Left-Right Shunt Natural history & Principles of Management Dr ranjith mp

Ventricular Septal Defect

Incidence Most common congenital heart defect in children Incidence is 8 per 1000 live births Echo studies- 5 to 50 per 1,000 newborns Ooshima A et al. Cardiology 1995;86:402-406. No sex preference , except in subarterial defect

Racial variation Muscular defects 10% in the west 5% in western ASIAN WESTERN Doubly commited subarterial Multiple ventricular septal defects are rare Doubly-commited subarterial defect requiring repair is 30% Muscular defects 10% in the west 5% in western Ferreira Martins JD et al.Cardiol Young 2000; 10: 464–73.

Ventricular Septal Defect Pathologic anatomy of IVS

Ventricular Septal Defect Soto et al classification of VSD Perimembranous (membranous/ infracristal )-70-80% Muscular- 5-20% Central- mid muscular Apical Marginal- along RV septal junction Swiss cheese septum – multiple defects Inlet/ AV canal type-5-8% Supracrital (Conal/ infundibular/subpulmonary/doubly committed subarterial)- 5-7% Benigno soto et al. Br HeartJ 1980; 43: 332-343

Hemodynamic classification Restrictive- less than one third of aortic root LVSP > > RVSP Pulm /Aortic systolic pressure ratio < 0.3 Qp / Qs<1.4:1 Moderately restrictive RVSP high, but less than LVSP Qp/Qs 1.4:2.2 Non restrictive - The size of aortic orifice RVSP , LVSP, PA Aortic systolic pressures are equal Qp/Qs >2.2 Flow determined by PVR

Malalignment type of VSD Anterior more common than posterior Usually involves the infundibular septum Occurs as if there is a door that moves round on a hinge

Natural History of VSD The outcome and natural history influenced by Position & Size Number of defects Anatomic structures in the vicinity of the defect Association of other malformation Age at which the defect is recognized Sex of the patient

Natural History of VSD Cardiac failure Spontaneous diminution in size or closure Right or Left ventricular outflow tract obstruction Aortic regurgitation Pulmonary vascular obstructive disease Infective endocarditis

Cardiac failure Rare in small VSD as size limits the L-R shunt In large VSD the relative resistances of the systemic and pulmonary circulations regulate flow Shunt occurs mainly in systole Shunt directly to PA Enlargement of LA, LV,PA

Cardiac failure After birth decline in PVR to adult level by 7to 10 days In large VSDs, the rate of this process is delayed Small VSD the shunt is small & remain asymptomatic Moderate sized VSD symptoms by 1to 6 months Rarely, adults present with new exercise intolerance .) Rudolph AM, et al.Pediatrics 1965;36:763-772.

Cardiac failure Large VSD congestive heart failure in first few weeks Risk for recurrent pulmonary infection high If survives without therapy - pulmonary vascular disease develop in the first few years of life Symptoms “get better” as Qp/Qs returns to 1:1 Intervention at this time - a shorter life expectancy than if the defect were left open Fuster V, et al.Cardiovasc Clin. 1980;10:161–197.

Spontaneous diminution in size Occurs in both perimembranous and muscular Closure is documented in the fetus & in the adult VSD diagnosed in the fetus - 46% closed in utero & 23.1% in the first year, while 30.8% remained patent In this study 15.8% of defects < 3 mm remained patent in comparison to 71.4% > 3mm at 1yr Nir A et al.Pediatr Cardiol 1990; 11: 208–10.

Spontaneous diminution in size More frequent in <10 yrs of age Isolated VSD ( 124 pts) - 34% at 1 yr & 67% at 5 yr Female predominance Decreases substantially after 1 year of age Mehta AV et al. Tenn Med 2000; 93: 136–8. Farina MA et al . J Pediatr 1978; 93: 1065–6. Moe DG et al. Am J Cardiol 1987; 60: 674–8.

