Wrodzone wady serca – Patofizjologia i mechanizm

Wrodzone wady serca
Patofizjologia i mechanizm

Wrodzone wady serca (CHD) stanowią około 1% żywych urodzeń (8-10/1000) i są główną przyczyną śmiertelności niemowląt z wadami wrodzonymi. Powstają w wyniku zaburzeń rozwojowych serca w pierwszych 8 tygodniach ciąży, obejmujących mutacje w około 400 genach (np. NKX2.5, GATA4, TBX5), aberracje chromosomowe (trisomie 21, 18, 13, monosomia X) oraz mikrodelecje (np. 22q11.2). Etiologia jest wieloczynnikowa, z udziałem czynników genetycznych (15-20% przypadków) i środowiskowych, takich jak cukrzyca matczyna, infekcje wirusowe (różyczka), teratogeny (walproinian, izotretynoina, lit), alkohol, nikotyna i ekspozycja na rozpuszczalniki organiczne. Wady serca klasyfikuje się na przeciekowe lewo-prawe (np. ASD, VSD, PDA), prawo-lewe (np. tetralogia Fallota, TGA) oraz obstrukcyjne (koarktacja aorty), które prowadzą do różnorodnych zaburzeń hemodynamicznych, przeciążenia objętościowego lub ciśnieniowego, nadciśnienia płucnego i niewydolności serca.

Wrodzone wady serca – patogeneza i mechanizm

Wrodzone wady serca (ang. Congenital Heart Defects, CHD) są najczęstszym typem wad wrodzonych, występującym u około 1% żywych urodzeń (8-10 przypadków na 1000 żywych urodzeń), co czyni je główną przyczyną śmiertelności niemowląt spośród wszystkich wad wrodzonych¹². Są to strukturalne nieprawidłowości serca lub dużych naczyń krwionośnych obecne przy urodzeniu, powstałe w wyniku zaburzeń rozwoju serca w życiu płodowym³⁴.

Rozwój serca w życiu płodowym

Wrodzone wady serca rozwijają się we wczesnych tygodniach ciąży, gdy serce przechodzi od prostej struktury rurowej do w pełni ukształtowanego narządu. Proces ten rozpoczyna się około 22 dni po zapłodnieniu, a większość istotnych wad serca formuje się w pierwszych 8 tygodniach rozwoju płodu, często jeszcze przed tym, jak matka dowiaduje się o ciąży⁵⁶. W tym kluczowym okresie poszczególne etapy rozwoju serca muszą następować w określonej kolejności i czasie. Gdy któryś z etapów nie zachodzi prawidłowo lub następuje w niewłaściwym momencie, może dojść do powstania wady serca⁷.

Przypadkowe zaburzenie rozwoju serca może powodować różne nieprawidłowości strukturalne, takie jak ubytki przegrody, nieprawidłowe połączenia naczyń, zmiany w zastawkach lub nieprawidłowy rozwój komór serca⁸. Serce rozwija się w złożonej sekwencji zdarzeń obejmujących wzrost komórek, migrację komórek i zaprogramowaną śmierć komórek (apoptozę), które są regulowane przez liczne geny⁹.

Etiologia wrodzonych wad serca

Mimo postępów w medycynie, dokładna etiologia wrodzonych wad serca pozostaje w wielu przypadkach nieznana. Uważa się, że około 15-20% wszystkich wrodzonych wad serca jest związanych ze znanymi schorzeniami genetycznymi, podczas gdy w pozostałych 80-85% przypadków przyczyna pozostaje nieustalona¹⁰¹¹. Większość wrodzonych wad serca wynika najprawdopodobniej z połączenia czynników genetycznych i środowiskowych¹².

Czynniki genetyczne

Czynniki genetyczne odgrywają istotną rolę w patogenezie wrodzonych wad serca¹³:

Mutacje genowe – zidentyfikowano około 400 genów związanych z patogenezą wrodzonych wad serca. Około 10-30% strukturalnych wad serca wynika z mutacji genetycznych¹⁴. Mutacje genów kodujących czynniki transkrypcyjne serca (np. NKX2.5, GATA4, TBX5) czy geny dla receptorów i ligandów odpowiedzialnych za szlaki sygnałowe rozwoju serca (np. Notch i Jagged) mogą prowadzić do powstania wad serca¹⁵.
Zaburzenia chromosomowe – wrodzone wady serca często występują w skojarzeniu z zespołami chromosomowymi takimi jak zespół Downa (trisomia 21), zespół Edwardsa (trisomia 18), zespół Patau (trisomia 13) czy zespół Turnera (monosomia X)¹⁶. U około 50% dzieci z zespołem Downa występują wrodzone wady serca, najczęściej w postaci ubytków przegrody¹⁷.
Mikrodelecje i mikroduplikacje chromosomowe – zmiany w liczbie kopii genów (CNV) w określonych regionach chromosomów mogą powodować wady serca. Przykładem jest zespół delecji 22q11.2 (zespół DiGeorge’a)¹⁸.
Dziedziczenie rodzinne – stwierdzono, że niektóre typy wrodzonych wad serca mają tendencję do występowania rodzinnego. Ryzyko wystąpienia wady serca u dziecka jest 3-krotnie wyższe, jeśli jedno z rodziców lub rodzeństwo ma wrodzoną wadę serca¹⁹.

Czynniki środowiskowe

Wśród czynników środowiskowych, które mogą przyczyniać się do rozwoju wrodzonych wad serca, wymienia się²⁰²¹:

Choroby matki – cukrzyca przedciążowa lub rozwinięta w pierwszym trymestrze ciąży, fenyloketonuria matczyna, toczeń rumieniowaty układowy czy otyłość mogą zwiększać ryzyko wystąpienia wad serca u płodu²².
Infekcje wirusowe – zakażenie różyczką podczas ciąży może powodować wady serca u płodu. Także inne infekcje wirusowe i gorączkowe mogą zwiększać ryzyko²³.
Leki i substancje chemiczne – niektóre leki przyjmowane w czasie ciąży, takie jak leki przeciwpadaczkowe (zwłaszcza zawierające walproinian), izotretynoina (lek na trądzik), lit (stosowany w leczeniu depresji) mogą zwiększać ryzyko wad serca²⁴.
Alkohol i nikotyna – spożywanie alkoholu i palenie tytoniu w czasie ciąży może prowadzić do wad serca u płodu²⁵.
Narażenie na rozpuszczalniki organiczne – kobiety narażone na działanie niektórych rozpuszczalników organicznych mogą być bardziej narażone na urodzenie dziecka z wrodzoną wadą serca²⁶.

Mechanizmy patofizjologiczne wrodzonych wad serca

Konsekwencje fizjologiczne wrodzonych wad serca są różnorodne i zależą od typu oraz nasilenia wady. Mogą one prowadzić do zaburzeń hemodynamicznych o różnym nasileniu – od ledwo wykrywalnego szmeru serca u bezobjawowego dziecka, do ciężkiej sinicy, niewydolności serca lub zapaści krążeniowej^1″>27.

Główne mechanizmy patofizjologiczne

Wrodzone wady serca można sklasyfikować na podstawie ich wpływu na przepływ krwi w następujący sposób²⁸²⁹:

Przeciekowe wady serca z przepływem lewo-prawym – powodujące zwiększony przepływ krwi przez płuca. W tych wadach natlenowana krew z lewej części serca jest kierowana z powrotem do płuc (zamiast do krążenia systemowego), co stwarza redundancję w krążeniu i powoduje przeciążenie objętościowe lewej komory oraz zwiększone ciśnienie w płucach³⁰.
Przeciekowe wady serca z przepływem prawo-lewym – powodujące zmniejszony przepływ krwi przez płuca i sinicę. W tych wadach krew uboga w tlen jest kierowana bezpośrednio do krążenia systemowego z pominięciem płuc, co prowadzi do niedotlenienia organizmu³¹.
Wady powodujące zwężenie lub niedrożność – ograniczające przepływ krwi przez serce lub naczynia. Wywołują one gradient ciśnienia, który zwiększa obciążenie następcze i może prowadzić do przerostu komór³².
Złożone wady serca – obejmujące kombinacje powyższych mechanizmów³³.

Patofizjologia najczęstszych wad serca

Wśród najczęstszych wrodzonych wad serca, ich patofizjologia prezentuje się następująco:

Ubytek przegrody międzyprzedsionkowej (ASD) – powoduje przeciek lewo-prawy na poziomie przedsionków, prowadząc do poszerzenia prawego przedsionka i prawej komory, ze zwiększonym powrotem żylnym do lewego przedsionka³⁴.
Ubytek przegrody międzykomorowej (VSD) – powoduje przeciek lewo-prawy na poziomie komór, gdzie krew z lewej komory jest wyrzucana w czasie skurczu do prawej komory i dalej do krążenia płucnego, co powoduje przeciążenie objętościowe lewego przedsionka i lewej komory³⁵. Konsekwencje hemodynamiczne zależą od wielkości ubytku oraz stosunku oporu naczyniowego płucnego do systemowego³⁶:
- Duży, nierestrykcyjny VSD powoduje wyrównanie ciśnień między komorami, znaczny przeciek lewo-prawy, przeciążenie objętościowe lewej komory i nadciśnienie płucne³⁷.
- Mały, restrykcyjny VSD zachowuje gradient ciśnień między komorami, a przeciek jest ograniczony³⁸.
Przetrwały przewód tętniczy (PDA) – powoduje przeciek lewo-prawy z aorty do tętnicy płucnej podczas skurczu i rozkurczu, zwiększając przepływ płucny i prowadząc do przeciążenia objętościowego lewej części serca³⁹⁴⁰.
Tetralogia Fallota – klasyczny przykład wady siniczej charakteryzujący się czterema nieprawidłowościami: ubytkiem przegrody międzykomorowej, zwężeniem drogi odpływu prawej komory, dekstropozycją aorty i przerostem prawej komory. Z powodu zwężenia drogi odpływu prawej komory, krew przepływa przez VSD z prawej do lewej komory, tworząc przeciek prawo-lewy, omijając krążenie płucne i powodując sinicę⁴¹⁴².
Przełożenie wielkich pni tętniczych (TGA) – charakteryzuje się nieprawidłowym połączeniem komór z naczyniami – prawa komora jest połączona z aortą, a lewa komora z tętnicą płucną. To tworzy dwa równoległe krążenia zamiast szeregowego, co skutkuje sinicą i potencjalnie niewydolnością serca⁴³.
Koarktacja aorty – zwężenie aorty, które zwiększa obciążenie następcze lewej komory i może prowadzić do przerostu lewej komory oraz niewydolności serca⁴⁴.

