion criteria (3,248 in Era 1; 5,378 in Era 2; 2,748 in Era 3). Waitlist mortality declined significantly across eras (21%, 17%, 13%, P<0.001). The prevalence at listing of major risk factors for mortality declined across eras including a reduction by 47% in ECMO use (11% to 6%, P<0.001), 33% in ventilator use (27% to 18%, P<0.001), 26% in dialysis use (2.5% to 1.8%, P=0.08); in contrast VAD use at listing increased by 243% (6% to 15%, P<0.001). Infant mortality declined significantly (27% to 20%, P<0.001) with a 48% decline in mortality for blood group O patients (relative to the background decline for all blood groups) and a 69% decline in infant VAD mortality (P<0.01). In Era 3, RCM and re-transplant patients not eligible for status 1A without exception had higher mortality than 1A DCM patients on LVAD support (16% vs 5.3%, P<0.01). Pediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system suggesting opportunities for allocation improvement may still exist.

Recipient Morbid Obesity Worsens Post Heart Transplantation Survival

PurposeMorbid obesity (body mass index (BMI) ≥ 35kg/m2) is a relative contraindication for a heart transplant (HT). However, the clinical outcome of these HT recipients is not well established. This study examined the clinical outcome of morbidly obese patients who underwent HT in The United States.MethodsWe included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5-, and 10-year survival of those with a BMI≥ 35 kg/m2 and BMI = 18.5-34.99 kg/m2. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio.Results36,115 adult HT recipients were included: 2638 (7.3%) morbidly obese. The median (inter-quartile range) age was 55 (46, 62) years, 24.7% were female, and follow-up was 4.1 (1.1, 8.3) years. Morbidly obese patients had more hypertension (p<0.0001), diabetes (p<0.0001), and VAD use (p<0.0001). Survival among morbidly obese compared to other group was lower at 30-day, 1-, 5- , and 10-years. After adjustment for known risks, morbid obesity was associated with higher post-transplant 30-day (HR 1.64, 95% CI 1.37-1.97), 1-year (HR 1.50, 1.33-1.69), 5-year (HR 1.36, 1.24-1.49), and 10-year mortality risk (HR 1.28, 1.19-1.39).ConclusionSurvival following HT was significantly lower in recipients with morbid obesity. The risk associated with BMI≥ 35kg/m2 should be considered at the time of transplant assessment. Morbid obesity (body mass index (BMI) ≥ 35kg/m2) is a relative contraindication for a heart transplant (HT). However, the clinical outcome of these HT recipients is not well established. This study examined the clinical outcome of morbidly obese patients who underwent HT in The United States. We included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5-, and 10-year survival of those with a BMI≥ 35 kg/m2 and BMI = 18.5-34.99 kg/m2. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio. 36,115 adult HT recipients were included: 2638 (7.3%) morbidly obese. The median (inter-quartile range) age was 55 (46, 62) years, 24.7% were female, and follow-up was 4.1 (1.1, 8.3) years. Morbidly obese patients had more hypertension (p<0.0001), diabetes (p<0.0001), and VAD use (p<0.0001). Survival among morbidly obese compared to other group was lower at 30-day, 1-, 5- , and 10-years. After adjustment for known risks, morbid obesity was associated with higher post-transplant 30-day (HR 1.64, 95% CI 1.37-1.97), 1-year (HR 1.50, 1.33-1.69), 5-year (HR 1.36, 1.24-1.49), and 10-year mortality risk (HR 1.28, 1.19-1.39). Survival following HT was significantly lower in recipients with morbid obesity. The risk associated with BMI≥ 35kg/m2 should be considered at the time of transplant assessment.

Long-Term Outcome of LVAD in Duchenne Population with End Stage Cardiomyopathy

Purpose The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy (DMD-DCM). Methods We collected data of end stage DMD-DCM patients who were implanted with LVAD in our center (group 1) and the ones in regular follow-up because not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD heart failure (HF) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. All data during long-term follow-up were recorded including echocardiography, ECG examination, laboratory blood tests, BNP dosing and assessment of nutritional status and respiratory function. Survival of the groups was represented by Kaplan Meier analysis and compared by log rank. Results A total of eight DMD-DCM patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The most prominent complications were bleeding and infections with one episode of acute heart failure that was successfully treated. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After one year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) together with a significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank Conclusion Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function. LVAD improved outcomes in patients with LVAD when compared to those without.

