Natural history of
right to left shunts
Presenter - Dr. Dinanath Kumar
DM SENIOR RESIDENT, SMS MEDICAL COLLEGE, INDIA
• Congenital heart disease can be categorized into two basic types, acyanotic and cyanotic.
• Cyanotic lesions can be divided into 1)Tetralogy of Fallot (TOF) physiology, 2)Transposition of
Great Arteries (TGA) physiology and 3)Admixture physiology.
• “Presence of non restrictive VSD with decreased pulmonary blood flow sufficient to reduce
pulmonary artery pressure , (not necessarily RVOT obstruction) leading to bidirectional or
right to left shunt across VSD”
• As there is a non restrictive VSD, depending on the degree of PS, a volume of deoxygenated
blood from RV will flow through the VSD into systemic circulation.
DORV with subaortic VSD and pulmonary stenosis
Single ventricle with PS
d TGA with VSD with PS
cc TGA with VSD with PS
AVCD with VSD with pulmonary stenosis
• Oxygenated blood flows back into lungs and deoxygenated blood flows back into the body
creating two parallel circuits. Saturation depends on amount of mixing at the level of atria,
ventricles or great arteries.
Complete transposition of great arteries
DORV with subpulmonic VSD
• Complete mixing of pulmonary and systemic venous return in a common
receiving chamber (at venous level, cardiac chamber or great artery level),
before it is pumped into systemic and pulmonary circulations is called
• Therefore, in admixture lesions the aortic and pulmonary artery saturations
Totally anomalous pulmonary venous connection (TAPVC),
Atresia of one of the atrioventricular valves (Tricuspid atresia, mitral
Semilunar valve atresia (pulmonary atresia including hypoplastic right heart
syndrome, aortic atresia including hypoplastic left heart syndrome),
Complete deficiency of atrial septum as in common atrium, and
Single ventricle physiology (double inlet ventricle)
Complete deficiency of conotruncal and trunco-aortic septum as in truncus
Ann Pediatr Cardiol. 2011 Jan-Jun; 4(1): 53–59
Variants of TOF
Monology of Fallot – Presently TOF is considered a monology from which all
four characteristic features result “anterior and cephalad deviation of
outlet(infundibular) septum relative to septomarginal trabeculation”.
TOF subclassified into 3 categories
1. TOF with pulmonary stenosis
2. TOF with pulmonary atresia
3. TOF with absent pulmonary valve
1. TOF with PS
• Commonest cyanotic CHD
– Incidence – 1 per 3600 live births (Apitz c, LANCET 2009:1462-1471)
– Sibling recurrence risk of 2.5% if one sibling was affected,
and 8% if two or more siblings were affected. (Nora JJ, Nora AH. Am J Med Genet
– Recurrence risk of 1.4% if the affected parent was male and
2.6% if the affected parent was female.(Nora JJ, Nora AH. Am J Cardiol 1987;59:459-463).
– Equally common in males and females
• Usually diagnosed in early infancy
– Because of appearance of cyanosis or a prominent systolic
• Natural history is determined mainly by degree of RVOT
Site of RVOT obstruction
Based upon the results of autopsy findings and surgical finding at open heart surgery
Singapore medical journal vol. 14, No.3, sept 1973
Age of onset of cyanosis
3-12 months of age
N = 213
Singapore medical journal vol. 14, No.3, sept 1973
Based on study of natural history of TOF in 213 cases over a period of 10 years.
By 5 to 8 years of age, most children are conspicuously cyanotic, with cyanosis closely
coupled to the severity of pulmonary stenosis.
TOF with PS- clinical features
• Clinical course in early infancy
o Often benign
o Mild to moderate cyanosis tends to increase
– Increased oxygen requirements of the growing infant rather than with progressive obstruction to
o May be punctuated by cyanotic spells
• Squatting for relief of dyspnea is a hallmark of Fallot’s tetralogy
• JVP is normal.
• Pulmonary stenosis- Murmur is maximal in the third left ICS because the stenosis is infundibular.
• No VSD murmur as shunt is balanced
• ECG - Normal PR interval; RAD with clockwise depolarisation; RVH
- Transition from monophasic R wave to rS pattern in V2
- LAD with counterclockwise depolarisation in TOF with AVSD
CXR – coeur en sabot or boot shaped/GOLF CLUB WOOD appearance- results from a small underfilled
left ventricle that lies above a horizontal ventricular septum, inferior to which is a concentrically
hypertrophied RV and right aortic arch present.
• Potentially lethal
• Equally common in less cyanosed patients
• Peak incidence between 2-6 months of age, but may occur till 2 years; rare in
– Typically after awakening from a long deep sleep (early morning or during naps
in the day time)
– Possible triggers are feeding, crying, bowel movement, fever.
– Vulnerable respiratory control mechanisms (which are especially sensitive after
prolonged deep sleep) react to the sudden increase in cardiac output. Venous
return increases and in the face of fixed obstruction to RVOT, increasing right-
to-left shunt and hypoxemia. Sleep-sensitive respiratory center and carotid
body overreact to this increased hypoxemia provoking hyperpnoea, which in
turn further increases the cardiac output perpetuating the cycle. Infundibular
contraction reinforces this pattern but does not initiate it.
• Timely management must, else may culminate in hypoxic brain injury,
stroke or death
Survival pattern based on 566 necropsy cases of TOF-
• Two third(66%) alive at 1 year
• Half(49%) at 3 years
• Quarter(24%) at 10 years
Thereafter, the instantaneous risk of death remains constant at
6.4% per year, with 11% alive at age 20 years, 6% at age 30
years, and 3% at age 40 years
Instantaneous risk of death greatest in first year
Bertranou et al: Life expectancy without surgery in tetralogy of Fallot.
