Requiring Heart Transplantation Research Articles

The Fontan Liver after Cardiac Transplantation

Fontan associated liver disease (FALD) is a serious complication of Fontan physiology. In those requiring heart transplant (HT), risk stratification related to liver impairment remains challenging. This multi-center study sought to characterize survival and the natural history of FALD after HT alone. Biochemical, imaging and pathologic data were collected retrospectively for all Fontans who underwent HT at 11 pediatric institutions from 2001-2019. Statistical analysis included Wilcoxon signed rank test and univariate Cox proportional hazard regression. Two blinded radiologists reviewed all imaging for consistency. Of 109 transplanted Fontan pts, 56% had decreased ventricular function and 31% had protein losing enteropathy; pts had HT at a median age of 13.7 yrs (IQR 9.5, 17.7), and were 9.9 yrs (4.6, 13.9) out from Fontan operation. Median Fontan pressure pre-HT was 16 mmHg (14, 19) and cardiac index 3 L/min/m2 (2.6, 3.5). Of 100 pts with pre-HT liver imaging (91 ultrasounds, 37 CTs, 18 MRIs), 78% had abnormalities, including nodular contours, hyper enhancing lesions, and fibrotic/cirrhotic changes. Endoscopy noted varices in 5 of 12 pre-HT pts screened, and evidence of sinusoidal dilation/bridging fibrosis in all 12 liver biopsies. Pre-HT lab values were mostly normal and did not differ significantly at 1 yr follow-up except total bilirubin decreased (Table 1). Post-HT imaging in 80 pts frequently showed persistent abnormalities without progression (72%). Eighteen pts died (median time to death from HT 0.6 yrs [0.1, 3.4]) with 2 deaths possibly related to FALD; 1 pt suffered a GI bleed 6 wks after HT, while a second died at 2 months with portal hypertension and pulmonary AVMs. No abnormal lab values, cath hemodynamics or imaging were associated with death. FALD at the time of HT was not a significant cause of early mortality in this cohort. Abnormal liver features persisted on early post HT follow-up imaging without progression of disease or associated lab aberrations indicating HT may improve long term prognosis.

Contemporary Outcomes of Heart Transplantation in Adult Patients with Congenital Heart Disease and Prior Intracardiac Repair: Analysis from UNOS Database

Number of adult congenital heart disease (ACHD) patients who require heart transplantation (HT) has increased. However, transplant rate for these patients has remained low. The potential reason of this phenomenon could be surgical complexity related to anatomical abnormalities and multiple prior surgeries. In this study, we sought to determine the HT outcomes of ACHD patients who had prior cardiac surgery using United Network for Organ Sharing (UNOS) database. Between January 2008 and March 2019, ACHD patients who had prior cardiac surgery and subsequent HT were identified from the UNOS database. As a control group, adult patients without congenital heart disease who had prior sternotomy and subsequent HT were extracted.Propensity score matching (PSM) was used to compare outcomes between two groups. There were 793 ACHD group and 8400 control. Unadjusted comparison shows that ACHD were younger (p<.0001), gender female (p<.0001), and less likely to have diabetes mellitus (p<.0001), history of smoking (p<.0001), automatic implantable cardioverter and defibrillator implantation (p<.0001), and ventricular assist device support (p<.0001). PSM compared 403 patients in each group. 30-day mortality was significantly higher in ACHD group compared to control (12% vs. 8%, Log-rank p=0.039). ACHD group had higher incidence of postoperative dialysis (22% vs. 14%, p=0.0042) and permanent pacemaker (5.2 %vs. 2.2 %, p=0.026). There was no difference in long-term survival between groups (ACHD 68% vs. non ACHD 61% at 10 years, Log-rank p=0.49). ACHD patients with prior intracardiac repair carried higher operative risk but long-term outcome was equivalent to non-ACHD patients with prior sternotomy.

