JOURNAL OF MAGNETIC RESONANCE IMAGING 41:730–737 (2015)
Original Research
Progression of Right Ventricular Dilation in Repaired Tetralogy of Fallot Sujatha Buddhe, MD, MS,1,2* Amee Shah, MD,1 and Wyman W. Lai, MD, MPH1 Purpose: To evaluate factors associated with rapid rate of progression (ROP) of right ventricular (RV) dilation by cardiac MRI in repaired tetralogy of Fallot (TOF) patients. Materials and Methods: All patients with repaired TOF with two MRIs were included. RV volumes and function were assessed by MRIs performed on a GE 1.5 Tesla (T) platform. The ROP of RV dilation was calculated as the difference between the last and first RV indexed enddiastolic volumes (iEDV) divided by the time difference. Subjects were divided into two groups: Group I—rapid ROP (top quartile of ROP) and Group II—slower ROP (lower three quartiles). Results: A total of 61 subjects were included. Mean age was 18.0 6 9.7 years and duration between MRIs 3.4 6 2.1 years. Median ROP for RV iEDV was 2.0 (12.7 to 27.8) mL/m2/year. Fifteen subjects were in Group I and 46 in Group II. RV iEDV, RV ejection fraction, RV indexed end-systolic volume (iESV) were significantly different between groups. By multivariable analysis, RV iESV was the only independent parameter associated with rapid RV dilation (P < 0.01). Conclusion: There was no significant change in RV iEDV in majority of repaired TOF subjects. RV iESV was the best parameter associated with more rapid RV dilation. Key Words: pediatrics; right ventricle; tetralogy of Fallot; progression; dilation J. Magn. Reson. Imaging 2015;41:730–737. C 2014 Wiley Periodicals, Inc. V
PULMONARY REGURGITATION (PR) is a common complication after tetralogy of Fallot (TOF) repair (1). Significant PR is usually well tolerated in childhood (2). However, in the long term, it has a detrimental effect on right ventricular (RV) function and exercise capacity and leads to an increased risk of arrhythmia and sudden cardiac death (3). 1 Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University Medical Center, Division of Pediatric Cardiology, New York, New York, USA. 2 Seattle Children’s Hospital, Division of Pediatric Cardiology, Seattle, Washington, USA. *Address reprint requests to: S.B., Division of Pediatric Cardiology, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105. E-mail: [email protected] Received December 6, 2013; Accepted February 12, 2014. DOI 10.1002/jmri.24610 View this article online at wileyonlinelibrary.com. C 2014 Wiley Periodicals, Inc. V
MRI has evolved during the last two decades as the reference standard imaging modality for the assessment of PR and RV dilation (4). Several studies have suggested pulmonary valve replacement (PVR) threshold values of RV end-diastolic and end-systolic volumes that are associated with postoperative normalization of RV size and function (5,6). The rate of progression of RV dilation varies among different individuals after TOF repair (7). However, there are no longitudinal data available on the rate of progression of RV dilation by MRI and on factors that are associated with this rate. This information would be very useful in determining the frequency of repeating diagnostic investigations like MRI in patients post TOF repair before reaching the PVR threshold values. There are also differences in progression of dilation and function between different segments of the RV. The RV infundibulum has been shown to have significant regional differences in function compared with the RV sinus (8). Infundibular size and function has been shown to significantly impact the assessment of global RV function (9). Also, the infundibular size may have impact on the progression of RV dilation. There are limited data on progression of infundibular dilation by MRI in TOF patients and its effect on progression of global RV dilation. Our primary hypothesis is that the rate of progression of RV dilatation is associated with other MRI parameters. Our secondary hypothesis is that the RV infundibular size and function have significant impact on the rate of progression of RV dilation. MATERIALS AND METHODS This was a retrospective cohort study. The study was approved by the Institutional Review Board. Patients with repaired TOF who had MRI between January 2004 and October 2012 at our institution were eligible for this study. Inclusion criteria were children and young adults with repaired TOF having at least two MRIs in this time period. Exclusion criteria were subjects with poor image quality, significant arrhythmias, and individuals who had PVR or tricuspid valve surgeries in between MRIs. All demographic, surgical, echocardiographic, and MRI data were reviewed. The demographic data collected included patient’s age, gender, height, weight,