The American Journal of CARDIOLOGY September 1978; 458-466
Major causes of death in TOF
108 deaths among 186 cases over 10 years
• Cyanotic spells – 62%
– 81% of hypoxemic deaths occured in the first 3 years of life
• CVA – 17%
– Occurred in first 5 years of age
– Combi of ischemia and h’rrage
• Brain abscess - 13%
– Occur after 5 years of age
Singapore medical journal vol. 14, No.3, sept 1973
Heart failure in TOF
• Neonatal RV is well equipped to eject against systemic vascular
resistance because the nonrestrictive VSD permits decompression
into the aorta
• Heart failure rarely reported in TOF patients <10 years
• However, biventricular failure in the first few weeks of life
1. Pulmonary atresia with excessive flow through large systemic
2. Absent pulmonary valve volume overload of pressure overloaded
3. Accesory tricuspid leaflet tissue that partially occludes the VSD and
causes suprasystemic RVSP with RV failure
Heart failure in TOF
• Heart failure is however common in adult patients with TOF
• Higgins et al reported the incidence of HF in 25 TOF patients >20 years to be 33 percent
for cyanotic and 38 percent for acyanotic patients (Am J Cardiol 29:837-846; 1972 )
• Possible causes
1. Systemic HTN-increases LV and RV afterload and can induce RV or B/V failure
2. Acquired calcific stenosis of the biventricular aortic valve-imposes increased afterload on both RV
3. Aortic valve regurgitation-causes RV failure by imposing volume overload on the already
4. Infective endocarditis of aortic valve-result in catastrophic acute severe biventricular AR
The life history of TOF who reach adulthood without surgery/ palliation
suggest that longevity in TOF is determined predominantly by
early development of collateral circulation to the lungs and
Slow progressive narrowing of initially mild infundibular stenosis with age.
Tetralogy of Fallot in adults: A report on 147 patients
Presented here is the clinical and hemodynamic profile of 147 patients,
above the age of 18 with tetralogy of Fallot
• 25.8% of patients had cardiomegaly and 15.6 per cent were in CHF
• 23.1 % had a reticular pattern in the lung fields due to bronchial
• 9.5 per cent had systemic hypertension and 6.7 per cent had aortic
• Prominent “a” wave greater than 10 mm Hg was present in 10.9 %
• RVEDP increased in 23.8 % and LVEDP raised in 25.9 per cent
• Right aortic arch in 19.9 %, absent left pulmonary artery in 2.8%,
absent right pulmonary artery in 0.7 % and dextrocardia in 1.4 %
K.A. Abraham, George Cherian, V.Dayasagar Rao, I.P. Sukumar, S. Krishnaswami,
Stanley John, The American Journal of Medicine, May 1979 Pages 811-816
Pregnancy in adult TOF
• Poorly tolerated
– Gestation fall in SVR increases Rt to Lt shunt
– Labile SVR during labor and delivery results in abrupt
oscillations in hypoxemia.
• Fetal wastage is high
• Live born are small for gestational age
Singapore medical journal vol. 14, No.3, sept 1973
2. TOF with Pulmonary atresia
• 2% of all CHD. In Baltimore –Washington Infant Study(BWIS) , 20.3% of all forms of TOF.
• Pulmonary circulation supplied entirely by collateral arteries. Three types- Systemic arterial
collaterals; PDA and small diffuse pleural arterial plexuses.
• Systemic arterial collaterals are classified according to their origins as: (1) bronchial (2) direct
systemic arterial collaterals, originate from descending aorta, and (3) indirect systemic
arterial collaterals, originate from internal mammary, innominate, and subclavian arteries.
• Absent P2; Aortic ejection sound at upper right sternal border,originate in a dilated aorta.
• No pulmonary stenotic murmur of TOF
• Continuous murmur in >80% patients, originate in direct and indirect systemic collaterals.
Heard beneath clavicles, back, right and left of sternum, right and left axillae. Do not occur in
Fallot’s tetralogy with PS in which collaterals are confined to bronchial arteries
• ECG – with abundant collaterals, LAE because of increased flow into LA. Q waves with well-
developed R waves appear in leads V5-6 because of increased flow into LV(Vs TOF)
• CXR- lacy reticular pattern without the normal diminution in vessel caliber toward the
TOF with Pulmonary atresia -Survival pattern
• Chance of survival is significantly less when pulmonary atresia,
rather than stenosis, is present
• Life expectancy without surgery is
– 50% at 1 year
– 8% at 10 years
• Infants who die early probably lack major aorto-pulmonary collateral
– Death coincides with spontaneous closure of PDA
• Patients who reach adulthood often develop massive and sometimes
fatal hemoptysis related to large AP collaterals
American Journal of Cardiology 1978;42;458-456
3. Tetralogy of Fallot With Absent
• 3-6% of TOF patients
• Severe pulmonary regurgitation seen
• Disease hallmark - Main and branch pulmonary arteries massively
– This aneurysmal dilatation can lead to tracheobronchial
compression and respiratory distress, which is characteristic of this
• Ductus arteriosus is nearly always absent
• Pulmonary stenosis is typically mild, occurs at the annulus
Pulmonary artery branching in a healthy person and in a patient with absent
pulmonary valve syndrome.
Tetralogy of Fallot With Absent Pulmonary Valve - C/F
• Early cyanosis- In the immediate neonatal period, because of high PVR causing a right-to-left
• Cyanosis usually does not progress as it does in typical TOF
As PVR falls, the cyanosis decreases as the right to left shunt decreases
• After fall in PVR, respiratory difficulties are most prominent symptom. RV failure due to
massive volume overload of severe PR in addition to the resistance to discharge at pulm
• Palpation – dilated infundibulum is palpated in 3rd left ICS, and a dilated pulmonary trunk is
palpated in 2nd left ICS
- systolic thrill due to augmented RV stroke volume that is ejected rapidly across a
hypoplastic pulmonary annulus.
