Echocardiography in repaired Tetralogy of Fallot: Delineating the mechanisms of RV dysfunction
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1 Echocardiography in repaired Tetralogy of Fallot: Delineating the mechanisms of RV dysfunction Mark K. Friedberg, MD The Labatt Family Heart Center, Hospital for Sick Children Toronto, Ontario, Canada NO DISCLOSURES
2 Clinical problems Right ventricular dilatation and failure Left ventricular dysfunction Exercise intolerance Arrhythmia Sudden death
3 Mechanisms of ventricular dysfunction in TOF Right Ventricular Hypertrophy Myocardial and contractile abnormalities: Fibrosis Large VSD patch Residual RVOTO, branch PS -> increased afterload PR, TR, residual shunts -> increased preload RBBB, prolonged QRS, electro-mechanical dyssynchrony -> pump inefficiency and contractile abnormalities
4 Pathophysiology of dysfunction in TOF Geva, Journal of Cardiovascular Magnetic Resonance. 2011;13(1):9
5 Pre-operative TOF
6 Post-op RV enlargement and dysfunction
7 RV tissue velocities are reduced after TOF repair Vogel, Circulation 2001;103;
8 Strain and strain rate after TOF repair Weidemann, Am J Cardiol 2002;90:
9 RV longitudinal peak strain and strain rate RV lateral wall strain RV lateral wall strain rate TOF Control TOF Control ±5.1 vs ±8.5, p< ± 0.68 vs. -2.1±0.8, p=<0.001 Friedberg, AHJ, 2012
10 Association with exercise capacity Reduced RV longitudinal peak systolic SR was associated with: decreased exercise peak VO 2 (PE 0.14 (0.07), p=0.04) decreased % predicted peak VO 2 (PE 0.07 (0.03) p=0.04). Friedberg, AHJ, 2012
11 Diastolic function in TOF Friedberg, Eur Heart J Cardiovasc Imaging. 2012
12 Longitudinal diastolic strain rate Friedberg, Eur Heart J Cardiovasc Imaging. 2012
13 Biventricular assessment LV assessment Mainly RV assessment Author Year Objective/Hypothesis Study design Chowdhury Evaluate correlation between STE measures of Retrospective, RV function and changes in exercise capacity longitudinal. after PVR. Multicenter Before and after transcath. PVR Strain studies in rtof Patients/ Groups rtof RV to PA Other n Age (mean ± SD, years) Youth and adults 32.3 ± 17.0 Strain Modality Strain walls Main results Comments/conclusion 2D-STE LS LSR RV-FW RV-SW RV-GLS Improvements in RV LS (-16.9 ± 3.5% vs ± 4.3%) and strain rate (-0.9 ± 0.4 vs.-1.2 ± 0.4 s -1, all p <0.01) after PVR. STE predicted and not FAC or TAPSE improved outcomes in patients after PVR. Almeida- Morais Assess how RV-LS correlates with other parameters of RV function & CMR RV-EF. Retrospective, cross-sectional rtof 42 Adults 32 ± 8 2D-STE LS LSR RV-GLS RV-GLS=16.2 ± 3.7%, with linear correlation with TAPSE, (r= 0.40) and RV-EF (r= 0.45), all p<0.05 RV GLS correlated with echo parameters of RV function and CMR RV-EF. Toro K Evaluate the utility of strain for the assessment of RV systolic function. Retrospective, cross rtof sectional RV-EF 45% RV-EF<45% Children 12.6 ± ± 3.7 2D-STE LS RV-GLS RV-GLS correlates with CMR RV-EF (r= 0.76). RV GLS cutoff RV GLS is useful to assess RV systolic function in value of 18% had 78% sensitivity and 77% specificity for rtof. identifying RV-EF <45% (AUC 0.87). Gursu RV function and volumes by STE and CMR, before and after PVR. Retrospective, longitudinal, Before & after PVR rtof 15 Children and youth 2D-STE 14.5 ± 4.5 LS LSR RV-FW RV-SW (mid) Lower RV-LS and LSR before PVR was similar between asymptomatic and symptomatic patients. Significant improvement 6-months after PVR. STE is useful to assess RV function in rtof before and after PVR. Joynt Characterize changes in RV size and function in patients with PS, compared to those with rtof with similar PR. Retrospective, cross sectional 2:1 Matching by age and PR% PR patients PS after valvotomy rtof Adults 40.7 ± ± 12.5 CMR FT LS CS RV-FW RV-CS RVOT PS patients had preserved RV-EF and better RV-CS, LS and RVOT Differential effects