- Email: [email protected]
Serial Doppler assessment of diastolic function before and after the Fontan operation
Serial Doppler Assessment of Diastolic Function Before and After the Fontan Operation Margarete Olivier, MD, Patrick W. O’Leary, MD, V. Shane Pankratz, PhD, Christine M. Lohse, BS, Barbara E. Walsh, RCDS, A. Jamil Tajik, MD, and James B. Seward, MD, Rochester, Minnesota
Serial Doppler echocardiography was used to evaluate the effects of the Fontan operation (FO) on diastolic ventricular function in 55 patients with univentricular heart. Examinations were performed before operation, before postoperative discharge, and 6 months to 6 years postoperatively. Preoperatively, early diastolic atrioventricular valve (E) flow was reduced and deceleration times prolonged relative to healthy children. All pulmonary vein diastolic flow variables, except diastolic velocity, were increased relative to control subjects. After FO, E/atrial velocity and E/atrial time velocity integral ratios were decreased whereas deceleration and iso-
The modified Fontan operation (FO)
volumic relaxation time remained constant. Diastolic pulmonary vein forward flow increased after FO. These data suggest inherently abnormal ventricular relaxation in the univentricular heart and that changes in flow patterns observed postoperatively were subtle and likely a result of reduced ventricular preload after FO. Overall, diastolic function most probably remained stable after FO. This information can be used as a benchmark for further diastolic function assessment in patients with surgically palliated univentricular heart. (J Am Soc Echocardiogr 2003;16:1136-43.)
1 is the preferred palliative procedure for patients with a univentricular heart (UVH). The FO separates systemic and pulmonary circulation, eliminating cardiac volume overload and cyanosis. Despite improving survival after FO,2 a variety of adverse late sequelae contribute to significant morbidity and ongoing mortality in these patients. Ventricular failure remains a common cause of death after FO.3 Systolic dysfunction is known to be preceded by impaired diastolic function,4 however, there are limited data describing diastolic ventricular performance in patients before5 or after6-11 FO. Pulsed wave (PW) Doppler echocardiography is used in the assessment of diastolic function in many different cardiac disease states.12-16 Doppler assessment of diastolic function in children has also been reported and reference values for the pediatric age group have been established.17-19 The objective of this study was to use PW Doppler echocardiography to define Doppler parameters reflecting diastolic function in patients with UVH and
to compare these values with findings reported in a control group of healthy children (NC). We also sought to describe the changes in these parameters after FO. Ideally, diastolic filling patterns would show improvement as a result of decreased volume load and improved oxygenation after FO.
From the Division of Pediatric Cardiology (M.O., P.W.O.), the Section of Biostatistics (V.S.P., C.M.L.), and the Division of Cardiovascular Diseases and Internal Medicine (P.W.O., B.E.W., A.J.T., J.B.S.), Mayo Clinic, Rochester. Reprint requests: Patrick W. O’Leary, MD, Division of Pediatric Cardiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1067/S0894-7317(03)00635-7
Control Population
1136
METHODS Patients Undergoing FO We reviewed the medical and surgical records and the preoperative echocardiograms of all patients who underwent a FO at the Mayo Clinic in Rochester, Minn, between 1992 and 1997. Only patients with complete preoperative PW Doppler assessment of pulmonary vein (PV) and atrioventricular (AV) valve flow were included. Patients were excluded if they had any rhythm other than in sinus, AV valve regurgitation of more than mild degree, complex forms of anomalous PV return, or if the postoperative follow-up was less than 6 months.
The control group (n ⫽ 223; mean age, 10.6 ⫾ 4 years; range, 2-18 years) was composed of children from a local elementary and a local high school who had been prospectively recruited.18 These children had no history of cardiac or pulmonary disease, and their hearts were anatomically normal as assessed by 2-dimensional and Doppler echocardiography. PW Doppler data on mitral
Journal of the American Society of Echocardiography Volume 16 Number 11
Olivier et al 1137
and PV flow from this group18 were used for comparison with data from patients undergoing FO. Examinations and Comparisons Performed Between Groups Doppler data obtained from patients with a UVH before FO were compared with those seen in NC.18 Also, serial assessment of diastolic function in patients with UVH undergoing FO was carried out at 3 points in time (immediately before the FO [Echo I], before hospital discharge after the FO [Echo II], and at least 6 months postoperatively [Echo III]). Comparisons of Doppler data measured at Echo I, II, and III were then performed. Doppler Assessment of Diastolic Function Echocardiographic technique. All echocardiographic studies were performed with commercially available cardiac ultrasound systems. Ejection fraction (EF) was calculated using the modified Quinones technique for patients with left ventricular morphology and adequate M-mode tracings.20 All other patients had EF calculated using a biplane Simpson’s rule, with orthogonal images obtained at the cardiac apex or the subcostal window.20 The Doppler examination was performed at the cardiac apex. PW Doppler interrogation of AV valve and PV flow was performed in accordance with previously published recommendations.18,21 AV valve flow was evaluated with the sample volume placed near the tip of the valve leaflets. When 2 AV valves were present, the 1 connected to the PV atrium was evaluated. PV flow was studied with the sample volume at least 5 mm proximal to the insertion of the PV into the atrium. Signal measurement. All results were recorded on .75-in videotapes for subsequent analysis. Doppler signals were measured with use of an offline analysis system (Nova Microsonics Imagevue DCR, Mahwah, NJ). Three consecutive measurements were averaged for each variable. AV valve flow was evaluated during early (E) ventricular filling and at atrial (A) contraction, and peak velocities and time velocity integral (TVI) of E and A waves were measured. AV valve deceleration time (DT) and A-wave duration were determined. To characterize the relative contributions of the E and A waves to ventricular filling, the ratios of E/A velocities and E/A TVI were calculated. An AV valve flow signal was considered fused if separate E and A waves could not be distinguished or if the E at A velocity was greater than half of the E velocity (or both). Figure 1 illustrates the modified method to measure isovolumic relaxation time. PV signals were divided into systolic and diastolic forward flow and reversed flow at A contraction, as previously described.18 For each component, the peak velocity and TVI and the ratios of these parameters were determined. The duration of A reversal flow was measured. Diastolic filling fraction was calculated as [diastolic TVI/(systolic TVI ⫹ diastolic TVI)].
Statistical Analysis Clinical characteristics and Doppler parameters for patients who underwent FO were summarized with means,
Figure 1 Diagram of technique for measuring isovolumic relaxation time (IRT). AV, Atrioventricular; ECG, electrocardiogram; ET, ejection time.
SD, medians, and ranges. The Doppler measurements from Echo I were compared with the Doppler readings obtained from NC using analysis of covariance, adjusting for age and heart rate. Because the age and heart rate distributions differed between the patients undergoing FO and the NC, the Doppler measurements could not be simply summarized with means and SD. Therefore, least squares means and their associated SE were used to summarize these comparisons. Least squares means represent the expected value of each measurement after adjusting for age and heart rate. Moreover, Doppler parameters at the 3 echocardiograms (Echo I, II, and III) were compared between pairs of time points using paired t tests or Wilcoxon signed rank tests. These Doppler parameters were also compared using repeated measures analysis of covariance after adjusting for age and heart rate. Pairwise comparisons between the echocardiograms were performed only for those Doppler parameters that reached significance in the repeated measures analysis of the 3 time points. All analyses were conducted using software (SAS statistical package, Version 6.12, SAS Institute Inc, Cary, NC). P values less than .05 were considered statistically significant.
RESULTS Patients with UVH The study population consisted of 55 patients (26 female; median age, 5.5 years; range, 1.7-26 years). Preoperative ventricular morphology, previous palliative procedures, and type of Fontan connections created are summarized in Table 1. Table 2 contains clinical and hemodynamic data recorded at or
Journal of the American Society of Echocardiography November 2003
1138 Olivier et al
Table 1 Diagnoses, previous palliative procedures, and type of Fontan connection Diagnosis
N
DILV TA HLHS PA/IVS Other
24 7 4 4 16
Table 3 Atrioventricular valve flow in patients before Fontan procedure compared with healthy children
Previous palliation
N
Fontan connection
N
BDCPA BT shunt AP shunt PA banding
27 8 4 10
APA IAC ECC FTN
39 3 14 9
AP, Aortopulmonary; APA, atriopulmonary anastomosis; BDCPA, bidirectional cavopulmonary anastomosis; BT, Blalock-Taussig; DILV, doubleinlet left ventricle; ECC, extracardiac conduit; FTN, fenestration; HLHS, hypoplastic left heart syndrome; IAC, intracardiac conduit; PA, pulmonary artery; PA/IVS, pulmonary atresia with intact Ventricular septum; TA, tricuspid atresia.
