Methods

This was a retrospective observational study, approved by the institutional review ethics board.

We included postoperative TOF patients who underwent complete echocardiographic follow-up studies in the echocardiography laboratory at The Hospital for Sick Children. Patients included were ≥7 years of age at time of echocardiography, and the period of recruitment was between April 2008 and April 2010. Patients were identified from our echocardiographic reporting database, and only patients who underwent comprehensive RV and LV diastolic assessments were included in this study. A complete assessment was defined as the availability of mitral and tricuspid inflow pulsed-wave inflow velocities, pulmonary venous pulsed-wave traces, tissue Doppler velocity traces at the mitral and tricuspid annuli, and a pulsed-wave Doppler tracing at the level of the pulmonary valve or the proximal pulmonary trunk. In the study period, 234 patients after TOF repair between 7 and 18 years after TOF repair underwent echocardiographic studies in our laboratory. Before April 2008, the full diastolic RV and LV assessment was not part of our routine clinical protocol in every patient. We introduced the full diastolic functional protocol in April 2008. Full implementation of this protocol by all sonographers and reviewers was achieved throughout the study period. In the present study, we included only patients with complete diastolic data. In total, 112 of 234 studies were identified with good-quality diastolic data sets. Only those patients were included for further analysis and measurements. The patients excluded from the study had the same clinical characteristics (age, type of repair, and time after repair) compared with the patients included in the study.

All two-dimensional (2D) and Doppler measurements were performed offline using a SyngoDx workstation (Siemens Healthcare, Erlangen, Germany) by a single observer. Restrictive RV physiology was defined as the presence of EDFF in the main pulmonary artery during atrial contraction as detected by pulsed-wave Doppler in the main pulmonary artery in at least three consecutive cardiac cycles. Two independent reviewers confirmed this finding. Group 1 consisted of patients with no EDFF and group 2 of patients with EDFF in three consecutive cardiac cycles. If no good pulsed Doppler tracing was obtained in the main pulmonary artery, the patient was excluded from the study because of incomplete data. In the patients with EDFF, the duration of EDFF was measured from the onset of EDFF until the onset of the systolic pulmonary ejection wave. RV outflow tract peak velocity was measured using continuous-wave Doppler. Pulmonary regurgitation was qualitatively assessed on the basis of color Doppler flow reversal in the main pulmonary artery. It was graded as mild to moderate if flow reversal was seen only in the main pulmonary artery and not in the pulmonary branches and severe if flow reversal originated from the distal branch pulmonary arteries.

Cardiac dimensions were measured according to the recommendations published by the American Society of Echocardiography on quantification in pediatric echocardiography. Right atrial (RA) dimensions were measured from the apical four-chamber view and included RA length, RA width (midcavity dimension of the right atrium), and RA area. Two-dimensional dimensions were not indexed, while RA area measurements were indexed for body surface area. Two-dimensional measurements performed to determine RV size included RV length (apical four-chamber, base-to-apex measurement), RV diameter 1 (apical four-chamber, diameter just below the tricuspid valve [TV] annulus), RV diameter 2 (apical four-chamber, diameter at the midcavity level), and RV areas, all measured per American Society of Echocardiography guidelines. RV end-diastolic dimension was measured from the parasternal long-axis and short-axis views. RV end-diastolic dimension Z scores were calculated using the parasternal short-axis dimension. The TV and mitral valve annuli were measured from the apical four-chamber view and the pulmonary valve annulus from the parasternal long-axis RV outflow tract view. All valve annular measurements were expressed as Z scores. Left atrial (LA) measurements were obtained from the apical four-chamber and two-chamber views. LA length and LA volume were calculated using apical four-chamber and two-chamber views. For calculation of LA volume, the area-length method was used ([0.85 × four-chamber LA area × two-chamber LA area]/LA length). LA volumes were indexed for body surface area. LV length (base-to-apex distance) and LV area were measured from the apical four-chamber view. LV end-diastolic dimension, interventricular septal thickness, and left ventricular posterior wall thickness were measured from short-axis views at papillary muscle level and were expressed as Z scores. For all Z score calculations, we used our own laboratory reference values and Z score formula obtained in a normal control population in our laboratory.

RV diastolic function was assessed by measuring TV inflow peak E and A velocities and tricuspid pulsed tissue Doppler velocities obtained at the TV annulus (peak early diastolic velocity [E′], peak late diastolic velocity [A′], and the E/E′ ratio). TV inflow duration (from the onset of the E wave to the end of the A wave) and the time from closure to opening of the TV were calculated on the tricuspid inflow traces. On the tissue tricuspid annular Doppler traces, we measured the time between the end of the S′ wave and the onset of the E′ wave, which we refer to as RV relaxation time. Measurements were averaged over two cycles. The time between the end of the A′ wave and the onset of the S′ wave was also measured and averaged over two cardiac cycles. This measurement was called RV contraction time. S′-wave duration was measured in two cardiac cycles and averaged. Finally, on the tricuspid tissue Doppler traces, the time intervals from the onset of the QRS complex to the peak S′ and peak E′ waves were measured.

