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Atrial and Ventricular Mechanics in Patients after Fontan-Type Procedures: Atriopulmonary Connection versus Extracardiac Conduit
Atrial and Ventricular Mechanics in Patients after Fontan-Type Procedures: Atriopulmonary Connection versus Extracardiac Conduit Shu-juan Li, MD, Sophia J. Wong, BSc,, and Yiu-fai Cheung, MD, Hong Kong, China
Background: Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures, which may affect atrial and ventricular filling. The aim of this study was to test the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, atriopulmonary connection (APC) and extracardiac conduit, which have distinctly different systemic venous hemodynamics. Methods: This was a cross-sectional, case-control study of 28 Fontan patients (13 with APC, 15 with extracardiac conduit) aged 19.8 6 6.5 years and 26 healthy controls. Atrial and systemic ventricular myocardial deformation was determined using speckle-tracking echocardiography, while ventricular volumes and systolic dyssynchrony index were assessed using three-dimensional echocardiography. Results: Compared with controls, patients had significantly lower values of global ventricular longitudinal, circumferential, and radial systolic strain in all three directions, reduced systolic and early diastolic strain rates (SRs) in more than one dimension, lower ejection fractions, and worse ventricular dyssynchrony. For atrial deformation, patients had lower global and positive strain and conduit and reservoir SRs and delayed electromechanical coupling. Among patients, those with APC had significantly lower ventricular longitudinal strain and early diastolic SRs, worse ventricular dyssynchrony, and reduced atrial positive and negative strain and conduit and active contractile SRs. Atrial global strain (r = 0.60, P = .001) and conduit SR (r = 0.49, P = .008) correlated positively with systemic ventricular early diastolic SR. Conclusions: Atrial and ventricular mechanics are impaired in patients after Fontan-type operation, which is worse with APC than extracardiac conduit. (J Am Soc Echocardiogr 2014;-:---.) Keywords: Atrium, Ventricle, Cardiac mechanics, Speckle-tracking echocardiography, Fontan procedure
Fontan-type procedures involve palliative surgery for patients with functional single ventricles.1 Since the first report of success in 1971,2 the initially described operation has undergone several modifications, from atriopulmonary connection (APC) through lateral tunnel to extracardiac conduit (EC) procedures.3,4,5 Long-term complications of Fontan-type procedures, in particular in patients with APC, are well documented.1,6,7 These include atrial arrhythmias, venous thromboembolism, compression of pulmonary veins, protein-losing enteropathy, atrioventricular valvar regurgitation, and progressive systemic ventricular dysfunction. Notwithstanding
From the Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. Dr Li is a research fellow from The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China. Reprint requests: Yiu-fai Cheung, MD, Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.01.027
the relatively smaller number of patients with APC compared with those with lateral tunnel or EC in the present era, these patients are frequently encountered among patients who had functional single ventricles palliated in an earlier surgical era with longer term followup. In these symptomatic patients, conversion of the Fontan circuit from APC to EC has been reported to improve functional class, reverse protein-losing enteropathy, and enable better control of refractory cardiac arrhythmias,8,9,10,11 although these outcomes are not guaranteed. The atrial and ventricular performance in the two different types of Fontan procedures, however, is unclear. Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures. In APC, progressive dilation of the right atrium causes greater fluid energy losses and increases the energy required to move blood from the caval vein to the pulmonary arteries. By contrast, flow in total cavopulmonary connection and EC is hemodynamically more organized and uniform and hence more efficient.12,13,14 Differences in systemic venous flow dynamics in various Fontan-type procedures may have implications for atrial and ventricular filling and mechanics. In the present study, we tested the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, APC and EC (Figure 1), which have distinctly different systemic venous hemodynamics. We further explored potential relationships between atrial and ventricular mechanics in Fontan patients. 1
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Abbreviations
APC = Atriopulmonary connection
Journal of the American Society of Echocardiography - 2014
METHODS Subjects
This was a cross-sectional, casecontrol echocardiographic study of patients who had undergone SR = Strain rate Fontan-type procedures and healthy, age-matched controls. SRcon = Atrial conduit strain Of the 32 patients recruited, rate three with APC were excluded because of a loss of sinus rhythm, and one with EC was excluded because of a suboptimal acoustic window. A total of 28 patients, 13 with APC and 15 with EC, were hence included in the final analysis. The following data were retrieved from the case notes: cardiac diagnosis, age at surgery, history of shunt operation, type of Fontan procedure, existence of fenestration, history of cardiac arrhythmias, current medications, and duration of follow-up since operation. Twenty-six healthy subjects were recruited as controls. These included healthy volunteers; subjects identified in the cardiac clinic with functional murmurs, nonspecific chest pain, and palpitation without an organic cause; and healthy siblings of patients. Body weight and height were measured, and body mass index and surface area were calculated accordingly. In patients, pulse oximetry and electrocardiography were performed. All subjects underwent echocardiographic assessment as described below. The institutional review board approved the study, and all adult subjects and parents of minors gave informed written consent. EC = Extracardiac conduit
Doppler Echocardiographic Assessment Echocardiographic assessments were performed using the Vivid 7 ultrasound system (GE Vingmed Ultrasound AS, Horten, Norway). The averages of echocardiographic indices measured from three cardiac cycles were obtained for statistical analysis. Color Doppler flow mapping was performed to assess semiquantitatively the degree of systemic atrioventricular valvar regurgitation.15 Regurgitation was graded as trivial to mild if the regurgitant jet did not cross two thirds of the systemic atrium, moderate if beyond, and severe if the jet reached the posterior wall. Pulsed-wave Doppler examination was performed to obtain the systemic atrioventricular valvar early (E) and late (A) diastolic inflow velocities and E/A ratio. Tissue spectral Doppler imaging was performed with the sample volume positioned at the base of the right-sided and left-sided free wall–atrioventricular valve annular junction in patients and at the ventricular septum and left ventricular free wall–mitral valve annular junction in controls to obtain the following indices: the peak myocardial velocities at systole (s), early diastole (e), and late diastole (a); the e/a ratio; and the E/e ratio. Assessment of Ventricular Mechanics Mechanics of the systemic ventricle were assessed using twodimensional speckle-tracking echocardiography.16 Two-dimensional echocardiographic recordings were analyzed offline using twodimensional strain software (EchoPAC; GE Vingmed Ultrasound AS). Deformation of the dominant functional single ventricle in Fontan patients and the left ventricle in control subjects was assessed (Figure 2). Global systemic ventricular longitudinal systolic strain and systolic and diastolic strain rate (SR) were determined from the apical four-chamber view, while circumferential and radial strain and SR were assessed from the midventricular short-axis. The right-sided and left-sided ventricular free walls for functional single ventricle
and left ventricular free wall and ventricular septum in structurally normal hearts were divided respectively into three segments (basal, middle, and apical) for quantification of regional longitudinal strain. Assessment of Atrial Mechanics Mechanics of the pulmonary venous atrial chamber were determined also using speckle-tracking echocardiography, with tracing of the entire atrial contours.17 Left atrial deformation was assessed in patients with APC and in controls, while the two atria were regarded as a common atrium in patients with EC because these patients either had right atrial isomerism with almost complete deficiency of atrial septum or had undergone atrial septectomy. The onset of the P wave was used as the reference point for the determination of peak positive strain, peak negative strain, and total strain (Figure 2). The atrial active contractile SR, atrial conduit SR (SRcon), and reservoir SR, were then derived accordingly.18 Atrial electromechanical coupling was evaluated by measuring the time from onset of the P wave to peak negative strain19 and normalized to the square root of the RR interval. Real-Time Three-Dimensional Echocardiography Full-volume ventricular data sets were acquired from the apical fourchamber view using the matrix-array transducer and analyzed offline with commercial four-dimensional analysis software (TomTec Imaging Systems, Unterschleissheim, Germany). The endocardial borders were traced and used to derive the end-systolic and end-diastolic volumes and ejection fraction. The systolic dyssynchrony index of the systemic ventricle was calculated as the standard deviation of time taken to reach minimum regional volume for each of the 16 ventricular segments as a percentage of the cardiac cycle.20 Statistical Analysis All data are expressed as mean 6 SD. Absolute values of strain and SR were used to facilitate interpretation. Ventricular volumes were indexed to body surface area. Intraobserver and interobserver variability was assessed in 10 patients and reported as the coefficients of variation, calculated by dividing the standard deviation of differences between measurements by the mean and expressed as a percentage. Differences in demographic, clinical, and echocardiographic parameters between groups were compared using unpaired Student’s t tests, Fisher’s exact tests, and c2 test as appropriate. Pearson’s correlation analysis was used to study relationships between atrial and ventricular deformation parameters and ejection fraction. P values < .05 were considered statistically significant. All statistical analyses were performed using SPSS version 16.0 (SPSS, Inc, Chicago, IL).
