Heart and heart-liver transplantation in adults with failing Fontan physiology.

BACKGROUND: As the population of patients with a Fontan palliation grows so does, the number of patients with cardiac failure necessitating orthotopic heart transplant (OHT) and combined heart-liver transplant (CHLT). There is recent evidence that current era cardiac transplant in Fontan patients has improved outcomes, but most studies have a preponderance of pediatrics patients in their cohorts. We examine our institutional experience with adult OHT and CHLT transplantation for failed Fontan physiology. METHODS AND RESULTS: Retrospective analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to May 31, 2017. We identified 20 patients with single-ventricle physiology and Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range 19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis. The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days (range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178), there was one mortality occurring at 34 months post-OHT due to coronary vasculopathy. Most frequent early postoperative complications included bleeding and infection (55% and 20%, respectively) and surgical reintervention for bleeding complications (n = 8, 40%). One CHLT patient experienced clinically significant hepatic rejection requiring admission and steroid treatment. CONCLUSIONS: Despite inherent risks and complexities of OHT or CHLT in patients with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative complications are common and may require surgical reintervention. Continued observation of practices and unifying themes may help improve patient selection, pre- and postoperative treatment and ultimately outcomes.

Association Between Hematologic and Inflammatory Markers and 31 Thrombotic and Hemorrhagic Events in Berlin Heart Excor Patients.

Bleeding and thrombotic events remain a significant cause of morbidity in pediatric patients supported with ventricular assist devices (VADs). The objective of this study is to identify the association between markers of anticoagulation and bleeding and thrombosis events during Berlin Heart ExCor support. A retrospective, single-center analysis of 9 patients supported with the Berlin Heart ExCor was performed. Inflammatory and anticoagulation parameters including C-reactive protein, fibrinogen, partial thromboplastin time (PTT), and platelet count were measured at 48 and 24 h before and after bleeding or thrombosis events. Patients served as their own controls, and the same parameters were measured during a control period where subjects did not experience either event. All patients received the anticoagulation regimen proposed by Berlin Heart. A total of 31 bleeding or thrombotic events were identified and matched to 18 control events. Patient with predominantly thrombotic events tended to weigh less than those with bleeding events (Δ7.7 kg, p < 0.001). PTT levels were higher before and after bleeding (Δ17.36, p = 0.002) and thrombosis (Δ8.75, p < 0.001) events relative to control. Heparin dose decreased after a thrombosis event (Δ-5.67, p = 0.097), and this decrease was significantly different from control (p = 0.032). Non-collinearity between heparin dose and PTT should prompt further inflammatory and hematological investigation. In addition, heavier patients were more prone to bleeding complications. The role of inflammation in the development of thrombus or hemorrhages in the pediatric VAD population needs to be studied further.

Major elective non-cardiac operations in adults with congenital heart disease.

OBJECTIVE: To assess the impact of congenital heart disease (CHD) on resource utilisation and clinical outcomes in patients undergoing major elective non-cardiac operations. BACKGROUND: Due to advances in congenital cardiac management in recent years, more patients with CHD are living into adulthood and are requiring non-cardiac operations. METHODS: The 2010-2018 Nationwide Readmissions Database was used to identify all adults undergoing major elective operations (pneumonectomy, hepatectomy, hip replacement, pancreatectomy, abdominal aortic aneurysm repair, colectomy, gastrectomy and oesophagectomy). Multivariable regression models were used to categorise key clinical outcomes. RESULTS: Of an estimated 4 941 203 adults meeting inclusion criteria, 5234 (0.11%) had a previous diagnosis of CHD. Over the study period, the incidence of CHD increased from 0.06% to 0.17%, p<0.001. CHD patients were on average younger (63.3±14.8 vs 64.4±12.5 years, p=0.004), had a higher Elixhauser Comorbidity Index (3.3±2.2 vs 2.3±1.8, p<0.001) and received operations at high volume centres more frequently (66.6% vs 62.0%, p=0.003). Following risk adjustment, these patients had increased risk of in-hospital mortality (adjusted risk ratio (ARR): 1.76, 95% CI 1.25 to 2.47), experienced longer hospitalisation durations (+1.6 days, 95% CI 1.3 to 2.0) and cost more (+$8370, 95% CI $6686 to $10 055). Furthermore, they were more at risk for in-hospital complications (ARR: 1.24 95% CI 1.17 to 1.31) and endured higher adjusted risk of readmission at 30 days (ARR: 1.32 95% CI 1.13 to 1.54). CONCLUSIONS: Adults with CHD are more frequently comprising the major elective operative cohort for non-cardiac cases. Due to the inferior clinical and financial outcomes suffered by this population, perioperative risk stratification may benefit from the inclusion of CHD as a factor that portends unfavourable outcomes.

