Ruth Heying

The Fontan circulation: who controls cardiac output?

In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.

Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants

Background Melody valved stents (Medtronic Inc, Minneapolis, Minnesota, USA) have become a very competitive therapeutic option for pulmonary valve replacement in patients with congenital heart disease. After adequate prestenting of the right ventricular outflow tract (RVOT) Melody valved stents have a good medium term functional result but are exposed to infective endocarditis (IE). Patients and methods Retrospective study of tertiary centre Congenital Heart Disease database; to compare incidence of IE in three different types of valved conduits in RVOT: Melody valved stent, cryopreserved homograft (European Homograft Bank) and Contegra graft (Medtronic Inc). Results Between 1989 and 2013, 738 conduits were implanted in 677 patients. 107 Melody valved stents were implanted in 107 patients; IE occurred in 8 (7.5%) patients during a follow-up of 2.0 years (IQR 2.4 years, range 0.3–7.8 years). 577 Homografts were implanted in 517 patients; IE occurred in 14 patients (2.4%) during a median follow-up of 6.5 years (IQR 9.2 years; range 0.1–23.7 years). Finally, 54 Contegra grafts were implanted in 53 patients; 11 patients (20.4%) had IE during a follow-up of 8.8 years (IQR 7.7 years; range 0.2–3.5 years). Survival free of IE by Kaplan–Meier for homografts was 98.7% at 5 years and 97.3% at 10 years; for Contegra 87.8% at 5 years and 77.3% at 10 years and for Melody 84.9% at 5 years (log-rank test; p<0.001). Conclusions The Contegra conduit and Melody valved stents have a significantly higher incidence of IE than homografts. IE is a significant threat for long-term conduit function.

Off-label use of percutaneous pulmonary valved stents in the right ventricular outflow tract: time to rewrite the label?

Percutaneous pulmonary valve implantation is now considered feasible and safe. “Native” right ventricular outflow tract (RVOT), small diameter conduits (<16 mm) and relatively large RVOT with a dynamic outflow aneurysm are currently considered off‐label uses. Extending indications creates concerns of safety, ethics, reimbursement, and liability.

Fibronectin-binding proteins and clumping factor A in Staphylococcus aureus experimental endocarditis: FnBPA is sufficient to activate human endothelial cells

Surface molecules of Staphylococcus aureus are involved in the colonization of vascular endothelium which is a crucial primary event in the pathogenesis of infective endocarditis (IE). The ability of these molecules to also launch endothelial procoagulant and proinflammatory responses, which characterize IE, is not known. In the present study we investigated the individual capacities of three prominent S. aureus surface molecules; fibronectin-binding protein A (FnBPA) and B (FnBPB) and clumping factor A (ClfA), to promote bacterial adherence to cultured human endothelial cells (ECs) and to activate phenotypic and functional changes in these ECs. Non-invasive surrogate bacterium Lactococcus lactis, which, by gene transfer, expressed staphylococcal FnBPA, FnBPB or ClfA molecules were used. Infection of ECs increased 50- to 100-fold with FnBPA- or FnBPB-positive recombinant lactococci. This coincided with EC activation, interleukin-8 secretion and surface expression of ICAM-1 and VCAM-1 and concomitant monocyte adhesion. Infection with ClfA-positive lactococci did not activate EC. FnBPA-positive L. lactis also induced a prominent tissue factor-dependent endothelial coagulation response that was intensified by cell-bound monocytes. Thus S. aureus FnBPs, but not ClfA, confer invasiveness and pathogenicity to non-pathogenic L. lactis organisms indicating that bacterium-EC interactions mediated by these adhesins are sufficient to evoke inflammation as well as procoagulant activity at infected endovascular sites.

Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor-binding protein

Adhesion of Staphylococcus aureus to blood vessels under shear stress requires von Willebrand factor (VWF). Several bacterial factors have been proposed to interact with VWF, including VWF-binding protein (vWbp), a secreted coagulase that activates the hosts prothrombin to generate fibrin. We measured the adhesion of S aureus Newman and a vWbp-deficient mutant (vwb) to VWF, collagen, and activated endothelial cells in a microparallel flow chamber. In vivo adhesion of S aureus was evaluated in the mesenteric circulation of wild-type (WT) and VWF-deficient mice. We found a shear-dependent increase in adhesion of S aureus to the (sub)endothelium that was dependent on interactions between vWbp and the A1-domain of VWF. Adhesion was further enhanced by coagulase-mediated fibrin formation that clustered bacteria and recruited platelets into bacterial microthrombi. In vivo, deficiency of vWbp or VWF as well as inhibition of coagulase activity reduced S aureus adhesion. We conclude that vWbp contributes to vascular adhesion of S aureus through 2 independent mechanisms: shear-mediated binding to VWF and activation of prothrombin to form S aureus-fibrin-platelet aggregates.

