1. Ali Mahajerin Non-Invasive Cardiology Conference December 12, 2007
Atrial Septal Defects
Ali Mahajerin
Non-Invasive Cardiology Conference
December 12, 2007

2. Introduction
Atrial septal defect (ASD) is detected in 1 child per 1500 live births, and accounts for 5-10% of congenital heart defects.
ASDs make up 30-40% of all congenital heart disease detected in adults (second only to bicuspid aortic valve).
ASDs occur in women 2-3 times as often as men.

3. Introduction
ASDs can occur in different anatomic portions of the atrial septum.
ASDs can be isolated or occur with other congenital cardiac anomalies.
Functional consequences of ASDs are related to the anatomic location of the defect, its size, and the presence or absence of other cardiac anomalies.

4. Embryology

6. Classification Primum ASD Secundum ASD Sinus venosus defects
Coronary sinus defects
(Patent foramen ovale)

7. Primum ASD Make up ~15% of all ASDs.
Occur if the septum primum does not fuse with the endocardial cushions, leaving a defect at the base of the interatrial septum that is usually large.
Usually not isolated – primum ASDs are typically associated with anomalies of the AV valves (such as cleft mitral valve) and defects of the ventricular septum (VSDs) or a common AV canal.

8. Secundum ASD Make up ~70% of all ASDs.
Occur twice as often in females.
Typically located within the area bordered by the limbus of the fossa ovalis.
Defects vary in size, from <3 mm to >20 mm.

9. Secundum ASD May be associated with other ASDs.
Multiple defects can be seen if the floor of the fossa ovalis (AKA valve of the foramen ovale) is fenestrated.
Ten to twenty percent have a functional mitral valve prolapse
May be related to changing LV geometry associated with RV volume overload

10. Sinus venosus ASD Make up ~10% of ASDs.
Characterized by malposition of the insertion of the SVC or IVC straddling the atrial septum.
Often associated with anomalous pulmonary venous return – the RUL/RML pulmonary veins may connect with the junction of the SVC and RA in the setting of a superior sinus venosus ASD.

11. Coronary Sinus Septal Defects
Less than 1% of ASDs
Defects in the inferior/anterior atrial septum region that includes the coronary sinus orifice.
Defect of at least a portion of the common wall separating the coronary sinus and the left atrium – AKA “unroofed coronary sinus”
Can be associated with a persistent left SVC draining into the coronary sinus.

12. Patent Foramen Ovale
Not truly an “ASD” because no septal tissue is missing.
Oxygenated blood from the IVC crosses the foramen ovale in utero.
At birth, the flap normally closes due to
Reduced right heart pressure and PVR
Elevated LA pressure.
Flap fusion is complete by age two in 70-75% of children; the remainder have a PFO.

13. Pathophysiology of ASDs
Not an issue in utero – flow is occurring through the foramen ovale.
After birth, generally LA pressure > RA pressure:
PVR falls (lungs have expanded)
SVR rises (placenta has been removed)
Pulmonary venous blood flow is increased; all flows into LA
Left-to-right shunting occurs across the ASD – this depends on the size of the defect, the relationship of PVR and SVR, and the compliance of RV and LV.
Brief R-to-L shunting also occurs during cardiac cycle in children (during inspiration, LA pressure decreased and RA pressure increased) – causes mild neonatal cyanosis.

14. Pathophysiology of ASDs
Generally L-to-R flow across ASD
Occurs mainly in late ventricular systole and early diastole; some augmentation during atrial systole.
The volume of pulmonary blood flow is greater than systemic blood flow because of this circuit.
Qp/Qs can be as high as 8:1, though in asymptomatic young adults is usually 2:1 to 5:1.

15. Pathophysiology - consequences
Right-sided volume overload leads to dilation of right-sided chambers.
Main pulmonary arteries dilate, and pulmonary vascularity is increased.
Eventual development of pulmonary hypertension.
RV function can become decreased.
Eisenmenger syndrome, with RV failure and right-to-left shunting of blood.

16. Clinical Manifestations
Children may be asymptomatic; may have easy fatigability, exertional dyspnea. Underdeveloped, more prone to respiratory infections.
Most patients with shunt flow ≥ 2:1 will be symptomatic and require correction by age 40.
Exercise intolerance, fatigue, dyspnea, and overt heart failure are the common presentations in adulthood.
Risk of atrial arrhythmias increases with age and PA pressure.
Pulmonary hypertension and Eisenmenger syndrome – 50% occurrence in unoperated ASDs.

