- Email: [email protected]
Should Tricuspid Annuloplasty be Performed With Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot?
Author's Accepted Manuscript
Should Tricuspid Annuloplasty be Performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot? Mustafa Kurkluoglu MD, Anitha S. John MD, PhD, Russell Cross MD, David Chung MBBS, Can Yerebakan MD, David Zurakowski PhD, Richard A. Jonas MD, Pranava Sinha MD www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1043-0679(15)00105-7 http://dx.doi.org/10.1053/j.semtcvs.2015.07.003 YSTCS751
To appear in:
Semin Thoracic Surg
Cite this article as: Mustafa Kurkluoglu MD, Anitha S. John MD, PhD, Russell Cross MD, David Chung MBBS, Can Yerebakan MD, David Zurakowski PhD, Richard A. Jonas MD, Pranava Sinha MD, Should Tricuspid Annuloplasty be Performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot?, Semin Thoracic Surg, http://dx.doi.org/10.1053/j.semtcvs.2015.07.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Should Tricuspid Annuloplasty be performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in repaired Tetralogy of Fallot?
Running head: Concomitant tricuspid annuloplasty with PVR
Mustafa Kurkluoglu, MDa Anitha S. John, MD, PhDc Russell Cross, MDc David Chung, MBBSa Can Yerebakan, MDa David Zurakowski, PhDb Richard A. Jonas, MDa Pranava Sinha, MDa
a- Department of Cardiovascular Surgery, Children’s National Health System, Washington, DC, United States b- Departments of Anesthesia and Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States c- Department
of
Cardiology,
Washington, DC, United States
Corresponding Author: Pranava Sinha, MD Department of Cardiovascular Surgery
Children’s
National
Health
System,
Children's National Medical Center Assistant Professor Surgery and Pediatrics The George Washington University Medical Center 111 Michigan Avenue NW Washington DC 20010 Phone: 202-476-2020 Fax: 202-476-5572 Email: [email protected]
Disclosure Statement: The authors did not receive any financial support for the study and declare that they have no conflict of interest
Keywords: CHD; tetralogy of Fallot, Tricuspid Valve, Pulmonary Valve
Presented at the STS 50th Annual Meeting, January 25-29, 2014. Orlando, Florida
Central Message: In patients with pulmonary regurgitation after tetralogy of Fallot a reduction in the tricuspid valve size is seen after pulmonary valve replacement. Perspective Statement: In patients with pulmonary regurgitation after tetralogy of Fallot a reduction in the tricuspid valve size is seen after pulmonary valve
replacement, suggestive of a more conservative approach towards concomitant surgical management of tricuspid regurgitation. The RV dilation is differential (inflow sparing). cMRI protocols for these patients should include assessment of tricuspid valve size indices in addition to RV assessment to improve understanding and management of TR. Central Picture: Figure 2 ABC
ABSTRACT Objectives: Indications for prophylactic tricuspid annuloplasty in patients with pulmonary regurgitation after tetralogy of Fallot repair are unclear and often extrapolated from acquired functional tricuspid regurgitation data in adults, where despite correction of primary left heart pathology, progressive tricuspid annular dilation is noted beyond a threshold diameter > 4cms (21mm/m2).
We
hypothesized that unlike in adult functional tricuspid regurgitation, in pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot the tricuspid valve size is likely to regress after pulmonary valve replacement. Methods: 43 consecutive patients who underwent pulmonary valve replacement from 2005 until 2012 at a single institution were retrospectively reviewed. Absolute and indexed tricuspid annulus diameters, tricuspid annulus Z-scores, grade of tricuspid regurgitation along with right ventricular size and function indices were recorded before and after pulmonary valve replacement.
Results: Preoperative and postoperative echocardiographic data were available in all patients. A higher tricuspid valve Z-score correlated with greater tricuspid regurgitation both preoperatively (P=0.005) and postoperatively (P=0.02).
An
overall reduction in the absolute and indexed tricuspid annulus diameter and tricuspid valve Z-scores were seen postoperatively, with greater absolute as well as percentage reduction seen with larger preoperative tricuspid annulus diameter index (P = 0.007) and higher tricuspid annulus Z-scores (P = 0.06). Conclusions: In pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot, reduction in the tricuspid valve size is seen after pulmonary valve replacement. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone.
INTRODUCTION: Tetralogy of Fallot (TOF) patients who undergo transannular patch repair develop pulmonary insufficiency (PI), volume overload of the right ventricle (RV), and RV dilatation.
