TETRALOGY OF FALLOT FOR THE ADULT CARDIOLOGIST

Anne-Marie Anagnostopoulos, MDNon-Invasive ConferenceDecember 9, 2009

Outline

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

Special Thanks

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

History of Tetralogy of Fallot 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”

History

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.

Epidemiology

Overall, congenital heart disease is rare

However, of the cyanotic congenital heart abnormalities, TOF is the most common

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

Anatomy and Embryology

The fundamental embryologic malformation in TOF is abnormal development of the cono- truncus (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

2D Echo TOF

Source: Feigenbaum’s 6th Ed.

Spectrum of Tetralogy

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

TOF:Pulmonary Atresia and VSD

• 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

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)

Surgical Repair

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

Palliative Shunts

Glenn Shunt

2D Echo Glenn Shunt: SVC->PA

Source: Feigenbaum’s 6th Ed.

Surgical Repair – Transannular Patch

Patients post-repair do well up to ~25 yrs post-operatively

Modes of death:Sudden cardiac deathArrhythmiasCongestive heart

failure

Natural History

Nollert G. JACC 1997; 30:1374

The Adult with Repaired TOF Patients often remain asymptomatic Although decreased exercise

capacity can often be elicited with objective testing

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)

Sequelae of TOF Repair

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

Imaging in Repaired TOF

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

Pulmonary Regurgitation

Nearly universal Severity is dictated by:

compliance of the RV capacitance of the pulmonary

arteries

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

Pulmonary Regurgitation

Courtesy A. Valente

Effects of Chronic PR

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.

Effects of Chronic PR

Compensatory mechanisms exist up to a certain point, but ultimately these mechanisms fail

Courtesy A. Valente MD

Effects of Chronic PR

Good RV Function Poor RV Function

Courtesy A. Valente

Severity of Pulmonary Regurgitation

• Prospective study of 34 adults with repaired TOF• Echocardiogram & cardiac MRI within 3 months• Median age 33 yrs (12 yrs)• Mean time since initial surgical repair 25 8 yrs• 13 subjects had undergone transannular patch• 6 subjects had undergone bioprosthetic PVR

Silversides C. JASE 2003; 16: 1057

Pulmonary Regurgitation

% 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

Silversides C. JASE 2003; 16: 1057

• In addition, PHT <100ms had highest sensitivity and specificity for detecting significant PR (RF >20%)

Geva T. JACC 2004; 43(6): 1068

Biventricular Interaction

Median age from repair 21 years

Unfavorable ventricular-ventricular 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

RV Function by Echocardiography Often adults with repaired TOF

cannot undergo CMR due to devices Myocardial Performance Index (MPI)

has been shown to correlate with MRI RVEF

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 timeSchwerzmann, M. AJC

2007;99:1593

RV MPI Correlation With CMR RVEF

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

RV MPI Correlation With CMR RVEF

Schwerzmann, M. AJC 2007;99:1593

Regional Wall Motion Abnormality

Davlouros et al. JACC 2002; 40:2044

• 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

Pulmonary Valve Replacement

Operative risk is small: mortality < 2%

What criteria should we use in patient selection?

Traditional indication: patient symptoms Is there a risk to waiting until patients

develop symptoms?

*Oosterhof T. Heart 2007; 93: 506

Patients may not detect subtle changes in exercise capacity

By the time patients notice symptoms, problems may be severe and irreversible

Predictors of Adverse Outcome

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 eventsKnauth A. Heart 2008; 94: 211-16.

Proposed Criteria for PVR

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 RVEDVi > 160 cc/m2 ( z > 5) RVESVi > 70 cc/m2

LVEDVi < 65cc/m2

RVEF < 45% RVOT aneurysm LVEF < 50%

Geva T. STCVS 2006; 9:11.

Aortic Root Dilation

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

Predictors of Arrhythmia and SCD 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

Recommendations

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 CHBGeva T. STCVS 2006; 9:11.

Summary

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

References

Feingenbaum’s Echo Textbook, 6th Ed.

Echocardiography in Pediatric and Congenital Heart Disease Editors Lai, Mertens, Cohen, Geva 2009

Yale Congenital Heart Disease website: www.med.yale.edu/intmed/cardio/chd/

Braunwald’s Textbook Heart Disease