Mechanizmy molekularne i epigenetyczne

Coraz więcej dowodów wskazuje na znaczenie mechanizmów epigenetycznych w patogenezie wrodzonych wad serca⁴⁵. Mechanizmy te obejmują:

Metylację DNA – zmiana wzorców metylacji DNA może wpływać na ekspresję genów regulujących rozwój serca⁴⁶.
Modyfikacje histonów – zmiany w metylacji histonów mogą zaburzać prawidłową ekspresję genów w rozwijającym się sercu. Badania wykazały, że mutacje de novo w genach zaangażowanych w metylację histonów występują częściej u dzieci z wrodzonymi wadami serca⁴⁷.
Niekodujące RNA – mikroRNA i długie niekodujące RNA regulują ekspresję genów podczas rozwoju serca, a ich zaburzenia mogą prowadzić do wad serca⁴⁸.

Badania genomu wykazały, że dzieci z wrodzonymi wadami serca mają 7,5 razy większe prawdopodobieństwo wystąpienia uszkadzających mutacji de novo w genach ekspresjonowanych w rozwijającym się sercu niż zdrowe dzieci. Takie mutacje mogą przyczyniać się do ponad 10% wszystkich przypadków wrodzonych wad serca⁴⁹.

Krwioobieg płodowy a wrodzone wady serca

W krwiobiegu płodowym wymiana gazowa odbywa się w łożysku. Natlenowana krew z łożyska przepływa przez żyłę pępowinową do żyły głównej dolnej przez przewód żylny (ductus venosus), omijając krążenie wątrobowe. W sercu, większość natlenowanej krwi jest kierowana z prawego przedsionka do lewego przedsionka przez otwór owalny (foramen ovale). Z lewego przedsionka krew jest pompowana do lewej komory i do aorty, aby dotrzeć do krążenia systemowego. Mała część krwi jest pompowana z prawego przedsionka do prawej komory i tętnicy płucnej. Z tętnicy płucnej krew jest kierowana do aorty przez przewód tętniczy (ductus arteriosus), omijając płuca⁵⁰.

Wrodzone wady serca mogą zaburzać ten delikatny układ. W życiu płodowym wiele wad serca nie powoduje objawów, ponieważ płód otrzymuje natlenowaną krew z łożyska, a otwór owalny (FO) lub przewód tętniczy (DA) mogą zwiększać przepływ krwi systemowej. Po zamknięciu się tych struktur wkrótce po urodzeniu, większość wrodzonych wad serca staje się objawowa⁵¹.

Niektóre wrodzone wady serca (np. hipoplazja lewego serca, krytyczne zwężenie zastawki aortalnej, koarktacja aorty) są zależne od utrzymania drożności przewodu tętniczego dla zapewnienia przepływu krwi systemowej. Inne (np. atrrezja płucna czy ciężka tetralogia Fallota) wymagają drożności przewodu dla zapewnienia przepływu płucnego⁵².

Procesy adaptacyjne i komplikacje

W odpowiedzi na zaburzenia hemodynamiczne spowodowane wrodzonymi wadami serca, organizm uruchamia mechanizmy adaptacyjne, które z czasem mogą prowadzić do dalszych komplikacji⁵³:

Przerost i przebudowa mięśnia sercowego – w odpowiedzi na przeciążenie objętościowe lub ciśnieniowe dochodzi do przerostu i remodelingu komór serca⁵⁴.
Rozwój nadciśnienia płucnego – długotrwały zwiększony przepływ przez płuca prowadzi do uszkodzenia naczyń płucnych, hiperplazji ścian naczyń i nadciśnienia płucnego. Z czasem może rozwinąć się nieodwracalna choroba naczyń płucnych i zespół Eisenmengera, w którym kierunek przecieku zmienia się z lewo-prawego na prawo-lewy⁵⁵⁵⁶.
Niewydolność serca – przeciążenie objętościowe lub ciśnieniowe może prowadzić do niewydolności serca, szczególnie w przypadku dużych przecieków lewo-prawych lub wad obstrukcyjnych⁵⁷.
Zaburzenia rytmu serca – mogą wynikać z nieprawidłowości strukturalnych serca lub być następstwem przerostu i przebudowy mięśnia sercowego⁵⁸.
Infekcyjne zapalenie wsierdzia – dzieci z wrodzonymi wadami serca są bardziej narażone na rozwój infekcyjnego zapalenia wsierdzia, szczególnie po zabiegach kardiochirurgicznych⁵⁹.
Powikłania neurologiczne – wrodzone wady serca mogą prowadzić do zaburzeń rozwoju neurologicznego poprzez różne mechanizmy, w tym nieprawidłowości hemodynamiczne w okresie płodowym, niedotlenienie lub udar⁶⁰.

W przypadku dzieci z ciężkimi wrodzonymi wadami serca stwierdzono także zaburzenia immunologiczne. Obserwuje się u nich zmniejszoną liczbę i dojrzałość komórek immunologicznych, co zwiększa podatność na powikłania infekcyjne. Rolę w tym procesie może odgrywać zarówno sama wada, jak i następująca po niej odpowiedź zapalna⁶¹⁶².

Najnowsze badania wskazują również na związek między niewydolnością serca u niemowląt z wrodzonymi wadami serca a zapaleniem jelit spowodowanym zaburzeniami mikrobioty jelitowej. U takich dzieci obserwuje się zmniejszoną różnorodność mikrobioty jelitowej, zwiększoną liczebność bakterii chorobotwórczych i zmniejszoną liczebność bakterii korzystnych. Prowadzi to do nasilenia reakcji zapalnej jelit i wzrostu poziomu czynników prozapalnych, co może być związane z progresją niewydolności serca⁶³⁶⁴.

Patofizjologia wrodzonych wad serca a rozwój mózgu

Coraz więcej dowodów wskazuje na ścisły związek między wrodzonymi wadami serca a zaburzeniami rozwoju mózgu⁶⁵. Związek ten może wynikać z kilku mechanizmów:

Wspólne szlaki rozwojowe – serce i mózg rozwijają się jednocześnie w życiu płodowym, dzieląc wspólne szlaki genetyczne. Dlatego nieprawidłowy rozwój serca może wpływać na rozwój neurologiczny poprzez te wspólne szlaki⁶⁶.
Zaburzenia hemodynamiczne wewnątrzmaciczne – płody z wrodzonymi wadami serca doświadczają nieprawidłowych zmian hemodynamicznych, które prowadzą do zmian w krążeniu mózgowym. Przeciek krwi w wadach serca prowadzi do znacznego zmniejszenia przepływu krwi w głównych naczyniach mózgowych, co może upośledzać rozwój mózgu⁶⁷⁶⁸.
Nieprawidłowości strukturalne mózgu – badania rezonansem magnetycznym u noworodków z wrodzonymi wadami serca wykazały zmniejszoną objętość mózgu w stosunku do wieku ciążowego, zmniejszony metabolizm oraz opóźnione fałdowanie i rozwój kory mózgowej w porównaniu do zdrowych noworodków⁶⁹.
Uszkodzenie prekursorów oligodendrocytów i neuronów podpłytowych – u niemowląt z wrodzonymi wadami serca prowadzi do upośledzenia procesu mielinizacji i rozwoju szlaków istoty białej, potencjalnie wpływając na łączność neuronalną⁷⁰.

Te zmiany strukturalne mózgu mogą przyczyniać się do zwiększonego ryzyka zaburzeń neurorozwojowych, w tym zaburzeń ze spektrum autyzmu (ASD) u dzieci z wrodzonymi wadami serca⁷¹.

Podsumowanie patogenezy wrodzonych wad serca

Patogeneza wrodzonych wad serca jest złożona i wieloczynnikowa. Obejmuje zarówno czynniki genetyczne, jak i środowiskowe, które zaburzają prawidłowy rozwój serca w okresie życia płodowego. Nieprawidłowości strukturalne serca prowadzą do zaburzeń hemodynamicznych, które wywołują kaskadę procesów adaptacyjnych i patofizjologicznych, wpływających nie tylko na układ sercowo-naczyniowy, ale również na rozwój innych układów, szczególnie układu nerwowego i immunologicznego. Zrozumienie tych złożonych mechanizmów jest kluczowe dla opracowania skutecznych metod profilaktyki, wczesnej diagnostyki i leczenia wrodzonych wad serca⁷²⁷³.

Pomimo znacznych postępów w zrozumieniu i leczeniu wrodzonych wad serca, dokładne mechanizmy leżące u podstaw ich rozwoju pozostają nie w pełni wyjaśnione. Potrzebne są dalsze badania, szczególnie w zakresie interakcji między genami a środowiskiem oraz roli mechanizmów epigenetycznych, aby lepiej zrozumieć patogenezę wrodzonych wad serca i opracować nowe strategie terapeutyczne⁷⁴⁷⁵.