Heart Transplantation Outcomes in Adults with Postpartum Cardiomyopathy

Postpartum cardiomyopathy (PPCM) is a prevalent cause of end-stage heart failure in women, from which about 10% will require heart transplantation. We aimed to further evaluate long-term heart transplant (HT) outcomes in this cohort of patients and compare them to all other heart transplant recipients. The UNOS registry was queried for all cardiac transplants in the registry from 1987 to 2019 to compare characteristics and outcomes for PPCM-patients and all other HT patients. Hazard ratios (HR) were calculated using multivariate Cox proportional hazard regression analysis. Survival curves were generated with the Kaplan Meier method. Between 1987 and 2019, 63,142 patients received a heart transplant. Of these patients, 666 women had a heart transplant in which the indication was PPCM. These patients tended to be younger (p<0.001), less likely to have diabetes (p<0.001), and less likely to smoke (p<0.001). About 48% of all PPCM patients requiring HT were African American. PPCM-patients were more likely to have required prior cardiac surgery (p<0.001) and higher frequency of support pre-transplant (p<0.001), including intra-aortic balloon pump (IABP) (p=0.006), ventricular assist device (VAD) (p < 0.001) but not extracorporeal membrane oxygenation (ECMO) (p=0.47). PPCM patients had fewer median days on the wait list prior to heart transplant (57.5 vs 83.0 days, p<0.001). In the PPCM group, there was significantly greater incidence of pre-transplant panel reactive antibodies > 20% (22.2% vs. 9.4%, p<0.001). The overall post-transplant survival was significantly lower in the PPCM group (Figure, p<0.001). Despite being a younger cohort with less chronic medical issues, PPCM had worse survival compared to non-PPCM patients with increased sensitization as well as increased use of IABP and VAD support. Further study is warranted to address these findings.

The Cause of the Bleeding and Thrombosis in Patients with Implanted Left Ventricular Assist Devices

Chronic heart failure (CHF) is one of the most severe and adverse diseases of the cardiovascular system, which requires heart transplantation (HT) for patient. Implantation of the left ventricular assist device (LVAD) is the treatment option instead of HT. LVAD can be implanted as a bridge to transplantation and destination therapy (DT). Unfortunately, DT of the LVAD has side effects such as bleeding and thrombosis. These side effects occur because of the non-physiological high shear stress of the LVAD, which causes platelet degradation. However, side effects might occur because of the genetic polymorphisms in coagulation factors, platelet receptors etc. The purpose of the study is to identify the influence of the coagulation factor F5, F7 and FGB polymorphisms in LVAD patients. Venous blood samples were recruited from 100 patients with implanted LVAD at the National Research Center for Cardiac Surgery. Patients were prescribed with the dose of the warfarin according to the clinical protocol. Patients were divided into two groups: 1.Case study - patients with side effects; 2. Control study - patients without side effects. Genomic DNA was extracted by using the PureLink™ Genomic DNA Mini Kit (Invitrogen, UK). Genotyping of polymorphisms F5 (rs6025), F7 (rs6046) and FGB (rs1800790) was done by real-time polymerase chain reaction with TaqMan probes. Genotyping results of Factor Leiden V (F5) showed that most of the patients (99%) has wild type of genotype (C/C) which has no risk to thrombosis. On other hand, genotyping results of F7 and fibrinogen beta (FGB) polymorphisms presented different percentage results from F5. Results of polymorphism F7 showed wild type of genotype G/G in 76% patients, whereas only 3% patients has mutant genotype A/A which has no risk to thrombosis. Mutant genotype A/A of FGB polymorphism was expressed only in 3% of patients, which has high risk to thrombosis. Mutant version of polymorphisms shows that some LVAD patients have high risk to side effects apart from high shear stress. The study has presented that side effects might happen because of the individual genome differences in LVAD patients. Some patients demonstrated high risk of side effects on destination therapy as well as according to genotyping results too.