on RV systolic function strain compared with rtof. Greater differences in RV-CS than LS. between PS and rtof, largely related to Late gadolinium enhancement in the RVOT was more frequent differences in the RVOT. in patients with TOF (70.2% vs 45.8%). Anwar Characterize regional RV systolic function by Retrospective, cross PR patients comparing patients with rtof to patients with sectional PS after valvar PS. Matched by PR% and duration balloon dilation rtof Yamada Assess the location and time course of LV dysfunction in patients with rtof using layerspecific strain analysis. Menting Assess LV and RV global and regional function by STE strain and its relation with conventional parameters of RV function in rtof. Li Evaluate RV and LV function in asymptomatic rtof patients and identify parameters of early dysfunction. Latus Assess RV & LV function and interventricular interactions in rtof patients with & without RVOTO. Yim Assess the impact of surgical PVR on ventricular mechanics in pediatric rtof patients. Orwat Assess if CMR myocardial deformation relates to symptoms and provides prognostic information Kawakubo Evaluate RV/LV function and to investigate the agreement between semi-automatic and manual measurements. Berganza* Evaluate the correlation of CMR-FT ventricular strain to conventional CMR ventricular function parameters Mese Investigate echo STE GLS and GCS at rest and during exercise in rtof Prospective, longitudinal Prospective, crosssectional Retrospective, cross sectional Matched by age and gender Retrospective, cross sectional Matched by age and type of surgery Retrospective, longitudinal Before and after PVR Prospective, multicenter, longitudinal rtof Healthy controls 1=4-10 years 2=11-20 years 3=21-43 years rtof Healthy controls rtof Healthy controls rtof RVOTO No RVOTO Children 15.2 ± ± 2.5 Adults Children (4-43 years) Adults 32.8 ± 9.5 Children 5.4 ± ± 4.9 Youth and adults 16.2 ± 6.9 rtof 50 Children 12.6 ± 3.4 rtof No CV events CV events Retrospective, cross Ischemic sectional Retrospective, cross rtof sectional Prospective, cross sectional Non-Ischemic rtof Healthy controls rtof Healthy controls Adults 16 IQR 12,20 18 IQR 14,25 Adults 47 ± 19 Children 12.4 ± ± 4.5 Children 13.5 ± ± 0.3 CMR FT LS 2D-STE LS CS 2D-STE LS LSR 2D-STE LS LSR CS RS CMR-FT LS CS RS 2D-STE LS CS CMR-FT LS CS CMR-FT LS CMR-FT 2D 3D LS CS RS 2D-STE LS CS RV-GLS RVOT LV-GLS Endo Mid Epi RV-FW RV-SW RV-GLS LV-GLS RV-FW LV-GLS LV-CS LV-RS RV-LS RV-CS RV-RS LV-LS LV-CS LV-RS RV-FW LV-GLS LV-CS RV-LS RV-CS LV-LS LV-CS RV-FW LV-FW RV-LS RV-CS RV-RS LV-LS LV-CS LV-RS RV-GLS LV-GLS LV-CS Normal and similar RV-EF between rtof and PS. RV-GLS was worse in both groups compared to normal but comparable to each other. RVOT LS was worse than RV GLS in rtof, but not in PS. LS is diminished in PS and rtof subjects with preserved RV EF. Transannular patch could explain worse RVOT strain in rtof. Basal and papillary endocardial CS values were decreased in Potential sub-endocardial damage in the LV basal rtof 1 compared with controls. Except for papillary epicardial and papillary levels in young patients with rtof, CS, basal/papillary CS and LS of all 3 layers were decreased in extending from endocardium to epicardium and rtof compared with controls. Except for papillary epicardial CS, from base to apex. all other values were decreased in rtof compared with controls. Lower RV-FW strain than controls, especially in the apical RV-FW strain and SR are decreased in rtof adults, segment (-15.9 ± 7.4 vs %, P<0.001), and lower RV-LSR. especially in apical segments suggesting apical LV-GLS was also lower, mainly due to low septal strain. function Is most affected rtof RVs Regional and global RV LS and SR were impaired in children with STE can identify early RV and LV systolic rtof. LV CS, RS and SR were reduced in patients with rtof, but dysfunction in rtof