- diastolic thrill of PR
• P2 absent. SAWING WOOD murmur- long, loud, harsh mid-systolic murmur followed by a
shorter harsh diastolic murmur
• ECG (vs TOF e PS)- tall monophasic R wave in lead V1 extends to adjacent precordial
leads, in contrast to TOF with PS in which tall right precordial R wave is confined to lead V1
Tetralogy of Fallot With Absent Pulmonary Valve: Natural History
• Patients divided into 2 groups
1. children with severe respiratory difficulties during the neonatal period –
immediately after birth or in the first week of life.
>75% of infants with severe pulmonary complications (e.g., atelectasis,
pneumonia) die during infancy if treated only medically.
2. children with less airway compromise who tend to be identified later in life.
Do well for 5 to 20 years. They become symptomatic later and die from
intractable right-sided heart failure.
• > 96% chance of survival to hospital discharge.
• Of surviving infants, >90% are expected to be
alive 30 years after repair.
• Long term survival is not normal. For 30 yr old,
0.5% annual risk of death (3 times higher than
baseline for males and 8 times higher for
4. Double Outlet Right Ventricle
• DORV occurs in < 1% of all CHD
• Defined as ‘Both great arteries and arterial trunks arise
exclusively from the morphologic RV; neither semilunar valve
is in fibrous continuity with either AV valve; and usually, a VSD
is present and represents the only outlet from the LV.’ Neufeld et
• Conus present below each arterial valve
• VSD present which provides the only exit for LV
– May be subaortic or subpulmonary
– Location of VSD determines intracardiac streaming
DORV- major clinical patterns
A. Subaortic VSD, no PS, low PVR: resembles nonrestrictive perimembranous VSD.
B. Subaortic VSD, no PS, high PVR: resembles Eisenmenger’s syndrome.
C. Subaortic VSD with PS: resembles Fallot’s tetralogy.
D. Subpulmonary VSD with no PS: resembles D TGA with nonrestrictive VSD.
DORV with S/A VSD with PS
• 40% of all DORV(moss)
• PS present in 40-70% of cases of DORV with a subaortic VSD
• PS rare in subpulmonary VSD
• PS secondary to
– Underdeveloped subpulmonary conus
– Stenotic bicuspid PV
• PS serves to reduce PBF. May be initially absent or mild and
then develop and progress.
Clinical Features and Natural History of DORV with VSD with PS
• 1.Cyanosis more prominent than TOF and appears soon after birth
• Overall history similar to those of children with TOF
– Cyanotic patients squat;Polycythemia and hypercyanotic spells observed
• 2 no VSD murmur(moss).
???Murmur of VSD dates from birth at lower left sternal border
– Obligatory flow across VSD; does not await the neonatal fall in PVR.
– Holosystolic if mild PS and decrescendo if severe PS
– 3.Systolic thrill generated by VSD
• Murmur of PS- long harsh midsystolic, second and third left ICS
• ECG- 4.PR prolonged; 5.RAD with counterclockwise depolarisation (Vs TOF)
• However survival inferior as compared to TOF, with few attaining adulthood.
DORV with Subpulmonary VSD (Taussig-Bing anomaly)
• About 50% patients have congenital malformations of aortic arch, including
coarctation, interruption, and PDA, in addition to subaortic stenosis.
• With elevation in PVR- reversed differential cyanosis. Toes are less cyanotic
and less clubbed than the fingers because oxygenated blood from LV flows
through the subpulmonary VSD into the pulmonary trunk and through PDA
into descending aorta, whereas unoxygenated blood RV flows into the aorta
and to upper extremities.
• Severe pulmonary vascular obstructive disease develops early in life, as
seen in patients with D-TGA.
• Thrill in 2nd left ICS because VSD is subpulmonary
• VSD murmur at 2nd left ICS
• ECG- RAD with clockwise depolarisation; RVH
BOX LIKE Configuration – marked rightward convexity of enlarged RA together with
marked leftward convexity of enlarged infundibulum
• Congenital defect of tricuspid valve
– attachment of septal or septal+posterior leaflets is displaced apically
– anterior leaflet is enlarged.
– OS ASD in 1/3rd and most of the rest have PFO.
• 0.3-0.7 % of congenital heart disease
– 28 folds increased risk with maternal ingestion of lithium
• Incidence : M=F
• Cyanosis with normal or reduced pulmonary blood flow and a dominant LV
• The septal leaflet normally exhibits a slight but distinct apical displacement of its basal
attachment compared with the mitral valve: 15 mm in children, and 20 mm in adults
• Apical displacement of septal leaflet by >15 mm in children and >20 mm in adults or at
least 8mm/m2 BSA is considered diagnostic.
• Widely split S1- Delayed tricuspid valve closure due to complete RBBB and increased
excursion of the large size anterior leaflet
• Wide splitting S2- result of delay in the pulmonary component caused by complete RBBB
• Right sided S3 and S4 produce a distinctive triple or quadruple rhythm
• Systolic murmur of TR maximal over the displaced tricuspid valve, and therefore most
prominent in a relatively leftward location toward the apex.
• Tall peaked Himalayan P waves and PR interval prolongation- prolonged conduction in the
• Prolonged HV intervals- due to lengthened and impaired conduction within the atrialized RV
• QRS axis –inferior. Left axis deviation represents type B preexcitation
• RBBB- result of prolonged activation of the atrialized RV
• Bizarre second QRS attached to preceding normal QRS originates in the atrialized RV
• Type B WPW preexcitation- right bypass pathway
• Supraventricular tachycardia, Atrial fibrillation or flutter
• Arrhythmogenic atrialized RV- polymorphic VT
Natural history of Ebstein anomaly
• Determined by
– Morphological derangement of tricuspid leaflets
– Hemodynamic burden imposed on a functionally inadequate RV
– LV function
– Atrial rhythm
The clinical course of Ebstein’s anomaly ranges from intrauterine death to
asymptomatic survival to late adulthood
• In a review of 220 patients with Ebstein’s anomaly, the most common presentation
varied with age at presentation(Dearani JA. Annals of Thoracic Surgery,Pages 106–117,March 2000)
Fetuses- an abnormal routine prenatal scan(86%)
Neonates- cyanosis (74%)
Infants- heart failure (43%)
Children- incidental murmur (63%)
Adolescents and adults- arrhythmias (42%), decrease exercise tolerance,
fatigue, or right sided heart failure
• Outlook is dismal
• Fetal hydrops occurs as a rule
• Recognized cause of death in utero
• Functionally inadequate RV unable to cope up with high neonatal
PVR Augmented TR leads to R to L shunt across PFO/ASD,
resulting in cyanosis
• As PVR falls, neonatal TR and R to L shunt decrease and disappears
and patient improves. The shunt subsequently reappears as filling
pressure rises in the functionally abnormal RV.
