TY - JOUR
AU - Cox, Natasha
AB - Abstract Open in new tabDownload slide Open in new tabDownload slide OBJECTIVES Right ventricular dysfunction predicts death in patients with hypoplastic left heart syndrome (HLHS), but differences in morphology and loading conditions make calculation of the ejection fraction (EF), a challenging measure of its function. Our goal was to evaluate how strain measurements with cardiac magnetic resonance feature tracking could be used to evaluate right ventricular function in patients with HLHS. METHODS A systematic search of the literature was performed by 2 independent researchers using the terms ‘population’, ‘intervention’, ‘comparison’, ‘outcome’ and ‘time criteria’. PubMed and the Ovid database were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Our review included 8 studies with 608 participants with ventricular strain values obtained using cardiac magnetic resonance feature tracking. After stage I palliation, global strain was reduced in patients after a hybrid procedure and a right ventricle-to-pulmonary artery conduit compared with a modified Blalock–Taussig shunt despite similar EFs. Global longitudinal strain did not differ between stage II and stage III (Fontan) palliation. Fontan patients had significantly impaired global longitudinal and circumferential strain compared to the left ventricular strain of the controls. Studies of Fontan patients that included patients with HLHS who were part of a cohort with a single right ventricle showed impaired global circumferential strain compared with the cohort with a single left ventricle, with controls, and over time. In this group, impaired global circumferential strain was associated with major adverse cardiac events. CONCLUSIONS Cardiac magnetic resonance feature tracking can be used in patients with HLHS to evaluate RV strain and demonstrate differences between surgical strategies, over time and compared with controls. It could be used alongside clinical symptoms and EF values to detect ventricular dysfunction. Hypoplastic left heart syndrome, Cardiac magnetic resonance, Ventricular strain INTRODUCTION Hypoplastic left heart syndrome (HLHS) is a group of congenital heart defects with a non-apex-forming left ventricle (LV), in which the right ventricle (RV) assumes a systemic role. This role includes (i) mitral and aortic atresia associated with a ‘slit-like’ LV; (ii) mitral stenosis and aortic atresia, which can be associated with a ‘small (LV) cavity with a thick parietal wall’; (iii) mitral and aortic stenosis that can be associated with a ‘miniature’ LV; (iv) mitral atresia, aortic stenosis and a ventricular septal defect; and (v) a hypoplastic left heart complex with a hypoplastic aorta and an LV that is small or unable to support systemic circulation. Occasionally, there is LV dilation associated with mitral regurgitation and an enlarged left atrium [1]. The size and shape of the hypoplastic LV can have a significant impact on RV geometry and evaluation by imaging [2–4]. Although the Single Ventricle Reconstruction trial did not find any effect of LV size on RV function or death, other studies found worse RV function and prognosis in the subgroup of patients with HLHS with mitral stenosis and aortic atresia [3–5]. This result has been attributed to the compression of the RV cavity by the poorly contractile LV cavity without an outflow and inadequate myocardial perfusion of the hypertrophied LV wall [4, 5]. The surgical staged palliation of patients with HLHS begins with stage I palliation, where unobstructed systemic outflow (via arch reconstruction in the Norwood procedure or a ductal stent in the hybrid procedure) and controlled pulmonary blood flow [via a modified Blalock–Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery (RVPA) conduit in the Norwood procedure, or pulmonary artery bands in the hybrid procedure] are established. This stage is followed by a stage II superior bidirectional cavopulmonary connection at 4–6 months of age, and a completion Fontan (total cavopulmonary connection) at 18–48 months of age [6]. In clinical practice, an ejection fraction (EF) measured with cardiac magnetic resonance (CMR) is currently considered the gold standard for non-invasive evaluation of RV systolic function in patients with HLHS [1, 7]. Although a visual estimation of systolic RV function on echocardiography is widely used in patients with HLHS, it is prone to error due the anterior position of the RV, which may limit acoustic windows and the effect of the shape of the accompanying hypoplastic LV [2, 7]. The volumes estimated from ultrasound tend to be smaller than those obtained by CMR due to shadowing phenomena and different inclusion criteria for the ventricular volume [8]. In addition, the common presence of atrioventricular valve (AVV) regurgitation and of changing loading conditions between different stages of surgical palliation in HLHS makes accurate EF calculation challenging [1, 2, 7, 9]. Instead, CMR can be used to measure ventricular deformation without geometric assumptions and allows quantitative evaluation of regional function with good reproducibility [10–12]. Myocardial strain measurement was shown to be less dependent on loading conditions than on the EF [11]. Strain measurement with cardiac magnetic resonance feature tracking (CMR-FT) can be obtained from standard images with short post-processing times by manually tracing either endocardial or endocardial and epicardial borders and activating an automated software algorithm that tracks the feature over the cardiac cycle and by frame [10, 13]. Strain values measure myocardial shortening or lengthening in the circumferential and longitudinal directions (negative values) and thickening or thinning in the radial direction (positive values) [14]. Values of a greater magnitude reflect improved motion [4]. Global strain values are obtained by averaging the peak strain values of predefined segments or based on the entire region of interest [15]. This situation has been previously described in speckle-tracking echocardiography, which remains dependent on suitable acoustic windows [16]. Therefore, the method of global strain calculation might have important implications for the calculation of strain values in different palliative approaches for HLHS, e.g. right ventriculotomy in RVPA. Global circumferential strain (GCS) has been shown to correlate with late gadolinium enhancement, which is used