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Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?
International Journal of Cardiology xxx (xxxx) xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?* Vidhya Annavajjhala a, Anne Marie Valente b, Leo Lopez c, Ritu Sachdeva d, Julie S. Glickstein e, Shobha S. Natarajan f, Sujatha Buddhe g, Karen Altmann e, Brian D. Soriano g, John L. Colquitt h, Carolyn A. Altman h, Nao Sasaki c, Charlotte Sakarovitch a, Theresa A. Tacy a, Tal Geva b, Elif Seda Selamet Tierney a, * a
Lucile Packard Children’s Hospital, Stanford University Medical Center, Palo Alto, CA, USA Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA c Nicklaus Children’s Hospital, Miami, FL, USA d Emory University School of Medicine and Children’s Healthcare of Atlanta Sibley Heart Center Cardiology, Atlanta, GA, USA e Morgan Stanley Children’s Hospital of New York, Columbia University Medical Center, New York, NY, USA f The Children’s Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA g University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA h Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 May 2019 Received in revised form 14 August 2019 Accepted 27 September 2019 Available online xxx
Background: Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations. Methods: This was a multi-center (n ¼ 8) retrospective review of TTE reports in children 11 years of age who have had complete TOF repair. We included 10 patients from each participating center (n ¼ 80) and scored 2 outpatient follow-up TTE reports on each patient. The adherence rate was based on completeness of TTE reporting elements derived from the guidelines. Results: We reviewed 160 TTE reports on 80 patients. Median age was 4.4 months (IQR 1.5-6.6) and 3.6 years (IQR 1.3-6.4) at the time of complete surgical repair and first TTE report, respectively. The median adherence rate to recommended reporting elements was 61% (IQR 53e70). Of the 160 reports, 9 (7%) were 80% adherent and 40 (25%) were 70% adherent. Quantitative measurements of right ventricular outflow tract (RVOT), right ventricular (RV) size and function, and branch pulmonary arteries were least likely to be reported. Conclusions: Overall adherence to the most recent published imaging guidelines for surveillance of children with repaired TOF patients was suboptimal, especially for reporting of RVOT, RV size and function, and branch pulmonary arteries. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes. © 2019 Elsevier B.V. All rights reserved.
Keywords: Tetralogy of Fallot Echocardiography Guidelines Adherence
1. Introduction Long-term outcomes of patients after repair of tetralogy of Fallot
* The author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. * Corresponding author. 750 Welch Road, Outpatient Heart Center, Palo Alto, CA, 94306, USA. E-mail address: [email protected] (E.S. Selamet Tierney).
(TOF) are impacted by residual anatomic and hemodynamic abnormalities such as pulmonary valve regurgitation or stenosis, right ventricular (RV) dilation and biventricular dysfunction [1,2]. There is an increased incidence of arrhythmias (~43%), exercise intolerance (28% had severely decreased exercise capacity with <50% predicted peak oxygen consumption), heart failure (12% NYHA functional class III), and sudden cardiac death beginning in early adulthood, which are often attributed to these abnormalities [3e5]. Therefore, longitudinal clinical surveillance is crucial in this patient
https://doi.org/10.1016/j.ijcard.2019.09.075 0167-5273/© 2019 Elsevier B.V. All rights reserved.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
2
V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx
Nomenclature
Abbreviations RV Right ventricle RVOT Right ventricular outflow tract PA Pulmonary artery TOF Tetralogy of Fallot TTE Transthoracic echocardiography
population. Transthoracic echocardiography (TTE) remains the primary tool for evaluating young children after TOF repair and provides clinicians with information that helps clinical decision making. In February 2014, the American Society of Echocardiography published multimodality non-invasive imaging guidelines for patients after TOF repair [6]. The goal of this document was to provide imaging guidelines to optimize data acquisition and help augment clinical decision making. The document recommends a list of major reporting elements with multiple subcomponents that should be addressed during routine TTE assessment for surveillance in this patient population (Supplemental Table). In this multicenter study, we sought to determine the adherence to these guidelines. 2. Methods This was a multi-center retrospective review of TTE reports performed in children who had undergone complete repair of TOF with pulmonary stenosis or atresia. We included 10 patients from each of the eight participating centers (n ¼ 80) including Boston Children’s Hospital, Children’s Healthcare of Atlanta, Children’s Hospital of Philadelphia, Lucile Packard Children’s Hospital at Stanford (Core Institution), Morgan Stanley Children’s Hospital of New York, Nicklaus Children’s Hospital, Seattle Children’s Hospital and Texas Children’s Hospital. The project was approved by the Institutional Review Boards at the participating centers. De-identified TTE reports were reviewed and scored at the Core Institution by a single reviewer. Data were collected and managed using REDCap electronic data capture tools hosted at the Stanford Center for Clinical Informatics [7]. Criteria for inclusion were pediatric patients 11 years of age status post