Editing Tetralogy of Fallot (section)

== Pathophysiology ==
[[File:Tetralogy of fallot video.webm|thumb|Video explanation]]
In healthy individuals, the human heart develops around the 20th day of gestation, when the outer endocardial tubes merge into a single cardiac tube. Thereafter, the cardiac tube begins to fold, developing into the atrium and ventricle. The right ventricle is dominant prior to birth, receiving 65% of the venous return to the heart, and is the main contributor of blood flow to the lower part of the body, the placenta, and the lungs. Though the exact cause of TOF is unknown, an association that has been observed is an anterior deviation of the infundibular septum that results in a misaligned VSD, with an overriding aorta causing a subsequent right ventricular obstruction.<ref name="Diaz-Frias_2021" />

Different factors such as pulmonary stenosis can also contribute with the right ventricular outflow obstruction. During tet spells, a decrease in systemic vascular resistance or an increase in pulmonary resistance would be physiologically observed.

The main anatomic defect in TOF is the anterior deviation of the pulmonary outflow septum.<ref name="Curr2016" /> This defect results in narrowing of the right ventricular outflow tract (RVOT), override of the aorta, and a VSD.<ref>{{Cite book |title=Harrison's principles of internal medicine | vauthors = Jameson JL, Kasper DL, Fauci AS, Hauser SL, Longo DL, Loscalzo J |isbn=9781259644047|edition=20th |location=New York|oclc=990065894|date=2018 }}{{page?|date=October 2024}}</ref>

=== Four malformations ===
"[[Tetralogy]]" denotes four parts, here implying the syndrome's four anatomic defects.<ref name="NIH2011Sym" /> This is not to be confused with the similarly named [[teratology]], a field of medicine concerned with abnormal development and congenital malformations (including tetralogy of Fallot). Below are the four [[heart]] malformations that present together in tetralogy of Fallot:

[[Image:Heart tetralogy fallot.svg|thumb|Heart with tetralogy of fallot A: Pulmonary stenosis; B: Overriding aorta; C: Ventricular septal defect (VSD); D: Right ventricular hypertrophy]]
[[Image:Heart normal.svg|thumb|Normal heart]]
{| class="wikitable"
|-
! Condition
! Description
|-
| [[Pulmonary stenosis|Pulmonary Infundibular Stenosis]]
| A narrowing of the right ventricular outflow tract. It can occur at the [[pulmonary valve]] (valvular stenosis) or just below the [[heart|pulmonary valve]] (infundibular stenosis).<ref name="NIH2011What" /> Infundibular pulmonic stenosis is mostly caused by the overgrowth of the heart muscle wall (hypertrophy of the septoparietal trabeculae),<ref name=gatzoulis/> however, the events leading to the formation of the overriding aorta are also believed to be a cause. The pulmonic stenosis is the major cause of the malformations, with the other associated malformations acting as compensatory mechanisms to the pulmonic stenosis.<ref>{{cite journal | vauthors = Bartelings MM, Gittenberger-de Groot AC | title = Morphogenetic considerations on congenital malformations of the outflow tract. Part 1: Common arterial trunk and tetralogy of Fallot | journal = International Journal of Cardiology | volume = 32 | issue = 2 | pages = 213–230 | date = August 1991 | pmid = 1917172 | doi = 10.1016/0167-5273(91)90329-N }}</ref> The degree of stenosis varies between individuals with TOF and is the primary determinant of symptoms and severity. This malformation is infrequently described as ''sub-pulmonary stenosis'' or ''subpulmonary obstruction''.<ref>{{cite journal | vauthors = Anderson RH, Weinberg PM | title = The clinical anatomy of tetralogy of fallot | journal = Cardiology in the Young | volume = 15 | issue = Suppl 1 | pages = 38–47 | date = February 2005 | pmid = 15934690 | doi = 10.1017/s1047951105001010 | s2cid = 31250764 }}</ref>
|-
| [[Overriding aorta]]
| An [[aortic valve]] with biventricular connection, that is, it is situated above the ventricular septal defect and connected to both the right and the left ventricle. The degree to which the aorta is attached to the right ventricle is referred to as its degree of "override." The aortic root can be displaced toward the front (anteriorly) or directly above the septal defect, but it is always abnormally located to the right of the root of the pulmonary artery. The degree of override is extremely variable, with 5–95% of the valve being connected to the right ventricle.<ref name=gatzoulis/>
|-
| [[Ventricular septal defect]] (VSD)
| A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum (the outlet septum), and in the majority of cases is single and large. In some cases, thickening of the septum (septal hypertrophy) can narrow the margins of the defect.<ref name=gatzoulis>Gatzoulis MA, Webb GD, Daubeney PE. (2005) ''Diagnosis and Management of Adult Congenital Heart Disease''. Churchill Livingstone, Philadelphia. {{ISBN|0-443-07103-9}}. {{page?|date=October 2024}}</ref>
|-
| [[Right ventricular hypertrophy]]
| The [[right ventricle]] is more muscular than normal, causing a characteristic boot-shaped ([[coeur-en-sabot]]) appearance as seen by chest X-ray. Due to the misarrangement of the external ventricular septum, the right ventricular wall increases in size to deal with the increased obstruction to the right outflow tract. This feature is now generally agreed to be a secondary anomaly, as the level of hypertrophy tends to increase with age.<ref>{{cite journal | vauthors = Anderson RH, Tynan M | title = Tetralogy of Fallot – a centennial review | journal = International Journal of Cardiology | volume = 21 | issue = 3 | pages = 219–232 | date = December 1988 | pmid = 3068155 | doi = 10.1016/0167-5273(88)90100-3 }}</ref>
|}

