{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:58:10Z","timestamp":1784944690537,"version":"3.55.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/501100001352","name":"National University of Singapore (NUS)","doi-asserted-by":"publisher","award":["Young Investigator Award 2015"],"award-info":[{"award-number":["Young Investigator Award 2015"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National University of Singapore Graduate School of Integrated Sciences","award":["PhD Scholarship"],"award-info":[{"award-number":["PhD Scholarship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p> Studies have suggested the effect of blood flow forces in pathogenesis and progression of some congenital heart malformations. It is therefore of interest to study the fluid mechanic environment of the malformed prenatal heart, such as the tetralogy of Fallot (TOF), especially when little is known about fetal TOF. In this study, we performed patient-specific ultrasound-based flow simulations of three TOF and seven normal human fetal hearts. TOF right ventricles (RVs) had smaller end-diastolic volumes (EDVs) but similar stroke volumes (SVs), whereas TOF left ventricles (LVs) had similar EDVs but slightly increased SVs compared with normal ventricles. Simulations showed that TOF ventricles had elevated systolic intraventricular pressure gradient (IVPG) and required additional energy for ejection but IVPG elevations were considered to be mild relative to arterial pressure. TOF RVs and LVs had similar pressures because of equalization via ventricular septal defect (VSD). Furthermore, relative to normal, TOF RVs had increased diastolic wall shear stresses (WSS) but TOF LVs were not. This was caused by high tricuspid inflow that exceeded RV SV, leading to right-to-left shunting and chaotic flow with enhanced vorticity interaction with the wall to elevate WSS. Two of the three TOF RVs but none of the LVs had increased thickness. As pressure elevations were mild, we hypothesized that pressure and WSS elevation could play a role in the RV thickening, among other causative factors. Finally, the endocardium surrounding the VSD consistently experienced high WSS because of RV-to-LV flow shunt and high flow rate through the over-riding aorta. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Blood flow forces are thought to cause congenital heart malformations and influence disease progression. We performed novel investigations of intracardiac fluid mechanics of tetralogy of Fallot (TOF) human fetal hearts and found essential differences from normal hearts. The TOF right ventricle (RV) and left ventricle had similar and elevated pressure but only the TOF RV had elevated wall shear stress because of elevated tricuspid inflow, and this may contribute to the observed RV thickening. TOF hearts also expended more energy for ejection. <\/jats:p>","DOI":"10.1152\/ajpheart.00235.2018","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T15:22:38Z","timestamp":1536938558000},"page":"H1649-H1659","source":"Crossref","is-referenced-by-count":34,"title":["Human fetal hearts with tetralogy of Fallot have altered fluid dynamics and forces"],"prefix":"10.1152","volume":"315","author":[{"given":"Hadi","family":"Wiputra","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Kit","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 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