730
Progression of Right Ventricle Dilation
and body surface area. Surgical data included time, age, and type of repair, including data on prior shunts. Image Acquisition MRI studies were performed on two identical GE TwinSpeed Signa HDx 1.5 Tesla (T) v. 14 scanners using commercially available multichannel coils (GE Healthcare, Milwaukee, Wisconsin). Acquisitions were obtained at end expiration or with three excitations in subjects who could not perform breathholding. Multislice, electrocardiographic-triggered steady state free precession imaging sequences of the ventricles in the short-axis plane were obtained (slice thickness 6 to 9 mm; 0 mm interslice gap; repetition time 3.0 to 4.0 ms; echo time 1.4 to 1.8 ms; flip angle 45 ; receiver bandwidth 125 kHz; acquisition matrix 224 to 264 160 to 192; field of view 360 to 420 mm; views per segment 12 to 24; and 30 phases/cardiac cycle). Off-line volume measurements were performed using the Mass Analytical Software System Version Proto 6.0. (Medis, the Netherlands). All RV measurements were repeated by a single investigator (S.B., 1 year experience). A second observer repeated the measurements in 20 randomly selected subjects to test for interobserver variability (A.S., 3 years experience). Contour tracing was performed manually in the short axis data sets after review of cine images in movie mode. The phase of end diastole was defined visually by the observer as the phase with the largest LV volume and end systole was defined separately for the RV and LV as the phase with the smallest RV and LV volumes, respectively. Epicardial and endocardial contours were manually drawn in end-diastole and endocardial borders were drawn in end-systole. For the RV, trabeculations, and papillary muscles were included as part of the RV volume. In short-axis datasets, only the area of the RV outflow tract below the level of pulmonary valve was included in the RV volume. At the inflow portion of the RV, only the area of the blood pool surrounded by trabeculated ventricular myocardium was included in the RV volume. For the LV, the trabeculation and papillary muscles were segmented as part of the myocardium. The workstation calculated end-systolic and end-diastolic RV and LV volumes using the method of summation of discs. The SV was calculated by subtracting the end-systolic volume (ESV) from the end-diastolic volume (EDV). The ejection fraction (EF) was calculated by dividing the SV by the EDV. Right and left ventricular mass was calculated as the volume of the ventricle muscle (difference between epicardial and endocardial volume in end-diastole) multiplied by the specific weight of the tissue (1.05 g/cm3). The RV infundibulum was traced separately. As previously described, the border between the infundibulum and the sinus was defined by the muscular ring comprised of the septal band, moderator band, anterior papillary muscle group of the tricuspid valve, and the parietal band as detailed by Van Praagh et al (10,11). The boundary between the sinus and the infundibulum was traced in multislice short-axis cine images so that the parietal, moderator, and septal bands were included in the
731