complete repair of TOF with pulmonary valve stenosis or atresia who have undergone two outpatient TTEs (ECHO 1 and ECHO 2 in temporal order) performed at least six months apart between March 2014 and March 2016. We chose this age group as the acoustic windows tend to be better in younger children and pre-adolescents compared to older patients with larger body sizes. Patients who underwent a re-intervention after complete TOF repair were also included. The centers were invited to participate in the study in June 2016. The study inclusion dates were chosen 1) to capture the TTEs performed after the publication date of the guidelines, and 2) to ensure that the TTEs were obtained prior to the date when the invitation was sent to the centers to avoid a response bias. The centers identified two patients who met the inclusion criteria by medical record review. We analyzed two de-identified outpatient follow-up TTE reports performed between March 2014 to March 2016 on each patient. Each center was given instructions to randomly select patients who met inclusion criteria using a random number generator on Microsoft Excel or their preferred program to obtain random patients which provided a heterogenous population. Additional data collected (on a study form filled by the centers) included age at TTE,
age at complete TOF repair, additional medical and surgical diagnoses, study performance limitations (poor acoustic windows, “patient cooperation”, or time constraints), and any interval imaging by modalities other than TTE. Separate scoring sheets were derived for patients with and without a right ventricular to pulmonary artery (RV-to-PA) conduit (Appendix). The scoring was based on the TTE reporting elements and subcomponents (pertinent positives and negatives) derived from the guidelines. The highest possible scores for patients with conduit and without a conduit were 16.5 and 17.5 respectively. The adherence score for each TTE report was calculated as a percentage of the sum total of the subcomponent scores divided by the highest possible score. The subcomponents scores were also calculated as a percentage by dividing the absolute total subcomponent score by the highest possible subcomponent score. In order to assess inter-observer variability, a second investigator scored the reports using the same method on a randomly selected subset of 8 individual patients (total of 16 reports), which was derived using a random number generator on Microsoft Excel. The second reader was blinded to the initial scores. The outcome measure was the adherence rate to the guidelines which was defined as the ratio of the total calculated score to the highest possible score x 100. Statistical analysis was performed using GraphPad Prism (Version 7.0) and SAS Software (Version 9.4; SAS Institute, Cary, NC). Descriptive statistics were calculated for all variables of interest and included medians with 25the75th percentiles (interquartile range, IQR) or counts with percentages when appropriate. To assess the association of the adherence rate with variables of interest (age, body surface area, and reported barriers), we ran a linear mixed regression model to take into account the repeated measurement within each patient and the clustered design within centers. Therefore, the patient nested into centers are considered as random effect and the variable of interest as a fixed effect in the linear regression of total score. Our sample size calculation showed that we required 138 reports to obtain a 95% confidence level, a desired total width of confidence interval of 5 and a standard deviation of the variable of 15 to detect clinically relevant differences. Adherence rates were also compared between ECHO 1 and ECHO 2 on the same patients as well as patients with an RV-to-PA conduit and without an RV-to-PA conduit. Intra-class correlation coefficient analysis was used to calculate inter-observer variability. Statistical significance was defined by a p-value <0.05. 3. Results One hundred and sixty TTE reports were scored on 80 individual patients (47 males, 59%). The median age was 4.4 months (IQR 1.56.6) at the time of complete surgical repair and 3.6 years (IQR 1.36.4) at the time of ECHO 1. Of the 80 patients, 20 (25%) had a surgical repair requiring a RV-to-PA conduit. Of the 160 reports, 9 (7%) were 80% adherent and 40 (25%) were 70% adherent (Fig. 1). The median total score was 61% (IQR 53e70). There was no significant difference in adherence rate between TTE reports in patients with and without an RV-to-PA conduit (p ¼ 0.34). The intra-class correlation coefficient used to assess inter-observer variability of TTE report scoring was 0.91 (95% CI: 0.74-0.97). Adherence to the guidelines was lowest when reporting quantitative measurements of RV size and function as well as branch pulmonary arteries. The overall median adherence rates for assessment of RV size was 33% (IQR 11e33), RV function was 20% (IQR 20e40) and 33% (IQR 33e67) for the branch pulmonary arteries (Fig. 2). Further breakdown of RV and PA subcomponents are listed in Table 1.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx
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that the mean adherence rate ranged from 52 ± 13% to 70 ± 9% (p < 0.0001) and the variability (standard deviation) between patients from the same center ranged from 9% to 13%. Comparison of the two TTE reports (ECHO 1 and ECHO 2) on the same patient showed no difference in adherence rate (mean difference 0.01, p ¼ 0.47).
4. Discussion
`Fig. 1. Adherence rate (%) of reporting to current guidelines.
