Current Status of Fetal Cardiac Intervention

McElhinney, Doff B.; Tworetzky, Wayne; Lock, James E.

doi:10.1161/circulationaha.109.870246

Cited by 147 publications

(125 citation statements)

References 74 publications

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“…Still, fetal death occurs in about 10% of fetal tachyarrhythmia cases, and even more in hydropic fetuses. Transplacental digoxin treatment is 71% effective in cases involving nonhydropic fetuses and 10% effective in hydropic fetuses [7]. Transplacental transfer of digoxin to the fetus is limited because digoxin is a substrate for the efflux transporter P-gp, which is highly expressed in human placenta [8], and is also expressed in BeWo cells [9].…”

Section: Introductionmentioning

confidence: 99%

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

et al. 2015

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Background: Fetal arrhythmias can lead to fetal congestive heart failure and hydrops fetalis. Digoxin (the first-line treatment) has low transplacental permeability and high risk of maternal side effects. Biodegradable digoxin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles may increase digoxin transport across BeWo b30 cell monolayers (an in vitro model of trophoblast in human placenta) by reducing the drug's interaction with P-gp. Results/methodology: The nanoparticles showed high encapsulation efficiency and sustained release over 48 h. Transport studies revealed significantly increased permeability across BeWo cell layers of digoxin-loaded nanoparticles when compared with free digoxin. P-gp inhibition also increased the permeability of digoxin, but not digoxin-loaded nanoparticles. Conclusion: This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes.

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Section: Introductionmentioning

confidence: 99%

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

et al. 2015

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“…6,38 Pressure-flow characteristics in general become increasingly unfavorable at reduced outflow diameters, for conventional end-hole type standard aortic outflow cannula configurations. Post intervention recovery has been reported to be suboptimal 24,34,41 and unless better aortic cannulation techniques are developed, the incidence of cannula-related problems can be expected to grow in proportion to the increased utilization of cardiopulmonary bypass (CPB) procedures or continuous-flow pediatric blood pumps. Poor perfusion of the aortic arch is hypothesized as a cause for neurological complications which may attribute to increased stroke risk on account of dislodged emboli transported in a non-physiologic flow field created by a single high speed cannula jet.…”

Section: Introductionmentioning

confidence: 99%

Aortic Outflow Cannula Tip Design and Orientation Impacts Cerebral Perfusion During Pediatric Cardiopulmonary Bypass Procedures

et al. 2013

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Abstract-Poor perfusion of the aortic arch is a suspected cause for peri-and post-operative neurological complications associated with cardiopulmonary bypass (CPB). High-speed jets from 8 to 10FR pediatric/neonatal cannulae delivering 1 L/min of blood can accrue sub-lethal hemolytic damage while also subjecting the aorta to non-physiologic flow conditions that compromise cerebral perfusion. Therefore, we emphasize the importance of cannulation strategy and hypothesize engineering better CPB perfusion through a redesigned aortic cannula tip. This study employs computational fluid dynamics to investigate novel diffuser-tipped aortic cannulae for shape sensitivity to cerebral perfusion, in an in silico cross-clamped aortic arch model modeled with fixed outflow resistances. 17 parametrically altered configurations of an 8FR end-hole and several diffuser cone angled tips in combination with jet incidence angles toward or away from the head-neck vessels were studied. Experimental pressure-flow characterizations were also conducted on these cannula tip designs. An 8FR end-hole aortic cannula delivering 1 L/min along the transverse aortic arch was found to give rise to backflow from the brachicephalic artery (BCA), irrespective of angular orientation, for the chosen ascending aortic insertion location. Parametric alteration of the cannula tip to include a diffuser cone angle (tested up to 7°) eliminated BCA backflow for any tested angle of jet incidence. Experiments revealed that a 1 cm long 10°diffuser cone tip demonstrated the best pressure-flow performance improvement in contrast with either an end-hole tip or diffuser cone angles greater than 10°. Performance further improved when the diffuser was preceded by an expanded four-lobe swirl inducer attachment-a novel component. In conclusion, aortic cannula orientation is crucial in determining net head-neck perfusion but precise angulations and insertion-depths are difficult to achieve practically. Altering the cannula tip to include a diffuser cone angle has been shown for the first time to have potential in ensuring a net positive outflow at the BCA. Cannula insertion distanced from the BCA inlet may also avoid backflow owing to the Venturi effect, but the diffuser tipped cannula design presents a promising solution to mitigate this issue irrespective of in vivo cannula tip orientation.

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“…6,8,12 The clinical relevance of defining the origins of congenital cardiovascular malformations relates to the high incidence of heart defects in humans (approximately 1% of live births and a much higher percentage of the pregnancies that end unsuccessfully in the first trimester), the requirement for medical and surgical intervention in at least 25% of these children in the first year of life, and the life-long impact of congenital heart disease on health, employment, and subsequent generations. 16,19 The broad based and international investigation that integrates comparative and developmental biology, the molecular genetics of invertebrate and vertebrate animal models, multimodal and predictive bioengineering approaches early 10 and expanding data sets from advanced human fetal imaging 20 and intervention 18 has reached the tipping point where observed congenital cardiovascular malformations can now be coupled to unique sequences of spatio-temporal events that trigger predictable altered developmental trajectories. One of the outcomes of this expanding knowledge base will be altered clinical management strategies designed to redirect developing structures towards preferred states that optimize fetal cardiovascular structure and function, 18 postnatal successful interventions, and improved quality of life.…”

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confidence: 99%