If left uncorrected, patients can develop RV dysfunction,
ventricular arrhythmias, and tricuspid regurgitation (TR) (1, 2). Functional TR is also common in acquired left-sided valvular or ischemic heart disease secondary to pulmonary hypertension with resulting RV pressure and volume overload. Increasing evidence from this group of patients suggests that an absolute or indexed tricuspid valve annular size rather than the grade of TR is a better indicator of tricuspid valve pathology, and the addition of prophylactic tricuspid annuloplasty for tricuspid annular diameter (TAD) of >4cm
or TAD indexed to body surface area (TADI) of >21mm/m2 at the time of primary left heart surgery improves long-term outcomes (3-6). The indications for tricuspid annuloplasty for adult functional TR have often been extrapolated to patients with TR due to dilated right ventricles after TOF repair with transannular patch. These patients however are different from the adult functional TR patients as they have purely volume overloaded RVs, and in the absence of pressure overload the tricuspid annulus is more likely to regress upon reduction of RV volume load with pulmonary valve replacement (PVR). In this study, we examined the changes in TR and tricuspid valve size [TAD, TADI & tricuspid valve Z-scores (TVZ)] after PVR in patients with severe pulmonary regurgitation.
Our aim was to understand the indications for
prophylactic concomitant tricuspid valve annuloplasty at the time of PVR in this group of patients.
PATIENTS AND METHODS: After obtaining waiver of documentation of informed consent from the Institutional Review Board, data on all consecutive patients with repaired TOF who underwent surgical PVR between 2005 and 2012 for pulmonary regurgitation were retrospectively reviewed. Patients with diagnosis other than TOF (e.g. post balloon or surgical pulmonary valvotomy for congenital pulmonary stenosis) undergoing PVR were excluded. Demographic, echocardiographic,
available cardiac MRI (cMRI) data, operative and postoperative data were analyzed. Criteria for pulmonary valve replacement included severe pulmonary insufficiency with the presence of symptoms. In patients who were asymptomatic, patients were referred for surgery at the recommendation of the primary cardiologists if two or more criteria were present: RVEDVI>150 ml/m2 or Z-score >4 (In patients whose body surface area falls outside published normal data: RV/LV end-diastolic volume ratio >2); RVESVI>80 ml/m2; RVEF<47%; LVEF<55%; large RVOT aneurysm. (7, 8) Echocardiographic and cMRI measurements: On transthoracic echocardiogram, the tricuspid annulus was measured in the apical 4- chamber view in late diastole at the time of maximal tricuspid opening. Measurements were taken on the preoperative echocardiogram and at the last follow up in all patients. This measurement was used as the absolute tricuspid annulus diameter (TAD), and indexed to body surface area (BSA) as TADI (TADI=TAD/BSA). Tricuspid valve annulus Z-scores (TVZ) were calculated using published standards (9). An integrative approach using multiple parameters as recommended by the American Society of Echocardiography Task force (10, 11) was used for grading TR into mild, moderate, severe or nil. Using standard cMRI techniques right ventricular dimensions and ejection fraction (RVEF) were calculated. Tricuspid annulus was measured in 2 perpendicular dimensions using the short axis view on cine imaging. Similar to echocardiograms, measured TAD was indexed to BSA to calculate TADI. To prevent inter-observer variability, all echocardiograms were read by a single
echocardiographer (co-author AJ). Similarly all cMRI data was reviewed by a single cardiac radiologist (co-author RC).
Statistical Analysis: Paired t-tests were used to compare pre and postoperative echocardiographic TV parameters (TR grade, TAD, TADI, and TVZ). cMRI and echocardiographic measurements of the tricuspid valve were compared using Pearson correlation for correlation and Bland-Altman method for determining agreement with 95% confidence limits. cMRI data were analyzed for correlation between preoperative TADI and RV size (right ventricular end diastolic volume indexed- RVEDVI; right ventricular end systolic volume indexed- RVESVI) and right ventricular ejection fraction (RVEF). Two-tailed values of P < 0.05 were considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics (version 21.0, IBM, Armonk, NY).
RESULTS: A total of 43 patients who underwent pulmonary valve replacement during the study period were included in the study group. Demographic data of the study group are summarized in Table 1.
No tricuspid valve interventions were
performed on any patient. There was no mortality in the series. Median duration of follow up was 50 days.
Preoperative and postoperative
echocardiographic data were available in all patients. Pre- and post-operative echocardiographic data are summarized in Table 2.
All patients had cMRI preoperatively, however as many studies were performed at outside referring centers, direct measurement of the study endpoints was possible in 27 patients only. No postoperative cMRI data was available. cMRI data is summarized in Table 3. A larger TVZ-score correlated with greater TR both preoperatively (P = 0.005); and postoperatively (P= 0.02). (Figure 1) An overall reduction in the TAD (P<0.001), TADI (P=0.001) and TVZ (P<0.001) scores as measured by echocardiography was seen with pulmonary valve replacement (Table 2) (Figure 2A, B & C), irrespective of the preoperative tricuspid valve size, with greater absolute reduction (r = 0.84, P<0.001) and percentage reduction (r = 0.61, P<0.001) reduction seen with larger TADI (P=0.007) and higher Z-scores (P=0.06) (Figure 3). Using cMRI data alone, there was poor correlation between pre-operative TADI and pre-operative RV volumes [RVEDV: r = -0.09, P = 0.68; RVESV: r = -0.26, P = 0.22] or RV function [RVEF: r = 0.08, P = 0.67]. Although preoperative echocardiographic and cMRI modalities were moderately correlated with TAD and TADI (r = 0.65, P< 0.001), Bland-Altman paired analysis indicated poor agreement between these two modalities as indicated by very wide 95% limits of agreement from-7.1 mm/m2 to + 5.3 mm/m2.