The adherence rate for qualitative assessment of both RV size and volume was 99.4% and 97.3% respectively. Quantitative measurements of the RV outflow tract, pulmonary valve, and reporting of Doppler gradients was suboptimal with a median score of 67% (IQR 48e75). Of the 160 TTE reports, 73 (45%) reported the qualitative assessment of left ventricular systolic function, 86 (54%) of the reports had quantitative assessment of left ventricular systolic function using either the 5/6 area* length method or the Simpson’s Biplane method as recommended by the guidelines [6] and 1 did not contain either qualitative or quantitative left ventricular functional assessment. Relationships between age, body surface area, barriers reported (poor acoustic windows, patient agitation, time limitations) and adherence demonstrated that adherence rate increased on average by 1% for each year of age (p ¼ 0.0072), and by 1.3% for each increase of 0.1 m2 body surface area (p ¼ 0.0071). Of the 160 TTE reports, 39 (24.4%) documented the presence of a study performance limitation that resulted in a limited/suboptimal echo. Adherence rate was higher in reports that did not document barriers (62.2 ± 11.3% vs 57.6 ± 13.6%); however, after accounting for repeated measurements and clusters, the difference was not statistically significant (p ¼ 0.16). Comparison of the adherence rate across centers (Fig. 3) showed
The Multimodality Non-Invasive Imaging Guidelines by the American Society of Echocardiography recommends a list of major reporting elements with several subcomponents that should be addressed during routine TTE in children with repaired TOF [6]. In this multicenter study, we sought to determine the adherence to these recommended reporting elements. Our results demonstrated that overall adherence to these guidelines was suboptimal with significant variation among centers. There are limited data on adherence to imaging guidelines in pediatric cardiology. Sachdeva et al. [8] examined the effect of published pediatric appropriate use criteria on TTE use in clinical practice at multiple centers and similarly found that the published guideline had minimal effect on physician practice and also significant variability amongst the centers [8]. However, a follow-up study evaluating the effectiveness of educational intervention after publication of the appropriate use criteria resulted in some improvement in the appropriateness of 4542 TTE’s ordered after the educational intervention across the centers participating in the study (72.5%e76.2%, p ¼ 0.04) [9]. It has also been shown that adherence to physician training and qualification guidelines for performance of pediatric transesophageal echocardiography impacts immediate outcomes such as adequacy of echocardiographic recordings and decision to return to cardiac bypass based on the echocardiographic findings [10]. Our results demonstrated that the overall adherence to the guidelines was suboptimal, especially for reporting of quantitative assessment of RV size, RV function, RV outflow tract, and the branch pulmonary arteries. We speculate that the complex anatomy of the RV along with the heavily trabeculated walls and poor endocardial definition could have contributed to lower scores in the subsections pertaining to quantitative assessment of RV size and RV function [11]. Although the guidelines recommend quantification of RV
Fig. 2. Adherence rates within subsections.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
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V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx Table 1 Breakdown of right ventricular and pulmonary artery subcomponents. A. Right Ventricular Size and Volume Sub-components Tricuspid valve annulus dimension Septal flattening (diastole) Base Mid-ventricular level Diastolic length Diaphragmatic wall thickness Qualitative assessment of right ventricular volume B. Right Ventricular Function Sub-components TAPSE Pulsed Doppler peak s’ Fractional area change (%) E/e’ ratio Qualitative assessment of right ventricular function C. Branch Pulmonary Arteries Sub-components Dimensions of one or both branch PAs Mention of presence or absence of PA obstruction
Adherence rate (%) 18.8 38.1 0 0 0 0.6 99.4 Adherence rate (%) 23.8 16.3 10.6 3.1 97.3 Adherence rate (%) 45 71.8
E: peak early filling velocity, e’- early diastolic peak velocity, s’-systolic velocity, PA: pulmonary artery, TAPSE: tricuspid annular plane systolic excursion.
function, in reality, very few echocardiographic laboratories use this on a routine basis due to the challenges stated above [12,13]. Interestingly, a recent study in pediatric patient with D-looped transposition of the great arteries who underwent arterial switch operation with the LeCompte maneuver reported suboptimal visualization of the branch pulmonary arteries by TTE regardless of their age [14]. Although this is a different patient cohort, this study highlights the importance of instituting a systematic approach to evaluating the branch pulmonary arteries. Of note, only 54% of the reports mentioned left ventricular ejection fraction (5/6 area*length or biplane method) despite the known association of left and right ventricular dysfunction, with impaired clinical status and adverse outcomes [2]. Measures of diastolic function (E/e’) were also were rarely commented on (3.1%). Interestingly, while qualitative estimation of left ventricular systolic function was less common than the quantitative evaluation, this was reversed for right ventricular systolic function. A possible explanation is that quantitative assessment of left
Fig. 3. Box-and-whisker plot showing the distribution of the adherence rate (%) within each center. The mean adherence rate (%) ranges from 52 ± 13% to 70 ± 9% (p < 0.0001) across the centers, and the variability (standard deviation) between patients from the same center ranged from 9% to 13%.