Spontaneous diminution in size Rare in malaligned VSD In outlet VSD closure only in 4% All of the defects closed were initially < 4 mm Tomita H et al. Jpn Circ J 2001; 65: 364–6

Mechanisms of spontaneous closure Different for perimembranous and muscular Perimembranous Reduplication of tricuspid valve tissue Progressive adherence of the septal leaflet of the tricuspid valve about the margins of the VSD Aneurysmal transformation of the membranous septum (appearance on angiography) Early systolic click & late crescendo systolic murmur Anderson RH et al . Am J Cardiol 1983; 52: 341–5. Freedom et al. Circulation 1974; 49: 375–84.

Mechanisms of spontaneous closure Muscular- direct apposition of muscular borders Large subarterial defect don’t close Closure of a perimembranous defect by adhesion of the tricuspid leaflets to the defect margin. Closure of a small muscular defect by a fibrous tissue plug. Closure of a muscular defect by hypertrophied muscle bundles in the right ventricle Closure of a defect in subaortic location by adhesion of the prolapsed aortic valve cusp

Right ventricular outflow tract obstruction Incidence 3% to 7%. Mechanism:- Hypertrophy of malaligned infundibular septum Hypertrophy of right ventricular muscle bundles Prolapsing aortic valve leaflet High incidence in Right sided aortic arch Horizontal RVOT Nadas AS et al . Circulation 1977; 56(No.2, Suppl. I): 1–87. Corone P et al. Circulation 1977; 55: 908–15. Pongiglione G et al . Am J Cardiol 1982; 50: 776–80. Varghese PJ et al . Br Heart J 1970; 32: 537–46. Tyrrell MJ et al. Circulation 1970; 41 & 42(Suppl. III): 113.

Aortic valve prolapse VSD with direct contact with the aortic valve are most prone to develop AVP All the perimembranous defects All doubly committed juxtaarterial defects Most of muscular outlet defects Characteristic deformity of aortic cusp-nadir of the cusp is elongated

Aortic valve prolapse RCC (60-70%) , NCC (10-15%) , both in 10-20% Non-coronary cusp prolapse in perimembranous type Left coronary cusp prolapse extremely rare AR may be due to incompetent bicuspid aortic valve Rarely prolapsed valve cusp may perforate

Aortic valve prolapse Pathogenesis Anatomic factors for normal competence Leaflet support by diastolic apposition Infundibular support from below Intrinsic structural abnormality Progressive discontinuity between aortic valve annulus & media

Aortic valve prolapse Pathogenesis Hemodynamic factor ‘’Venturi effect’’ VSD is restrictive, Qp/Qs<2 , absence of PAH Komai H et al.Ann Thorac Surg 64:1146-1149, 1997

Natural history of Aortic valve prolapse Unknown exact prevalence (2% to 7%) Rare before 2 years More severe - additional volume load Aneurysm of sinuses of Valsalva may develop Nadas AS et al . Circulation 1977; 56(No.2, Suppl. I): 1–87.

VSD with AR- Indian scenario 362 Patients. 37 (10.2%) had AR Mean age 13.4 years ( 2-45),male to female ratio 5:1 31 (84%) had infracristal & 6 (16%) supracristal VSD Infracristal VSD-RCC prolapse in 14 (48%) &NCC in 12 (41%) and both RCC and NCC in 3 (11%) Supracristal VSD - RCC prolapse in 5 (83%),NCC in 1 Two patients the AR was due to bicuspid aortic valve PA pressure normal in 26(70.2%), L-R shunt 1.5:1 or less in 23 (62%) No relationship- severity of AR & location of VSD Somanath HS et al. Indian Heart J. 1990 Mar-Apr;42(2):113-6.

