Tetralogy of Fallot Across the Lifespan: A Focus on the Right Ventricle

Abstract

Tetralogy of Fallot is a cyanotic congenital heart disease, for which various surgical techniques allow patients to survive to adulthood. Currently, the natural history of corrected tetralogy of Fallot is underlined by progressive right ventricular (RV) failure due to pulmonic regurgitation and other residual lesions. The underlying cellular mechanisms that lead to RV failure from chronic volume overload are characterized by microvascular and mitochondrial dysfunction through various regulatory molecules. On a clinical level, these cardiac alterations are commonly manifested as exercise intolerance. The degree of exercise intolerance can be objectified and aid in prognostication through cardiopulmonary exercise testing. The timing for reintervention on residual lesions contributing to RV volume overload remains controversial; however, interval assessment of cardiac function and volumes by echocardiography and magnetic resonance imaging may be helpful. In patients who develop clinically important RV failure, clinicians should aim to maintain a euvolemic state through the use of diuretics while paying particular attention to preload and kidney function. In patients who develop signs of cardiogenic shock from right heart failure, stabilization through the use of inotropes and pressor is indicated. In special circumstances, the use of mechanical support may be appropriate. However, cardiologists should pay particular attention to residual lesions that may impact the efficacy of the selected device.

Figure 1

Diagram and gross dissection of the right ventricle in tetralogy of Fallot. (A) Diagram showing the characteristic features of the right ventricle in tetralogy of Fallot and the names of various muscle structures (with their abbreviations), and (B) a heart specimen opened through the right ventricular outflow tract. The overriding aortic valve is visible through the ventricular septal defect (asterisk). PV, pulmonary valve; TV, tricuspid valve.

Figure 2

Dissections of a heart with tetralogy of Fallot. Dissections showing the myoarchitecture in tetralogy of Fallot. (A) The subepicardium with obliquely oriented strands on the sternocostal surface of the right ventricle (RV). (B) They continue onto the diaphragmatic surface apart from an area near the base (open arrow). (C) Deeper in, the oblique strands become more circumferential forming a thick middle layer like in the left ventricle (LV). (D) The strands in the right ventricular outflow tract displayed. OS, outlet septum; PV, pulmonary valve; SMT, septomarginal trabeculation; TV, tricuspid valve; VIF, ventriculo-infundibular fold.

Figure 3

Cardiopulmonary exercise stress test highlighting the physiology limitations in unrepaired and repaired tetralogy of Fallot (ToF). (A-C) Cardiopulmonary stress testing of a 30-year-old patient with unrepaired ToF, severe right ventricular outflow tract obstruction, and a bicuspid aortic valve with severe stenosis. The patient stops exercising soon after reaching anaerobic threshold (17 mL/kg/min), with a severely reduced peak oxygen consumption (peak VO₂) (19 mL/kg/min, 39% of predicted as noted in (A)) and a raised VE/VCO₂ slope. There is a reduced heart rate reserve (HRR) with a reduced chronotropic index (ratio of purple to green arrow in (C)) and a low O₂ pulse (flat blue line in (C)). This patient desaturated from 90% to 80% at peak exercise, with a blunted blood pressure response (systolic blood pressure 96-106 mm Hg at peak exercise). The above cardiopulmonary exercise testing findings are a combination of the severe bilateral obstructive lesions, reduced pulmonary blood flow, and right-left shunting (translating into inefficient ventilation). (D-F) Cardiopulmonary stress testing of a patient with repaired ToF and moderate residual pulmonary stenosis. This patient exercised beyond the anaerobic threshold but reached a peak VO₂ of only 70% of predicted (mildly impaired as noted in (D)), with a raised VE/VCO₂ slope as shown in (E), attributable to the pulmonary stenosis and reduced pulmonary blood flow. (F) There is a good HRR and mildly reduced O₂ pulse. VE/VCO₂, minute ventilation to carbon dioxide production.

Figure 4

Diagram delineating predicted peak oxygen consumption (peak VO₂) in various congenital heart diseases. Patients with repaired tetralogy of Fallot (ToF) (in red) have a median peak VO₂ in the mildly impaired region, suggesting that the majority of patients have at least mild exercise intolerance due to a combination of the congenital defect, residual lesions, and detraining. The box size proportionate to the sample size. ASD, atrial septal defect; AVSD, atrioventricular septal defect; CHD, congenital heart disease; PAH-CHD, pulmonary arterial hypertension related to CHD; systemic RV, systemic right ventricle; TGA, transposition of great arteries.

Figure 5

Echocardiographic images of right ventricle (RV) dilatation across the lifespan in repaired tetralogy of Fallot (ToF). Figure delineating progressive changes of the RV anatomy on echocardiography in the same patient after ToF repair. (A) The RV is highlighted within 1 month after repair, (B) the RV is shown 3 years after repair, and (C) the RV is shown 6 years postoperatively. This figure emphasizes that most of the RV remodelling occurs within the first 3 years with significant basal bulging. After 6 years from repair, there was some additional apical dilatation. RV function remained stable with a fractional area change of 43%, RV free wall strain −20%, and RV ejection fraction estimated by 3-dimensional echocardiography at 43%.

Figure 6

Myocardial strain imaging of the right ventricle in repaired tetralogy of Fallot. (A) 2-dimensional myocardial strain imaging. The pattern of activation includes an early septal-apical activation alongside basal-lateral prestretch and postsystolic shortening. (B) M-mode image showing a “septal flash” (arrows).