Early Heart Transplantation Research Articles

Clinical and Pathoanatomical Characteristics of Hypoplastic Left Heart Syndrome a Clinical Case

Hypoplastic left heart syndrome (HLHS) is a common congenital heart defect, accounting for 4 to 16% of cases, and is one of the most prognostically unfavorable, involving single-­ventricle hemodynamics. HLHS involves hypoplasia of the left ventricle, often in combination with atresia and/or stenosis of the aortic and/or mitral valves, as well as hypoplasia of various parts of the aorta. Intrauterine reduction in blood flow to the left heart structures at early stages of fetal development subsequently leads to severe changes in cardiac structures, often not amenable to surgical correction. Objective. To study the clinical and morphological features of HLHS using a clinical case as an example. Materials and Methods. The patient was a child from the first pregnancy, which was complicated by anemia and first-­trimester preeclampsia. The defect was diagnosed prenatally at 23/24 weeks. At 39 weeks, labor was induced, and the infant was hospitalized in the intensive care unit with symptoms of cardiac and respiratory failure. On the 6th day of life, surgical treatment was performed — a Norwood operation, which is a single-­ventricle hemodynamic surgical correction of the defect. Despite intensive care measures, multiple organ failure progressed, leading to the development of disseminated intravascular coagulation (DIC) and subsequent death on the 10th day of life. Results. Autopsy, including staining of the myocardium with Masson’s trichrome and hematoxylin and eosin, showed pronounced plethora of the microcirculatory vessels with formation of erythrocyte thrombi. Pronounced perivascular edema and fraying of muscle fibers were detected. Fibroelastosis of the endocardium of the left ventricle was observed, characterized by pronounced sclerotic thickening due to significant proliferation of fibrous tissue, with the spread of connective tissue strands into the myocardium. Endocardial fibroelastosis is a component of HLHS and one of the determining factors in the outcome of cardiac surgery. Conclusion. The results of this work indicate the complexity of HLHS as a developmental defect, the severity of its clinical manifestations, and the limited prospects of currently existing surgical treatment methods. These patients may require heart transplantation in the first days of life. A potential alternative to early postnatal heart transplantation may be the development of methods for intrauterine correction of the existing developmental defect.

Comparison of HTK-Custodiol and St-Thomas solution as cardiac preservation solutions on early and midterm outcomes following heart transplantation.

The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation (HTx) outcomes. We retrospectively compared our adult HTx performed with 2 different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. From January 2009 to December 2020, 154 consecutive HTx of adult patients, followed up in pre- and post-transplantation by 2 different tertiary centres, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in 2 groups accordingly. There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The 2 groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to the St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5-60.2) vs 71.8 (31.8-127), P < 0.001], rejection scores [0.08 (0.0-0.25) vs 0.14 (0.05-0.5), P = 0.036] and 30-day mortality rate (2.5% vs 14.7%, P = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, P = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol versus St-Thomas: hazard ratio = 0.20, 95% confidence interval: 0.069-0.60, P = 0.004). This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after HTx, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.

Thromboembolic complications following implantation of durable left-ventricular assist devices.