Outcomes of ECMO versus VAD in Children with Congenital Heart Disease as a Bridge to Transplant in Recent Era: Analysis from United Network for Organ Sharing Database

<h3>Purpose</h3> To compare the clinical characteristics, risk factors, and overall survival (waitlist and post-transplant) outcomes in children with congenital heart disease (CHD) bridged to transplantation with either a VAD vs. ECMO vs. no-mechanical circulatory support (MCS). <h3>Methods</h3> The study included 2899 primary heart transplantations in children <18 years with CHD between 2010 and 2019 from the UNOS database. Patients who had ECMO or VAD at listing or while listed were included and their waitlist and post-transplant outcomes compared with CHD patients who did not require MCS. <h3>Results</h3> Of all, 466(16%) had ECMO and 200(7%) VAD at the time of listing or while listed (Figure-1 A-B). There was an increasing VAD utilization trend during the last decade over ECMO (<i>p</i><0.01). The 90 days post-MCS survival was better with the use of VAD compared to ECMO (67% vs. 49%, p<.01) (Figure-2). More patients in the VAD group (70%) were transplanted compared to ECMO (47%), the transplantability rate was decreased with older age (odds ratio (OR), 0.91; 0.95% confidence interval (CI), 0.86-0.95), lower BMI (OR, 0.93; 95% CI, 0.89-0.98) and lower albumin < 3g/dL (OR, 0.6; 95% CI, 0.53-0.7). Multivariate model predicted that lower BMI (OR, 1.12; 95% CI, 1.06-1.18), pre-transplant ECMO (OR, 2.19; 95% CI, 1.39-3.45), and higher bilirubin (OR, 1.15; 95% CI, 0.97-1.36) decreased 1-year post-transplant survival. Patients transplanted with VAD had better 1-year survival than ECMO (88% vs. 70%, p=0.01) (Figure-3). <h3>Conclusion</h3> Waiting list survival of children with CHD supported by durable VAD is better compared to ECMO support. The long-term posttransplantation outcomes of CHD patients supported by VAD is similar to non-MCS patients and better than ECMO supported patients. The transition from ECMO to VAD while listed results in similar outcomes to VAD-first, so every effort should be made to select CHD patients eligible for VAD as a bridge to transplantation.

Severe Recipient Obesity Decreases Post Heart Transplant Survival

<h3>Purpose</h3> Severe obesity, defined as body mass index (BMI) ≥ 40 kg/m², is a contraindication for a heart transplant (HT). However, practice varies across transplant centers. This study examined the post-transplant survival of these patients who underwent HT in the United States. <h3>Methods</h3> We included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5- and 10-year survival of those with a BMI≥ 40 kg/m² with BMI = 18.5-39.99 kg/m² using the Kaplan-Meier method. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio. <h3>Results</h3> 36,115 adult HT recipients were included: 275 (0.8%) severely obese. The median (inter-quartile range) age was 55 (46, 62) years, and 25.4% were female. Severely obese patients had more hypertension (p=0.0019), diabetes (p<0.0001), and VAD use (p<0.0001). During a median follow-up of 4.1 (1.1, 8.3) years, 11,219 (30.3%) recipients died. Survival among severely obese compared to other groups was lower at 30-day, 1-, 5-, and 10-years (Figure; p<0.0001 for all). After adjustment for known risks, morbid obesity was associated with significantly higher post-transplant 30-day (HR 1.75, 95% CI 1.28-2.73; p=0.0125), 1-year (HR 1.44, 1.04-1.99; p=0.0260), 5-year (HR 1.27, 1.00-1.61; p=0.0541), and 10-year mortality risk (HR 1.31, 1.07-1.60; p=0.0094). <h3>Conclusion</h3> Survival following HT was significantly lower in recipients with severe obesity. Severe obesity should be addressed before HT is considered.

Anti-hypertensive treatment in the immediate post-operative period and 1year after pediatric heart transplantation.

Hypertension is a known complication of pediatric heart transplantation. We sought to identify factors associated with anti-hypertensive use in pediatric heart transplant recipients immediately post-transplant and oral anti-hypertensive use at discharge and 1-year post-transplant. Retrospective chart review was conducted of patients ≤18years who underwent heart transplantation at two major heart transplant centers between August 1, 2009 and December 31, 2017 with ≥1-year follow-up. Exclusion criteria included re-transplant, multi-organ recipients, survival <1year, and comorbidities associated with hypertension. Anti-hypertensive use was recorded during initial ICU stay, at discharge, and 1-year post-transplant. Univariate and multivariate analyses determined associations of demographic and diagnostic factors and need for anti-hypertensives. There were 188 patients that met inclusion criteria. Anti-hypertensive infusions were required in the ICU post-transplant in 46 patients (24.5%) for a median of 3days (1-21days). Oral anti-hypertensives were required in 58 patients (30.9%) at discharge and 1-year post-transplant. Anti-hypertensive infusion in the ICU post-transplant was associated with donor-to-recipient weight ratio. Oral anti-hypertensive use at discharge was associated with weight ratio and pretransplant VAD use, and at 1-year, post-transplant was associated with age at transplant, steroid use at discharge, and oral anti-hypertensive use at discharge. Hypertension is common immediately following and 1-year post-transplant. Weight ratio was the only independent predictor of anti-hypertensive use in the early post-transplant period, whereas VAD use was also associated with anti-hypertensive use at discharge. Anti-hypertensive use 1-year post-transplant was not associated with those factors, but rather with age at transplant and steroid use.

