Mechanical Circulatory Support as Bridge to Pediatric Heart Transplantation

Fueled by the uncertainty and the time required to obtain a donor heart, mechanical circulatory support (MCS) forms an essential part of end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) use is limited to a few days before serious complications like bleeding occur. Prolonged support in terms of ventricular assist device (VAD) as a bridge to transplantation (BTT) became mandatory to overcome death on the waiting list. Within the last decade, VADs in adults have evolved drastically with the introduction of continuous flow (cf) devices. Increased miniaturization of VADs and new support strategies have increased its use in the pediatric population even in small children and patients with congenital heart disease (CHD). Nevertheless, patient and device selection in this patient population remain challenging to achieve optimal outcome and decrease complication rates. This comes with the need for care providers specialized in this field. Size issues and anatomical diversity make decision making complex and unique when compared to general adult practice. Neonates with single ventricle physiology are the highest risk candidates for VADs. This chapter reviews the most relevant durable VADs used in children including the rapid evolution of using adult designed cf-VADs to support children with anatomical normal hearts and CHD

Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

Background: Heart failure (HF) patients with atrial fibrillation (AF) often have conduction system disorders, which may be worsened by β-blocker therapy.Objective: In a post hoc analysis we examined the prevalence of bradycardia and its association with adverse events (AEs) and failure to achieve target dose in the GENETIC-AF trial.Methods: Patients randomized to metoprolol (n = 125) or bucindolol (n = 131) entering 24-week efficacy follow-up and receiving study medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) heart rate (HR) &lt;60 beats per minute (bpm) and severe bradycardia &lt;50 bpm.Results: Mean HR in sinus rhythm (SR) was 62.6 ± 12.5 bpm for metoprolol and 68.3 ± 11.1 bpm for bucindolol (P &lt; .0001), but in AF HRs were not different (87.5 bpm vs 89.7 bpm, respectively). Episodes per patient for bucindolol vs metoprolol were 0.82 vs 2.08 (P &lt; .001) for bradycardia and 0.24 vs 0.57 for severe bradycardia (P &lt; .001), with 98.9% of the episodes occurring in SR. Patients experiencing bradycardia had a 4.15-fold higher prevalence of study medication dose reduction (P &lt;.0001) compared to patients without bradycardia. Fewer patients receiving metoprolol were at target dose (61.7% vs 74.9% for bucindolol, P &lt; .0001) at ECG recordings, and bradycardia AEs were more prevalent in the metoprolol group (13 vs 1 for bucindolol, P = .001). On multivariate analysis of 21 candidate bradycardia predictors including presence of a device with pacing capability, bucindolol treatment was associated with the greatest degree of prevention (Zodds ratio -4.24, P &lt; .0001).Conclusion: In AF-prone HF patients bradycardia may limit the effectiveness of β blockers, and this property is agent-dependent.</p

Conceptual Art

Providing a re-examination of what Osborne identifies as a major turning point in contemporary art, this monograph takes a chronological and stylistic look at conceptual art from its “pre-history” (1950-1960) to contemporary practices that use conceptual strategies. Osborne surveys the development of the movement in relation to the social, cultural and political contexts within which it evolved. With extended captions, key works are compiled according to ten themes that also serve to present a collection of critical texts, artists’ statements, interviews and commentaries. Includes biographical notes on artists (6 p.) and authors (2 p.), a bibliography (2 p.) and an onomastic index (4 p.) Circa 150 bibl. ref

Antithrombotic therapy in pediatric ventricular assist devices: Multicenter survey of the European EXCOR Pediatric Investigator Group

Objectives: Mechanical circulatory support for pediatric heart failure patients with the Berlin Heart EXCOR ventricular assist system is the only approved and established bridging strategy for recovery or heart transplantation. In recent years, the burden of thromboembolic events has led to modifications of the recommended antithrombotic therapy. Therefore, we aimed to assess modifications of antithrombotic practice among the European EXCOR Pediatric Investigator Group members. Methods: We sent a questionnaire assessing seven aspects of antithrombotic therapy to 18 European hospitals using the EXCOR device for children. Returned questionnaires were analyzed and identified antithrombotic strategies were descriptively compared to “Edmonton protocol” recommendations developed for the US EXCOR pediatric approval study. Results: Analysis of 18 received surveys revealed substantial deviations from the Edmonton protocol, including earlier start of heparin therapy at 6–12 h postoperatively and in 50% of surveyed centers, monitoring of heparin effectiveness with aPTT assay, administering vitamin K antagonists before 12 months of age. About 39% of centers use higher international normalized ratio targets, and platelet inhibition is changed in 56% including the use of clopidogrel instead of dipyridamole. Significant inter-center variability with multiple deviations from the Edmonton protocol was discovered with only one center following the Edmonton protocol completely. Conclusion: Current antithrombotic practice among European EXCOR users representing the treatment of more than 600 pediatric patients has changed over time with a trend toward a more aggressive therapy. There is a need for systematic evidence-based evaluation and harmonization of developmentally adjusted antithrombotic management practices in prospective studies toward revised recommendations

Paediatric aortic valve replacement using decellularized allografts

OBJECTIVES Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and mechanical AVR imposes constant anticoagulation with the inherent risks. METHODS The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres. RESULTS A total of 106 children (77 boys) were operated (mean age 10.1 ± 4.8 years, DAH diameter 20.5 ± 3.8 mm). A total of 60 (57%) had undergone previous surgical interventions: 34 with 1, 15 with 2 and 11 with ≥3. There was one early death in a 12-year-old girl, who underwent her fourth aortic valve operation, due to intracerebral haemorrhage on extracorporeal membrane oxygenation after coronary reimplantation problems following 3-sinus reconstruction 1 year earlier. One 2-year-old patient died due to sepsis 2 months postoperatively with no evidence for endocarditis. In addition, a single pacemaker implantation was necessary and a 2.5-year-old girl underwent successful HTx due to chronic myocardial failure despite an intact DAH. After a mean follow-up of 3.30 ± 2.45 years, primary efficacy end points mean peak gradient (18.1 ± 20.9 mmHg) and regurgitation (mean 0.61 ± 0.63, grade 0-3) were very good. Freedom from death/explantation/endocarditis/bleeding/stroke at 5 years was 97.8 ± 1.6/85.0 ± 7.4/100/100/100% respectively. Calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.9 years), lower than in Ross patients (9.4 years) and in the same range as mechanical AVR (12.8 years). CONCLUSIONS Even though the overall number of paediatric DAH patients and the follow-up time span are still limited, our data suggest that DAHs may present a promising additional option for paediatric AVR

Mechanical circulatory support of systemic ventricle in adults with transposition of great arteries

We report the successful use of the implantable ventricular assist device HeartWare (HeartWare International Inc., Framingham, MA) to support the systemic circulation in two adult patients with transposition of the great arteries (TGA). One had undergone the Senning procedure as a neonate; the other had congenitally corrected TGA and dextrocardia with palliation in adulthood. It is possible to implant the HeartWare pump into the morphological right ventricle with cannulation of either the diaphragmal surface or the free wall without additional changes in implantation technique and employing off-pump insertion