Anne-Marie Anagnostopoulos, MD
Non-Invasive Conference
December 9, 2009

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History and Epidemiology
Anatomy and Embryology
Spectrum of TOF
Surgical Repair
Imaging The Adult with Repaired TOF
Summary

 Special thanks to Dr. Anne Marie Valente who helped me enormously

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1671: Stenson first describes pathology of what would later be confirmed as TOF
1888: Etienne-Louis Fallot first recognizes a group of complex cardiac malformations that leads to cyanosis and identifies 4 abnormalities: pulmonary stenosis, VSD, dextroposition of the aorta, and RVH
 Fallot postulated that these abnormalities resulted from abnormal development of the subpulmonary infundibulum and pulmonary valve.
1924: Abbott and Dawson name the malformation “Tetralogy of Fallot”

 From Wikipedia:
 E. L. A. Fallot.
Contribution à l’anatomie pathologique de la maladie bleue
(cyanose cardiaque).
Marseille médical, 1888,
25: 77-93, 138-158, 207-
223, 341-354, 370-386,
403-420.

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Overall, congenital heart disease is rare
However, of the cyanotic congenital heart abnormalities, TOF is the most common
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TOF has an incidence of approximately 32.6 per 100,000 live births
The success of early surgical repair has led to a large population of adults with repaired TOF

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The fundamental embryologic malformation in TOF is abnormal development of the conotruncus (also known as: conal septum, subpulmonary infundibulum)
There is hypoplasia of the conotruncus and anterior/superior displacement of the infundibular septum
This results in failure of ventricular septation, subpulmonary and/or pulmonary valve stenosis and overriding aorta

The Worlds Best Anatomical Charts. Anatomical Chart Company Skokie, IL. ISBN 0-9603730-5-5.

Anatomy and Embryology in Tetralogy of Fallot
Figures Emily Flynn, Echocardiography in Pediatric and Congenital Heart Disease Editors Lai,
Mertens, Cohen, Geva 2009

Anatomy and Embryology –
Simplified Diagram

Source:
Feigenbaum’s
6 th Ed.

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There is a spectrum of anatomy in TOF with an associated variation in clinical presentation
Children with minimal pulmonary stenosis are at one end and can be “pink”
At the other extreme is a form of TOF with pulmonary valve atresia and VSD (severely blue)
In the latter case, life is sustained by PDA or aorto-pulmonary collateral vessels

• Obliterated subpulmonary infundibulum
• Marked anterior/left shift of conal septum
• Figure Emily Flynn,
Echocardiography in Pediatric and
Congenital Heart Disease Editors
Lai, Mertens, Cohen, Geva 2009

Anatomy and Embryology:
Coronary Anomalies
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Because the aortic root is rotated in TOF, coronary artery anomalies can occur
Most common (3%) is origin of LAD from RCA
Double LAD occurs 1.8% of time
Least common anomalies are single RCA or
LCA (0.3% and 0.2% respectively)

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Symptomatic infants are repaired early – can be palliated with a variety of shunts
Asymptomatic children are usually electively repaired early as well
Surgery involves repair of the VSD and enlargement of the RVOT with infundibular septum resection +/- use of a transannular patch
This can usually be performed in one step as long as pulmonary artery and its main branches are of adequate size
The surgery uniformally results in pulmonic regurgitation

Glenn Shunt

Source:
Feigenbaum’s
6 th Ed.

Patients post-repair do well up to ~25 yrs postoperatively
Modes of death:
Sudden cardiac death
Arrhythmias
Congestive heart failure
Nollert G. JACC 1997; 30:1374

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Patients often remain asymptomatic
Although decreased exercise capacity can often be elicited with objective testing
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Clinical Presentation: heart failure, dyspnea on exertion, atrial and ventricular arrhythmias, syncope, sudden death
ECG findings include RAD, RVH/RAA and
RBBB; QRS duration can be prolonged
(>180ms is important to note)

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Residual lesions:
 Ventricular septal defect
 Branch pulmonary artery stenosis
Tricuspid regurgitation
Pulmonary regurgitation
Progressive RV dilation and dysfunction
Progressive LV dysfunction
Aortic root dilation
Exercise intolerance, heart failure, arrhythmias and sudden cardiac death
Courtesy A. Valente MD

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Non-invasive imaging is the mainstay of longitudinal follow-up in previously repaired
TOF
Echocardiography is used to evaluate: residual VSD/PS, Ao Root size and associated
AR, PR, and RV/LV function
CMR is used to determine RV volumes and severity of PR
Often these modalities are used in a complementary fashion

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Nearly universal
Severity is dictated by:
 compliance of the RV
 capacitance of the pulmonary arteries
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Early: presence of RVH ( ↓ RV compliance) and small PAs ( ↓ capacitance) →↓ PR
Late: dilation and thinning of the RV ( ↑ compliance) and dilation of the PAs ( ↑ capacitance) →↑ PR
Courtesy A. Valente MD

Courtesy A. Valente

 Adaptive mechanisms in chronic PR
 increased RV end-diastolic volume
 increased RV stroke volume
 These mechanisms compensate for the hemodynamic burden placed on the RV for many years
 Studies in the 1970’s – 1980’s on survivors of TOF repair were largely asymptomatic (based on self-reporting)

Geva T. STCVS 2006; 9:11.