LV diastolic function was assessed using pulsed Doppler of the mitral inflow and pulmonary veins and tissue Doppler velocities at the mitral lateral annulus. On the mitral inflow tracing, E and A velocities, the E/A ratio, E-wave deceleration time, mitral valve inflow duration, and A-wave duration were calculated. Isovolumetric relaxation time (IVRT) was measured on the basis of a pulsed tracing obtained in between LV inflow and outflow. Pulsed tissue Doppler traces were analyzed by measuring peak E′, A′, and S′ velocities. The E/E′ ratio was calculated. On the mitral tissue Doppler traces, we also measured the IVRT as the time between the end of the S′ wave and the onset of the E′ wave. Isovolumetric contraction time was measured as the time between the end of the A′ wave and the onset of the S′ wave. Both measurements were averaged over two cardiac cycles. Additionally, on the mitral tissue Doppler tracing, the time intervals from the onset of the QRS complex to the peak S′ and peak E′ were measured. On the pulmonary venous traces, peak systolic (S), peak diastolic (D), and peak A-wave reversal velocities were measured. A-wave reversal duration was measured as illustrated in Figure 2 . Measurements obtained over two cardiac cycles were averaged.

Typical pulmonary venous tracing in patient with restrictive RV physiology. Notice the large pulmonary venous A-wave reversals during atrial contraction. The arrows indicate the increased peak reversal velocity, and the time between the red lines indicates the pulmonary venous duration, which is also prolonged.

In all patients, 12-lead electrocardiograms were obtained at the time of echocardiography. On the electrocardiogram, QRS duration was measured.

Results

In total, 112 patients could be identified as fulfilling the inclusion criteria for the study. On the basis of the presence of EDFF in three consecutive cardiac cycles, 58 patients (52%) were identified as meeting Doppler criteria for restrictive RV physiology, while 54 patients (48%) did not have EDFF and were considered to have nonrestrictive RV physiology. Table 1 compares the general patient characteristics between both groups. RV outflow tract gradients were not different between the groups as mean peak velocities were not different, and in none of the groups could a patient with significant outflow tract obstruction >3 m/sec be identified. The percentage of patients with severe pulmonary regurgitation was not different between the groups, with 63% in the nonrestrictive group and 67% in the restrictive group having severe pulmonary regurgitation. None of the patients had more than a mild degree of tricuspid regurgitation.

RV and LV Diastolic Function

RV diastolic measurements are shown in Table 4 . No significant differences in tricuspid inflow peak E and A waves were noted. Also, tricuspid peak annular tissue Doppler velocities E′ and A′ were not different between both groups. This resulted in the E/E′ ratio being identical between both groups. Also, the timing parameters, including tricuspid inflow duration and tissue Doppler–based early RV relaxation time, were not different between both groups.

Table 4

RV diastolic measurements

Variable	Nonrestrictive	Restrictive	P
TV E (m/sec)	0.76 ± 0.12	0.76 ± 0.19	NS
TV A (m/sec)	0.5 ± 0.12	0.5 ± 0.15	NS
TV inflow time (msec)	444 ± 110	427 ± 137	NS
TV E′ (m/sec)	0.11 ± 0.03	0.11 ± 0.02	NS
TV A′ (m/sec)	0.05 ± 0.01	0.05 ± 0.02	NS
TV S′ (m/sec)	0.08 ± 0.02	0.09 ± 0.02	NS
Tissue Doppler RV relaxation time (msec)	63 ± 30	70 ± 29	NS
Tissue Doppler RV contraction time (msec)	102 ± 43	105 ± 31	NS
TV E/E′ ratio	7.8 ± 3.2	7.0 ± 2.5	NS

Data are expressed as mean ± SD.

Table 5 compares LV diastolic properties between the restrictive and the nonrestrictive group. On the mitral inflow pattern, early LV diastolic parameters, including peak mitral valve E-wave velocity, IVRT, peak E′ velocity, and the E/E′-ratio, were not significantly different between the groups. Similarly, deceleration time and A-wave and A′ velocities were not different. Mitral inflow A-wave duration was longer in the RV restrictive group (88 ± 14 vs 102 ± 16 msec, P < .001).

Table 5

LV diastolic measurements

Variable	Nonrestrictive	Restrictive	P
MV E (m/sec)	1.1 ± 0.18	1.1 ± 0.22	NS
MV A (m/sec)	0.48 ± 0.2	0.49 ± 0.12	NS
MV E/A ratio	2.2 ± 0.6	2.3 ± 0.7	NS
MV A duration (msec)	88 ± 14	102 ± 16	<.001
MV deceleration time (msec)	150 ± 60	160 ± 40	NS
MV IVRT (msec)	66 ± 9.7	66 ± 9.1	NS
PV S velocity (m/sec)	0.48 ± 0.21	0.60 ± 0.16	<.05
PV D velocity (m/sec)	0.87 ± 0.16	0.89 ± 0.14	NS
PV A velocity (m/sec)	0.27 ± 0.09	0.37 ± 0.11	<.001
PV A duration (msec)	104 ± 35	134 ± 28	<.001
PV A duration − MV A duration (msec)	11.4 ± 31.2	29.9 ± 23.1	.0007
MV E′ (m/sec)	0.16 ± 0.04	0.16 ± 0.04	NS
MV A′ (m/sec)	0.06 ± 0.02	0.06 ± 0.01	NS
MV S′ (m/sec)	0.08 ± 0.02	0.09 ± 0.01	NS
MV E/E′ ratio	7.1 ± 3.1	7.7 ± 2.7	NS
MV systolic time (tissue Doppler S′ duration) (msec)	272 ± 42	271 ± 33	NS
Tissue Doppler IVRT (msec)	66.5 ± 28	66 ± 20.9	NS
Tissue Doppler isovolumetric contraction time (msec)	81.5 ± 32	78.5 ± 21	NS

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