DISCUSSION: Pulmonary regurgitation after TOF repair leads to severe RV volume overload, and TR. While believed to be secondary to right ventricular dilation, the exact mechanism of TR in these patients is unknown. Criteria for concomitant prophylactic tricuspid annuloplasty in this patient group are not clear, and are often modeled from data on adult functional TR patients where tricuspid valve intervention is predominantly based on the size of the valve as increasing evidence shows persistence, or even appearance of new TR and RV dysfunction despite adequate correction of the primary left heart lesions (12-15). It has been noted that beyond a threshold size, a dilated tricuspid annulus continues to dilate even after correction of the left heart pathology, addition of tricuspid annuloplasty above a threshold TADI of 21mm/m2 (3) or an absolute TAD of >3.5cms (16) or >4 cm (5) leads to better long-term outcomes (3-6). A significant number of ACHD patients are still cared for at either adult centers or by adult practitioners (17), with a greater chance of inappropriate translation of adult cardiac indications and practices to this patient population. This is the first study which looks at the effects of PVR on tricuspid valve dimensions in patients with repaired TOF with PI. A positive correlation between TADI and TVZ-scores and the grade of TR supports annular dilation as the mechanism of TR in these patients. However, lack of correlation between preoperative RV volumes and function and tricuspid annular dilation (TAD or TADI) suggest that tricuspid valve dilation in TOF patients with PI is not
proportional to RV dilation or dysfunction, and that other mechanisms may be responsible for tricuspid valve annular dilation. Our study shows that, unlike functional TR patients, the dilated tricuspid annulus in repaired TOF patients with PI regresses after PVR. A greater absolute and proportional regression in the size of the TAD suggests less need for surgical remodeling with an annuloplasty in these patients. With significant reduction in the tricuspid valve size seen at short to intermediate term follow up [median (IQR) of 50 (6-738) days], even greater improvement is expected with long-term remodeling of the right ventricle after PVR. The only other study looking at the need for tricuspid valve repair in patients with TOF needing PVR found no difference in TR with or without tricuspid annuloplasty in 35 patients at up to 3 years postoperatively (18). However the grade of TR, the study endpoint, and tricuspid valve annular size were not taken into account. The drawbacks of echocardiographic assessment of RV size and volume are well known and cMRI is the gold standard in assessment of TOF patients with PI (7). While poor correlation between estimated RV volumes by cMRI and echocardiogram
are well
known,
we
found
good
correlation
between
echocardiograms and cMRI with regards to tricuspid valve size measurements. However poor statistical agreement between the values underlines the need for complimentary use of both these modalities in decision making for these patients. While cMRI is used for measurement of RV volumes and function indices in repaired TOF patients, tricuspid valve assessment by MRI is often limited to
estimation of the regurgitant fraction, and decisions with regards to the tricuspid valve are often made on the echocardiographic data alone. The ability of MRI in being able to post-facto measure a three dimensional dynamic structure such as the tricuspid annulus, could provide further insight into mechanisms and treatment strategies of TR and should be incorporated in standard protocols for assessment of these patients.
Our study has the limitations of being a single center, small volume retrospective study, a relatively younger cohort of patients, with lack of postoperative MRI data. However, it clearly shows that tricuspid annulus regresses in size after PVR in patients with TOF, and tricuspid annuloplasty should not be considered based on tricuspid annular size alone. Larger multicenter prospective trials with longer follow-up are required to define criteria for tricuspid valve interventions in these patients.
CONCLUSION: In pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot repair, reduction in tricuspid valve size is seen after pulmonary valve replacement. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone. Further studies to define criteria for tricuspid valve interventions in these patients are required.
REFERENCE: 1.
Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008 December 2, 2008;118(23):2395-451. 2.
Bouzas B, Kilner PJ, Gatzoulis MA. Pulmonary regurgitation: not a benign
lesion. Eur Heart J 2005 Mar;26(5):433-9. 3.
Colombo T, Russo C, Ciliberto GR, et al. Tricuspid regurgitation secondary to
mitral valve disease: tricuspid annulus function as guide to tricuspid valve repair. Cardiovasc Surg 2001 Aug;9(4):369-77. 4.
Dreyfus GD, Corbi PJ, Chan KMJ, Bahrami T. Secondary Tricuspid
Regurgitation or Dilatation: Which Should Be the Criteria for Surgical Repair? Ann Thorac Surg 2005 January 1, 2005;79(1):127-32. 5.
Benedetto U, Melina G, Angeloni E, et al. Prophylactic tricuspid annuloplasty
in patients with dilated tricuspid annulus undergoing mitral valve surgery. J Thorac Cardiovasc Surg 2012 Mar;143(3):632-8. 6.
Van de Veire NR, Braun J, Delgado V, et al. Tricuspid annuloplasty prevents
right ventricular dilatation and progression of tricuspid regurgitation in patients
with tricuspid annular dilatation undergoing mitral valve repair. The Journal of Thoracic and Cardiovascular Surgery 2011;141(6):1431-9. 7.