to identify myocardial fibrosis, which has in turn been associated with systolic dysfunction and ventricular arrhythmias [11, 17]. Previous studies in patients with HLHS undergoing staged palliation have shown that circumferential and radial strain values derived from CMR-FT can be used as indices of circumferential contraction and correlate with changes of global ventricular function [18]. This designation is important because RV dysfunction predicts death throughout the different stages of surgical palliation, including late deaths in patients after Fontan completion [1, 19]. The cause of RV dysfunction in HLHS remains incompletely understood, is likely multifactorial and differs among palliation strategies [20, 21]. In normal hearts, the RV has a thinner wall than the LV, and its separate inflow and outflow tracts are better suited to variations in preload rather than in afterload, which is problematic when it is committed to systemic resistance after surgical palliation for HLHS [22]. The first procedure confers the highest risk of death during staged palliation [23]. In the first interstage period, death is associated with recurrent, residual or progressive disease such as restrictive atrial septal defect, aortic arch obstruction, systemic-to-pulmonary artery shunt stenosis, pulmonary artery distortion, coronary insufficiency and AVV regurgitation, leading to progressive hypoxaemia and myocardial dysfunction [24]. AVV regurgitation can arise at any stage of palliation and can contribute to ventricular dysfunction due to resulting volume overload and ventricular dilatation; it can also negatively affect pulmonary blood flow [25]. Cardiac troponin I can be used to detect early signs of ischaemia, and a rise in brain natriuretic peptide (BNP) can be used to detect ventricular dysfunction because BNP usually decreases after the volume unloading procedure [1, 26]. In Fontan patients, ventricular dysfunction has been related to chronic hypoxia, multiple operations and diffuse fibrosis [27]. Ventricular fibrosis is associated with an increased collagen I to collagen III expression ratio but was not associated with ventricular failure in a small cohort of young Fontan patients [28]. However, in a cohort of late Fontan survivors, myocardial fibrosis evidenced by positive late gadolinium enhancement was associated with adverse ventricular mechanics and ventricular arrhythmias [29]. After the completion of stage III palliation, early detection of impaired systemic ventricle function and unfavourable haemodynamic blood flow patterns is crucial in the regular follow-up of Fontan patients, some of whom may require a transplant for a failing Fontan circulation [1, 30]. Targets of medical therapy in patients with HLHS consist mainly of afterload reduction in the systemic and pulmonary circulation. Although angiotensin-converting enzyme inhibitors are widely used for LV dysfunction, evidence in patients with HLHS is lacking. Use of pulmonary vasodilators such as phosphodiesterase-5 inhibitors was shown to improve cardiac output in Fontan patients [31]. Molecular changes that occur in the myocytes of patients with HLHS include downregulation of ß1-adrenoreceptors, preserved cyclic adenosine monophosphate and increased calcium/calmodulin-dependent protein kinase II activity, introducing potential targets for medical management such as ß-blockers [32, 33]. Recently, stem cell therapy has been studied to achieve myocardial protection and regeneration in patients with a dysfunctional systemic RV (SRV) [22]. The goal of our review was to investigate whether and how ventricular strain analysis obtained with CMR-FT could be used in patients with HLHS to assess RV function. PATIENTS AND METHODS Search strategy This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines [34]. A comprehensive search of the literature was conducted on Ovid and PubMed databases. Boolean operators were used to broaden the search results, utilizing a combination of the following search keywords: (HLHS OR hypoplastic left heart syndrome) AND (CMR OR magnetic resonance) AND strain, and Fontan AND CMR AND strain (Table 1). Table 1: Scope of the review in PICOT format Problem . Intervention . Comparison . Outcome . HLHS (newborn, infant, child, adult) Characterisation of ventricular strain as assessed by CMR-FT Control Single left ventricle (SLV) Feasibility of measurement Ventricular strain value Any clinical outcome Problem . Intervention . Comparison . Outcome . HLHS (newborn, infant, child, adult) Characterisation of ventricular strain as assessed by CMR-FT Control Single left ventricle (SLV) Feasibility of measurement Ventricular strain value Any clinical outcome Open in new tab Table 1: Scope of the review in PICOT format Problem . Intervention . Comparison . Outcome . HLHS (newborn, infant, child, adult) Characterisation of ventricular strain as assessed by CMR-FT Control Single left ventricle (SLV) Feasibility of measurement Ventricular strain value Any clinical outcome Problem . Intervention . Comparison . Outcome . HLHS (newborn, infant, child, adult) Characterisation of ventricular strain as assessed by CMR-FT Control Single left ventricle (SLV) Feasibility of measurement Ventricular strain value Any clinical outcome Open in new tab In PICOT format, the scope of the review could be framed as follows: Since CMR-FT is a relatively new technology, case series and cohort studies predominate in the current literature. Therefore, these studies were also included in the review despite their lower level in the hierarchy of evidence (B or C). Eligibility criteria Studies that were peer-reviewed and published in English were included in the analysis. Eligible studies were either retrospective or prospective studies on the use of CMR-FT to assess ventricular function in patients of any age with HLHS. Quality assessment Two reviewers independently evaluated the quality of the included studies using the Critical Appraisal Skills Programme for cohort studies: recruitment; outcome measurement; confounding factors; follow-up; and generalizability. Data extraction Two reviewers (MG and NC) independently screened the titles and abstracts of all identified references and determined their eligibility to be included in the analysis. The 2 reviewers then independently reviewed full texts of eligible articles and extracted the data into a data input sheet (Microsoft Excel for Mac 2017, Microsoft