Background
Patients with single–right ventricle (RV) physiology are at increased risk for myocardial dysfunction and mechanical dyssynchrony. Newer echocardiographic modalities may be better able to quantitate right ventricular function in this unique population. The aim of this study was to use two-dimensional speckle analysis of strain and strain rate to quantify systolic function and dyssynchrony in single-RV post-Fontan patients and compare them with values for controls.
Methods
Patients with single RV who underwent Fontan palliation and patients with normal biventricular anatomy were studied. Two-dimensional speckle echocardiography was used to measure strain, strain rate, time to peak, and longitudinal displacement in a 6-segment model of the RV. Independent t tests were used to compare group means. P values < .05 were considered significant.
Results
Thirteen patients were studied in each group. There was no significant difference in age between single-RV patients and controls (6.60 ± 2.07 vs 5.75 ± 1.83 years, respectively). Single-RV strain values were significantly lower in all 6 segments compared with values in controls (basal interventricular septum [IVS], −14.28 ± 7.78% vs −22.00 ± 2.36%; mid IVS, −17.70 ± 4.54% vs −22.99 ± 2.71%; apical IVS, −19.46 ± 4.97% vs −25.42 ± 4.06%; basal RV, −22.40 ± 5.7% vs −41.42 ± 5.42%; mid RV, −21.20 ± 3.21% vs −39.67 ± 6.04%; apical RV, −20.70 ± 4.90% vs −33.68 ± 3.90%). Systolic strain rate and longitudinal displacement were also lower in the free wall and apical IVS in single-RV patients compared with controls. The modified Yu index for strain time to peak was longer in the single-RV patients (43.16 ± 13.63 vs 21.72 ± 7.25 ms).
Conclusion
Significant differences in strain analysis between single-RV patients and patients with biventricular physiology exist at a relatively young age. Future studies are needed to determine the clinical significance of these differences.
Patients with single-right ventricle (RV) physiology may be at increased risk for myocardial dysfunction and dyssynchrony. Currently, no method is performed universally to quantitate right ventricular function, especially in single-RV physiology. Qualitative assessment of the RV is usually documented, but quantitative assessment has been limited by the complex crescent shape of this chamber. As a result, traditional measurements of left ventricular function cannot be applied. Newer techniques such as Doppler tissue imaging (DTI) and speckle-tracking echocardiography (STE) may overcome some of these difficulties.
Although DTI-derived velocities have been used to evaluate right ventricular function, assessment is limited by the influence of overall heart motion, cardiac rotation, transducer positioning, and tethering. Strain imaging by DTI overcomes these limits but is still characterized by angle dependency. Two-dimensional STE has been introduced as an angle-independent method to characterize local and global myocardial deformation. These measurements may be less preload dependent compared with DTI values and thus quantitate contractility better.
The objective of this study was to use STE to analyze strain, strain rate, and time to peak in children with single-RV physiology who underwent Fontan palliation and compare them with values in age-matched control patients to determine differences.
Methods
Study Population
Patients with single morphologic RV physiology who underwent Fontan or Kawashima palliation were recruited. Patients who had cardiac hospitalizations, cardiac surgery, or cardiac catheterization procedures within the past 3 months were excluded. Patients undergoing long-term pacing were also excluded. This cohort therefore consisted of single-RV patients who were cardiovascularly stable. Age-matched control subjects were recruited and prospectively identified by echocardiography to be normal. Any control subjects who had anatomic cardiac abnormalities were excluded. All patients were recruited from the cardiology clinic. Cardiac diagnosis, age, weight, oxygen saturation on room air at rest, gender, and surgical dates were documented. Rhythm and QRS duration were determined by 12-lead electrocardiography in both cohorts. QRS duration was measured in lead V 1 for consistency. The institutional review board approved this prospective cross-sectional study.
Echocardiographic Protocol
Echocardiography was performed by a single echocardiographer (C.L.C.) using a Vivid 7 or Vivid I echocardiographic platform (GE Healthcare, Wauwatosa, WI) with acoustic frequencies appropriate for patient size. In single-RV patients, views equivalent to an apical 4-chamber view were obtained. Images were taken in triplicate in 3 beat cycles optimized for the visualization of the epicardial and endocardial borders of the single RV and control RV at frame rates of 60 to 100 Hz, as previously reported. Right ventricular fractional area change ([right ventricular diastolic area − right ventricular systolic area]/right ventricular diastolic area) was measured for both cohorts in the apical 4-chamber view. DTI of the right ventricular free wall at the level of the annulus was performed, and the myocardial performance index was calculated as another measure of overall right ventricular function ( Figure 1 ).