Intervention in VSD with AVP Indicated for both perimembranous and subarterial VSDs when more than trivial AR Subarterial VSDs >5 mm - closed regardless of AVP Restrictive perimembranous VSD with AVP but without AI, surgery indications are less clear Follow up regularly Surgery is indicated only if AI develops Elgamal MA et al . Ann Thorac Surg 68:1350-1355, 1999 Lun K et al. Am J Cardiol 87:1266-1270, 2001 Gabriel HM et al. J Am Coll Cardiol 39:1066-1071, 2002

Left ventricular outflow tract obstruction Usually above the ventricular septal defect Etiology:- Progression of the pre-existing lesion Acquired Two types:- Muscular Fibromuscular

Left ventricular outflow tract obstruction Three major structures are responsible Posteriorly malaligned outlet septum Septal deviation ( anteroseptal twist) Muscular protrusion of the left ventricular aspect of the septum Anterolateral muscle bundle Muscular protrusion between LCC & AML- present normally in 40% (Very rarely “Mitral arcade”) Careful echo assessment of the LVOT should be performed in all cases of VSD before surgery Moene RJ et al. Pediatr Cardiol 1982;2: 107–14.

Pulmonary vascular obstructive disease Incidence - 5% to 22% Rare in small & Moderate-size VSDs Down syndrome – early development of PAH No overall sex predilection Keith JD et al. Heart Disease in Infancy and Childhood. 1978: 320–79.

Pulmonary vascular obstructive disease Survival rate for patients with VSD by pulmonary artery systolic pressure 42 men and 37 women, 18 to 59 years (mean 34 yrs) 67 patients treated medically and 12 surgically All patients were followed up for 1 month to 25 yrs ( mean 9yrs) The solid line indicates a pressure less than 50 mm Hg (n = 36) Dashed line indicates a pressure of 50 mm Hg or greater (n = 17) Ellis JH 4th et al . Am Heart J. 1987;114:115-205

Pulmonary vascular obstruction Eisenmenger complex, develops in 10% to 15% most commonly in the 2 nd & 3rddecades of life common causes of death "sudden" or "unknown“ Development of pulmonary vascular disease after surgery depends on age at procedure is done Infants with VSD and increased pulmonary artery pressure - repair between 3 and 12 months

Infective endocarditis 18.7 per 10000 person-years in non operated cases Operated VSD 7.3 per 10000 person-years Higher in small defect & lower during childhood Patients with a proven episode of endocarditis are considered at increased risk for recurrent infection so surgical closure may be recommended Gersony WM et al.Circulation 1993; 87(Suppl. I):I-121–I-126.

Arrhythmias Patients with VSD have a high incidence of arrhythmia Ventricular tachycardias in 5.7% Sudden death is 4.0% SVT, mostly AF, is also prevalent Age and pulmonary artery pressure are the best predictors of arrhythmias The odds ratio of serious arrhythmias increases 1.51 for every 10-year increase in age 1.49 for 10mm Hg increase in mean PA pressure Wolfe RR et al. Circulation. 1993;87:I89-101

Improvement of symptoms in VSD Closing defect - soft S2, high frequency & shorter murmur Increasing PVR : increased RV pulsations ,S2 loud & narrow split Infundibular hypertrophy & resulting decreased L to R shunt : S2 decreases in intensity ,crescendo-decrescendo systolic murmur in the ULSB

Indications for Operation Heart failure not controlled by medical therapy VSD should be operated with in 6 month of life Qp/Qs is 2 or more surgical closure needed regardless of PA pressure VSD with PVR more than 4 unit during 6-12 months VSD with elevated PVR first seen after infancy Moderate VSD with no size change in childhood

Postoperative Sequelae Right bundle branch block 33.3% undergoing transatrial repair 78.9% to 11% in repair via a right ventricular incision Transpulmonary approach has the lowest incidence Complete heart block in 1 to 2% Pulmonary hypertension in (4% ) Sinus node dysfunction (4%) Progressive aortic valve insufficiency (16%) Abe T et al . Jpn Circ J 1983; 47: 328–35. Roos-Hesselin JW et al. Eur Heart J 2004;25:1057-1062.

Patent Ductus Arteriosus

Introduction Incidence of isolated PDA in term infants - 1 in 2,000 Female predominance - 3:1 High incidence- Prematurity, Maternal rubella Genetic inheritance- Autosomal recessive with incomplete penetrance

Natural History of PDA Congestive heart failure Infective endarteritis Pulmonary vascular disease Aneurysmal formation Thromboembolism Calcification

Congestive heart failure CHF resulting from an isolated PDA either develops in infancy or during adult life HF in infancy usually occurs before of 3 mths of age Initially left heart failure, later right heart failure Good response to drugs initially, but is not maintained

Infective endarteritis Major cause of death in earlier era Incidence - 0.45% to 1.0% per annum Vegetations usually found at the PA end of the duct May cause recurrent pulmonary embolism Infection may also cause a ductal aneurysm Cosh JA. Br Heart J 1957; 19: 13–22.