The Contegra conduit in the right ventricular outflow tract is an independent risk factor for graft replacement

OBJECTIVE A large spectrum of congenital heart diseases requires valved conduits to establish an anatomical continuity between the right ventricle outflow tract (RVOT) and the pulmonary artery. The aim of the present study was to compare the incidence of graft replacement in patients receiving the Contegra conduit (bovine jugular vein graft) with that in patients receiving a homograft implanted in the RVOT. METHODS We reviewed a total of 347 conduits (Contegra 54; homografts 293) implanted in the RVOT from 1989 to 2003 in 323 patients (median age 12.7 years, range 4 days-69 years). Indications were Tetralogy of Fallot (n = 148), Ross operation (n = 89), truncus arteriosus communis (n = 47), pulmonary valve atresia (n = 30), double-outlet right ventricle (n = 15), transposition of the great arteries (n = 12), and endocarditis (n = 6). Follow-up was 99.4% complete (mean time: 5.9 years; range: 0-14.2 years). RESULTS Freedom from graft replacement at 1, 5, and 10 years of follow-up in the Contegra and homograft groups were 98.1 ± 1.9%, 78.3 ± 5.8%, and 63.5 ± 7.2% and 99.6 ± 0.4%, 94.0 ± 1.6%, and 81.4 ± 3.4%, respectively (log-rank test, p < 0.001). Independent predictors of graft replacement of the whole sample population were: graft size ≤ 20 mm (hazard ratio (HR) 3.6), age ≤ 10.4 years (HR 3.0), the non-anatomical position of the graft (HR 2.9), and the use of the Contegra conduit (HR 2.5). The multivariable analysis carried out on the propensity-score-matched population confirmed three independent predictors of graft replacement: graft size ≤ 20 mm (HR 8.0), the non-anatomical position of the graft (HR 2.3), and the use of the Contegra conduit (HR 3.7). CONCLUSIONS Besides size of the graft, age of the patients, and the non-anatomical position of the graft, the use of the Contegra conduit was found to be an independent risk factor for graft replacement in the RVOT. Patients receiving this conduit were more than twice as likely to undergo re-operation for graft replacement as those receiving a homograft.

Dexamethasone Pretreatment Provides Antiinflammatory and Myocardial Protection in Neonatal Arterial Switch Operation

BACKGROUND This prospective double-blinded randomized study tested the hypothesis that preoperative treatment with dexamethasone would attenuate inflammatory priming of the myocardium, reduce the systemic inflammatory reaction upon cardiac operation, and provide organ protection in neonates. METHODS Twenty neonates (age, 8 to 21 days) with transposition of the great arteries scheduled for arterial switch operation were included. Nine received dexamethasone (1 mg/kg body weight) 4 hours before cardiopulmonary bypass, and 11 received natrium chloride. We studied intramyocardial messenger RNA expression of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor-α (TNF-α), as well as IL-10 and expression of TNF-α on protein level in right atrial tissue taken before institution of CPB. We measured plasma levels of IL-6, IL-10, lipopolysaccharide binding protein, and cardiac troponin T. Cytokine expression was related to postoperative outcome. RESULTS Pretreatment with dexamethasone led to a significant decrease in myocardial expression of IL-6, IL-8, IL-1β, and TNF-α messenger RNA and to a decrease in protein synthesis of TNF-α. Plasma concentrations of IL-6 were significantly lower and those of IL-10 significantly higher in pretreated patients. This was associated with lower cardiac troponin T values and lower dobutamine requirement. Levels of lipopolysaccharide binding protein were significantly higher postoperatively in pretreated neonates. CONCLUSIONS Dexamethasone administration before arterial switch operation leads to a shift in the myocardial and systemic cytokine expression profile in neonates with transposition of the great arteries, with downregulation of proinflammatory and upregulation of antiinflammatory cytokines. Lower myocardial cell damage and lower catecholamine requirement suggest myocardial protection in treated patients.