Two-dimensional STE
Values for strain and strain rate by STE were obtained. Images (not in Digital Imaging and Communications in Medicine format) were analyzed offline by a single observer (N.M.) on an EchoPAC 7 workstation (GE Healthcare). The endocardial borders of the single RV and the control RV in an apical 4-chamber view were traced from the septal-atrioventricular annular hinge point to the apical septum, to the right ventricular lateral wall at the lateral-atrioventricular annular hinge point. The automated epicardial-to-endocardial computer-generated border, or region of interest (ROI), was adjusted to include the epicardium. ROIs at 0, 1, 2, or 3 hash marks were documented. Tracking was accepted only if visual inspection showed adequate tracking and if the software indicated adequate tracking for all segments (green). Patients whose segments did not track well because of artifacts or inadequate visualization of the lateral epicardial borders of the RV were excluded. Measurements of strain, displacement, and strain rate were manually made for the basal septum, mid septum, apical septum, basal RV, mid RV, and apical RV ( Figures 2 A and 2 B). Measurements of global ventricular strain and global strain rate, including systolic (S), early diastolic (E), and late diastolic (A), were performed. A curved M-mode was referenced to evaluate peak S, E, and A measurements. Similar measurements were made for the control patients’ left ventricles (LV).
Dyssynchrony
Time to peak strain (from QRS onset) was measured for all 6 segments in triplicate. The standard deviation of these values was then calculated to give a modified Yu index. The timing of tricuspid valve opening was also measured manually in triplicate.
Statistical Analysis
Means and standard deviations were computed to describe the data. Independent t tests were used to compare group means. Pearson’s correlation was performed to test for associations between QRS duration and measurements of dyssynchrony. P values < .05 were considered significant.
Results
Demographics
Fourteen patients with single RVs who underwent Fontan or Kawashima palliation and 16 age-matched control children, who were clinically stable, were consented for the study. One patient with hypoplastic left-heart syndrome and 3 control patients were excluded because of poor tracking, so this study consisted of 13 patients in each group. Excluded patients did not differ significantly from control patients. There was no significant difference in age or weight between groups ( Table 1 ). Clinic letters documented good activity in 12 of the single-RV patients, with 1 patient showing signs of decreased exercise tolerance. The majority of the single-RV patients had hypoplastic left hearts underwent extracardiac nonfenestrated Fontan procedures. All single-RV patients underwent Fontan palliation secondary to hypoplastic LVs. Time from Fontan or Kawashima procedure to study echocardiography was 4.0 ± 2.4 years (median, 4.1 years; range, 1.0-8.4 years). Of the 13 patients with single-RV physiology, 11 were treated with enalapril, digoxin, or both medications at the primary cardiologist’s discretion. One patient with a hypoplastic left heart and 1 with a double-outlet RV were on neither enalapril nor digoxin.
| Characteristic | Controls | Single-RV patients | P |
|---|---|---|---|
| Age (y) | 5.7 ± 1.8 | 6.5 ± 2.1 | NS |
| Saturation (%) | 98.3 ± 1.2 | 94.5 ± 5.1 | .02 |
| Weight (kg) | 21.8 ± 5.1 | 20.6 ± 3.9 | NS |
| Operative procedure | |||
| Kawashima | 1 | ||
| Lateral tunnel Fontan | |||
| Fenestrated | 2 | ||
| Nonfenestrated | 1 | ||
| Extracardiac Fontan | |||
| Fenestrated | 1 | ||
| Nonfenestrated | 8 | ||
| Diagnosis | |||
| Unbalanced atrioventricular septal defect | 1 | ||
| Hypoplastic left-heart syndrome | 10 | ||
| Double-outlet right ventricle | 2 | ||
| Medications | |||
| Digoxin | 6 | ||
| Enalapril | 11 |
All control patients were in normal sinus rhythm. Eleven single-RV patients were in normal sinus rhythm, and 2 single-RV patients were in low right atrial rhythms. No patient was in a junctional rhythm, atrial flutter, or atrial fibrillation on 12-lead electrocardiography. Heart rates during acquisition were 87.8 ± 11.4 and 83.8 ± 16.6 beats/min for control and single-RV patients, respectively ( P = NS). QRS duration was significantly lower in the control than the single-RV patients (78.5 ± 5.6 vs 106.1 ± 23.6 ms, respectively; P < .01).