ventricle is more commonly practiced by the imager/sonographer who automatically enters these indices in the TTE report whereas the TTE reader most likely focuses on qualitative assessment of right ventricle in these studies as part of the clinical evaluation. Analysis of study performance limitations to obtaining pertinent echocardiographic data showed a positive correlation between total score, age, and body surface area. This could potentially be due to older patients being able to lay still for a longer period than younger patients, resulting in acquisition of more complete information. It is also conceivable that adherence increases with age as the concerns with RV size and function increase as these patients get older. Interestingly, although 24% of the reports documented a reason for suboptimal image acquisition or incomplete data, there was no statistically significant difference in total scores compared to reports that did not mention a barrier. This could be due to incomplete documentation of barriers during the procedure. None of the echocardiogram reports listed time constraints as a potential study performance limitation. Reasons for poor adherence most likely differ among each center and could be due to insufficient knowledge, training, or lack of adequate promotion of the guidelines. Providing a checklist to the sonographers and quarterly review of guidelines with sonographers and cardiologists might improve the poor adherence. It is also conceivable that clinical priorities differ amongst centers as well as clinical providers who might not all agree with all the elements recommended by the guidelines. While we believe that adherence to the recommended echo guidelines would be helpful for the communication between caretakers of the individual patients, it remains, however, questionable if this would ultimately affect the final treatment of the individual patients, bearing in mind that many functional parameters for RV and RVOT in TOF are often operator-dependent, resulting probably in a wider variability in measurements than in allocated management decisions. Furthermore, evaluation of postop TOF patients with and without conduit in the clinic by clinical examination (including ECG and chest x-ray), echocardiography, magnetic resonance imaging (MRI), computerized tomography (CT), and finally cardiac catheterization to guide decision making with regards to re-intervention has become more or less standardized in tertiary centers around the world. As progression of such lesions is usually slow, the clinical cardiologist who sees these patients in the outpatient clinic will most likely be keen on
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx
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obtaining more definitive imaging data using other modalities as the next step based on current “suboptimal” TTE reporting. This study highlights the need for incorporation of an educational component as well as a clinical implementation phase as guidelines are created and rolled out to inform providers with the best clinical practice. Given the results of this study, the next steps for this purpose might involve an educational intervention followed by collection of data on implementation and impact on clinical outcomes for further fine-tuning of the guidelines.
https://doi.org/10.1016/j.ijcard.2019.09.075.
5. Limitations
References
There are several limitations to our study. This retrospective, multicenter study only looked at the documented echocardiogram reports and not the actual images. Differences in documentation could be secondary to institutional protocols including variations in the reporting templates and might not represent lack of acquired imaging data and true adherence to the imaging protocol as recommended by the guidelines. Additionally, it is possible that the study inclusion period started too early after the publication of guidelines and therefore there was not enough time for some centers to adjust their TTE reports to the current guidelines. Finally, we elected not to define “good adherence”. Instead, we described a median adherence rate of 61% as suboptimal which might not be generally applicable.
[1] A. Frigiola, A.N. Redington, S. Cullen, M. Vogel, Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot, Circulation 110 (11 Suppl 1) (2004) II153eII157. [2] T. Geva, B.M. Sandweiss, K. Gauvreau, J.E. Lock, A.J. Powell, Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging, J. Am. Coll. Cardiol. 43 (2004) 1068e1074. [3] M.A. Gatzoulis, S. Balaji, S.A. Webber, et al., Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study, Lancet 356 (9234) (2000) 975e981. [4] A. Samman, M. Schwerzmann, O.H. Balint, et al., Exercise capacity and biventricular function in adult patients with repaired tetralogy of Fallot, Am. Heart J. 156 (1) (2008) 100e105. [5] A.M. Valente, K. Gauvreau, G.E. Assenza, et al., Rationale and design of an International Multicenter Registry of patients with repaired tetralogy of Fallot to define risk factors for late adverse outcomes: the INDICATOR cohort, Pediatr. Cardiol. 34 (1) (2013) 95e104. [6] A.M. Valente, S. Cook, P. Festa, et al., Multimodality imaging guidelines for patients with repaired tetralogy of fallot: a report from the American society of echocardiography: developed in collaboration with the society for cardiovascular magnetic resonance and the society for pediatric radiology, J. Am. Soc. Echocardiogr. 27 (2) (2014) 111e141. [7] P.A. Harris, R. Taylor, R. Thielke, J. Payne, N. Gonzalez, J.G. Conde, Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support, J. Biomed. Inform. 42 (2) (2009) 377e381. [8] R. Sachdeva, P.S. Douglas, M.S. Kelleman, et al., Effect of release of the first pediatric appropriate use criteria on transthoracic echocardiogram ordering practice, Am. J. Cardiol. 118 (2016) 1545e1551. [9] R. Sachdeva, P.S. Douglas, M.S. Kelleman, et al., Educational intervention for improving the appropriateness of transthoracic echocardiograms ordered by pediatric cardiologists, Congenit. Heart Dis. 12 (3) (2017) 373e381. [10] J.G. Stevenson, Adherence to physician training guidelines for pediatric transesophageal echocardiography affects the outcome of patients undergoing repair of congenital cardiac defects, J. Am. Soc. Echocardiogr. 12 (3) (1999) 165e172. [11] L.L. Mertens, M.K. Friedberg, Imaging the right ventricle–current state of the art, Nat. Rev. Cardiol. 7 (10) (2010) 551e563. [12] C. Srinivasan, R. Sachdeva, W.R. Morrow, S.B. Greenberg, H.V. Vyas, Limitations of standard echocardiographic methods for quantification of right ventricular size and function in children and young adults, J. Ultrasound Med. 30 (4) (2011) 487e493. [13] L.G. Rudski, W.W. Lai, J. Afilalo, L. Hua, M.D. Handschumacher, K. Chandrasekaran, S.D. Solomon, E.K. Louie, N.B. Schiller, Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American society of echocardiography endorsed by the European association of echocardiography, a registered branch of the European society of cardiology, and the Canadian society of echocardiography, J. Am. Soc. Echocardiogr. 23 (7) (2010), 685-713-718. [14] S.M. Lang, R.L. Crawford, P. Shivaram, et al., Feasibility of transthoracic echocardiography evaluation of pulmonary arteries following arterial switch operation, Pediatr. Cardiol. (2018), https://doi.org/10.1007/s00246-018-19241926. Available from:.