RESULTS Subjects The 28 patients (19 men) aged 19.8 6 6.5 years were studied 13.4 6 6.2 years after undergoing Fontan-type procedures. Situs solitus was present in 14 patients, while an abnormal situs was present in the other 14 patients (situs inversus in seven, right atrial isomerism in six, and left atrial isomerism in one). Ventricular-arterial connection was single outlet with pulmonary atresia in 14 patients, concordant in seven, discordant in three, double outlet from the right ventricle in three, and double outlet from the left ventricle in one. Before
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Figure 1 Illustrations of (A) APC and (B) EC Fontan procedures. Ao, aorta; IVC, inferior vena cava; RA, right atrium; RPA, right pulmonary artery; SVC, superior vena cava.
Figure 2 Representative ventricular and atrial strain and SR curves in a patient with APC, a patient with with EC, and a control subject. Peak negative (white arrow) and positive (yellow arrow) atrial strain is highlighted. SRa, Ventricular late diastolic SR; SRac, atrial active contractile SR; SRe, ventricular early diastolic SR; SRres, atrial reservoir SR; SRs, ventricular systolic SR.
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Table 1 Demographic data and clinical parameters of patients after APC and EC Fontan procedures Variable
Age (y) Age at Fontan procedure (y) Follow-up duration (y) Male/female Body weight (kg) Body height (cm) Body mass index (kg/m2) History of shunt insertion (yes/no) History of pulmonary arterial banding (yes/no) Fenestration (yes/no or closed by device) Ventricular morphology (left/ right/indeterminate) Oxygen saturation (%) QRS duration (msec)
APC (n = 13)
EC (n = 15)
P
23.7 6 6.3 16.4 6 4.5 .002* 5.0 6 5.0 7.8 6 2.9 .08 18.8 6 3.1 8.5 6 3.6 <.001* 8/5 11/4 .51 59.3 6 13.2 47.5 6 13.8 .03* 163.3 6 8.1 155.7 6 10.9 .049* 22.1 6 3.4 19.3 6 4.5 .08 6/7 11/4 .14 1/12
1/14
.92
3/10
6/9
.34
11/1/1
4/8/3
<.001*
94.1 6 2.6 93.6 6 4.6 111.0 6 23.0 114.5 6 14.7
.74 .62
Data are expressed as mean 6 SD or as numbers. *Statistically significant.
univentricular palliation, 17 patients underwent modified BlalockTaussig shunt procedures and two underwent pulmonary arterial banding. History of atrial tachycardia or flutter was present in 6 patients. Twenty-two patients were taking warfarin and two were receiving aspirin as anticoagulation prophylaxis. Five patients were receiving heart failure medications, of whom four were put on enalapril, two on digoxin, and two on diuretics. Three patients were taking bblockers. All patients were in sinus rhythm, and none had pacemakers implanted at the time of the study. Age (19.8 6 6.5 vs 19.6 6 5.6 years, P = .92), sex distribution (16 male and 10 female vs 19 male and nine female, P = .63), body weight (53.0 6 14.6 vs 56.0 6 10.6 kg, P = .38), and body mass index (20.6 6 4.2 vs 20.4 6 5.5 kg/m2, P = .88) were similar between patients and controls. Demographic and clinical parameters of the two groups of Fontan patients are shown in Table 1. Because of evolution of the Fontan-type procedure with time, patients with APC were significantly older, followed up for a longer duration, and had larger body sizes compared with those with EC (P < .05 for all). Patients with APC were more likely to have systemic ventricles of left ventricular morphology, while those with EC were more likely to have a right or indeterminate ventricular morphology (P < .001).
Doppler and Three-Dimensional Echocardiographic Assessment Doppler color flow mapping showed trivial to mild degrees of atrioventricular valvar regurgitation in 22 patients and none in six patients. Table 2 summarizes the Doppler and three-dimensional echocardiographic parameters in patients and controls. Compared with controls, patients had significantly lower systemic atrioventricular E velocities and E/A ratios; reduced left-sided ventricular free wall s, e, and a velocities and e/a ratios; and reduced right-sided s and e velocities. The E/e ratios of both the left-sided and right-sided ventricular walls were greater in patients than controls. Comparisons between subgroups of patients revealed that patients with APC had significantly lower e velocities and e/a ratios of the
right-sided ventricular free wall and greater E/e ratios than those with EC. Regarding three-dimensional echocardiographic parameters, patients had significantly greater end-systolic volumes, lower ejection fractions, and greater systolic mechanical dyssynchrony of the systemic ventricle. Within patient groups, patients with APC had significantly smaller end-systolic and end-diastolic volumes, lower ejection fractions, and greater dyssynchrony of the systemic ventricle compared with those with EC. Ventricular Mechanics The coefficients of variation for intraobserver and interobserver measurement of ventricular longitudinal strain were 5.9% and 8.5%, for circumferential strain were 7.8% and 12.5%, and for radial strain were 13.0% and 15.2%, respectively. Figure 3 shows systemic ventricular global strain and SR in patients and controls. Compared with controls, Fontan patients had significantly lower global systolic longitudinal, radial, and circumferential strain. Regional longitudinal strain assessment showed that strain values of all but one segment were significantly lower values in patients than controls (Table 3). Furthermore, patients had significantly lower ventricular systolic longitudinal and circumferential SRs and early diastolic longitudinal and radial SRs than controls, although their late diastolic circumferential SRs appeared greater. Comparisons between patient subgroups revealed that patients with APC had significantly lower longitudinal systolic strain and early diastolic SRs (Figure 3) and regional strain (Table 3) than those with EC. Among patients, systemic ventricular ejection fraction correlated positively with global systolic longitudinal strain (r = 0.58, P = .001) and global systolic radial strain (r = 0.60, P = .001) and negatively with systolic dyssynchrony index (r = 0.55, P = .002) (Figure 4, top). Atrial Mechanics The coefficients of variation for intraobserver and interobserver measurement of atrial total strain were 5.6% and 7.0%, for atrial active contractile SR were 8.1% and 9.2%, for SRcon were 5.7% and 10.5%, and for atrial reservoir SR were 7.6% and 11.1%, respectively. Comparisons of global atrial strain and SRs between patients and controls are shown in Figure 5. Compared with controls, patients had significantly lower atrial global and positive strain, atrial reservoir SR, and SRcon. Comparisons of the patient subgroups showed that patients with APC had significantly lower negative, positive, and global atrial strain and SRcon and atrial active contractile SR. To identify the role of active atrial contraction during atrial deformation, the negative/global strain ratio was calculated.18 This strain ratio was significantly greater in patients than controls (0.52 6 0.12 vs 0.3 6 0.06, P < .001) but similar between patients with APC and those with EC (0.53 6 0.15 vs 0.51 6 0.1, P = .81). Atrial electromechanical coupling was significantly longer in patients than controls (194 6 38 vs 158 6 19 msec, P < .001). Additionally, the coupling also tended to be longer in patients with APC than those with EC (206 6 38 vs 183 6 36 msec, P = .11). Among patients, ventricular early diastolic SR correlated positively with global strain (r = 0.60, P = .001) and atrial SRcon (r = 0.49, P = .008) (Figure 4, bottom). For the entire cohort, these correlations were even stronger (r = 0.77, P < .001, and r = 0.70, P < .001, respectively). Additionally, the timing of atrial electromechanical coupling was found to correlate negatively with ventricular early diastolic SR (r = 0.39, P = .004).