• Transient neonatal cyanosis that recurs a decade or more later is an
uncommon but distinctive and usually benign feature of Ebstein’s
• Neonatal presentation associated with poor prognosis
– 20% die in 1 month, and less than 50% survive to 5 years
– Cause: HF/Hypoxia
Presentation in Infancy
• Associated with less risk of death and milder symptoms
10% to 20% mortality rate during the first year of life for infants with
Ebstein anomaly not undergoing surgical intervention.
Kumar AE, Fyler DC, Miettinen OS, et al. Ebstein anomaly: Clinical
profile and natural history. Am J Cardiol 1971;28:84â€“95
• In the Watson series
505 cases of Ebstein's anomaly have been collected from 61 centres in 28 countries
– 72% of those under 1 year were in heart failure
– 71% of the children and adolescents had little or no disability
– 60% of adults >25 years had little or no disability
Of the 505, 77 (13.3%) died from natural causes
Presentation in childhod and adult life
• Acyanotic with normal sized heart
• 25-30% have SVT, atrial flutter or fibrillation
• 5-25% of ECGs show pre-excitation via a right bypass tract
• Decrease exercise tolerance
– RV fails to increase PBF.
• RV filling pressure rises again in adults, provoking R to L shunt and
reappearance of cyanosis
• Left ventricular dysfunction develops with time
– paradoxical motion of the ventricular septumreduced end-diastolic
– increase in fibrous tissue, and a decrease in cardiomyocytes in the free
wall and septum
– Altered LV geometry.
The Adult Patient with Ebstein Anomaly: Outcome in 72
Attie, Fause M.D.; Rosas, Martin M.D., Ph.D.; Rijlaarsdam, Maria M.D.;
Buendia, Alfonso M.D.; Zabal, Carlos M.D.; Kuri, Jorge M.D.; Granados,
• Studied 72 unoperated patients aged over 25 years with Ebstein anomaly to define the patterns of
presentation, anatomic characteristics, outcome, and predictive factors for survival at National
Institute of Cardiology, Mexico City, Mexico, from January 1, 1972, to December 31, 1997
• Severity as per echocardiography by estimating the septal leaflet attachment ratio (SLAr), defined
as the distance from the atrioventricular ring to the distal attachment of the septal leaflet ÷ the
total ventricular septal length, in a 4-chamber view at the end of diastole. 3 groups of severity
according to the impact on the median survival time (post hoc analysis): Echo-group 1, SLAr
<=0.44; Echo-group 2, SLAr, 0.45-0.60; and Echo-group 3, SLAr >=0.61.
• Followed for a mean period of 8.0 years (range, 1.6-22.0 yr).
• Mean age at diagnosis was 23.9 ± 10.4 years
• Most common clinical presentation was an arrhythmic event in 37 patients(51.4%),
supraventricular in 35 of these cases. Fifteen patients (22.7%) had atrial fibrillation or flutter at
• Of the 72 patients studied, 25 were dead at 20 years of follow-up, with an estimated cumulative
overall survival of 89% at 1 year, 76% at 10 years, 53% at 15 years, and 41% at 20 years of follow-
up. The median survival time was 31.6 (26.6-37.5 yr) in Echo-group 1; 16.9 (8.8-24.5 yr) in Echo-
group 2; and 7.25 (3.5-13.7 yr) in Echo-group 3.
• Predictors of cardiac-related death included male sex, degree of echocardiographic severity, and
cardiothoracic ratio >=0.65. During follow-up, morbidity was mainly related to arrhythmia and
refractory late hemodynamic deterioration.
What is Eisenmenger Complex?
“………..pulmonary hypertension at systemic level, due to a high
pulmonary vascular resistance (over 800 dynes sec./cm.'), with
reversed or bidirectional shunt through a large VSD (1.5 to 3 cm.
Normal Pulmonary vascular resistance =20-130(70)
Total pulmonary resistance 100-300(200)
Systemic vascular resistance 700-1600 (1100)
Eisenmenger Complex to Eisenmenger Syndrome
• “…….the syndrome described is essentially pulmonary hypertension
with reversed or bidirectional shunt, and it does not matter where
the shunt happens to be.”
Wood P Br Med J. 1958; 2:701-9.
*The Croonian Lectures delivered before the Royal College of Physicians of London on May 13, 1958.
6. EISENMENGER SYNDROME
Wood P Br Med J. 1958; 2:701-9.
The analysis is based on a consecutive series of 127 cases of Eisenmenger's syndrome studied
over a period of 11 years. 12 different anatomical abnormalities which may present in this way.
Eisenmenger Syndrome- Chitra Series
A Sahaet al Int J Cardio .45(1994)199-207
Eisenmenger Syndrome -Clinical Groups
Cyanosis since birth: TGA, Truncus, Univentricular hearts
Failure to thrive in infancy – A settled phase – Symptomatic
adolescent: Large VSD, PDA, AVSD
Insidious presentation: ASD
• Defects or complex lesions at risk to develop PH include the following:
1. Septal defects: ASD, VSD, AVSD, PDA, aorticopulmonary window
2. Single ventricle complexes: double-outlet right ventricle (DORV), double-
inlet left ventricle (DILV) (without adequate pulmonary stenosis)
3. Transposition of the great arteries
4. Truncus arteriosus MOSS ADAMS P1378
Eisenmenger syndrome starts in infancy in about 80% of cases of PDA and VSD, but in only 8% of
cases of ASD; it started in adult life in 92% of cases of ASD .