Heart Transplant Outcomes for Patients with Myocarditis

Myocarditis is a known etiology of both acute fulminant heart failure and chronic dilated cardiomyopathy requiring heart transplantation. We sought to evaluate the long-term post-transplant outcomes of pts with myocarditis. We evaluated the UNOS registry for all heart transplant (HT) recipients from 1987 to 2019. Comparisons between pt characteristics of HT recipients with myocarditis (N=649) and HT recipients without a diagnosis of myocarditis (N=62,493) are reported using standard statistical methods including Cox proportional hazards regression for survival analysis. Myocarditis HT recipients were younger (29.6 ± 20.7 vs. 46.8 ± 19.1, p<0.001) and more likely to be female (44.1% vs. 26.0%, p<0.001). Myocarditis HT recipients were less likely to be DM (6.6% vs. 20.7%, p<0.001) and to have undergone prior cardiac surgery (7.6% vs. 18.4%, p<0.001). In terms of transplant related factors, myocarditis HT recipients were likely to receive a younger donor (23.3 ± 15.0 vs. 28.3 ± 13.9, p<0.001) and have shorter ischemic times (p<0.001). Prior to transplant, the myocarditis HT recipients were a sicker cohort and more likely to require ECMO [6.0% vs. 1.0%, p<0.001), VAD support (34.4% vs. 25.0%, p<0.001), and MV (13.4% vs. 4.2%, p<0.001). Median (interquartile range) time on the wait list was significantly shorter for myocarditis HT recipients [37.0 (12.0, 100.0) days vs. 83.0 (26.0, 231.0) days, p<0.001]. There was a lower overall post-transplant mortality in the myocarditis HT recipients (26.0% vs. 34.2%, p<0.001). Myocarditis HT recipients tend to be a younger population with less underlying co-morbidities such as DM and prior cardiac surgery, but they are more likely to be more acutely sick at the time of heart transplantation requiring mechanical ventilation, ECMO, or VAD support. Myocarditis HT recipients have shorter organ wait times and have more favorable transplant related factors, and ultimately have a lower overall mortality compared to recipients without myocarditis.

Heart Transplant Outcomes for Patients with Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is a known etiology of both end-stage dilated and restrictive cardiomyopathy requiring heart transplantation. We sought to evaluate the long-term post-transplant outcomes of patients with CS compared to patients without CS. We evaluated the United Network of Organ Sharing (UNOS) registry for all heart transplant (HT) recipients from 1987 to 2019. Comparisons between patient characteristics of HT recipients with CS (N=288) and HT recipients without a diagnosis of CS (N=62,854) were reported using standard statistical methods including Cox proportional hazards regression for survival analysis. Sarcoid HT recipients were significantly older (52.4 ± 9.0 vs. 46.6 ± 19.2, p<0.001) and were more likely to be female (35.8% vs. 26.2%, p<0.001). Sarcoid HT recipients were also less likely to have diabetes (15.4% vs. 20.6%, p=0.03) and to have undergone prior cardiac surgery (12.2% vs. 18.3%, p=0.01). In terms of transplant related factors, sarcoid HT recipients were more likely to receive an older donor (32.1 ± 11.8 vs. 28.2 ± 14.0, p<0.001), but had similar ischemic times. Prior to transplant, the CS patients were less likely to require mechanical ventilation (0.3% vs. 4.3%, p=0.001), but had similar rate of ventricular assist device (VAD) and extracorporeal membrane oxygenation (ECMO) requirements. Median time on the wait list was similar between both groups, however there was a lower overall post-transplant mortality in the sarcoid HT recipients (p<0.001). Cardiac sarcoidosis HT recipients tended to be an older population with less underlying co-morbidities such as diabetes and prior cardiac surgery. They were more likely to receive older donors. Although sarcoid HT recipients have similar organ wait times as non-CS recipients, they ultimately have a lower overall mortality.

A current era analysis of ABO incompatible listing practice and impact on outcomes in young children requiring heart transplantation

Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes. Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children < 2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients. Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p < 0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p < 0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting. In the current era, primary listing for ABOi heart transplant has become routine for the majority of children < 2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile.