6. Conclusions The overall adherence to the most recent published imaging and reporting guidelines for echocardiographic surveillance of children with repaired TOF patients was suboptimal with significant variation across the centers. Suboptimal adherence to published reporting guidelines might diminish effective communication among those caring for these patients that require lifelong care and might potentially delay evaluation of possible complications after TOF repair. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes. We believe that this study brings a new light to guidelines in general, their implementation, and the implications of adherence. Declaration of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Appendix A. Supplementary data Supplementary data to this article can be found online at
Appendix Transthoracic echocardiogram scoring sheets for patients with right ventricular to pulmonary artery (RV-to-PA) conduits and for patients without RV-to-PA conduits (forms below).
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?* Vidhya Annavajjhala a, Anne Marie Valente b, Leo Lopez c, Ritu Sachdeva d, Julie S. Glickstein e, Shobha S. Natarajan f, Sujatha Buddhe g, Karen Altmann e, Brian D. Soriano g, John L. Colquitt h, Carolyn A. Altman h, Nao Sasaki c, Charlotte Sakarovitch a, Theresa A. Tacy a, Tal Geva b, Elif Seda Selamet Tierney a, * a
Lucile Packard Children’s Hospital, Stanford University Medical Center, Palo Alto, CA, USA Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA c Nicklaus Children’s Hospital, Miami, FL, USA d Emory University School of Medicine and Children’s Healthcare of Atlanta Sibley Heart Center Cardiology, Atlanta, GA, USA e Morgan Stanley Children’s Hospital of New York, Columbia University Medical Center, New York, NY, USA f The Children’s Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA g University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA h Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 May 2019 Received in revised form 14 August 2019 Accepted 27 September 2019 Available online xxx
Background: Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations. Methods: This was a multi-center (n ¼ 8) retrospective review of TTE reports in children 11 years of age who have had complete TOF repair. We included 10 patients from each participating center (n ¼ 80) and scored 2 outpatient follow-up TTE reports on each patient. The adherence rate was based on completeness of TTE reporting elements derived from the guidelines. Results: We reviewed 160 TTE reports on 80 patients. Median age was 4.4 months (IQR 1.5-6.6) and 3.6 years (IQR 1.3-6.4) at the time of complete surgical repair and first TTE report, respectively. The median adherence rate to recommended reporting elements was 61% (IQR 53e70). Of the 160 reports, 9 (7%) were 80% adherent and 40 (25%) were 70% adherent. Quantitative measurements of right ventricular outflow tract (RVOT), right ventricular (RV) size and function, and branch pulmonary arteries were least likely to be reported. Conclusions: Overall adherence to the most recent published imaging guidelines for surveillance of children with repaired TOF patients was suboptimal, especially for reporting of RVOT, RV size and function, and branch pulmonary arteries. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes. © 2019 Elsevier B.V. All rights reserved.
Keywords: Tetralogy of Fallot Echocardiography Guidelines Adherence
1. Introduction Long-term outcomes of patients after repair of tetralogy of Fallot
* The author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. * Corresponding author. 750 Welch Road, Outpatient Heart Center, Palo Alto, CA, 94306, USA. E-mail address: [email protected] (E.S. Selamet Tierney).