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Materiały źródłowe

#1 Overview of Congenital Cardiovascular Anomalies – Pediatrics – Merck Manual Professional Edition
https://www.merckmanuals.com/en-ca/professional/pediatrics/congenital-cardiovascular-anomalies/overview-of-congenital-cardiovascular-anomalies
Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births. Among birth defects, congenital heart disease is the leading cause of infant mortality. […] Environmental and genetic factors contribute to the development of congenital heart disease. […] Certain numerical chromosomal abnormalities (aneuploidies), such as trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and monosomy X (Turner syndrome), are strongly associated with congenital heart disease. […] Many other cases involve subchromosomal deletions (microdeletions), subchromosomal duplications, or single-gene mutations. […] No identifiable genetic etiology is detected in about 72% of patients with congenital heart disease. […] The physiologic consequences of congenital heart anomalies vary greatly, ranging from a heart murmur or discrepancy in pulses in an asymptomatic child to severe cyanosis, heart failure, or circulatory collapse.
#2 Pathophysiology, etiology, and recent advancement in the treatment of congenital heart disease – Document – Gale Academic OneFile
https://go.gale.com/ps/i.do?id=GALE%7CA600526469&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=15618811&p=AONE&sw=w
The most common birth anomaly occurring in infants is the congenital heart disease (CHD). It is the important cause of mortality and morbidity among children. […] Congenital heart disease (CHD) is major congenital anomalies, which consists of heart defects present from the birth. CHD among all birth defects is the main cause of death in infancy. It is the structural abnormality of heart or great vessels, detected either at the time of birth or later in life. […] Globally, CHD constitutes the major cause of mortality among children, especially in developing countries. It also accounts for more than 20% of infant’s death prenatally. The prevalence rate of CHD is estimated to be 8/1000 live births. […] The congenital heart defects can be life-threatening during early childhood, and infants born with this disorder are at much higher risk of mortality especially in the 1st year of life. Newborns with congenital heart disorders are symptomatic and soon identified after birth and some cases of CHD remains undiagnosed until or unless the disease progresses to a severe stage. The severity and type of diseases depend on the signs and symptoms. High morbidity and mortality rate is associated with critical cardiac lesions in infants and the risk increases as diagnosis and treatment gets delayed. Therefore, the screening process is very important tool in diagnosing CHD.
#3 Congenital heart defects in children – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-heart-defects-children/symptoms-causes/syc-20350074
A congenital heart defect is a problem with the structure of the heart that a child is born with. […] Congenital heart disease, also called a defect, refers to one or more problems with the heart structure that are present at birth. These abnormalities occur when the heart or blood vessels don’t form correctly in utero. […] Congenital heart disease can involve abnormalities in any of these structures, including the arteries, valves, chambers or the wall separating the chambers of the heart. These defects, depending on the severity and type, can affect the proper flow of blood and oxygen to the lungs and the body. […] It’s at this point in a baby’s development that congenital heart defects may begin to develop. Researchers aren’t sure what causes most types of congenital heart defects. They think that gene changes, certain medicines or health conditions, and environmental or lifestyle factors, such as smoking, may play a role.
#4 Congenital Heart Defects (CHDs) | Boston Children’s Hospital
https://www.childrenshospital.org/conditions/congenital-heart-defects
A congenital heart defect (CHD) is a structural problem of the heart that develops during pregnancy. About one out of 100 babies is born with a congenital heart defect. There are many types of congenital heart defects, ranging from simple to complex. Most are diagnosed and treated early in infancy. […] Many congenital heart diseases in babies have a genetic cause. Some known associations include: Chromosome abnormalities, such as Down syndrome, trisomy 18 and trisomy 13, and Turner syndrome; Microdeletion or microduplication syndromes, such as DiGeorge syndrome; Single gene defects; Environmental factors. […] Treatment is based on the specific type of congenital heart defect your child has and the severity of the defect. Some mild heart defects don’t need any treatment. Others can be treated with medications, interventional procedures, or surgery.
#5
#6
https://www.nhs.uk/conditions/congenital-heart-disease/causes/
Congenital heart disease is caused when something disrupts the normal development of the heart. […] It’s thought that most cases occur when something affects the heart’s development during the first 6 weeks of pregnancy. This is when the heart is developing from a simple tube-like structure into a shape more like a fully formed heart. […] While some things are known to increase the risk of congenital heart disease, no obvious cause is identified in most cases. […] Several genetic health conditions that a baby inherits from 1 or both parents can cause congenital heart disease. […] It’s also recognised that certain types of congenital heart disease run in families. […] Down’s syndrome is the most widely-known genetic condition that can cause congenital heart disease. […] About half of all children with Down’s syndrome have congenital heart disease. In many cases, this is a type of septal defect.
#7 Congenital Heart Disease – Stanford Medicine Children’s Health
https://www.stanfordchildrens.org/en/topic/default?id=congenital-heart-disease-90-P02346
According to the American Heart Association, about 9 of every 1,000 babies born in the U.S. have a congenital heart defect. This is a problem that occurs as the baby’s heart is developing during pregnancy, before the baby is born. Congenital heart defects are the most common birth defects. […] Congenital heart defects happen during this important first 8 weeks of the baby’s development. Specific steps must take place for the heart to form correctly. Often, congenital heart defects are a result of one of these steps not happening at the right time. […] Most congenital heart defects have no known cause. […] Some heart problems do occur more often in families, so there may be a genetic link to some heart defects. […] Congenital heart problems range from simple to complex. […] A baby may even „grow out” of some of the simpler heart problems, such as patent ductus arteriosus or atrial septal defect.
#8 Congenital heart defect – Wikipedia
https://en.wikipedia.org/wiki/Congenital_heart_defect
The genes regulating the complex developmental sequence have only been partly elucidated. Some genes are associated with specific defects. A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, -myosin heavy chain (MYH6) are associated with atrial septal defects. […] There is a complex sequence of events that result in a well formed heart at birth and disruption of any portion may result in a defect. The orderly timing of cell growth, cell migration, and programmed cell death („apoptosis”) has been studied extensively and the genes that control the process are being elucidated. […] The ductus arteriosus stays open because of circulating factors including prostaglandins. The foramen ovale stays open because of the flow of blood from the right atrium to the left atrium. As the lungs expand, blood flows easily through the lungs and the membranous portion of the foramen ovale (the septum primum) flops over the muscular portion (the septum secundum). If the closure is incomplete, the result is a patent foramen ovale.
#9 Congenital heart defect – Wikipedia
https://en.wikipedia.org/wiki/Congenital_heart_defect
The genes regulating the complex developmental sequence have only been partly elucidated. Some genes are associated with specific defects. A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, -myosin heavy chain (MYH6) are associated with atrial septal defects. […] There is a complex sequence of events that result in a well formed heart at birth and disruption of any portion may result in a defect. The orderly timing of cell growth, cell migration, and programmed cell death („apoptosis”) has been studied extensively and the genes that control the process are being elucidated. […] The ductus arteriosus stays open because of circulating factors including prostaglandins. The foramen ovale stays open because of the flow of blood from the right atrium to the left atrium. As the lungs expand, blood flows easily through the lungs and the membranous portion of the foramen ovale (the septum primum) flops over the muscular portion (the septum secundum). If the closure is incomplete, the result is a patent foramen ovale.
#10 Children’s Heart | About CHDs | Congenital Heart Defects
https://www.childrensheartfoundation.org/about-chds/chd-facts.html
Congenital heart defects (CHDs) are problems present at birth that affect the structure and function of the heart. […] Common examples include holes in the inside walls of the heart and narrowed or leaky valves. In more severe forms of CHDs, blood vessels or heart chambers may be missing, poorly formed, and/or in the wrong place. […] Most causes of CHDs are unknown. Only 15-20% of all CHDs are related to known genetic conditions. […] Most CHDs are thought to be caused by a combination of genes and other risk factors, such as environmental exposures and maternal conditions. […] Environmental exposures that may be related to risk of having a CHD include the mothers diet and certain chemicals and medications. Maternal diabetes is a recognized cause of CHDs. […] A babys risk of having a CHD is increased by 3 times if the mother, father, or sibling has a CHD.
#11 Congenital Heart Disease | Causes, Types & Treatment
https://www.cincinnatichildrens.org/health/c/congenital-heart-disease
One out of every 100 infants born in the United States has a congenital (present at birth) heart defect. Heart defects occur as the babys heart is developing during pregnancy before the baby is born. Congenital heart defects are the most common birth defect. […] Congenital heart defects happen during these first eight weeks of the babys development. […] Congenital heart defects are a result of crucial development steps not occurring at the right time, or in the correct order. This means the child may be born with a single blood vessel where two vessels should be. Or there may be a hole between two heart chambers that should be separated. […] Some congenital heart defects occur if the mother had a certain disease while pregnant (like rubella) or was taking certain medicines (like anti-seizure medicines).
#12 Congenital heart disease: types, pathophysiology, diagnosis, and treatment options
https://pmc.ncbi.nlm.nih.gov/articles/PMC11224996/
Congenital heart disease (CHD) is a structural abnormality of the heart and/or great vessels and patients with CHD are at an increased risks of various morbidities throughout their lives and reduced longterm survival. […] Unfortunately, the exact etiology and pathophysiology of some CHD remain unclear. […] The etiology of CHD is complicated and the underlying pathogenesis remains unclear in approximately 50% of patients with CHD. However, several environmental and genetic factors are found to be involved in the pathogenesis of CHD. […] Approximately 400 gene abnormalities are associated with the pathogenesis of CHD and 10-30% of structural CHD cases are due to genetic mutations. […] Compared with the general population, patients with CHD have an increased risk of various morbidities throughout their lives and reduced longterm survival.
#13 Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways | Egyptian Journal of Medical Human Genetics | Full Text
https://jmhg.springeropen.com/articles/10.1186/s43042-020-0050-1