Percutaneous pulmonary valve implantation for free pulmonary regurgitation following conduit-free surgery of the right ventricular outflow tract

INTRODUCTION Pulmonary regurgitation (PR) following surgery of the right ventricular outflow tract (RVOT) is not innocent and leads to significant right heart dysfunction over time. Recent studies have demonstrated that percutaneous valves can be implanted in conduit free outflow tracts with good outcomes. OBJECTIVES To evaluate in patients with severe PR--anticipated to require future pulmonary valve replacement--the feasibility and safety of pre-stenting dilated non-stenotic patched conduit-free right ventricular outflow tracts before excessive dilation occurs, followed by percutaneous pulmonary valve implantation (PPVI). PATIENTS AND METHODS Twenty seven patients were evaluated, but only 23 were deemed suitable based on the presence of an adequate retention zone ≤ 24 mm defined by semi-compliant balloon interrogation of the RVOT. A 2 step procedure was performed: first the landing zone was prepared by deploying a bare stent, followed 2 months later by valve implantation. RESULTS RVOT pre-stenting with an open cell bare metal stent (Andrastent XXL range) was performed at a median age of 13.0 years (range: 6.0-44.9) with a median weight of 44.3 kg (range: 20.0-88.0). Ninety six percent (22/23) of patients proceeded to PPVI a median of 2.4 months (range: 1.4-3.4) after initial pre-stent placement. Twenty one Melody valves and one 26 mm Edwards SAPIEN™ valve were implanted. Complications consisted of embolization of prestent (n = 1), scrunching (n = 4) and mild stent dislocation (n = 2). During follow-up, no stent fractures were observed and right ventricular dimensions decreased significantly. CONCLUSIONS Post-surgical conduit-free non-stenotic RVOT with free pulmonary regurgitation can be treated percutaneously with a valved stent if anatomical (predominantly size) criteria are met. In experienced hands, the technique is feasible with low morbidity.

Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity

IntroductionCardiac surgery with cardiopulmonary bypass (CPB) is associated with the activation of inflammatory mediators that possess prothrombotic activity and could cause postoperative haemostatic disorders. This study was conducted to investigate the effect of cardiac surgery on prothrombotic activity in children undergoing cardiac surgery for complex cardiac defects.MethodsEighteen children (ages 3 to 163 months) undergoing univentricular palliation with total cavopulmonary connection (TCPC) (n = 10) or a biventricular repair (n = 8) for complex cardiac defects were studied. Prothrombotic activity was evaluated by measuring plasma levels of prothrombin fragment 1+2 (F1+2), thromboxane B2 (TxB2), and monocyte chemoattractant protein-1 (MCP-1). Anti-thrombotic activity was evaluated by measuring levels of tissue factor pathway inhibitor (TFPI) before, during, and after cardiac surgery.ResultsIn all patients, cardiac surgery was associated with a significant but transient increase of F1+2, TxB2, TFPI, and MCP-1. Maximal values of F1+2, TxB2, and MCP-1 were found at the end of CPB. In contrast, maximal levels of TFPI were observed at the beginning of CPB. Concentrations of F1+2 at the end of CPB correlated negatively with the minimal oesophageal temperature during CPB. Markers of prothrombotic activity returned to preoperative values from the first postoperative day on. Early postoperative TFPI levels were significantly lower and TxB2 levels significantly higher in patients with TCPC than in those with biventricular repair. Thromboembolic events were not observed.ConclusionOur data suggest that children with complex cardiac defects undergoing cardiac surgery show profound but transient imbalance between pro- and anti-thrombotic activity, which could lead to thromboembolic complications. These alterations are more important after TCPC than after biventricular repair but seem to be determined mainly by low antithrombin III.

Volume load paradox while preparing for the Fontan: not too much for the ventricle, not too little for the lungs

Ventricular dysfunction is frequently encountered in Fontan patients. Cardiologists and cardiac surgeons have, therefore, mainly focused on preservation of cardiac function, limiting the early volume overload as much as possible both in magnitude and duration. This resulted in improved cardiac function but, in some patients, also in poor pulmonary artery (PA) growth which in turn resulted in a poor final Fontan circuit. The volume requirements for optimal growth and development of the ventricle and the lungs are different and divergent. Avoiding overload of the ventricle is important, but excessive protection from volume overload may not be necessary and may result in PA hypoplasia, which in turn will severely affect the Fontan circuit.