(TOF) are impacted by residual anatomic and hemodynamic abnormalities such as pulmonary valve regurgitation or stenosis, right ventricular (RV) dilation and biventricular dysfunction [1,2]. There is an increased incidence of arrhythmias (~43%), exercise intolerance (28% had severely decreased exercise capacity with <50% predicted peak oxygen consumption), heart failure (12% NYHA functional class III), and sudden cardiac death beginning in early adulthood, which are often attributed to these abnormalities [3e5]. Therefore, longitudinal clinical surveillance is crucial in this patient
https://doi.org/10.1016/j.ijcard.2019.09.075 0167-5273/© 2019 Elsevier B.V. All rights reserved.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
2
V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx
Nomenclature
Abbreviations RV Right ventricle RVOT Right ventricular outflow tract PA Pulmonary artery TOF Tetralogy of Fallot TTE Transthoracic echocardiography
population. Transthoracic echocardiography (TTE) remains the primary tool for evaluating young children after TOF repair and provides clinicians with information that helps clinical decision making. In February 2014, the American Society of Echocardiography published multimodality non-invasive imaging guidelines for patients after TOF repair [6]. The goal of this document was to provide imaging guidelines to optimize data acquisition and help augment clinical decision making. The document recommends a list of major reporting elements with multiple subcomponents that should be addressed during routine TTE assessment for surveillance in this patient population (Supplemental Table). In this multicenter study, we sought to determine the adherence to these guidelines. 2. Methods This was a multi-center retrospective review of TTE reports performed in children who had undergone complete repair of TOF with pulmonary stenosis or atresia. We included 10 patients from each of the eight participating centers (n ¼ 80) including Boston Children’s Hospital, Children’s Healthcare of Atlanta, Children’s Hospital of Philadelphia, Lucile Packard Children’s Hospital at Stanford (Core Institution), Morgan Stanley Children’s Hospital of New York, Nicklaus Children’s Hospital, Seattle Children’s Hospital and Texas Children’s Hospital. The project was approved by the Institutional Review Boards at the participating centers. De-identified TTE reports were reviewed and scored at the Core Institution by a single reviewer. Data were collected and managed using REDCap electronic data capture tools hosted at the Stanford Center for Clinical Informatics [7]. Criteria for inclusion were pediatric patients 11 years of age status post complete repair of TOF with pulmonary valve stenosis or atresia who have undergone two outpatient TTEs (ECHO 1 and ECHO 2 in temporal order) performed at least six months apart between March 2014 and March 2016. We chose this age group as the acoustic windows tend to be better in younger children and pre-adolescents compared to older patients with larger body sizes. Patients who underwent a re-intervention after complete TOF repair were also included. The centers were invited to participate in the study in June 2016. The study inclusion dates were chosen 1) to capture the TTEs performed after the publication date of the guidelines, and 2) to ensure that the TTEs were obtained prior to the date when the invitation was sent to the centers to avoid a response bias. The centers identified two patients who met the inclusion criteria by medical record review. We analyzed two de-identified outpatient follow-up TTE reports performed between March 2014 to March 2016 on each patient. Each center was given instructions to randomly select patients who met inclusion criteria using a random number generator on Microsoft Excel or their preferred program to obtain random patients which provided a heterogenous population. Additional data collected (on a study form filled by the centers) included age at TTE,
age at complete TOF repair, additional medical and surgical diagnoses, study performance limitations (poor acoustic windows, “patient cooperation”, or time constraints), and any interval imaging by modalities other than TTE. Separate scoring sheets were derived for patients with and without a right ventricular to pulmonary artery (RV-to-PA) conduit (Appendix). The scoring was based on the TTE reporting elements and subcomponents (pertinent positives and negatives) derived from the guidelines. The highest possible scores for patients with conduit and without a conduit were 16.5 and 17.5 respectively. The adherence score for each TTE report was calculated as a percentage of the sum total of the subcomponent scores divided by the highest possible score. The subcomponents scores were also calculated as a percentage by dividing the absolute total subcomponent score by the highest possible subcomponent score. In order to assess inter-observer variability, a second investigator scored the reports using the same method on a randomly selected subset of 8 individual patients (total of 16 reports), which was derived using a random number generator on Microsoft Excel. The second reader was blinded to the initial scores. The outcome measure was the adherence rate to the guidelines which was defined as the ratio of the total calculated score to the highest possible score x 100. Statistical analysis was performed using GraphPad Prism (Version 7.0) and SAS Software (Version 9.4; SAS Institute, Cary, NC). Descriptive statistics were calculated for all variables of interest and included medians with 25the75th percentiles (interquartile range, IQR) or counts with percentages when appropriate. To assess the association of the adherence rate with variables of interest (age, body surface area, and reported barriers), we ran a linear mixed regression model to take into account the repeated measurement within each patient and the clustered design within centers. Therefore, the patient nested into centers are considered as random effect and the variable of interest as a fixed effect in the linear regression of total score. Our sample size calculation showed that we required 138 reports to obtain a 95% confidence level, a desired total width of confidence interval of 5 and a standard deviation of the variable of 15 to detect clinically relevant differences. Adherence rates were also compared between ECHO 1 and ECHO 2 on the same patients as well as patients with an RV-to-PA conduit and without an RV-to-PA conduit. Intra-class correlation coefficient analysis was used to calculate inter-observer variability. Statistical significance was defined by a p-value <0.05. 3. Results One hundred and sixty TTE reports were scored on 80 individual patients (47 males, 59%). The median age was 4.4 months (IQR 1.56.6) at the time of complete surgical repair and 3.6 years (IQR 1.36.4) at the time of ECHO 1. Of the 80 patients, 20 (25%) had a surgical repair requiring a RV-to-PA conduit. Of the 160 reports, 9 (7%) were 80% adherent and 40 (25%) were 70% adherent (Fig. 1). The median total score was 61% (IQR 53e70). There was no significant difference in adherence rate between TTE reports in patients with and without an RV-to-PA conduit (p ¼ 0.34). The intra-class correlation coefficient used to assess inter-observer variability of TTE report scoring was 0.91 (95% CI: 0.74-0.97). Adherence to the guidelines was lowest when reporting quantitative measurements of RV size and function as well as branch pulmonary arteries. The overall median adherence rates for assessment of RV size was 33% (IQR 11e33), RV function was 20% (IQR 20e40) and 33% (IQR 33e67) for the branch pulmonary arteries (Fig. 2). Further breakdown of RV and PA subcomponents are listed in Table 1.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
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that the mean adherence rate ranged from 52 ± 13% to 70 ± 9% (p < 0.0001) and the variability (standard deviation) between patients from the same center ranged from 9% to 13%. Comparison of the two TTE reports (ECHO 1 and ECHO 2) on the same patient showed no difference in adherence rate (mean difference 0.01, p ¼ 0.47).