Impact of Changes in the US Heart Allocation System on Waitlist Mortality and Listing Practices

In October 2018, the US changed the donor heart allocation policy from a three-tiered status system to a six-tiered system, with higher priority given to those with temporary mechanical circulatory support. The purpose of the current study was to examine changes in listing practices and waitlist mortality before and after the implementation of the new allocation system. Retrospective analysis was performed of adult patients being listed for heart transplant between May 2018-March 2019 as identified in the UNOS database. Exclusions included multi-organ listing and previous transplant. Patients were grouped by era according to initial list date before or after October 18, 2018. Waitlist survival was censored at 6 months or upon transplant. During the study period, 3,933 patients were listed, with 2,001 prior to allocation change (Era 1, 50.9%) and 1,932 after allocation change (Era 2, 49.1%). No differences were noted between patients listed in age, gender, diagnosis, dialysis, and mechanical ventilation. ECMO at listing was 2.3% vs. 2.6% in Eras 1 & 2, respectively (p=0.557). IABP at listing was more common in Era 2 (4.4% vs. 8.6%, p<0.001), while VAD use was similar (29.8% vs. 28.9%, p=0.547). In Era 1, 521 (26.0%) patients were listed as status 1A, with 892 (44.6%) patients as status 1B. In Era 2, 55 (2.9%) of patients were listed as new status 1, 270 (14.0%) as new status 2, and 211 (10.9%) as new status 3. A trend towards decreased probability of staying on the waitlist was noted in the Era 2 (Figure, p=0.051). However, when censored for removal from the waitlist for reasons other than transplant, waitlist survival was similar (p=0.791). The new allocation system has led to the listing of more patients with intra-aortic balloon pumps, without changes in temporary mechanical support at listing. The new allocation system is associated with more frequent removal from the waiting list due to reasons other than mortality. Continued examination of outcomes with the new system is warranted.

Waitlist Mortality in US Children Listed for Heart Transplant - Where are We Now?

Studies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors such as heart allocation system refinements, patient selection, greater ABO incompatible (ABOI) HT, and rise in VAD use are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist. All children <18 years listed for isolated HT from 1999-2019 were identified using OPTN data and grouped into 3 eras (Era 1: 1999-2006; Era 2: 2006-2016; Era 3: 2016-2019) based on when UNOS revised the heart allocation system. Cox proportional hazards modeling was used to identify factors associated with death/deterioration. Overall, 10,730 patients met inclusion criteria (3,397 in Era 1; 5,359 in Era 2; 1,974 in Era 3). Waitlist mortality declined significantly across eras (22%, 17%, 14%, P<0.001). The prevalence at listing of major risk factors for mortality declined across eras including a reduction by 50% in ECMO use (12%, 9%, 6%, P<0.001), by 32% in ventilator use (28%, 22%, 19%, P<0.001), by 38% in dialysis use (2.4%, 2.0%, 1.5%, P<0.001), while VAD use at listing increased 8-fold (2%, 8%, 14%, P<0.001). Infant mortality declined significantly (27%, 25%, 21%, P<0.001) with a 40% decline in mortality unique to blood group O patients (relative to background decline for all blood groups); infant VAD mortality declined by 36% (P<0.01). In Era 3, RCM and re-transplant patients not eligible for status 1A without exception have higher mortality than 1A DCM patients on LVAD support (12% vs. 4.3%, P<0.01). Pediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection, and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system, suggesting opportunities for allocation improvement may still exist.

Long-Term Outcome of LVAD in Duchenne Population with End Stage Cardiomyopathy

The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy. We collected data of DMD patients with end-stage cardiomyopathy implanted with LVAD in our center (group 1) and the ones in regular follow-up not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD HF (heart failure) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. During long-term follow-up all data were recorded including echocardiography, ECG examination, laboratory blood tests, and respiratory function. Survival was represented by Kaplan Meier analysis and compared by log rank. A total of 8 DMD patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸ whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After 1 year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) and significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank&lt0.001), with a 5-year increase in life expectancy. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of EF due to a significant ventricular unloading coupled with chronic therapy. LVAD improved outcomes in patients with LVAD when compared to those without. An integration of outpatient DMD HF clinic and patient-centered palliative care will most likely increase the quality of life and delivery of care for this population.