As the utilization of left-ventricular assist devices (LVADs) continues to rise and patients experience extended survival duration with these devices, the overall incidence of adverse events and complications has shown anotable increase. Among the major adverse events, thromboembolic complications are particularly significant. The aim of this study is to present our experience and assess the risk of thromboembolic complications after implantation of durable continuous-flow left-ventricular assist devices (CF-LVAD) in patients with end-stage heart failure. From 2007 to 2022, 169 left ventricular continuous-flow durable mechanical assist devices were implanted at our institute. Three types of devices were employed: HeartMate II (n = 54, 32%), HeartMate 3 (n = 70, 41.4%), and Heart Ware (n = 45, 26.6%). The data were extracted from the EUROMACS register. Thromboembolic complication, pump thrombosis was observed in 11/169 patients (6.5%), with 2patients experiencing stroke after embolism to the central nervous system. Among these cases, 10 patients (90.9%) were equipped with the Heart Ware device while 1 patient (9.1%) had the Heart Mate II device implanted. Nine patients received the durable device as abridge to transplant therapy and two as abridge to candidacy. The overall mean age of the patients was 47.6±10.2 years, with 2 women and 10 men. The pump thrombosis was managed through thrombolytic therapy, high-intensity heparin anticoagulation protocol, pump exchange, pump explantation, and early heart transplant. The combined hospital and long-term mortality rate was 4/11 patients (36.4%). Based on our experience, thromboembolic complications presenting primarily as pump thromboses, were arelatively common phenomenon experienced in association with the second-generation continuous-flow devices, but rarely seen with the third-generation devices. Thrombolysis followed by early heart transplantation proved to be asafe treatment option (Tab. 1, Ref. 14). Text in PDF www.elis.sk Keywords: durable mechanical assist device, durable left ventricular assist devices, outcomes, thromboembolic complications.

PO-01-147 ACTIVATION OF AUTOPHAGY ATTENUATES PROGRESSION OF ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

Studies of autophagy in ARVC are quite rare. Even autophagy had the opposite effects in desmin-related cardiomyopathy and dilated cardiomyopathy. This study aimed to explore the regulatory role of autophagy in the progression of ARVC. The ARVC cardiomyocytes (HL-1/shJup) were treated with autophagy activator (rapamycin) and inhibitor (chloroquine) to manipulate autophagy activity. Western blotting and immunofluorescence determined the changes of disease progression and signaling pathways. Then, autophagy was manipulated in cardiac tissue-specific Jup knockout mice to confirm the cell-derived findings. The autophagy activity of HL-1/shJup cell line was higher than that of control cells. In HL-1/shJup cells, the upstream signaling pathway of autophagy was active. During rapamycin treatment, the proteins related to lipogenesis and fibrogenesis in HL-1/shJup cells were reduced. In contrast, chloroquine treatment had the opposite effect. Moreover, rapamycin decreased and chloroquine increased intracellular oil droplet accumulation in HL-1/shJup cells. In addition, there was no significant change in Wnt/Hippo signaling pathways in cardiomyocytes after rapamycin treatment. Instead, the protein expression of the transcription factor SREBP1 that regulates lipogenesis and lysyl oxidase (LOX) that promotes fibrosis were related to the regulatory mechanism of autophagy. In ARVC mice, activated/inhibited autophagy also reduced/increased RV distance, arrhythmia, and lipogenesis through SREBP1, but not in wild-type mice. Autophagy plays a protective role in ARVC by regulating lipogenesis to attenuate disease progression. Based on this study, autophagy activators may be used in combination with existing drugs in patients with ARVC disease in the future to provide additional protection for early heart failure or heart transplantation.

Abstract 13076: A Rare Stopgain Variant in SLC25A2 Associates With Low Nitric Oxide and Poor Clinical Outcome in Hypoplastic Left Heart Syndrome