Pulmonary vascular obstructive disease No definite data on incidence “Differential cyanosis” Eisenmenger patients do not tolerate PDA closure

Aneurysm of the duct Described either pre- or postnatally Likely develops in the third trimester due to abnormal intimal cushion formation or elastin expression Incidence varies from 1.5% to 8.8% Dyamenahalli U et al. J Am Coll Cardiol 2000; 36: 262–9. Jan SL et al. J Am Coll Cardiol 2002; 16: 342–7.

Aneurysm of the duct Complications Thromboembolism Dissection Rupture Tracheal compression Left recurrent laryngeal nerve palsy Pulmonary artery obstruction Regression can occur, presumably due to thrombosis and subsequent organization

Treatment of PDA As many ducts will eventually close in premature infants approach to treatment is different - preterm infant Vs mature, child Beyond infancy, closure reported in 0.6% per year Medical therapy Treatment of Heart failure Ductal closure with drugs Surgical Therapy Campbell M et al.Heart 1968;30:4–13.

Ductal closure with drugs Indomethacin Rates of success varying between 18% to 89% Major determinants of success were gestational and postnatal age Less chance of closure-Extreme prematurity, very low birth weight, and advanced postnatal age The rate of re-opening is highest in the extreme premature( 1/3) & less than 1/10 those weighing 1500 g Mahony et al. N Engl J Med 1982;306: 506-510.

Ductal closure with drugs Ibuprofen Comparable rate of ductal closure to Indomethacin Less effect on renal function Increased incidence of Pulmonary hypertension Gournay V et al. Lancet 2004;364:1939-1944.

Intervention in PDA Coils closure for <3 mm, >97% success, zero mortality Larger PDAs - specialized devices >98% complete closure rate at 6 months

Indications for intervention in PDA Symptomatic moderate or large PDA with L to R shunt Prior history endarteritis [class1] Reasonable in small L to R shunt with normal-sized heart chambers when the PDA is audible by auscultation[IIa] May be considered in bidirectional PDA shunt due to PAH and obstructive pulmonary vascular disease but reversible to pure L to R shunting with pulmonary vasodilators [IIb]

Atrial Septal Defect

Introduction Incidence is 1 child per 1,500 live births More frequent in females than males by about 2:1 Most ASDs occur sporadically; however, a few families have the defect as a genetic abnormality. Mutation in-TBX5, NKX2.5 , GATA4, Myosin heavy chain 6 Samanek M et al. Pediatr Cardiol1999;20:411–7

Natural History of ASD The natural history depends on Size of the defect Rt. & Lt. ventricular diastolic compliance Pulmonary-to-systemic vascular resistance

Natural History of ASD Hemodynamic/anatomic abnormalities resulting from a secundum atrial septal defect include Right ventricular and atrial volume overload Pulmonary vascular obstructive disease Tricuspid valve and/or pulmonary valve regurgitation Supraventricular tachyarrhythmias

Natural history Shunt direction & magnitude are variable and age dependent In fetal life, RV noncompliance, a result of high pulmonary vascular resistance, allows nearly unidirectional right-to-left flow at the atrial level Immediately after birth, with RV compliance comparable to that of the LV, there may be little net shunting through ASD With the physiological fall in pulmonary vascular resistance, the RV thins, compliance increases, left-to-right shunt develops

Natural history With similarly sized ASDs, adults have larger shunts .) Four common clinical presentations of ASD in adult Progressive shortness of breath with exertion Pulmonary vascular obstructive disease Atrial arrhythmia stroke or other systemic ischemic event

Natural history Most infants with ASDs are asymptomatic They may present at 6 to 8 weeks of age with a soft systolic ejection murmur and possibly a fixed and widely split S2 CHF rare in the first decades of life but it can become common once the patient is older than 40 yrs

Atrial arrhythmia Atrial arrhythmia may be the first presenting sign (13% in older than 40 & 52% in older than 60 yrs of age) Prevention of Atrial arrhythmia is one of the reasons for repairing ASD in young asymptomatic patients (Silversides CK et al. Heart. 2004;90:1194 –1198.) Subsequent development of AF may depend more on the patient’s age at intervention and may occur despite surgery in patients > 25 years of age St. John Sutton MG,et al. Circulation 1981;64:402-409. Murphy JG, et al. N Engl J Med. 1990;323:1645–1650

Pulmonary vascular obstruction Uncommon in ASD Incidence is 5% to 10% of untreated ASDs Predominantly in females Sinus venosus ASDs have higher pulmonary artery pressures & resistances than patients with secundum Vogel M et al. Heart 1999; 82: 30–3.

Pulmonary vascular obstructive disease Craig and Selzer in 1968 studied 128 adult patients Significant PAH developed in 22% of the series This complication usually develops when the patient is between 20 and 40 years of age Cherian et al studied 709 pts.of isolated ASD PASP was > 50 mmHg in 17% PAH was present in 13% of patients under 10 yrs 14% of those aged 11 to 20 years Eisenmenger syndrome 9% Craig RJ et al. Circulation 1968; 37: 805–15. Cherian G et al. Am Heart J 1983; 105: 952–7.

Spontaneous Closure Spontaneous closure most likely in ASDs <7 to 8 mm Younger age at diagnosis A review of 101 infants -mean age of diagnosis 26 days average follow-up of 9 months. Spontaneous closure in all 32 ASDs <3 mm 87% of 3- to 5-mm ASDs 80% of 5- to 8-mm ASDs None of 4 infants with defects >8 mm Radzik D, et al. J Am Coll Cardiol. 1993;22:851-853.

Spontaneous Closure A follow up of 84 children for 4 years showed a spontaneous closure or decreased size in 89% with a 4-mm ASD 79% with a 5- to 6-mm defect 7% with a defect >6 mm Helgason H, et al. Pediatr Cardiol.1999;20:195-199. Even infants with CHF can have spontaneous reduction in the size of the ASD years after the diagnosis Occasionally, spontaneous closure will occur as late as 16 years.

Indications for Intervention Evidence of Rt. sided cardiac volume loading, Qp:Qs > 1.5:1 Symptomatic patients (principally exercise related) PVR < 7 WU – closure is usually well tolerated Need to be mindful of elevated LVEPD Pts may need diuretic therapy after closure For PVR >7 WU and PA pressures >50% need to perform O2 and NO study

Indications for Intervention Elective repair frequently has been deferred until the child is at least 4 years of age. Early operation has been recommended for those infants and young children who have unremitting heart failure or associated pulmonary hypertension contraindication :- pulmonary hypertension with Rt. to Lt shunting at rest Pulmonary vascular resistance of 14 WU

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MCQ’s

1.All are true regarding natural history of VSD except? In large VSDs, the rate of decline in pulmonary vascular resistance after birth is delayed In Down syndrome the development of CHF is delayed CHF symptoms get worsen initially as pulmonary vascular resistance increases Adults may present with new symptom of exercise intolerance

2.False statement regarding natural history of VSD is? Usually moderate sized VSDs can be managed medically without surgical intervention during infancy Intervention to close the VSD with PAH would shorter life expectancy than if the defect were left open There is enlargement of LA, LV, RV and PA in moderate sized VSDs Development of PAH may occur in as many as a quarter of patients with large defects who undergo surgery after 2 years of age.

3.False statement regarding natural history of VSD is? In outlet VSD 25 % will close by 2yrs Isolated VSD closure rate - 34% at 1 yr & 67% at 5 yr Closure is rare in malaligned VSD Closure more frequent in <10 yrs of age

4. VSD with Aortic valve prolapse, false statement? Rare before 2 years Prevalence 2% to 7% Right coronary cusp prolapse extremely rare Non-coronary cusp prolapse in perimembranous type

5.All are major mechanism for development of LVOT obstruction in VSD except ? Posteriorly malaligned outlet septum Septal deviation or anteroseptal twist Anterolateral muscle bundle Mitral arcade

6. Regarding infective endocarditis in VSD false statement is ? Incidence higher in large defect Incidence lower during childhood Operated VSD 7.3 per 10000 person-years Surgical closure may be recommended in Patients with a proven episode of endocarditis

7. A term infant is born with a large ventricular septal defect 7. A term infant is born with a large ventricular septal defect. At what age is this infant MOST likely to first demonstrate clinical findings of congestive cardiac failure? 2 days 2 weeks 2 months 6 months 12 months

8.True statement regarding LVOT obstruction in VSD is Anterolateral muscle bundle present normally in 60% of infants Anteriorly malaligned outlet septum is a major cause Usually occurs below the ventricular septal defect Septal deviation is a muscular protrusion of the left ventricular aspect of the septum

9.Which one of the following statements is incorrect regarding ductus arteriosus? It is a shunt from the pulmonary artery to the aorta in the fetus Blood flow may take place from the aorta to the pulmonary artery after birth, prior its closing Right to left blood flow increases with the first breath after birth due to falling pulmonary vascular resistance The smooth muscle in its walls is sensitive to rising PO2

10. The commonest presentation for an ASD in infants ? Breathlessness Failure to thrive Asymptomatic murmur Recurrent chest infections Arrhythmias

Answers

1.All are true regarding natural history of VSD except? In large VSDs, the rate of decline in pulmonary vascular resistance after birth is delayed In Down syndrome the development of CHF is delayed CHF symptoms get worse initially as pulmonary vascular resistance increases Adults may present with new symptom of exercise intolerance

2.False statement regarding natural history of VSD is? Usually moderate sized VSDs can be managed medically without surgical intervention during infancy Intervention to close the VSD with PAH would shorter life expectancy than if the defect were left open There is enlargement of LA, LV, RV and PA in moderate sized VSDs. Development of PAH may occur in as many as a quarter of patients with large defects who undergo surgery after 2 years of age.

3.False statement regarding natural history of VSD is? In outlet VSD 25 % will close by 2yrs Isolated VSD closure rate - 34% at 1 yr & 67% at 5 yr Closure is rare in malaligned VSD Closure more frequent in <10 yrs of age

4. VSD with Aortic valve prolapse, false statement? Rare before 2 years Prevalence 2% to 7% Right coronary cusp prolapse extremely rare Non-coronary cusp prolapse in perimembranous type

5.All are major mechanism for development of LVOT obstruction in VSD except ? Posteriorly malaligned outlet septum Septal deviation or anteroseptal twist Anterolateral muscle bundle Mitral arcade

6. Regarding infective endocarditis in VSD false statement is ? Incidence higher in large defect Incidence lower during childhood Operated VSD 7.3 per 10000 person-years Surgical closure may be recommended in Patients with a proven episode of endocarditis

7. A term infant is born with a large ventricular septal defect 7. A term infant is born with a large ventricular septal defect. At what age is this infant MOST likely to first demonstrate clinical findings of congestive cardiac failure? 2 days 2 weeks 2 months 6 months 12 months

8.True statement regarding LVOT obstruction in VSD is Anterolateral muscle bundle present normally in 60% of infants Anteriorly malaligned outlet septum is a major cause Usually occurs below the ventricular septal defect Septal deviation is a muscular protrusion of the left ventricular aspect of the septum

9.Which one of the following statements is incorrect regarding ductus arteriosus? It is a shunt from the pulmonary artery to the aorta in the fetus Blood flow may take place from the aorta to the pulmonary artery after birth, prior its closing Right to left blood flow increases with the first breath after birth due to falling pulmonary vascular resistance The smooth muscle in its walls is sensitive to rising PO2

10. The commonest presentation for an ASD in infants ? Breathlessness Failure to thrive Asymptomatic murmur Recurrent chest infections Arrhythmias