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Table 2 Doppler and three-dimensional echocardiographic parameters Variable
Pulsed Doppler of systemic atrioventricular inflow E wave (cm/sec) A wave (cm/sec) E/A ratio Doppler tissue imaging Left-sided free wall s (cm/sec) e (cm/sec) a (cm/sec) e/a ratio E/e ratio Right-sided free wall in patients/ventricular septum in controls s (cm/sec) e (cm/sec) a (cm/sec) e/a ratio E/e ratio 3D echocardiography Indexed EDV (mL/m2) Indexed ESV (mL/m2) EF (%) SDI (%)
APC (n = 13)
EC (n = 15)
All patients (n = 28)
Controls (n = 26)
58.2 6 11.0 42.8 6 11.8 1.5 6 0.5
64.5 6 17.8 51.5 6 23.0 1.5 6 0.6
61.6 6 15.1† 47.5 6 18.9 1.5 6 0.5†
87.1 6 12.8 40.5 6 10.3 2.3 6 0.8
7.6 6 2.8 9.9 6 4.5 6.2 6 1.5 1.6 6 0.8 8.6 6 7.9
6.4 6 1.8 10.2 6 3.4 6.4 6 1.3 1.7 6 0.6 7.5 6 5.4
7.0 6 2.3† 9.9 6 3.9† 6.3 6 1.4† 1.6 6 0.7† 7.4 6 4.7†
11.9 6 2.1 18.3 6 2.5 7.1 6 1.2 2.6 6 0.6 4.8 6 0.8
5.2 6 1.4 4.3 6 1.4* 5.2 6 2.2 0.9 6 0.3* 15.3 6 6.6*
5.6 6 0.8 8.3 6 2.5 5.7 6 1.3 1.5 6 0.7 9.0 6 5.5
5.4 6 1.1† 6.4 6 2.9† 5.3 6 2.0 2.4 6 6.4 11.9 6 6.7†
7.8 6 1.5 12.7 6 2.0 6.1 6 1.4 2.2 6 0.4 7.0 6 1.2
33.1 6 14.0* 21.0 6 12.8* 38.6 6 11.8 9.2 6 2.4*
57.0 6 22.3 33.3 6 13.9 41.5 6 6.6 6.2 6 1.4
45.9 6 22.2 27.6 6 14.6† 40.1 6 9.3† 7.6 6 2.4†
38.3 6 8.8 16.5 6 3.9 56.9 6 3.5 4.6 6 0.9
EDV, End-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; SDI, systolic dyssynchrony index; 3D, three-dimensional. Data are expressed as mean 6 SD. *P < .05, APC versus EC. † P < .05, all patients versus controls.
DISCUSSION The present study shows that Fontan patients have impaired systemic ventricular deformation, ventricular mechanical dyssynchrony, abnormal atrial function, and evidence of atrial electromechanical coupling delay. Additionally, we found that patients with APC have worse atrial and ventricular mechanics compared with those with EC. Possible abnormal atrioventricular interaction in patients is further suggested by associations between indices of atrial deformation and systemic ventricular early diastolic SR. To our knowledge, this is the first study to systemically evaluate and compare atrial and ventricular mechanics between two different Fontan-type procedures. Previous studies have focused primarily on mechanics of the functional single ventricle in the Fontan circulation. We and others have shown previously reduced systolic and diastolic myocardial tissue velocities,21,22 decreased segmental and global systolic strain,16,23 increased myocardial performance index,24 and evidence of mechanical dyssynchrony16 in Fontan patients, mainly in those with EC. The abnormal ventricular mechanics found in our patient cohorts therefore agree with those reported. What has not been clearly documented previously, however, is the finding in this study of worse systolic and diastolic ventricular mechanics in patients with APC compared with those with EC. The smaller ventricular volumes found in patients with APC suggests that differences in ventricular preload between the two patient subgroups might explain their differences in ventricular mechanics. Greater power loss and reduced flow in the dilated right atrium in
APC, in contrast to the hemodynamically more efficient noncomplaint EC,12,13,14 may result in more severe underfilling of the systemic ventricle. Chronic severe reduction of preload may trigger a vicious cycle of ‘‘disuse hypofunction’’ of the systemic ventricle characterized by ventricular remodeling, reduction of compliance, further impairment of ventricular filling, and eventually reduction in cardiac output.1 The greater E/e ratio, shown to correlate well with ventricular end-diastolic pressure in functional single ventricles,25 found in our APC subgroup further attests to the worse ventricular compliance with aggravation of ventricular underfilling. Other factors may potentially also account for the observed differences in ventricular mechanics between the two patient subgroups. With changing practice in pediatric cardiac surgery, APC has become an obsolete procedure. Notwithstanding, there are patients with APC who are currently followed up in the adult congenital heart disease clinics. The confounding influence of differences in the era when the surgery was performed, age at study, and follow-up duration of the two subgroups on ventricular mechanics cannot therefore be excluded. Furthermore, the prevalence of systemic left ventricular morphology is greater in the APC group. Nonetheless, better rather than worse functioning of a morphologic left ventricle has been described in the setting of functionally single ventricles.26,27 Notwithstanding the wealth of data on the function of the single ventricle after Fontan-type procedures, little is known of the function and mechanics of the pulmonary venous atrium. Atrial function is of particular relevance in Fontan patients given the impaired diastolic filling and evidence of progressive worsening with time of ventricular
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Figure 3 Comparisons of ventricular strain and SR between patients and controls (left) and between patients with APC and those with EC. C, circumferential; L, longitudinal; R, radial. *P < .05, patients versus controls; #P < .05, APC versus EC. compliance.28 Data on atrial function in Fontan patients are scarce. Stines et al.29 reported indirect evidence of abnormal atrial properties on the basis of findings of reduced late diastolic annular and atrioventricular valvar inflow velocities and increased Doppler-derived atrial filling fraction in Fontan patients after total cavopulmonary connections. On the other hand, Khoo et al.18 directly interrogated atrial deformation using speckle-tracking echocardiography across the different stages of univentricular repair. They found persistently decreased atrial compliance, reduced early diastolic emptying, and increased reliance on active atrial contraction for ventricular filling both before and after Fontan palliation by total cavopulmonary connection. Our findings of reduced atrial strain and SRs at different phases of the cardiac cycle suggest impaired atrial pump, conduit, and reservoir function and agree with those reported previously.18 Additionally, our finding of increased atrial negative/global strain ratios in patients is also consistent with an increased reliance on active atrial contraction for ventricular filling.
The finding of atrial electromechanical delay, which may affect atrial pump function,19 in our patients warrants further comments. Left atrial electromechanical delay has been described in patients with mitral stenosis30 and nonischemic dilated cardiomyopathy31 and been shown to predict development of atrial fibrillation.32 In adults after Fontan-type procedures, atrial arrhythmias have been reported to occur with a prevalence ranging from 11% to 60%.7,33,34 Whether delay in electromechanical coupling in Fontan patients predicts the development of atrial arrhythmias requires further investigations. Although the mechanism of altered atrial function and electromechanical delay in our patients remains to be clarified, potential contributing factors may include previous atriotomy and fibrotic atrial wall. The finding of worse atrial mechanics and electromechanical delay in patients with APC than those with EC is intriguing. Gross dilation of right atrium in the setting of APC with distortion of interatrial septum may be a possible culprit, although this remains speculative. Atrioventricular diastolic interaction is
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Table 3 Regional systemic ventricular longitudinal strain Variable
Left-sided free wall Basal Middle Apical Right-sided free wall in patients/ ventricular septum in controls Basal Middle Apical
APC (n = 13)
EC (n = 15)
All patients (n = 28)
Controls (n = 26)
16.8 6 6.9 13.8 6 5.5* 15.0 6 5.7
20.9 6 4.9 18.7 6 4.3 17.0 6 8.0
19.0 6 6.2† 16.4 6 5.4† 16.1 6 6.9†
22.6 6 4.4 21.0 6 2.8 21.2 6 5.3
11.2 6 4.6* 14.0 6 4.7* 19.1 6 7.2
24.7 6 6.9 21.4 6 5.1 17.2 6 6.1
18.4 6 9.0 18.0 6 6.1† 18.1 6 6.6†
20.9 6 2.1 22.4 6 1.6 23.9 6 4.5
Data are expressed as mean 6 SD. *P < .05, APC versus EC. † P < .05, all patients versus controls.