P3686A novel desmin gene variant as an important cause of biventricular arrhythmogenic cardiomyopathy

Abstract Introduction Arrhythmogenic Cardiomyopathy (AC) is typically caused by mutations in the desmosomal genes, however non-desmosomal genes have been increasingly implicated. Desmin gene (DES) mutations have been previously reported in AC, but in many cases there are insufficient data to support their pathogenicity. Purpose We assessed our AC cohort for DES gene mutations and describe the clinical phenotype associated with a recurring variant present in 3 unrelated families. Methods Genetic testing was performed using next-generation sequencing for 41 genes in a total of 138 AC probands with a definite diagnosis of AC based on the revised 2010 Task Force diagnostic criteria. All candidate variants were confirmed using Sanger sequencing. Clinical and genetic cascade screening were expanded to the first-degree relatives of the probands. Retained tissue from deceased individuals was used for genetic testing. All living mutation carriers underwent clinical assessment including physical examination, 12-lead ECG, signal-averaged ECG, echocardiography, cardiac magnetic resonance imaging (MRI) and 24h Holter-monitoring. Results Two DES gene variants, p.Ser298Leu (n=1) and p.Leu115Ile (n=3), were identified in 4 out of the 138 probands (3%). The former coexisted with a pathogenic DSP gene mutation and has not been further evaluated. The latter is a novel variant, absent in control databases (gnomAD) and was the only variant present in 3 unrelated families (see figure). One carrier required heart transplant (A-II-1), two died suddenly (A-III-1, B-II-1) and one died of non-cardiac causes (B-I-2). Detailed clinical information was present in 8 mutation carriers (2 male, age 45±19 years). Seven (88%) had a definite diagnosis and one had a borderline diagnosis of AC. All cases (100%) had right ventricular (RV) wall motion abnormalities, 6 (75%) had a dilated RV, 6 (75%) a dilated LV and 6 (75%) had LV dysfunction (mild in 5 and severe in 1). LV late gadolinium enhancement (LGE) was present in all 6 carriers that had a cardiac MRI with a circumferential sub-epicardial distribution (see figure, case A-III-2). Non-sustained ventricular tachycardia (VT) was present in 7 (88%) and sustained VT in 2 cases (25%). The ventricular ectopic burden per 24h ranged from 426 to 10583 with a median value of 820. Figure 1 Conclusion Variants of the DES gene are rare causes of AC. The novel p.Leu115Ile variant seems to be prevalent in a large UK-based cohort and it causes a biventricular form of AC, with a characteristic scar pattern on MRI and severe outcomes. Acknowledgement/Funding Alexandros Protonotarios is supported by a BHF Clinical Research Training Fellowship no. FS/18/82/34024

Cost-Effectiveness of Percutaneous Lymphatic Embolization for Management of Plastic Bronchitis.

Plastic bronchitis is a dreaded complication of single ventricle physiology occurring following palliation via Fontan procedure. Medical management of plastic bronchitis often fails, requiring heart transplantation. Percutaneous lymphatic embolization is an emerging treatment for plastic bronchitis. To determine the cost-effectiveness of competing management strategies, a modified Markov model was constructed with patients transiting through treatments-medical management, lymphatic embolization, or heart transplantation from a hospital system perspective. Health state transitions were modeled using an institutional review board-approved retrospective review of the Children's Hospital of Pennsylvania's plastic bronchitis cohort. Medication pricing data were obtained from the National Inpatient Sample. Differences in costs and quality-adjusted life years (QALYs) over a five-year horizon for each group were determined. The incremental cost-effectiveness ratio was then calculated. The mean cost of lymphatic embolization from procedure performance was US$340,941, US$385,841 for heart transplantation, and US$594,520 for medical management. The mean quality-adjusted survival of lymphatic embolization yielded an additional 0.66 QALYs (P < .03) relative to heart transplantation and 1.3 (P < .0001) relative to medical management. Orthotopic heart transplantation yielded an additional 0.66 QALYs (P = .06) when comparing heart transplantation to medical management. Compared to medical management, lymphatic embolization generated an incremental cost-effectiveness ratio of US$192,105. Similarly, compared to heart transplantation, lymphatic embolization yielded an incremental cost-effectiveness ratio of US$68,030. Of the available plastic bronchitis treatments, with a willingness to pay of US$150,000, lymphatic embolization produces an incremental cost-effectiveness ratio within the bounds considered to be cost-effective, potentially causing financial benefits to the health system.

Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy

Introduction and ObjectivesDilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS). Methods and ResultsGenetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively. ConclusionOur results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.

Biallelic mutation in MYH7 and MYBPC3 leads to severe cardiomyopathy with left ventricular noncompaction phenotype.

Dominant mutations in the MYH7 and MYBPC3 genes are common causes of inherited cardiomyopathies, which often demonstrate variable phenotypic expression and incomplete penetrance across family members. Biallelic inheritance is rare but allows gaining insights into the genetic mode of action of single variants. Here, we present three cases carrying a loss-of-function (LoF) variant in a compound heterozygous state with a missense variant in either MYH7 or MYBPC3 leading to severe cardiomyopathy with left ventricular noncompaction. Most likely, MYH7 haploinsufficiency due to one LoF allele results in a clinical phenotype only in compound heterozygous form with a missense variant. In contrast, haploinsufficiency in MYBPC3 results in a severe early-onset ventricular noncompaction phenotype requiring heart transplantation when combined with a de novo missense variant on the second allele. In addition, the missense variant may lead to an unstable protein, as overall only 20% of the MYBPC3 protein remain detectable in affected cardiac tissue compared to control tissue. In conclusion, in patients with early disease onset and atypical clinical course, biallelic inheritance or more complex variants including copy number variations and de novo mutations should be considered. In addition, the pathogenic consequence of variants may differ in heterozygous versus compound heterozygous state.

A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrils

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.

Cardiac Segmental Strain Analysis in Pediatric Left Ventricular Noncompaction Cardiomyopathy

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent left ventricular trabeculations, often leading to myocardial dysfunction and death or heart transplantation. Although diagnostic echocardiographic criteria exist for LVNC, segmental speckle-tracking strain patterns have not been described in pediatric LVNC. The objectives of this study were to characterize segmental noncompaction, evaluate segmental speckle-tracking strain, and characterize peak strain values in children with LVNC with adverse clinical outcomes. Echocardiographic noncompaction/compaction ratios and segmental radial, circumferential, and longitudinal strain were measured retrospectively in children with LVNC (January 2000 to June 2013). Segmental strain of the cohort was compared with that in control subjects matched by age and body surface area. One hundred one pediatric patients with LVNC were included (median age 2.8years; range, 0-19.4years); 71 patients survived (benign group) and 30 patients did not survive or required heart transplantation (adverse group). The adverse group was younger at diagnosis (P=.03), with lower ejection fractions (P<.0001) compared with the benign group. Both groups demonstrated increased noncompaction/compaction ratios within apical segments, with significantly increased involvement in antero- and inferolateral midpapillary segments in the adverse group (P<.005). Radial, circumferential, and longitudinal strain of nearly all left ventricular segments were significantly decreased in the adverse compared with the benign group and in pediatric LVNC patients compared with control subjects. Global radial (7.4±9.7% vs 19.6±16.5%, P<.0001), circumferential (-8.4±7.0% vs -18.9±6.9%, P<.0001), and longitudinal (-7.1±5.2% vs -11.8±5.3%, P<.0001) strain were all significantly decreased in the adverse group compared with the benign group. Segmental radial, circumferential, and longitudinal strain are decreased in pediatric patients with LVNC compared with control subjects and lowest in those with adverse compared with benign outcomes. LVNC appears to be a global disease affecting deformation in all regions, including compacted myocardial segments.