AV flow
NC
Pre-Fontan
E velocity, cm/s A velocity, cm/s A duration, ms DT, ms E TVI, cm A TVI, cm E/A velocity E/A TVI
LSM (SE) 89 (1.0) 41 (0.7) 139 (1.5) 156 (1.5) 12.6 (0.2) 3.7 (0.08) 2.2 (0.04) 3.5 (0.07)
LSM (SE) 76 (2.4)* 56 (1.6)* 147 (3.4) 175 (3.4)* 10.7 (0.4)* 5.3 (0.2)* 1.4 (0.05)* 2.0 (0.1)*
A, Atrial filling wave; AV, atrioventricular; DT, deceleration time; E, early filling wave; LSM, least squares means; NC, healthy children; TVI, time velocity integral. *Patients before Fontan vs control subjects, P ⬍ .0001.
Table 2 Characteristics of patients undergoing Fontan procedure at 3 time points Echo I
Weight, kg Heart rate, bpm Systolic BP, mm Hg Diastolic BP, mm Hg EF, % LAP, mm Hg VEDP, mm Hg Qp/Qs
Echo III
Mean ⴞ SD Median (range)
Characteristic
Height, cm
Echo II
114 ⫾ 29 107 (69-186) 23 ⫾ 16 18 (11-83) (91 ⫾ 14)
113 ⫾ 28 106 (69-186) 24 ⫾ 16 18 (11-83) (102 ⫾ 18)*
123 ⫾ 28†‡ 115 (91-184) 27 ⫾ 16†‡ 20 (13-71) (82 ⫾ 16)†‡
90 (62-120) (99 ⫾ 15)
100 (64-140) (102 ⫾ 11)
80 (51-111) (107 ⫾ 13)
99 (69-136) (60 ⫾ 10)
100 (75-125) (60 ⫾ 9.0)
104 (86-140) (60 ⫾ 11)
60 (40-80) 52 ⫾ 9* 52 (30-68) ND
60 (40-80) 54 ⫾ 7 55 (40-69) ND
ND
ND
ND
ND
59 (45-88) 56 ⫾ 7 56 (45-71) 9 ⫾ 2.5 9 (2-16) (9.5 ⫾ 2.7) 10 (1-15) 1.2 ⫾ 0.8 0.8 (0.5-4)
Data are expressed as mean ⫾ SD and median (range). BP, Blood pressure; EF, ejection fraction; LAP, left atrial pressure; ND, not determined; Qp/Qs, pulmonary-to-systemic shunt flow ratio; VEDP, ventricular end-diastolic pressure. Echo I, preoperative examination; Echo II, examination before postoperative discharge, Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II; †P ⬍ .05 Echo I vs III. ‡P ⬍ .05 Echo II vs III.
around the time of the 3 echocardiographic examinations. Availability of AV Valve and PV Flow Signals in Patients with UVH All 55 patients had complete Echo I studies. An Echo II echocardiogram of adequate Doppler quality was obtained in 50 patients (91%). Echo II was obtained
at a median of 10 days after FO (range: 6-37 days). A total of 28 patients (51%) had an Echo III echocardiogram analyzed. These studies were obtained a median interval of 1.8 years after FO (range: 0.5-6.2 years). Diastolic Filling Patterns Before FO Compared with NC Table 3 summarizes the AV Doppler data from Echo I and comparisons made between the patients and NC, after adjusting for age and heart rate. Patients with a UVH before the FO (Echo I) showed an adjusted mean E/A velocity ratio of 1.4 versus 2.2 for NC. Despite the presence of E/A ratios ⬎1, E AV valve flow was significantly reduced, with a significant shift toward filling by A contraction, compared with NC (P ⬍ .001). In addition, average DT was approximately 20 milliseconds longer in the group of patients with UVH than in NC (P ⬍ .001). PV flow values at Echo I and the comparison with NC (adjusting for age and heart rate) are summarized in Table 4. These data demonstrated a nearly equal distribution of systolic and diastolic forward flow (diastolic filling fraction: 0.54) with a slight predominance of diastolic velocity (systolic/diastolic velocity: 0.8) in patients with UVH. However, PV flow in NC was systolic dominant in all variables except velocity. Comparison with NC revealed that patients with UVH had significantly increased PV diastolic forward flow. This was reflected by increased diastolic TVI and diastolic filling fraction, and a consequent decrease in the ratio of systolic to diastolic TVI (P ⬍ .001). However, PV diastolic flow velocity was not significantly different between the groups. A reversal velocity was slightly increased for patients before FO relative to NC. In contrast, A reversal durations were significantly shorter in patients with UVH (102 milliseconds) than the reversal durations recorded in NC (130 milliseconds, Table 4).
Journal of the American Society of Echocardiography Volume 16 Number 11
Table 4 Pulmonary venus flow data in patients before Fontan procedure compared with healthy children PV flow
NC
Pre-Fontan
Systolic velocity, cm/s Diastolic velocity, cm/s AR velocity, cm/s AR duration, ms Systolic TVI, cm Diastolic TVI, cm AR TVI, cm Velocitysys/dias TVIsys/dias Diastolic filling fraction
LSM (SE) 44 (0.7) 57 (0.7) 21 (0.4) 130 (1.9) 11.1 (0.2) 9.4 (0.2) 1.6 (0.1) 0.8 (0.02) 1.2 (0.02) 0.46 (0.01)
LSM (SE) 45 (1.4) 55 (1.4) 27 (1.4)* 102 (4.4)* 9.9 (0.4) 11.1 (0.3)* 1.8 (0.1) 0.8 (0.03) 0.9 (0.04)* 0.54 (0.01)*
AR, Atrial reversal; LSM, least squares means; NC, healthy children, PV, pulmonary venous; TVI, time velocity integral; TVIsys/dias, systolic/diastolic TVI ratio; Velocitysys/dias, systolic/diastolic velocity ratio. *Patients before Fontan vs NC, P ⬍ .0001.
Changes in Diastolic Filling Patterns in Patients After FO Systolic ventricular function, as assessed by EF, remained stable after FO (Table 2). Immediate postoperative EF showed a decrease relative to Echo I (52% vs 56%, P ⬍ .05), but the magnitude of the difference was not clinically important. EF at Echo III was not significantly different from the EF observed at either of the other studies. AV valve and PV Doppler data at Echo I, II, and III are summarized in Tables 5 and 6. A schematic illustration of the average Doppler signals from each of the 3 echocardiograms is provided in Figure 2. Changes at Echo II There were univariately significant decreases in E TVI and the E/A TVI ratio relative to Echo I (Table 5). However, no AV valve flow parameters at Echo II differed from preoperative values by multivariate analysis, which accounted for age and heart rate. At early postoperative follow-up, PV forward flow (Table 6) was characterized by increased diastolic velocity (P ⬍ .001), diastolic TVI (P ⬍ .001), and diastolic filling fraction (P ⬍ .02) compared with Echo I (adjusting for age and heart rate). Changes at Echo III When preoperative AV valve Doppler data (Echo I) were compared with the Echo III values by multivariate analysis (adjusting for age and heart rate), a significant increase in A velocity (P ⬍ .02) and A TVI (P ⬍ .002) were seen. There was also a significant decrease in the E/A velocity ratio (P ⬍ .02) and the E/A TVI ratio (P ⬍ .001). Univariate analysis of PV flow parameters at Echo III revealed increased diastolic velocity and diastolic filling fraction relative to the preoperative findings. An increase in the AR velocity, but not in the AR duration, was also observed
Olivier et al 1139
by univariate comparison. After adjustment for age and heart rate, PV diastolic velocity (P ⬍ .001) and diastolic TVI (P ⬍ .008) were increased. There was no change in AR duration on multivariate analysis. When the Echo III versus Echo II echocardiograms were compared, AV valve Doppler data remained unchanged. PV flow at Echo III demonstrated an increase in diastolic TVI and a consequent decrease in the systolic/diastolic TVI ratio compared with Echo II on univariate comparison. However, no significant changes in PV flow were detectable on multivariate comparison of Echo II and Echo III.