infundibulum (Fig. 1). RV infundibular volume percent was calculated as the (RV infundibular end-diastolic volume/RV global end-diastolic volume) 100. As per the clinical protocol, phase contrast (PC) images were obtained in the main pulmonary artery and ascending aorta. PC images were analyzed using C 3.6 with phantom correction. A GE ReportCARDV region of interest (ROI) was drawn for each vessel, and net flow rate (mL/min) was calculated for each. Flows were corrected in the MPA by applying the corresponding baseline shift that zeroed the flow in the phantom using the reporting software as previously described (12). The pulmonary regurgitation (PR) fraction percent was calculated using forward and reverse flow measured during a cardiac cycle as (reverse flow volume/forward flow volume) 100. MRI Data The MRI data that were collected included global RV end-diastolic volume (EDV), RV end-systolic volume (ESV), RV ejection fraction (EF), and PR. RV volumes were indexed to the body surface area (Haycock formula). The RV sinus and infundibular volumes and EFs were also measured. The presence of RV outflow tract (RVOT) narrowing or aneurysm and branch pulmonary artery sizes were also reviewed. RVOT aneurysm was defined as outward movement during systole of part of the ventricular wall or its reconstructed outflow tract. Pulmonary regurgitation was graded as mild (40%). Rate of progression (ROP) of RV dilation was defined as the difference between the last and first indexed RV end-diastolic volumes (RV iEDV) divided by the number of years between MRIs. Subjects were divided into two groups based on the distribution of the ROP of RV dilation: Group I—rapid ROP (top quartile of ROP) and Group II—slower ROP (lower three quartiles of ROP). Echocardiogram and EKG Data Echocardiographic data including degree of tricuspid regurgitation (TR), pulmonary stenosis (PS), and PR were collected. TR or PR was graded as mild, moderate, and severe by subjective assessment, and PS was defined as at least mild when the peak systolic gradient was >20 mmHg by echocardiogram. QRS duration was measured on the most recent electrocardiogram (ECG) before MRI. Statistics The differences in characteristics between the groups were analyzed. All data were reported as mean and standard deviation (SD) or median (range) for continuous variables and frequency for categorical variables. The two groups were compared using independent sample t-test, Mann-Whitney U-test, Fisher’s exact, or Chi-square tests depending on the type and distribution of the data. Multiple groups were compared by
732
Buddhe et al.
Figure 1. Short axis steady-state free precession (SSFP) stack by MRI showing RV infundibular measurements from base to apex. The border between the infundibulum and the sinus was defined by the muscular ring comprised of the septal band, moderator band, anterior papillary muscle group of the tricuspid valve, and the parietal band. The parietal, moderator, and septal bands were included in the infundibulum.
analysis of variance or Kruskal Wallis test depending on the distribution of the data. All statistical analyses were performed using SAS software version 9.3 (SAS Institute, Cary, NC). Multivariable logistic regression analysis was performed to determine the significant variables associated with progression of RV dilation. All the parameters that were significant at P < 0.1 level by univariate analysis were entered into the multivariable model. Receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity of parameters associated with rapid progression of RV dilation. Statistical significance was defined as P < 0.05.
divided into two groups: Group I—rapid progression (top quartile with ROP 6.2 to 27.8 mL/m2/year) and Group II—slower progression (lower three quartiles with ROP 12.7 to 5.4 mL/m2/year).
RESULTS Of 63 subjects, two were excluded due to poor image quality secondary to arrhythmia and artifact. A total of 61 subjects with repaired TOF were included in the study. Four of the studies (two subjects, 3%) were performed without breathholding. Thirty percent of the subjects had a history of pulmonary atresia (TOF/ PA) and 20% had absent pulmonary valve (TOF/APV). TOF repair included a transannular patch in 55%, no patch in 17%, and a conduit in 28%. The mean age was 18.0 6 9.7 years and the median duration between MRIs was 3.0 (range, 0.4–7.5) years. Median rate of progression (ROP) for RV iEDV was 2.0 (range, 12.7 to 27.8) mL/m2/year. Figure 2 is a histogram showing the distribution of ROP. The subjects were
Figure 2. Histogram showing distribution of the rate of progression (ROP) of RV dilation (mL/m2/year). RV iEDV: RV indexed end-diastolic volume. The vertical line separates the Group I (top quartile) from the Group II (other three quartiles).