Genetic factors are postulated to play a significant role in the pathogenesis of CHDs. […] Point mutations of cardiac transcription factor genes, single nucleotide polymorphism (SNPs), aneuploidy, and chromosomal copy number variants (CNV) are directly associated with CHDs. […] Mutations in genes encoding for receptors and ligands, which are responsible for cardiac morphogenesis signaling pathways such as Notch and Jagged respectively are implicated in the etiology of CHDs. […] Several well-established cardiac transcription factors that are highly expressed in cardiogenic plates such as NKX2.5, GATA4, and TBX5 have been extensively studied in both human and animal experiments. […] The association of mutations with clinical manifestations is of paramount importance; NKX2.5 mutation associated ASD was found to present with cardiac conduction defects; thus, patients with mutation in NKX2.5 have an increased risk of cardiac arrest. […] Overall, more than 40 NKX2.5 transcription factor different mutations have been identified, causing impaired protein function and have a negative impact on transcriptional activity.
#14 Congenital heart disease: types, pathophysiology, diagnosis, and treatment options
https://pmc.ncbi.nlm.nih.gov/articles/PMC11224996/
Congenital heart disease (CHD) is a structural abnormality of the heart and/or great vessels and patients with CHD are at an increased risks of various morbidities throughout their lives and reduced longterm survival. […] Unfortunately, the exact etiology and pathophysiology of some CHD remain unclear. […] The etiology of CHD is complicated and the underlying pathogenesis remains unclear in approximately 50% of patients with CHD. However, several environmental and genetic factors are found to be involved in the pathogenesis of CHD. […] Approximately 400 gene abnormalities are associated with the pathogenesis of CHD and 10-30% of structural CHD cases are due to genetic mutations. […] Compared with the general population, patients with CHD have an increased risk of various morbidities throughout their lives and reduced longterm survival.
#15 Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways | Egyptian Journal of Medical Human Genetics | Full Text
https://jmhg.springeropen.com/articles/10.1186/s43042-020-0050-1
Genetic factors are postulated to play a significant role in the pathogenesis of CHDs. […] Point mutations of cardiac transcription factor genes, single nucleotide polymorphism (SNPs), aneuploidy, and chromosomal copy number variants (CNV) are directly associated with CHDs. […] Mutations in genes encoding for receptors and ligands, which are responsible for cardiac morphogenesis signaling pathways such as Notch and Jagged respectively are implicated in the etiology of CHDs. […] Several well-established cardiac transcription factors that are highly expressed in cardiogenic plates such as NKX2.5, GATA4, and TBX5 have been extensively studied in both human and animal experiments. […] The association of mutations with clinical manifestations is of paramount importance; NKX2.5 mutation associated ASD was found to present with cardiac conduction defects; thus, patients with mutation in NKX2.5 have an increased risk of cardiac arrest. […] Overall, more than 40 NKX2.5 transcription factor different mutations have been identified, causing impaired protein function and have a negative impact on transcriptional activity.
#16 Overview of Congenital Cardiovascular Anomalies – Pediatrics – Merck Manual Professional Edition
https://www.merckmanuals.com/en-ca/professional/pediatrics/congenital-cardiovascular-anomalies/overview-of-congenital-cardiovascular-anomalies
Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births. Among birth defects, congenital heart disease is the leading cause of infant mortality. […] Environmental and genetic factors contribute to the development of congenital heart disease. […] Certain numerical chromosomal abnormalities (aneuploidies), such as trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and monosomy X (Turner syndrome), are strongly associated with congenital heart disease. […] Many other cases involve subchromosomal deletions (microdeletions), subchromosomal duplications, or single-gene mutations. […] No identifiable genetic etiology is detected in about 72% of patients with congenital heart disease. […] The physiologic consequences of congenital heart anomalies vary greatly, ranging from a heart murmur or discrepancy in pulses in an asymptomatic child to severe cyanosis, heart failure, or circulatory collapse.
#17
https://www.nhs.uk/conditions/congenital-heart-disease/causes/
Congenital heart disease is caused when something disrupts the normal development of the heart. […] It’s thought that most cases occur when something affects the heart’s development during the first 6 weeks of pregnancy. This is when the heart is developing from a simple tube-like structure into a shape more like a fully formed heart. […] While some things are known to increase the risk of congenital heart disease, no obvious cause is identified in most cases. […] Several genetic health conditions that a baby inherits from 1 or both parents can cause congenital heart disease. […] It’s also recognised that certain types of congenital heart disease run in families. […] Down’s syndrome is the most widely-known genetic condition that can cause congenital heart disease. […] About half of all children with Down’s syndrome have congenital heart disease. In many cases, this is a type of septal defect.
#18 Congenital Heart Defects (CHDs) | Boston Children’s Hospital
https://www.childrenshospital.org/conditions/congenital-heart-defects
A congenital heart defect (CHD) is a structural problem of the heart that develops during pregnancy. About one out of 100 babies is born with a congenital heart defect. There are many types of congenital heart defects, ranging from simple to complex. Most are diagnosed and treated early in infancy. […] Many congenital heart diseases in babies have a genetic cause. Some known associations include: Chromosome abnormalities, such as Down syndrome, trisomy 18 and trisomy 13, and Turner syndrome; Microdeletion or microduplication syndromes, such as DiGeorge syndrome; Single gene defects; Environmental factors. […] Treatment is based on the specific type of congenital heart defect your child has and the severity of the defect. Some mild heart defects don’t need any treatment. Others can be treated with medications, interventional procedures, or surgery.
#19 Children’s Heart | About CHDs | Congenital Heart Defects
https://www.childrensheartfoundation.org/about-chds/chd-facts.html
Congenital heart defects (CHDs) are problems present at birth that affect the structure and function of the heart. […] Common examples include holes in the inside walls of the heart and narrowed or leaky valves. In more severe forms of CHDs, blood vessels or heart chambers may be missing, poorly formed, and/or in the wrong place. […] Most causes of CHDs are unknown. Only 15-20% of all CHDs are related to known genetic conditions. […] Most CHDs are thought to be caused by a combination of genes and other risk factors, such as environmental exposures and maternal conditions. […] Environmental exposures that may be related to risk of having a CHD include the mothers diet and certain chemicals and medications. Maternal diabetes is a recognized cause of CHDs. […] A babys risk of having a CHD is increased by 3 times if the mother, father, or sibling has a CHD.
#20 Cyanotic Heart Disease – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK500001/
Congenital heart disease (CHD) are structural abnormalities of the heart or intrathoracic great vessels occurring during fetal development. CHD is the most common type of birth defect and the leading cause of death in children with congenital malformations. CHD can be subdivided in non-cyanotic CHD and cyanotic CHD which is also called critical congenital heart disease (CCHD). CCHD can be further classified into 3 different types of lesions: right heart obstructive lesions, left heart obstructive lesions, and mixing lesions. […] The etiology of CHD is still largely unknown. Many cases of CHD are multifactorial and result from a combination of genetic predisposition and environmental risk factors. CCHD is usually isolated and sporadic, but it can also be associated with genetic syndromes. Approximately 15% to 20% of infants with CCHD are related to known chromosomal abnormalities, most of these are aneuploidies (trisomy 21, 13, and 18 and Turner syndrome). Potential environmental risk factors include maternal illnesses, including diabetes and phenylketonuria, maternal exposure to toxins or drugs and viral infections during pregnancy.
#21 Congenital Heart Defects (CHDs) | Boston Children’s Hospital
https://www.childrenshospital.org/conditions/congenital-heart-defects
A congenital heart defect (CHD) is a structural problem of the heart that develops during pregnancy. About one out of 100 babies is born with a congenital heart defect. There are many types of congenital heart defects, ranging from simple to complex. Most are diagnosed and treated early in infancy. […] Many congenital heart diseases in babies have a genetic cause. Some known associations include: Chromosome abnormalities, such as Down syndrome, trisomy 18 and trisomy 13, and Turner syndrome; Microdeletion or microduplication syndromes, such as DiGeorge syndrome; Single gene defects; Environmental factors. […] Treatment is based on the specific type of congenital heart defect your child has and the severity of the defect. Some mild heart defects don’t need any treatment. Others can be treated with medications, interventional procedures, or surgery.
#22
https://www.nhs.uk/conditions/congenital-heart-disease/causes/
Women with diabetes have a higher risk of giving birth to a baby with congenital heart disease than women who don’t have diabetes. […] The increased risk is thought to be caused by high levels of the hormone insulin in the blood, which may interfere with the normal development of a foetus. […] If a pregnant woman drinks too much alcohol during pregnancy, it can have a poisonous effect on the tissue of the foetus. […] Children with foetal alcohol spectrum disorder can have congenital heart disease, such as atrial or ventricular septal defects. […] A rubella infection can cause multiple birth defects, including congenital heart disease. […] Women who get flu during the first trimester of pregnancy are at greater risk of having a baby with congenital heart disease than the general population.
#23 Congenital heart disease | Heart and Stroke Foundation
https://www.heartandstroke.ca/heart-disease/conditions/congenital-heart-disease
Congenital heart disease is a heart condition you are born with. The word congenital means present at birth. Congenital heart disease can range from very minor conditions which never cause problems, to more serious conditions that require treatment. […] A congenital heart defect happens when the chambers, walls or valves of your heart or the blood vessels near the heart dont develop normally before birth. […] Congenital heart defects can be categorized in two ways. […] Stenosis is a narrowing or obstruction in heart valves, arteries or veins that affects the flow of blood. Atresia is when a passageway in the body is abnormally shut or has not formed properly. Different types of stenosis and atresia can partly or completely block blood flow in the heart. […] In many cases, the cause of congenital heart disease is unknown. However, known causes include: exposure of the fetus to maternal illnesses such as diabetes, German measles (rubella), fever illnesses and issues with metabolizing an amino acid during pregnancy (phenylketonuria).
#24 Congenital heart defects and critical CHDs | March of Dimes
https://www.marchofdimes.org/find-support/topics/planning-baby/congenital-heart-defects-and-critical-chds
Some babies have heart defects because of changes in their chromosomes or genes. Certain gene changes (also called mutations) are linked to heart defects. At least 15 in 100 (15 percent) of CHDs are linked to genetic or chromosomal conditions. […] Having one of these conditions may increase your risk of having a baby with a CHD: Lupus, Maternal phenylketonuria (PKU), Obesity, Preexisting diabetes, Rubella. […] Taking certain medicines may increase your baby’s risk of having a CHD. […] Some things in your life and environment (where and how you live) may increase your chances of having a baby with a CHD. These include: Drinking alcohol during pregnancy, Smoking before or during pregnancy.
#25 Congenital heart disease | Better Health Channel
https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/congenital-heart-disease
Alcohol a mother who drinks large amounts of alcohol during pregnancy may increase the risk of congenital heart disorders. […] Maternal health factors such as unmanaged diabetes and poor nutrition during pregnancy may increase the risk. […] Maternal age babies of older women are more likely to have a birth defect than babies of younger women.
