Vicious circle between progressive right ventricular dilatation and pulmonary regurgitation in patients after tetralogy of Fallot repair? Right heart enlargement promotes flow reversal in the left pulmonary artery

Kato et al. Journal of Cardiovascular Magnetic Resonance (2016) 18:34 DOI 10.1186/s12968-016-0254-1 RESEARCH Open Access Vicious circle between progressive right ventricular dilatation and pulmonary regurgitation in patients after tetralogy of Fallot repair? Right heart enlargement promotes flow reversal in the left pulmonary artery Atsuko Kato1†, Christian Drolet1,2†, Shi-Joon Yoo1,3, Andrew N. Redington1,4 and Lars Grosse-Wortmann1,3* Abstract Background: The left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation (PR) in patients after tetralogy of Fallot (TOF) repair, but the mechanism of this difference is not well understood. This study aimed to analyze the interplay between heart and lung size, mediastinal geometry, and differential PR. Methods: Forty-eight Cardiovascular Magnetic Resonance (CMR) studies in patients after TOF repair were analyzed. In addition to the routine blood flow and ventricular volume quantification cardiac angle between the thoracic anterior-posterior line and the interventricular septum, right and left lung areas as well as right and left hemithorax areas were measured on an axial image. Statistical analysis was performed to compare flow parameters between RPA and LPA and to assess correlation among right ventricular volume, pulmonary blood flow parameters and lung area. Results: There was no difference between LPA and RPA diameters. The LPA showed significantly less total forward flow (2.49 ± 0.87 L/min/m2 vs 2.86 ± 0.89 L/min/m2; p = 0.02), smaller net forward flow (1.40 ± 0.51 vs 1.89 ± 0. 60 mL/min/m2; p = <0.001), and greater regurgitant fraction (RF) (34 ± 10 % vs 43 ± 12 %; p = 0.001) than the RPA. There was no difference in regurgitant flow volume between RPA and LPA (p = 0.29). Indexed right ventricular end-diastolic volume (RVEDVi) correlated with LPA RF (R = 0.48, p < 0.001), but not with RPA RF (p = 0.09). Larger RVEDVi correlated with a more leftward cardiac axis (R = 0.46, p < 0.001) and with smaller left lung area (R = −0.58, p < 0.001). LPA RF, but not RPA RF, correlated inversely with left lung area (R = −0.34, p = 0.02). The follow-up CMRs in 20 patients showed a correlation of the rate of RV enlargement with the rates of LPA RF worsening (R = 0.50, p = 0.03), and of increasing left lung compression (R = −0.55, p = 0.012). Conclusion: An enlarged and levorotated heart is associated with left lung compression and impaired flow into the left lung. Keywords: Differential pulmonary blood flow, Pulmonary regurgitation, Tetralogy of Fallot, Right ventricular enlargement, Cardiovascular magnetic resonance * Correspondence: † Equal contributors 1 Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto M5G 1X8, ON, Canada 3 Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kato et al. Journal of Cardiovascular Magnetic Resonance (2016) 18:34 Page 2 of 8 Background Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Early postoperative outcomes after closure of the ventricular septal defect and reconstruction of the right ventricular outflow tract are excellent in the majority of patients [1]. However, chronic pulmonary regurgitation (PR) after TOF repair is a major determinant of long-term outcomes. Right ventricular (RV) dilation, resulting from PR, is associated with exercise intolerance, ventricular arrhythmia, and mortality [2–4]. Despite a wealth of evidence for the association of PR and RV dilation, the driving forces behind PR remain incompletely understood [5–8]. Cardiovascular Magnetic Resonance (CMR) is the gold standard for the quantification of PR and RV volume [9–12]. Using phase-contrast CMR, we previously demonstrated that PR is greater in the left pulmonary artery (LPA) than in the right pulmonary artery (RPA) in pediatric patients after TOF repair [13]. The size of each branch pulmonary artery did not explain the difference in flow reversal. Harris and colleagues [14], confirming our findings of a greater RF in the LPA, found evidence that higher pulmonary vascular resistance (PVR) in the left lung may be responsible for the augmented diastolic flow reversal. However, the support for this mechanism was indirect and the etiology of a unilaterally elevated left-sided PVR remains unclear. Based on these previous reports and our clinical observations, we hypothesized that compression of the left lung, as a result of cardiomegaly and rotation of the heart into the left chest, leads to greater LPA flow reversal. The objective of this study was to assess the relationship between heart size, mediastinal geometry and differential pulmonary regurgitation. surgical procedure, were retrospectively collected from the patients’ medical records. This study was approved by the institutional research ethics board, and consent was waived. Methods We retrospectively analyzed the CMR studies performed in patients after TOF repair at our institution between June 2007 and November 2009. Patients with a RV to pulmonary artery conduit, status post stent implantation in the main pulmonary artery (MPA) or branch pulmonary arteries, more than mild discrete branch pulmonary artery narrowing defined by gradient >20 mmHg estimated via Doppler echocardiography, less than mild MPA regurgitation, defined as a regurgitant fraction (RF) <10 %, were excluded. Likewise, those with dextrocardia, congenital absence of the pulmonary valve, or a previous pulmonary valve replacement were excluded. The first CMR during the study period was included. For those patients who had undergone more than one CMR up until March 2016, the latest CMR study before pulmonary valve replacement was included as follow-up to delineate the change in geometric, volumetric, and flow parameters relative to the others. Clinical data including age at CMR, age at surgery, CMR All patients underwent clinical CMR examinations at 1.5 T ('Avanto', Siemens Healthcare, Erlangen, Germany). The protocol consisted of scout imaging of the entire thorax in the axial plane using standard ECG gated steady state free precession (SSFP) imaging. A stack of SSFP short axis cine loops for ventricular volumetry a (...truncated)