Compensatory mechanisms exist up to a certain point, but ultimately these mechanisms fail
Courtesy A. Valente MD

Good RV Function Poor RV Function
Courtesy A. Valente

Severity of Pulmonary Regurgitation
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Prospective study of 34 adults with repaired TOF
Echocardiogram & cardiac MRI within 3 months
Median age 33 yrs (
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12 yrs)
Mean time since initial surgical repair 25
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8 yrs
13 subjects had undergone transannular patch
6 subjects had undergone bioprosthetic PVR
Silversides C. JASE 2003; 16: 1057

% PR and volume are inversely related to the pressure half-time: r = -0.6, p <0.001
Mild PR
Severe PR
Silversides C. JASE 2003; 16: 1057

Pulmonary Regurgitation
• In addition, PHT <100ms had highest sensitivity and specificity for detecting significant PR (RF
>20%) Silversides C. JASE 2003; 16: 1057

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Median age from repair 21 years
Unfavorable ventricularventricular interaction
Confirmatory data that RV mechanics are only part of the problem
Patients repaired at older age, more likely to have poor clinical status later
Geva T. JACC 2004; 43(6): 1068

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Often adults with repaired TOF cannot undergo CMR due to devices
Myocardial Performance Index (MPI) has been shown to correlate with MRI RVEF
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Retrospective study of 57 adults (repaired
TOF) with a CMR and Echo within 6 months of each other
RV MPI = (Doppler duration of TR-RV ejection time)/RV ejection time
Schwerzmann, M. AJC 2007;99:1593

MPI = (a-b)/b
Schwerzmann, M. AJC 2007;99:1593

Schwerzmann, M. AJC 2007;99:1593

Regional Wall Motion Abnormality
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85 subjects repaired
TOF underwent MRI
RVOT outflow aneurysm/akinesia present in 57%
No significant difference in the type of repair
Aneurysm/akinesia negative effect on
RVEF
Davlouros et al. JACC 2002; 40:2044

 Operative risk is small: mortality < 2%
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 What criteria should we use in patient selection?
 Traditional indication: patient symptoms
 Is there a risk to waiting until patients develop symptoms?
 Patients may not detect subtle changes in exercise capacity
 By the time patients notice symptoms, problems may be severe and irreversible
*Oosterhof T. Heart 2007; 93: 506

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88 subjects with repaired TOF
 Surgical repair between 1966-1987
 CMR between 1997-2001
Median follow-up from MRI 4.2 yrs
22 subjects had a major clinical event
 4 deaths
 8 sustained VT
 10 change in NYHA class from good to poor
 Larger RVEDV, LVEF<50%, RVEF<45% by CMR predicted adverse events
Knauth A. Heart 2008; 94: 211-16.

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Balance between patient’s clinical status
(exercise capacity, heart failure symptoms, arrhythmia) and quantitative information
Decision to do PVR is quite variable center to center
 Repaired TOF with moderate or severe PR (PR
RF >25% by CMR) and > 2 criteria
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RVEDVi > 160 cc/m 2 ( z > 5)
RVESVi > 70 cc/m 2
 LVEDVi < 65cc/m 2
 RVEF < 45%
 RVOT aneurysm
 LVEF < 50%
Geva T. STCVS 2006; 9:11.

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Aortic root dilation occurs in a subset of repaired TOF adults and can lead to significant AR
May be a result of R  L shunt prior to repair though not fully understood why it progresses after
A small retrospective study identified risk factors for Ao root dilation (defined as Ao root size observed:expected
>1.5)
Therefore it is important to closely follow Ao root size with imaging longterm

Aortic Root Dilation
Niwa, K. Circulation 2002;106:1374

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A study in England evaluated data from 793 repaired TOF patients
QRS duration >180ms was found to be predictive of
SCD and ventricular arrhythmias
Older age at repair was associated with
Afib/AFlutter and SCD
QRS duration rate of change may also be significant predictor of
SCD
Gatzoulis, M. Lancet 2002; 356:95

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ECG (QRS duration): every 12 months
Exercise Testing: every 24-36 months
Echo: every 24 months
CMR (RVEDVi, RV/LV EF): every 24 months
EP testing: when clinically indicated
Echo and CMR are used together
 Authors from CHB
Geva T. STCVS 2006; 9:11.

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Because of successful childhood repair, larger population of adults with repaired TOF exists and can present to adult cardiologists
Pulmonary Regurgitation is predominant hemodynamic abnormality leading to RV dilation and dysfunction
Timing of surgery for PR is an area of great interest as clinical symptoms do not always correlate with severity of
PR and RV dysfunction.
Echo and CMR are used together to follow repaired patients long term
Aortic root dilation occurs in a subset of patients and must also be followed closely
QRS duration >180 ms is an important predictor of ventricular arrhythmias and SCD

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Feingenbaum’s Echo Textbook, 6 th Ed.
Echocardiography in Pediatric and
Congenital Heart Disease Editors Lai,
Mertens, Cohen, Geva 2009
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Yale Congenital Heart Disease website: www.med.yale.edu/intmed/cardio/chd/
Braunwald’s Textbook Heart Disease