Patients with repaired tetralogy of Fallot suffer from intra- and inter-ventricular cardiac dyssynchrony: a cardiac magnetic resonance study

Abstract

Aims: Patients with repaired tetralogy of Fallot (rTOF) frequently have right bundle branch block. To better understand the contribution of cardiac dyssynchrony to dysfunction, we developed a method to quantify left (LV), right (RV), and inter-ventricular dyssynchrony using standard cine cardiac magnetic resonance (CMR).

Methods and results: Thirty patients with rTOF and 17 healthy controls underwent cine CMR. Patients were imaged twice to assess inter-test reproducibility. Circumferential strain curves were generated with a custom feature-tracking algorithm for 12 LV and 12 RV segments in each of 4-7 short-axis slices encompassing the ventricles. Temporal offsets (TOs, in ms) of the strain curves relative to a patient-specific reference curve were calculated. The intra-ventricular dyssynchrony index (DI) for each ventricle was computed as the standard deviation of the TOs. The inter-ventricular DI was calculated as the difference in median RV and median LV TOs. Compared with controls, patients had a greater LV DI (21 ± 8 vs. 11 ± 5 ms, P < 0.001) and RV DI (60 ± 19 vs. 47 ± 17 ms, P = 0.02). RV contraction was globally delayed in patients, resulting in a greater inter-ventricular DI with the RV contracting 45 ± 25 ms later than the LV vs. 12 ± 29 ms earlier in controls (P < 0.001). Inter-test reproducibility was moderate with all coefficients of variation ≤22%. Both LV and RV DIs were correlated with measures of LV, but not RV, function.

Conclusion: Patients with rTOF have intra- and inter-ventricular dyssynchrony, which can be quantified from standard cine CMR. This new approach can potentially help determine the contribution of dyssynchrony to ventricular dysfunction in future studies.

Keywords: Cardiac magnetic resonance; Dyssynchrony; Magnetic resonance imaging; Tetralogy of Fallot.

Figure 1:

Illustration of the endocardial feature-tracking algorithm. Short-axis images from the apex to the valve plane were selected for processing (A) and endocardial boundaries were semi-automatically defined (B). Twelve nodes were defined on the first image frame (C) and were tracked to the next image frame (D) using the displacement field that was computed based on local changes in the image intensity patterns (E).

Figure 2:

Quantification of dyssynchrony from circumferential strain curves. (A) An example of a segmental strain curve (blue) compared with the patient-specific reference curve (red). (B) Cross-correlation analysis was used to derive the TO for each segment. (C) The LV TOs from a representative patient are colour coded on a bullseye (red: early contraction; blue: late contraction; white: synchronous contraction compared with the reference curve). (D) A schematic showing the distribution of TOs in the LV and RV and definition of DIs.

Figure 3:

Representative LV (A) and RV (B) circumferential segments with corresponding strain curves. Note that the normal LV (C) has the most synchronous contraction with all strain curves peaking at roughly the same time, while the patient LV (E) exhibits a less coordinated contraction. Strain curves from the RV segments are less synchronous compared with the LV in both controls (D) and patients (F). Also note that the timing of contraction in the patient RV (F) occurs later in the cardiac cycle compared with the control (D).

Figure 4:

Patients with rTOF (n = 30) have elevated left (A), right (B), and inter-ventricular (C) DIs compared with controls (n = 17). Note that for the inter-ventricular DI, positive values represent early RV contraction, whereas negative values correspond to delayed RV contraction. The outlier (red arrow) is the only patient with LBBB.

Figure 5:

Global and regional median TOs in the LV (B) and RV (C) in patients and controls. *P < 0.05 between the three LV/RV regions (A) in patients. ⁺P < 0.05 between RVOT and the other two RV regions in controls.

Figure 6:

Average TOs of controls (A and B, n = 17) and patients with rTOF (C and D, n = 30) mapped onto a bullseye. The TOs are colour coded from red (≥200 ms earlier than the reference curve) to blue (≥200 ms later than the reference curve).

Figure 7:

All DIs show good to acceptable inter-test (A–C, n = 18) and excellent inter-observer (D–F, n = 10) reproducibility in patients with rTOF. Note that inter-test reproducibility is limited to 18 patients since the first 12 patients were randomly selected and used to optimize the methodology. Inter-observer analysis is reported in 10 patients.

Figure 8:

Correlations between measures of ventricular function and DIs. LV EDV correlated with both LV (A) and RV (B) DIs. LV EF correlated with LV DI (C) but not with RV DI (D).