17. Physical Exam Findings
Wide, fixed splitting of S2 (delayed closure of pulmonic valve with reduced respiratory variation)
Midsystolic pulmonary flow or ejection murmur
Usually over 2nd intercostal space
Peaks in early-to-mid systole, ends before S2
Palpable RV heave
Usually no audible murmur across the ASD
Eisenmenger’s sequellae: cyanosis, clubbing
Murmur of MR if cleft MV also present (primum ASD)

18. EKG Findings Right atrial enlargement d/t vol overload (tall P wave)
RVH – RAD, RSR’ in V1, R>S in V1.
Atrial tachyarrhythmias – a.fib, atrial flutter
AV delay – often with primum ASD in association with LAFB and RBBB (the rim of an ostium primum defect is near the His bundle).

19. Chest X-Ray Findings Dilation of RA and RV
Enlarged main pulmonary arteries and pulmonary vessels, without redistribution to apical vessels.
Left atrial enlargement if associated mitral regurgitation.

20. Echocardiography and ASDs
Some clues to the presence of ASD:
Abrupt discontinuity of the septum, and slight thickening at its termination
RA enlargement, RV enlargement/dilation
Dilated pulmonary arteries
Increased flow velocity in the PA and across TV
Paradoxical motion and diastolic flattening of the ventricular septum
TTE is usually definitive in secundum ASDs.
TEE will help with sizing defects, and identifying sinus venosus defects.

21. Two-Dimensional TTE Apical four-chamber view Subcostal view
Can often see ostium primum ASD in this view.
Shadowing and echo dropout (especially in the area of the fossa ovalis) may lead to false positives.
Subcostal view
Often more reliable - can visualize entire atrial septum.
Sensitivity for ASD detection:
Primum ASD: 100%
Secundum ASD: 89%
Sinus venosus ASD: 44%

22. Color Doppler TTE
Can confirm the presence of the ASD, estimate the defect size, and evaluate the efficacy of surgery.
Flow extends from mid-systole to mid-diastole; second phase of flow coincident with atrial systole.
May have brief R-L shunting.
Usually not a high velocity jet.
Must avoid confusing the low-velocity shunt flow with normal venous and AV valve flow.

23. Contrast Echo Administer agitated saline contrast through IV.
Apical four-chamber view is usually optimal.
Bubbles in the LA suggests right-to-left shunting
at the atrial level if 3 bubbles within 3 cardiac cycles following complete opacification of the RA. Delayed bubbles may be due to pulmonary AVMs – may be less phasic in appearance.
Large ASDs may have nearly continuous shunting, but smaller ASDs may be more phasic with respiration.
May see “negative contrast effect” if mainly left-to-right shunt.

24. Contrast Echo - PFOs
Often a small, hemodynamically insignificant left-to-right shunt present in PFO based on the unsealed overlap of foraminal valve.
The shunt is often phasic with respiration.
Maneuvers such as Valsalva or cough, which transiently increase R heart pressure, may allow the occult R-to-L shunt component of a PFO to become evident.

25. Contrast Echo

26. Negative contrast effect

27. Transesophageal Echo
TEE is superior to TTE in visualizing the interatrial septum and identifying all types of ASDs.
With contrast or Doppler, TEE can detect any brief right-to-left shunting that may occur with transient increases in right-sided pressure.
TEE is much more sensitive than TTE for detection of left-to-right shunt as negative right atrial contrast (93% vs. 58% in one study).
TEE can detect flow through multiple ASDs.

28. Transesophageal Echo
Estimation of defect size using the diameter of the Doppler color flow jet correlates with surgical findings.
Since ASDs are not necessarily round, TEE helps with determining both their size and shape. This is especially important when percutaneous closure is being contemplated.
TEE is often used when contrast echo suggests shunting, but a defect can’t be visualized on TTE. The TEE then helps to differentiate between a PFO and a true ASD.
TEE is particularly helpful for diagnosis of sinus venosus ASDs.

29. TEE

30. TEE

31. Cardiac MR Can provide excellent details regarding: Shunt flow
Defect size
Pulmonary venous return
Large sinus venosus ASD
Qp/Qs 2.7
Anomalous return of right upper pulmonary vein to RA
Increased RV cavity size, normal RV function

32. Cardiac MR
Qp/Qs = 2.0
Dilated RA, increased RV cavity size, evidence of RV volume overload
Normal pulmonary veins

33. Cardiac MR
Severely increased RV size, mild RV free wall hypokinesis, volume overload, dilated RA
No significant AR or MR, normal LV
Sinus venosus ASD with significant L-to-R shunt
Qp/Qs 3.03
Normal pulmonary venous return – the right upper pulmonary vein enters the LA at its junction with the RA and empties in the region of the ASD.