Corporation, Redmond, WA, USA), which included: Descriptive data: first author’s name, country, year of publication, number of patients, age of patients; Methodological data: study design, follow-up time, baseline comparability of groups; and Outcome data: strain data, main findings of the study. RESULTS Literature search outcome The search produced 140 records identified through database searching and 1 additional record identified through reference review. After duplicate removal, 102 records were screened and 86 records were excluded after title and abstract review. A total of 16 full-text articles were assessed for eligibility; 8 articles about the use of CMR-FT in the assessment of ventricular function in HLHS were included in the analysis (Fig. 1). Figure 1: Open in new tabDownload slide Preferred Reporting Items for Systematic Reviews and Meta‐Analysis flow diagram of literature searching and selection process used for the identification of eligible studies. CMR: cardiac magnetic resonance; HLHS: hypoplastic left heart syndrome. Figure 1: Open in new tabDownload slide Preferred Reporting Items for Systematic Reviews and Meta‐Analysis flow diagram of literature searching and selection process used for the identification of eligible studies. CMR: cardiac magnetic resonance; HLHS: hypoplastic left heart syndrome. Methodological quality and characteristics of selected studies Of the 8 studies included in the review, 2 were prospective, 5 were retrospective and in 1 the mode of patient recruitment was not stated. No study was randomized. The characteristics of selected studies including sample size, outcome measures, acknowledgement of confounders, follow-up period and generalizability are shown in Table 2. Table 2: Characteristics of selected studies Author . Year . Country . Type of study/ recruitment . Sample size (n) . Outcome measurement . Confounders acknowledged . Follow-up . Generalizability . Latus et al. [36] 2018 UK, Germany Retrospective Norwood (42), hybrid (44) GLS, GCS, GRS, EF Yes 24.3 ± 8.7 months Norwood I, 19.8+ to 12.7 months hybrid Yes Salehi Ravesh et al. [13] 2018 Germany Prospective Post-BCPC (14), post-TCPC (41) Specific strain values not given; EF Yes 0 Yes Stoll et al. [37] 2020 UK Not stated HLHS (16), other systemic RV (16), control (16) GLS, GCS, EF No 0 Not known Wong et al. [4] 2017 UK, USA Retrospective MBTS (59), RVPA (34) SLS, SCS, SRS, EF Yes 0 Yes Ghelani et al. [38] 2018 USA Retrospective Fontan—single RV (82; of which 62 HLHS), single LV (101) GLS, GCS, EF Yes 6.2 (3.6–9.5) years Mixed group of Fontan patients Kato et al. [27] 2017 Canada Retrospective Fontan—single RV (8; of which 6 HLHS), single LV (13), control (24) GLS, GCS, GRS, EF Yes 0 Mixed group of Fontan patients Latus et al. [30] 2020 Germany Retrospective Fontan—single RV (13, of which 10 HLHS), single LV (24) SLS, SCS, SRS, EF Yes 5.3 ± 0.9 years Mixed group of Fontan patients Meyer et al. [39] 2020 Holland Prospective Fontan—single RV (11, of which 3 HLHS), single LV (40) GLS, GCS, GRS, EF Yes 2.1 (2.0–2.3) years Mixed group of Fontan patients Author . Year . Country . Type of study/ recruitment . Sample size (n) . Outcome measurement . Confounders acknowledged . Follow-up . Generalizability . Latus et al. [36] 2018 UK, Germany Retrospective Norwood (42), hybrid (44) GLS, GCS, GRS, EF Yes 24.3 ± 8.7 months Norwood I, 19.8+ to 12.7 months hybrid Yes Salehi Ravesh et al. [13] 2018 Germany Prospective Post-BCPC (14), post-TCPC (41) Specific strain values not given; EF Yes 0 Yes Stoll et al. [37] 2020 UK Not stated HLHS (16), other systemic RV (16), control (16) GLS, GCS, EF No 0 Not known Wong et al. [4] 2017 UK, USA Retrospective MBTS (59), RVPA (34) SLS, SCS, SRS, EF Yes 0 Yes Ghelani et al. [38] 2018 USA Retrospective Fontan—single RV (82; of which 62 HLHS), single LV (101) GLS, GCS, EF Yes 6.2 (3.6–9.5) years Mixed group of Fontan patients Kato et al. [27] 2017 Canada Retrospective Fontan—single RV (8; of which 6 HLHS), single LV (13), control (24) GLS, GCS, GRS, EF Yes 0 Mixed group of Fontan patients Latus et al. [30] 2020 Germany Retrospective Fontan—single RV (13, of which 10 HLHS), single LV (24) SLS, SCS, SRS, EF Yes 5.3 ± 0.9 years Mixed group of Fontan patients Meyer et al. [39] 2020 Holland Prospective Fontan—single RV (11, of which 3 HLHS), single LV (40) GLS, GCS, GRS, EF Yes 2.1 (2.0–2.3) years Mixed group of Fontan patients BCPC: bidirectional cavopulmonary connection; EF: ejection fraction; GCS: global circumferential strain; GLS: global longitudinal strain; GRS: global radial strain; HLHS: hypoplastic left heart syndrome; LV: left ventricle; MBTS: modified Blalock–Taussig shunt; RV: right ventricle; RVPA: right ventricle-to-pulmonary artery; SCS: systolic circumferential strain; SLS: systolic longitudinal strain; SRS: systolic radial strain; TCPC: total cavopulmonary connection. Open in new tab Table 2: Characteristics of selected studies Author . Year . Country . Type of study/ recruitment . Sample size (n) . Outcome measurement . Confounders acknowledged . Follow-up . Generalizability . Latus et al. [36] 2018 UK, Germany Retrospective Norwood (42), hybrid (44) GLS, GCS, GRS, EF Yes 24.3 ± 8.7 months Norwood I, 19.8+ to 12.7 months hybrid Yes Salehi Ravesh et al. [13] 2018 Germany Prospective Post-BCPC (14), post-TCPC (41) Specific strain values not given; EF Yes 0 Yes Stoll et al. [37] 2020 UK Not stated HLHS (16), other systemic RV (16), control (16) GLS, GCS, EF No 0 Not known Wong et al. [4] 2017 UK, USA Retrospective MBTS (59), RVPA (34) SLS, SCS, SRS, EF Yes 0 Yes Ghelani et al. [38] 2018 USA Retrospective Fontan—single RV (82; of which 62 HLHS), single LV (101) GLS, GCS, EF Yes 6.2 (3.6–9.5) years Mixed group of Fontan patients Kato et al. [27] 2017 Canada Retrospective Fontan—single RV (8; of which 6 HLHS), single LV (13), control (24) GLS, GCS, GRS, EF Yes 0 Mixed group of Fontan patients Latus et al. [30] 2020 Germany Retrospective Fontan—single RV (13, of which 10 HLHS), single LV (24) SLS, SCS, SRS, EF Yes 5.3 ± 0.9 years Mixed group of Fontan patients Meyer et al. [39] 2020 Holland Prospective Fontan—single RV (11, of which 3 HLHS), single LV (40) GLS, GCS, GRS, EF Yes 2.1 (2.0–2.3) years Mixed group of Fontan patients Author . Year . Country . Type of study/ recruitment . Sample size (n) . Outcome measurement . Confounders acknowledged . Follow-up . Generalizability . Latus et al. [36] 2018 UK, Germany Retrospective Norwood (42), hybrid (44) GLS, GCS, GRS, EF Yes 24.3 ± 8.7 months Norwood I, 19.8+ to 12.7 months hybrid Yes Salehi Ravesh et al. [13] 2018 Germany Prospective Post-BCPC (14), post-TCPC (41) Specific strain values not given; EF Yes 0 Yes Stoll et al. [37] 2020 UK Not stated HLHS (16), other systemic RV (16), control (16) GLS, GCS, EF No 0 Not known Wong et al. [4] 2017 UK, USA Retrospective MBTS (59), RVPA (34) SLS, SCS, SRS, EF Yes 0 Yes Ghelani et al. [38] 2018 USA Retrospective Fontan—single RV (82; of which 62 HLHS), single LV (101) GLS, GCS, EF Yes 6.2 (3.6–9.5) years Mixed group of Fontan patients Kato et al. [27] 2017 Canada Retrospective Fontan—single RV (8; of which 6 HLHS), single LV (13), control (24) GLS, GCS, GRS, EF Yes 0 Mixed group of Fontan patients Latus et al. [30] 2020 Germany Retrospective Fontan—single RV (13, of which 10 HLHS), single LV (24) SLS, SCS, SRS, EF Yes 5.3 ± 0.9 years Mixed group of Fontan patients Meyer et al. [39] 2020 Holland Prospective Fontan—single RV (11, of which 3 HLHS), single LV (40) GLS, GCS, GRS, EF Yes 2.1 (2.0–2.3) years Mixed group of Fontan patients BCPC: bidirectional cavopulmonary connection; EF: ejection fraction; GCS: global circumferential strain; GLS: global longitudinal strain; GRS: global radial strain; HLHS: hypoplastic left heart syndrome; LV: left ventricle; MBTS: modified Blalock–Taussig shunt; RV: right ventricle; RVPA: right ventricle-to-pulmonary artery; SCS: systolic circumferential strain; SLS: systolic longitudinal strain; SRS: systolic radial strain; TCPC: total cavopulmonary connection. Open in new tab Patient characteristics and outcomes Only 4 studies reported data exclusively on patients with HLHS. Due to this limited availability, studies that included patients with HLHS as part of their pooled data analysis were also included. The results of these studies should be interpreted with caution because they might not be entirely representative of patients with HLHS. They are marked light grey in all tables included in the review. The review included patients with HLHS after stage I, II and III palliation. In addition, different types of stage I palliations were included, namely MBTS, RVPA and a hybrid approach. Patient characteristics and RV strain values are presented in Table 3. Statistically significant results are marked in bold. Studies were examined for confounders such as gestational age, age at operation and AVV regurgitation [24, 33, 35]. Table 3: Patient characteristics and strain measurements Study name . Year . Age . Patients (n) . Patient subset . GLS (%) . GCS (%) . GRS (%) . EF (%) . Latus et al. [38] 2018 Norwood: mean age 2.4 ± 0.8 months 86 MBTS (42) −16.5 ± 5.5 −18.4 ± 5.6 21.5 ± 9.5 59.4 ± 10.3 Hybrid mean age 2.0 ± 1.0 months Hybrid (44) −13.2 ± 5.9; P = 0.008 −14.7 ± 5.6; P = 0.001 13.9 ± 8.7; P = 0.0002 59.2 ± 9.0, P = 0.91 Salehi Ravesh et al. [13] 2018 Median age 4.9 years (1.6–17.0) 55 BCPC (14) Values not given 55 [50, 66] TCPC (41) P = 0.23 52 [31, 69]; P = 0.80 Stoll et al. [37] 2017 Mean age 20 ± 2 years 48 HLHS (16) −13 ± 4 −13 ± 4 54 ± 10 Systemic right ventricle (16) −12 ± 3 −12 ± 4 50 ± 11 Control (16) −18 ± 5; P < 0.001 RV: −13 ± 3; P = 0.6; LV: −16 ± 3; P = 0.004 62 ± 5; P < 0.05 Wong et al. [4] 2017 Stage 1 scan mean age 103 ± 24 days (MBTS); stage 2 scan mean age 172 ± 38 days (MBTS) 93 MBTS (59) −14.78 ± 5.68 (systolic) −16.90 ± 5.14 (systolic mid-strain) 24.76 ± 11.89 (systolic mid-strain) 57.9 ± 8.3 Stage 1 scan mean age 141 ± 57 days (RVPA); stage 2 scan mean age 177 ± 65 days (RVPA) RVPA (34) −12.23 ± 4.52; P = 0.023 −12.97 ± 4.63; P = 0.006 16.22 ± 8.05; P = 0.0001 56.5 ± 8.5; P = 0.44 Ghelani et al. [38] 2018 Median age 16 (11–23) 193 Single right ventricle (82) of which 62 HLHS −18 (−21, −14) −21 (−14, −17) 53 (47–58) Single left ventricle (101) −17 (−19, −13); P = 0.310 −25 (−29, −20); P < 0.001 55 (47–60); P = 0.347 Kato et al. [27] 2017 Mean age 9.7 ± 4.6 years 45 Single right ventricle (8) of which 6 HLHS −13.4 ± 3.0; P = 0.043 (control); P = 0.752 (SLV) −14.9 ± 4.0; P < 0.001 (control); P = 0.034 (SLV) 19.7 ± 4.5; P < 0.001 (control); P < 0.001 (SLV) 47 ± 1; P = 0.008 Single left ventricle (13) −13.9 ± 3.5; P = 0.061 −18.9 ± 2.6; P < 0.001 29.8 ± 6.2; P < 0.001 47 ± 8; P < 0.001 Control (24) −17.0 ± 4.8 −24.6 ± 3.0 39.3 ± 8.4 59 ± 5 Latus et al. [30] 2020 Age at baseline CMR (SVR) 14.6 ± 5.9 years 37 Baseline CMR—SRV (13; 10 HLHS) −8.6 ± 4.5 (systolic) −14.9 ± 5.1 22.9 ± 11.6 50 ± 16 Age at baseline CMR (overall) 13.4 ± 6.0 years Baseline CMR—overall −11.3 ± 6.6; P = 0.09 −17.4 ± 6.2; P = 0.002 26.8 ± 11.7; P = 0.09 56 ± 13; P = 0.005 Age at follow-up CMR (SRV) 19.9 ± 6.1 years Follow-up CMR—SRV −9.5 ± 3.4 −16.9 ± 5.4 22.9 ± 12.2 52 ± 10 Age at follow-up CMR (overall) 18.6 ± 6.2 years Follow-up CMR—overall −11.6 ± 5.0; P = 0.10 −18.9 ± 6.7; P = 0.03 26.3 ± 14.3; P = 0.18 56 ± 8; P = 0.03 Meyer et al. [39] 2020 Age 15.7 (12.9–22.0) years 51 Initial (3 HLHS) −19.1 (−21.4, −15.1) −21.6 (−27.0, −19.4) 40.2 (22.3,54.6) 57 (49–62) Follow-up (2 years) 17.7 (−20.0, −14.1); P = 0.342 −19.0 (−21.1, −16.0); P = 0.037 36.0 (18.2,51.0); P = 0.383 57 (52–63); P = 0.504 Study name . Year . Age . Patients (n) . Patient subset . GLS (%) . GCS (%) . GRS (%) . EF (%) . Latus et al. [38] 2018 Norwood: mean age 2.4 ± 0.8 months 86 MBTS (42) −16.5 ± 5.5 −18.4 ± 5.6 21.5 ± 9.5 59.4 ± 10.3 Hybrid mean age 2.0 ± 1.0 months Hybrid (44) −13.2 ± 5.9; P = 0.008 −14.7 ± 5.6; P = 0.001 13.9 ± 8.7; P = 0.0002 59.2 ± 9.0, P = 0.91 Salehi Ravesh et al. [13] 2018 Median age 4.9 years (1.6–17.0) 55 BCPC (14) Values not given 55 [50, 66] TCPC (41) P = 0.23 52 [31, 69]; P = 0.80 Stoll et al. [37] 2017 Mean age 20 ± 2 years 48 HLHS (16) −13 ± 4 −13 ± 4 54 ± 10 Systemic right ventricle (16) −12 ± 3 −12 ± 4 50 ± 11 Control (16) −18 ± 5; P < 0.001 RV: −13 ± 3; P = 0.6; LV: −16 ± 3; P = 0.004 62 ± 5; P < 0.05 Wong et al. [4] 2017 Stage 1 scan mean age 103 ± 24 days (MBTS); stage 2 scan mean age 172 ± 38 days (MBTS) 93 MBTS (59) −14.78 ± 5.68 (systolic) −16.90 ± 5.14 (systolic mid-strain) 24.76 ± 11.89 (systolic mid-strain) 57.9 ± 8.3 Stage 1 scan mean age 141 ± 57 days (RVPA); stage 2 scan mean age 177 ± 65 days (RVPA) RVPA (34) −12.23 ± 4.52; P = 0.023 −12.97 ± 4.63; P = 0.006 16.22 ± 8.05; P = 0.0001 56.5 ± 8.5; P = 0.44 Ghelani et al. [38] 2018 Median age 16 (11–23) 193 Single right ventricle (82) of which 62 HLHS −18 (−21, −14) −21 (−14, −17) 53 (47–58) Single left ventricle (101) −17 (−19, −13); P = 0.310 −25 (−29, −20); P < 0.001 55 (47–60); P = 0.347 Kato et al. [27] 2017 Mean age 9.7 ± 4.6 years 45 Single right ventricle (8) of which 6 HLHS −13.4 ± 3.0; P = 0.043 (control); P = 0.752 (SLV) −14.9 ± 4.0; P < 0.001 (control); P = 0.034 (SLV) 19.7 ± 4.5; P < 0.001 (control); P < 0.001 (SLV) 47 ± 1; P = 0.008 Single left ventricle (13) −13.9 ± 3.5; P = 0.061 −18.9 ± 2.6; P < 0.001 29.8 ± 6.2; P < 0.001 47 ± 8; P < 0.001 Control (24) −17.0 ± 4.8 −24.6 ± 3.0 39.3 ± 8.4 59 ± 5 Latus et al. [30] 2020 Age at baseline CMR (SVR) 14.6 ± 5.9 years 37 Baseline CMR—SRV (13; 10 HLHS) −8.6 ± 4.5 (systolic) −14.9 ± 5.1 22.9 ± 11.6 50 ± 16 Age at baseline CMR (overall) 13.4 ± 6.0 years Baseline CMR—overall −11.3 ± 6.6; P = 0.09 −17.4 ± 6.2; P = 0.002 26.8 ± 11.7; P = 0.09 56 ± 13; P = 0.005 Age at follow-up CMR (SRV) 19.9 ± 6.1 years Follow-up CMR—SRV −9.5 ± 3.4 −16.9 ± 5.4 22.9 ± 12.2 52 ± 10 Age at follow-up CMR (overall) 18.6 ± 6.2 years Follow-up CMR—overall −11.6 ± 5.0; P = 0.10 −18.9 ± 6.7; P = 0.03 26.3 ± 14.3; P = 0.18 56 ± 8; P = 0.03 Meyer et al. [39] 2020 Age 15.7 (12.9–22.0) years 51 Initial (3 HLHS) −19.1 (−21.4, −15.1) −21.6 (−27.0, −19.4) 40.2 (22.3,54.6) 57 (49–62) Follow-up (2 years) 17.7 (−20.0, −14.1); P = 0.342 −19.0 (−21.1, −16.0); P = 0.037 36.0 (18.2,51.0); P = 0.383 57 (52–63); P = 0.504 BCPC: bidirectional cavopulmonary connection; CMR: cardiac magnetic resonance; EF: ejection fraction; GCS: global circumferential strain; GLS: global longitudinal strain; GRS: global radial strain; HLHS: hypoplastic left heart syndrome; LV: left ventricle; MBTS: modified Blalock–Taussig shunt; RV: right ventricle; RVPA: right ventricle to pulmonary artery; SLV: single left ventricle; SRV: single right ventricle; TCPC: total cavopulmonary connection. Open in new tab Table 3: Patient characteristics and strain measurements Study name . Year . Age . Patients (n) . Patient subset . GLS (%) . GCS (%) . GRS (%) . EF (%) . Latus et al. [38] 2018 Norwood: mean age 2.4 ± 0.8 months 86 MBTS (42) −16.5 ± 5.5 −18.4 ± 5.6 21.5 ± 9.5 59.4 ± 10.3 Hybrid mean age 2.0 ± 1.0 months Hybrid (44) −13.2 ± 5.9; P = 0.008 −14.7 ± 5.6; P = 0.001 13.9 ± 8.7; P = 0.0002 59.2 ± 9.0, P = 0.91 Salehi Ravesh et al. [13] 2018 Median age 4.9 years (1.6–17.0) 55 BCPC (14) Values not given 55 [50, 66] TCPC (41) P = 0.23 52 [31, 69]; P = 0.80 Stoll et al. [37] 2017 Mean age 20 ± 2 years 48 HLHS (16) −13 ± 4 −13 ± 4 54 ± 10 Systemic right ventricle (16) −12 ± 3 −12 ± 4 50 ± 11 Control (16) −18 ± 5; P < 0.001 RV: −13 ± 3; P = 0.6; LV: −16 ± 3; P = 0.004 62 ± 5; P < 0.05 Wong et al. [4] 2017 Stage 1 scan mean age 103 ± 24 days (MBTS); stage 2 scan mean age 172 ± 38 days (MBTS) 93 MBTS (59) −14.78 ± 5.68 (systolic) −16.90 ± 5.14 (systolic mid-strain) 24.76 ± 11.89 (systolic mid-strain) 57.9 ± 8.3 Stage 1 scan mean age 141 ± 57 days (RVPA); stage 2 scan mean age 177 ± 65 days (RVPA) RVPA (34) −12.23 ± 4.52; P = 0.023 −12.97 ± 4.63; P = 0.006 16.22 ± 8.05; P = 0.0001 56.5 ± 8.5; P = 0.44 Ghelani et al. [38] 2018 Median age 16 (11–23) 193 Single right ventricle (82) of which 62 HLHS −18 (−21, −14) −21 (−14, −17) 53 (47–58) Single left ventricle (101) −17 (−19, −13); P = 0.310 −25 (−29, −20); P < 0.001 55 (47–60); P = 0.347 Kato et al. [27] 2017 Mean age 9.7 ± 4.6 years 45 Single right ventricle (8) of which 6 HLHS −13.4 ± 3.0; P = 0.043 (control); P = 0.752 (SLV) −14.9 ± 4.0; P < 0.001 (control); P = 0.034 (SLV) 19.7 ± 4.5; P < 0.001 (control); P < 0.001 (SLV) 47 ± 1; P = 0.008 Single left ventricle (13) −13.9 ± 3.5; P = 0.061 −18.9 ± 2.6; P < 0.001 29.8 ± 6.2; P < 0.001 47 ± 8; P < 0.001 Control (24) −17.0 ± 4.8 −24.6 ± 3.0 39.3 ± 8.4 59 ± 5 Latus et al. [30] 2020 Age at baseline CMR (SVR) 14.6 ± 5.9 years 37 Baseline CMR—SRV (13; 10 HLHS) −8.6 ± 4.5 (systolic) −14.9 ± 5.1 22.9 ± 11.6 50 ± 16 Age at baseline CMR (overall) 13.4 ± 6.0 years Baseline CMR—overall −11.3 ± 6.6; P = 0.09 −17.4 ± 6.2; P = 0.002 26.8 ± 11.7; P = 0.09 56 ± 13; P = 0.005 Age at follow-up CMR (SRV) 19.9 ± 6.1 years Follow-up CMR—SRV −9.5 ± 3.4 −16.9 ± 5.4 22.9 ± 12.2 52 ± 10 Age at follow-up CMR (overall) 18.6 ± 6.2 years Follow-up CMR—overall −11.6 ± 5.0; P = 0.10 −18.9 ± 6.7; P = 0.03 26.3 ± 14.3; P = 0.18 56 ± 8; P = 0.03 Meyer et al. [39] 2020 Age 15.7 (12.9–22.0) years 51 Initial (3 HLHS) −19.1 (−21.4, −15.1) −21.6 (−27.0, −19.4) 40.2 (22.3,54.6) 57 (49–62) Follow-up (2 years) 17.7 (−20.0, −14.1); P = 0.342 −19.0 (−21.1, −16.0); P = 0.037 36.0 (18.2,51.0); P = 0.383 57 (52–63); P = 0.504 Study name . Year . Age . Patients (n) . Patient subset . GLS (%) . GCS (%) . GRS (%) . EF (%) . Latus et al. [38] 2018 Norwood: mean age 2.4 ± 0.8 months 86 MBTS (42) −16.5 ± 5.5 −18.4 ± 5.6 21.5 ± 9.5 59.4 ± 10.3 Hybrid mean age 2.0 ± 1.0 months Hybrid (44) −13.2 ± 5.9; P = 0.008 −14.7 ± 5.6; P = 0.001 13.9 ± 8.7; P = 0.0002 59.2 ± 9.0, P = 0.91 Salehi Ravesh et al. [13] 2018 Median age 4.9 years (1.6–17.0) 55 BCPC (14) Values not given 55 [50, 66] TCPC (41) P = 0.23 52 [31, 69]; P = 0.80 Stoll et al. [37] 2017 Mean age 20 ± 2 years 48 HLHS (16) −13 ± 4 −13 ± 4 54 ± 10 Systemic right ventricle (16) −12 ± 3 −12 ± 4 50 ± 11 Control (16) −18 ± 5; P < 0.001 RV: −13 ± 3; P = 0.6; LV: −16 ± 3; P = 0.004 62 ± 5; P < 0.05 Wong et al. [4] 2017 Stage 1 scan mean age 103 ± 24 days (MBTS); stage 2 scan mean age 172 ± 38 days (MBTS) 93 MBTS (59) −14.78 ± 5.68 (systolic) −16.90 ± 5.14 (systolic mid-strain) 24.76 ± 11.89 (systolic mid-strain) 57.9 ± 8.3 Stage 1 scan mean age 141 ± 57 days (RVPA); stage 2 scan mean age 177 ± 65 days (RVPA) RVPA (34) −12.23 ± 4.52; P = 0.023 −12.97 ± 4.63; P = 0.006 16.22 ± 8.05; P = 0.0001 56.5 ± 8.5; P = 0.44 Ghelani et al. [38] 2018 Median age 16 (11–23) 193 Single right ventricle (82) of which 62 HLHS −18 (−21, −14) −21 (−14, −17) 53 (47–58) Single left ventricle (101) −17 (−19, −13); P = 0.310 −25 (−29, −20); P < 0.001 55 (47–60); P = 0.347 Kato et al. [27] 2017 Mean age 9.7 ± 4.6 years 45 Single right ventricle (8) of which 6 HLHS −13.4 ± 3.0; P = 0.043 (control); P = 0.752 (SLV) −14.9 ± 4.0; P < 0.001 (control); P = 0.034 (SLV) 19.7 ± 4.5; P < 0.001 (control); P < 0.001 (SLV) 47 ± 1; P = 0.008 Single left ventricle (13) −13.9 ± 3.5; P = 0.061 −18.9 ± 2.6; P < 0.001 29.8 ± 6.2; P < 0.001 47 ± 8; P < 0.001 Control (24) −17.0 ± 4.8 −24.6 ± 3.0 39.3 ± 8.4 59 ± 5 Latus et al. [30] 2020 Age at baseline CMR (SVR) 14.6 ± 5.9 years 37 Baseline CMR—SRV (13; 10 HLHS) −8.6 ± 4.5 (systolic) −14.9 ± 5.1 22.9 ± 11.6 