patients with preserved RVnot LV-GLS. RV GLS and SR were related to RV-EF (r=-0.64, r2=- EF. 0.60) and PR (r= -0.48; r2 = -0.49). RVOTO group showed higher RV-CS and RV-RS values, whereas Residual RVOTO is associated with better RV RV-LS did not differ between the groups. Interventricular strain and less interventricular dyssynchrony and dyssynchrony was higher in the group without RVOTO while LV- may therefore reduce RV remodeling. LS and LV intraventricular synchrony were impaired in the RVOTO group. LV and RV LS were reduced early post-operatively, followed by recovery of biventricular systolic strain by mid-term follow-up, even increasing in individual segments above pre-operative values. Patients with larger pre-operative RV volumes had lower RV strain post-operatively. LV-CS and RV-LS were independent predictors of outcome. LV LS, RS, CS and RV LS were related to the risk of death and nearmissed death. An increase in global and regional RV strain beyond pre-operative values suggests RV reverse remodeling and adaptation in children after PVR. CMR myocardial deformation parameters relate to symptoms and clinical deterioration in patients with ToF and predict adverse outcome independent of established risk markers. The optimal LS cut-off for diagnoses the LV and RV dysfunction The semi-automatic LS analysis can evaluate LV were: LV-FW =-7.8%; sensitivity, 83%; specificity, 91%, RV-FW =- and RV dysfunction. 15.7%; sensitivity, 92%; specificity, 68%). Excellent correlations between manual and semi-automatic measurements for LV and RV-FW. 3D LV-CS was reduced in rtof patients (-10.1 ± 3 vs ± 3D CS can detect early myocardial dysfunction 1.9%, p< 0.01). Strong correlation between 3D LV-CS 3D and before reduction in EF. indexed RV end diastolic volume, as well as a strong correlation between 2D LV-LS and RV-EF. RV STE during exercise had low feasibility. A progressive reduction in LV-GLS occurred in rtof during exercise, while LV- CS did not change significantly. Myocardial deformation analysis during exercise can enhance detection of sub-clinical ventricular dysfunction in rtof. Larios and Friedberg, Curr Opin Cardiol. 2017
14 Why is RV strain reduced after TOF repair?
15 8y girl doing well after TOF repair
16 PR is associated with reduced regional contractility Frigiola, Circulation 2004;110;II-153-II-157 Eyskens, EJE, 2010, 11, 341
17 Short-term changes in RV deformation following PVR n Pre PVR (mean ± SD) Post PVR (mean ± SD) p- value Strain IVS % ± ± Strain RV % ± ± Strain Rate IVS (s -1 ) ± ± Strain Rate RV (s -1 ) ± ± Septal Strain% Pre-Post PPVI Septal Strain % pre post Series1 Series2 Series3 Series4 Series5 Series6 Series7 Series8 Series9 Series Moiduddin, Am J Cardiol. 2009;104:862
18 Regional RV strain mid-term after surgical PVR N=50 Early: months post-pvr Mid: months post-pvr Yim, Int J CV Imag 2017 ;33:
19 Strain and SR after PVR in TOF Knirsch, Pediatr Cardiol; :
20 PVR for RV volume loading Decreased RVEDVi and RVESVi Subjective improvement Unchanged RV EF Unchanged exercise capacity Harrild, Circulation, 2009
21 Function after PVR in TOF: Relief of volume load Coats, European Heart Journal;2007, 28, 1886
22 Function after PVR in TOF: Relief of pressure load Coats, Circulation. 2006;113:
23 Its not volume loading alone: TOF vs. ASD RV strain RV strain rate Dragulescu, IJC, 2012
24 There appear to be other factors driving RV dysfunction in rtof
25 Regional fibrosis in TOF Babu-Narayan, Circulation. 2006;113:
26 RV regional wall motion abnormalities in TOF Normal TOF Vogel, Circ 2001;103;
27 Reduced deformation is associated with prolonged QRS Weidemann, Am J Cardiol 2002;90:
28 N=48 Am Heart J 2013;165:551-7
29 RV mechanical delay ±159 vs. 71.0±92 ms, p=0.008 TOF Control Friedberg, Am Heart J 2013;165:551-7