[[File:PLC Fallots tetralogy.jpg|thumb|Fallot's tetralogy specimen, from the UCT Pathology Learning Centre]]

There is anatomic variation between the hearts of individuals with tetralogy of Fallot.<ref name="Curr2016" /> Primarily, the degree of right ventricular outflow tract obstruction varies between patients and generally determines clinical symptoms and disease progression.<ref name="Curr2016" />

Presumably, this arises from an unequal growth of the [[aorticopulmonary septum]] (aka pulmonary outflow septum).<ref name="Munoz_2010" />{{rp|199}} The aorta is too large, thus "overriding," and this "steals" from the pulmonary artery, which is therefore stenosed. This then prevents ventricular wall closure, therefore VSD, and this increases the pressures on the right side, and so the R ventricle becomes bigger to handle the work.<ref name="Munoz_2010" />{{rp|199}}

=== Additional anomalies ===

In addition, tetralogy of Fallot may present with other anatomical anomalies, including:<ref name="Francois_2016"/>{{rp|66–68}}<ref>{{cite journal | vauthors = Hennein HA, Mosca RS, Urcelay G, Crowley DC, Bove EL | title = Intermediate results after complete repair of tetralogy of Fallot in neonates | journal = The Journal of Thoracic and Cardiovascular Surgery | volume = 109 | issue = 2 | pages = 332–342, 344; discussion 342–343 | date = February 1995 | pmid = 7531798 | doi = 10.1016/S0022-5223(95)70395-0 | doi-access = free }}</ref>
* stenosis of the [[left pulmonary artery]], in 40%
* a [[bicuspid pulmonary valve]], in 60%
* [[right-sided aortic arch]], in 25%
* [[coronary artery]] anomalies, in 10%
* a patent [[Foramen ovale (heart)|foramen ovale]] or [[atrial septal defect]], in which case the syndrome is sometimes called a pentalogy of Fallot<ref name="pmid7787464">{{cite journal | vauthors = Cheng TO | title = Pentalogy of Cantrell vs pentalogy of Fallot | journal = Texas Heart Institute Journal | volume = 22 | issue = 1 | pages = 111–112 | year = 1995 | pmid = 7787464 | pmc = 325224 }}</ref>
* an [[atrioventricular septal defect]]
* partially or totally [[anomalous pulmonary venous return]]

Tetralogy of Fallot with [[pulmonary atresia]] (''pseudotruncus arteriosus'') is a severe variant<ref name="pmid19079949">{{cite journal | vauthors = Farouk A, Zahka K, Siwik E, Erenberg F, Al-Khatib Y, Golden A, Karimi M, Uddin M, Hennein HA | display-authors = 6 | title = Individualized approach to the surgical treatment of tetralogy of Fallot with pulmonary atresia | journal = Cardiology in the Young | volume = 19 | issue = 1 | pages = 76–85 | date = February 2009 | pmid = 19079949 | doi = 10.1017/S1047951108003430 | doi-broken-date = 2024-11-14 | s2cid = 2529238 }}</ref> in which there is complete obstruction (atresia) of the right ventricular outflow tract, causing an absence of the pulmonary trunk during embryonic development.<ref name="Francois_2016"/>{{rp|67–68}} In these individuals, blood shunts completely from the right ventricle to the left where it is pumped only through the aorta. The lungs are perfused via extensive collaterals from the systemic arteries, and sometimes also via the ductus arteriosus.<ref name="Francois_2016"/>{{rp|67–68}}