It is not practical to perform frequent cMRI to determine the optimal timing of PVR to normalize the RV volume and prevent RV dysfunction in patients after TOF repair. We considered it ideal that parameters measured in the daily clinical setting can indicate the optimal timing of cMRI as the gold standard for the evaluation of the RV volume and function.
In chronic PR, the RV systolic function is initially preserved, and many cases remain relatively free of symptoms. Once the compensatory mechanisms cannot be maintained, the RV mass-to-volume ratio decreases, then the RVESV increases, RVEF decreases, and patients finally fall into RV dysfunction. The RV dysfunction is also associated with RV wall stress due to RV afterload from RVOT obstruction, RV fibrosis, RVOT aneurysm at the site of transannular patch, an impaired RV diastolic function, and left ventricular (LV) dysfunction [1–3, 9–11] .
In order to increase the chances for the patient to reach a normal RV volume after the repair, Therrien et al. recommended PVR be undertaken before the RVEDVI reaches 170 ml/m2 or the RVESVI reaches 85 ml/m2 . PVR is recommended to be performed under the condition that the RVEDVI is <160-170 ml/m2 and the RVESVI is <80-90 ml/m2, as thresholds for the normalization of the RV volume after PVR [4–8].
In this study, each resting QRS duration, plasma BNP level, and CTR demonstrated good positive correlations with RVEDVI and RVESVI long after TOF repair. The QRS duration and plasma BNP level also showed good negative correlations with RVEF long after TOF repair. Many studies have reported that the resting QRS duration reflects progressive RV dilatation (increased RVEDVI and RVESVI), and RVEDVI or RVESVI have been reported to be correlated with the RVEF [1, 6, 11–13].
Some studies reported that BNP and NT-pro BNP reflected the RVEDVI and RVEF of patients after TOF repair [14, 15]. In present study, the plasma BNP level was also correlated with the RV volume in patients after TOF repair. However, the use of the plasma BNP level for the estimation of RV volume during outpatient follow-up was thought to be complex as it requires logarithmic transformation. Moreover, Eindhoven et al. reported that NT-pro BNP was correlated with the systolic RV function, but more strongly correlated with the systolic LV function and dimensions. They said that the likelihood that NT-pro BNP will be released from the right ventricle is generally lower in comparison to left ventricle .
In the present study, only the post-PVR QRS duration showed good correlations with both post-PVR RVEDVI and RVESVI. This indicates that the QRS duration is a good marker of the RV volume both before and after PVR in patients after TOF repair .
In their report of 26 cases, Huysduynen et al. noted that the change in the QRS duration (ΔQRS duration) from before to after PVR is also correlated with the change in RVEDVI (ΔRVEDVI). They considered that RV dilatation may increase the QRS duration by increasing the distance that the electrical activation front has to move in the right ventricle, and they considered that the relationship between RVEDVI and the QRS duration also applies to the ΔRVEDVI and the ΔQRS duration before and after PVR .
The positive correlation between RVEDVI and the QRS duration in our data yielded a cutoff value of the QRS duration of 160 ms when RVEDVI 170 ml/m2 was used as the threshold for RV normalization by Therrien et al.. QRS duration >160 ms could detect patients with RVEDVI >170ml/m2 and RVESVI >85 ml/m2 with high sensitivity and high specificity.
In the present study, both RVEDVI and RVESVI normalized after PVR in most patients (RVEDVI, all 5 patients; RVESVI, 4 of 5 patients) in the N group, although RVESVI did not normalize in 6 of 7 patients in the W group. Because RVESVI has been reported to have a better relationship with RVEF than RVEDVI [1, 6, 12], our results are considered to have clinical significance. The post-PVR RVEF was maintained at >40% in 4 of 5 patients in the N group; however, the post-PVR RVEF was maintained at <40% in 6 of the 7 patients in the W group.
Geva et al. also used a cutoff value of QRS duration of ≥160 ms to predict persistent post-PVR RV dilatation and dysfunction, and suggested that a QRS duration of <140 ms was associated with a normal RV size and function after PVR . Cocomello et al. reported that patients with a QRS duration approaching 160 ms or those with RVEDVI ≥ 166 ml/m2 or RVESVI ≥ 89 ml/m2 should be considered for PVR to prevent a gradual increase of RV volume after PVR . These 2 studies support the validity of our results regarding the cutoff value of QRS duration (160 ms) after TOF repair.
Scherptong et al. reported that a severely prolonged QRS duration (>180ms) was associated with an increased incidence of adverse outcomes, and PVR should be performed before severe QRS prolongation occurrs .
Romeo et al. reported that the QRS duration could be used as a biomarker for RV volumetric and functional change, and as a risk factor for late adverse outcomes, and that if PVR can be performed early enough to prevent the progression of QRS prolongation, it may reduce the incidence of adverse events after PVR .
Regarding the question of whether the QRS duration can be used as a preoperative assessment of the RV volume in outpatients after TOF repair, there was a tendency for the QRS duration to change simultaneously with the RV volume in each case after surgery, although this was only observed in a small number of cases. In other words, RVEDVI increased in patients with a prolonged QRS, while RVEDVI did not change in patients with a steady QRS duration (Fig. 5). Such a change in QRS is essential for the continuous use of the QRS duration as an indicator of RV volume progression long after TOF repair. To the best of our knowledge, limited studies have focused on the QRS duration as an indication for PVR for RV enlargement due to PR [8,18].
Considering additional factors of QRS prolongation, right bundle branch block (RBBB) due to RV infundibular resection or RVOT incision in TOF repair influences the QRS prolongation. In this study, the QRS duration of TAP cases tended to be wider than that of pulmonary valve sparing cases in each generation after TOF repair (Fig. 5). In our study, 14 of the 15 PVR cases (the one exception had a narrow QRS duration of 92 ms) showed RBBB before PVR. RBBB due to infundibular resection will progress with RV dilatation from PR after TOF repair.
The QRS duration was a useful marker of the RV volume and RVEF; however, this study lacked sufficient power to determine whether the QRS duration can be used directly as a threshold to predict RV normalization after PVR. After TOF repair, we recommend that cMRI to evaluate the RV volume for the optimal timing of PVR be performed before the QRS duration reaches 160 ms.
The present study was associated with some limitations, including its retrospective and monocentric design. The relatively small number of patients in this study resulted in a loss of statistical power. Not all patients could perform cMRI more than once after TOF repair, and a cMRI volume study could not be performed in all PVR patients. Our study requires validation by a further study of a larger population.