Introduction: Mitochondrial respiration defects accompanied by low nitric oxide (NO) are associated with heart failure in congenital heart disease (CHD) patients with hypoplastic left heart syndrome (HLHS). Here we investigated the genetic etiology of low NO in patients with CHD. Hypothesis: Mutations in mitochondrial-related genes involved in NO metabolism contributes to the low NO associated risk for heart failure and need for heart transplantation in HLHS. Methods and Results: We performed a case-control association study among 588 white CHD cases including 41 with HLHS, and 24,143 white controls from the genome aggregation database (gnomAD). A rare conserved stopgain variant (rs562886845) in SLC25A2 encoding mitochondrial ornithine transporter was significantly enriched among the HLHS patients with poor clinical outcome (Group II, Table 1), with 15.8% carrying this mutation, yielding odds ratio of 17.07 ( p = 5.23 х 10 -4 ) in comparison to CHD patients without left ventricular outflow tract obstruction or 7.63 ( p =2.68 х 10 –3 ) in comparison to gnomAD control cohort. Significantly, SLC25A2 is the only mitochondrial transporter exporting asymmetric dimethylarginine, a natural NO synthase inhibitor. The three HLHS patients with this SLC25A2 variant showed very low nasal NO (nNO), a proxy for endogenous NO production capacity. All three patients had received heart transplant, with two being heterozygous and one homozygous for this variant. Significantly, the HLHS patient with the homozygous mutation had nNO at background levels (2.8 nl/min at 7 years of age as compared to &gt;200 nl/min expected nNO). Conclusions: Our findings uncovered an essential role for SLC25A2 in determining NO production capacity in patients with HLHS. As all three HLHS patients with this variant and very low nNO survived with heart transplant, this variant should be further investigated as a genetic marker for predicting the need for early heart transplant in HLHS.

SURVIVAL, VENTRICULAR ARRHYTHMIA, AND IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR USEFULNESS IN A COHORT OF PATIENTS WITH TOXIC DILATED CARDIOMYOPATHY

SURVIVAL, VENTRICULAR ARRHYTHMIA, AND IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR USEFULNESS IN A COHORT OF PATIENTS WITH TOXIC DILATED CARDIOMYOPATHY

Clinical Exome Sequencing Revealed a De Novo FLNC Mutation in a Child with Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare disease of the myocardium caused by mutations in several genes including TNNT2, DES, TNNI3, MYPN and FLNC. Individuals affected by RCM often develop heart failure at a young age, requiring early heart transplantation. A 7-year-old patient was referred for genetic testing following a diagnosis of restrictive cardiomyopathy. Clinical exome sequencing analysis identified a likely pathogenic mutation in the FLNC gene [(NM_001458.5 c.6527_6547dup p.(Arg2176_2182dup)]. Its clinical relevance was augmented by the fact that this variant was absent in the parents and was thus interpreted as de novo. Genetic testing is a powerful tool to clarify the diagnosis, guide intervention strategies and enable cascade testing in patients with pediatric-onset RCM.

Clinical Factors Associated with Renal Outcome After Heart Transplantation.

Cardiorenal syndrome (CRS) frequently occurs in end-stage heart failure patients waiting for heart transplantation (HT). Decision-making regarding simultaneous heart and kidney transplantation is an unresolved issue in these patients. We investigated clinical factors associated with renal outcome after HT. A total of 180 patients who received HT from 1996 to 2015 were included. Factors associated with early post-HT chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] < 60 mL/minute/1.73 m2 within 1 year post-HT), post-HT end-stage kidney disease (ESKD), and significant renal function improvement (%ΔeGFR > 15%) at 1 year post-HT were analyzed. Early post-HT CKD and post-HT ESKD developed in 61 (33.9%) and 8 (4.4%) of 180 patients, respectively. Old age was only independently associated with early post-HT CKD and preexisting CKD tended to be associated with early post-HT CKD. Old age and preexisting CKD were independently associated with post-HT ESKD. Low pre-HT eGFR and preoperative renal replacement therapy were not associated with early post-HT CKD or post-HT ESKD. Young age, low pre-HT eGFR, and high %ΔeGFR 1 month post-HT were independently associated with significant renal function improvement. Preoperative renal function, including preoperative RRT, was not associated with post-HT mortality. In conclusion, preexisting CKD may impact renal outcomes after HT, but preoperative severe renal dysfunction, even that severe enough to require RRT, may not be a contraindication for HT alone. Our data suggest the necessity of early HT in end-stage heart failure patients with CRS and the importance of careful management during the early postoperative period.