Progression of Right Ventricle Dilation
733
Table 1 Patient Characteristics Variables 2
ROP (mL/m /yr) Age (years) * Male gender y QRS duration (ms) * Age at surgery (yrs) Time since surgery (yrs) * Time between MRIs (yrs) *
Group I (n¼15)
Group II (n¼46)
14.0 (6.2 to 27.8) 18.8 6 10.7 10 (67%) 141 6 31 1.9 (0.01 to 7.0) 16.0 6 9.2 1.1 (0.4 to 7.2)
0.2 (12.7 to 5.4) 17.7 6 9.5 23 (50%) 143 6 25 1.9 (0.02 to 9.0) 14.2 6 7.2 3.8 (1.1 to 7.5)
P-value
Original Research
Progression of Right Ventricular Dilation in Repaired Tetralogy of Fallot Sujatha Buddhe, MD, MS,1,2* Amee Shah, MD,1 and Wyman W. Lai, MD, MPH1 Purpose: To evaluate factors associated with rapid rate of progression (ROP) of right ventricular (RV) dilation by cardiac MRI in repaired tetralogy of Fallot (TOF) patients. Materials and Methods: All patients with repaired TOF with two MRIs were included. RV volumes and function were assessed by MRIs performed on a GE 1.5 Tesla (T) platform. The ROP of RV dilation was calculated as the difference between the last and first RV indexed enddiastolic volumes (iEDV) divided by the time difference. Subjects were divided into two groups: Group I—rapid ROP (top quartile of ROP) and Group II—slower ROP (lower three quartiles). Results: A total of 61 subjects were included. Mean age was 18.0 6 9.7 years and duration between MRIs 3.4 6 2.1 years. Median ROP for RV iEDV was 2.0 (12.7 to 27.8) mL/m2/year. Fifteen subjects were in Group I and 46 in Group II. RV iEDV, RV ejection fraction, RV indexed end-systolic volume (iESV) were significantly different between groups. By multivariable analysis, RV iESV was the only independent parameter associated with rapid RV dilation (P < 0.01). Conclusion: There was no significant change in RV iEDV in majority of repaired TOF subjects. RV iESV was the best parameter associated with more rapid RV dilation. Key Words: pediatrics; right ventricle; tetralogy of Fallot; progression; dilation J. Magn. Reson. Imaging 2015;41:730–737. C 2014 Wiley Periodicals, Inc. V
PULMONARY REGURGITATION (PR) is a common complication after tetralogy of Fallot (TOF) repair (1). Significant PR is usually well tolerated in childhood (2). However, in the long term, it has a detrimental effect on right ventricular (RV) function and exercise capacity and leads to an increased risk of arrhythmia and sudden cardiac death (3). 1 Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University Medical Center, Division of Pediatric Cardiology, New York, New York, USA. 2 Seattle Children’s Hospital, Division of Pediatric Cardiology, Seattle, Washington, USA. *Address reprint requests to: S.B., Division of Pediatric Cardiology, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105. E-mail: [email protected] Received December 6, 2013; Accepted February 12, 2014. DOI 10.1002/jmri.24610 View this article online at wileyonlinelibrary.com. C 2014 Wiley Periodicals, Inc. V
MRI has evolved during the last two decades as the reference standard imaging modality for the assessment of PR and RV dilation (4). Several studies have suggested pulmonary valve replacement (PVR) threshold values of RV end-diastolic and end-systolic volumes that are associated with postoperative normalization of RV size and function (5,6). The rate of progression of RV dilation varies among different individuals after TOF repair (7). However, there are no longitudinal data available on the rate of progression of RV dilation by MRI and on factors that are associated with this rate. This information would be very useful in determining the frequency of repeating diagnostic investigations like MRI in patients post TOF repair before reaching the PVR threshold values. There are also differences in progression of dilation and function between different segments of the RV. The RV infundibulum has been shown to have significant regional differences in function compared with the RV sinus (8). Infundibular size and function has been shown to significantly impact the assessment of global RV function (9). Also, the infundibular size may have impact on the progression of RV dilation. There are limited data on progression of infundibular dilation by MRI in TOF patients and its effect on progression of global RV dilation. Our primary hypothesis is that the rate of progression of RV dilatation is associated with other MRI parameters. Our secondary hypothesis is that the RV infundibular size and function have significant impact on the rate of progression of RV dilation. MATERIALS AND METHODS This was a retrospective cohort study. The study was approved by the Institutional Review Board. Patients with repaired TOF who had MRI between January 2004 and October 2012 at our institution were eligible for this study. Inclusion criteria were children and young adults with repaired TOF having at least two MRIs in this time period. Exclusion criteria were subjects with poor image quality, significant arrhythmias, and individuals who had PVR or tricuspid valve surgeries in between MRIs. All demographic, surgical, echocardiographic, and MRI data were reviewed. The demographic data collected included patient’s age, gender, height, weight,
