Congenitally corrected transposition of the great arteries (CCTGA)

Abstract

A 33-year-old man presented with a 3-week history of breathlessness and cough. He disclosed that he was informed regarding a heart defect as a child in his home country but was unaware of its nature and was never followed up. Examination revealed a pansystolic murmur (loudest at the apex), a hyperdynamic, displaced apex, and pulmonary oedema. An ECG showed atrial fibrillation with a regular broad-complex ventricular rhythm. Following electrical cardioversion, the ECG revealed complete heart block, therefore explaining the regular atrial fibrillation. An urgent transthoracic echocardiography (TTE) confirmed the anatomy of congenitally corrected transposition of the great arteries (CCTGA) with torrential tricuspid regurgitation and impaired systemic right ventricle. Cardiac MRI identified a ventricular septal defect which was not visible on TTE. The patient showed a transient improvement following fluid offloading and ACE inhibition, with a more definitive improvement after cardiac resynchronisation therapy (CRT).

Background

Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart defect characterised by the combination of atrioventricular (AV) and ventriculo-arterial discordance.¹ Despite its anatomical complexity, this defect can go unnoticed in early life and manifest clinically in adulthood.² The diagnosis of CCTGA should be considered in patients presenting with heart failure and/or high-grade AV block at a young age as noted in this case.^{3 4} This case emphasises the importance of life-long specialist surveillance of all patients with this diagnosis, with an accent on monitoring for worsening of tricuspid regurgitation (TR), development of higher degrees of AV block and deterioration in systemic right ventricle (RV) function to allow for timely intervention. We highlight key imaging modalities required for the diagnosis of CCTGA, along with the management options for these patients. We also discuss the uncommon entity of regular atrial fibrillation which should alert the physician to search for the presence of high degree AV block.

Case presentation

A 33-year-old Caucasian male presented to the emergency department at our institution with a 3-week history of worsening dry cough and non-exertional dyspnoea. He denied chest pain, palpitations, syncope, fever or haemoptysis, but described poorer appetite and mild weight loss. He was a smoker of 20 cigarettes a day, denied illicit substance use and had not travelled for a few months prior to presentation. He never required hospitalisation or regular medication. He had been told about a heart condition as a child in his native country but was unaware of its nature. He was under the impression that this would not interfere with his life and had hence never sought to follow it up after immigrating.

On initial examination, he was tachypnoeic at rest and desaturating to 92% on room air. He had a good volume radial pulse at a regular rate of 75 beats per minute (bpm) and a non-invasive blood pressure of 90/60 mm Hg. Palpation of the precordium revealed a hyperdynamic and displaced apex beat. On auscultation, there was a harsh pansystolic murmur loudest at the apex and along the lower sternal border, radiating to the left axilla, as well as bilateral coarse inspiratory crepitations up to the mid-zones. N-terminal-prohormone brain natriuretic peptide levels were significantly elevated at 6845 pg/mL (upper limit of normal: 125 pg/mL), with marginal elevation of liver enzymes.

Investigations

Initial 12-lead ECG (figure 1A) showed atrial fibrillation (AF) with a regular broad-complex ventricular rhythm at a rate of 75 bpm. This was consistent with AF and concurrent complete heart block (CHB), with a ventricular escape rhythm. The QRS complexes had a ‘pseudo-delta wave’ appearance (indicated with red circle in figure 1A) with a left bundle branch block pattern and inferior axis. Chest X-ray (figure 1C) showed marked cardiomegaly, a narrow vascular pedicle with absent aortic knuckle, splaying of the carina and interstitial and alveolar oedema.

Figure 1.

Initial investigations. (A) First 12-lead ECG showing atrial fibrillation with a regular broad-complex ventricular rhythm at 75 bpm, with the QRS having a pseudo-delta wave appearance (circled in red). (B) ECG following successful electrical cardioversion confirming third-degree atrioventricular block. (C) Chest X-ray at presentation showing gross cardiomegaly, splaying of the carina suggesting left atrial dilatation, marked interstitial and hilar congestion and upper lobe venous diversion, as well as a narrow vascular pedicle and absent aortic knuckle suggesting parallel great arterial arrangement.