MO422ACUTE KIDNEY INJURY AFTER HEART TRANSPLANTATION , INCIDENCE AND PREDICTIVE FACTORS

Abstract Background and Aims Abruptly decreased kidney function is one of the common scenarios after heart transplantation and the risk factors for renal dysfunction in this population can be various. The purpose of the present study was to determine the incidence and predictors for renal dysfunction among 126 patients in early postoperative heart transplantation period between January 2015 and November 2019. Method The study was conducted at the department of cardio-thoracic intensive care unit of an affiliated teaching hospital. 126 patients had cardiac transplantation surgery during four years. Information from these patients collected on a daily basis using standardized forms. Results Out of 126 heart transplant recipients 58.7 % (n=74) developed AKI and 10% (n=13) required renal replacement therapy after transplant. After performing univariate analysis, predictors of AKI were: age, duration of anesthesia, cold ischemia time, Voluven (Starch) dose, pre-operative BUN, creatinine and serum albumin, level of liver function tests, and Hemoglubin at three-days post-transplant and urine output of less than 200ml/ hour at six-hours post-transplant. Conclusion The findings of our study suggest that longer duration of graft ischemic time, history of previous cardiac operation and transfusion of more than four blood units can independently predict the chance of developing AKI following heart transplant. Therapies, which target these modifiable risk factors, may offer protection against this complication.

Cardiomyopathy phenotyping and risk-stratification in danon disease

Abstract Background Danon Disease (DD) is a rare, X-linked vacuolar myopathy due to mutations in Lysosomal Associated Membrane Protein 2 (LAMP-2). Though it is strongly associated with severe cardiomyopathy, heart failure and sudden death, there is no data on typical cardiac magnetic resonance (CMR) imaging characteristics in DD and their association with clinical severity and outcome. Purpose To phenotype and risk-stratify DD patients. Methods CMR scans of confirmed DD patients recruited in a global registry were prospectively analyzed for biventricular volumes, ejection fraction (EF), left ventricular (LV) strain, mass (LVM) and late gadolinium enhancement (LGE) in a core-lab blinded fashion. A major adverse cardiac event (MACE) was a composite of death, heart transplant and implantable cardioverter defibrillator (ICD) for secondary prevention. Results 12 DD patients (5 males [42%], median age 13 yrs [interquartile range (IQR) 5]) were included. LV hypertrophy (LVH) was present in 10/12 (83%), associated with LV dilation in 2 females. LVH was typically asymmetric in females (5/7) and concentric in males (3/5); right ventricular (RV) hypertrophy frequent in females (4/7). LV strain was reduced (global circumferential strain [GCS] −12±4%) and LGE common (73%), often extensive and always sparing the basal-mid septum. LGE was strongly associated with heart failure (BNP r=0.9, p=0.0021). Patients with MACE (6 [50%], median follow-up 2.9 yrs) had elevated LVM (241±63 g, p=0.032), impaired LV strain (GCS: −9.8±3.9, p=0.02) and higher LGE mass (median 56 g [IQR 35], p=0.021) compared to those without events during follow-up (LVM 155±56 g, GCS −14.9±1.6, LGE mass 0 g [IQR 8]). CMR characteristics were predictors of MACE (LV strain: hazard ratio [HR] 1.4, p=0.021; LGE mass: HR 1.1, p=0.03). Conclusions LGE sparing the basal-mid septum was pathognomonic in DD. LVH with reduced LV strain was the most common DD phenotype but the spectrum included LV dilation and RV hypertrophy in females. CMR characteristics (LV strain and LGE) were associated with heart failure and predicted worse outcome (heart transplant and fatal arrhythmias). CMR phenotyping and risk-stratification of this severe and underrecognized cardiomyopathy may aid diagnosis and clinical management in DD patients who need selection for early heart transplant, ICD implantation and targeted gene therapy. Danon Disease Phenotypes and Outcome Funding Acknowledgement Type of funding source: Other. Main funding source(s): National Institute of Health and Rocket Pharmaceuticals

MitraClip implantation followed by insertion of a left ventricular assist device in patients with advanced heart failure.