Figure 4 Scatterplots showing correlations between ventricular ejection fraction (EF) and parameters of ventricular deformation (top) and between ventricular early diastolic SR (SRe) and indices of atrial deformation (bottom). Blue circles represent patients with APC, and red circles represent patients with EC. SDI, Systolic dyssynchrony index. further reflected in our patients by the association between atrial strain, SRcon, and electromechanical coupling with systemic ventricular early diastolic SR. Increased reliance on atrial contraction as aforementioned in Fontan patients may hence represent a compensatory mechanism. Nonetheless, the existence of atrial dysfunction shown in this and in previous studies18,29 suggests that the compensation is likely to be suboptimal, probably more so in patients with APC. The amount of native atrial tissue incorporated into the Fontan circuit differs among patients with APC and those with EC. Chronic and progressive dilation of the greater amount of atrial tissue in APC may cause greater fluid energy losses, an increase in the energy required to propel forward flow of blood to the pulmonary arteries,12,13,14 and impaired ventricular filling as discussed above and consequently may affect exercise capacity. In symptomatic patients with failing
APCs, conversion to an EC Fontan circuit has been shown to improve functional class and peak oxygen uptake during exercise.9,10,11 The latter has been proposed to reflect an improvement in cardiac stroke volume.11 Indeed in our patients with EC, the greater ventricular volumes imply better ventricular filling, which may in turn be related to the greater magnitude and rate of atrial deformation and shorter time needed for electromechanical coupling. A prospective study is required, however, to clearly define the changes in atrial and ventricular mechanics with Fontan conversion. Several limitations to this study warrant comments. First, we did not include patients with lateral tunnels, because EC has been the main approach for total cavopulmonary connection at our institution. Nonetheless, systemic venous flow dynamics are similar between the two approaches.
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Figure 5 Comparisons of atrial strain and SR between patients and controls (left) and between patients with APC and those with EC. SRac, Atrial active contractile SR; SRres, atrial reservoir SR. *P < .05, patients versus controls; #P < .05, APC versus EC. Second, as alluded to earlier, the prevalence of systemic left ventricular morphology was greater in the APC group. Nonetheless, given the documented better functioning of a morphologic left ventricle in the setting of functionally single ventricles,26,27 our findings of worse ventricular deformation in the APC subgroup may suggest an intrinsic hemodynamic flaw of the APC circuit. Third, in the present study we used four-dimensional analysis software from TomTec to evaluate the functional ventricle. Our group has previously applied this technique to assess left ventricular mechanics in patients with tricuspid atresia.16 Although Khoo et al.35 reported only a 50% success of applying the four-dimensional right ventricular analysis software to image the subpulmonary and systemic right ventricles, recent studies have reported greater success using TomTec four-dimensional echocardiographic view to measure volumes of functional single ventricles with a right ventricular morphology.36,37 Fourth, tissue Doppler–derived myocardial velocities of regional segments might have been influenced by their close proximity to rudimentary cardiac chambers. Nonetheless, additional assessment of global ventricular strain and SR by speckle-tracking would probably minimize the errors of regional myocardial assessment. Finally, this was a cross-sectional study, and further longitudinal studies to track the changes in atrial and ventricular mechanics before and after Fontan conversion are warranted.
CONCLUSIONS Atrial and ventricular mechanics are impaired in patients after Fontantype operations, which is worse with APC than EC.
REFERENCES 1. Gewillig M. The Fontan circulation. Heart 2005;91:839-46. 2. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971;26: 240-8. 3. de Leval MR, Kilner P, Gewilliq M, Bull C. Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex Fontan operations. Experimental studies and early clinical experience. J Thorac Cardiovasc Surg 1988;96:682-95. 4. Bridges ND, Lock JE, Castaneda AR. Baffle fenestration with subsequent transcatheter closure. Modification of the Fontan operation for patients at increased risk. Circulation 1990;82:1681-9. 5. Black MD, van Son JA, Haas GS. Extracardiac Fontan operation with adjustable communication. Ann Thorac Surg 1995;60:716-8. 6. d’Udekem Y, Iyengar AJ, Cochrane AD, Grigg LE, Ramsay JM, Wheaton GR, et al. The Fontan procedure: contemporary techniques have improved long-term outcomes. Circulation 2007;116:I157-64. 7. Stephenson EA, Lu M, Berul CI, Etheridge SP, Idriss SF, Margossian R, et al. Arrhythmias in a contemporary Fontan cohort: prevalence and clinical associations in a multicenter cross-sectional study. J Am Coll Cardiol 2010; 56:890-6. 8. Van Son JA, Mohr FW, Hambsch J, Schneider P, Hess H, Haas GS. Conversion of atriopulmonary or lateral atrial tunnel cavopulmonary anastomosis to extracardiac conduit Fontan modification. Eur J Cardiothorac Surg 1999;15:150-7. 9. Agnoletti G, Borghi A, Vignati G, Crupi GC. Fontan conversion to total cavopulmonary connection and arrhythmis ablation: clinical and functional results. Heart 2003;89:193-8. 10. Sheikh AM, Tang AT, Roman K, Baig K, Mehta R, Morgan J, et al. The failing Fontan circulation: successful conversion of atriopulmonary connections. J Thorac Cardiovasc Surg 2004;128:60-6. 11. Giardini A, Pace Napoleone C, Specchia S, Donti A, Formigari R, Oppido G, et al. Conversion of atriopulmonary Fontan to extracardiac
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total cavopulmonary connection improves cardiopulmonary function. Int J Cardiol 2006;113:341-4. 12. Greenberg SB, Morrow WR, Imamura M, Drummond-Webb J. Magnetic resonance flow analysis of classic and extracardiac Fontan procedures: the seesaw sign. Int J Cardiovasc Imaging 2004;20:397-405. 13. Van Haesdonck JM, Mertens L, Sizaire R, Montas G, Purnode B, Daenen W, et al. Comparison by computerized numeric modeling of energy losses in different Fontan connections. Circulation 1995;92: 322-6. 14. Low HT, Chew YT, Lee CN. Flow studies on atriopulmonary and cavopulmonary connections of the Fontan operations for congenital heart defects. J Biomed Eng 1993;15:303-7. 15. Ohuchi H, Kagisaki K, Miyazaki A, Kitano M, Yazaki S, Sakaguchi H, et al. Impact of the evolution of the Fontan operation on early and late mortality: a single-center experience of 405 patients over 3 decades. Ann Thorac Surg 2011;92:1457-67. 16. Ho PK, Lai CT, Wong SJ, Cheung YF. Three-dimensional mechanical dyssynchrony and myocardial deformation of the left ventricle in patients with tricuspid atresia after Fontan procedure. J Am Soc Echocardiogr 2012;25:393-400. 17. Kutty S, Padiyath A, Li L, Peng Q, Rangamani S, Schuster A, et al. Functional maturation of left and right atrial systolic diastolic performance in infants, children, and adolescents. J Am Soc Echocardiogr 2013;26: 398-409. 18. Khoo NS, Smallhorn JF, Kaneko S, Kutty S, Altamirano L, Tham EB. The assessment of atrial function in single ventricle hearts from birth to Fontan: a speckle-tracking study by using strain and strain rate. J Am Soc Echocardiogr 2013;26:756-64. 19. Todaro MC, Choudhuri I, Belohlavek M, Jahangir A, Careri S, Oreto L, et al. New echocardiographic techniques for evaluation of left atrial mechanics. Eur Heart J Cardiovasc Imaging 2012;13:973-84. 20. Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ. Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation 2005;112:992-1000. 21. Bassareo PP, Tumbarello R, Piras A, Mercuro G. Evaluation of regional myocardial function by Doppler tissue imaging in univentricular heart after successful Fontan repair. Echocardiography 2010;27:702-8. 22. Hershenson JA, Zaidi AN, Texter KM, Moiduddin N, Stefaniak CA, Hayes J, et al. Differences in tissue Doppler imaging between single ventricles after the Fontan operation and normal controls. Am J Cardiol 2010;106:99-103. 23. Singh GK, Cupps B, Pasque M, Woodard PK, Holland MR, Ludomirsky A. Accuracy and reproducibility of strain by speckle-tracking in pediatric subjects with normal heart and single ventricular physiology: a twodimensional speckle-tracking echocardiography and magnetic resonance imaging correlative study. J Am Soc Echocardiogra 2010;23:1143-52. 24. Myers KA, Leung MT, Potts MT, Potts JE, Sandor GGS. Noninvasive assessment of vascular function and hydraulic power and efficiency in pediatric Fontan patients. J Am Soc Echocardiogr 2013;26:1221-7.