DISCUSSION Patients after FO have been described as having ventricular filling patterns consistent with abnormal relaxation.6-9 Our patients, both before and after FO, had AV valve inflow patterns that demonstrated reduced E diastolic filling, increased forward flow at A contraction, and longer DT than NC. These filling shifts are similar to those observed in patients with abnormal relaxation patterns.22,23 However, unlike previous descriptions of abnormal or delayed relaxation, all E/A ratios remained ⬎1 and isovolumic relaxation time was within the previously described normal range.18 Analysis of PV flow velocities and velocity ratios before FO demonstrated few differences from NC. However, PV A reversals had a shorter duration for patients with UVH than in NC. This is usually thought to be a sign of low filling pressures.22 Preoperative PV Doppler signals had a nearly equal distribution of systolic and diastolic flow with a ratio of systolic to diastolic velocity of 0.8 and diastolic filling fraction of 0.54. These patterns are not consistent with the systolic dominance to forward flow that one expects from prior descriptions of abnormal relaxation. It appears that these hearts are transitioning toward, but not quite reaching, the expected abnormal relaxation pattern. In fact, AV valve and PV flow patterns seen in the UVH group before FO more closely resemble the normal adult pattern than that of abnormal relaxation (Figure 3). However, this patient group had a median age of only 5.5 years, making the presence of a normal adult filling pattern distinctly abnormal. It may be that the abnormality in ventricular diastolic function is mild enough that it impacts only AV valve flow, whereas PV flow is relatively insulated. Alternatively, excellent atrial function or compliance in these young patients may explain the unique AV and PV flow pattern observed in this study. From a clinical perspective, the abnormality of diastolic function present in these highly selected patients must be relatively mild, because they were all survivors of FO and had invasively documented
Journal of the American Society of Echocardiography November 2003
1140 Olivier et al
Table 5 Atrioventricular valve flow variables and IRT in patients undergoing Fontan operation at 3 time points Echo I
A velocity, cm/s A duration, ms E at A velocity, cm/s E/A velocity ratio Deceleration time, ms E wave TVI, cm A wave TVI, cm E/A TVI ratio IRT, ms
Echo III
Mean ⴞ SD Median (range)
Variable
E velocity, cm/s
Echo II
77 ⫾ 18 75 (43-125) 62 ⫾ 19 59 (31-111) 145 ⫾ 22 139 (113-196) 26 ⫾ 14 28 (2-61) 1.3 ⫾ 0.4 1.2 (0.5-2.7) 167 ⫾ 31 166 (121-213) 10 ⫾ 2.9 9.7 (3.6-15.7) 5.9 ⫾ 2.0 5.7 (2.7-10.7) 1.9 ⫾ 1.0 1.8 (0.4-5.3) 51 ⫾ 10.9 53 (39-67)
70 ⫾ 16 69 (44-100) 63 ⫾ 18 57 (38-97) 136 ⫾ 21 144 (97-179) 28 ⫾ 11 26 (13-51) 1.2 ⫾ 0.3 1.2 (0.6-1.8) 148 ⫾ 32 153 (102-210) 7.8 ⫾ 3.3* 9.7 (3.6-15.7) 5.5 ⫾ 1.8 6.0 (2.1-8.8) 1.5 ⫾ 0.6* 1.4 (0.6-3.1) 45 ⫾ 13.6 40 (36-75)
72 ⫾ 13 73 (51-99) 60 ⫾ 13 64 (26-82) 156 ⫾ 19 157 (105-199) 25 ⫾ 10 25 (11-41) 1.2 ⫾ 0.3 1.1 (0.9-2.2) 163 ⫾ 30 162 (92-215) 9.1 ⫾ 2.3 9.2 (4.5-14.1) 6.0 ⫾ 1.2 6.2 (3.8-8.0) 1.5 ⫾ 0.5 1.4 (1.0-2.9) 56 ⫾ 33.1 44 (37-123)
P ⬍ .05 ⬃ significant by univariate analysis (see Results section for multivariate analysis). A, Atrial filling wave; A duration, duration of atrial filling wave; E, early filling wave; IRT, isovolumic relaxation time; TVI, time velocity integral. Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II.
Table 6 Pulmonary Vein flow variables of patients undergoing Fontan operation at 3 time points Echo I
Diastolic velocity, cm/s AR velocity, cm/s AR duration, ms Systolic TVI, cm Diastolic TVI, cm Systolic/diastolic TVI Systolic/diastolic velocity Diastolic filling fraction
Echo III
Mean ⴞ SD Median (range)
Variable
Systolic velocity, cm/s
Echo II
45 ⫾ 12 45 (22-68) 54 ⫾ 9 55 (36-47) 36 ⫾ 16 34 (19-60) 105 ⫾ 39 101 (67-173) 9.4 ⫾ 3.0 9.5 (4.3-20.2) 10.5 ⫾ 3.2 10.4 (5.1-20.7) 1.0 ⫾ 0.4 0.9 (0.4-1.6) 0.8 ⫾ 0.3 0.9 (0.4-1.6) 0.5 ⫾ 0.1 0.5 (0.3-0.8)
49 ⫾ 18 47 (22-101) 69 ⫾ 19* 70 (18-119) 50 ⫾ 17 47 (30-72) 85 ⫾ 25 87 (55-128) 9.2 ⫾ 5.1 7.7 (3.0-34.5) 11.9 ⫾ 4.2* 11.7 (1.7-21.5) 0.9 ⫾ 1.1 0.8 (0.3-7.9) 0.8 ⫾ 0.5* 0.7 (0.3-3.9) 0.6 ⫾ 0.1* 0.6 (0.1-0.8)
53 ⫾ 20† 52 (23-91) 70 ⫾ 20† 70 (33-107) 35 ⫾ 22† 29 (19-93) 94 ⫾ 39 99 (49-164) 11 ⫾ 5.9 10.3 (5.1-36.4) 14.4 ⫾ 6.4†‡ 13.1 (4.3-30.8) 1.0 ⫾ 1.0†‡ 0.7 (0.2-5.1) 0.8 ⫾ 0.4 0.7 (0.3-1.5) 0.6 ⫾ 0.2† 0.6 (0.2-0.8)
P ⬍ .05 ⬃ significant on univariate analysis (see “Results” section for multivariate analysis). AR, Atrial reversal; TVI, time velocity integral. Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II; †P ⬍ .05 Echo I vs III; ‡P ⬍ .05 Echo II vs III.
low ventricular end-diastolic pressures at the time of Echo I (Table 2). The transitional nature of the flow pattern observed in this study points out 2 important aspects
of diastolic function assessment. The first is that diastolic ventricular performance needs to be thought of as a continuum (Figure 3).21 These patients had Doppler patterns that were between
Journal of the American Society of Echocardiography Volume 16 Number 11
Olivier et al 1141
that of their age-matched control subjects and classic abnormal relaxation. Logically, this position on the continuum should represent a mild degree of impairment in diastolic performance and should be associated with low filling pressures. Secondly, when evaluating diastolic performance one must compare all data with an age-appropriate control group. Without such a control group, it would have been impossible to interpret these findings correctly or even to detect that these patients had diastolic dysfunction at all. Impact of the FO on Ventricular Diastolic Performance Comparison of late postoperative Doppler findings with Echo I showed a significant shift toward ventricular filling by A contraction (increased A velocity and TVI, decreased E/A velocity and E/A TVI ratios) and increased PV diastolic forward flow. DT and isovolumic relaxation time remained unchanged after FO. The differences observed are probably best explained by the preload reduction associated with conversion to the Fontan circulation.24 Therefore, we conclude that diastolic ventricular performance was actually unchanged during follow-up in this group of patients with UVH. Although we were unable to document an improvement in diastolic performance, the fact that no deterioration occurred is gratifying. A much longer period of follow up will be required to determine if this stability in diastolic function will persist.
Figure 2 Schematic of ventricular filling patterns before and after Fontan operation. A, Atrial filling wave; AV, atrioventricular; D, diastolic filling wave; DT, deceleration time; E, early filling wave; Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively; FFxdias, diastolic filling fraction; PV, pulmonary venous; PVAR, PV atrial reversal; S, systolic filling wave.
Previous Descriptions of Diastolic Filling Patterns in Patients with UVH Our postoperative observation of reduced E AV valve flow was consistent with earlier findings6-11 for patients after FO. This has previously been attributed to incoordinate ventricular relaxation occurring both immediately7 and late after FO.6,8,9 However, our study observed that postoperative Doppler flow patterns were actually similar to preoperative findings. The fact that these abnormalities in diastolic filling could be detected preoperatively argues that abnormal diastolic performance is inherent to these hearts, rather than being the result of FO. PV flows before FO were characterized by a nearly equal distribution of systolic and diastolic flow with increased diastolic flow values relative to NC. Rychik et al5 had observed an overall predominance of PV systolic flow for patients with UVH before FO. This difference is probably best explained by the younger mean patient age in the population of Rychik et al.5 Very young healthy children have been shown to have predominantly systolic PV flow, which shifts to a slight diastolic dominance in later childhood.17,18
Figure 3 Spectrum of Doppler flow patterns in diastolic dysfunction extended to include normal diastolic function in children. A, Atrial filling wave; AV, atrioventricular; D, diastolic filling wave, E, early filling wave; S, systolic; VAR, venous atrial reversal.