AimsMitral valve regurgitation (MR) is common in patients with advanced heart failure (HF). Percutaneous mitral valve repair (PMVR) via MitraClip (MC) has emerged as a feasible treatment strategy for these high‐risk patients. However, as HF often further progresses, there is a frequent need for left ventricular assist device (LVAD) implantation in these patients. We aimed to investigate whether prior MC implantation affects the subsequent LVAD implantation and outcome.Methods and resultsThirty‐seven patients with advanced HF and significant MR who underwent LVAD implantation were retrospectively analysed. Follow‐up data were collected at 1 year after LVAD implantation. Primary endpoint was all‐cause mortality. Secondary endpoint included peri‐operative parameters and clinical development depicted as New York Heart Association (NYHA) class and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Seventeen patients initially received a MC device (MC group), resulting in a significant reduction in MR grade. After MC, NYHA class and INTERMACS level further worsened, leading to subsequent LVAD implantation after a median time of 475 days in the MC group. At LVAD implantation, overall characteristics were comparable with those of the patients undergoing LVAD implantation without prior MC placement (no‐MC group). Procedural data revealed a higher incidence of right ventricular (RV) failure needing mechanical RV assistance and a longer need for nitric oxide ventilation in the MC group after LVAD implantation. One‐year survival was slightly better in the no‐MC group compared with the MC group [41% (n = 7/17) vs. 65% (n = 13/20); P = 0.15], albeit event‐free survival was comparable between both groups, MC and no‐MC.ConclusionsLVAD implantation after MC is feasible and safe. However, in patients with advanced HF and severe MR, PMVR may only delay a needed LVAD implantation and thereby lead to poorer peri‐operative RV function and impaired outcome. Arguably, these patients might benefit from the timely management of advanced HF by the means of early LVAD implantation or heart transplantation.

Statistical performance of 16 posttransplant risk scores in a contemporary cohort of heart transplant recipients.

Accurate risk stratification of early heart transplant failure is required to avoid futile transplants and rationalize donor selection. We aimed to evaluate the statistical performance of existing risk scores on a contemporary cohort of heart transplant recipients. After an exhaustive search, we identified 16 relevant risk scores. From the UNOS database, we selected all first noncombined adult heart transplants performed between 2014 and 2017 for validation. The primary endpoint was death or retransplant during the first year posttransplant. For all scores, we analyzed their association with outcomes, sensitivity, specificity, likelihood ratios, and discrimination (concordance index and overlap of individual scores). The cohort included 9396 patients. All scores were significantly associated with the primary outcome (P<.001 for all scores). Their likelihood ratios, both negative and positive, were poor. The discriminative performance of all scores was limited, with concordance index ranging from 0.544 to 0.646 (median 0.594) and an important overlap of individual scores between patients with or without the primary endpoint. Subgroup analyses revealed important variation in discrimination according to donor age, recipient age, and the type of assist device used at transplant. Our findings raise concerns about the use of currently available scores in the clinical field.

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.

Outcomes in adults with congenital heart disease and heterotaxy syndrome: A single-center experience.