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25. Menon SC, Gray R, Tani LY. Evaluation of ventricular filling pressures and ventricular function by Doppler echocardiography in patients with functional single ventricle: correlation with simultaneous cardiac catheterization. J Am Soc Echocardiogr 2011;24:1220-5. 26. Petko C, Hansen JH, Scheewe J, Rickers C, Kramer HH. Comparison of longitudinal myocardial deformation and dyssynchrony in children with left and right ventricular morphology after the Fontan operation using two-dimensional speckle-tracking. Congenit Heart Dis 2012;7:16-23. 27. Kaneko S, Khoo NS, Smallhorn JF, Tham EB. Single right ventricles have impaired systolic and diastolic function compared to those of left ventricular morphology. J Am Soc Echocardiogr 2012;25:1222-30. 28. Cheung YF, Penny DJ, Redington AN. Serial assessment of left ventricular diastolic function after Fontan procedure. Heart 2000;83:420-4. 29. Stines JR, Hershenson JA, Hayes J, Stefaniak CA, Texter KM, Zaidi AN, et al. Echocardiographic assessment of atrial properties in single ventricles vs. normal controls. Congenit Heart Dis 2011;6:247-52. 30. Ozer N, Yavuz B, Can I, Atalar E, Aksoyek S, Ovunc K, et al. Doppler tissue evaluation of intra-atrial and interatrial electromechanical delay and comparison with P-wave dispersion in patients with mitral stenosis. J Am Soc Echocardiogr 2005;18:945-8. 31. Pala S, Tigen K, Karaahmet T, Dundar C, Kilicgedik A, Guler A, et al. Assessment of atrial electromechanical delay by tissue Doppler echocardiography in patients with nonischemic dilated cardiomyopathy. J Electrocardiol 2010;43:344-50. 32. Cho GY, Jo SH, Kim MK, Kim HS, Park WJ, Choi YJ, et al. Left atrial dyssynchrony assessed by strain imaging in predicting future development of atrial fibrillation in patients with heart failure. Int J Cardiol 2009;134: 336-41. 33. Giannakoulas G, Dimopoulos K, Yuksel S, Inuzuka R, PijuanDomenech A, Hussain W, et al. Atrial tachyarrhythmias late after Fontan operation are related to increase in mortality and hospitalization. Int J Cardiol 2012;157:221-6. 34. Miyazaki A, Sakaguchi H, Ohuchi H, Yamada O, Kitano M, Yazaki S, et al. The clinical course and incidence of supraventricular tachyarrhythmias after extra-cardiac conduit Fontan procedures in relation to an atrial situs. Circ J 2011;75:413-20. 35. Khoo NS, Young A, Occleshaw C, Cowan B, Zeng ISL, Gentles TL. Assessments of right ventricular volume and function using threedimensional echocardiography in older children and adults with congenital heart disease: comparison with cardiac magnetic resonance imaging. J Am Soc Echocardiogr 2009;22:1279-88. 36. Soriano BD, Hoch M, Ithuralde A, Geva T, Powell AJ, Kussman BD, et al. Matrix-array 3-dimensional echocardiographic assessment of volumes, mass, and ejection fraction in young pediatric patients with a functional single ventricle: a comparison study with cardiac magnetic resonance. Circulation 2008;117:1842-8. 37. Marx GR, Shirali G, Levine JC, Guey LT, Cnota JF, Baffa JM, et al. A multi-center study comparing shunt type in the Norwood procedure for single-ventricle lesions: 3-dimensional echocardiographic analysis. Circ Cardiovascu Imaging 2013;6:934-42.
Background: Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures, which may affect atrial and ventricular filling. The aim of this study was to test the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, atriopulmonary connection (APC) and extracardiac conduit, which have distinctly different systemic venous hemodynamics. Methods: This was a cross-sectional, case-control study of 28 Fontan patients (13 with APC, 15 with extracardiac conduit) aged 19.8 6 6.5 years and 26 healthy controls. Atrial and systemic ventricular myocardial deformation was determined using speckle-tracking echocardiography, while ventricular volumes and systolic dyssynchrony index were assessed using three-dimensional echocardiography. Results: Compared with controls, patients had significantly lower values of global ventricular longitudinal, circumferential, and radial systolic strain in all three directions, reduced systolic and early diastolic strain rates (SRs) in more than one dimension, lower ejection fractions, and worse ventricular dyssynchrony. For atrial deformation, patients had lower global and positive strain and conduit and reservoir SRs and delayed electromechanical coupling. Among patients, those with APC had significantly lower ventricular longitudinal strain and early diastolic SRs, worse ventricular dyssynchrony, and reduced atrial positive and negative strain and conduit and active contractile SRs. Atrial global strain (r = 0.60, P = .001) and conduit SR (r = 0.49, P = .008) correlated positively with systemic ventricular early diastolic SR. Conclusions: Atrial and ventricular mechanics are impaired in patients after Fontan-type operation, which is worse with APC than extracardiac conduit. (J Am Soc Echocardiogr 2014;-:---.) Keywords: Atrium, Ventricle, Cardiac mechanics, Speckle-tracking echocardiography, Fontan procedure
Fontan-type procedures involve palliative surgery for patients with functional single ventricles.1 Since the first report of success in 1971,2 the initially described operation has undergone several modifications, from atriopulmonary connection (APC) through lateral tunnel to extracardiac conduit (EC) procedures.3,4,5 Long-term complications of Fontan-type procedures, in particular in patients with APC, are well documented.1,6,7 These include atrial arrhythmias, venous thromboembolism, compression of pulmonary veins, protein-losing enteropathy, atrioventricular valvar regurgitation, and progressive systemic ventricular dysfunction. Notwithstanding
From the Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. Dr Li is a research fellow from The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China. Reprint requests: Yiu-fai Cheung, MD, Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.01.027
the relatively smaller number of patients with APC compared with those with lateral tunnel or EC in the present era, these patients are frequently encountered among patients who had functional single ventricles palliated in an earlier surgical era with longer term followup. In these symptomatic patients, conversion of the Fontan circuit from APC to EC has been reported to improve functional class, reverse protein-losing enteropathy, and enable better control of refractory cardiac arrhythmias,8,9,10,11 although these outcomes are not guaranteed. The atrial and ventricular performance in the two different types of Fontan procedures, however, is unclear. Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures. In APC, progressive dilation of the right atrium causes greater fluid energy losses and increases the energy required to move blood from the caval vein to the pulmonary arteries. By contrast, flow in total cavopulmonary connection and EC is hemodynamically more organized and uniform and hence more efficient.12,13,14 Differences in systemic venous flow dynamics in various Fontan-type procedures may have implications for atrial and ventricular filling and mechanics. In the present study, we tested the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, APC and EC (Figure 1), which have distinctly different systemic venous hemodynamics. We further explored potential relationships between atrial and ventricular mechanics in Fontan patients. 1
2 Li et al
Abbreviations
APC = Atriopulmonary connection
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METHODS Subjects
This was a cross-sectional, casecontrol echocardiographic study of patients who had undergone SR = Strain rate Fontan-type procedures and healthy, age-matched controls. SRcon = Atrial conduit strain Of the 32 patients recruited, rate three with APC were excluded because of a loss of sinus rhythm, and one with EC was excluded because of a suboptimal acoustic window. A total of 28 patients, 13 with APC and 15 with EC, were hence included in the final analysis. The following data were retrieved from the case notes: cardiac diagnosis, age at surgery, history of shunt operation, type of Fontan procedure, existence of fenestration, history of cardiac arrhythmias, current medications, and duration of follow-up since operation. Twenty-six healthy subjects were recruited as controls. These included healthy volunteers; subjects identified in the cardiac clinic with functional murmurs, nonspecific chest pain, and palpitation without an organic cause; and healthy siblings of patients. Body weight and height were measured, and body mass index and surface area were calculated accordingly. In patients, pulse oximetry and electrocardiography were performed. All subjects underwent echocardiographic assessment as described below. The institutional review board approved the study, and all adult subjects and parents of minors gave informed written consent. EC = Extracardiac conduit