Geva T. Indications and Timing of Pulmonary Valve Replacement After
Tetralogy of Fallot Repair. Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual 2006;9(1):11-22. 8.
Geva T. Indications for pulmonary valve replacement in repaired tetralogy of
fallot: the quest continues. Circulation 2013 Oct 22;128(17):1855-7. 9.
Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for
calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 2008 Aug;21(8):922-34. 10.
Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for
evaluation of the severity of native valvular regurgitation with two-dimensional and doppler echocardiography. Journal of the American Society of Echocardiography 2003;16(7):777-802. 11.
Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the
Management of Patients With Valvular Heart DiseaseA Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology 2014;63(22):e57-e185. 12.
Sagie A, Schwammenthal E, Newell JB, et al. Significant tricuspid
regurgitation is a marker for adverse outcome in patients undergoing percutaneous balloon mitral valvuloplasty. J Am Coll Cardiol 1994 Sep;24(3):696-702.
13.
Sagie A, Schwammenthal E, Padial LR, Vazquez de Prada JA, Weyman AE,
Levine RA. Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol 1994 Aug;24(2):446-53. 14.
Sagie A, Schwammenthal E, Palacios IF, et al. Significant tricuspid
regurgitation does not resolve after percutaneous balloon mitral valvotomy. J Thorac Cardiovasc Surg 1994 Oct;108(4):727-35. 15.
Porter A, Shapira Y, Wurzel M, et al. Tricuspid regurgitation late after mitral
valve replacement: clinical and echocardiographic evaluation. J Heart Valve Dis 1999 Jan;8(1):57-62. 16.
Shiran A, Sagie A. Tricuspid Regurgitation in Mitral Valve Disease: Incidence,
Prognostic Implications, Mechanism, and Management. Journal of the American College of Cardiology 2009;53(5):401-8. 17.
Karamlou T, Diggs BS, Ungerleider RM, Welke KF. Adults or big kids: what is
the ideal clinical environment for management of grown-up patients with congenital heart disease? Ann Thorac Surg 2010;90(2):573-9. 18.
Kogon B, Patel M, Leong T, McConnell M, Book W. Management of moderate
functional tricuspid valve regurgitation at the time of pulmonary valve replacement: is
concomitant
2010;31(6):843-8.
tricuspid
valve
repair
necessary?
Pediatric
cardiology
TABLES
Table 1: Demographic data Variables (N=43)
Value
Male, no. (%)
27(62.8%)
Age at the time of PVR, median (IQR), years
17.2 (12.8-28.7)
Weight at the time of PVR, mean±SD, kgs
56.1 ± 21.9
BSA at the time of PVR, mean±SD, m2
1.53 ± 0.38
Time since TOF repair, mean±SD, years
18.7 ± 10.2
Duration of follow up, median (IQR), days
50 (6-738)
PVR: Pulmonary valve replacement; BSA: Body surface area; SD: Standard deviation; IQR: Interquartile range
Table 2: Preoperative and postoperative echocardiographic data Parameter (N=43)
Preoperative
Postoperative
P value
TAD in mm, mean + SD
30 ± 5
28 ± 6
<0.001
TADI in mm/m2, mean + SD
20.95±7.24
19.39±5.37
0.001
TVZ, median (IQR)
0.82 (0.26-1.22)
0.3 (-0.18 -0.79)
<0.001
TR Grade, mean+ SD
2.1 ± 0.3
2.0 ± 0.3
0.08
TAD: Tricuspid annulus diameter; TADI: Tricuspid annular diameter index to body surface area (TADI= TAD/BSA); TVZ: Tricuspid valve Z-score; TR: Tricuspid regurgitation (Grading 0-nil, 1-trivial, 2- mild, 3- Moderate, 4-Severe)
Table 3: Preoperative cMRI data Variable (N=27)
Mean
SD
TAD mm
30.12
6.53
TADI mm/m2
20.13
3.78
RVEDVI ml/m2
164.52
39.34
RVESVI ml/m2
92.36
39.10
PR fraction %
44.72
13.13
RVEF %
45.45
11.24
RVEDVI: Right ventricular end diastolic volume indexed to body surface area (RVEDVI= RVEDV/ BSA); RVESVI, Right ventricular end systolic volume indexed to body surface area (RVESVI=RVESV/BSA); TAD: Tricuspid annulus diameter; TADI: Tricuspid annular diameter index to body surface area (TADI= TAD/BSA); RVEF: Right ventricular ejection fraction; PR:
Pulmonary
regurgitation
FIGURE LEGENDS Figure 1- Severity of tricuspid regurgitation (TR) compared to tricuspid valve Zscores (TVZ) both pre and postoperatively. * Significant larger TVZ scores noted in moderate TR group compared to mild TR group both preoperatively (P=.005) and postoperatively (P=.02) Figure 2 Significant reduction in (A) tricuspid valve annulus diameter in mm (TAD), (B) tricuspid valve annulus diameter indexed in mm/m 2 (TADI), and (C) tricuspid valve Z scores (TVZ); after pulmonary valve replacement as measured by echocardiography. Horizontal transverse lines denote mean preoperative and postoperative values. Figure 3- Relation between preoperative tricuspid annulus diameter index mm/m2 (TADI) demonstrating a greater reduction in (A) absolute TADI and (B) percentage size reduction in TADI after pulmonary valve replacement
Figure 1
Figure 2a
Figure 2B
Figure 2c
Figure 3
Should Tricuspid Annuloplasty be Performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot? Mustafa Kurkluoglu MD, Anitha S. John MD, PhD, Russell Cross MD, David Chung MBBS, Can Yerebakan MD, David Zurakowski PhD, Richard A. Jonas MD, Pranava Sinha MD www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1043-0679(15)00105-7 http://dx.doi.org/10.1053/j.semtcvs.2015.07.003 YSTCS751
To appear in:
Semin Thoracic Surg
Cite this article as: Mustafa Kurkluoglu MD, Anitha S. John MD, PhD, Russell Cross MD, David Chung MBBS, Can Yerebakan MD, David Zurakowski PhD, Richard A. Jonas MD, Pranava Sinha MD, Should Tricuspid Annuloplasty be Performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot?, Semin Thoracic Surg, http://dx.doi.org/10.1053/j.semtcvs.2015.07.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Should Tricuspid Annuloplasty be performed with Pulmonary Valve Replacement for Pulmonary Regurgitation in repaired Tetralogy of Fallot?