Pulmonary microvascular injury stimulates the production of elastase enzymes and growth
factors (that is, insulin-like growth factor I and TGF), which may cause medial hypertrophy,
cellular intimal proliferation, progressive occlusion, and eventual destruction of small arterioles
Why more common with post tricuspid shunts?
Post tricuspid lesion ( non restrictive): Soon after birth , direct shunting of blood at
systemic arterial pressure before neonatal PAH has regressed. Lowering of PVR to
normal is prevented by a sufficient increase of flow to keep the pressure at
systemic level. So long as pulmonary hypertension is maintained, vasoconstrictor
tone is not inhibited and the muscular pulmonary arteries do not involute.
not only delays the natural fall in pulmonary vascular resistance, but
also promotes hypertensive changes.
Pretricuspid lesion : Soon after birth, shunting of low pressure blood occurs into the
non compliant neonatal RV. Low pressure shunt flow at rest is not sufficient to
maintain the pulmonary pressure at systemic level. PVR falls to normal before the
relatively slow involution of the right ventricle after birth. So after RV involution L
R shunted high volume blood now actually goes into a low resistance compliant
pulmonary circulation, and does not promote hypertensive changes till late in life.
Once the PVR falls appreciably, much larger flows are necessary to maintain high
• During first 2 years of life, pulmonary hypertension at systemic level maintains the
hypertrophied and contracted state of the muscular pulmonary arteries,
• After about 2 years of continuous pulmonary hypertension, reactive intimal fibrosis
tends to obliterate the lumen of muscular arteries. The obliterative process
replaces vasoconstriction as the chief cause of high PVR. The pulmonary blood flow
at this stage may be no greater than the systemic flow, and repairing the defect is
• As life advances, between 20 and 30 years,thrombo-obstructive lesions develop in
the larger pulmonary arteries and herald the beginning of the downhill course.
Dyspnea – Most common symptom. Eisenmenger PDA is the best tolerated, nearly half of such cases having only
slight breathlessness on effort or none at all. But VSD and ASD had effort intolerance of average grade 2.5 (3/4
grade higher than in PDA. The lack of symptoms in PDA with reversed shunt is attributed to the relatively normal
oxygen tension of blood going to the head and neck.
Hemoptysis- In woods series, it occurred in 33% cases of Eisenmenger VSD and 25% cases of Eisenmenger ASD. At
necropsy the common cause of these haemorrhages was pulmonary infarction from pulmonary artery thrombosis.
In Chitra series hemoptysis occurred in 17% cases.
Other symptoms- Paradoxical embolism, Cerebral abscess, Symptoms of hyperviscosity, Symptoms due to bleeding
A Sahaet al Int J
ES: Underlying CHD
Characteristic VSD PDA ASD
Usual age of ES < 2 years < 2 years 20 – 40 years
- Yes (50%) -
Cardiomegaly - - Yes
Second H S (S2) Single Narrow/normal Wide & fixed
Parasternal heave - - Yes
TR murmur - - Yes
PR murmur - Yes -
Complete AVCD – 30% by 7-12 months , 90% by 3-5 yrs .
TGA Intact IVS – 1% by 2 month, 34% by > 12 mo.
TGA with VSD/PDA – 20% by 2 mon,, 80% by > 12 mo
Faster at high altitude, in Down syndrome( alveolar hypoplasia,
Development of Eisenmenger Syndrome- complex CHD
A retrospective study of 201 patients with Eisenmenger syndrometo determine the long-term survival
pattern and variables affecting long-term survival and complications occurring during follow-up
Followed up for variable duration over a period of 16 years from 1976 to 1992.
Age of presentation varied from 3 months to 62 years (mean +/- standard deviation 19.23 +/- 12.62
A total of 12 different anatomic lesions were seen—the most common three being ventricular septal
defect (33.33%), atrial septal defect (29.85%), and patent ductus arteriosus (14.23%).
Twenty patients died during a mean follow-up period of 54.6 +/- 54.47 months.
Sudden cardiac deaths (30%), congestive heart failure (25%) and haemoptysis (15%) were the most
predominant causes of death. Mean age of death was 25 +/- 5 years
Prognosis for patients with Eisenmenger syndrome of various aetiology.
Saha A, Balakrishnan KG, Jaiswal PK, Venkitachalam CG, Tharakan J, Titus T, Kutty R.
Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum,.
Int J Cardiol. 1994; 45:199-207
Eisenmenger Syndrome -Cause of death
A Saha et al Int J Cardio .45(1994)199-207
Mean age of death in years
Cause of death
Post Op(surgical repair of defect) 26%
Sudden death (VF) 14%
SABE, Cerebral Thrombosis,
Cerebral abscess, Pregnancy
Wood P Br Med J. 1958; 2:701-9
Natural History of Eisenmenger Syndrome -Survival
Atrial Ventricular Aorto
1 year 97.8 96.8 97.18 97.18
5 year 79.78 91.08 87.93 86.95
10 year 72.53 82.53 87.93 79.64
15 year 72.53 82.53 43.96 76.98
p = non significant across all groups
Saha et al Int Jou Cardiology 45(1194) 199-207
Long Term Survival in Eisenmenger physiology
Diller G et al. Eur Heart J 2006;27:1737-1742
ES – Survival better than IPAH
ES exhibits better life expectancy than idiopathic PAH. The long-term prognosis of patients with
Eisenmenger syndrome is better than that of patients with IPAH
Patients with ES commonly survived into the third or fourth decade of life. Patients with ES carry
a survival rate of 80% at 10 years, 77% at 15 years, and 42% at 25 years.