Doppler Echocardiographic Assessment Echocardiographic assessments were performed using the Vivid 7 ultrasound system (GE Vingmed Ultrasound AS, Horten, Norway). The averages of echocardiographic indices measured from three cardiac cycles were obtained for statistical analysis. Color Doppler flow mapping was performed to assess semiquantitatively the degree of systemic atrioventricular valvar regurgitation.15 Regurgitation was graded as trivial to mild if the regurgitant jet did not cross two thirds of the systemic atrium, moderate if beyond, and severe if the jet reached the posterior wall. Pulsed-wave Doppler examination was performed to obtain the systemic atrioventricular valvar early (E) and late (A) diastolic inflow velocities and E/A ratio. Tissue spectral Doppler imaging was performed with the sample volume positioned at the base of the right-sided and left-sided free wall–atrioventricular valve annular junction in patients and at the ventricular septum and left ventricular free wall–mitral valve annular junction in controls to obtain the following indices: the peak myocardial velocities at systole (s), early diastole (e), and late diastole (a); the e/a ratio; and the E/e ratio. Assessment of Ventricular Mechanics Mechanics of the systemic ventricle were assessed using twodimensional speckle-tracking echocardiography.16 Two-dimensional echocardiographic recordings were analyzed offline using twodimensional strain software (EchoPAC; GE Vingmed Ultrasound AS). Deformation of the dominant functional single ventricle in Fontan patients and the left ventricle in control subjects was assessed (Figure 2). Global systemic ventricular longitudinal systolic strain and systolic and diastolic strain rate (SR) were determined from the apical four-chamber view, while circumferential and radial strain and SR were assessed from the midventricular short-axis. The right-sided and left-sided ventricular free walls for functional single ventricle
and left ventricular free wall and ventricular septum in structurally normal hearts were divided respectively into three segments (basal, middle, and apical) for quantification of regional longitudinal strain. Assessment of Atrial Mechanics Mechanics of the pulmonary venous atrial chamber were determined also using speckle-tracking echocardiography, with tracing of the entire atrial contours.17 Left atrial deformation was assessed in patients with APC and in controls, while the two atria were regarded as a common atrium in patients with EC because these patients either had right atrial isomerism with almost complete deficiency of atrial septum or had undergone atrial septectomy. The onset of the P wave was used as the reference point for the determination of peak positive strain, peak negative strain, and total strain (Figure 2). The atrial active contractile SR, atrial conduit SR (SRcon), and reservoir SR, were then derived accordingly.18 Atrial electromechanical coupling was evaluated by measuring the time from onset of the P wave to peak negative strain19 and normalized to the square root of the RR interval. Real-Time Three-Dimensional Echocardiography Full-volume ventricular data sets were acquired from the apical fourchamber view using the matrix-array transducer and analyzed offline with commercial four-dimensional analysis software (TomTec Imaging Systems, Unterschleissheim, Germany). The endocardial borders were traced and used to derive the end-systolic and end-diastolic volumes and ejection fraction. The systolic dyssynchrony index of the systemic ventricle was calculated as the standard deviation of time taken to reach minimum regional volume for each of the 16 ventricular segments as a percentage of the cardiac cycle.20 Statistical Analysis All data are expressed as mean 6 SD. Absolute values of strain and SR were used to facilitate interpretation. Ventricular volumes were indexed to body surface area. Intraobserver and interobserver variability was assessed in 10 patients and reported as the coefficients of variation, calculated by dividing the standard deviation of differences between measurements by the mean and expressed as a percentage. Differences in demographic, clinical, and echocardiographic parameters between groups were compared using unpaired Student’s t tests, Fisher’s exact tests, and c2 test as appropriate. Pearson’s correlation analysis was used to study relationships between atrial and ventricular deformation parameters and ejection fraction. P values < .05 were considered statistically significant. All statistical analyses were performed using SPSS version 16.0 (SPSS, Inc, Chicago, IL).
RESULTS Subjects The 28 patients (19 men) aged 19.8 6 6.5 years were studied 13.4 6 6.2 years after undergoing Fontan-type procedures. Situs solitus was present in 14 patients, while an abnormal situs was present in the other 14 patients (situs inversus in seven, right atrial isomerism in six, and left atrial isomerism in one). Ventricular-arterial connection was single outlet with pulmonary atresia in 14 patients, concordant in seven, discordant in three, double outlet from the right ventricle in three, and double outlet from the left ventricle in one. Before
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Li et al 3
Figure 1 Illustrations of (A) APC and (B) EC Fontan procedures. Ao, aorta; IVC, inferior vena cava; RA, right atrium; RPA, right pulmonary artery; SVC, superior vena cava.
Figure 2 Representative ventricular and atrial strain and SR curves in a patient with APC, a patient with with EC, and a control subject. Peak negative (white arrow) and positive (yellow arrow) atrial strain is highlighted. SRa, Ventricular late diastolic SR; SRac, atrial active contractile SR; SRe, ventricular early diastolic SR; SRres, atrial reservoir SR; SRs, ventricular systolic SR.
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Table 1 Demographic data and clinical parameters of patients after APC and EC Fontan procedures Variable
Age (y) Age at Fontan procedure (y) Follow-up duration (y) Male/female Body weight (kg) Body height (cm) Body mass index (kg/m2) History of shunt insertion (yes/no) History of pulmonary arterial banding (yes/no) Fenestration (yes/no or closed by device) Ventricular morphology (left/ right/indeterminate) Oxygen saturation (%) QRS duration (msec)
APC (n = 13)
EC (n = 15)
P
23.7 6 6.3 16.4 6 4.5 .002* 5.0 6 5.0 7.8 6 2.9 .08 18.8 6 3.1 8.5 6 3.6 <.001* 8/5 11/4 .51 59.3 6 13.2 47.5 6 13.8 .03* 163.3 6 8.1 155.7 6 10.9 .049* 22.1 6 3.4 19.3 6 4.5 .08 6/7 11/4 .14 1/12
1/14
.92
3/10
6/9
.34
11/1/1
4/8/3
<.001*
94.1 6 2.6 93.6 6 4.6 111.0 6 23.0 114.5 6 14.7
.74 .62
Data are expressed as mean 6 SD or as numbers. *Statistically significant.
univentricular palliation, 17 patients underwent modified BlalockTaussig shunt procedures and two underwent pulmonary arterial banding. History of atrial tachycardia or flutter was present in 6 patients. Twenty-two patients were taking warfarin and two were receiving aspirin as anticoagulation prophylaxis. Five patients were receiving heart failure medications, of whom four were put on enalapril, two on digoxin, and two on diuretics. Three patients were taking bblockers. All patients were in sinus rhythm, and none had pacemakers implanted at the time of the study. Age (19.8 6 6.5 vs 19.6 6 5.6 years, P = .92), sex distribution (16 male and 10 female vs 19 male and nine female, P = .63), body weight (53.0 6 14.6 vs 56.0 6 10.6 kg, P = .38), and body mass index (20.6 6 4.2 vs 20.4 6 5.5 kg/m2, P = .88) were similar between patients and controls. Demographic and clinical parameters of the two groups of Fontan patients are shown in Table 1. Because of evolution of the Fontan-type procedure with time, patients with APC were significantly older, followed up for a longer duration, and had larger body sizes compared with those with EC (P < .05 for all). Patients with APC were more likely to have systemic ventricles of left ventricular morphology, while those with EC were more likely to have a right or indeterminate ventricular morphology (P < .001).