Running head: Concomitant tricuspid annuloplasty with PVR
Mustafa Kurkluoglu, MDa Anitha S. John, MD, PhDc Russell Cross, MDc David Chung, MBBSa Can Yerebakan, MDa David Zurakowski, PhDb Richard A. Jonas, MDa Pranava Sinha, MDa
a- Department of Cardiovascular Surgery, Children’s National Health System, Washington, DC, United States b- Departments of Anesthesia and Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States c- Department
of
Cardiology,
Washington, DC, United States
Corresponding Author: Pranava Sinha, MD Department of Cardiovascular Surgery
Children’s
National
Health
System,
Children's National Medical Center Assistant Professor Surgery and Pediatrics The George Washington University Medical Center 111 Michigan Avenue NW Washington DC 20010 Phone: 202-476-2020 Fax: 202-476-5572 Email: [email protected]
Disclosure Statement: The authors did not receive any financial support for the study and declare that they have no conflict of interest
Keywords: CHD; tetralogy of Fallot, Tricuspid Valve, Pulmonary Valve
Presented at the STS 50th Annual Meeting, January 25-29, 2014. Orlando, Florida
Central Message: In patients with pulmonary regurgitation after tetralogy of Fallot a reduction in the tricuspid valve size is seen after pulmonary valve replacement. Perspective Statement: In patients with pulmonary regurgitation after tetralogy of Fallot a reduction in the tricuspid valve size is seen after pulmonary valve
replacement, suggestive of a more conservative approach towards concomitant surgical management of tricuspid regurgitation. The RV dilation is differential (inflow sparing). cMRI protocols for these patients should include assessment of tricuspid valve size indices in addition to RV assessment to improve understanding and management of TR. Central Picture: Figure 2 ABC
ABSTRACT Objectives: Indications for prophylactic tricuspid annuloplasty in patients with pulmonary regurgitation after tetralogy of Fallot repair are unclear and often extrapolated from acquired functional tricuspid regurgitation data in adults, where despite correction of primary left heart pathology, progressive tricuspid annular dilation is noted beyond a threshold diameter > 4cms (21mm/m2).
We
hypothesized that unlike in adult functional tricuspid regurgitation, in pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot the tricuspid valve size is likely to regress after pulmonary valve replacement. Methods: 43 consecutive patients who underwent pulmonary valve replacement from 2005 until 2012 at a single institution were retrospectively reviewed. Absolute and indexed tricuspid annulus diameters, tricuspid annulus Z-scores, grade of tricuspid regurgitation along with right ventricular size and function indices were recorded before and after pulmonary valve replacement.
Results: Preoperative and postoperative echocardiographic data were available in all patients. A higher tricuspid valve Z-score correlated with greater tricuspid regurgitation both preoperatively (P=0.005) and postoperatively (P=0.02).
An
overall reduction in the absolute and indexed tricuspid annulus diameter and tricuspid valve Z-scores were seen postoperatively, with greater absolute as well as percentage reduction seen with larger preoperative tricuspid annulus diameter index (P = 0.007) and higher tricuspid annulus Z-scores (P = 0.06). Conclusions: In pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot, reduction in the tricuspid valve size is seen after pulmonary valve replacement. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone.
INTRODUCTION: Tetralogy of Fallot (TOF) patients who undergo transannular patch repair develop pulmonary insufficiency (PI), volume overload of the right ventricle (RV), and RV dilatation.