#26
https://www.nhs.uk/conditions/congenital-heart-disease/causes/
There are several medicines linked to an increased risk of a baby being born with congenital heart disease. […] Pregnant mothers with PKU who don’t do this are more likely to give birth to a baby with congenital heart disease than the general population. […] Women who are exposed to some organic solvents may be more likely to give birth to a baby with congenital heart disease than the general population.
#28
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
Congenital heart disease occurs in 8 children for every 1000 liveborns. Out of these 50% are significant in the sense that they produce haemodynamic effects. This article will focus on the pathophysiology of some of the commonly encountered congenital heart defects. […] The commonest physiology that is seen in patients with congenital heart disease is left to right shunts. A physiological left to right shunt is when oxygenated blood returns back to the lungs to get re-oxygenated. This creates a redundancy in the circulation. In patients with left to right shunt, there is an increased venous return from the lungs via the pulmonary veins to the left atrium and the left ventricle (LV). This creates a volume overload on the LV. […] The physiological alterations associated with left to right shunt lesions at the ventricular or great artery level are determined principally by the size of the defect and the post-natal changes in systemic (SVR) and pulmonary (PVR) vascular resistances.
#29 Childhood Heart Conditions & CHD | Lurie Children’s
https://www.luriechildrens.org/en/specialties-conditions/congenital-heart-disease/
Congenital heart disease refers to when an issue occurs during the development of the heart and a child is then born with a heart abnormality. Some people refer to this as a heart condition. Approximately 1 in 100 babies are born with a congenital heart condition. Common congenital heart conditions are due to issues with the valves in the heart, holes in the heart which can result in abnormal blood flow to the lungs or body, or low oxygen levels sometimes referred to as a blue baby. There may also be abnormalities or weak heart muscle or an abnormal electrical system. […] Treatment is dependent on several factors including the specific diagnosis and the physiology of the patient, among others. The conditions mentioned above typically require surgery or an interventional procedure. At Lurie Childrens, our Heart Center team individualizes treatment plans based on each patients needs.
#30
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
Congenital heart disease occurs in 8 children for every 1000 liveborns. Out of these 50% are significant in the sense that they produce haemodynamic effects. This article will focus on the pathophysiology of some of the commonly encountered congenital heart defects. […] The commonest physiology that is seen in patients with congenital heart disease is left to right shunts. A physiological left to right shunt is when oxygenated blood returns back to the lungs to get re-oxygenated. This creates a redundancy in the circulation. In patients with left to right shunt, there is an increased venous return from the lungs via the pulmonary veins to the left atrium and the left ventricle (LV). This creates a volume overload on the LV. […] The physiological alterations associated with left to right shunt lesions at the ventricular or great artery level are determined principally by the size of the defect and the post-natal changes in systemic (SVR) and pulmonary (PVR) vascular resistances.
#31 Pediatric Congenital Heart Defects: A Nursing Guide
https://simplenursing.com/pediatric-nursing-congenital-heart-defects/
Ventricular septal defect â a hole in the ventricles causes blood to go to the right side of the heart, thus; increasing pressure and size. […] Patent ductus arteriosus â here, the atriums are normal, but the pulmonary aorta is problematic because a connection between the pulmonary artery and the aorta has been created. The consequence of this abnormal connection is that deoxygenated blood gets mixed with oxygenated blood and this mixture goes to the rest of the body. […] Atrial-ventricular canal â with the presence of an extra-large canal or hole, the AV canal can be categorized into atrial septal defect and ventricular septal defect. This condition is commonly seen in clients with Down Syndrome. […] With decreased pulmonary blood flow, there is decreased blood flow into the lungs. Therefore, the primary manifestation would be cyanosis or bluish discoloration of the skin.
#32 Congenital Heart Disease – Cardiovascular Pathophysiology for Pre-Clinical Students
https://pressbooks.lib.vt.edu/cardiovascularpathophysiology/chapter/chapter-6-congenital-heart-disease/
ASDs allow blood flow between the atria. As the pressure in the left atria is higher than that in the left, blood flows from left to right. This causes volume overload of the right side of the heart. This excessive load may lead to right ventricular compliance being reduced as remodeling takes place. The reduced compliance can elevate right-side pressure and thereby reduce the left-right shunt. […] The manifestations of a VSD depend on the VSD size and the relative resistance of the pulmonary and systemic circulationsâall of which will determine the direction of blood flow. […] The diminished lumen causes increased afterload on the left ventricle. […] The high resistance of the stenosed pulmonic valve causes the blood in the right ventricle to exit through VSD and enter the left ventricle forming a right-left shunt, bypassing the pulmonary circulation. Consequently, blood with venous PO2 enters the systemic circulation and hypoxemia/cyanosis results. The degree of hypoxemia/cyanosis that occurs depends on the degree of pulmonic stenosis.
#33 Congenital Heart Disease – Stanford Medicine Children’s Health
https://www.stanfordchildrens.org/en/topic/default?id=congenital-heart-disease-90-P02346
Again, in some cases there will be a mix of several heart defects. This creates a more complex problem that can fall into several of these categories. […] Some of the problems that cause too much blood to pass through the lungs include the following: Patent ductus arteriosus (PDA). […] Atrial septal defect (ASD). […] Ventricular septal defect (VSD). […] Atrioventricular canal (AVC or AV canal). […] Some of the problems that cause too little blood to pass through the lungs include the following: Tricuspid atresia. […] Pulmonary atresia. […] Transposition of the great arteries. […] Tetralogy of Fallot. […] Double outlet right ventricle (DORV). […] Truncus arteriosus. […] Some of the problems that cause too little blood to travel to the body include the following: Coarctation of the aorta (CoA).
#34
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
With transition to extra-uterine circulation there is a decrease in the PVR with a simultaneous increase in SVR. This usually happens between 2-6 weeks of life and causes manifestation of left to right shunts in the form of congestive heart failure. […] Any manoeuvres that decrease the PVR such as administration of oxygen, nitric oxide, or low arterial carbon dioxide tension and alkalosis will increase the left to right shunt. This increase in left to right shunt will be at the cost of decreased systemic output. […] With continued left to right shunting of blood, there is damage to the pulmonary vasculature ultimately causing hyperplasia of the vessel walls and pulmonary hypertension. […] In an ASD, there is a left to right shunt at the atrial level. This results in dilatation of right atrium and right ventricle with increased pulmonary venous return to the left atrium.
#35
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
In VSD, there is a left to right shunt across the ventricular level. This shunting occurs during systole and blood from LV is ejected in systole to the pulmonary circulation and causes a volume overload to the left atrium and the LV. […] In a PDA, there is a left to right shunt during systole and diastole from the aorta to the pulmonary artery. […] In truncus arteriosus, the pulmonary arteries are connected to the aorta. A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure. […] In this condition, the pulmonary venous return is to the right heart. There is complete mixing of blue and red blood. […] In a Tetrology of Fallot, due to presence of RV outflow tract obstruction, there is a right to left shunt across the large non-restricted VSD.
#36 Ventricular Septal Defects: Background, Anatomy, Pathophysiology
https://emedicine.medscape.com/article/892980-overview
A defect in the interventricular septum allows communication between the systemic and pulmonary circulations. As a result, flow moves from a region of high pressure to a region of low pressurethat is, from the LV to the RV (a left-to-right shunt). The pathophysiologic effects of a VSD derive from the hemodynamic effects secondary to a left-to-right shunt and from changes in the pulmonary vasculature. […] A left-to-right shunt at the ventricular level has three hemodynamic consequences: Increased LV volume load, Excessive pulmonary blood flow and elevated pulmonary artery pressures, Reduced systemic cardiac output. […] Blood flow through the defect from the LV to the RV results in oxygenated blood entering the pulmonary artery (PA). The addition of this extra blood to the normal pulmonary flow from the vena cava increases blood flow to the lungs and subsequently increases pulmonary venous return into the left atrium (LA) and ultimately into the LV. This increased LV volume results in LV dilatation and then hypertrophy. It increases end-diastolic pressure and consequently LA pressure, then raises pulmonary venous pressure.
#37 Ventricular Septal Defects: Background, Anatomy, Pathophysiology
https://emedicine.medscape.com/article/892980-overview
The anatomic factor is the size of the VSD. (The location of the VSD is irrelevant in terms of the degree of the shunt.) In a normal heart, RV pressure is about 25-30% that of the LV. In a large VSD, this pressure difference is no longer maintained, because a large hole offers no resistance to blood flow. Consequently, these defects are called nonrestrictive VSDs. […] However, in a small VSD, the normal pressure difference between the ventricles is maintained. These defects are called restrictive VSDs because blood flow across the defects is restricted, so that the normal pressure difference is maintained. […] The physiologic factor is the resistance of the pulmonary vascular bed. […] Pulmonary vascular disease is ultimately an irreversible condition and may occur over time in individuals with a large left-to-right shunt. It may also occur in the absence of a shunt; this condition is called primary pulmonary hypertension. A characteristic series of histologic changes ranging from grade I to grade VI has been described.
#38 Ventricular Septal Defects: Background, Anatomy, Pathophysiology
https://emedicine.medscape.com/article/892980-overview
The anatomic factor is the size of the VSD. (The location of the VSD is irrelevant in terms of the degree of the shunt.) In a normal heart, RV pressure is about 25-30% that of the LV. In a large VSD, this pressure difference is no longer maintained, because a large hole offers no resistance to blood flow. Consequently, these defects are called nonrestrictive VSDs. […] However, in a small VSD, the normal pressure difference between the ventricles is maintained. These defects are called restrictive VSDs because blood flow across the defects is restricted, so that the normal pressure difference is maintained. […] The physiologic factor is the resistance of the pulmonary vascular bed. […] Pulmonary vascular disease is ultimately an irreversible condition and may occur over time in individuals with a large left-to-right shunt. It may also occur in the absence of a shunt; this condition is called primary pulmonary hypertension. A characteristic series of histologic changes ranging from grade I to grade VI has been described.
#39
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
In VSD, there is a left to right shunt across the ventricular level. This shunting occurs during systole and blood from LV is ejected in systole to the pulmonary circulation and causes a volume overload to the left atrium and the LV. […] In a PDA, there is a left to right shunt during systole and diastole from the aorta to the pulmonary artery. […] In truncus arteriosus, the pulmonary arteries are connected to the aorta. A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure. […] In this condition, the pulmonary venous return is to the right heart. There is complete mixing of blue and red blood. […] In a Tetrology of Fallot, due to presence of RV outflow tract obstruction, there is a right to left shunt across the large non-restricted VSD.