Doppler and Three-Dimensional Echocardiographic Assessment Doppler color flow mapping showed trivial to mild degrees of atrioventricular valvar regurgitation in 22 patients and none in six patients. Table 2 summarizes the Doppler and three-dimensional echocardiographic parameters in patients and controls. Compared with controls, patients had significantly lower systemic atrioventricular E velocities and E/A ratios; reduced left-sided ventricular free wall s, e, and a velocities and e/a ratios; and reduced right-sided s and e velocities. The E/e ratios of both the left-sided and right-sided ventricular walls were greater in patients than controls. Comparisons between subgroups of patients revealed that patients with APC had significantly lower e velocities and e/a ratios of the
right-sided ventricular free wall and greater E/e ratios than those with EC. Regarding three-dimensional echocardiographic parameters, patients had significantly greater end-systolic volumes, lower ejection fractions, and greater systolic mechanical dyssynchrony of the systemic ventricle. Within patient groups, patients with APC had significantly smaller end-systolic and end-diastolic volumes, lower ejection fractions, and greater dyssynchrony of the systemic ventricle compared with those with EC. Ventricular Mechanics The coefficients of variation for intraobserver and interobserver measurement of ventricular longitudinal strain were 5.9% and 8.5%, for circumferential strain were 7.8% and 12.5%, and for radial strain were 13.0% and 15.2%, respectively. Figure 3 shows systemic ventricular global strain and SR in patients and controls. Compared with controls, Fontan patients had significantly lower global systolic longitudinal, radial, and circumferential strain. Regional longitudinal strain assessment showed that strain values of all but one segment were significantly lower values in patients than controls (Table 3). Furthermore, patients had significantly lower ventricular systolic longitudinal and circumferential SRs and early diastolic longitudinal and radial SRs than controls, although their late diastolic circumferential SRs appeared greater. Comparisons between patient subgroups revealed that patients with APC had significantly lower longitudinal systolic strain and early diastolic SRs (Figure 3) and regional strain (Table 3) than those with EC. Among patients, systemic ventricular ejection fraction correlated positively with global systolic longitudinal strain (r = 0.58, P = .001) and global systolic radial strain (r = 0.60, P = .001) and negatively with systolic dyssynchrony index (r = 0.55, P = .002) (Figure 4, top). Atrial Mechanics The coefficients of variation for intraobserver and interobserver measurement of atrial total strain were 5.6% and 7.0%, for atrial active contractile SR were 8.1% and 9.2%, for SRcon were 5.7% and 10.5%, and for atrial reservoir SR were 7.6% and 11.1%, respectively. Comparisons of global atrial strain and SRs between patients and controls are shown in Figure 5. Compared with controls, patients had significantly lower atrial global and positive strain, atrial reservoir SR, and SRcon. Comparisons of the patient subgroups showed that patients with APC had significantly lower negative, positive, and global atrial strain and SRcon and atrial active contractile SR. To identify the role of active atrial contraction during atrial deformation, the negative/global strain ratio was calculated.18 This strain ratio was significantly greater in patients than controls (0.52 6 0.12 vs 0.3 6 0.06, P < .001) but similar between patients with APC and those with EC (0.53 6 0.15 vs 0.51 6 0.1, P = .81). Atrial electromechanical coupling was significantly longer in patients than controls (194 6 38 vs 158 6 19 msec, P < .001). Additionally, the coupling also tended to be longer in patients with APC than those with EC (206 6 38 vs 183 6 36 msec, P = .11). Among patients, ventricular early diastolic SR correlated positively with global strain (r = 0.60, P = .001) and atrial SRcon (r = 0.49, P = .008) (Figure 4, bottom). For the entire cohort, these correlations were even stronger (r = 0.77, P < .001, and r = 0.70, P < .001, respectively). Additionally, the timing of atrial electromechanical coupling was found to correlate negatively with ventricular early diastolic SR (r = 0.39, P = .004).
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Table 2 Doppler and three-dimensional echocardiographic parameters Variable
Pulsed Doppler of systemic atrioventricular inflow E wave (cm/sec) A wave (cm/sec) E/A ratio Doppler tissue imaging Left-sided free wall s (cm/sec) e (cm/sec) a (cm/sec) e/a ratio E/e ratio Right-sided free wall in patients/ventricular septum in controls s (cm/sec) e (cm/sec) a (cm/sec) e/a ratio E/e ratio 3D echocardiography Indexed EDV (mL/m2) Indexed ESV (mL/m2) EF (%) SDI (%)
APC (n = 13)
EC (n = 15)
All patients (n = 28)
Controls (n = 26)
58.2 6 11.0 42.8 6 11.8 1.5 6 0.5
64.5 6 17.8 51.5 6 23.0 1.5 6 0.6
61.6 6 15.1† 47.5 6 18.9 1.5 6 0.5†
87.1 6 12.8 40.5 6 10.3 2.3 6 0.8
7.6 6 2.8 9.9 6 4.5 6.2 6 1.5 1.6 6 0.8 8.6 6 7.9
6.4 6 1.8 10.2 6 3.4 6.4 6 1.3 1.7 6 0.6 7.5 6 5.4
7.0 6 2.3† 9.9 6 3.9† 6.3 6 1.4† 1.6 6 0.7† 7.4 6 4.7†
11.9 6 2.1 18.3 6 2.5 7.1 6 1.2 2.6 6 0.6 4.8 6 0.8
5.2 6 1.4 4.3 6 1.4* 5.2 6 2.2 0.9 6 0.3* 15.3 6 6.6*
5.6 6 0.8 8.3 6 2.5 5.7 6 1.3 1.5 6 0.7 9.0 6 5.5
5.4 6 1.1† 6.4 6 2.9† 5.3 6 2.0 2.4 6 6.4 11.9 6 6.7†
7.8 6 1.5 12.7 6 2.0 6.1 6 1.4 2.2 6 0.4 7.0 6 1.2
33.1 6 14.0* 21.0 6 12.8* 38.6 6 11.8 9.2 6 2.4*
57.0 6 22.3 33.3 6 13.9 41.5 6 6.6 6.2 6 1.4
45.9 6 22.2 27.6 6 14.6† 40.1 6 9.3† 7.6 6 2.4†
38.3 6 8.8 16.5 6 3.9 56.9 6 3.5 4.6 6 0.9
EDV, End-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; SDI, systolic dyssynchrony index; 3D, three-dimensional. Data are expressed as mean 6 SD. *P < .05, APC versus EC. † P < .05, all patients versus controls.