If left uncorrected, patients can develop RV dysfunction,
ventricular arrhythmias, and tricuspid regurgitation (TR) (1, 2). Functional TR is also common in acquired left-sided valvular or ischemic heart disease secondary to pulmonary hypertension with resulting RV pressure and volume overload. Increasing evidence from this group of patients suggests that an absolute or indexed tricuspid valve annular size rather than the grade of TR is a better indicator of tricuspid valve pathology, and the addition of prophylactic tricuspid annuloplasty for tricuspid annular diameter (TAD) of >4cm
or TAD indexed to body surface area (TADI) of >21mm/m2 at the time of primary left heart surgery improves long-term outcomes (3-6). The indications for tricuspid annuloplasty for adult functional TR have often been extrapolated to patients with TR due to dilated right ventricles after TOF repair with transannular patch. These patients however are different from the adult functional TR patients as they have purely volume overloaded RVs, and in the absence of pressure overload the tricuspid annulus is more likely to regress upon reduction of RV volume load with pulmonary valve replacement (PVR). In this study, we examined the changes in TR and tricuspid valve size [TAD, TADI & tricuspid valve Z-scores (TVZ)] after PVR in patients with severe pulmonary regurgitation.
Our aim was to understand the indications for
prophylactic concomitant tricuspid valve annuloplasty at the time of PVR in this group of patients.
PATIENTS AND METHODS: After obtaining waiver of documentation of informed consent from the Institutional Review Board, data on all consecutive patients with repaired TOF who underwent surgical PVR between 2005 and 2012 for pulmonary regurgitation were retrospectively reviewed. Patients with diagnosis other than TOF (e.g. post balloon or surgical pulmonary valvotomy for congenital pulmonary stenosis) undergoing PVR were excluded. Demographic, echocardiographic,
available cardiac MRI (cMRI) data, operative and postoperative data were analyzed. Criteria for pulmonary valve replacement included severe pulmonary insufficiency with the presence of symptoms. In patients who were asymptomatic, patients were referred for surgery at the recommendation of the primary cardiologists if two or more criteria were present: RVEDVI>150 ml/m2 or Z-score >4 (In patients whose body surface area falls outside published normal data: RV/LV end-diastolic volume ratio >2); RVESVI>80 ml/m2; RVEF<47%; LVEF<55%; large RVOT aneurysm. (7, 8) Echocardiographic and cMRI measurements: On transthoracic echocardiogram, the tricuspid annulus was measured in the apical 4- chamber view in late diastole at the time of maximal tricuspid opening. Measurements were taken on the preoperative echocardiogram and at the last follow up in all patients. This measurement was used as the absolute tricuspid annulus diameter (TAD), and indexed to body surface area (BSA) as TADI (TADI=TAD/BSA). Tricuspid valve annulus Z-scores (TVZ) were calculated using published standards (9). An integrative approach using multiple parameters as recommended by the American Society of Echocardiography Task force (10, 11) was used for grading TR into mild, moderate, severe or nil. Using standard cMRI techniques right ventricular dimensions and ejection fraction (RVEF) were calculated. Tricuspid annulus was measured in 2 perpendicular dimensions using the short axis view on cine imaging. Similar to echocardiograms, measured TAD was indexed to BSA to calculate TADI. To prevent inter-observer variability, all echocardiograms were read by a single
echocardiographer (co-author AJ). Similarly all cMRI data was reviewed by a single cardiac radiologist (co-author RC).
Statistical Analysis: Paired t-tests were used to compare pre and postoperative echocardiographic TV parameters (TR grade, TAD, TADI, and TVZ). cMRI and echocardiographic measurements of the tricuspid valve were compared using Pearson correlation for correlation and Bland-Altman method for determining agreement with 95% confidence limits. cMRI data were analyzed for correlation between preoperative TADI and RV size (right ventricular end diastolic volume indexed- RVEDVI; right ventricular end systolic volume indexed- RVESVI) and right ventricular ejection fraction (RVEF). Two-tailed values of P < 0.05 were considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics (version 21.0, IBM, Armonk, NY).
RESULTS: A total of 43 patients who underwent pulmonary valve replacement during the study period were included in the study group. Demographic data of the study group are summarized in Table 1.
No tricuspid valve interventions were
performed on any patient. There was no mortality in the series. Median duration of follow up was 50 days.
Preoperative and postoperative
echocardiographic data were available in all patients. Pre- and post-operative echocardiographic data are summarized in Table 2.
All patients had cMRI preoperatively, however as many studies were performed at outside referring centers, direct measurement of the study endpoints was possible in 27 patients only. No postoperative cMRI data was available. cMRI data is summarized in Table 3. A larger TVZ-score correlated with greater TR both preoperatively (P = 0.005); and postoperatively (P= 0.02). (Figure 1) An overall reduction in the TAD (P<0.001), TADI (P=0.001) and TVZ (P<0.001) scores as measured by echocardiography was seen with pulmonary valve replacement (Table 2) (Figure 2A, B & C), irrespective of the preoperative tricuspid valve size, with greater absolute reduction (r = 0.84, P<0.001) and percentage reduction (r = 0.61, P<0.001) reduction seen with larger TADI (P=0.007) and higher Z-scores (P=0.06) (Figure 3). Using cMRI data alone, there was poor correlation between pre-operative TADI and pre-operative RV volumes [RVEDV: r = -0.09, P = 0.68; RVESV: r = -0.26, P = 0.22] or RV function [RVEF: r = 0.08, P = 0.67]. Although preoperative echocardiographic and cMRI modalities were moderately correlated with TAD and TADI (r = 0.65, P< 0.001), Bland-Altman paired analysis indicated poor agreement between these two modalities as indicated by very wide 95% limits of agreement from-7.1 mm/m2 to + 5.3 mm/m2.