The postoperative predominance of PV diastolic flow in the current study has been previously observed in patients after FO.10,11,25 However, the cited studies did not present preoperative data. Therefore, it was not possible to say whether this flow pattern was related to the congenital malformation or associated with transition to the FO circulation. Our data support the conclusion that ventricular relaxation is inherently abnormal in these patients rather than being the result of the FO. Limitations Diastolic ventricular function is influenced by many factors, including age and heart rate.18 Comparisons of Doppler variables in this study were adjusted for these parameters, but other confounding factors, such as varying ventricular morphology,26 could not
1142 Olivier et al
be completely eliminated. In addition, the retrospective nature of the study did not allow us to gate the Doppler signals to the phase of respiration or to consistently perform preload reduction maneuvers, (ie, Valsalva). However, these patients were all studied as a part of routine clinical evaluations and at least 3 consecutive cycles of Doppler data were measured and averaged. Our results should, therefore, reflect the resting or average state of the patient (ie, nonfasting and spontaneously breathing). The defined inclusion criteria also resulted in a study population characterized by a favorable diastolic hemodynamic profile: those able to have and survive FO. Consequently, Doppler data in this study probably reflect relatively optimal diastolic function for patients with UVH. Further studies will be required to determine the filling patterns in the UVH with poor diastolic function. In addition, all patients studied were in sinus rhythm. Other rhythms, particularly junctional rhythm, will significantly change the flow signals recorded. Therefore, one cannot directly apply these results to patients who are in rhythms that lack AV synchrony. Lastly, the length of postoperative follow up was relatively short, and we will need more time to truly define long-term diastolic ventricular performance in these patients and what influence it has on their clinical status after FO. Conclusion and Clinical Implications Complete, serial Doppler diastolic filling assessment of patients with UVH before and after FO has not been previously reported. These patients demonstrated decreased E AV valve flow, longer DT, and increased PV diastolic flow relative to NC both before and after FO. These data suggest an inherent, but mild abnormality of ventricular diastolic performance for patients with UVH and relatively normal systolic EF. This was observed even though this group had adequate diastolic function by clinical evaluation and catheter-measured ventricular enddiastolic pressures. The filling patterns observed were transitional, between those of healthy children and the pattern of abnormal relaxation. During the relatively short course of our study, ventricular diastolic function seemed to remain stable. The changes in the Doppler filling patterns observed postoperatively are best explained by the decrease in ventricular preload resulting from conversion to a Fontan circulation. The data reported in this study will serve as a preliminary clinical benchmark, describing the Doppler patterns associated with low ventricular filling pressures and clinically adequate diastolic function for patients with UVH both before and after FO. Knowledge of these Doppler patterns and use of age and heart rate appropriate normal values should
Journal of the American Society of Echocardiography November 2003
make the noninvasive recognition of diastolic dysfunction for patients with complex congenital heart diseases simpler and more accurate. It is also possible that we may be able to decrease the frequency with which invasive evaluation of ventricular diastolic function is necessary in these patients. Before this can occur, a much larger body of information will be required, especially data describing the Doppler patterns associated with high filling pressures and poor diastolic function in these patients. REFERENCES 1. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971;26:240-8. 2. Cetta F, Feldt RH, O’Leary PW, Mair DD, Warnes CA, Driscoll DJ, et al. Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992. J Am Coll Cardiol 1996;28:480-6. 3. Driscoll DJ, Offord KP, Feldt RH, Schaff HV, Puga FJ, Danielson GK. Five- to fifteen-year follow-up after Fontan operation. Circulation 1992;85:469-96. 4. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:1565-74. 5. Rychik J, Fogel MA, Donofrio MT, Goldmuntz E, Cohen MS, Spray TL, et al. Comparison of patterns of pulmonary venous blood flow in the functional single ventricle heart after operative aortopulmonary shunt versus superior cavopulmonary shunt. Am J Cardiol 1997;80:922-6. 6. Penny DJ, Rigby ML, Redington AN. Abnormal patterns of intraventricular flow and diastolic filling after the Fontan operation: evidence for incoordinate ventricular wall notion. Br Heart J 1991;66:375-8. 7. Penny DJ, Lincoln C, Shore DF, Xiao HB, Rigby ML, Redington AN. The early response of the systemic ventricle during transition to the Fontan circulation–an acute hypertrophic cardiomyopathy? Cardiol Young 1992;2:78-84. 8. Frommelt PC, Snider AR, Meliones JN, Vermilion RP. Doppler assessment of pulmonary artery flow patterns and ventricular function after the Fontan operation. Am J Cardiol 1991; 68:1211-5. 9. Cheung YF, Penny DJ, Redington AN. Serial assessment of left ventricular diastolic function after Fontan procedure. Heart 2000;83:420-4. 10. Milanesi O, Stellin G, Colan S, Facchin P, Crepaz R, Biffanti R, et al. Systolic and diastolic performance late after the Fontan procedure for a single ventricle and comparison of those undergoing operation at ⬍ 12 months of age and at ⬎ 12 months of age. Am J Cardiol 2002;89:276-80. 11. Hagler DJ, Cordes TM. Complete echocardiographic assessment of the postoperative Fontan patient. Echocardiography 1995;12:529-43. 12. Klein AL, Hatle LK, Taliercio CP, Oh JK, Kyle RA, Gertz MA, et al. Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis: a Doppler echocardiography study. Circulation 1991;83:808-16. 13. Xie GY, Berk MR, Smith MD, Gurley JC, DeMaria AN. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol 1994; 24:132-9. 14. Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic and diastolic dysfunction in patients with clinical
Journal of the American Society of Echocardiography Volume 16 Number 11
15.
16.
17.
18.
19.
20.
diagnosis of dilated cardiomyopathy: relation to symptoms and prognosis. Circulation 1994;90:2772-9. Moskowitz WB, Schieken RM, Mosteller M, Bossano R. Altered systolic and diastolic function in children after “successful” repair of coarctation of the aorta. Am Heart J 1990; 120:103-9. Gidding SS, Snider AR, Rocchini AP, Peters J, Farnsworth R. Left ventricular diastolic filling in children with hypertrophic cardiomyopathy: assessment with pulsed Doppler echocardiography. J Am Coll Cardiol 1986;8:310-6. Abdurrahman L, Hoit BD, Banerjee A, Khoury PR, Meyer RA. Pulmonary venous flow Doppler velocities in children. J Am Soc Echocardiogr 1998;11:132-7. O’Leary PW, Durongpisitkul K, Cordes TM, Bailey KR, Hagler DJ, Tajik AJ, et al. Diastolic ventricular function in children: a Doppler echocardiographic study establishing normal values and predictors of increased ventricular end-diastolic pressure. Mayo Clin Proc 1998;73:616-28. Schmitz L, Koch H, Bein G, Brockmeier K. Left ventricular diastolic function in infants, children, and adolescents: reference values and analysis of morphologic and physiologic determinants of echocardiographic Doppler flow signals during growth and maturation. J Am Coll Cardiol 1998;32:1441-8. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography: from the American Society of Echocardiography committee on
Olivier et al 1143
21.
22.
23.
24.
25.
26.
standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr 1989;2:358-67. Rakowski H, Appleton C, Chan KL, Dumesnil JG, Honos G, Jue J, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the investigators of consensus on diastolic dysfunction by echocardiography. J Am Soc Echocardiogr 1996;9:736-60. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta stone. J Am Coll Cardiol 1997;30:818. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246-70. Nishimura RA, Abel MD, Hatle LK, Tajik AJ. Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography: effect of different loading conditions. Circulation 1990;81:1488-97. Rydberg A, Teien DE, Karp K, Vermilion RP, Ludormirsky A. Pulmonary venous blood flow pattern in patients with univentricular hearts following total cavo-pulmonary connection. Clin Physiol 1998;18:131-8. Akagi T, Benson LN, Gilday DL, Ash J, Green M, Williams WG, et al. Influence of ventricular morphology on diastolic filling performance in double-inlet ventricle after the Fontan procedure. J Am Coll Cardiol 1993;22:1948-52.
