Natural history of right to left

shunts

Presenter - Dr. Dinanath KumarDM 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. TOF 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.

Classical TOF, 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 TGA physiology• 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

Admixture physiology• 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 admixture physiology.

• Therefore, in admixture lesions the aortic and pulmonary artery saturations

are equal.

Totally anomalous pulmonary venous connection (TAPVC), Atresia of one of the atrioventricular valves (Tricuspid atresia, mitral atresia), 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

arteriosus.Ann Pediatr Cardiol. 2011 Jan-Jun; 4(1): 53–59

Tetrology of fallot

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 1988;29:137-142).

– 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

murmur• Natural history is determined mainly by degree of

RVOT obstruction

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

12%

73%

15%

at birth3-12 months of ageafter infancy

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 infancyo Often benigno Mild to moderate cyanosis tends to increase

– Increased oxygen requirements of the growing infant rather than with progressive obstruction to RVOT.

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.

Hypoxic spells

• Potentially lethal • Equally common in less cyanosed patients• Peak incidence between 2-6 months of age, but may occur till 2 years; rare in adults. • Mechanism-

– 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

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

accompanies 1. Pulmonary atresia with excessive flow through large systemic

arterial collaterals.2. Absent pulmonary valve volume overload of pressure overloaded

RV. 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 causes1. Systemic HTN-increases LV and RV afterload and can induce RV or B/V failure2. Acquired calcific stenosis of the biventricular aortic valve-imposes increased afterload on both RV and LV3. Aortic valve regurgitation-causes RV failure by imposing volume overload on the already pressure-

overloaded RV4. 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 collaterals.

• 9.5 per cent had systemic hypertension and 6.7 per cent had aortic regurgitation.

• 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

12% all deaths

17% of deaths

<2years62% alldeaths

24%

Singapore medical journal vol. 14, No.3, sept 1973

11%

6%

3%

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 periphery.

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 arteries– 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 Pulmonary Valve

• 3-6% of TOF patients

• Severe pulmonary regurgitation seen

• Disease hallmark - Main and branch pulmonary arteries massively dilated– This aneurysmal dilatation can lead to tracheobronchial compression

and respiratory distress, which is characteristic of this syndrome

• 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 shunt

• 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 annulus.

• 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 groups1. 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.

r TOF

• > 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 females).

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 al;Circulation 1961;23:603

• 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 patternsA. 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

5.Ebstein anomaly

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.

Clinical features

• 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.

ECG• Tall peaked Himalayan P waves and PR interval prolongation- prolonged conduction in the

large RA.• 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

Fetal Ebstein’s

• Outlook is dismal• Fetal hydrops occurs as a rule• Recognized cause of death in utero

Neonatal Presentation

• 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 anomaly.

• Neonatal presentation associated with poor prognosis– 20% die in 1 month, and less than 50% survive to 5 years– Cause: HF/Hypoxia

Circulation. 2007.115.277-285

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;28:84–95

• 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 volume– 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 Unoperated Patient

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 presentation• 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.

MEDICINE 2000

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. across).”

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 window2. Single ventricle complexes: double-outlet right ventricle (DORV), double-inlet left

ventricle (DILV) (without adequate pulmonary stenosis)3. Transposition of the great arteries4. Truncus arteriosus MOSS ADAMS P1378

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 window2. Single ventricle complexes: double-outlet right ventricle (DORV), double-inlet left

ventricle (DILV) (without adequate pulmonary stenosis)3. Transposition of the great arteries4. 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 pulmonary pressure.

• 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 without benefit.

• 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 diathesis

Chitra series

A Sahaet al Int J Cardio .45(1994)19

9-207

ES: Underlying CHD ES: Underlying CHD

Characteristic VSD PDA ASD

Usual age of ES

< 2 years < 2 years 20 – 40 years

Differential Cyanosis

- 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, Tracheomalacia)

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 years).

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

VSD 20.37+-5.95

ASD 26.71+/-6.65

PDA 27+-21.49

Cause of death

Hemoptysis 29%

Post Op(surgical repair of defect) 26%

CHF 17%

Sudden death (VF) 14%

SABE, Cerebral Thrombosis, Cerebral abscess, Pregnancy

5%

Wood P Br Med J. 1958; 2:701-9

Natural History of Eisenmenger Syndrome -Survival

% survival

Atrial Ventricular Aortopulmonary

All

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 groupsSaha 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 IPAHPatients 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 death

Eisenmenger Syndrome and Pregnancy

• Mortality of abortion in ES –6%

Pregnancy carries 30-50% maternal mortality

7.Complete Transposition of Great Arteries

• 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.

Clinical features• 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 VSD or 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 flow• 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.

Interatrial communication VSD PDA

• 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. [Circulation. 1969;40:237-262]

• Overall death rate- 30% in 1st week, 50% in 1st month, 90% in 1st year, 98.6% in the first decade.

• 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.

Circulation. 1969;40:237-262

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% Conduction defects.

• 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.

ECG- • 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% per year.

9.Univentricular Heart• 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

from LV.

• 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 TOF

• ECG 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 univentricular heart

Outlet chamber is located anterosuperiorly at the base of heart

Outlet chamber is inverted (left sided) in B & DOutlet 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 may occur

• 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 early death

Overall survival

• 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 decade.

• Univentricular heart of RV type– 50% dead at 4 years

1. Am. J. Cardiol. 1984

10. Pulmonary Stenosis with Interatrial Communication

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 birth

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 Connection

• 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 months.

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.

THANK U…

• 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 months.

• 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.

• Unifocalisation-

Etiologies of cyanotic CHD with reduced PBF

• RVH on ECG1. TOF – most common2. DORV with S/A VSD with PS3. Eisenmenger’s syndrome4. D TGA with PS or TGA with VSD with PVOD

• LVH on ECG1. Tricuspid atresia2. Pulmonary atresia with intact ventricular septum with small RV.(>3/4 of all Pulm atresia)

• BVH on ECG1. SV with PS2. PTA type II or III with a hypoplastic PA

• RBBB1. Ebstein’s anomaly

Etiologies of cyanotic CHD with increased PBF

• RVH on ECG1. D TGA with intact ventricular septum(ASD with normal PAP with N PVR).2. TAPVC3. HLHS4. DORV with S/A VSD with N PVR; DORV with S/P VSD.

• LVH or BVH on ECG1. 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

Syndromic TOF• 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 TOF1. 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 3 ESM.

• Assess severity of TOF- onset of cyanosis; aortic click; length of murmur