730
Progression of Right Ventricle Dilation
and body surface area. Surgical data included time, age, and type of repair, including data on prior shunts. Image Acquisition MRI studies were performed on two identical GE TwinSpeed Signa HDx 1.5 Tesla (T) v. 14 scanners using commercially available multichannel coils (GE Healthcare, Milwaukee, Wisconsin). Acquisitions were obtained at end expiration or with three excitations in subjects who could not perform breathholding. Multislice, electrocardiographic-triggered steady state free precession imaging sequences of the ventricles in the short-axis plane were obtained (slice thickness 6 to 9 mm; 0 mm interslice gap; repetition time 3.0 to 4.0 ms; echo time 1.4 to 1.8 ms; flip angle 45 ; receiver bandwidth 125 kHz; acquisition matrix 224 to 264 160 to 192; field of view 360 to 420 mm; views per segment 12 to 24; and 30 phases/cardiac cycle). Off-line volume measurements were performed using the Mass Analytical Software System Version Proto 6.0. (Medis, the Netherlands). All RV measurements were repeated by a single investigator (S.B., 1 year experience). A second observer repeated the measurements in 20 randomly selected subjects to test for interobserver variability (A.S., 3 years experience). Contour tracing was performed manually in the short axis data sets after review of cine images in movie mode. The phase of end diastole was defined visually by the observer as the phase with the largest LV volume and end systole was defined separately for the RV and LV as the phase with the smallest RV and LV volumes, respectively. Epicardial and endocardial contours were manually drawn in end-diastole and endocardial borders were drawn in end-systole. For the RV, trabeculations, and papillary muscles were included as part of the RV volume. In short-axis datasets, only the area of the RV outflow tract below the level of pulmonary valve was included in the RV volume. At the inflow portion of the RV, only the area of the blood pool surrounded by trabeculated ventricular myocardium was included in the RV volume. For the LV, the trabeculation and papillary muscles were segmented as part of the myocardium. The workstation calculated end-systolic and end-diastolic RV and LV volumes using the method of summation of discs. The SV was calculated by subtracting the end-systolic volume (ESV) from the end-diastolic volume (EDV). The ejection fraction (EF) was calculated by dividing the SV by the EDV. Right and left ventricular mass was calculated as the volume of the ventricle muscle (difference between epicardial and endocardial volume in end-diastole) multiplied by the specific weight of the tissue (1.05 g/cm3). The RV infundibulum was traced separately. As previously described, the border between the infundibulum and the sinus was defined by the muscular ring comprised of the septal band, moderator band, anterior papillary muscle group of the tricuspid valve, and the parietal band as detailed by Van Praagh et al (10,11). The boundary between the sinus and the infundibulum was traced in multislice short-axis cine images so that the parietal, moderator, and septal bands were included in the
731
infundibulum (Fig. 1). RV infundibular volume percent was calculated as the (RV infundibular end-diastolic volume/RV global end-diastolic volume) 100. As per the clinical protocol, phase contrast (PC) images were obtained in the main pulmonary artery and ascending aorta. PC images were analyzed using C 3.6 with phantom correction. A GE ReportCARDV region of interest (ROI) was drawn for each vessel, and net flow rate (mL/min) was calculated for each. Flows were corrected in the MPA by applying the corresponding baseline shift that zeroed the flow in the phantom using the reporting software as previously described (12). The pulmonary regurgitation (PR) fraction percent was calculated using forward and reverse flow