Serial Doppler echocardiography was used to evaluate the effects of the Fontan operation (FO) on diastolic ventricular function in 55 patients with univentricular heart. Examinations were performed before operation, before postoperative discharge, and 6 months to 6 years postoperatively. Preoperatively, early diastolic atrioventricular valve (E) flow was reduced and deceleration times prolonged relative to healthy children. All pulmonary vein diastolic flow variables, except diastolic velocity, were increased relative to control subjects. After FO, E/atrial velocity and E/atrial time velocity integral ratios were decreased whereas deceleration and iso-
The modified Fontan operation (FO)
volumic relaxation time remained constant. Diastolic pulmonary vein forward flow increased after FO. These data suggest inherently abnormal ventricular relaxation in the univentricular heart and that changes in flow patterns observed postoperatively were subtle and likely a result of reduced ventricular preload after FO. Overall, diastolic function most probably remained stable after FO. This information can be used as a benchmark for further diastolic function assessment in patients with surgically palliated univentricular heart. (J Am Soc Echocardiogr 2003;16:1136-43.)
1 is the preferred palliative procedure for patients with a univentricular heart (UVH). The FO separates systemic and pulmonary circulation, eliminating cardiac volume overload and cyanosis. Despite improving survival after FO,2 a variety of adverse late sequelae contribute to significant morbidity and ongoing mortality in these patients. Ventricular failure remains a common cause of death after FO.3 Systolic dysfunction is known to be preceded by impaired diastolic function,4 however, there are limited data describing diastolic ventricular performance in patients before5 or after6-11 FO. Pulsed wave (PW) Doppler echocardiography is used in the assessment of diastolic function in many different cardiac disease states.12-16 Doppler assessment of diastolic function in children has also been reported and reference values for the pediatric age group have been established.17-19 The objective of this study was to use PW Doppler echocardiography to define Doppler parameters reflecting diastolic function in patients with UVH and
to compare these values with findings reported in a control group of healthy children (NC). We also sought to describe the changes in these parameters after FO. Ideally, diastolic filling patterns would show improvement as a result of decreased volume load and improved oxygenation after FO.
From the Division of Pediatric Cardiology (M.O., P.W.O.), the Section of Biostatistics (V.S.P., C.M.L.), and the Division of Cardiovascular Diseases and Internal Medicine (P.W.O., B.E.W., A.J.T., J.B.S.), Mayo Clinic, Rochester. Reprint requests: Patrick W. O’Leary, MD, Division of Pediatric Cardiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1067/S0894-7317(03)00635-7
Control Population
1136
METHODS Patients Undergoing FO We reviewed the medical and surgical records and the preoperative echocardiograms of all patients who underwent a FO at the Mayo Clinic in Rochester, Minn, between 1992 and 1997. Only patients with complete preoperative PW Doppler assessment of pulmonary vein (PV) and atrioventricular (AV) valve flow were included. Patients were excluded if they had any rhythm other than in sinus, AV valve regurgitation of more than mild degree, complex forms of anomalous PV return, or if the postoperative follow-up was less than 6 months.
The control group (n ⫽ 223; mean age, 10.6 ⫾ 4 years; range, 2-18 years) was composed of children from a local elementary and a local high school who had been prospectively recruited.18 These children had no history of cardiac or pulmonary disease, and their hearts were anatomically normal as assessed by 2-dimensional and Doppler echocardiography. PW Doppler data on mitral
Journal of the American Society of Echocardiography Volume 16 Number 11
Olivier et al 1137
and PV flow from this group18 were used for comparison with data from patients undergoing FO. Examinations and Comparisons Performed Between Groups Doppler data obtained from patients with a UVH before FO were compared with those seen in NC.18 Also, serial assessment of diastolic function in patients with UVH undergoing FO was carried out at 3 points in time (immediately before the FO [Echo I], before hospital discharge after the FO [Echo II], and at least 6 months postoperatively [Echo III]). Comparisons of Doppler data measured at Echo I, II, and III were then performed. Doppler Assessment of Diastolic Function Echocardiographic technique. All echocardiographic studies were performed with commercially available cardiac ultrasound systems. Ejection fraction (EF) was calculated using the modified Quinones technique for patients with left ventricular morphology and adequate M-mode tracings.20 All other patients had EF calculated using a biplane Simpson’s rule, with orthogonal images obtained at the cardiac apex or the subcostal window.20 The Doppler examination was performed at the cardiac apex. PW Doppler interrogation of AV valve and PV flow was performed in accordance with previously published recommendations.18,21 AV valve flow was evaluated with the sample volume placed near the tip of the valve leaflets. When 2 AV valves were present, the 1 connected to the PV atrium was evaluated. PV flow was studied with the sample volume at least 5 mm proximal to the insertion of the PV into the atrium. Signal measurement. All results were recorded on .75-in videotapes for subsequent analysis. Doppler signals were measured with use of an offline analysis system (Nova Microsonics Imagevue DCR, Mahwah, NJ). Three consecutive measurements were averaged for each variable. AV valve flow was evaluated during early (E) ventricular filling and at atrial (A) contraction, and peak velocities and time velocity integral (TVI) of E and A waves were measured. AV valve deceleration time (DT) and A-wave duration were determined. To characterize the relative contributions of the E and A waves to ventricular filling, the ratios of E/A velocities and E/A TVI were calculated. An AV valve flow signal was considered fused if separate E and A waves could not be distinguished or if the E at A velocity was greater than half of the E velocity (or both). Figure 1 illustrates the modified method to measure isovolumic relaxation time. PV signals were divided into systolic and diastolic forward flow and reversed flow at A contraction, as previously described.18 For each component, the peak velocity and TVI and the ratios of these parameters were determined. The duration of A reversal flow was measured. Diastolic filling fraction was calculated as [diastolic TVI/(systolic TVI ⫹ diastolic TVI)].
Statistical Analysis Clinical characteristics and Doppler parameters for patients who underwent FO were summarized with means,
Figure 1 Diagram of technique for measuring isovolumic relaxation time (IRT). AV, Atrioventricular; ECG, electrocardiogram; ET, ejection time.
SD, medians, and ranges. The Doppler measurements from Echo I were compared with the Doppler readings obtained from NC using analysis of covariance, adjusting for age and heart rate. Because the age and heart rate distributions differed between the patients undergoing FO and the NC, the Doppler measurements could not be simply summarized with means and SD. Therefore, least squares means and their associated SE were used to summarize these comparisons. Least squares means represent the expected value of each measurement after adjusting for age and heart rate. Moreover, Doppler parameters at the 3 echocardiograms (Echo I, II, and III) were compared between pairs of time points using paired t tests or Wilcoxon signed rank tests. These Doppler parameters were also compared using repeated measures analysis of covariance after adjusting for age and heart rate. Pairwise comparisons between the echocardiograms were performed only for those Doppler parameters that reached significance in the repeated measures analysis of the 3 time points. All analyses were conducted using software (SAS statistical package, Version 6.12, SAS Institute Inc, Cary, NC). P values less than .05 were considered statistically significant.
RESULTS Patients with UVH The study population consisted of 55 patients (26 female; median age, 5.5 years; range, 1.7-26 years). Preoperative ventricular morphology, previous palliative procedures, and type of Fontan connections created are summarized in Table 1. Table 2 contains clinical and hemodynamic data recorded at or
Journal of the American Society of Echocardiography November 2003
1138 Olivier et al
Table 1 Diagnoses, previous palliative procedures, and type of Fontan connection Diagnosis
N
DILV TA HLHS PA/IVS Other
24 7 4 4 16
Table 3 Atrioventricular valve flow in patients before Fontan procedure compared with healthy children
Previous palliation
N
Fontan connection
N
BDCPA BT shunt AP shunt PA banding
27 8 4 10
APA IAC ECC FTN
39 3 14 9
AP, Aortopulmonary; APA, atriopulmonary anastomosis; BDCPA, bidirectional cavopulmonary anastomosis; BT, Blalock-Taussig; DILV, doubleinlet left ventricle; ECC, extracardiac conduit; FTN, fenestration; HLHS, hypoplastic left heart syndrome; IAC, intracardiac conduit; PA, pulmonary artery; PA/IVS, pulmonary atresia with intact Ventricular septum; TA, tricuspid atresia.