30 Association between RV strain, delay &exercise Increased RV delay was associated with: Decreased RV longitudinal strain (PE 6.31 (2.30), p=0.007) Decreased RV strain rate (PE (3.84), p=0.004). Increased interventricular (RV-LV) delay was associated with: Increased QRS duration (EST 0.129, SE 0.058, p=0.03) Reduced RV ejection fraction (EST -2.95, SE 1.275, p=0.02). Reduced RV longitudinal peak systolic SR was associated with: Decreased exercise peak VO2 (PE 0.14 [0.07], P =.04) Percentage predicted peak VO2 (PE 0.07 [0.03], P =.04). Friedberg, Am Heart J 2013;165:551-7
31 Interventricular Delay in TOF Inverse relation between max workload during exercise and InterV-delay (r= -0.52; p=0:01) D Andrea et al. Eur J Echo March 2004
32 Interventricular Delay in TOF Higher PV-Ao PEP delay negatively correlated with: %VO2max (r=-0.25, p=0.03) %VO2max at AT (r=-0.33, p=0.008). Yim, In progress
33 LV dysfunction in TOF LV circumferential and radial strain are significantly reduced in children and adolescents after TOF repair and are associated with pulmonary regurgitation and RV dilatation. J Am Soc Echocardiogr 2012;25:
34 Exercise induced dispersion in children after tetralogy of Fallot repair Roche, Heart, 2010
35 Effects of Regional Dysfunction and Late Gadolinium Enhancement on Global Right Ventricular Function and Exercise Capacity in Patients With Repaired Tetralogy of Fallot Rachel M. Wald, Idith Haber, Ron Wald, Anne Marie Valente, Andrew J. Powell and Tal Geva Circulation 2009;119; ; originally published online Mar 2, 2009; DOI: /CIRCULATIONAHA Circulation is published by the American Heart Association Greenville Avenue, Dallas, TX Patients with subnormal exercise Copyright 2009 American Heart Association. All rights reserved. Print ISSN: Online ISSN: capacity had more global and regional RV dysfunction. The online version of this article, along with updated information and services, is located on the World Wide Web at: Subnormal exercise capacity was more closely associated with RVOT EF than global RV EF.
36 RV electro-mechanical dyssynchrony in TOF Mechanisms of Right Ventricular Electromechanical Dyssynchrony and Mechanical Inefficiency in Children After Repair of Tetralogy of Fallot Wei Hui, Cameron Slorach, Andreea Dragulescu, Luc Mertens, Bart Bijnens and Mark K. Friedberg Circ Cardiovasc Imaging. published online May 1, 2014; Circulation: Cardiovascular Imaging is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Copyright 2014 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: als.org/ by guest on May 2, 2014 Downloaded from by guest on May 2, 2014
37 Electro-mechanical dyssynchrony in TOF Right-sided septal flash in a TOF patient Left sided septal flash in a TOF patient
38
39 Pulmonary RV Resynchronization Janousek, Circ Cardiovasc Imaging Sep;10(9). pii: e006424
40 Am J Cardiol 2015;115:676
41 RVEDV correlated with preprocedure QRS duration (r 0.34, p <0.002) but there was no correlation after PPVI. pulmonary regurgitation -circles pulmonary stenosis squares mixed triangles Am J Cardiol 2011;107:
42 16 year old; TOF/PA Is CRT indicated? PV replacement (25mm mosaic valve, age 8y) Poor RV function (MRI RVEF 25%, RVEDVi 125 ml/m 2, LVEF 49% LVEDVi 79 ml/m2) No RVOTO/PA stenoses, Low RV pressure : RVSp ~41 mmhg (sbp 113 mmhg) Unable to obtain VO 2 ; workload 97 W (60% predicted). ECG: RBBB, LAD, QRS ~ 170ms
43 Is CRT indicated?
44 Summary Regional RV dysfunction in TOF is important and correlates with reduced global function and exercise intolerance Regional wall motion abnormalities may correlate with propensity for arrhythmia RV electromechanical dyssynchrony is associated with RV systolic and diastolic dysfunction and may be a pathophysiological factor in RV regional and global dysfunction, exercise intolerance and heart failure beyond PR alone The value of RV dyssynchrony as a measure of dysfunction and as a predictor of outcomes is unknown
45 Thank you
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