DISCUSSION: Pulmonary regurgitation after TOF repair leads to severe RV volume overload, and TR. While believed to be secondary to right ventricular dilation, the exact mechanism of TR in these patients is unknown. Criteria for concomitant prophylactic tricuspid annuloplasty in this patient group are not clear, and are often modeled from data on adult functional TR patients where tricuspid valve intervention is predominantly based on the size of the valve as increasing evidence shows persistence, or even appearance of new TR and RV dysfunction despite adequate correction of the primary left heart lesions (12-15). It has been noted that beyond a threshold size, a dilated tricuspid annulus continues to dilate even after correction of the left heart pathology, addition of tricuspid annuloplasty above a threshold TADI of 21mm/m2 (3) or an absolute TAD of >3.5cms (16) or >4 cm (5) leads to better long-term outcomes (3-6). A significant number of ACHD patients are still cared for at either adult centers or by adult practitioners (17), with a greater chance of inappropriate translation of adult cardiac indications and practices to this patient population. This is the first study which looks at the effects of PVR on tricuspid valve dimensions in patients with repaired TOF with PI. A positive correlation between TADI and TVZ-scores and the grade of TR supports annular dilation as the mechanism of TR in these patients. However, lack of correlation between preoperative RV volumes and function and tricuspid annular dilation (TAD or TADI) suggest that tricuspid valve dilation in TOF patients with PI is not
proportional to RV dilation or dysfunction, and that other mechanisms may be responsible for tricuspid valve annular dilation. Our study shows that, unlike functional TR patients, the dilated tricuspid annulus in repaired TOF patients with PI regresses after PVR. A greater absolute and proportional regression in the size of the TAD suggests less need for surgical remodeling with an annuloplasty in these patients. With significant reduction in the tricuspid valve size seen at short to intermediate term follow up [median (IQR) of 50 (6-738) days], even greater improvement is expected with long-term remodeling of the right ventricle after PVR. The only other study looking at the need for tricuspid valve repair in patients with TOF needing PVR found no difference in TR with or without tricuspid annuloplasty in 35 patients at up to 3 years postoperatively (18). However the grade of TR, the study endpoint, and tricuspid valve annular size were not taken into account. The drawbacks of echocardiographic assessment of RV size and volume are well known and cMRI is the gold standard in assessment of TOF patients with PI (7). While poor correlation between estimated RV volumes by cMRI and echocardiogram
are well
known,
we
found
good
correlation
between
echocardiograms and cMRI with regards to tricuspid valve size measurements. However poor statistical agreement between the values underlines the need for complimentary use of both these modalities in decision making for these patients. While cMRI is used for measurement of RV volumes and function indices in repaired TOF patients, tricuspid valve assessment by MRI is often limited to
estimation of the regurgitant fraction, and decisions with regards to the tricuspid valve are often made on the echocardiographic data alone. The ability of MRI in being able to post-facto measure a three dimensional dynamic structure such as the tricuspid annulus, could provide further insight into mechanisms and treatment strategies of TR and should be incorporated in standard protocols for assessment of these patients.
Our study has the limitations of being a single center, small volume retrospective study, a relatively younger cohort of patients, with lack of postoperative MRI data. However, it clearly shows that tricuspid annulus regresses in size after PVR in patients with TOF, and tricuspid annuloplasty should not be considered based on tricuspid annular size alone. Larger multicenter prospective trials with longer follow-up are required to define criteria for tricuspid valve interventions in these patients.
CONCLUSION: In pure volume-overload conditions such as patients with pulmonary regurgitation after tetralogy of Fallot repair, reduction in tricuspid valve size is seen after pulmonary valve replacement. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone. Further studies to define criteria for tricuspid valve interventions in these patients are required.
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Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008 December 2, 2008;118(23):2395-451. 2.
Bouzas B, Kilner PJ, Gatzoulis MA. Pulmonary regurgitation: not a benign
lesion. Eur Heart J 2005 Mar;26(5):433-9. 3.
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mitral valve disease: tricuspid annulus function as guide to tricuspid valve repair. Cardiovasc Surg 2001 Aug;9(4):369-77. 4.
Dreyfus GD, Corbi PJ, Chan KMJ, Bahrami T. Secondary Tricuspid
Regurgitation or Dilatation: Which Should Be the Criteria for Surgical Repair? Ann Thorac Surg 2005 January 1, 2005;79(1):127-32. 5.
Benedetto U, Melina G, Angeloni E, et al. Prophylactic tricuspid annuloplasty
in patients with dilated tricuspid annulus undergoing mitral valve surgery. J Thorac Cardiovasc Surg 2012 Mar;143(3):632-8. 6.