34. Cardiac MR
Large primum ASD, Qp/Qs 2.3; possible associated membranous VSD.
Normal LV cavity size; LVEF 66%, effective forward LVEF 43%. Increased RV size, RVEF 51%.
Main PA diameter 37
Paradoxical interventricular septal motion c/w RV volume overload
Mod-severe MR with likely cleft anterior leaflet of MV
Biatrial enlargement

35. 3D Echo

36. Estimation of Shunt Flow Ratio
Operative closure of an ASD traditionally recommended when the ratio of pulmonary blood flow to systemic blood flow (Qp/Qs) is greater than 1.5:1 or 2:1.
Can estimate Qp/Qs from TTE measurements using Pulsed Doppler echocardiography. Cardiac MR is also useful for further assessment of Qp/Qs ratio.
Correlation between Doppler imaging and cardiac catheterization techniques for this measurement is good.

37. Estimation of Shunt Flow Ratio
First measure stroke volume through each valve: Stroke Volume (Q) = CSA x VTI
Left-sided stroke volume is measured from LVOT (diameter measured in parasternal long axis view).
Maximum Doppler flow velocity apical to aortic valve (VTILVOT) taken in apical four-chamber view.
Right-sided velocity time integral (VTIPA) measured in PA well before bifurcation.
PA diameter measured at the same level as VTIPA.

38. Estimation of Shunt Flow Ratio
Substitution into stroke volume ratio gives:
Qp/Qs = (PAdiam)2 x VTIPA
(LVOTdiam)2 x VTILVOT
Diameters of LVOT and PA are squared – exact measurement of these values is especially important.
PA diameter can be difficult to assess in some patients; this is the term that is most often responsible for inaccurate estimates of the shunt ratio.

39. Natural History of ASDs
Most ASDs <8mm close spontaneously in infants.
Spontaneous closure is unusual in children and adults; defects often become progressively larger.
Most patients with a significant shunt flow ratio (Qp:Qs > 2:1) will be symptomatic and require closure by age 40.
Increasing size of the ASD may preclude percutaneous closure.

40. Natural History of ASDs
Life expectancy is not normal, though many patients live to advanced age.
Natural survival beyond age is <50%.
The attrition rate after age 40 is ~6% per year.
Advanced pulmonary hypertension seldom occurs before the third decade.
Atrial fibrillation is a late complication; stroke is a potential complication of ASD (ongoing investigation into this issue).

41. Indications for Defect Closure
1.) Symptoms
Exercise intolerance, fatigue, dyspnea, heart failure
Atrial tachyarrhythmias?
Occur in 20% and often the presenting symptom
Not an indication by itself (incidence may not be reduced after surgery).

42. Indications for Defect Closure
2.) Defect Size and Qp/Qs
Larger ASDs impose a greater hemodynamic burden on the RV.
In the absence of pulmonary hypertension, Qp/Qs is closely correlated with the size of the ASD.
Qp/Qs > 2:1 is a well-established indication, though many authors advocate 1.7:1 or even 1.5:1.
AHA recommends a threshold Qp/Qs ≥ 1.5:1, but these guidelines exclude patients > 21 years of age.
Canadian Cardiac Society recommends Qp/Qs >2:1, or >1.5:1 in the presence of reversible pulmonary hypertension.

43. Surgical Closure Median sternotomy is the
traditional approach; minimally
invasive approaches are emerging.
Pericardial or Dacron patches
are used.
Primary closure of the defect is not recommended.
Can repair other defects at the same time (such as cleft mitral valve if primum ASD).
Intraoperative TEE useful to assess adequacy of repair; can also assess for any new TR or MR that is occurring from tension of the repair.

44. Surgery: Efficacy
Does surgery still benefit patients who are older at the time of diagnosis?
Attie et al. prospectively evaluated 473 pts. over age 40 diagnosed with secundum ASDs, randomized to surgery vs. medical Rx
Mean age 51
Median follow-up of 7.3 years.
Qp/Qs ratio 2.3 ± 0.7
Primary endpoints = death, PE, major arrhythmia, embolic CVA, recurrent pulmonary infection, functional class deterioration, or heart failure.
Attie F, et al. JACC 2001; 38(7):

45. Attie F, et al. JACC 2001; 38(7):

46. Composite primary endpoint occurred more frequently with medical than surgical therapy (21 vs 11 percent, H.R. 2.0).
Overall mortality not statistically different, but there was a nonsignificant trend toward higher sudden death rate with medical treatment (2.9 vs 0.9 percent).
Multivariate analysis (adjusted for age at entry, mean PASP > 35 mmHg, previous atrial tachyarrhythmia, and C.I. < 3.5 L/m2) had a significantly higher mortality with medical management (H.R. 4.1).