AV flow
NC
Pre-Fontan
E velocity, cm/s A velocity, cm/s A duration, ms DT, ms E TVI, cm A TVI, cm E/A velocity E/A TVI
LSM (SE) 89 (1.0) 41 (0.7) 139 (1.5) 156 (1.5) 12.6 (0.2) 3.7 (0.08) 2.2 (0.04) 3.5 (0.07)
LSM (SE) 76 (2.4)* 56 (1.6)* 147 (3.4) 175 (3.4)* 10.7 (0.4)* 5.3 (0.2)* 1.4 (0.05)* 2.0 (0.1)*
A, Atrial filling wave; AV, atrioventricular; DT, deceleration time; E, early filling wave; LSM, least squares means; NC, healthy children; TVI, time velocity integral. *Patients before Fontan vs control subjects, P ⬍ .0001.
Table 2 Characteristics of patients undergoing Fontan procedure at 3 time points Echo I
Weight, kg Heart rate, bpm Systolic BP, mm Hg Diastolic BP, mm Hg EF, % LAP, mm Hg VEDP, mm Hg Qp/Qs
Echo III
Mean ⴞ SD Median (range)
Characteristic
Height, cm
Echo II
114 ⫾ 29 107 (69-186) 23 ⫾ 16 18 (11-83) (91 ⫾ 14)
113 ⫾ 28 106 (69-186) 24 ⫾ 16 18 (11-83) (102 ⫾ 18)*
123 ⫾ 28†‡ 115 (91-184) 27 ⫾ 16†‡ 20 (13-71) (82 ⫾ 16)†‡
90 (62-120) (99 ⫾ 15)
100 (64-140) (102 ⫾ 11)
80 (51-111) (107 ⫾ 13)
99 (69-136) (60 ⫾ 10)
100 (75-125) (60 ⫾ 9.0)
104 (86-140) (60 ⫾ 11)
60 (40-80) 52 ⫾ 9* 52 (30-68) ND
60 (40-80) 54 ⫾ 7 55 (40-69) ND
ND
ND
ND
ND
59 (45-88) 56 ⫾ 7 56 (45-71) 9 ⫾ 2.5 9 (2-16) (9.5 ⫾ 2.7) 10 (1-15) 1.2 ⫾ 0.8 0.8 (0.5-4)
Data are expressed as mean ⫾ SD and median (range). BP, Blood pressure; EF, ejection fraction; LAP, left atrial pressure; ND, not determined; Qp/Qs, pulmonary-to-systemic shunt flow ratio; VEDP, ventricular end-diastolic pressure. Echo I, preoperative examination; Echo II, examination before postoperative discharge, Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II; †P ⬍ .05 Echo I vs III. ‡P ⬍ .05 Echo II vs III.
around the time of the 3 echocardiographic examinations. Availability of AV Valve and PV Flow Signals in Patients with UVH All 55 patients had complete Echo I studies. An Echo II echocardiogram of adequate Doppler quality was obtained in 50 patients (91%). Echo II was obtained
at a median of 10 days after FO (range: 6-37 days). A total of 28 patients (51%) had an Echo III echocardiogram analyzed. These studies were obtained a median interval of 1.8 years after FO (range: 0.5-6.2 years). Diastolic Filling Patterns Before FO Compared with NC Table 3 summarizes the AV Doppler data from Echo I and comparisons made between the patients and NC, after adjusting for age and heart rate. Patients with a UVH before the FO (Echo I) showed an adjusted mean E/A velocity ratio of 1.4 versus 2.2 for NC. Despite the presence of E/A ratios ⬎1, E AV valve flow was significantly reduced, with a significant shift toward filling by A contraction, compared with NC (P ⬍ .001). In addition, average DT was approximately 20 milliseconds longer in the group of patients with UVH than in NC (P ⬍ .001). PV flow values at Echo I and the comparison with NC (adjusting for age and heart rate) are summarized in Table 4. These data demonstrated a nearly equal distribution of systolic and diastolic forward flow (diastolic filling fraction: 0.54) with a slight predominance of diastolic velocity (systolic/diastolic velocity: 0.8) in patients with UVH. However, PV flow in NC was systolic dominant in all variables except velocity. Comparison with NC revealed that patients with UVH had significantly increased PV diastolic forward flow. This was reflected by increased diastolic TVI and diastolic filling fraction, and a consequent decrease in the ratio of systolic to diastolic TVI (P ⬍ .001). However, PV diastolic flow velocity was not significantly different between the groups. A reversal velocity was slightly increased for patients before FO relative to NC. In contrast, A reversal durations were significantly shorter in patients with UVH (102 milliseconds) than the reversal durations recorded in NC (130 milliseconds, Table 4).
Journal of the American Society of Echocardiography Volume 16 Number 11
Table 4 Pulmonary venus flow data in patients before Fontan procedure compared with healthy children PV flow
NC
Pre-Fontan
Systolic velocity, cm/s Diastolic velocity, cm/s AR velocity, cm/s AR duration, ms Systolic TVI, cm Diastolic TVI, cm AR TVI, cm Velocitysys/dias TVIsys/dias Diastolic filling fraction
LSM (SE) 44 (0.7) 57 (0.7) 21 (0.4) 130 (1.9) 11.1 (0.2) 9.4 (0.2) 1.6 (0.1) 0.8 (0.02) 1.2 (0.02) 0.46 (0.01)
LSM (SE) 45 (1.4) 55 (1.4) 27 (1.4)* 102 (4.4)* 9.9 (0.4) 11.1 (0.3)* 1.8 (0.1) 0.8 (0.03) 0.9 (0.04)* 0.54 (0.01)*
AR, Atrial reversal; LSM, least squares means; NC, healthy children, PV, pulmonary venous; TVI, time velocity integral; TVIsys/dias, systolic/diastolic TVI ratio; Velocitysys/dias, systolic/diastolic velocity ratio. *Patients before Fontan vs NC, P ⬍ .0001.
Changes in Diastolic Filling Patterns in Patients After FO Systolic ventricular function, as assessed by EF, remained stable after FO (Table 2). Immediate postoperative EF showed a decrease relative to Echo I (52% vs 56%, P ⬍ .05), but the magnitude of the difference was not clinically important. EF at Echo III was not significantly different from the EF observed at either of the other studies. AV valve and PV Doppler data at Echo I, II, and III are summarized in Tables 5 and 6. A schematic illustration of the average Doppler signals from each of the 3 echocardiograms is provided in Figure 2. Changes at Echo II There were univariately significant decreases in E TVI and the E/A TVI ratio relative to Echo I (Table 5). However, no AV valve flow parameters at Echo II differed from preoperative values by multivariate analysis, which accounted for age and heart rate. At early postoperative follow-up, PV forward flow (Table 6) was characterized by increased diastolic velocity (P ⬍ .001), diastolic TVI (P ⬍ .001), and diastolic filling fraction (P ⬍ .02) compared with Echo I (adjusting for age and heart rate). Changes at Echo III When preoperative AV valve Doppler data (Echo I) were compared with the Echo III values by multivariate analysis (adjusting for age and heart rate), a significant increase in A velocity (P ⬍ .02) and A TVI (P ⬍ .002) were seen. There was also a significant decrease in the E/A velocity ratio (P ⬍ .02) and the E/A TVI ratio (P ⬍ .001). Univariate analysis of PV flow parameters at Echo III revealed increased diastolic velocity and diastolic filling fraction relative to the preoperative findings. An increase in the AR velocity, but not in the AR duration, was also observed
Olivier et al 1139
by univariate comparison. After adjustment for age and heart rate, PV diastolic velocity (P ⬍ .001) and diastolic TVI (P ⬍ .008) were increased. There was no change in AR duration on multivariate analysis. When the Echo III versus Echo II echocardiograms were compared, AV valve Doppler data remained unchanged. PV flow at Echo III demonstrated an increase in diastolic TVI and a consequent decrease in the systolic/diastolic TVI ratio compared with Echo II on univariate comparison. However, no significant changes in PV flow were detectable on multivariate comparison of Echo II and Echo III.