#40 Patent Ductus Arteriosus (PDA) – Pediatrics – MSD Manual Professional Edition
https://www.msdmanuals.com/professional/pediatrics/congenital-cardiovascular-anomalies/patent-ductus-arteriosus-pda
Patent ductus arteriosus (PDA) is a persistence of the fetal connection (ductus arteriosus) between the aorta and pulmonary artery after birth. […] Patent ductus arteriosus accounts for 5 to 10% of congenital heart anomalies; the male:female ratio is 1:3. […] If this normal process does not occur, the ductus arteriosus will remain patent. […] Physiologic consequences depend on ductal size. A small ductus rarely causes symptoms. A large ductus causes a large left-to-right shunt. If uncorrected, over time, a large shunt results in left heart enlargement, pulmonary artery hypertension, and elevated pulmonary vascular resistance, ultimately leading to Eisenmenger syndrome. […] Over time, a large shunt causes left heart enlargement, pulmonary artery hypertension, and elevated pulmonary vascular resistance, ultimately leading to Eisenmenger syndrome if untreated.
#41
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
In VSD, there is a left to right shunt across the ventricular level. This shunting occurs during systole and blood from LV is ejected in systole to the pulmonary circulation and causes a volume overload to the left atrium and the LV. […] In a PDA, there is a left to right shunt during systole and diastole from the aorta to the pulmonary artery. […] In truncus arteriosus, the pulmonary arteries are connected to the aorta. A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure. […] In this condition, the pulmonary venous return is to the right heart. There is complete mixing of blue and red blood. […] In a Tetrology of Fallot, due to presence of RV outflow tract obstruction, there is a right to left shunt across the large non-restricted VSD.
#42 Congenital Heart Disease – Cardiovascular Pathophysiology for Pre-Clinical Students
https://pressbooks.lib.vt.edu/cardiovascularpathophysiology/chapter/chapter-6-congenital-heart-disease/
ASDs allow blood flow between the atria. As the pressure in the left atria is higher than that in the left, blood flows from left to right. This causes volume overload of the right side of the heart. This excessive load may lead to right ventricular compliance being reduced as remodeling takes place. The reduced compliance can elevate right-side pressure and thereby reduce the left-right shunt. […] The manifestations of a VSD depend on the VSD size and the relative resistance of the pulmonary and systemic circulationsâall of which will determine the direction of blood flow. […] The diminished lumen causes increased afterload on the left ventricle. […] The high resistance of the stenosed pulmonic valve causes the blood in the right ventricle to exit through VSD and enter the left ventricle forming a right-left shunt, bypassing the pulmonary circulation. Consequently, blood with venous PO2 enters the systemic circulation and hypoxemia/cyanosis results. The degree of hypoxemia/cyanosis that occurs depends on the degree of pulmonic stenosis.
#43
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
In transposition of great arteries there is ventriculo-arterial discordance; RV connected to aorta and LV to pulmonary artery. This creates a parallel circulation in contrast to a normal series circulation. […] In a patient with DORV depending on the relationship of the great arteries and the VSD, there can be manifestation of one of the 3 physiology: VSD physiology with left to right shunt and congestive heart failure, Tet physiology in the face of pulmonary stenosis causing paucity of pulmonary blood flow causing cyanosis, or a transposition physiology causing cyanosis with congestive heart failure. […] In a patient with Fontan repair, the IVC and SVC blood is directed passively to the pulmonary circulation. The only source of blue blood to the systemic circulation is from the coronary sinus. […] In conclusion, there is a complex cardiac and respiratory physiology that is created by congenital heart disease. An understanding of the pathophysiology is extremely important for safe anaesthetic management of these patients.
#44 Pediatric Congenital Heart Defects: A Nursing Guide
https://simplenursing.com/pediatric-nursing-congenital-heart-defects/
Tetralogy of Fallot (TOF) is the main condition for decreased pulmonary blood flow. […] With Tetralogy of Fallot, the client has a right to left shunting of blood with the defect of the obstruction going to the pulmonary outflow; meaning, there is not enough blood flowing into the lungs, but there is increased blood flowing into the aorta. […] In this congenital heart defect, there is an obstruction of the cardiac chambers. […] Coarctation of the aorta â a narrowed aorta caused by twisting. […] Pulmonic stenosis â narrowing of the pathway going to the lungs. […] Aortic stenosis â narrowing and hardening of the aorta. […] Also called as âtrans of great vessels,â the transposition of great arteries happens when saturated and de-saturated oxygen gets mixed up. […] With the transposition of great arteries, the right side of the heart pumps de-oxygenated blood back to the body, and the left side pumps oxygenated blood right back to the lungs. Because of this mixed-up structure, there will be severe cyanosis because the body does not receive blood with oxygen.
#45 Genetic and epigenetic mechanisms in the development of congenital heart diseases | World Journal of Pediatric Surgery
https://wjps.bmj.com/content/4/2/e000196
To our knowledge, although numerous literatures have discussed the genetic mechanisms of CHD, few have comprehensively elaborated the genetic and epigenetic mechanisms of CHD. In this review, we focus on CHD origin from the etiology of genetics and epigenetics. Chromosomal abnormalities and gene mutations in genetics, and DNA methylations, histone modifications and on-coding RNAs in epigenetics are summarized in detail. Moreover, we expect that rapidly emerging data could provide a further understanding of genetics and epigenetics in the development of CHD and also a basis for further exploring the early diagnosis and individualized therapy of CHD. […] Epigenetics, which refers to the mechanisms of changed gene expression that are independent of DNA sequence, provides a new way to understand the pathogenesis of CHD. To date, three canonical mechanisms of epigenetics include DNA methylation, histone modification and non-coding RNAs. The increasing evidence suggests that the aberrant regulation of gene expression by epigenetics is a key factor in the development of cardiovascular diseases, which have attracted attention to focus on the role of epigenetics in CHD.
#46 New light on congenital heart disease < Yale School of Medicine
https://medicine.yale.edu/news/medicineatyale/article/new-light-on-congenital-heart-disease/
Most interestingly, many of the newly identified mutations affect proteins that orchestrate normal development by helping to turn genes on and off at the proper times by altering the chemical marks on histone proteins, which provide a scaffold that DNA is wrapped around in the cell nucleus. This mechanism is known as epigenetic control. […] Ten of the de novo mutations found in CHD patients occurred in genes required for the addition or removal of methyl groups at two sites on one of the histones. These two methylation sites play a critical role in turning genes on and off. […] In embryonic stem cells and in developing embryos, key developmental genes appear to have both of these marks, and scientists have hypothesized that this methylation pattern is particularly important in the developing embryo, when genes must turn on and off at precise times in particular cell types to ensure proper development.
#47 New light on congenital heart disease < Yale School of Medicine
https://medicine.yale.edu/news/medicineatyale/article/new-light-on-congenital-heart-disease/
Most interestingly, many of the newly identified mutations affect proteins that orchestrate normal development by helping to turn genes on and off at the proper times by altering the chemical marks on histone proteins, which provide a scaffold that DNA is wrapped around in the cell nucleus. This mechanism is known as epigenetic control. […] Ten of the de novo mutations found in CHD patients occurred in genes required for the addition or removal of methyl groups at two sites on one of the histones. These two methylation sites play a critical role in turning genes on and off. […] In embryonic stem cells and in developing embryos, key developmental genes appear to have both of these marks, and scientists have hypothesized that this methylation pattern is particularly important in the developing embryo, when genes must turn on and off at precise times in particular cell types to ensure proper development.
#48 Genetic and epigenetic mechanisms in the development of congenital heart diseases | World Journal of Pediatric Surgery
https://wjps.bmj.com/content/4/2/e000196
To our knowledge, although numerous literatures have discussed the genetic mechanisms of CHD, few have comprehensively elaborated the genetic and epigenetic mechanisms of CHD. In this review, we focus on CHD origin from the etiology of genetics and epigenetics. Chromosomal abnormalities and gene mutations in genetics, and DNA methylations, histone modifications and on-coding RNAs in epigenetics are summarized in detail. Moreover, we expect that rapidly emerging data could provide a further understanding of genetics and epigenetics in the development of CHD and also a basis for further exploring the early diagnosis and individualized therapy of CHD. […] Epigenetics, which refers to the mechanisms of changed gene expression that are independent of DNA sequence, provides a new way to understand the pathogenesis of CHD. To date, three canonical mechanisms of epigenetics include DNA methylation, histone modification and non-coding RNAs. The increasing evidence suggests that the aberrant regulation of gene expression by epigenetics is a key factor in the development of cardiovascular diseases, which have attracted attention to focus on the role of epigenetics in CHD.
#49 New light on congenital heart disease < Yale School of Medicine
https://medicine.yale.edu/news/medicineatyale/article/new-light-on-congenital-heart-disease/
Up to 10 percent of congenital heart defects caused by non-inherited gene mutations similar to those previously implicated in autism […] Recently School of Medicine scientists contributed to a sweeping new search for genetic mutations in children with unexplained heart abnormalities that uncovered several hundred non-inherited mutations that may help shed light on how such problems arise during fetal development. […] The study compared the genomes of children with severe congenital heart disease (CHD) to the genomes of their healthy parents to try to determine whether de novo mutationsmutations that, rather than being passed from parent to child, arise spontaneously in egg, sperm, or early embryo cellsare involved in these disorders. […] Children with heart defects, they found, were 7.5 times more likely to have damaging de novo mutations in genes expressed in the developing heart than were healthy children, and such mutations appear to contribute to more than 10 percent of all cases.
#50 Cyanotic Heart Disease – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK500001/
In fetal circulation, gas exchange occurs in the placenta. From the placenta, oxygenated blood travels through the umbilical vein into the Inferior vena cava (IVC) through the ductus venosus (DV), bypassing the liver circulation. In the heart, most of the oxygenated blood is shunted from the right atrium to the left atrium through the foramen ovale (FO). From the left atrium, blood is pumped to the left ventricle and into the aorta to reach systemic circulation. A small portion of blood is pumped from the right atrium to right ventricle and the pulmonary artery. From the pulmonary artery, blood is shunted to the aorta through the ductus arteriosus (DA), bypassing the lungs. Deoxygenated blood return to the placenta by the umbilical arteries. […] CCHD is silent in fetal life because fetus receives oxygenated blood from the placenta and either the FO or DA can increase systemic blood flow. After DA and FO closure soon after birth, most CCHD become symptomatic. Cyanosis may be caused by persistence of fetal circulation, right-to-left shunting across the FO and ductus DA in the presence of pulmonary outflow tract obstruction or persistent pulmonary hypertension of the newborn.
