Department of Cardiology, Blacktown Hospital, Sydney, NSW, Australia
Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
University of Sydney, Sydney, NSW, Australia
Clinical History
A 25-year-old male with repaired Tetralogy of Fallot (TOF) presented for his routine follow up appointment but had noted progressive exertional dyspnoea. He was diagnosed with TOF antenatally and underwent non-valve sparing transannular patch repair at the age of 1 year. At routine paediatric follow up aged 14 years, his ascending aorta on echocardiography measured 90mm. He had an urgent aortic valve and root replacement (Bentall procedure). Intra-operatively, it was noted that there was only an aberrant right coronary artery arising directly from the left main coronary artery (single coronary artery). A bridging saphenous vein graft was used to attach the replaced aortic root to the single coronary artery (Cabrol repair).
A few years following this procedure, his mother suffered an aortic dissection requiring emergent surgical repair. His maternal aunt was diagnosed with mesenteric ischemia due to a superior mesenteric artery aneurysm. This prompted genetic testing which at the time demonstrated a genetic mutation in the fibrillin gene as a variant of uncertain significance. This mutation was re-classified 20 years later as a pathogenic mutation, consistent with a diagnosis of Marfan syndrome in our patient.
At the clinic visit, his vital signs were within normal limits. ECG demonstrated sinus rhythm with right bundle branch block and QRS duration of 182 ms (Figure 1).
 |
| Figure 1. ECG demonstrating right bundle branch block with QRS duration 182 ms. |
Echocardiography demonstrated a mildly dilated right ventricle with moderate pulmonary stenosis (peak gradient 50mmHg) and moderate to severe regurgitation. The branch pulmonary arteries were unobstructed. The aortic arch was moderately dilated with flow acceleration in the ascending aorta. The prosthetic mechanical aortic valve functioned normally with a mean gradient of 17mmHg. He had two subsequent hospital admissions with atrial fibrillation with no clear trigger. Cardiovascular magnetic resonance imaging (CMR) was also performed, with images acquired via a Aera 1.5 Tesla (Siemens Healthineers AG, Erlangen, Germany) system.
CMR Findings
Reporting the cardiac MRI with two rare and distinct pathologies that were exerting quite different haemodynamic stresses on the heart was challenging and required a return to “sequential segmental analysis” to elucidate the combined effect of both pathologies. There was situs solitus and levocardia with conventional systemic and pulmonary venous return. The right atrium was mildly dilated with mild tricuspid valve regurgitation. The right ventricle was severely dilated with an indexed right ventricular end-diastolic volume (RVEDVi) of 192mL/m2 and a RV ejection fraction (EF) of 31%. The severity of the RV dilatation and ventricular dysfunction was under-estimated by echocardiography. Flow data demonstrated mild pulmonary regurgitation. The right ventricular outflow tract is depicted in Movies 1 and 2, with a RV long-axis view shown in Movie 3.
 |
| Movie 1. Cine balanced steady state free precession (bSSFP) short axis base showing right ventricular chamber dilation and aneurysmal right ventricular outflow tract. |
 |
| Movie 2. Cine bSSFP axial section depicting the right ventricular outflow tract with pulmonary valve stenosis and insufficiency. |
 |
| Movie 3. Cine bSSFP right ventricular long-axis view showing the aneurysmal right ventricular outflow tract. |
The pulmonary trunk and branch pulmonary arteries were dilated; a A 3–Dimensional multi-planar rendering of the pulmonary vasculature is illustrated in Movie 4.
 |
| Movie 4. 3- Dimensional multi-planar rendering of pulmonary vasculature. |
The left atrium and ventricle were of normal size with normal LV systolic function. The indexed left ventricular end-diastolic volume (LVEDVi) measured 81ml/m2. A 4-chamber cardiac view is demonstrated in Movie 5 with the left ventricular outflow tract (LVOT) and origin of Cabrol repair shown in Movie 6.
 |
| Movie 5. Cine bSSFP 4 chamber view with right ventricular dilation. |
 |
| Movie 6. Cine bSSFP LVOT with the mechanical aortic valve and the origin of Cabrol repair. |
Of note, there was acute angulation of the aortic root graft just superior to the origin of the coronary graft. A Cine sequence of the LVOT and acute iatrogenic angulation of the ascending aorta is demonstrated in Movie 7. This likely explained the flow acceleration seen on echocardiography. The aortic arch was mildly dilated, however there was no focal dissection. A 3-Dimensional whole heart sequence can be appreciated in Movie 8.
 |
| Movie 7. Cine bSSFP coronal off axis of the LVOT showing acute angulation of the ascending aorta. |
 |
| Movie 8. 3-dimensional whole heart sequence sagittal plane showing the folding of the proximal ascending aorta without evidence of dissection and dilation of the pulmonary arteries. |
Tissue characterisation demonstrated normal native T1 and T2 times with no significant late gadolinium enhancement of LV myocardium. A small patch of late gadolinium enhancement (LGE) was present in the RV insertion point and is commonly observed in TOF patients, however the clinical significance of this remains unclear.