47. Surgery: Efficacy
Konstantinides et al. retrospectively evaluated 179 patients with isolated ASDs diagnosed after age 40 (91% secundum, 3% primum, 6% sinus venosus)
Compared 84 pts. (47%) who underwent surgery vs. 95 pts. (53%) who were treated medically.
Mean age 54±7 years for the surgery group, 57±10 years for the medical therapy group.
Mean follow-up period 8.9±5.2 years
Cardiac symptoms reported in 94% at presentation.
“The decision not to operate was based on the judgment of the cardiologists and cardiac surgeons involved in each case.”
Konstantinides S, et al. NEJM 1995; 333(8):

48. Konstantinides S, et al. NEJM 1995; 333(8): 469-73.

49. Surgery: Efficacy
Multivariate analysis revealed a reduced mortality from all cause in the surgical group (relative risk 0.31; 95% C.I ).
Ten-year survival rate was 95% in surgical group, 84% in medically treated group.
Surgical treatment prevented functional deterioration (11% vs. 34%, relative risk 0.21, 95% C.I ) and improved functional status (32% vs. 3%, p=0.002).
Incidence of new atrial arrhythmias or stroke was not significantly different.
Konstantinides S, et al. NEJM 1995; 333(8):

50. Long-Term Surgical Outcomes
Surgery before the age of 25 yields in 30-year survival rates comparable to age- and sex-matched controls.
At years of age, surgical survival is reduced, though not significantly if PA pressures are normal.
If PASP > 40 mmHg, late survival is 50% less than control rates, though life expectancy in surgically treated older patients is better than that of medically treated patients.
No benefit of surgery in reducing the incidence of AF, though the patient’s age at the time of closure is the most important predictor of the development of atrial arrhythmias.

51. Percutaneous Closure
An alternative to surgical closure for secundum ASDs with appropriate anatomic characteristics.
Defect < 30mm diameter
Prefer a rim of tissue at least 5mm around the defect to prevent obstruction of coronary sinus, R pulmonary veins, vena cavae, or AV valves.
Approximately half to two-thirds of secundum ASDs in adults meet these criteria.

52. Amplatzer Occlusion Device
Introduced in 1996.
Approved for percutaneous ASD closure in 2001 by F.D.A.
Over 90,000 have been manufactured and delivered to date.
Consists of two round disks made of Nitinol (nickel + titanium) wire mesh linked together by a short connecting waist.

53. Amplatzer Occlusion Device
Advantages over other devices:
Can be delivered through smaller catheters
It is self-centering but can be repositioned easily
Has round retention disks that extend radially beyond the defect, which results in a much smaller overall size and firmer contact with the atrial septum
Shape enhances endothelialization and reducing the risk of residual shunting

54. Secundum ASD

55. Secundum ASD

56. Amplatzer - catheter

57. Amplatzer – crossing the septum

58. Amplatzer – deployment of left atrial disc

59. Amplatzer – seating against interatrial septum

60. Amplatzer – deployment of right atrial disc

61. Amplatzer – releasing the device

62. Amplatzer – minimal residual shunt

63. Post-Procedure TTE

64. Post-Procedure TTE

65. Post-Procedure TTE

66. Post-Procedure TTE

67. Percutaneous Closure - Outcomes
Chan et al. showed successful implantation of Amplatzer device in 93 of 100 patients (mean age 13.3 years).
Procedure time ranging 30 to 180 minutes.
Seven failures
Total ASD occlusion rate at 3 months = 99% for the 93 successes.
Masura et al. showed no deaths or significant complications, along with all defects remaining completely closed, in 151 patients (mean age 11.9 years) at long-term follow-up (median time 78 months).
Chan KC, et al. Heart 1999; 82(3):
Masura J, et al. JACC 2005; 45(4):

68. Percutaneous Closure - Complications
Early complications
Device embolization or malposition requiring surgery (2.4%)
Atrial fibrillation (2.4%)
Heart block, effusion, thrombus in LAA (2.2%)
Thrombus formation (both in LA and RA)
Need aspirin and plavix for at least 6 months
Rare complications: cardiac perforation, sudden death
Long-term complication: device erosion (0.1% of cases) – risk factors include deficient aortic rim (25/28 cases), deficient superior rim, and oversized device.