50 ± 16 Age at baseline CMR (overall) 13.4 ± 6.0 years Baseline CMR—overall −11.3 ± 6.6; P = 0.09 −17.4 ± 6.2; P = 0.002 26.8 ± 11.7; P = 0.09 56 ± 13; P = 0.005 Age at follow-up CMR (SRV) 19.9 ± 6.1 years Follow-up CMR—SRV −9.5 ± 3.4 −16.9 ± 5.4 22.9 ± 12.2 52 ± 10 Age at follow-up CMR (overall) 18.6 ± 6.2 years Follow-up CMR—overall −11.6 ± 5.0; P = 0.10 −18.9 ± 6.7; P = 0.03 26.3 ± 14.3; P = 0.18 56 ± 8; P = 0.03 Meyer et al. [39] 2020 Age 15.7 (12.9–22.0) years 51 Initial (3 HLHS) −19.1 (−21.4, −15.1) −21.6 (−27.0, −19.4) 40.2 (22.3,54.6) 57 (49–62) Follow-up (2 years) 17.7 (−20.0, −14.1); P = 0.342 −19.0 (−21.1, −16.0); P = 0.037 36.0 (18.2,51.0); P = 0.383 57 (52–63); P = 0.504 BCPC: bidirectional cavopulmonary connection; CMR: cardiac magnetic resonance; EF: ejection fraction; GCS: global circumferential strain; GLS: global longitudinal strain; GRS: global radial strain; HLHS: hypoplastic left heart syndrome; LV: left ventricle; MBTS: modified Blalock–Taussig shunt; RV: right ventricle; RVPA: right ventricle to pulmonary artery; SLV: single left ventricle; SRV: single right ventricle; TCPC: total cavopulmonary connection. Open in new tab Study outcomes In their first study, Latus et al. evaluated the strain values of 86 patients with HLHS after stage I palliation. Both groups were age and sex matched, and there were no differences in the underlying HLHS subtype, birth weight and severity of tricuspid valve regurgitation. CMR studies were performed on a 3 T system (Magnetom Verio, Siemens, Germany) in a hybrid and a 1.5 T scanner (Achieva, Philips Healthcare, Best, the Netherlands) in Norwood patients, with a slice thickness of 4–6 mm. The values of global peak strain and strain rate were recorded by tracking the endocardium. Patients who underwent the Norwood procedure with an MBTS were compared to patients who underwent the hybrid procedure. Despite comparable EFs, patients after the hybrid procedure demonstrated significantly impaired global longitudinal strain (GLS), GCS and global radial strain (GRS) compared to patients after the Norwood procedure (Table 3). There was no statistically significant difference in survival between the groups [36]. Wong et al. compared strain values of 93 patients with HLHS after their stage I palliation with either MBTS or an RVPA conduit. Birth weight, age at the stage I and II procedures and tricuspid regurgitation at either stage were similar between the 2 groups. However, patients who underwent MBTS were significantly younger at their first scan compared with patients with an RVPA conduit. Studies for the group of patients with MBTS were performed on the Philips Achieva scanner; the magnetic resonance imaging (MRI) vendor for the RVPA group was not reported. The 4-chamber view was used to measure RV longitudinal function, and tracking the endocardium was used to provide strain data. Global strain was recorded as the mean of the segmental strain values for systolic strain. Despite a preserved EF, patients who underwent the RVPA procedure demonstrated significantly impaired systolic longitudinal strain, systolic circumferential strain and systolic radial strain compared to patients after the MBTS procedure (Table 3). Patients with RVPA also had lower EFs at stage II palliation compared with MBTS, although the value remained within the normal range [4]. Salehi Ravesh et al. compared the longitudinal strain measured by CMR-FT and speckle-tracking echocardiography in 55 patients with HLHS. Demographic data included age at examination, gender, body surface area and grade of tricuspid valve regurgitation. CMR examinations were performed on a 3 T scanner (Achieva TX-series; Philips Healthcare, the Netherlands) with a median temporal resolution of 28.8 ms. The RV was divided into 7 segments by tracing the endo- and epicardial borders in both phases. For each segment, the peak longitudinal strain was recorded, and the GLS was calculated as the mean of all segments. The sample included 14 patients after stage II (bidirectional cavopulmonary connection) and 41 after stage III palliation (total cavopulmonary connection or Fontan completion). There was no difference in GLS between CMR-FT- and echocardiography-derived data, but the agreement was poor for regional longitudinal strain. GLS was negatively correlated with EF (r = −0.45; P < 0.001). Patients after stage II and III did not have significantly different GLS. GCS and GRS were not evaluated [13]. Stoll et al. compared 16 patients with HLHS to 16 controls and 16 patients with an SRV of other aetiologies. Demographic data on confounders, MRI vendor and details on strain measurement were not provided. Patients with HLHS had significantly impaired EF and SLS compared to controls and had a significantly impaired SCS compared to the LV of the controls (Table 3). However, there was no difference in SLS between HLHS and other forms of SRV [37]. Ghelani et al. compared strain values in patients with SRV and with an SLV that comprised a heterogeneous group of patients with a Fontan circulation, including 62 patients with HLHS. Demographic data on age at operation were provided. Moderate AVV regurgitation was present in a significantly higher number of patients in the RV group. CMR examinations were performed on a 1.5 T scanner (Philips Healthcare, the Netherlands) with a typical temporal resolution of 30–40 ms. GCS and GLS were calculated using feature tracking analysis on the steady-state free precession ventricular short-axis and 4-chamber images at the midcavity level by tracking the endocardial border. Patients with an SRV had significantly impaired GCS but not GLS compared with SLV (Table 3). Impaired circumferential strain was associated with a worse composite outcome that included all-cause mortality, a heart transplant or listing for a heart transplant [39]. Kato et al. completed a study that compared a group of 21 patients with a Fontan circulation, including 6 patients with HLHS, with 24 controls. Demographic data included age at operation, which was similar between groups, whereas other confounders were not reported. CMR examinations were performed on a 1.5 T scanner (Magnetom Avanto, Siemens Healthcare, Germany). Longitudinal strain was obtained from a horizontal long-axis view, corresponding to the 4-chamber view in a normal heart, tracking the endocardial border. Circumferential and radial strains were assessed in the basal, mid and apical short axes and averaged