measured during a cardiac cycle as (reverse flow volume/forward flow volume) 100. MRI Data The MRI data that were collected included global RV end-diastolic volume (EDV), RV end-systolic volume (ESV), RV ejection fraction (EF), and PR. RV volumes were indexed to the body surface area (Haycock formula). The RV sinus and infundibular volumes and EFs were also measured. The presence of RV outflow tract (RVOT) narrowing or aneurysm and branch pulmonary artery sizes were also reviewed. RVOT aneurysm was defined as outward movement during systole of part of the ventricular wall or its reconstructed outflow tract. Pulmonary regurgitation was graded as mild (40%). Rate of progression (ROP) of RV dilation was defined as the difference between the last and first indexed RV end-diastolic volumes (RV iEDV) divided by the number of years between MRIs. Subjects were divided into two groups based on the distribution of the ROP of RV dilation: Group I—rapid ROP (top quartile of ROP) and Group II—slower ROP (lower three quartiles of ROP). Echocardiogram and EKG Data Echocardiographic data including degree of tricuspid regurgitation (TR), pulmonary stenosis (PS), and PR were collected. TR or PR was graded as mild, moderate, and severe by subjective assessment, and PS was defined as at least mild when the peak systolic gradient was >20 mmHg by echocardiogram. QRS duration was measured on the most recent electrocardiogram (ECG) before MRI. Statistics The differences in characteristics between the groups were analyzed. All data were reported as mean and standard deviation (SD) or median (range) for continuous variables and frequency for categorical variables. The two groups were compared using independent sample t-test, Mann-Whitney U-test, Fisher’s exact, or Chi-square tests depending on the type and distribution of the data. Multiple groups were compared by
732
Buddhe et al.
Figure 1. Short axis steady-state free precession (SSFP) stack by MRI showing RV infundibular measurements from base to apex. The border between the infundibulum and the sinus was defined by the muscular ring comprised of the septal band, moderator band, anterior papillary muscle group of the tricuspid valve, and the parietal band. The parietal, moderator, and septal bands were included in the infundibulum.
analysis of variance or Kruskal Wallis test depending on the distribution of the data. All statistical analyses were performed using SAS software version 9.3 (SAS Institute, Cary, NC). Multivariable logistic regression analysis was performed to determine the significant variables associated with progression of RV dilation. All the parameters that were significant at P < 0.1 level by univariate analysis were entered into the multivariable model. Receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity of parameters associated with rapid progression of RV dilation. Statistical significance was defined as P < 0.05.
divided into two groups: Group I—rapid progression (top quartile with ROP 6.2 to 27.8 mL/m2/year) and Group II—slower progression (lower three quartiles with ROP 12.7 to 5.4 mL/m2/year).
RESULTS Of 63 subjects, two were excluded due to poor image quality secondary to arrhythmia and artifact. A total of 61 subjects with repaired TOF were included in the study. Four of the studies (two subjects, 3%) were performed without breathholding. Thirty percent of the subjects had a history of pulmonary atresia (TOF/ PA) and 20% had absent pulmonary valve (TOF/APV). TOF repair included a transannular patch in 55%, no patch in 17%, and a conduit in 28%. The mean age was 18.0 6 9.7 years and the median duration between MRIs was 3.0 (range, 0.4–7.5) years. Median rate of progression (ROP) for RV iEDV was 2.0 (range, 12.7 to 27.8) mL/m2/year. Figure 2 is a histogram showing the distribution of ROP. The subjects were
Figure 2. Histogram showing distribution of the rate of progression (ROP) of RV dilation (mL/m2/year). RV iEDV: RV indexed end-diastolic volume. The vertical line separates the Group I (top quartile) from the Group II (other three quartiles).
Progression of Right Ventricle Dilation
733
Table 1 Patient Characteristics Variables 2
ROP (mL/m /yr) Age (years) * Male gender y QRS duration (ms) * Age at surgery (yrs) Time since surgery (yrs) * Time between MRIs (yrs) *
Group I (n¼15)
Group II (n¼46)
14.0 (6.2 to 27.8) 18.8 6 10.7 10 (67%) 141 6 31 1.9 (0.01 to 7.0) 16.0 6 9.2 1.1 (0.4 to 7.2)
0.2 (12.7 to 5.4) 17.7 6 9.5 23 (50%) 143 6 25 1.9 (0.02 to 9.0) 14.2 6 7.2 3.8 (1.1 to 7.5)
P-value