Conclusion
The patient had significant RV dilatation and moderate systolic dysfunction meeting criteria for pulmonary valve replacement in Tetralogy of Fallot. The measured pulmonary regurgitation by flows were under-estimated due to technical factors on CMR requiring correlation with echocardiography. The flow measurements through the main pulmonary artery (MPA) were impacted by motion artefact from the prosthetic valve. Ectasia of the great vessels due to connective tissue disease further add to the inaccuracies of flow measurements due to eccentric wall shear stress and non-laminar flow. Incidentally, there was an iatrogenic supra-aortic obstruction due to angulation of the replaced aortic graft. There was no evidence of increased afterload on the left system because of this defect.
The case was discussed in the combined medical and surgical adult congenital heart disease multidisciplinary meeting (MDT) and surgical management was suggested by consensus. Additional investigations included an objective exercise test where he had reduced exercise capacity and ambulatory blood pressure monitoring where there was no significant systemic hypertension. He underwent a redo-sternotomy for pulmonary valve replacement. The acute aortic angulation was repaired by modification of the ascending aortic graft, and he also had a stochastic trajectory analysis of ranked signals (STAR) procedure in view of prior atrial fibrillation. He made an uneventful recovery and was discharged home in two weeks.
Perspective
The combination of TOF and Marfan syndrome is exceedingly rare, with only four case reports found on our literature search [1-4]. CMR is the clinical reference technique for pulmonary regurgitation assessment in repaired TOF [5] and is superior compared to transthoracic echocardiography in assessment of RV size and function for this population group [6].
In addition to being the preferred imaging modality, CMR in this case was key in deciphering the mechanism of symptoms in a patient where two distinct pathologies exerted different haemodynamic loads on different cardiac chambers. CMR highlighted the fundamental process of sequential segmental analysis and allowed for exclusion of common related complications for both TOF and Marfan syndrome. By visualising the RVOT better than echocardiography in a patient with prior transannular patch repair, we were able to appreciate the true severity of RV dilatation rather than relying on apical views on echocardiography. Adding to this complexity, echocardiography demonstrated abnormal flow in the ascending aorta, which was particularly concerning given the known history of Marfan’s syndrome and familial history of aortic dissection. Coronary computed tomography angiography and aortography did not show dissection or significant ostial obstruction. CMR allowed clear visualisation of the ascending aorta in a 3D construct which allowed the iatrogenic angulation to be diagnosed. In this setting, CMR also offers assessment of left ventricular parameters, providing a detailed understanding of haemodynamic impacts of this aortic angulation, which were not present. Although not available at the treating tertiary centre, 4D flow would improve accuracy of flow assessments and in early detection of abnormal wall shear stress in patients with Marfan syndrome.
CMR also allowed assessment of branch pulmonary arteries and provided anatomical relationships that would be important to exclude in a TOF patient with exercise limitation and tissue characterisation ensured that there was no significant underlying cardiomyopathy or arrhythmia substrate.
Overall, integration of multi-modality imaging data, sequential segmental analysis, case discussion, imaging reviews at multidisciplinary meetings and a clear discussion with the patient regarding the CMR findings are required to detangle such rare and complex cases. The role of CMR in this case was vital for diagnosis and long-term planning, highlighting the utility of CMR in functional, volumetric, and haemodynamic analysis in the setting of repaired, complex congenital cardiac lesions.
Click here to view the CMR images.
References
- Bouzas, B., P.J. Kilner, and M.A. Gatzoulis, Pulmonary regurgitation: not a benign lesion. European Heart Journal, 2005. 26(5): p. 433-439.
- Di Salvo, G., et al., Imaging the adult with congenital heart disease: a multimodality imaging approach—position paper from the EACVI. European Heart Journal – Cardiovascular Imaging, 2018. 19(10): p. 1077-1098.
- Blalock, S.E., et al., Interstudy variability in cardiac magnetic resonance imaging measurements of ventricular volume, mass, and ejection fraction in repaired tetralogy of fallot: A prospective observational study. Journal of Magnetic Resonance Imaging, 2013. 38(4): p. 829-835.
- Pannu, H.S., G.L. Avasthi, and N.K. Sood, Tetralogy of Fallots co-existing with Marfan’s syndrome–an uncommon association. J Assoc Physicians India, 2001. 49: p. 290-1.
- Ross, J.K. and F. Gerbode, The Marfan syndrome associated with an unusual interventricular septal defect. J Thorac Cardiovasc Surg, 1960. 39: p. 746-50.
- Abraham, A.S., M. Atkinson, and W.M. Mitchell, Fallot’s tetralogy with some features of Marfan’s syndrome and survival to 58 years. Br Heart J, 1961. 23(1): p. 110-2.
- Singla, P., et al., Marfan’s Syndrome with Tetralogy of Fallot in an Adult Female with Bronchiectasis: An Unacquainted Manifestation. Amrita Journal of Medicine, 2021. 17(2): p. 54-57.
- Holst, K.A., et al., Risk factors and early outcomes of multiple reoperations in adults with congenital heart disease. Ann Thorac Surg, 2011. 92(1): p. 122-30.
Case prepared by:
Anna Baritussio, MD, PhD
Editorial Team, Cases of SCMR
Department of Cardiac, Thoracic, Vascular Sciences and Public Heath
Padua University Hospital
Padua, Italy