A transthoracic echocardiogram (TTE) was performed as part of an urgent cardiology review. It revealed normal atrial arrangement, however, identified AV discordance with the left atrium connected to the morphological RV (recognised following identification of a moderator band (marked with a red arrow in figure 2A), prominent trabeculae at the apex and chordal attachments to the interventricular septum) via the tricuspid valve (TV) (figure 2A). The great arteries showed parallel arrangement with the aorta (recognisable as the great vessel bearing coronary origins) coming off the RV and the pulmonary artery (identified by its bifurcation) coming off the left ventricle. This double discordance pattern is diagnostic of CCTGA. There was free TR as a result of failure of leaflet coaptation with associated severe left atrial dilatation (figure 2B). The systemic RV was severely dilated with severely impaired systolic function. The consensus by the caring physicians regarding the clinical decline was secondary to the acute development of AF and hence urgent direct current cardioversion (DCCV) was performed, with subsequent ECGs confirming the presence of underlying third-degree AV block (figure 1B).

Figure 2.

Imaging leading to diagnosis. (A) Transthoracic echocardiographic apical four-chamber view confirming atrioventricular discordance. The morphological RV can be identified by the moderator band (marked with red arrow) and the associated tricuspid valve; the latter recognisable from its more apical offset. (B) Colour Doppler on the systemic tricuspid valve confirming a large coaptation defect with torrential tricuspid regurgitation. (C) Cardiac MRI in axial view showing abnormal parallel great arterial arrangement confirming the presence of transposed great vessels. (D) Cardiac MRI in coronal view showing the aorta coming off the dilated systemic RV confirming ventriculo-arterial discordance. Ao, ascending aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.

Subsequent cardiac magnetic resonance (CMR) corroborated the findings of severe systemic TR (regurgitant fraction 70%) and systemic RV dilatation (indexed end-diastolic volume 351 mL/m²) and impaired function (ejection fraction 49%). CMR identified a peri-membranous ventricular septal defect (VSD) with a systemic to pulmonary shunt (Qp:Qs=1.9:1) which was not visible on TTE, as well as delineated the parallel great arterial arrangement in greater detail (figure 2C, D). Cardiac catheterisation documented a pulmonary vascular resistance of 4 WU.

Treatment

The patient tolerated the CHB well (ventricular response rate of 50–60 bpm) with an initial degree of symptomatic improvement with loop diuresis and low dose enalapril. Surgical TV replacement was deemed too high-risk mainly in the light of severe RV impairment. After multidisciplinary discussion, consensus was reached for the patient to undergo cardiac resynchronisation therapy (CRT) implantation which took place a few weeks after diagnosis.

Outcome and follow-up

The patient made a significant symptomatic improvement following CRT insertion, he denied exertional dyspnoea and noted that he began gaining the weight he lost prior to presentation. His quality of life improved substantially, and he was able to return to work with no limitations.

Discussion

CCTGA (also referred to as L-TGA) is rare and accounts for approximately 0.05%–1% of all congenital heart defects, with a slight male preponderance.^{1 4} CCTGA is one of the most common congenital cardiac conditions associated with sudden cardiac death in adults.⁵ Morphologically, it is characterised by discordance of both AV and ventriculo-arterial connections (double discordance). As a consequence, systemic venous return still reaches the lungs (pumped by a subpulmonary left ventricle) and oxygenated pulmonary venous blood is directed to the body (by a systemic RV).¹ Most cases of CCTGA have at least one concomitant structural abnormality, the most common being a VSD.⁶ The coronary arteries usually arise from the aortic sinuses adjacent to the pulmonary trunk, with the right-sided coronary artery having the epicardial distribution of the normal left coronary artery, while the left-sided coronary artery is arranged as a morphologically right coronary artery, although other variations have been documented.¹ Malalignment of atrial and ventricular septae leads to abnormal positioning of the AV node and bundle of His resulting in a fragile conduction system. Hence, giving rise to a high risk of AV block during TV and VSD surgery and an incremental incidence of AV block with increasing age.³