DISCUSSION The present study shows that Fontan patients have impaired systemic ventricular deformation, ventricular mechanical dyssynchrony, abnormal atrial function, and evidence of atrial electromechanical coupling delay. Additionally, we found that patients with APC have worse atrial and ventricular mechanics compared with those with EC. Possible abnormal atrioventricular interaction in patients is further suggested by associations between indices of atrial deformation and systemic ventricular early diastolic SR. To our knowledge, this is the first study to systemically evaluate and compare atrial and ventricular mechanics between two different Fontan-type procedures. Previous studies have focused primarily on mechanics of the functional single ventricle in the Fontan circulation. We and others have shown previously reduced systolic and diastolic myocardial tissue velocities,21,22 decreased segmental and global systolic strain,16,23 increased myocardial performance index,24 and evidence of mechanical dyssynchrony16 in Fontan patients, mainly in those with EC. The abnormal ventricular mechanics found in our patient cohorts therefore agree with those reported. What has not been clearly documented previously, however, is the finding in this study of worse systolic and diastolic ventricular mechanics in patients with APC compared with those with EC. The smaller ventricular volumes found in patients with APC suggests that differences in ventricular preload between the two patient subgroups might explain their differences in ventricular mechanics. Greater power loss and reduced flow in the dilated right atrium in
APC, in contrast to the hemodynamically more efficient noncomplaint EC,12,13,14 may result in more severe underfilling of the systemic ventricle. Chronic severe reduction of preload may trigger a vicious cycle of ‘‘disuse hypofunction’’ of the systemic ventricle characterized by ventricular remodeling, reduction of compliance, further impairment of ventricular filling, and eventually reduction in cardiac output.1 The greater E/e ratio, shown to correlate well with ventricular end-diastolic pressure in functional single ventricles,25 found in our APC subgroup further attests to the worse ventricular compliance with aggravation of ventricular underfilling. Other factors may potentially also account for the observed differences in ventricular mechanics between the two patient subgroups. With changing practice in pediatric cardiac surgery, APC has become an obsolete procedure. Notwithstanding, there are patients with APC who are currently followed up in the adult congenital heart disease clinics. The confounding influence of differences in the era when the surgery was performed, age at study, and follow-up duration of the two subgroups on ventricular mechanics cannot therefore be excluded. Furthermore, the prevalence of systemic left ventricular morphology is greater in the APC group. Nonetheless, better rather than worse functioning of a morphologic left ventricle has been described in the setting of functionally single ventricles.26,27 Notwithstanding the wealth of data on the function of the single ventricle after Fontan-type procedures, little is known of the function and mechanics of the pulmonary venous atrium. Atrial function is of particular relevance in Fontan patients given the impaired diastolic filling and evidence of progressive worsening with time of ventricular
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Figure 3 Comparisons of ventricular strain and SR between patients and controls (left) and between patients with APC and those with EC. C, circumferential; L, longitudinal; R, radial. *P < .05, patients versus controls; #P < .05, APC versus EC. compliance.28 Data on atrial function in Fontan patients are scarce. Stines et al.29 reported indirect evidence of abnormal atrial properties on the basis of findings of reduced late diastolic annular and atrioventricular valvar inflow velocities and increased Doppler-derived atrial filling fraction in Fontan patients after total cavopulmonary connections. On the other hand, Khoo et al.18 directly interrogated atrial deformation using speckle-tracking echocardiography across the different stages of univentricular repair. They found persistently decreased atrial compliance, reduced early diastolic emptying, and increased reliance on active atrial contraction for ventricular filling both before and after Fontan palliation by total cavopulmonary connection. Our findings of reduced atrial strain and SRs at different phases of the cardiac cycle suggest impaired atrial pump, conduit, and reservoir function and agree with those reported previously.18 Additionally, our finding of increased atrial negative/global strain ratios in patients is also consistent with an increased reliance on active atrial contraction for ventricular filling.
The finding of atrial electromechanical delay, which may affect atrial pump function,19 in our patients warrants further comments. Left atrial electromechanical delay has been described in patients with mitral stenosis30 and nonischemic dilated cardiomyopathy31 and been shown to predict development of atrial fibrillation.32 In adults after Fontan-type procedures, atrial arrhythmias have been reported to occur with a prevalence ranging from 11% to 60%.7,33,34 Whether delay in electromechanical coupling in Fontan patients predicts the development of atrial arrhythmias requires further investigations. Although the mechanism of altered atrial function and electromechanical delay in our patients remains to be clarified, potential contributing factors may include previous atriotomy and fibrotic atrial wall. The finding of worse atrial mechanics and electromechanical delay in patients with APC than those with EC is intriguing. Gross dilation of right atrium in the setting of APC with distortion of interatrial septum may be a possible culprit, although this remains speculative. Atrioventricular diastolic interaction is
Li et al 7
Journal of the American Society of Echocardiography Volume - Number -
Table 3 Regional systemic ventricular longitudinal strain Variable
Left-sided free wall Basal Middle Apical Right-sided free wall in patients/ ventricular septum in controls Basal Middle Apical
APC (n = 13)
EC (n = 15)
All patients (n = 28)
Controls (n = 26)
16.8 6 6.9 13.8 6 5.5* 15.0 6 5.7
20.9 6 4.9 18.7 6 4.3 17.0 6 8.0
19.0 6 6.2† 16.4 6 5.4† 16.1 6 6.9†
22.6 6 4.4 21.0 6 2.8 21.2 6 5.3
11.2 6 4.6* 14.0 6 4.7* 19.1 6 7.2
24.7 6 6.9 21.4 6 5.1 17.2 6 6.1
18.4 6 9.0 18.0 6 6.1† 18.1 6 6.6†
20.9 6 2.1 22.4 6 1.6 23.9 6 4.5
Data are expressed as mean 6 SD. *P < .05, APC versus EC. † P < .05, all patients versus controls.
Figure 4 Scatterplots showing correlations between ventricular ejection fraction (EF) and parameters of ventricular deformation (top) and between ventricular early diastolic SR (SRe) and indices of atrial deformation (bottom). Blue circles represent patients with APC, and red circles represent patients with EC. SDI, Systolic dyssynchrony index. further reflected in our patients by the association between atrial strain, SRcon, and electromechanical coupling with systemic ventricular early diastolic SR. Increased reliance on atrial contraction as aforementioned in Fontan patients may hence represent a compensatory mechanism. Nonetheless, the existence of atrial dysfunction shown in this and in previous studies18,29 suggests that the compensation is likely to be suboptimal, probably more so in patients with APC. The amount of native atrial tissue incorporated into the Fontan circuit differs among patients with APC and those with EC. Chronic and progressive dilation of the greater amount of atrial tissue in APC may cause greater fluid energy losses, an increase in the energy required to propel forward flow of blood to the pulmonary arteries,12,13,14 and impaired ventricular filling as discussed above and consequently may affect exercise capacity. In symptomatic patients with failing
APCs, conversion to an EC Fontan circuit has been shown to improve functional class and peak oxygen uptake during exercise.9,10,11 The latter has been proposed to reflect an improvement in cardiac stroke volume.11 Indeed in our patients with EC, the greater ventricular volumes imply better ventricular filling, which may in turn be related to the greater magnitude and rate of atrial deformation and shorter time needed for electromechanical coupling. A prospective study is required, however, to clearly define the changes in atrial and ventricular mechanics with Fontan conversion. Several limitations to this study warrant comments. First, we did not include patients with lateral tunnels, because EC has been the main approach for total cavopulmonary connection at our institution. Nonetheless, systemic venous flow dynamics are similar between the two approaches.
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Journal of the American Society of Echocardiography - 2014
Figure 5 Comparisons of atrial strain and SR between patients and controls (left) and between patients with APC and those with EC. SRac, Atrial active contractile SR; SRres, atrial reservoir SR. *P < .05, patients versus controls; #P < .05, APC versus EC. Second, as alluded to earlier, the prevalence of systemic left ventricular morphology was greater in the APC group. Nonetheless, given the documented better functioning of a morphologic left ventricle in the setting of functionally single ventricles,26,27 our findings of worse ventricular deformation in the APC subgroup may suggest an intrinsic hemodynamic flaw of the APC circuit. Third, in the present study we used four-dimensional analysis software from TomTec to evaluate the functional ventricle. Our group has previously applied this technique to assess left ventricular mechanics in patients with tricuspid atresia.16 Although Khoo et al.35 reported only a 50% success of applying the four-dimensional right ventricular analysis software to image the subpulmonary and systemic right ventricles, recent studies have reported greater success using TomTec four-dimensional echocardiographic view to measure volumes of functional single ventricles with a right ventricular morphology.36,37 Fourth, tissue Doppler–derived myocardial velocities of regional segments might have been influenced by their close proximity to rudimentary cardiac chambers. Nonetheless, additional assessment of global ventricular strain and SR by speckle-tracking would probably minimize the errors of regional myocardial assessment. Finally, this was a cross-sectional study, and further longitudinal studies to track the changes in atrial and ventricular mechanics before and after Fontan conversion are warranted.
CONCLUSIONS Atrial and ventricular mechanics are impaired in patients after Fontantype operations, which is worse with APC than EC.
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