4. Discussion
`Fig. 1. Adherence rate (%) of reporting to current guidelines.
The adherence rate for qualitative assessment of both RV size and volume was 99.4% and 97.3% respectively. Quantitative measurements of the RV outflow tract, pulmonary valve, and reporting of Doppler gradients was suboptimal with a median score of 67% (IQR 48e75). Of the 160 TTE reports, 73 (45%) reported the qualitative assessment of left ventricular systolic function, 86 (54%) of the reports had quantitative assessment of left ventricular systolic function using either the 5/6 area* length method or the Simpson’s Biplane method as recommended by the guidelines [6] and 1 did not contain either qualitative or quantitative left ventricular functional assessment. Relationships between age, body surface area, barriers reported (poor acoustic windows, patient agitation, time limitations) and adherence demonstrated that adherence rate increased on average by 1% for each year of age (p ¼ 0.0072), and by 1.3% for each increase of 0.1 m2 body surface area (p ¼ 0.0071). Of the 160 TTE reports, 39 (24.4%) documented the presence of a study performance limitation that resulted in a limited/suboptimal echo. Adherence rate was higher in reports that did not document barriers (62.2 ± 11.3% vs 57.6 ± 13.6%); however, after accounting for repeated measurements and clusters, the difference was not statistically significant (p ¼ 0.16). Comparison of the adherence rate across centers (Fig. 3) showed
The Multimodality Non-Invasive Imaging Guidelines by the American Society of Echocardiography recommends a list of major reporting elements with several subcomponents that should be addressed during routine TTE in children with repaired TOF [6]. In this multicenter study, we sought to determine the adherence to these recommended reporting elements. Our results demonstrated that overall adherence to these guidelines was suboptimal with significant variation among centers. There are limited data on adherence to imaging guidelines in pediatric cardiology. Sachdeva et al. [8] examined the effect of published pediatric appropriate use criteria on TTE use in clinical practice at multiple centers and similarly found that the published guideline had minimal effect on physician practice and also significant variability amongst the centers [8]. However, a follow-up study evaluating the effectiveness of educational intervention after publication of the appropriate use criteria resulted in some improvement in the appropriateness of 4542 TTE’s ordered after the educational intervention across the centers participating in the study (72.5%e76.2%, p ¼ 0.04) [9]. It has also been shown that adherence to physician training and qualification guidelines for performance of pediatric transesophageal echocardiography impacts immediate outcomes such as adequacy of echocardiographic recordings and decision to return to cardiac bypass based on the echocardiographic findings [10]. Our results demonstrated that the overall adherence to the guidelines was suboptimal, especially for reporting of quantitative assessment of RV size, RV function, RV outflow tract, and the branch pulmonary arteries. We speculate that the complex anatomy of the RV along with the heavily trabeculated walls and poor endocardial definition could have contributed to lower scores in the subsections pertaining to quantitative assessment of RV size and RV function [11]. Although the guidelines recommend quantification of RV
Fig. 2. Adherence rates within subsections.
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
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V. Annavajjhala et al. / International Journal of Cardiology xxx (xxxx) xxx Table 1 Breakdown of right ventricular and pulmonary artery subcomponents. A. Right Ventricular Size and Volume Sub-components Tricuspid valve annulus dimension Septal flattening (diastole) Base Mid-ventricular level Diastolic length Diaphragmatic wall thickness Qualitative assessment of right ventricular volume B. Right Ventricular Function Sub-components TAPSE Pulsed Doppler peak s’ Fractional area change (%) E/e’ ratio Qualitative assessment of right ventricular function C. Branch Pulmonary Arteries Sub-components Dimensions of one or both branch PAs Mention of presence or absence of PA obstruction
Adherence rate (%) 18.8 38.1 0 0 0 0.6 99.4 Adherence rate (%) 23.8 16.3 10.6 3.1 97.3 Adherence rate (%) 45 71.8
E: peak early filling velocity, e’- early diastolic peak velocity, s’-systolic velocity, PA: pulmonary artery, TAPSE: tricuspid annular plane systolic excursion.