Outpatient Weaning of Inotropes is Achievable in Patients with Advanced Heart Failure

Purpose Patients admitted with advanced decompensated systolic heart failure (ADHF) typically require inotropes . Those who cannot be bridged to advanced heart failure therapies are discharged home on inotropes (as a palliative measure or until eligible for advanced therapies). Continuous inotrope infusion exposes patients to increased risk of arrhythmias and mortality. It is unknown whether such patients can be weaned off inotropic support in an outpatient setting. Methods In a single-center observational study of patients admitted with ADHF between 2016-2018, we studied demographics, clinical history, physical exam data, and laboratory data. We determined functional status and compliance with medical therapies of patients who were successfully weaned off inotropes. Creatinine , electrolytes, vital signs, and physical exam findings were followed weekly/biweekly during weaning and followed post-wean for ≥60 days. Results 9 patients (mean age 49 y; 5 males) were successfully weaned off inotropes in an outpatient setting. All had been discharged home on milrinone or dobutamine infusion. Only 1 patient had ischemic cardiomyopathy ; 2 had required mechanical support during hospitalization. Median length of stay after inotrope initiation was 8 days with median 78 days on inotropes prior to weaning. 6 patients were started on sacubitril/valsartan, which was uptitrated during weaning, of whom 3 tolerated the maximum dose. The other patients were uptitrated on angiotensin converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARB). 60 days post-wean, all 9 patients reported doing well with NYHA Class IIIa (n=5), Class IV (n=1), and Class II (n=3) symptoms. On longitudinal follow-up, 1 patient was hospitalized 1-year post-wean, was subsequently restarted on inotropes and required heart transplantation . Conclusion With close monitoring and gentle uptitration of afterload-reducing agents, it is feasible to wean patients with ADHF off inotropes in an outpatient setting.

Heart Transplantation in Muscular Dystrophy: Selection is Crucial for Success

Purpose Patients with muscular dystrophy may have an associated cardiomyopathy, resulting in advanced heart failure requiring transplantation. However, the skeletal muscle dysfunction can result in respiratory impairment, dysphagia, and inability to participate in rehabilitation after heart transplantation. The purpose of this study was to describe the characteristics and outcomes of muscular dystrophy patients undergoing heart transplantation at our center. Methods We reviewed patients at our center status post heart transplantation between 2010 and 2017. Of the 646 patients, we identified 10 with muscular dystrophy. The demographics, clinical characteristics, and outcomes of these 10 patients with muscular dystrophy were compared to the 646patients without muscular dystrophy transplanted during this time period. Results The muscular dystrophy patients were all deemed acceptable to proceed by a neurologist with expertise in muscular dystrophy. They were younger (45 years vs 56 years; p = 0.006); had younger donors (27 years vs 35 years, p = 0.05); had lower creatinine (0.95 mg/dL vs 1.15 mg/dL; P = 0.01); and less pre-transplant diabetes (13% vs 52%; p = 0.03). There was no difference in sensitization, CMV IgG mismatch status, or Status 1A listing. The muscular dystrophy patients had 100% 1- and 5-year survival (Figure) and there was no difference in the incidence of cellular rejection, antibody-mediated rejection, or allograft vasculopathy between groups. Conclusion Patients with muscular dystrophy-associated cardiomyopathy may require heart transplantation. This analysis indicates that carefully selected patients can have excellent outcomes and therefore should be considered candidates for advanced heart failure therapies.

In Hospital Outcomes in Adult Congenital Heart Disease Patients with Fontan Undergoing Heart Transplantation - A Decade Nationwide Analysis from 2004 until 2014

Purpose Treatment of adult congenital heart disease (ACHD) patients who require heart transplantation (HT) remains challenging due to limited donors and high perioperative and wait-list mortality. Those patients with single ventricle physiology palliated with Fontan are at the highest risk of early mortality due to multi-organ involvement; in addition, few centers are capable of safely transplant them. We sought to evaluate trends and outcomes of HT in these patients. Methods Using the U. S Nationwide Inpatient Sample (NIS) database, we identified all adults aged at least 18 years old who underwent HT from 2004-2014. We then identified those with specific ICD-9 codes to include tricuspid atresia, hypoplastic left heart syndrome and common ventricle, who in order to survive to age 18, must have been palliated with a Fontan procedure. Multivariate regression models were created to adjust for potential confounders. Results A total of 93 Fontan patients underwent HT during the study time (0.5% of all heart transplants). Compared to non-Fontan heart transplantations, Fontan patients were younger, with higher incidence of liver disease and coagulopathy (baseline demographics are shown in table 1). Fontan patients receiving HT had higher mortality during transplant hospitalization compared to non-Fontan patients (26.3% vs. 5.3% OR 18.10, CI 5.06 - 65.0 p Conclusion Fontan patients undergoing HT have exceptionally high inpatient mortality, which is nearly 5 times that of non-Fontan heart transplant recipients. The role of delayed referral, underlying liver disease, and other factors in this high mortality need to be explored.