to calculate global strain values. Patients with a Fontan circulation had significantly impaired GCS and GRS compared to the controls. In addition, patients with an SRV had significantly impaired GLS compared to the controls as well as impaired GCS and GRS compared to patients with SLV (Table 3) [27]. In their 2020 study, Latus et al. included a group of 37 patients with a Fontan circulation, of whom 10 had HLHS. The reported frequency and severity of AVV regurgitation were similar between groups at baseline and at follow-up, whereas the Qp/Qs was significantly reduced at follow-up. CMR studies were performed on a 3 T scanner (Siemens Magnetom Verio BV19, Germany) with a temporal resolution of 25–30 phases. Global peak strain and strain rate were recorded by tracking the endocardial border. Patients underwent 1 CMR study at baseline and a follow-up study at least 4 years later to assess the evolution of the ventricular strain over time. Patients with SRV had significantly impaired GCS (but not GLS or GRS), and EFs at both measurement points were compared with those of the remainder of the cohort (Table 3) [30]. Meyer et al. included only 3 patients with HLHS among the 51 patients with a Fontan circulation they studied with a baseline and follow-up CMR 2 years later. Demographic data on confounders were not provided. CMR studies were performed on a 1.5 T scanner (Siemens, Magnetom Avanto, Germany) with a temporal resolution of 20–40 ms. The longitudinal strain of the free wall was recorded, and the GLS was assessed in a 4-chamber view by tracking the endocardial border. GCS, but not GLS or GRS, deteriorated significantly over time whereas the EF remained unchanged (Table 3). When the authors analysed the hypoplastic and systemic ventricle as a unit, combined GCS and GLS significantly deteriorated over time and were significantly impaired compared to the measurements that were made on the systemic ventricle alone [39]. DISCUSSION Quantitative assessment of ventricular strain derived from CMR-FT is feasible because it can be calculated from standard images using CMR-FT software [10]. Although strain can also be derived from speckle-tracking echocardiography, in 1 study, ventricular strain analysis could be performed for all CMR data sets whereas 28% of apical segments of the systemic ventricle could not be analysed using echocardiography due to poor image quality [13]. Previous studies in patients with HLHS undergoing staged palliation have shown that strain values derived from CMR-FT can be used as indices of contraction and correlate with changes in ventricular function [18]. Our review showed that in patients following their stage I procedure, differences in strain values between surgical strategies exist despite comparable EF. GLS, GCS and GRS appear reduced in the hybrid and RVPA groups compared with the MBTS group [4, 36]. Unfortunately, the reported studies offer only limited data on the correlation between these values and outcomes. Although Latus et al. reported 3 patients who had heart transplants after having the hybrid procedure, no statistically significant difference in mortality was found between the hybrid and MBTS groups. Among patients undergoing the Norwood procedure in the single-ventricle reconstruction trial, the RVPA group demonstrated better 1-year transplant-free survival compared with the MBTS group. At 6 years, transplant-free survival was again higher, although the difference was not statistically significant in the RVPA group [40]. Wilder et al. [41] showed better 4-year survival in patients in the RVPA compared with the MBTS and hybrid groups, although there was a trend towards better survival with the hybrid procedure in low-birth weight infants. Several possible explanations exist for impaired RV function following the stage I procedure. First, the RV is subject to myocardial injury during cardioplegic arrest in the neonatal period with the Norwood procedure [20]. In patients with MBTS, diastolic run-off into the pulmonary circulation leads to volume overload and coronary insufficiency [20, 21, 23]. In the RVPA group, ventricular dysfunction might arise from the right ventricular incision, but reduction in diastolic run-off results in increased diastolic pressures that might contribute to better myocardial perfusion and thus better ventricular function [20, 21]. In the hybrid group, ventricular function might be affected by reduced myocardial perfusion due to retrograde coronary perfusion, although this approach offers the benefit of delaying the time to cardiopulmonary bypass and its adverse myocardial effects [20]. After MBTS and RVPA, some patients have similar cases of myocyte hypertrophy, but a higher degree of cardiac remodelling was found in the RVPA group with more widespread fibrosis, higher content of collagen III and lower content of collagen I [21]. Positive late right ventricular myocardial enhancement in patients after the Norwood procedure has been related to myocardial ischaemia and fibrosis [42]. Notably, in infants before or after stage 1 palliation, RV failure can occur in the absence of fibrosis, with the attenuated fibrotic response attributed to the young age of these patients [28]. Recent studies on cardiomyocyte proliferation show that the number of cardiomyocytes can increase after birth until adolescence, but this effect is most prominent in infancy, and if abnormal, may be implicated in myocardial dysfunction [43]. It is possible that changes in strain patterns and values represent evidence of early remodelling related to pressure or volume loads or myocardial ischaemia, but further studies are needed to evaluate these changes over time and in the context of clinical outcomes to determine if they represent a constructive or maladaptive response. For example, early dysfunction in the RVPA and hybrid groups detected by strain analysis might lead to early remodelling while the infant heart is still able to regenerate, conferring a survival advantage in the intermediate period. This outcome might be different from long-term mortality, where ventricular dysfunction due to chronic volume or pressure overload leads to maladaptive remodelling as the regenerative capability wanes and eventually results in heart failure and ventricular arrhythmias with resultant morbidity and mortality in all groups. Not enough is known, however, about strain values and their relationship with clinical outcomes after stage