function, in reality, very few echocardiographic laboratories use this on a routine basis due to the challenges stated above [12,13]. Interestingly, a recent study in pediatric patient with D-looped transposition of the great arteries who underwent arterial switch operation with the LeCompte maneuver reported suboptimal visualization of the branch pulmonary arteries by TTE regardless of their age [14]. Although this is a different patient cohort, this study highlights the importance of instituting a systematic approach to evaluating the branch pulmonary arteries. Of note, only 54% of the reports mentioned left ventricular ejection fraction (5/6 area*length or biplane method) despite the known association of left and right ventricular dysfunction, with impaired clinical status and adverse outcomes [2]. Measures of diastolic function (E/e’) were also were rarely commented on (3.1%). Interestingly, while qualitative estimation of left ventricular systolic function was less common than the quantitative evaluation, this was reversed for right ventricular systolic function. A possible explanation is that quantitative assessment of left
Fig. 3. Box-and-whisker plot showing the distribution of the adherence rate (%) within each center. The mean adherence rate (%) ranges from 52 ± 13% to 70 ± 9% (p < 0.0001) across the centers, and the variability (standard deviation) between patients from the same center ranged from 9% to 13%.
ventricle is more commonly practiced by the imager/sonographer who automatically enters these indices in the TTE report whereas the TTE reader most likely focuses on qualitative assessment of right ventricle in these studies as part of the clinical evaluation. Analysis of study performance limitations to obtaining pertinent echocardiographic data showed a positive correlation between total score, age, and body surface area. This could potentially be due to older patients being able to lay still for a longer period than younger patients, resulting in acquisition of more complete information. It is also conceivable that adherence increases with age as the concerns with RV size and function increase as these patients get older. Interestingly, although 24% of the reports documented a reason for suboptimal image acquisition or incomplete data, there was no statistically significant difference in total scores compared to reports that did not mention a barrier. This could be due to incomplete documentation of barriers during the procedure. None of the echocardiogram reports listed time constraints as a potential study performance limitation. Reasons for poor adherence most likely differ among each center and could be due to insufficient knowledge, training, or lack of adequate promotion of the guidelines. Providing a checklist to the sonographers and quarterly review of guidelines with sonographers and cardiologists might improve the poor adherence. It is also conceivable that clinical priorities differ amongst centers as well as clinical providers who might not all agree with all the elements recommended by the guidelines. While we believe that adherence to the recommended echo guidelines would be helpful for the communication between caretakers of the individual patients, it remains, however, questionable if this would ultimately affect the final treatment of the individual patients, bearing in mind that many functional parameters for RV and RVOT in TOF are often operator-dependent, resulting probably in a wider variability in measurements than in allocated management decisions. Furthermore, evaluation of postop TOF patients with and without conduit in the clinic by clinical examination (including ECG and chest x-ray), echocardiography, magnetic resonance imaging (MRI), computerized tomography (CT), and finally cardiac catheterization to guide decision making with regards to re-intervention has become more or less standardized in tertiary centers around the world. As progression of such lesions is usually slow, the clinical cardiologist who sees these patients in the outpatient clinic will most likely be keen on
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075
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obtaining more definitive imaging data using other modalities as the next step based on current “suboptimal” TTE reporting. This study highlights the need for incorporation of an educational component as well as a clinical implementation phase as guidelines are created and rolled out to inform providers with the best clinical practice. Given the results of this study, the next steps for this purpose might involve an educational intervention followed by collection of data on implementation and impact on clinical outcomes for further fine-tuning of the guidelines.
https://doi.org/10.1016/j.ijcard.2019.09.075.
5. Limitations
References
There are several limitations to our study. This retrospective, multicenter study only looked at the documented echocardiogram reports and not the actual images. Differences in documentation could be secondary to institutional protocols including variations in the reporting templates and might not represent lack of acquired imaging data and true adherence to the imaging protocol as recommended by the guidelines. Additionally, it is possible that the study inclusion period started too early after the publication of guidelines and therefore there was not enough time for some centers to adjust their TTE reports to the current guidelines. Finally, we elected not to define “good adherence”. Instead, we described a median adherence rate of 61% as suboptimal which might not be generally applicable.
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6. Conclusions The overall adherence to the most recent published imaging and reporting guidelines for echocardiographic surveillance of children with repaired TOF patients was suboptimal with significant variation across the centers. Suboptimal adherence to published reporting guidelines might diminish effective communication among those caring for these patients that require lifelong care and might potentially delay evaluation of possible complications after TOF repair. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes. We believe that this study brings a new light to guidelines in general, their implementation, and the implications of adherence. Declaration of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Appendix A. Supplementary data Supplementary data to this article can be found online at
Appendix Transthoracic echocardiogram scoring sheets for patients with right ventricular to pulmonary artery (RV-to-PA) conduits and for patients without RV-to-PA conduits (forms below).
Please cite this article as: V. Annavajjhala et al., Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.09.075