Life expectancy reduced by about 20 years. Unwarranted surgical closure hastens
Eisenmenger Syndrome and Pregnancy
• Mortality of abortion in ES –6%
Pregnancy carries 30-50% maternal mortality
7.Complete Transposition of Great
• Represents 5% to 8% of CHD but accounts for 25% of deaths from CHD in the first year of life#
• Males:females = 4:1, unless there is juxtaposition of the atrial appendages.
• D TGA seldom occurs in firstborns; but in offspring of mothers who have had three or more pregnancies,
a twofold increase in incidence rate has been reported.
• VA discordance is associated with AV concordance.
• The great arteries rise in parallel and do not cross.
• Conal inversion Subaortic portion of the conus persists and subpulmonary conus is absorbed. The
aortic valve moves anteriorly, and the pulmonary valve moves inferoposteriorly into fibrous continuity
with the mitral valve. Pulmonary/mitral continuity exists because a left-sided subpulmonary conus is
absent, and aortic/tricuspid discontinuity exists because a right-sided subaortic conus is present.
#KEITH, J. D., ROWE, R. D., AND VLAD, P.: Heart Macmillan Co., 1958, p. 471.
• Cyanosis on day 1 in >90% of infants with an intact ventricular septum. Mild
cyanosis with delayed onset is a feature of D TGA with a nonrestrictive VSDor PDA.
• Subpulmonary stenosis in15% of cases. Pulmonary valve stenosis is uncommon.
• Pulmonary ejection sound originate in dilated hypertensive posterior pulmonary
trunk. Loud A2 as aorta is anterior
• Midsystolic murmur of sub pulmonary stenosis is present at birth in 3rd left ICS.
With nonrestrictive VSD, PS murmur varies inversely in length and loudness with
the degree of stenosis, as in Fallot's tetralogy.
• Holosystolic murmur of VSD( in D TGA without PS) awaits the neonatal fall inPVR
• CXR- When PBF is increased, the cardiac silhouette has appearance of a tilted egg
lying on its side pointing downward and to the left. Right border of the egg consists
of the right atrium, and the convex left border is the left ventricle.
-Thymic shadow absent (versus DORV)
• Survival depends on intercirculatory communications and the pulmonary blood
• Volume of effective bidirectional mixing depends on depends on the location and
size of the communication that joins the two circulations and on the magnitude of
pulmonary blood flow.
• Pulmonary vascular disease is prevalent in patients with D TGA, especially in the
presence of a nonrestrictive VSD or a large PDA. It is found in 20% of infants before
2 months of age, and in about 80% after 1 year.
• Early pulmonary vascular disease is more prevalent with a nonrestrictive VSD and
complete transposition than with an equivalent isolated VSD.
• Precipitating causes of death: In 1st week , anoxia is the major cause, 2nd to 4th
week, CHF is about equally common. After 1 month, mainly CHF and operation.
• Overall death rate- 30% in 1st week, 50% in 1st month, 90% in 1st year, 98.6% in the
• Overall survival- 70% at 1 week, 50% at 1 month, 10% at 1 year.
• Nonrestrictive VSD with pulmonary vascular disease carries a survival of 30% at 6
months, 20% at 1 year.
• Moderate PS improves longevity by regulating pulmonary blood flow, with survival
of 75% at 1 year.
• Most reaching teenage have a non restrictive VSD with pulmonary vascular disease
or pulmonary stenosis.
• Poorest survival when foramen ovale is restrictive, ventricular septum is intact and
the ductus is closed
• The average life expectancy at birth is 0.65 years; at 1 week of age, 0.87 years; at 1
month, 1.12 years; and at 1 year, 3.92 years.
8. Congenitally Corrected
Transposition of the Great Arteries
• The double discordance—atrioventricular and ventriculoarterial—
physiologically corrects the discordance intrinsic to each
• Prevalence rate - 0.5% of CHD or approximately 1 in 13,000 live births.
• Male:Female = 1.5:1
• Virtually all patients have coexisting cardiac malformations—
Ventricular septal defect- 80%- nonrestrictive PM VSD, typically extends
into inlet and trabecular septum.
Pulmonary stenosis- 50%
Abnormalities of the left AV valve(Ebstein like)- 90%
• S1 soft- due to 1)PR prolongation; 2)malformed anteriorly tricuspid leaflet is small and poorly mobile.
• VSD murmur- is analogous to VSD murmur in hearts without ventricular inversion
• PS murmur – 3rd left ICS as stenosis is subpulmonary
• Left AV valve regurgitation- murmur like PSM of MR but radiates toward the left sternal edge rather than into
the axilla because the malformed tricuspid leaflets direct the jet medially within the left atrium.
• Regular AV node- does not make contact with infranodal right and left bundle as atrial septum is malaligned
with the inlet ventricular septum.
• Anomalous AV node with a bundle penetrates the AV fibrous annulus and descends for a long distance before
branching. Right bundle is concordant with morphologic RV and left bundle withmorphologic LV. With age
conduction fibers are replaced with fibrous tissue, which is responsible for acquired AV block. CHB at birth
results from discontinuity between the anterior AV node and the ventricular septum.
1. Disturbance in conduction
AV conduction- 1st degree HB to CHB in >75% patient when all ages are included. Overall incidence rate of
CHB is about 30%. 5% patients are born with congenital CHB , acquired CHB continues to develop at about
2% per year.
WPW syndrome; supraventricular tachycardia, atrial fibrillation, and atrial flutter
2. QRS pattern of ventricular inversion
Inversion of the right and left bundle results in septal activation from right to left. Q waves appear in right
precordial leads and are absent in left precordial leads.
• The physiologic consequences of congenitally corrected transposition depend on
Functional adequacy of a subaortic morphologic RV and
Coexisting congenital malformations
• Symptoms and clinical course depend on coexisting malformations, but longevity
principally depends on the vulnerability of the subaortic morphologic RV
• 20% to 30% of patients die in the first year. Infant mortality is related to CHF.
Survival is then relatively constant, with an attrition rate of approximately 1% to 2%
• 1% of congenital heart disesase
• M:F = 2-4:1
• 90 % of cases it is LV
– An outlet chamber present at its base anterosuperiorly. Non inverted means right anterosup and
inverted means left ant sup position of outlet chamber.
– LV communicates with it via an outlet foramen
• Discordant great vessels(transposed)- aorta arise discordantly from outlet chamber and pulm trunk
• Neonates comes to attention because of CHF, cyanosis or murmur
• A prominent systolic murmur at the mid left sternal border originates in the outlet foramen when
pulmonary blood flow is increased
• Pulmonary stenotic murmurs are prominent at the mid or lower left sternal border when the stenosis
is subpulmonary, and vary inversely in length and loudness according to the degree of stenosis as in
Single morphologic LV with inverted outlet chamber- QRS axis is directed inferior and to the right..
Ventricular depolarization is clockwise, so Q waves appear in leads 2, 3, and aVF.
Single morphologic LV with non-inverted outlet chamber- QRS axis tends to be directed leftward and
superior—left axis deviation . LVH. Precordial QRS patterns are stereotyped
Various types of
Outlet chamber is located
anterosuperiorly at the
base of heart
Outlet chamber is inverted
(left sided) in B & D
Outlet chamber is
noninverted (right sided) in
A & C
PS present in C & D
Streaming of blood
• The streams of RA venous blood and LA oxygenated blood remain
separated remarkably in LV
• Separation greatest when
– PVR is low
– outlet chamber inverted (left sided)
• This phenomenon of streaming results in LA blood entering aorta and
RA blood entering the pulmonary trunk
• Restrictive outlet foramen, which consitutes a form of subaortic
stenosis diverts more blood into pulmonary circulation and can lead
to refractory CHF.
• PS if present leads to increased cyanosis.
Univentricular Heart with PS
• PS may be
– Either subpulmonary
– Or valvular with a bicuspid PV
• Degree of stenosis varies from mild to severe, even pulmonary atresia
• In Holmes heart (univentricular heart of LV type with concordant
great vessels), subpulmonary stenosis occurs as a rule
• Like TOF, squatting to relieve dyspnoea and hypoxic spells observed
Natural history of Univentricular Heart with PS
• History dependent on degree of PS, presence and degree of
subaortic stenosis and PVR
• Infants with SV with PS have reduced PBF which prevents CHF,
hence moderate PS is physiologically desirable.
• Severe PS/ pulmonary atresia leads to profound cyanosis and
• Univentricular heart of LV type
– Annual attrition rate is 4.8%
– 50% dead at 14 years of age
– With PS survival into adolescence and early adulthood is
not rare. Longevity occasionally extends into 4th or 5th
• Univentricular heart of RV type
– 50% dead at 4 years
1. Am. J. Cardiol. 1984
10. Pulmonary Stenosis with Interatrial
Physiologic consequences of PS with an interatrial communication depend on
the degree of obstruction to RVOT and size of the interatrial communication
A restrictive interatrial communication is almost always a PFO, shunt is
right-to-left, and PS is necessarily severe clinically analogous to isolated
severe pulmonary valve stenosis, except for cyanosis that can be present at
A nonrestrictive interatrial communication is almost always an OS ASD,
shunt is left-to-right, and PS is necessarily mild to moderate clinically
resembles an isolated ASD
• Severe PS with a right-to-left shunt through PFO is more common than PS
with nonrestrictive ASD, irrespective of the direction of the shunt.
• Death is usually from right ventricular failure and less commonly from
hypoxia, cerebral abscess, or infective endocarditis
11.Congenital Anomalies of Vena Caval
• Two well-known anomalies of systemic veins are persistent left superior vena cava (SVC) and
infrahepatic interruption of the IVC with azygos continuation.
1. Persistent left SVC occurs in 0.3% of the general population and in 4.3% of CHD.
• The persistent left SVC is connected to the RA in 92% of cases and to the LA (producing cyanosis)
in the remainder.
• Isolated left SVC produces no physiologic derangements when it drains into RA via coronary sinus.
• A persistent left SVC is into LA causes right to left shunt and in a decrease in systemic arterial
oxygen saturation. The coronary sinus is usually absent with partial or complete unroofing of its
anterosuperior wall. Unroofing results in a connection between LA and RA—a coronary sinus type
of ASD. Associated cardiac anomalies almost invariably are present. Complex defects, such as cor
biloculare, conotruncal abnormalities, and asplenia syndrome, are commonly found.
• Cyanosis dates from birth or infancy. Cyanosis increases with effort because caval
venous return increases.
• Despite conspicuous cyanosis, paucity of symptoms- syndrome of cyanosis and
clubbing with normal heart.
• When a right SVC is absent or connects to the LA, the sinus node is absent, so the
atrial focus is ectopic.
• Adult survival is expected
2. Interrupted IVC with azygos continuation has been reported in about 3% of
children with CHD.
• Associated with complex cyanotic heart defects, such as polysplenia syndrome,
double-outlet RV, cor biloculare, and anomalies of pulmonary venous return.
12. Congenital Pulmonary Arteriovenous Fistula
• Approximately 75% of congenital pulmonary AV fistulae involve the lower lobes or right
middle lobe; they usually occur without coexisting CHD.
• Pulmonary AV fistulae occur in 5% to 30% of patients with telangiectasia, and
telangiectasia occur in 30% to 60% of patients with pulmonary AV fistulae
• Physiologic consequences of pulmonary AV fistulae depend on the amount of
unoxygenated blood delivered through the malformation and on the size of the
malformation, which tends to increase with age.