Race-based disparities in access to surgical palliation for hypoplastic left heart syndrome.

BACKGROUND: Racial disparities in outcomes have been shown to persist in many operative specialties, including the management of congenital heart disease. Using a demographic-adjusted methodology, we examined whether patient race influenced access to high-performing centers for the operative management of hypoplastic left heart syndrome. METHODS: The 2005-2017 National Inpatient Sample was queried to identify all pediatric (≤5 years) hospitalizations with an operation for hypoplastic left heart syndrome. A racial disparity index was generated for each hospital and defined as the proportion of White patients receiving operative management for hypoplastic left heart syndrome divided by the proportion of White patients admitted for respiratory failure. This methodology quantified hospital-level racial variation while adjusting for the local racial makeup of each center. RESULTS: Of the 17,275 patients who met inclusion criteria, 64.1% were managed at high-volume centers. Patients at high-volume centers had a similar distribution of operative type, age, and burden of comorbidities. The mean racial disparity index steadily grew from 1.06 at the lowest volume decile of operative volume to 1.51 at the highest, indicating an increasing proportion of White patients as volume increased. Using risk-adjusted analysis, each decile increase in hospital volume was associated with a 14% relative reduction in odds of mortality and a 0.06 increase in predicted racial disparity index. Increasing volume was further associated with reduced odds of non-home discharge but did not alter resource utilization. CONCLUSION: We demonstrate that high-volume centers disproportionally serve White patients and have superior clinical outcomes compared to low-volume centers. This study highlights the critical importance of equitable access to expert care for high-risk conditions such as hypoplastic left heart syndrome.

Orthotopic Heart and Combined Heart Liver Transplantation: the Ultimate Treatment Option for Failing Fontan Physiology.

Purpose of the Review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era. Recent Findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation. Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.

Obstruction of lateral tunnel fontan by an adjustable occluder device.

Innovative ways of adjusting Fontan fenestrations have been developed over the last two decades. Long-term complications have not been described. We successfully treated one such complication of Fontan conduit obstruction due to an adjustable occluder device.

Postoperative and short-term atrial tachyarrhythmia burdens after transcatheter vs surgical pulmonary valve replacement among congenital heart disease patients.

OBJECTIVE: We examined the atrial tachyarrhythmia (AT) burden among patients with congenital heart disease (CHD) following transcatheter (TC-) or surgical (S-) pulmonary valve replacement (PVR). DESIGN/SETTING: This was a retrospective observational study of patients who underwent PVR from 2010 to 2016 at UCLA Medical Center. PATIENTS: Patients of all ages who had prior surgical repair for CHD were included. Patients with a history of congenitally corrected transposition of the great arteries, underwent a hybrid PVR procedure, or had permanent atrial fibrillation (AF) without a concomitant ablation were excluded. OUTCOME MEASURES: The primary outcome was a time-to-event analysis of sustained AT. Sustained ATs were defined as focal AT, intra-atrial reentrant tachycardia/atrial flutter, or AF lasting at least 30 seconds or terminating with cardioversion or antitachycardia pacing. RESULTS: Two hundred ninety-seven patients (TC-PVR, n = 168 and S-PVR, n = 129) were included. During a median follow-up of 1.2 years, nine events occurred in TC-PVR group (5%) vs 23 events in S-PVR group (18%). In the propensity adjusted models, the following factors were associated with significant risk of AT after PVR: history of AT, age at valve implantation, severe right atrial enlargement, and S-PVR. In the secondary analysis, TC-PVR was associated with lower adjusted risk of AT events in the postoperative epoch (first 30 days), adjusted IRR 0.31 (0.14-0.97), P = .03, but similar risk in the short-term epoch, adjusted IRR 0.64 (0.14-2.94), P = .57. CONCLUSION: There was an increased risk of AT in the first 30 days following S-PVR compared to TC-PVR. Additional factors associated with risk of AT events after PVR were a history of AT, age at valve implantation, and severe right atrial enlargement.

Ventricular arrhythmia burden after transcatheter versus surgical pulmonary valve replacement.