Explantation of Mechanical Circulatory Support Devices to Recovery is Possible and Should Be Considered in Selected Conditions in Children

Purpose Although mechanical circulatory support devices in children are primarily utilised as a bridge to transplant, explantation to recovery is possible in selected cases. The purpose of this study is to report our national data of explantation of mechanical circulatory support devices to clinical recovery in children. Methods Retrospective study performed in two institutions from January 2007 to September 2018 (12 years). All children who had explanation of mechanical circulatory support devices were included. Relevant variables analysed were gender, age, weight at implantation, primary diagnosis, extracorporeal membrane oxygenation (ECMO) pre & post implantation, type of device used, need for bi-ventricular support, cardiopulmonary bypass time (CPB), arrhythmia before explantation and duration of mechanical device support. Primary outcome was survival after explantation. Secondary outcomes were arrhythmia after explantation, renal replacement therapy (RRT) during mechanical circulatory support, neurological complications and eventual need for heart transplantation. Results 19 children were eligible (females = 42%, mean age = 38 months, mean weight = 15.4 kilograms). Primary diagnosis included cardiomyopathy (n = 6, 31.6%), myocarditis (n = 12, 63.1%) and congenital heart disease (n = 1, 5.3%). 9 children pre-implant (47.4%) and 2 children post-implant (10.5%) required ECMO. Devices used were Berlin Heart (n = 16, 84.2%) and Levitronix (n = 3, 15.8%). Bi-ventricular support was needed in 4 children (21%). Mean CPB was 108.3 minutes. 5 children (26.3%) had arrhythmia pre-explantation. Mean duration of mechanical circulatory support was 43.9 days (range, 6 to 120 days). 17 children survived explantation (89.4%), of which 1 (5.3%) eventually required heart transplantation. RRT was required in 7 children (36.8%). 1 child had arrhythmia post-explantation (5.3%). 5 children had neurological complications (26.3%). Conclusion Explantation of mechanical circulatory support devices to clinical recovery is possible in selected cases in children. The option of device explantation or using them as a bridge to recovery should be considered in children especially if the primary diagnosis is myocarditis. This can mitigate the high risk of morbidities associated with their long-term usage as a bridge to transplant.

State of the art: Evaluation and prognostication of myocarditis using cardiac MRI.

Myocarditis encompasses both primary and secondary processes causing inflammation of the myocardium. Viral infections are a common secondary cause of myocarditis with important clinical relevance. Viral myocarditis has a varied clinical presentation, potentially resulting in significant morbidity and mortality. Acutely, systolic dysfunction and sudden cardiac death may ensue; chronically, myocarditis may result in a dilated cardiomyopathy requiring heart transplantation. Myocarditis is thought to be one of the most common causes of myocardial infarction with nonobstructive coronary arteries (MINOCA), with important consequences for cardiovascular outcomes. Patients with myocarditis are currently underdiagnosed. Cardiac MRI has evolved as the noninvasive test of choice, with cardiac MRI-specific diagnostic requirements defined in the Lake Louise Criteria (LLC). Detecting the presence of tissue edema, hyperemia, and necrosis in both acute and chronic stages form the foundation of the LLC. Cardiac MR for chronic myocarditis (greater than 8 weeks from symptom onset) has decreased sensitivity for diagnosis. Emerging sequences such as T1 and T2 parametric maps provide tissue characterization regarding inflammation without reliance on reference tissue, overcoming limitations of the LLC. Beyond diagnostic criteria, these imaging techniques have proven useful in further characterizing the diseased tissue, prognostication, and clinical decision-making. This review describes the utility and evolving use of cardiac MRI in clinical practice. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2018;47:1061-1071.