#51 Cyanotic Heart Disease – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK500001/
In fetal circulation, gas exchange occurs in the placenta. From the placenta, oxygenated blood travels through the umbilical vein into the Inferior vena cava (IVC) through the ductus venosus (DV), bypassing the liver circulation. In the heart, most of the oxygenated blood is shunted from the right atrium to the left atrium through the foramen ovale (FO). From the left atrium, blood is pumped to the left ventricle and into the aorta to reach systemic circulation. A small portion of blood is pumped from the right atrium to right ventricle and the pulmonary artery. From the pulmonary artery, blood is shunted to the aorta through the ductus arteriosus (DA), bypassing the lungs. Deoxygenated blood return to the placenta by the umbilical arteries. […] CCHD is silent in fetal life because fetus receives oxygenated blood from the placenta and either the FO or DA can increase systemic blood flow. After DA and FO closure soon after birth, most CCHD become symptomatic. Cyanosis may be caused by persistence of fetal circulation, right-to-left shunting across the FO and ductus DA in the presence of pulmonary outflow tract obstruction or persistent pulmonary hypertension of the newborn.
#52 Overview of Congenital Cardiovascular Anomalies – Pediatrics – Merck Manual Professional Edition
https://www.merckmanuals.com/en-ca/professional/pediatrics/congenital-cardiovascular-anomalies/overview-of-congenital-cardiovascular-anomalies
Varying amounts of deoxygenated venous blood are shunted to the left heart (right-to-left shunt), reducing systemic arterial oxygen saturation. […] Blood flow is obstructed, causing a pressure gradient across the obstruction. […] Some congenital heart anomalies (eg, bicuspid aortic valve, mild aortic stenosis) do not significantly alter hemodynamics. Other anomalies cause pressure or volume overload, sometimes causing heart failure. […] The ductus arteriosus is a normal connection between the pulmonary artery and aorta; it is necessary for proper fetal circulation. […] Some congenital cardiac disorders are dependent on the ductus arteriosus remaining open to maintain systemic blood flow (eg, hypoplastic left heart syndrome, critical aortic stenosis, coarctation of the aorta) or pulmonary blood flow (cyanotic lesions such as pulmonary atresia or severe tetralogy of Fallot).
#53 Congenital heart defects in children – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-heart-defects-children/symptoms-causes/syc-20350074
An altered connection can cause oxygen-poor blood to mix with oxygen-rich blood. This lowers the amount of oxygen sent through the body. The change in blood flow forces the heart and lungs to work harder. […] Heart valve problems include valves that are narrowed and don’t open completely or valves that don’t close completely. […] Some infants are born with several congenital heart defects. Very complex ones may cause significant changes in blood flow or undeveloped heart chambers. […] Most congenital heart defects result from changes that occur early as the baby’s heart is developing before birth. The exact cause of most congenital heart defects is unknown. But some risk factors have been identified. […] Possible complications of a congenital heart defect include congestive heart failure, infection of the lining of the heart and heart valves, irregular heartbeats, slower growth and development, stroke, and mental health disorders. […] Complications of congenital heart defects may occur years after the heart condition is treated.
#54 Congenital Heart Disease – Cardiovascular Pathophysiology for Pre-Clinical Students
https://pressbooks.lib.vt.edu/cardiovascularpathophysiology/chapter/chapter-6-congenital-heart-disease/
ASDs allow blood flow between the atria. As the pressure in the left atria is higher than that in the left, blood flows from left to right. This causes volume overload of the right side of the heart. This excessive load may lead to right ventricular compliance being reduced as remodeling takes place. The reduced compliance can elevate right-side pressure and thereby reduce the left-right shunt. […] The manifestations of a VSD depend on the VSD size and the relative resistance of the pulmonary and systemic circulationsâall of which will determine the direction of blood flow. […] The diminished lumen causes increased afterload on the left ventricle. […] The high resistance of the stenosed pulmonic valve causes the blood in the right ventricle to exit through VSD and enter the left ventricle forming a right-left shunt, bypassing the pulmonary circulation. Consequently, blood with venous PO2 enters the systemic circulation and hypoxemia/cyanosis results. The degree of hypoxemia/cyanosis that occurs depends on the degree of pulmonic stenosis.
#55
https://journals.lww.com/aoca/fulltext/2007/10010/pathophysiology_of_congenital_heart_diseases.2.aspx
With transition to extra-uterine circulation there is a decrease in the PVR with a simultaneous increase in SVR. This usually happens between 2-6 weeks of life and causes manifestation of left to right shunts in the form of congestive heart failure. […] Any manoeuvres that decrease the PVR such as administration of oxygen, nitric oxide, or low arterial carbon dioxide tension and alkalosis will increase the left to right shunt. This increase in left to right shunt will be at the cost of decreased systemic output. […] With continued left to right shunting of blood, there is damage to the pulmonary vasculature ultimately causing hyperplasia of the vessel walls and pulmonary hypertension. […] In an ASD, there is a left to right shunt at the atrial level. This results in dilatation of right atrium and right ventricle with increased pulmonary venous return to the left atrium.
#56 Patent Ductus Arteriosus (PDA) – Pediatrics – MSD Manual Professional Edition
https://www.msdmanuals.com/professional/pediatrics/congenital-cardiovascular-anomalies/patent-ductus-arteriosus-pda
Patent ductus arteriosus (PDA) is a persistence of the fetal connection (ductus arteriosus) between the aorta and pulmonary artery after birth. […] Patent ductus arteriosus accounts for 5 to 10% of congenital heart anomalies; the male:female ratio is 1:3. […] If this normal process does not occur, the ductus arteriosus will remain patent. […] Physiologic consequences depend on ductal size. A small ductus rarely causes symptoms. A large ductus causes a large left-to-right shunt. If uncorrected, over time, a large shunt results in left heart enlargement, pulmonary artery hypertension, and elevated pulmonary vascular resistance, ultimately leading to Eisenmenger syndrome. […] Over time, a large shunt causes left heart enlargement, pulmonary artery hypertension, and elevated pulmonary vascular resistance, ultimately leading to Eisenmenger syndrome if untreated.
#57 Congenital heart defects in children – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-heart-defects-children/symptoms-causes/syc-20350074
An altered connection can cause oxygen-poor blood to mix with oxygen-rich blood. This lowers the amount of oxygen sent through the body. The change in blood flow forces the heart and lungs to work harder. […] Heart valve problems include valves that are narrowed and don’t open completely or valves that don’t close completely. […] Some infants are born with several congenital heart defects. Very complex ones may cause significant changes in blood flow or undeveloped heart chambers. […] Most congenital heart defects result from changes that occur early as the baby’s heart is developing before birth. The exact cause of most congenital heart defects is unknown. But some risk factors have been identified. […] Possible complications of a congenital heart defect include congestive heart failure, infection of the lining of the heart and heart valves, irregular heartbeats, slower growth and development, stroke, and mental health disorders. […] Complications of congenital heart defects may occur years after the heart condition is treated.
#58 Congenital heart disease â¢ Heart Research Institute
https://www.hri.org.au/health/learn/cardiovascular-disease/congenital-heart-disease
Even if the heart defect has been repaired, people living with CHD are not cured. They are likely to require regular check-ups to monitor their heart and overall health throughout their life, as they can develop other health problems over time due to their CHD. […] The life span of someone born with a CHD depends on the specific CHD. Medical research has advanced heart operations and treatment such that 95 per cent of children born with CHD will now survive into adulthood, whereas in the past being born with CHD meant the baby was likely to die soon after birth or in childhood. […] Further research is required to improve the quality of life and life span of adults living with CHD. […] CHD can increase the risk of the heart tissue becoming infected. […] Some CHDs send more blood to the lungs than normal, causing the blood pressure in the arteries connecting the heart and lungs to be much higher than it should be. This can eventually cause the heart muscle to weaken and sometimes fail. […] In heart failure, the heart cannot pump enough blood around the body to meet the body’s needs. It may develop if the heart defect is significant, and it can occur shortly after birth or as a complication later in life.
#59 Congenital Heart Disease in Children | Doctor
https://patient.info/doctor/congenital-heart-disease-in-children
All forms of congenital heart disease, apart from ASD, carry a risk of infective endocarditis. […] A left-to-right shunt does not cause cyanosis but the high volume pumped by the right side may result in pulmonary hypertension and, if this builds up and exceeds systemic pressure, the shunt may reverse from right to left. […] Survival in children with congenital heart disease has increased substantially since the 1980s. […] However, children who have undergone surgery for congenital heart disease still have impaired survival compared to the general population and often need new operations or catheter-based procedures. […] Delayed diagnosis of congenital heart disease causes significant morbidity and mortality.
#60 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
There is increasing evidence demonstrating that children with congenital heart disease (CHD) have a greater risk of developing autism spectrum disorder (ASD) in later life. […] The comorbidities of ASD and CHD can be explained by the influence of common and rare variants that contribute to genetic risks. De novo mutations in chromatin remodelling genes, and common genetic loci in the development of brain and heart in utero, can lead to the co-occurrence of ASD and CHD. […] Foetuses with CHD may have abnormal haemodynamic changes and alteration of brain circulation in utero, resulting in impaired development of the brain, and increased risk of ASD. […] Abnormal brain development or brain injury as observed in MRI studies of infants with CHD may also contribute to the risk of ASD. […] The severity of CHD has a positive correlation with the risk of neurodevelopmental disorders, including ASD, attributed to presence of de novo mutations in chromatin remodelling genes, Notch signalling, and cilia function.
#61 Frontiers | Congenital Heart Disease: An Immunological Perspective
https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.701375/full
Congenital heart disease (CHD) poses a significant global health and economic burdenâdespite advances in treating CHD reducing the mortality risk, globally CHD accounts for approximately 300,000 deaths yearly. […] A challenge in addressing these morbidity and mortality risks is that little is known regarding the cause of many CHDs and current evidence suggests a multifactorial etiology. Some studies implicate an immune contribution to CHD development; however, the role of the immune system is not well-understood. Defining the role of the immune and inflammatory responses in CHD therefore holds promise in elucidating mechanisms underlying these disorders and improving upon current diagnostic and treatment options. […] Congenital heart diseases (CHDs) have been reported in anywhere from 3.7 to 75 per 1,000 live births depending on the population, methods of diagnosis, and severity of the disease. These heart defects form in utero due to abnormalities in the formation of the cardiac structures and conduction system.