I palliation for them to be used as a discriminator between surgical strategies. Only one study included the second interstage period of palliation for HLHS. It did not demonstrate any change in GLS between stage II and stage III groups as measured by CMR-FT, perhaps owing to the more stable haemodynamics after stage II palliation [13]. Differences in ventricular strain were also evaluated in Fontan patients. Stoll et al. [37] demonstrated no difference between GCS and GLS of patients with HLHS and SRV of other aetiology with a Fontan circulation. All studies demonstrated significantly impaired circumferential strain in SRV groups (including HLHS) compared with controls and SLV groups [27, 36, 38, 39]. Unlike patients after stage I palliation, some of the patients with an SRV and a Fontan circulation also had significantly lower EFs than the control group or comparator group with an SLV [27, 30]. This result could signal further progression of ventricular dysfunction due to the more advanced stage of the disease. Further studies are needed to delineate the principal or combination of causes for this dysfunction in conjunction with CMR-FT, such as MRI with late gadolinium enhancement to detect fibrosis and biopsy to detect fibrosis, hypertrophy or ischaemic changes. Although studies have shown that ventricular failure can occur in the absence of fibrosis in the early stages of HLHS palliation, this situation might be different in the older child or adolescent after the Fontan procedure, when the ability of the myocytes to proliferate is significantly reduced [28, 43]. Many patients with HLHS and a failing Fontan circulation eventually require a heart transplant [1]. In combination with clinical markers of decompensated disease, ventricular strain analysis with CMR-FT could signal an early warning about a failing Fontan circulation, prompting optimization of therapy and allowing for early planning for transplant listing if indicated. Last but not least, a more detailed regional ventricular strain analysis and assessment of intraventricular synchrony are possible with CMR-FT. Regional strain analysis could allow a more precise identification of sites of myocardial damage and/or remodelling, e.g. a ventriculotomy site in RVPA or areas of diminished myocardial perfusion in MBTS/hybrid groups. Limitations A major limitation of our study is the lack of available studies exclusively involving patients with HLHS after stage III palliation. Therefore, 4 studies that analysed a group of SRV patients (including HLHS) were included in the review. Including these studies limits the generalizability of a proportion of the results of this review; however, we have attempted to mitigate this outcome by alerting the reader to this situation by colour-coding the studies in the tables and discussing the individual studies separately, thereby highlighting them to the reader. Furthermore, Stoll et al. did not find significant differences in the calculated strains between patients with HLHS and SRV [37]. This heterogeneity of participants was one of the reasons that a meta-analysis was not possible for this study question. Other confounders such as birth weight, genetic syndromes, time of procedure, AVV regurgitation, aortic size or time of deep hypothermic circulatory arrest were not reported by all studies, so comparisons between groups should be made with caution. In contrast to echocardiography, the assessment of infants with MRI may necessitate sedation or general anaesthesia to obtain images of sufficient quality, adding to the anaesthetic burden of these children [30]. In addition, despite the superior spatial resolution in CMR, Ghelani et al. [38] reported occasions of suboptimal imaging data sets that led to the exclusion of such cases from analysis, although they did not report the underlying cause of the poor image quality, introducing a potential for bias. CONCLUSION In conclusion, further studies are needed to correlate strain values at different time points and different modes of surgical/interventional palliation of HLHS with clinical outcomes as well as their relationship to the effects of medical management, biomarkers of cardiac damage and dysfunction (troponin, BNP), late gadolinium enhancement as marker of fibrosis and tissue analysis. Until then, the use of CMR-FT ventricular strain analysis can be used alongside clinical assessment and established imaging modalities to inform our knowledge about the progression of HLHS at different stages of surgical palliation in a non-invasive and reproducible way, with the promise of guiding therapy for RV failure in the future. Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020. ACKNOWLEDGEMENTS We would like to acknowledge Dr. Mladen Gasparini for writing assistance and Dr. Sabyha Khan for assistance with literature sourcing. Conflict of interest: none declared. Author contributions Marisa Gasparini: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Software; Validation; Visualization; Writing—original draft; Writing—review & editing. Natasha Cox: Data curation; Formal analysis; Investigation; Methodology; Project administration; Validation; Writing—review & editing. Reviewer information European Journal of Cardio-Thoracic Surgery thanks John Simpson and the other, anonymous reviewer(s) for their contribution to the peer review process of this article. 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Google Scholar Crossref Search ADS PubMed WorldCat ABBREVIATIONS ABBREVIATIONS AVV Atrioventricular valve BNP Brain natriuretic peptide CMR Cardiac magnetic resonance CMR-FT Cardiac magnetic resonance feature tracking EF Ejection fraction GCS Global circumferential strain GLS Global longitudinal strain GRS Global radial strain HLHS Hypoplastic left heart syndrome LV Left ventricle MRI Magnetic resonance imaging RV Right ventricle RVPA Right ventricle-to-pulmonary artery SLV Single left ventricle SRV Systemic RV © The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Role of cardiac magnetic resonance strain analysis in patients with hypoplastic left heart syndrome in evaluating right ventricular (dys)function: a systematic review
JF - European Journal of Cardio-Thoracic Surgery
DO - 10.1093/ejcts/ezab105
DA - 2021-07-31
UR - https://www.deepdyve.com/lp/oxford-university-press/role-of-cardiac-magnetic-resonance-strain-analysis-in-patients-with-45Z1TLcW8a
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -