Different classifications and pathophysiology of total anomalous pulmonary venous connection

2. OUTLINE
• DEFINITION
• INCIDENCE
• EMBRYOLOGY
• CLASSIFICATION
• PATHOPHYSIOLOGY

4. • All the four pulmonary veins connect anomalously to a
systemic venous tributary of the right atrium or to the
right atrium proper but have no connection to the left
atrium.
• An inter atrial communication is essential for survival
• Very rarely, atrial septum may be intact – mixing via VSD/
PDA
TAPVR

6. INCIDENCE

7. • TAPVC is rare, representing 1.5–2% of all congenital
cardiovascular abnormalities .
• In a population-based registry, TAPVC represented
1.5% of all congenital cardiovascular malformations
and had a prevalence of 6.8/100 000 live births
• Sex ratio with supra-diaphragmatic TAPVC is almost
equal.
• Male predominance (3:1) is seen in infra-
diaphragmatic type of TAPVC
Bharati S, Lev M. Congenital anomalies of the pulmonary veins. Cardiovasc Clin 1973;5:23

8. Associated anomalies
• 2/3 are isolated
• PDA- 10-15%
• Common in heterotaxy syndromes
• Associated conditions :-
TGA
TOF
Single ventricle
Truncus arteriosus
Tricuspid atresia
HLHS
CoA
Asplenia or polysplenia

9. HISTORICAL LANDMARKS
1798 - 1st description by Wilson
1942 - autopsy series by Brody et al
1950 - Friedlich - 1st diagnosis by cardiac catheterisation
1951 - Muller- 1st surgical correction ( closed technique)
1956 - Lewis & Varco – surgery by hypothermia & inflow occlusion(open heart)
1956 - Kirklin - surgery on CPB
1957 – Darling, Rothney & Craig- 1st classification
1961 - Sloan – 1st surgery for infra cardiac variety by hypothermia & a period of
circulatory arrest
1967 - Dillard- surgery with DHCA without CPB.

10. Embryology
• The respiratory system develops as an
evagination from the foregut at 26 days.
• The venous plexus surrounding the early lung
buds drains into the cardinal and umbilico-
vitelline veins - part of the splanchnic
(systemic) venous system.

11. (A) Lateral view of the embryo. The foregut (green) gives rise to two lung buds (LB, putative
lungs). A splanchnic vascular network (pale blue) can be observed surrounding the LBs. The
venous tributaries drain into the sinus venosus (SV) to which is connected the non-
lumenized pulmonary vein and the midpharyngeal endothelial strand (MPES) that runs in
front of the gut from the venous to the arterial pole.

15. • A:At 27 to 29 days of gestation, the primordial lung buds are enmeshed by the vascular
plexus of the foregut (the splanchnic plexus). At this stage, there is no direct connection to
the heart. Instead, there are multiple connections to the umbilicovitelline and cardinal
venous systems. A small evagination can be seen in the posterior wall of the left atrium to
the left of the developing septum secundum

18. (B) The splanchnic plexus (indicated as the pale blue network covering the foregut
including the LB) is already connected to the endocardium of the primitive heart tube, by
means of the MPES.
In early developmental stages the route of drainage is from the pulmonary venous
plexus to the systemic veins via pulmonary-to-systemic venous connections.
(C) The endothelial anlage of the pulmonary veins has lumenized to become the
common pulmonary vein (CPV), allowing drainage of the splanchnic plexus not only
to the systemic veins but also into heart.
(D) The CPV grows and dilates, and becomes the main route of drainage of the
pulmonary venous blood.

20. (E) Central drainage period. At this stage, the primitive pulmonary-to-venous
connections have regressed entirely. The route of drainage of the pulmonary venous
blood is now directly into the heart. (F, G) Bifurcations of the CPV will be incorporated
into the left atrium (LA), contributing to the body of the LA. Usually four separate
pulmonary venous ostia can be recognized, although variations occur.

23. TAPVR occurs as a result of developmental failure or early atresia of
common pulmonary vein when collateral channels for pulmonary venous
return are available in the form of primitive connections between the
pulmonary venous plexus and the systemic veins.
The type of TAPVR is classified according to the persistent collateral
channels from pulmonary to systemic veins as follows:
• Supracardiac type includes connections to the left innominate vein, the
superior vena cava, or the azygos vein;
• Cardiac type includes connections to the coronary sinus or directly to
the right atrium; and
• Infracardiac type includes connections below the diaphragm to the
inferior vena cava, the portal vein, the hepatic veins, or the ductus
venosus

24. Embryologic basis of totally anomalous pulmonary venous connections.
B: Totally anomalous pulmonary venous connection results from failure to establish a normal
connection between the pulmonary venous plexus and the common pulmonary vein before the
connections with splanchnic venous system have regressed

26. Classification
• Based on
* Pathway of pulmonary veins to the right atrium
* Presence or absence of obstruction
* Nature of inter atrial communication.

27. CLASSIFICATIONS
• DARLINGS CLASSIFICATION
• NEILLS CLASSIFICATION
• SMITHS CLASSIFICATION
• BURROUGHS AND EDWARD CLASSIFICATION
• UK CHOWDHARY ET AL MIXED TAPVC
CLASSIFICATION
• HERLONGS CLASSIFICATION

28. • Type- I( a& b) Supracardiac : 50%
• Type II (a & b) Cardiac : 25%
• Type III Infra cardiac : 20%
• Type IV Mixed : 5%
Lab invest 1957;6:44
1

29. Supra cardiac-Type 1 a
• Most common(40%)
• 4 pv cc vertical
vein innominate
vein SVC
• Vertical vein pass
anterior to LPA & Left
bronchus
• When vv pass in b/w
obstruction ( vascular
vice)

32. Supracardiac- Type 1 b
• 4 pv cpv vertical
vein SVC- RA jn/
azygos
• More common in right
atrial isomerism, 90% of
whom have TAPVR

33. Cardiac- Type II a
• Coronary sinus type-
More common variant
• 4pv Cpv coronary
sinus RA

34. Type II b
• Right atrial type
• All 4 pulmonary veins
drain directly to the RA

36. Infra cardiac- type III
• 4 pv cpv vertical
vein  pass thro
esophageal hiatus(t 10)
antr to esophagus 
portal vein (65%)/
ductus venosus/
hepatic vein / IVC

38. Type IV - mixed
• A combination of any pathways
• Most common- supracardiac + cardiac

40. 248 patients over 15 yrs
168 boys; 80 girls
1 day to 24 yrs
Supra cardiac- 54%
Cardiac - 32.2%
Infra cardiac—3.6%
Mixed - 10.1%
Obstructed- 20%
Mortality- 19%
(Indian Heart J 2001; 53:
754–760)

41. • Right common cardinal vein
– SVC
– Azygos vein
• Left common cardinal vein
– Left innominate vein
– Coronary sinus
• Umbilico-vitelline system
– Hepatic vein
– Ductus venosus
– Portal vein
MIXED TYPES
Connection to:
2

42. Classification-Burroughs and Edwards
Total anomalous pulmonary venous connection. Am Heart J59:913,1960
3

43. Total anomalous pulmonary venous drainage :diagnostic criteria and a new classification. Am J Dis Child 101:41,1961
4

44. Mixed TAPVR
• Category I: bilateral and symmetrical connections
(2+2)
• Category II : bilateral and asymmetrical
connections (3+1)
• Category III : bizarre anatomic variants
A suggested new surgical classification for mixed totally anomalous pulmonary venous connection. Cardiol Young.2007;17:342-53.
5

45. Category 1: 2+ 2
A to D, Group of patients with bilateral and symmetrical connections
(“22” pattern of drainage).

46. Category II :3+1
A to F, Group of patients with bilateral and asymmetrical connections (“31” pattern of drainage)

47. Category III-Bizarre anatomic variants
A to E, Group of patients of bizarre anatomic variants of mixed total anomalous pulmonary
venous connection.

48. Herlong and colleagues suggested complete description
of the TAPVC including-
• Level of connections-
supracardiac,cardiac,infracardiac or mixed.
• Presence or absence of obstruction
• Cause of obstruction-extrinsic,intrinsic or obstructive
atrial septal communication.
Herlong et.al.Ann Thorac Surg 69(suppl):S56,2000
6

49. PATHOPHYSIOLOGY

50. Pathophysiology
• Fetal life: Negligible
consequence less
blood through lungs
and pulmonary vein
beginning of
pathological changes
• After birth : Obligatory
R L shunt

51. • None of the pulmonary veins connect normally to the left atrium, the
only source of blood to the left atrium is blood that is shunted from the
right atrium across the defect to the left side of the heart.
• The highly oxygenated blood from the lungs completely mixes with the
poorly oxygenated blood returning from the systemic circulation. This
causes an overload of the right atrium and right ventricle leading to
enlargement of chambers.
• The increased blood volume going into the lungs can lead to pulmonary
hypertension and pulmonary edema.

52. • TAPVC is incompatible with life unless there is
an associated defect present that allows for
shunting of blood from the highly pressured
right side of the heart.
• A patent foramen ovale or an ASD is usually
present.

53. LUNGS
Qp
LA
LVRV
RA
Qs
• Early onset & rapid progression of pulmonary vascular
changes
↑ muscularity & abnormal distal extension.
• Arterialisation of pulmonary veins
• Small thick walled PV.
• 20% show stenosis of individual PV or Confluence –
intimal fibrous hyperplasia
RA -enlarged & thick walled
RV- enlarged due to volume overload
LA- small due to absence of PV component
LV- Nl size & thickness; ↓ EDV due to IVS shift
PA- Enlarged
IAS- ASD/ PFO universal SIZE OF ASD
• Determines the
systemic
circulation.
• Usually large
adequate ASD/
PFO is present.
• A gradient of ≥
3 mmHg b/w
RA & LA
indicate that
the
communication
is restrictive.

54. Cardiac chambers
• RA -enlarged & thick walled
• RV- enlarged due to volume
overload
• LA- small due to absence of
PV component
• LV- Normal size & thickness;
↓ EDV due to IVS shift
• PA- enlarged
• IAS- ASD/ PFO universal

56. Pathophysiological Changes
• Obligatory mixing
• Obligatory Right to left shunt at ASD level
• Shunt at PDA level if Present
• Increased Pulmonary Flow
• Decreased or Normal Systemic flow
• Increased PVR
• PVH

57. Microscopic anatomy
• Early onset & rapid progression of pulmonary
vascular changes
• ↑ Muscularity & abnormal distal extension.
• Arterialisation of pulmonary veins
• Small thick walled PV.
• 20% show stenosis of individual pv or confluance –
intimal fibrous hyperplasia

58. The factors that influence the pathophysiology
of TAPVC include
1. Obligatory mixing of pulmonary and
systemic blood
2. Size of the atrial septal defect
3. Obstruction of the anomalous connection
4. Associated anomalies

60. 1. Obligatory mixing :
• The systemic blood flow must be provided from
right side of the heart
 Inter atrial communication
 Distensibility & compliance of both ventricles.

62. Determinant of Systemic Oxygen
saturation
• Degree of mixing
– if unrestricted mixing of blood returning to RAEqualization
of O2 saturation in all 4 chambers
– If restricted mixing-fetal pattern of preferential streaming of
SVCTVRVPA(PDADTA if PDA patent) vs
IVCPFOLALVAO
– Hence if
• Supracardiac TAPVC (SPaO2>SaO2)
• Infracardiac TAPVC (SaO2>SPaO2)
• Qp:Qs- directly determines SaO2
– Higher Qp:Qs- higher the SaO2
• Oxygenation- hampered by developing pulmonary edema

63. 2. SIZE OF ASD
• Determines the systemic circulation.
• Usually large adequate ASD/ PFO is present.
• A gradient of ≥ 3 mmHg b/w RA & LA indicate
that the communication is restrictive.

64. 3. Obstruction of the connection
• The presence of obstruction along the
anomalous channel is the most significant
factor in the hemodynamics
• Can be anatomic or functional

67. Causes of Obstruction
• Supracardiac- Ia- 40% ; Ib- 65%
- Extrinsic obstruction
- Intrinsic vertical vein obstruction
• Cardiac- least common- 20%
- At the coronary sinus opening
• Infracardiac- almost always(95-100%)
- Narrow & long vertical vein at the esophageal hiatus
- Hepatic capillary resistance
• Restrictive ASD/PFO

69. Pathophysiology of obstruction-Role of PFO/ ASD
Non restrictive
Low gradients across PFO/ASD
Low RAP
Low RV preloading
RV failure delayed
Restrictive
↑RAP
Gradient is more across PFO
Pulmonary edema
↑PAP& PVRI
RVF↓Qp & Cyanosis

70. Effect of Obstruction
• Key factor affecting the hemodynamics
• Effects
– ↓ Systemic blood flow- ↓ preload
– ↑ PVH
– ↑PVR
– ↓PBF
– Increased transudatedpulmonary
edemaimpaired ventilation and oxygenation
– Decreased SaO2

71. Determinant of Systemic flow
• If shunting through PFO/ASD (LV maintains the
Systemic perfusion)
– Preload
• Obstructed TAPVC- reduced filling
• Restriction at PFO
• Small poorly compliant LA
• Impaired LV filling- compliance,bulge of IVS towards LV
– Pump-Impaired LV function
– Afterload-eg. Hypoxemia↓/↑SVRsystemic blood
flow↑/↓
• If PDA dependent systemic perfusion
– RV performs the work of systemic perfusion
– Depends on SVR vs PVR
– RV function

72. Determinant of PVR
• Normal physiological drop in PVR increase in PBF
• Obstructed Return↑pulmonary venous
pressure↑transudatePulmonary
EdemaHypoxemiaArteriolar constriction↑PVR
• Mild or no obstruction- increased blood flowshear
stressendothelial proliferation to encroach
lumenpulmonary vascular obstructioncyanosis
• Pulmonary blood flow (balance b/w PA pressure and PVR)

73. Effect of feeding
• Hemodynamic compromise in infra cardiac
type.
• Compression at esophageal hiatus
• Increase in GI and portal blood flow ↑
portal & pulmonary venous pressure 
pulmonary oedema.

74. Pathophysiology of Non-obstructed
TAPVC without PDA
• Obligatory RL shunting at PFO/ASD
• RA pressure >LA pressure
• Hemodynamics mainly determined by
• PVR
• SVR
• Restriction at PFO/ASD
• Effect of changes in PVR
– Physiological fall in PVR post
natally↑Qp:Qsimproves SaO2
– Mechanism- ↓pvr↓RV afterload↓RV esv & ↑RV
ef↑RA pressure↑RV filling↑RV output(Frank
Starling Law)

75. Pathophysiology of non-obstructed
TAPVC without PDA cntd.
• Effect of changes in SVR
– Decreased SVR↓LV esv & ↑ LV EF↓LA
pressure↑rl Shunt↑SBF and ↓
PBFdecreased SaO2
– Increased SVR- opposite occurs
• Effect of size of PFO/ASD
– Non restrictive- little rise in RAP, adequate LV filling
achieved, systemic perfusion adequately maintained
– Restrictive -↑RAP to maintain adequate LV
filling↑RVVO↑Qp PVHblood returning to
↑RAPvicious cyclepulmonary edema and RV
failure

76. Pathophysiology of Non-obstructed
TAPVC with PDA
• PDA may affect the oxygen saturation in the
great arteries
• Depending on degree of mixing and
preferential streaming of blood & Variety of
TAPVR

77. Pathophysiology of obstructed TAPVC
with PDA
• Obstructed return Severe PVHPAHPA to
Ao Shunting via PDA
• Effects
– Prevents PAP from becoming supra systemic
– ↓PBF
– ↓pulmonary edema, ↓Qp:Qs, ↓Sao2
• Effects of hypoxemia- ↓SVR ↑RL shunting
via PDAfurther hypoxemiasympatho-
adrenal stimulation ↑SVR ↓RL shunt via
PFO/PDA ↓tissue perfusioncyanosis

78. Pathophysiology of obstructed TAPVC
without PDA
• Closure of PDA
– ↑PAP
– ↑PBF
– ↑Qp:Qs
– ↑Oxygenation
– Higher risk of pulmonary edema

79. Pathophysiology of Infracardiac TAPVC:
Role of Ductus venosus
• Blood bypasses the hepatic
sinusoids
• If ductus venosus widely
patent- no PVH/Pulmonary
Edema
• If Ductus venosus
closesincreased portal and
pulmonary venous
pressurePAH can develop

80. Inhaled O2
• If administered for cyanosis
without identifying TAPVC
– Risk of increased
pulmonary edema
• Increased PBF due to
pulmonary
vasodilation
• PDA
constrictionincrease
d PA pressurePE
Effect of PGE1
• 2 opposing effects
– ↑Qp-by pulmonary vasodilation
– ↓Qp- by keeping PDA patent
and RL shunting
• Final outcome depends which
effect predominated
• PGE1 especially helpful in
infradiaphragmatic TAPVC by
keeping the ductus venosus
patent
• Systemic vasodilation may
require inotropic support during
PGE1 administration

81. Natural history
• With obstruction, the lifespan is brief. Pulmonary edema and
right ventricular failure ensue within days to weeks of birth.
• Most infants die in the first few days or weeks of life and survival
for up to 3–4 months is exceptional .
• The natural history is unfavorable even in patients with
unobstructed.
• TAPVC, most of whom die within 3–6 months of birth; 75–90% of
symptomatic infants do not reach 1 year of life.
• Heart failure and infections are the major causes of mortality.
• The minority who present after the first year of life invariably
have a low pulmonary vascular resistance and a nonrestrictive
atrial septal defect.

82. Natural history
Long survivors :
• Large interatrial communication
• Non-obstructive pulmonary veins
• Low pulmonary vascular resistance
• Usually supradiaphragmatic TAPVC

83. Clinical features
TAPVC without Pulmonary Venous Obstruction
• Patients are usually asymptomatic at birth.
• Tachypnea and feeding difficulties are the initial
symptoms usually within first few weeks of life.
• Then infants have recurrent resp.tract infections and
failure to
thrive.
• Mild cyanosis is present because of adequate mixing of
blood.
• Gradually they develop right heart failure and

84. Clinical features cont.
• TAPVC with Pulmonary Venous Obstruction
• Tachypnea,tachycardia and cyanosis within few hours of
birth (usually did not appear in the first 12 hours of life).
• D/D Respiratory distress syndrome-symptoms within 12
hours of life.
• Dyspnea is severe because of marked pulmonary
venous congestion and cyanosis is marked because
of reduced pulmonary flow.
• If left untreated death may occur from pulmonary edema
and RV failure within few days or weeks of life.

85. Clinical features cont.
• Those who survive their first year almost always
have supradiaphragmatic connections,low
pulmonary vascular resistance and a nonrestrictive
atrial septal defect.
• When an infradiaphragmatic venous channel
traverses the esophageal hiatus feeding,crying and
straining cause additional compression that
aggravates the dyspnea and cyanosis
• (Lucas et.al. Am J
Roentgenol.86;561,1961)
• Newborns with infradiaphragmatic connections and
asplenia
may have major esophageal varices.

86. On examination
TAPVC without Pulmonary Venous Obstruction
• Mild cyanosis with features of CHF.
• Prominant precordium with left lower parasternal heave.
• S1 loud,S2 wide split and fixed with loud P2.RVS3 present.
• ESM 3-4/6 at upper sternal border ( ↑ pulmonary flow).
• PSM due to TR and MDM due to increased flow across TV may
be there.

87. On examination cont.
TAPVC with Pulmonary Venous Obstruction
• Clinical condition is grave with minimal cardiac
findings.
• Signs of PAH present.
• Apex impulse is of RV type.
• S1 normal,S2 closely split,P2 loud.
• A short systolic murmur due to pulmonary artery
dilatation.
• Liver is enlarged and tender.