OBJECTIVE: Comparative ventricular arrhythmia (VA) outcomes following transcatheter (TC-PVR) or surgical pulmonary valve replacement (S-PVR) have not been evaluated. We sought to compare differences in VAs among patients with congenital heart disease (CHD) following TC-PVR or S-PVR. METHODS: Patients with repaired CHD who underwent TC-PVR or S-PVR at the UCLA Medical Center from 2010 to 2016 were analysed retrospectively. Patients who underwent hybrid TC-PVR or had a diagnosis of congenitally corrected transposition of the great arteries were excluded. Patients were screened for a composite of non-intraoperative VA (the primary outcome variable), defined as symptomatic/recurrent non-sustained ventricular tachycardia (VT) requiring therapy, sustained VT or ventricular fibrillation. VA epochs were classified as 0-1 month (short-term), 1-12 months (mid-term) and ≥1 year (late-term). RESULTS: Three hundred and two patients (TC-PVR, n=172 and S-PVR, n=130) were included. TC-PVR relative to S-PVR was associated with fewer clinically significant VAs in the first 30 days after valve implant (adjusted HR 0.20, p=0.002), but similar mid-term and late-term risks (adjusted HR 0.72, p=0.62 and adjusted HR 0.47, p=0.26, respectively). In propensity-adjusted models, S-PVR, patient age at PVR and native right ventricular outflow tract (RVOT) (vs bioprosthetic/conduit outflow tract) were independent predictors of early VA after pulmonary valve implantation (p<0.05 for all). CONCLUSION: Compared with S-PVR, TC-PVR was associated with reduced short-term but comparable mid-term and late-term VA burdens. Risk factors for VA after PVR included a surgical approach, valve implantation into a native RVOT and older age at PVR.

Inflammation, oxidative stress, and glial cell activation characterize stellate ganglia from humans with electrical storm.

BACKGROUND: Neuronal remodeling in human heart disease is not well understood. METHODS: Stellate ganglia from patients with cardiomyopathy (CMY) and refractory ventricular arrhythmias undergoing cardiac sympathetic denervation (n = 8), and from organ donors with normal hearts (n = 8) collected at the time of organ procurement were compared. Clinical data on all subjects were reviewed. Electron microscopy (EM), histologic, and immunohistochemical assessments of neurotransmitter profiles, glial activation and distribution, and lipofuscin deposition, a marker of oxidative stress, were quantified. RESULTS: In CMY specimens, lipofuscin deposits were larger, and present in more neurons (26.3% ± 6.3% vs. 16.7% ± 7.6%, P < 0.043), than age-matched controls. EM analysis revealed extensive mitochondrial degeneration in CMY specimens. T cell (CD3+) infiltration was identified in 60% of the CMY samples, with one case having large inflammatory nodules, while none were identified in controls. Myeloperoxidase-immunoreactive neutrophils were also identified at parenchymal sites distinct from inflammatory foci in CMY ganglia, but not in controls. The adrenergic phenotype of pathologic samples revealed a decrease in tyrosine hydroxylase staining intensity compared with controls. Evaluation of cholinergic phenotype by staining for the vesicular acetylcholine transporter revealed a low but comparable number of cholinergic neurons in ganglia from both groups and demonstrated that preganglionic cholinergic innervation was maintained in CMY ganglia. S100 staining (a glial cell marker) demonstrated no differences in glial distribution and relationship to neurons; however, glial activation demonstrated by glial fibrillary acidic protein (GFAP) staining was substantially increased in pathologic specimens compared with controls. CONCLUSIONS: Stellate ganglia from patients with CMY and arrhythmias demonstrate inflammation, neurochemical remodeling, oxidative stress, and satellite glial cell activation. These changes likely contribute to excessive and dysfunctional efferent sympathetic tone, and provide a rationale for sympathectomy as a treatment for arrhythmias in this population. FUNDING: This work was made possible by support from NIH grants HL125730 to OAA, GM107949 to DBH, and HL084261 and OT2OD023848 to KS.

Atrial septal hematoma: after minimally invasive aortic valve replacement.

Interatrial septal hematoma is a very rare complication after mitral valve surgery. Unusually, it is the result of aortic valve disease, including aortic dissection. We report a case wherein interatrial septal hematoma followed minimally invasive aortic valve replacement in a 68-year-old woman. The hematoma was recognized upon intraoperative transesophageal echocardiography, but there was no evidence of accompanying aortic dissection. The interatrial septal hematoma was at first drained by needle, but recurrence prompted reoperation and plication of the interatrial septum. Finally, the hematoma resolved after correction of the coagulopathy. Catheter injury to the coronary sinus exacerbated by the retrograde administration of cardioplegic solution is thought to have caused the origin of the interatrial septal dissection.