DISCUSSION Patients after FO have been described as having ventricular filling patterns consistent with abnormal relaxation.6-9 Our patients, both before and after FO, had AV valve inflow patterns that demonstrated reduced E diastolic filling, increased forward flow at A contraction, and longer DT than NC. These filling shifts are similar to those observed in patients with abnormal relaxation patterns.22,23 However, unlike previous descriptions of abnormal or delayed relaxation, all E/A ratios remained ⬎1 and isovolumic relaxation time was within the previously described normal range.18 Analysis of PV flow velocities and velocity ratios before FO demonstrated few differences from NC. However, PV A reversals had a shorter duration for patients with UVH than in NC. This is usually thought to be a sign of low filling pressures.22 Preoperative PV Doppler signals had a nearly equal distribution of systolic and diastolic flow with a ratio of systolic to diastolic velocity of 0.8 and diastolic filling fraction of 0.54. These patterns are not consistent with the systolic dominance to forward flow that one expects from prior descriptions of abnormal relaxation. It appears that these hearts are transitioning toward, but not quite reaching, the expected abnormal relaxation pattern. In fact, AV valve and PV flow patterns seen in the UVH group before FO more closely resemble the normal adult pattern than that of abnormal relaxation (Figure 3). However, this patient group had a median age of only 5.5 years, making the presence of a normal adult filling pattern distinctly abnormal. It may be that the abnormality in ventricular diastolic function is mild enough that it impacts only AV valve flow, whereas PV flow is relatively insulated. Alternatively, excellent atrial function or compliance in these young patients may explain the unique AV and PV flow pattern observed in this study. From a clinical perspective, the abnormality of diastolic function present in these highly selected patients must be relatively mild, because they were all survivors of FO and had invasively documented
Journal of the American Society of Echocardiography November 2003
1140 Olivier et al
Table 5 Atrioventricular valve flow variables and IRT in patients undergoing Fontan operation at 3 time points Echo I
A velocity, cm/s A duration, ms E at A velocity, cm/s E/A velocity ratio Deceleration time, ms E wave TVI, cm A wave TVI, cm E/A TVI ratio IRT, ms
Echo III
Mean ⴞ SD Median (range)
Variable
E velocity, cm/s
Echo II
77 ⫾ 18 75 (43-125) 62 ⫾ 19 59 (31-111) 145 ⫾ 22 139 (113-196) 26 ⫾ 14 28 (2-61) 1.3 ⫾ 0.4 1.2 (0.5-2.7) 167 ⫾ 31 166 (121-213) 10 ⫾ 2.9 9.7 (3.6-15.7) 5.9 ⫾ 2.0 5.7 (2.7-10.7) 1.9 ⫾ 1.0 1.8 (0.4-5.3) 51 ⫾ 10.9 53 (39-67)
70 ⫾ 16 69 (44-100) 63 ⫾ 18 57 (38-97) 136 ⫾ 21 144 (97-179) 28 ⫾ 11 26 (13-51) 1.2 ⫾ 0.3 1.2 (0.6-1.8) 148 ⫾ 32 153 (102-210) 7.8 ⫾ 3.3* 9.7 (3.6-15.7) 5.5 ⫾ 1.8 6.0 (2.1-8.8) 1.5 ⫾ 0.6* 1.4 (0.6-3.1) 45 ⫾ 13.6 40 (36-75)
72 ⫾ 13 73 (51-99) 60 ⫾ 13 64 (26-82) 156 ⫾ 19 157 (105-199) 25 ⫾ 10 25 (11-41) 1.2 ⫾ 0.3 1.1 (0.9-2.2) 163 ⫾ 30 162 (92-215) 9.1 ⫾ 2.3 9.2 (4.5-14.1) 6.0 ⫾ 1.2 6.2 (3.8-8.0) 1.5 ⫾ 0.5 1.4 (1.0-2.9) 56 ⫾ 33.1 44 (37-123)
P ⬍ .05 ⬃ significant by univariate analysis (see Results section for multivariate analysis). A, Atrial filling wave; A duration, duration of atrial filling wave; E, early filling wave; IRT, isovolumic relaxation time; TVI, time velocity integral. Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II.
Table 6 Pulmonary Vein flow variables of patients undergoing Fontan operation at 3 time points Echo I
Diastolic velocity, cm/s AR velocity, cm/s AR duration, ms Systolic TVI, cm Diastolic TVI, cm Systolic/diastolic TVI Systolic/diastolic velocity Diastolic filling fraction
Echo III
Mean ⴞ SD Median (range)
Variable
Systolic velocity, cm/s
Echo II
45 ⫾ 12 45 (22-68) 54 ⫾ 9 55 (36-47) 36 ⫾ 16 34 (19-60) 105 ⫾ 39 101 (67-173) 9.4 ⫾ 3.0 9.5 (4.3-20.2) 10.5 ⫾ 3.2 10.4 (5.1-20.7) 1.0 ⫾ 0.4 0.9 (0.4-1.6) 0.8 ⫾ 0.3 0.9 (0.4-1.6) 0.5 ⫾ 0.1 0.5 (0.3-0.8)
49 ⫾ 18 47 (22-101) 69 ⫾ 19* 70 (18-119) 50 ⫾ 17 47 (30-72) 85 ⫾ 25 87 (55-128) 9.2 ⫾ 5.1 7.7 (3.0-34.5) 11.9 ⫾ 4.2* 11.7 (1.7-21.5) 0.9 ⫾ 1.1 0.8 (0.3-7.9) 0.8 ⫾ 0.5* 0.7 (0.3-3.9) 0.6 ⫾ 0.1* 0.6 (0.1-0.8)
53 ⫾ 20† 52 (23-91) 70 ⫾ 20† 70 (33-107) 35 ⫾ 22† 29 (19-93) 94 ⫾ 39 99 (49-164) 11 ⫾ 5.9 10.3 (5.1-36.4) 14.4 ⫾ 6.4†‡ 13.1 (4.3-30.8) 1.0 ⫾ 1.0†‡ 0.7 (0.2-5.1) 0.8 ⫾ 0.4 0.7 (0.3-1.5) 0.6 ⫾ 0.2† 0.6 (0.2-0.8)
P ⬍ .05 ⬃ significant on univariate analysis (see “Results” section for multivariate analysis). AR, Atrial reversal; TVI, time velocity integral. Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively. *P ⬍ .05 Echo I vs II; †P ⬍ .05 Echo I vs III; ‡P ⬍ .05 Echo II vs III.
low ventricular end-diastolic pressures at the time of Echo I (Table 2). The transitional nature of the flow pattern observed in this study points out 2 important aspects
of diastolic function assessment. The first is that diastolic ventricular performance needs to be thought of as a continuum (Figure 3).21 These patients had Doppler patterns that were between
Journal of the American Society of Echocardiography Volume 16 Number 11
Olivier et al 1141
that of their age-matched control subjects and classic abnormal relaxation. Logically, this position on the continuum should represent a mild degree of impairment in diastolic performance and should be associated with low filling pressures. Secondly, when evaluating diastolic performance one must compare all data with an age-appropriate control group. Without such a control group, it would have been impossible to interpret these findings correctly or even to detect that these patients had diastolic dysfunction at all. Impact of the FO on Ventricular Diastolic Performance Comparison of late postoperative Doppler findings with Echo I showed a significant shift toward ventricular filling by A contraction (increased A velocity and TVI, decreased E/A velocity and E/A TVI ratios) and increased PV diastolic forward flow. DT and isovolumic relaxation time remained unchanged after FO. The differences observed are probably best explained by the preload reduction associated with conversion to the Fontan circulation.24 Therefore, we conclude that diastolic ventricular performance was actually unchanged during follow-up in this group of patients with UVH. Although we were unable to document an improvement in diastolic performance, the fact that no deterioration occurred is gratifying. A much longer period of follow up will be required to determine if this stability in diastolic function will persist.
Figure 2 Schematic of ventricular filling patterns before and after Fontan operation. A, Atrial filling wave; AV, atrioventricular; D, diastolic filling wave; DT, deceleration time; E, early filling wave; Echo I, preoperative examination; Echo II, examination before postoperative discharge; Echo III, examination at least 6 months postoperatively; FFxdias, diastolic filling fraction; PV, pulmonary venous; PVAR, PV atrial reversal; S, systolic filling wave.
Previous Descriptions of Diastolic Filling Patterns in Patients with UVH Our postoperative observation of reduced E AV valve flow was consistent with earlier findings6-11 for patients after FO. This has previously been attributed to incoordinate ventricular relaxation occurring both immediately7 and late after FO.6,8,9 However, our study observed that postoperative Doppler flow patterns were actually similar to preoperative findings. The fact that these abnormalities in diastolic filling could be detected preoperatively argues that abnormal diastolic performance is inherent to these hearts, rather than being the result of FO. PV flows before FO were characterized by a nearly equal distribution of systolic and diastolic flow with increased diastolic flow values relative to NC. Rychik et al5 had observed an overall predominance of PV systolic flow for patients with UVH before FO. This difference is probably best explained by the younger mean patient age in the population of Rychik et al.5 Very young healthy children have been shown to have predominantly systolic PV flow, which shifts to a slight diastolic dominance in later childhood.17,18
Figure 3 Spectrum of Doppler flow patterns in diastolic dysfunction extended to include normal diastolic function in children. A, Atrial filling wave; AV, atrioventricular; D, diastolic filling wave, E, early filling wave; S, systolic; VAR, venous atrial reversal.