Echocardiography
All control patients had qualitatively normal biventricular function and no or trivial tricuspid regurgitation. Twelve single-RV patients had qualitatively normal right ventricular function, and 1 had mildly depressed right ventricular function. Three single-RV patients had trivial tricuspid regurgitation, 8 had mild tricuspid regurgitation, and 2 had moderate tricuspid regurgitation. Right ventricular fractional area change was significantly higher (51 ± 3% vs 37 ± 6%, P < .01) and the right ventricular myocardial performance index lower (0.35 ± 0.04 vs 0.53 ± 0.11, P < .01) in the control patients versus the single-RV patients.
Strain Analysis
The mean frame rates were 86.2 ± 18.8 and 92.1 ± 11.8 frames/s and the ROIs were 1.2 ± 0.7 and 1.4 ± 0.4 in control and single-RV patients, respectively ( P = NS). Strain was significantly higher in the control versus single-RV patients for all 6 segments ( Table 2 ). Global right ventricular strain was also significantly higher in the control patients (−31.1 ± 3.1% vs −18.0 ± 3.0%, P < .01). Displacement was significantly different between control and single-RV patients at the apical septum and at the basal, mid, and apical right ventricular segments ( Table 2 ). Similarly, strain rate was significantly higher in the corresponding segments for the control patients ( Table 2 ). Control patients also had higher global S (−2.01 ± 0.33 vs −1.11 ± 0.23 s −1 , P < .01), E (2.56 ± 0.46 vs 1.65 ± 0.39 s −1 , P < .01), and A (1.28 ± 0.36 vs 0.95 ± 0.34 s −1 , P = .02) strain rates versus single-RV patients.
| Strain (%) | Time to peak (ms) | Displacement (mm) | Strain rate (s −1 ) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Segments | Control | Single RV | P | Control | Single RV | P | Control | Single RV | P | Control | Single RV | P |
| Basal IVS | −22.0 ± 2.4 | −14.3 ± 7.8 | <.01 | 327.8 ± 37.8 | 339.5 ± 66.6 | NS | 8.2 ± 2.4 | 9.3 ± 1.9 | NS | −1.65 ± 0.27 | −1.46 ± 0.68 | NS |
| Mid IVS | −23.0 ± 2.7 | −17.7 ± 4.5 | <.01 | 308.3 ± 20.9 | 304.5 ± 49.7 | NS | 5.0 ± 2.4 | 6.7 ± 2.0 | NS | −1.62 ± 0.28 | −1.38 ± 0.37 | NS |
| Apical IVS | −25.4 ± 4.1 | −19.5 ± 5.0 | <.01 | 310.4 ± 25.4 | 302.8 ± 43.5 | NS | 1.3 ± 2.7 | 3.4 ± 2.1 | .04 | −2.01 ± 0.26 | −1.39 ± 0.41 | <.01 |
| Basal RV | −41.4 ± 5.4 | −22.4 ± 5.7 | <.01 | 334.8 ± 38.8 | 368.0 ± 46.8 | NS | 21.2 ± 3.3 | 9.9 ± 2.3 | <.01 | −3.54 ± 0.42 | −2.14 ± 0.72 | <.01 |
| Mid RV | −39.7 ± 6.0 | −21.2 ± 3.2 | <.01 | 328.8 ± 32.5 | 345.6 ± 51.1 | NS | 12.2 ± 3.2 | 5.7 ± 2.1 | <.01 | −2.90 ± 0.64 | −1.46 ± 0.28 | <.01 |
| Apical RV | −33.7 ± 3.9 | −20.7 ± 4.9 | <.01 | 313.3 ± 30.2 | 306.9 ± 38.1 | NS | 4.1 ± 2.9 | 0.8 ± 2.1 | <.01 | −2.4 ± 0.39 | −1.53 ± 0.36 | <.01 |
When comparing the control patients’ left ventricular free walls with the single-RV patients’ right ventricular free walls, only the apical segments were significantly different for strain values, though the basal and mid segments trended toward significance ( P = .08; Table 3 ). Left ventricular global strain in controls was significantly higher than global strain in single-RV patients (−24.2 ± 3.3% vs −18.0 ± 3.0%, P < .01). Displacement was significantly different in all 3 free wall segments between these 2 groups ( Table 3 ). Strain rate was different only in the apical free wall segment, though the mid free wall segment also trended toward significance ( P = .07; Table 3 ). The left ventricular free walls in controls also had higher global S (−1.44 ± 0.36 vs −1.11 ± 0.23 s −1 , P = .01) and E (2.76 ± 0.33 vs 1.65 ± 0.39 s −1 , P < .01) strain rates compared with the single-RV patients’ free walls. The global A strain rate was not different between the left ventricular and right ventricular free walls (0.92 ± 0.26 vs 0.95 ± 0.34 s −1 , P = NS).