• Net volume of blood reaching left side of heart is little if at all affected. As blood flow
through the malformation is increased, flow through uninvolved lung decreases by a
comparable amount. So cardiac output remain normal.
• The fistulae tend to increase in size and number with the passage of time and are
seldom recognized until adulthood.
• Mean patient age in a large series was 39 years (range, 3 years to 73 years), with a distinct
majority over age 20 years.
• Approximate mean ages of death: The mean age falls from 72 in normal subjects to 43 years
for PDA, to 41 years for ASD, to 35 years for AS, to 34 years for aortic coarctation, to 3I years
for all VSD, to 29 years for PS, to ,20 years for large VSD, and to 15 years for Fallot's tetralogy.
For other cyanotic malformations it is much lower, about 4 or 5 years, and for TGA only 10
Percentages of deaths each decade for normal subjects (on
left), for subjects withFallot's tetralogy and transposition (on
right), and for commoner cardiac malformations, generally
acyanotic at first (in between).
British Heart_Journal, I972, 34, 3-8.
• At birth, cyanotic malformations are about 20 per cent of all cardiac malformations.
But only Fallot's tetralogy and transposition of the great arteries reach an incidence
of the same order as several acyanotic malformations.
• The mortality of all cardiac malformations in the first year of life is very high, but
for truncus arteriosus and transposition it is about 90 per cent, so high that at
clinics for older children and adults few examples of the former are seen.
• Truncus arteriosus= Abbott gave the mean age of death in her 2I necropsies as 4
years. Bruins and Dekker (I968) say that 2 out of 3 patients die within the first 6
• Pulmonary atresia = Abbott (1936) found the mean age of death about 5 years,
and that about one-quarter of her cases had an intact ventricular septum.
British Heart_Journal, I972, 34, 3-8.
• Patients with TOF have undergone repair at earlier ages. The rationale for this trend is based on the belief that
earlier complete repair may be performed safely and that complications from additional palliative procedures,
long-standing cyanosis, and other infrequent but serious comorbidities, such as cerebral abscesses or strokes,
are avoided. There is speculation that long-standing right ventricular hypertension, in the setting of unrepaired
TOF, results in significant and possibly permanent myocardial changes, such as fibrosis, which may lead to
impaired systolic and diastolic properties. This, in turn, may result in a predisposition to functional impairment
of myocardial performance or possibly ventricular arrhythmias.
• Although it is currently accepted that evidence for hypercyanotic spells provides an important rationale for
earlier surgical intervention, propranolol has been suggested as having some efficacy in minimizing or
extinguishing the occurrence of these events
• patients who have a relative anemia and microcytosis are at elevated risk for cerebrovascular accidents. They
are also at increased risk for hypercyanotic spells.
• Most interventional procedures,are undertaken owing to two general indications: Relief of various levels of
pulmonary obstruction: balloon valvuloplasty or right ventricular outflow tract stent placement means for
reducing symptomatic cyanosis in patients with severe annular hypoplasia and Coil embolization of accessory
and duplicated sources of pulmonary blood flow prior to surgical correction
• Potential shortcomings with performing an initial palliative procedure, including pulmonary artery distortion,
additional ventricular volume loading, and the surgical risk attendant with a thoracotomy. Indications are
severe pulmonary artery hypoplasia and some patients with an aberrant course of the anterior descending
coronary artery from the right coronary artery
• If anatomically and surgically possible, pulmonary valve function is preserved by avoiding a transannular patch.
• A vertical infundibular and right ventricular incision is then made. If the pulmonary annulus is prohibitively
hypoplastic, then the incision is carried across the annular valvular apparatus. The ventricular septal defect may
be closed from either a ventricular or atrial approach. A combined transatrial and transpulmonary approach
has been proposed as a reliable and safe method . Resection of significant right ventricular obstruction can be
achieved through an atrial exposure, if required.
Etiologies of cyanotic CHD with
• RVH on ECG
1. TOF – most common
2. DORV with S/A VSD with PS
3. Eisenmenger’s syndrome
4. D TGA with PS or TGA with VSD with PVOD
• LVH on ECG
1. Tricuspid atresia
2. Pulmonary atresia with intact ventricular septum with small RV.(>3/4 of all Pulm atresia)
• BVH on ECG
1. SV with PS
2. PTA type II or III with a hypoplastic PA
1. Ebstein’s anomaly
Etiologies of cyanotic CHD with
• RVH on ECG
1. D TGA with intact ventricular septum(ASD with normal PAP with N PVR).
4. DORV with S/A VSD with N PVR; DORV with S/P VSD.
• LVH or BVH on ECG
1. PTA –(BVH)
2. Single ventricle without PS(LVH)
3. D TGA with nonrestrictive VSD with low PVR (BVH)
Causes of delayed cyanosis
• 1. TOF
• 2. eisenmenger synd
• 3. PS e PFO
• 4. Pulm AV fistula
• Tof occurs in presence of additional non cardiac congenital anomaly: 22q11.2 microdeletion;
trisomies(22,18,13); holt oram(TBX5); alagille(NOTCH2)
Genetic testing in TOF: only in children with syndromic TOF
Variants of TOF
1. TOF e pulm atresia. 2. TOF e absent pulm valve. 3. TOF e AVSD. 4. TOFe origin of one pulm artery from RV and
one from ascending aorta(left one)
LAD e counterclockwise
• TA of commonest type
• DORV S/A VSD no PS
• TOF-AV CANAL
• Primum ASD
• SV-NON INVERTED OC
• Maternal rulella PDA
• L to R shunt= weight more affected
• R to L shunt= both wt & ht affected
• Eisenmenger VSD (vs TOF)- hist of childhood LRTI, JVP a wave, dull pulm area, P2 loud, pulm ejection click, no gr
• Assess severity of TOF- onset of cyanosis; aortic click; length of murmur