Over the past decades, life expectancy of patients with congenital heart disease has dramatically increased. The prognosis of patients with tetralogy of Fallot (TOF) was invariably fatal until the development of palliative and later corrective surgical procedures. Repaired TOF has an excellent long-term prognosis, but survival is still suboptimal. Serious complications may develop late after total repair during infancy. These complications are usually the result of longstanding pulmonary regurgitation, leading to dilatation of the right ventricle, decreased exercise tolerance, an increased risk for severe arrhythmias, and even sudden death. Pulmonary valve replacement has beneficial effects on right ventricular size and function, provided it is performed early, before irreversible right ventricular dysfunction ensues. Moreover, pulmonary valve replacement is associated with an improvement in patients’ symptoms and exercise tolerance. Combined with arrhythmia surgery pulmonary valve replacement leads to a dramatic decrease in the incidence of fatal ventricular arrhythmias. Although late pulmonary valve replacement offers excellent mid-term results, homografts and xenografts, usually used for right ventricular outflow tract reconstruction, suffer late dysfunction and failure, committing patients and surgeons to further operations. Therefore, the timing of surgery must be carefully considered, weighing the up-front risks of surgery and possible repeat surgery against the risk of ongoing pulmonary regurgitation [1, 2]. Over the past years, many investigators have attempted to find the optimal moment of surgery [3–8], but presently there are no universally accepted criteria to determine optimal timing for valved conduit placement in patients with TOF.

A combination of clinical, electrocardiographic and imaging criteria is presently used to determine the timing of valve replacement. Exercise tolerance, signs of heart failure, prolonged QRS duration play an important role, but nowadays criteria based on cardiovascular imaging are gaining increased interest. In the past 20 years, cardiovascular magnetic resonance (CMR) imaging has become a predominant tool in the clinical management of patients with cardiovascular disease [9–15], in particular in patients with congenital heart disease [16–24]. CMR imaging has evolved into an imaging technique that provides adequate and unique information on residual problems in the follow-up of patients operated for TOF [8]. Spin-echo and gradient-echo CMR imaging allow detailed assessment of intracardiac and large vessel anatomy, which is particularly helpful in TOF patients with residual abnormalities of right ventricular outflow and/or pulmonary artery. Multisection gradient-echo cine CMR can be used to obtain accurate measurements of biventricular size, left and right ventricular ejection fraction, and wall mass. This allows serial follow-up of biventricular function. Knauth et al. showed that severe right ventricular dilatation and either left or right ventricular dysfunction assessed by CMR predicted major adverse clinical events [25].

At present, CMR velocity mapping is the only imaging technique available that provides practical quantification of pulmonary regurgitation volume. CMR velocity mapping can also be used to quantify right ventricular diastolic function in the presence of pulmonary regurgitation. Niezen et al. used CMR imaging to assess right ventricular diastolic function in young patients with corrected TOF and pulmonary regurgitation [26]. Nineteen children with repair of TOF and 12 healthy children were studied using CMR The authors showed impaired relaxation and restriction to filling affect right ventricular function in children with repair of TOF and pulmonary regurgitation. Based on the above-mentioned studies, CMR imaging may play a key role in indications, accurate diagnosis and prognosis, and timing of pulmonary valve replacement after TOF repair [27].

In a recent study, Oosterhof et al. analyzed preoperative thresholds of right ventricular volumes above which no decrease or normalization of right ventricular size takes place after surgery [28]. The authors studied 71 adult patients with corrected TOF, who underwent pulmonary valve replacement in a nationwide, prospective follow-up study. Patients were evaluated with CMR imaging both preoperatively and postoperatively. The authors could not find a threshold above which right ventricular volumes did not decrease after surgery. Preoperative right ventricular volumes were independently associated with right ventricular remodeling and also when corrected for a surgical reduction of the right ventricular outflow tract. However, normalization could be achieved when preoperative enddiastolic volume was <160 ml/m² or right ventricular endsystolic volume was <82 ml/m².

The purpose of the present study by Greenberg et al. reported in this issue, was to identify E- and A-wave flow patterns across the tricuspid valve in TOF patients [29]. Results from CMR phase contrast velocity-encoded flow quantification correlated well with measurements of right ventricular enlargement. The authors studied 33 children following TOF repair who had CMR examinations that included cine imaging to quantify ventricular size and function and flow analysis across the atria-ventricular valves to evaluate ventricle in-flow patterns. The E:A ratio was calculated for each patient and the population was separated into two different groups: alpha (E:A ratio ≥ 1.4) and beta (E:A ratio < 1.4) groups. A significant association was present between the group with E:A ratio < 1.4 and right ventricle enddiastolic volume index ≥ 140 ml/m² (P = 0.046), right ventricular endsystolic volume index ≥ 70 ml/m² (P = 0.02), and enddiastolic volume right ventricle to left ventricle ≥ 2.0 (P = 0.003). A reduction in the E:A wave ratio across the tricuspid valve was associated with right ventricular diastolic dysfunction and correlated well with right ventricular enlargement. The reduction in the E:A wave ratio across the tricuspid valve may be considered a new useful criterion for determining the timing of valved pulmonary conduit surgery in children following TOF repair.

The decision to operate adult patients with TOF for pulmonary regurgitation should be based on the balance between progressive right ventricular dilatation, exercise intolerance, symptoms, the occurrence of arrhythmias and the fact that further reoperations will be needed [30–34]. Research on the ideal valve for right ventricular outflow tract reconstruction is ongoing. Oosterhof et al. analyzed the long-term outcomes after pulmonary valve replacement in patients with a previous correction for TOF [35]. In a retrospective study, 158 adult patients who had undergone a pulmonary valve replacement after initial total correction for TOF in childhood, were identified from the Dutch CONCOR (CONgenital CORvitia) registry [36]. All patients underwent pulmonary valve replacement between June 1986 and June 2005. After 10 years of pulmonary valve replacement, 47% of the patients were free from homograft dysfunction and event-free survival after pulmonary valve replacement was 78%. Significant residual lesions directly after surgery influenced event-free survival. A smaller diameter of the pulmonary homograft and severe pre-surgical pulmonary regurgitation were related to early homograft dysfunction after surgery.

Prospective follow-up of patients with TOF with exercise testing and assessment of right ventricular size and function will better define the natural history of the disease. At present, CMR imaging plays a key role in assessing ventricular function and volumes, thereby predicting clinical outcomes and providing firm guidelines for timing of pulmonary valve replacement, especially in asymptomatic patients. The current study of Greenberg et al. [29] provides a valid additional CMR criterion to determine proper timing of surgery in adult patients with TOF and serious pulmonary regurgitation.