#62 Frontiers | Congenital Heart Disease: An Immunological Perspective
https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.701375/full
Despite these complications, there is little conclusive evidence on the specific cause of many structural CHDs, and collectively they are quite heterogeneous. Current research implicates a combination of genetic, epigenetic, and environmental factors as causative mechanisms underlying CHDs. […] A motivation for studying the link between immunology and heart disease is that structural CHDs are associated with reduced immune cell counts and maturity. […] The increased susceptibility to infectious complications among children with CHDs may be due in part to the inflammatory response. […] Better understanding this inflammatory response can aid in developing prophylactic treatments to prevent complications from CHDs. […] Since an understanding of the immune and inflammatory contributions to CHD is limited, we have chosen to highlight conditions that establish the range of CHDs with an immune association, and the long-term implications of these diseases.
#63 Relationship between heart failure and intestinal inflammation in infants with congenital heart disease | BMC Microbiology | Full Text
https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-024-03229-0
The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated. […] The intestinal tract is composed of many microorganisms and is the largest immune organ and endocrine system in the human body. […] Congenital heart disease (CHD) is the most common cause of HF in children. […] We hypothesized that HF in infants with CHD could lead to a disordered intestinal microbiota, which could aggravate the intestinal inflammatory response. […] Infants with CHD-related HF had a disordered intestinal microbiota, decreased diversity of intestinal microbes, increased levels of pathogenic bacteria and decreased levels of beneficial bacteria. […] The increased abundance of Enterococcus and the significant decrease in the diversity of the intestinal microbiota may exacerbate the intestinal inflammatory response, which may be associated with the progression of HF.
#64 Relationship between heart failure and intestinal inflammation in infants with congenital heart disease | BMC Microbiology | Full Text
https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-024-03229-0
The disordered intestinal microbiota in HF patients is mainly characterized by an increase in pathogenic bacteria and a decrease in beneficial bacteria, which aggravate the intestinal inflammatory reaction and increase the levels of intestinal inflammatory factors and toxin secretion. […] Our study showed that the intestinal proinflammatory factors IL-1, IL-4, IL-6, IL-17 A and TNF- were robustly increased in infants with HF and CHD, while the anti-inflammatory factor IL-10 was significantly decreased. […] Therefore, we hypothesize that the intestinal barrier is damaged after HF and that the amount of intestinal proinflammatory factors entering the circulation is increased, which exacerbates the systemic inflammatory response and the progression of HF. […] We hypothesize that when HF occurs, intestinal inflammatory factor levels increase, and the intestinal barrier breaks down; subsequently, proinflammatory factors enter the circulation through the intestine, which may be associated with the progression of HF.
#65 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
There is increasing evidence demonstrating that children with congenital heart disease (CHD) have a greater risk of developing autism spectrum disorder (ASD) in later life. […] The comorbidities of ASD and CHD can be explained by the influence of common and rare variants that contribute to genetic risks. De novo mutations in chromatin remodelling genes, and common genetic loci in the development of brain and heart in utero, can lead to the co-occurrence of ASD and CHD. […] Foetuses with CHD may have abnormal haemodynamic changes and alteration of brain circulation in utero, resulting in impaired development of the brain, and increased risk of ASD. […] Abnormal brain development or brain injury as observed in MRI studies of infants with CHD may also contribute to the risk of ASD. […] The severity of CHD has a positive correlation with the risk of neurodevelopmental disorders, including ASD, attributed to presence of de novo mutations in chromatin remodelling genes, Notch signalling, and cilia function.
#66 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
Comorbidities of ASD and CHD may arise due to the underlying genetic or haemodynamic changes during in utero or post-natal cardiac surgery. […] The development of both heart and brain occurs simultaneously, sharing common genetic pathways during foetal development. […] Therefore, abnormal heart development may precipitate neurodevelopmental disorders due to these shared pathways. […] Potential insult to the development of the brain in infants with CHD may occur during intrauterine life. […] Impairment in cerebral blood flow during in utero, post-natal, or post-operative repair also plays a significant role in the comorbidity of ASD and CHD. […] Neuroimaging studies of infants born with CHD often showed abnormalities of the brain structures which may lead to poor neurodevelopmental outcomes.
#67 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
The variability in brain development alterations among infants with CHD can be attributed to haemodynamic instability during cardiac procedures, potentially leading to intraoperative brain injuries arising from ischaemia or hypoxia. […] Understanding the association between ASD and CHD may aid the clinician in early diagnosis and intervention to tackle neurodevelopmental difficulties. […] The risk factors contributing to the development of ASD in patients with CHD encompass various elements. […] These risk factors include patient-specific factors, prenatal and perinatal conditions, brain abnormalities, the timing of surgical intervention, and cognitive impairments. […] Studies have shown that foetuses with CHD experience abnormal haemodynamic changes that result in alterations in brain circulation.
#68 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
The shunting of blood in CHD leads to significant reductions of blood-flow in the major cerebral vessels. […] Therefore, the development of ASD in CHD may be due to the burden of pulmonary and circulatory compromise, resulting from brain-sparing circulatory shift changes. […] Additionally, the time to corrective surgery is also an important determining factor, as more injury to the brain occurs when there is a longer wait to the corrective cardiac surgery in CHD infants. […] Infants with CHD have a high incidence of brain abnormalities, even with an absence of genetic syndrome. […] MRI studies of newborns with CHD showed reduced brain volume for gestational age, decreased metabolism, and delayed cortical folding and development compared to healthy newborns. […] Furthermore, term infants with cyanotic CHD demonstrated similar white matter anomalies and delays in myelination, which are observed in preterm infants.
#69 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
The shunting of blood in CHD leads to significant reductions of blood-flow in the major cerebral vessels. […] Therefore, the development of ASD in CHD may be due to the burden of pulmonary and circulatory compromise, resulting from brain-sparing circulatory shift changes. […] Additionally, the time to corrective surgery is also an important determining factor, as more injury to the brain occurs when there is a longer wait to the corrective cardiac surgery in CHD infants. […] Infants with CHD have a high incidence of brain abnormalities, even with an absence of genetic syndrome. […] MRI studies of newborns with CHD showed reduced brain volume for gestational age, decreased metabolism, and delayed cortical folding and development compared to healthy newborns. […] Furthermore, term infants with cyanotic CHD demonstrated similar white matter anomalies and delays in myelination, which are observed in preterm infants.
#70 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
Damage to the oligodendrocyte progenitor cells and subplate neurons in CHD infants results in impairment of the myelination process and development of white matter track, potentially affecting neural connectivity. […] These structural anomalies can result in emotional processing and social impairments in ASD, associated with atypical cortical and sub-cortical structures. […] Therefore, development of epilepsy syndrome in children with CHD may increase the risk of development of ASD. […] Moreover, infants with CHD have a higher rates of adverse perinatal outcomes, including preterm delivery, low birth weight, and perinatal or neonatal infection, all of which can contribute to the risk of developing ASD. […] There are two distinct chronological risk factors for the increased risk of ASD in children with CHD, which are during birth and early childhood.
#71 Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder – European Medical Journal
https://www.emjreviews.com/flagship-journal/article/genetics-and-pathophysiology-of-co-occurrence-of-congenital-heart-disease-and-autism-spectrum-disorder-j190124/
Damage to the oligodendrocyte progenitor cells and subplate neurons in CHD infants results in impairment of the myelination process and development of white matter track, potentially affecting neural connectivity. […] These structural anomalies can result in emotional processing and social impairments in ASD, associated with atypical cortical and sub-cortical structures. […] Therefore, development of epilepsy syndrome in children with CHD may increase the risk of development of ASD. […] Moreover, infants with CHD have a higher rates of adverse perinatal outcomes, including preterm delivery, low birth weight, and perinatal or neonatal infection, all of which can contribute to the risk of developing ASD. […] There are two distinct chronological risk factors for the increased risk of ASD in children with CHD, which are during birth and early childhood.
#72 Children’s Heart | About CHDs | Congenital Heart Defects
https://www.childrensheartfoundation.org/about-chds/chd-facts.html
Today, 95% of babies born with a non-critical CHD are expected to survive to at least 18 years of age. […] Approximately 25% of children born with a CHD will need heart surgery or other interventions in their first year of life to survive. […] Surgery is often not a cure for CHDs. Many individuals with CHDs require additional operation(s) and/or medications as adults. […] Because of advancements made through research, death rates from CHDs in the U.S. have declined by 37.5% since 1999. […] Despite the progress made in understanding and treating CHDs, more work is needed to determine the causes and best treatment options.
#73 Congenital heart disease: types, pathophysiology, diagnosis, and treatment options
https://pmc.ncbi.nlm.nih.gov/articles/PMC11224996/
The prevalence of sudden cardiac death (SCD) in patients with CHD is approximately 0.28-2.7% per year, which is 20-30-fold higher than that in the general population. […] Despite advances in the medical domain, some problems of CHD remain unclear. […] The management of CHD is challenging due to its overall prevalence. […] Therefore, an updated overview of the pathophysiology, diagnosis, and treatment of CHD is necessary.
#74 Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways | Egyptian Journal of Medical Human Genetics | Full Text
https://jmhg.springeropen.com/articles/10.1186/s43042-020-0050-1
The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. […] More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.
#75 Genetic and epigenetic mechanisms in the development of congenital heart diseases | World Journal of Pediatric Surgery
https://wjps.bmj.com/content/4/2/e000196
The interactions at multiple levels provide insights of the combinatorial regulation into the morphogenesis of heart and suggest they can partially compensate each others function. Phenotypic heterogeneity and incomplete penetrance of CHD complicate our understanding of the interactions between genetics and epigenetics in CHD. Future studies to focus on elucidating the epigenetic signals of genes associated with cardiac development pathways could throw light on the genetic and epigenetic mechanisms in the development of CHD.