Abstract 16661: Circulating microRNAs as Prognostic Biomarkers in Single Ventricle Heart Disease

Introduction: Despite significant improvements in surgical technique and post-surgical management, mortality remains high for infants with single ventricle congenital heart disease (SV) and the ability to risk-stratify infants with SV is limited. microRNAs (miRs) are short regulatory RNAs that modulate gene expression and miRs in the circulation are increasingly recognized as valuable biomarkers in a broad range of diseases. Hypothesis: Circulating miR profiles prior to surgical palliation may correlate with SV survival at one year and assist with risk-stratification in this population. Methods: Serum samples from subjects with SV (of right ventricular morphology) were obtained at the following time points: Pre-Norwood (n=71), Pre-Glenn (n=46) and Pre-Fontan (n=25). Outcomes were classified as alive versus death or heart transplant listing by one year of age. Serum was subject to three freeze/heat cycles to maximize miR release, then miRs were reverse transcribed using a pool of primers specific for each miR. Real-time PCR was performed in 384-well plates containing sequence-specific primers and TaqMan probes in the ABI7900HT. Results: Random forest analysis of Pre-Norwood samples demonstrates downregulation of miRs-194, -15b and -193b in patients who died or required heart transplant listing (n=22) compared to those who were alive (n=49). Hierarchical clustering based on these 3 specific miRs is demonstrated in Figure 1 (blue = alive, red = death/transplant). miRs-483-5p, -140-3p and -30b are differentially expressed between the Pre-Norwood, Pre-Glenn, and Pre-Fontan groups and are associated with each surgical stage. Conclusions: Circulating miRs demonstrate promise as prognostic biomarkers of 1-year outcome in the Pre-Norwood SV population. Circulating miR profiles are also distinct at each surgical stage. Notably, the identified miRs are known to regulate gene expression in other forms of heart disease and warrant further investigation.

Center volume and post-transplant survival among adults with congenital heart disease.

The number of adult congenital heart disease (ACHD) patients requiring heart transplantation (HT) continues to grow, and if they survive the first year after transplant, their long-term survival is at least equivalent to non-ACHD patients. The 1-year survival of ACHD patients with HT remains lower than non-ACHD patients. We evaluated the affect of transplant center volume on 1-year survival of ACHD patients. We analyzed United Network of Organ Sharing patients (age ≥18 years) who underwent their first orthotopic HT between January 1, 2000, and December 31, 2015, to assess the association between transplant center volume and 1-year survival of ACHD patients. We identified 827 ACHD patients at 113 centers who underwent HT during the study period. The average age of the recipients and donors was 36 ± 13 years (60% men and 84% Caucasian) and 28± 11 (63% men and 66% Caucasian), respectively. Of the ACHD patients undergoing HT, 27% (n = 60) were done at low-volume centers, 30% (n = 10) were reported at high-volume centers, and the remaining (n = 43) were at medium-volume centers. A total of 96 patients died within 30 days, including 37 (16.7%) at low-volume, 37 (10.2%) at medium-volume, and 22 (9.0%) at high-volume centers (p = 0.019). The average unadjusted Kaplan-Meier 30-day survival at low-volume centers was 83% ± 2%, which was significantly lower than medium-volume (90% ± 1%) and high-volume (91% ± 2%) centers (log-rank p < 0.05). Within 1 year, 154 patients had died, including 56 (36.4%) at low-volume, 60 (38.9%) at medium-volume, and 38 (24.7%) at high-volume centers (p = 0.011). Average unadjusted Kaplan-Meier 1-year survival at low-volume centers was 75% ± 3%, which was significantly lower than medium-volume (83% ± 2%) and high-volume (84% ± 2%) centers (log-rank p < 0.05). The 30-day and 1-year survival of ACHD patients undergoing HT is partly influenced by overall transplant center volume and, potentially, volume of ACHD HTs, with low-volume centers performing poorly relative to medium-volume and high-volume centers. The role of peri-operative care and multidisciplinary management in improving survival at low-volume centers required further investigations.