Heterotaxy syndrome (HS) is a condition in which the thoracoabdominal organs demonstrate an abnormal lateral arrangement and is often associated with congenital heart disease (CHD). Little is known about the adult HS population with CHD. To describe the outcomes and sociodemographics of the adult CHD population with HS. Records of patients 18years of age or older with diagnoses of both CHD and HS at Texas Children's Hospital from 1964 to 2018 were reviewed. Sixty-two patients met inclusion criteria. Median age was 22.7 [IQR 19.6-30.0] years; 26 (42%) were female; and 13 (21%) of patients had a gap in care of >3years. Median follow-up time in adulthood was 2.9 [IQR 1.3-8.2] years. Forty-three (69%) of patients had single ventricle heart disease, 31 (71%) of whom completed Fontan circulation. A total of 36 interventions occurred in 24 patients which included 16 cardiac catherization interventions, 13 electrophysiology-related procedures, and 18 surgical procedures including 2 orthotopic heart transplants. The median age for death or heart transplant was 45.3 (95%CI 34.3-56.1) years. Heart failure-free survival was 80.8±5.2%, 58.7±11.0%, and 31.1±15.7% at 20, 30, and 40years old, respectively. Cerebrovascular accident-free survival was 84.3±5.1%, 54.2±11.3%, and 40.6±14.5% at 20, 30, and 40years old, respectively. Tachyarrhythmia-free survival was 54.0±7.1%, 29.2±8.3%, and 19.5±9.7% at 20, 30, and 40years old and bradyarrhythmia-free survival was 66.0±6.3%, 41.7±9.4%, and 33.4±10.6% at ages 20, 30, and 40years, respectively. At a tertiary referral center, adult patients with CHD and HS have high rates of comorbidities and early death or heart transplant. Longitudinal surveillance and further exploration into factors associated with improved survival in this population are warranted.

Early conversion of classic Fontan conversion may decrease term morbidity: single centre outcomes.

The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts. A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion. A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure. Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.

Omental and deep inferior epigastric artery perforator flap coverage after heart transplantation to manage wide left ventricular assist device exposure with pocket infection

Infection is a serious potential complication after left ventricular assist device (LVAD) implantation. In general, infection of the device pocket, with device exposure, should be managed by early device removal and heart transplantation. However, because of the small number of donors in Japan, accelerating access to heart transplantation is often difficult and the LVAD can be widely exposed during the waiting period. We report our experience of successful heart transplantation in a patient with a widely exposed LVAD with pocket infection. A 48-year-old man suffered from heart failure due to idiopathic dilated cardiomyopathy. An LVAD was implanted, but postoperative infection led to blood pump exposure. Heart transplantation was performed 4months after LVAD exposure, at which time the epigastric skin defect measured 14 × 8cm. The skin defect could not be closed after heart transplantation, so it was covered by an omental flap with split-thickness skin grafts. 7 days postoperatively, the peritoneal suture broke and the intestinal tract prolapsed outside the body. Reintroduction of the prolapsed intestinal tract and deep inferior epigastric artery perforator (DIEP) flap coverage of the omental flap were performed. The postoperative course was uneventful. There have been no reports of the management of wide skin defects in the presence of infection when heart transplantation is performed. Omental flap placement was useful for controlling long-lasting infection. An omental flap placed in a patient with a wide epigastric skin defect should be covered by durable skin flap, such as a DIEP flap, to avoid intestinal prolapse.

Prognostic factors in paediatric restrictive cardiomyopathy

Restrictive cardiomyopathy (RCM) is the rarest and most serious form of heart muscle disease, accounting for 2–5% of pediatric cardiomyopathies. Identification of prognostic factors to identify high-risk patients that need to be addressed for early heart transplantation. We enrolled 47 patients that had a diagnosis of RCM between 1996 and 2017 in our center. The clinical, ultrasonography, and hemodynamic data were collected at the time of diagnosis, as well as genetic analysis in order to identify early predictors of poor prognosis (transplantation or death). The mean age at diagnosis was 5.9 years with a gender ratio of 1.76 (F/M). 57.5% had a pure RCM and 42.5% an hypertrophic cardiomyopathy with restrictive phenotype (HRCM). The median follow-up was 10.2 months. Overall survival at 1, 2 and 5 years was 43% 35% and 15% respectively. There was no statistically significant difference in terms of survival between RCM and HRCM (P = 0.651) and between age groups (P = 0.582). Clinical findings at diagnosis were dominated by congestive signs (63.9%), which were related to a poor outcome (P = 0/041). The relationship between a mildly altered left ventricular ejection fraction (LVEF 45-55%) and mortality was statistically significant (P = 0.01). Imaging findings didn’t show a late gadolinium enhancement. Regarding catheterism data, neither cardiac output nor pulmonary vascular resistance nor pulmonary capillary pressure were related to a poor outcome. The rentability of family screening was 60%: we identified 1 homozygous and 4 heterozygous mutations on TNNI3 gene including a neomutation, and 1 on MYH7 gene. Adverse prognostic factors were dominated by congestive signs at diagnosis and left ventricular dysfunction. Patient with these factors should be addressed early for Heart transplantation. Autosomic dominant mutation in TNNI3 was the most frequent genetic finding. Family screening and genetic counseling is thus important.