69. Surgery vs. Percutaneous Repair?
Du et al. evaluated 596 patients with secundum ASDs and Qp/Qs ≥ 1.5:1 – surgery vs. Amplatzer ASO
Nonrandomized; assigned according to patient’s option.
Median age 9.8 years in Amplatzer arm (442 patients), 4.1 years surgical arm (154 patients; p<0.001)
Twelve-month follow-up
Procedural success significantly higher with surgery (100 vs. 96 percent, p=0.006).
Percutaneous closure had significant reduction in complication rates (7 vs. 24 percent) and mean hospital stay (1.0 vs. 3.4 days).
Mortality 0% for both groups.
Du ZD, et al. JACC 2002; 39(11):

70. Surgery vs. Percutaneous Repair?
Du ZD, et al. JACC 2002; 39(11):

71. Surgery vs. Percutaneous Repair?
Bialkowski et al. prospectively compared closure and complication rates in 91 children with secundum ASDs over mean follow-up 3.9 years.
Mean age 8.1±4.7 years for surgery (44 pts.), 10.1±4.9 years for Amplatzer (47 pts.)
Surgery if ASDs unsuitable for percutaneous closure; 3 patients’ parents also requested surgery.
Closure rate similar in the two groups (95.5% vs. 97.5%).
Hospital stay 7.5 days vs. 2.2 days (p<0.001)
No deaths reported.
Bialkowski J, et al. Tex Heart Inst J 2004; 31:

72. Surgery vs. Percutaneous Repair?
Mild complications: small pericardial effusions, headaches, AV delay, atrial rhythm disturbances
Moderate complications: pneumonia, paroxysmal SVT, AV junctional rhythm
Severe complications: bleeding requiring reoperation, transient neurologic events.
Bialkowski J, et al. Tex Heart Inst J 2004; 31:

73. Surgery vs. Percutaneous Repair?
Butera et al. retrospectively evaluated 1268 patients with secundum ASDs.
Surgical group: mean age 22.4±18.9 years (range 1-81 years), female-male ratio 393:124.
Percutaneous group: mean age 29±19.8 years (range 9 mo-81 years), female-male ratio 415:336.
No post-operative deaths.
Overall complications higher for surgery (44 vs. 6.9 percent, p<0.0001).
Surgery was independently strongly related to the occurrence of total complication (OR 8.13, 95% CI ) and of major complications (OR 4.03, 95% CI ).
Hospital stay was shorter for percutaneous closure (3.2±0.9 vs. 8.0±2.8 days, p<0.0001).
Butera G, et al. AHJ 2006; 151:

74. Surgery vs. Percutaneous Repair?
Butera G, et al. AHJ 2006; 151:

75. Surgery vs. Percutaneous Repair?
Most reports show comparable procedural success.
Rate of complications is consistently lower with percutaneous closure.
Percutaneous closure associated with shorter hospital stays.
Many centers prefer implantation of percutaneous device to surgical repair when percutaneous approach seems feasible.

76. Stroke Risk?
Data are widely conflicting on the relationship between PFO, atrial septal aneurysm, and/or ASD and recurrent cerebral emboli.
Increased prevalence of PFO and ASA in cryptogenic stroke; less clear for ASD.
The role of defect closure vs. medical therapy for prevention of recurrent stroke is not well defined.
Aspirin is often used in setting of PFO or an isolated atrial septal aneurysm, and especially if PFO + ASA. Role of coumadin is not as clear – coumadin recommended if patient has a documented DVT/PE. Less data available for ASDs.
Surgical excision of an atrial septal aneurysm (without PFO or ASD) may be considered if aspirin or coumadin fail to prevent a recurrent embolic event.

77. Endocarditis Prophylaxis?
The 2007 AHA guidelines do not recommend antibiotic prophylaxis of endocarditis in isolated ASD, with the following exceptions:
Recently repaired ASD, whether by prosthetic material or device, during the first 6 months after repair (to allow for sufficient endothelialization).
Repaired ASD with a residual defect at the site or adjacent to the site of a prosthetic device.
The updated guidelines no longer include associated mitral regurgitation as an indication for prophylaxis.
Prophylaxis is no longer recommended for GI or GU procedures; above criteria apply to dental procedures or respiratory procedures that require biopsy of mucosa.
Wilson W, et al. Circulation 2007; 151:

78. Thank You!
Eli Gelfand
Jason Ryan