The postoperative predominance of PV diastolic flow in the current study has been previously observed in patients after FO.10,11,25 However, the cited studies did not present preoperative data. Therefore, it was not possible to say whether this flow pattern was related to the congenital malformation or associated with transition to the FO circulation. Our data support the conclusion that ventricular relaxation is inherently abnormal in these patients rather than being the result of the FO. Limitations Diastolic ventricular function is influenced by many factors, including age and heart rate.18 Comparisons of Doppler variables in this study were adjusted for these parameters, but other confounding factors, such as varying ventricular morphology,26 could not
1142 Olivier et al
be completely eliminated. In addition, the retrospective nature of the study did not allow us to gate the Doppler signals to the phase of respiration or to consistently perform preload reduction maneuvers, (ie, Valsalva). However, these patients were all studied as a part of routine clinical evaluations and at least 3 consecutive cycles of Doppler data were measured and averaged. Our results should, therefore, reflect the resting or average state of the patient (ie, nonfasting and spontaneously breathing). The defined inclusion criteria also resulted in a study population characterized by a favorable diastolic hemodynamic profile: those able to have and survive FO. Consequently, Doppler data in this study probably reflect relatively optimal diastolic function for patients with UVH. Further studies will be required to determine the filling patterns in the UVH with poor diastolic function. In addition, all patients studied were in sinus rhythm. Other rhythms, particularly junctional rhythm, will significantly change the flow signals recorded. Therefore, one cannot directly apply these results to patients who are in rhythms that lack AV synchrony. Lastly, the length of postoperative follow up was relatively short, and we will need more time to truly define long-term diastolic ventricular performance in these patients and what influence it has on their clinical status after FO. Conclusion and Clinical Implications Complete, serial Doppler diastolic filling assessment of patients with UVH before and after FO has not been previously reported. These patients demonstrated decreased E AV valve flow, longer DT, and increased PV diastolic flow relative to NC both before and after FO. These data suggest an inherent, but mild abnormality of ventricular diastolic performance for patients with UVH and relatively normal systolic EF. This was observed even though this group had adequate diastolic function by clinical evaluation and catheter-measured ventricular enddiastolic pressures. The filling patterns observed were transitional, between those of healthy children and the pattern of abnormal relaxation. During the relatively short course of our study, ventricular diastolic function seemed to remain stable. The changes in the Doppler filling patterns observed postoperatively are best explained by the decrease in ventricular preload resulting from conversion to a Fontan circulation. The data reported in this study will serve as a preliminary clinical benchmark, describing the Doppler patterns associated with low ventricular filling pressures and clinically adequate diastolic function for patients with UVH both before and after FO. Knowledge of these Doppler patterns and use of age and heart rate appropriate normal values should
Journal of the American Society of Echocardiography November 2003
make the noninvasive recognition of diastolic dysfunction for patients with complex congenital heart diseases simpler and more accurate. It is also possible that we may be able to decrease the frequency with which invasive evaluation of ventricular diastolic function is necessary in these patients. Before this can occur, a much larger body of information will be required, especially data describing the Doppler patterns associated with high filling pressures and poor diastolic function in these patients. REFERENCES 1. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971;26:240-8. 2. Cetta F, Feldt RH, O’Leary PW, Mair DD, Warnes CA, Driscoll DJ, et al. Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992. J Am Coll Cardiol 1996;28:480-6. 3. Driscoll DJ, Offord KP, Feldt RH, Schaff HV, Puga FJ, Danielson GK. Five- to fifteen-year follow-up after Fontan operation. Circulation 1992;85:469-96. 4. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:1565-74. 5. Rychik J, Fogel MA, Donofrio MT, Goldmuntz E, Cohen MS, Spray TL, et al. Comparison of patterns of pulmonary venous blood flow in the functional single ventricle heart after operative aortopulmonary shunt versus superior cavopulmonary shunt. Am J Cardiol 1997;80:922-6. 6. Penny DJ, Rigby ML, Redington AN. Abnormal patterns of intraventricular flow and diastolic filling after the Fontan operation: evidence for incoordinate ventricular wall notion. Br Heart J 1991;66:375-8. 7. Penny DJ, Lincoln C, Shore DF, Xiao HB, Rigby ML, Redington AN. The early response of the systemic ventricle during transition to the Fontan circulation–an acute hypertrophic cardiomyopathy? Cardiol Young 1992;2:78-84. 8. Frommelt PC, Snider AR, Meliones JN, Vermilion RP. Doppler assessment of pulmonary artery flow patterns and ventricular function after the Fontan operation. Am J Cardiol 1991; 68:1211-5. 9. Cheung YF, Penny DJ, Redington AN. Serial assessment of left ventricular diastolic function after Fontan procedure. Heart 2000;83:420-4. 10. Milanesi O, Stellin G, Colan S, Facchin P, Crepaz R, Biffanti R, et al. Systolic and diastolic performance late after the Fontan procedure for a single ventricle and comparison of those undergoing operation at ⬍ 12 months of age and at ⬎ 12 months of age. Am J Cardiol 2002;89:276-80. 11. Hagler DJ, Cordes TM. Complete echocardiographic assessment of the postoperative Fontan patient. Echocardiography 1995;12:529-43. 12. Klein AL, Hatle LK, Taliercio CP, Oh JK, Kyle RA, Gertz MA, et al. Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis: a Doppler echocardiography study. Circulation 1991;83:808-16. 13. Xie GY, Berk MR, Smith MD, Gurley JC, DeMaria AN. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol 1994; 24:132-9. 14. Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic and diastolic dysfunction in patients with clinical
Journal of the American Society of Echocardiography Volume 16 Number 11
15.
16.
17.
18.
19.
20.
diagnosis of dilated cardiomyopathy: relation to symptoms and prognosis. Circulation 1994;90:2772-9. Moskowitz WB, Schieken RM, Mosteller M, Bossano R. Altered systolic and diastolic function in children after “successful” repair of coarctation of the aorta. Am Heart J 1990; 120:103-9. Gidding SS, Snider AR, Rocchini AP, Peters J, Farnsworth R. Left ventricular diastolic filling in children with hypertrophic cardiomyopathy: assessment with pulsed Doppler echocardiography. J Am Coll Cardiol 1986;8:310-6. Abdurrahman L, Hoit BD, Banerjee A, Khoury PR, Meyer RA. Pulmonary venous flow Doppler velocities in children. J Am Soc Echocardiogr 1998;11:132-7. O’Leary PW, Durongpisitkul K, Cordes TM, Bailey KR, Hagler DJ, Tajik AJ, et al. Diastolic ventricular function in children: a Doppler echocardiographic study establishing normal values and predictors of increased ventricular end-diastolic pressure. Mayo Clin Proc 1998;73:616-28. Schmitz L, Koch H, Bein G, Brockmeier K. Left ventricular diastolic function in infants, children, and adolescents: reference values and analysis of morphologic and physiologic determinants of echocardiographic Doppler flow signals during growth and maturation. J Am Coll Cardiol 1998;32:1441-8. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography: from the American Society of Echocardiography committee on
Olivier et al 1143
21.
22.
23.
24.
25.
26.
standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr 1989;2:358-67. Rakowski H, Appleton C, Chan KL, Dumesnil JG, Honos G, Jue J, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the investigators of consensus on diastolic dysfunction by echocardiography. J Am Soc Echocardiogr 1996;9:736-60. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta stone. J Am Coll Cardiol 1997;30:818. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246-70. Nishimura RA, Abel MD, Hatle LK, Tajik AJ. Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography: effect of different loading conditions. Circulation 1990;81:1488-97. Rydberg A, Teien DE, Karp K, Vermilion RP, Ludormirsky A. Pulmonary venous blood flow pattern in patients with univentricular hearts following total cavo-pulmonary connection. Clin Physiol 1998;18:131-8. Akagi T, Benson LN, Gilday DL, Ash J, Green M, Williams WG, et al. Influence of ventricular morphology on diastolic filling performance in double-inlet ventricle after the Fontan procedure. J Am Coll Cardiol 1993;22:1948-52.