Survival to Stage II with Ventricular Dysfunction: Secondary Analysis of the Single Ventricle Reconstruction Trial.

Ventricular dysfunction affects survival in patients with single right ventricle (RV), and remains one of the primary indications for heart transplantation. Since it is challenging to predict the capacity of patients with ventricular dysfunction to proceed to the stage II procedure, we sought to identify factors that would be associated with death or heart transplantation without achieving stage II for single RV patients with ventricular dysfunction after Norwood procedure. The Single Ventricle Reconstruction (SVR) trial public-use database was used. Patients with a RV ejection fraction less than 44% or a RV fractional area of change less than 35% on the post-Norwood echocardiogram were included. Parametric risk hazard analysis was used to identify risk factors for death or transplantation without achieving stage II. Of 365 patients with ventricular function measurements on the post-Norwood echocardiogram, 123 (34%) patients had RV dysfunction. The transplantation-free survival was significantly lower for those with ventricular dysfunction compared to those with normal function (log rank Chi-square = 4.23, p = 0.04). Furthermore, having a Blalock-Taussig (BT) shunt, a large RV, a post-Norwood infectious complication, and a surgeon who performs five or less Norwood per year were independent risk factors for death or transplantation without achieving stage II. The predicted 6-month transplantation-free survival for patients with all four identified risk factors was 1% (70% CI 0-13%). Early heart transplantation referral might be considered for post-Norwood patients with BT shunt and RV dysfunction, especially if other high-risk features are present.

The impact of gender mismatching on early and late outcomes following heart transplantation.

AimsThe role of donor/recipient gender matching on the long‐term rejection process and clinical outcomes following heart transplantation (HT) outcomes is still controversial. We aim to investigate the impact of gender matching on early and long‐term outcome HT.Methods and resultsThe study population comprised 166 patients who underwent HT between 1991 and 2013 and were prospectively followed up in a tertiary referral centre. Early and late outcomes were assessed by the type of donor–recipient gender match (primary analysis: female donor–male recipient [FD–MR, n = 36] vs. male donor–male recipient [MD–MR, n = 109]). Early mortality, need for inotropic support, length of hospital stay, and major perioperative adverse events did not differ between the FD–MR and MD–MR groups. However, the FD–MR group experienced significantly higher rates of early major rejections per patient as compared with the MD–MR group (1.2 ± 1.6 vs. 0.4 ± 0.8; P = 0.001), higher rates of overall major rejections (16 vs. 5.5 per 100 person years; P < 0.05), and higher rate of cardiac allograft vasculopathy (43% vs. 20%; P = 0.01). Kaplan–Meier survival analysis showed that the cumulative probabilities of survival free of rejections and major adverse events were significantly higher in MD–MR group (P = 0.002 and 0.001, respectively). Multivariate analysis showed that FD–MR status was associated with >2.5‐fold (P = 0.03) increase in the risk for rejections and with a >3‐fold (P = 0.01) increase in the risk for major adverse events during follow‐up.ConclusionsDonor–recipient gender mismatch is a powerful independent predictor of early and late rejections and long‐term major adverse events following HT.

(1163) - The Fontan Liver after Cardiac Transplantation

Purpose 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. Methods 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. Results 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. Conclusion 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.