COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease.

Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Recovery of multipotent progenitors from the peripheral blood of patients requiring extracorporeal membrane oxygenation support.

RATIONALE: Studies have demonstrated that bone marrow-derived cells can be recruited to injured lungs through an unknown mechanism. We hypothesize that marrow progenitors are mobilized into the circulation of patients with cardiac and/or respiratory failure, and may then traffic to and incorporate into the sites of tissue injury. OBJECTIVES: To determine whether progenitor populations are increased in the blood of patients with severe acute cardiorespiratory failure placed on extracorporeal membrane oxygenation (ECMO). METHODS: Mononuclear cells from ECMO, umbilical cord, and control blood samples were evaluated in colony-forming assays for hematopoietic, mesenchymal, and epithelial cells. Progenitors were identified by proliferative and differentiative capacities, and confirmed by the expression of lineage-specific markers. MEASUREMENTS AND MAIN RESULTS: Significantly higher levels of hematopoietic progenitors were observed in ECMO (n = 41) samples than neonatal intensive care unit (n = 16) or pediatric intensive care unit controls (n = 14). Hematopoietic progenitor mobilization increased with time on ECMO support. Mesenchymal progenitors (MSC) were recovered from 18/58 ECMO samples with rapid sample processing (< 4 h) critical to their recovery. MSC were not recovered from normal controls. ECMO-derived MSC had osteogenic, chondrogenic, and adipogenic differentiation potential. The recovery of MSC did not influence survival outcome (61%). Epithelial progenitors were observed in eight ECMO samples but not in control samples. Their presence was associated with a lower survival trend (38%). CONCLUSIONS: Hematopoietic, mesenchymal, and epithelial progenitors were mobilized into the circulation of patients on ECMO. This may reflect a response to severe cardiopulmonary injury, blood-foreign surface interactions with the ECMO circuit, and/or hemodilution.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Diagnostic and Therapeutic Approach to Arrhythmias in Adult Congenital Heart Disease.

PURPOSE OF REVIEW: Adult survivors of congenital heart disease (CHD) are at increased risk of arrhythmia. The goal of this review is to outline diagnostic and therapeutic approaches to arrhythmia in adult CHD patients. RECENT FINDINGS: Macro-reentrant atrial tachyarrhythmia is the most common arrhythmia encountered in adults with CHD. Approximately 25% of hospitalizations associated with arrhythmia. The risk of ventricular arrhythmia is estimated as high as 25-100 times that for the general population and increased after two decades. Routine ambulatory monitoring is important for arrhythmia risk assessment in adults with CHD. There are limitations, potential adverse effects, and risk of recurrence with antiarrhythmic drugs, catheter ablation, and surgical approaches. Adults with CHD suffer various forms of arrhythmia, are at increased risk of sudden death, and require special consideration for medical and interventional therapy.

Effect of patent ductus arteriosus on pulmonary vascular disease.

The hemodynamic effects of a patent ductus arteriosus (PDA) are well known including systemic hypoperfusion and volume overload on the left ventricle. This article aims to provide a review of the long-standing effect of a hemodynamically significant PDA on the pulmonary vasculature and the role of cardiac catheterization in preterm infants with a PDA and pulmonary hypertension.

Fontan Liver Disease: Review of an Emerging Epidemic and Management Options.

OPINION STATEMENT: Adults with complex congenital heart disease that resulted in a Fontan procedure frequently experience late cardiac failure. Increasingly, liver disease is recognized as an important complication of single-ventricle anatomy and Fontan physiology; however, there is no consensus regarding liver evaluation in this population. Here, we review what is known about liver disease in this unique group and propose screening and prevention measures. We also review controversial treatment areas including assist devices and transplantation, with a review of outcomes in isolated heart and combined heart-liver transplant.

Transcaval puncture for access to the pulmonary venous atrium after the extracardiac total cavopulmonary connection operation.

BACKGROUND: Patients with surgically palliated total cavopulmonary connection are at risk for recurrent atrial arrhythmia requiring catheter ablation. Transcatheter procedures for those with extracardiac conduits (extracardiac-total cavopulmonary connection) are perhaps the most challenging because of exclusion of the venous circulation from the arrhythmia substrate. Puncture through the inferior vena cava to the pulmonary venous atrium may be an effective route for access in these patients. METHODS AND RESULTS: The pediatric and adult congenital surgical databases were explored for patients with extracardiac-total cavopulmonary connection and postoperative computed tomography imaging to assess for the presence of clinically relevant (>3 mm) apposition between the inferior vena cava and pulmonary venous atrium (cavoatrial overlap). The degree of overlap between the structures was measured by 2 blinded reviewers. Patients were stratified by surgical repair in childhood versus adult congenital heart disease. Thirty-seven patients were identified, with cavoatrial overlap observed in 9 (36%) of pediatric and 1 (9%) of adult congenital heart disease-repaired patients. Time elapsed after surgery was associated with cavoatrial overlap in the pediatric cohort (P=0.034) and was identified in all pediatric patients with computed tomography imaging ≥8 years after surgery. Three patients underwent successful transcaval puncture during the study period without complication. CONCLUSIONS: Puncture through a region of overlap between the inferior vena cava and pulmonary venous atrium is feasible. Cavoatrial overlap is present in a substantial proportion of patients undergoing extracardiac-total cavopulmonary connection in childhood and is associated with a longer time elapsed since surgery.

Development of lentiviral vectors with regulated respiratory epithelial expression in vivo.

Development of gene transfer vectors with regulated, lung-specific expression will be a useful tool for studying lung biology and developing gene therapies. In this study we constructed a series of lentiviral vectors with regulatory elements predicted to produce lung-specific transgene expression: the surfactant protein C promoter (SPC) for alveolar epithelial type II cell (AECII) expression, the Clara cell 10-kD protein (CC10) for Clara cell expression in the airway, and the Jaagskiete sheep retrovirus (JSRV) promoter for expression in both cell types. Transgene expression from the SPC and CC10 vectors was restricted to AECII and Clara cell lines, respectively, while expression from the JSRV vector was observed in multiple respiratory and nonrespiratory cell types. After intratracheal delivery of lentivector supernatant to mice, transgene expression was observed in AECII from the SPC lentivector, and in Clara cells from the CC10-promoted lentivector. Transgene expression was not detected in nonrespiratory tissues after intravenous delivery of CC10 and SPC lentiviral vectors to murine recipients. In summary, incorporation of genomic regulatory elements from the SPC and CC10 genes resulted in respiratory specific transgene expression in vitro and in vivo. These vectors will provide a useful tool for the study of lung biology and the development of gene therapies for lung disorders.