CCTGA associated with a large VSD or severe TR usually presents with congestive heart failure in infancy or childhood.⁶ On the other hand, patients with no or mild concomitant defects often have an uneventful childhood and adolescence with the condition manifesting during adulthood, most commonly due to the development of CHB, severe TR or systemic RV failure.^{2 6} Occasionally, the condition can manifest as a tachyarrhythmia, usually of supraventricular origin. In unoperated patients, atrial flutter or fibrillation are usually driven by atrial enlargement secondary to TR. Rarely, CCTGA can be an incidental finding following an abnormal ECG, a murmur heard during a routine physical examination or at imaging.⁷

Regular AF is an uncommon, yet important entity that physicians must be able to identify. It is often a result of digitalis effect which causes impaired AV conduction and increased junctional automaticity. However, it may also be a result of AF with concurrent CHB and a ventricular or junctional escape rhythm.⁸ The first ECG of the case shows AF with a regular broad-complex ventricular rhythm (figure 2A). The regularity of the ventricular rhythm supports CHB with a ventricular escape rather than slow, pre-excited AF. This is confirmed on the post-DCCV ECG that reveals CHB and a ventricular escape rhythm with the same QRS morphology as the initial ECG during AF (figure 2B). This effectively rules out pre-excitation which requires AV association.

TTE is the investigation of choice to confirm the diagnosis, however, CMR and cardiac CT offer further accurate imaging and information, including vascular anatomy, nature of concomitant congenital defects, quantification of chamber volume, ventricular function and valvular regurgitation (recommended by both European Society of Cardiology (ESC) and American Heart Association).^{4 9 10} Right and left heart pressures and the presence of luminal coronary artery disease (especially in older patients with atherosclerosis-related risk factors) are best assessed by invasive cardiac catheterisation.⁶

The treatment of CCTGA is dependent on several factors, including age of diagnosis, symptoms and the complications which would have already manifested at that stage. Medical management of CCTGA is limited, echoing the rarity of this condition and the scarce literature available. Treatment mainly consists of fluid offloading with loop diuretics and control of arrhythmias. Although afterload reduction with ACE inhibitors or angiotensin receptor blockers is often used, there is no supporting evidence of beneficial effects of these agents in patients with systemic RV dysfunction.¹¹ Significant TR has been identified as an independent predictor of death in CCTGA, and earlier TV replacement before RV dysfunction ensues (<40% ejection fraction) is advocated.^{10 12–14} TV replacement is indicated in patients with symptomatic severe TR and an ejection fraction of more than 40% (Class I recommendation).⁴ Whereas the double switch operation is an option in the paediatric population, it is not recommended in adults due to its high associated mortality, and indeed its recommendation has been removed altogether from the updated 2020 ESC guidelines.^{4 6}

Dyssynchrony induced by subpulmonary ventricular pacing can lead to worsening systemic RV function, while differences in septal activation can predispose to worsening of TR. As a consequence, biventricular pacing is often deemed a more appropriate form of pacing, and indeed this has been included as a new class IIa recommendation in the 2020 ESC guidelines.^{3 4 15} Radiofrequency ablation should be considered in patients with significant atrial arrhythmias or evidence of accessory pathways.³ In patients with severe systemic ventricular failure refractory to medical measures and CRT, referral for cardiac transplantation may be indicated.⁶

Learning points.

• Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart defect which may manifest in adult life.

• The combination of heart failure and atrioventricular block in young patients should raise the suspicion of CCTGA, while regular atrial fibrillation should alert the physician to search for the presence of high degree atrioventricular block or digitalis toxicity.

• Transthoracic echocardiogram is the key diagnostic imaging modality; however, cardiac MRI provides further detailed anatomy.

• The management of CCTGA is guided by symptoms, ejection fraction and the degree of heart block, if present.

• Life-long follow-up of all patients with CCTGA is recommended.

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