Van de Veire NR, Braun J, Delgado V, et al. Tricuspid annuloplasty prevents
right ventricular dilatation and progression of tricuspid regurgitation in patients
with tricuspid annular dilatation undergoing mitral valve repair. The Journal of Thoracic and Cardiovascular Surgery 2011;141(6):1431-9. 7.
Geva T. Indications and Timing of Pulmonary Valve Replacement After
Tetralogy of Fallot Repair. Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual 2006;9(1):11-22. 8.
Geva T. Indications for pulmonary valve replacement in repaired tetralogy of
fallot: the quest continues. Circulation 2013 Oct 22;128(17):1855-7. 9.
Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for
calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 2008 Aug;21(8):922-34. 10.
Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for
evaluation of the severity of native valvular regurgitation with two-dimensional and doppler echocardiography. Journal of the American Society of Echocardiography 2003;16(7):777-802. 11.
Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the
Management of Patients With Valvular Heart DiseaseA Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology 2014;63(22):e57-e185. 12.
Sagie A, Schwammenthal E, Newell JB, et al. Significant tricuspid
regurgitation is a marker for adverse outcome in patients undergoing percutaneous balloon mitral valvuloplasty. J Am Coll Cardiol 1994 Sep;24(3):696-702.
13.
Sagie A, Schwammenthal E, Padial LR, Vazquez de Prada JA, Weyman AE,
Levine RA. Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol 1994 Aug;24(2):446-53. 14.
Sagie A, Schwammenthal E, Palacios IF, et al. Significant tricuspid
regurgitation does not resolve after percutaneous balloon mitral valvotomy. J Thorac Cardiovasc Surg 1994 Oct;108(4):727-35. 15.
Porter A, Shapira Y, Wurzel M, et al. Tricuspid regurgitation late after mitral
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Prognostic Implications, Mechanism, and Management. Journal of the American College of Cardiology 2009;53(5):401-8. 17.
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the ideal clinical environment for management of grown-up patients with congenital heart disease? Ann Thorac Surg 2010;90(2):573-9. 18.
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concomitant
2010;31(6):843-8.
tricuspid
valve
repair
necessary?
Pediatric
cardiology
TABLES
Table 1: Demographic data Variables (N=43)
Value
Male, no. (%)
27(62.8%)
Age at the time of PVR, median (IQR), years
17.2 (12.8-28.7)
Weight at the time of PVR, mean±SD, kgs
56.1 ± 21.9
BSA at the time of PVR, mean±SD, m2
1.53 ± 0.38
Time since TOF repair, mean±SD, years
18.7 ± 10.2
Duration of follow up, median (IQR), days
50 (6-738)
PVR: Pulmonary valve replacement; BSA: Body surface area; SD: Standard deviation; IQR: Interquartile range
Table 2: Preoperative and postoperative echocardiographic data Parameter (N=43)
Preoperative
Postoperative
P value
TAD in mm, mean + SD
30 ± 5
28 ± 6
<0.001
TADI in mm/m2, mean + SD
20.95±7.24
19.39±5.37
0.001
TVZ, median (IQR)
0.82 (0.26-1.22)
0.3 (-0.18 -0.79)
<0.001
TR Grade, mean+ SD
2.1 ± 0.3
2.0 ± 0.3
0.08
TAD: Tricuspid annulus diameter; TADI: Tricuspid annular diameter index to body surface area (TADI= TAD/BSA); TVZ: Tricuspid valve Z-score; TR: Tricuspid regurgitation (Grading 0-nil, 1-trivial, 2- mild, 3- Moderate, 4-Severe)
Table 3: Preoperative cMRI data Variable (N=27)
Mean
SD
TAD mm
30.12
6.53
TADI mm/m2
20.13
3.78
RVEDVI ml/m2
164.52
39.34
RVESVI ml/m2
92.36
39.10
PR fraction %
44.72
13.13
RVEF %
45.45
11.24
RVEDVI: Right ventricular end diastolic volume indexed to body surface area (RVEDVI= RVEDV/ BSA); RVESVI, Right ventricular end systolic volume indexed to body surface area (RVESVI=RVESV/BSA); TAD: Tricuspid annulus diameter; TADI: Tricuspid annular diameter index to body surface area (TADI= TAD/BSA); RVEF: Right ventricular ejection fraction; PR:
Pulmonary
regurgitation
FIGURE LEGENDS Figure 1- Severity of tricuspid regurgitation (TR) compared to tricuspid valve Zscores (TVZ) both pre and postoperatively. * Significant larger TVZ scores noted in moderate TR group compared to mild TR group both preoperatively (P=.005) and postoperatively (P=.02) Figure 2 Significant reduction in (A) tricuspid valve annulus diameter in mm (TAD), (B) tricuspid valve annulus diameter indexed in mm/m 2 (TADI), and (C) tricuspid valve Z scores (TVZ); after pulmonary valve replacement as measured by echocardiography. Horizontal transverse lines denote mean preoperative and postoperative values. Figure 3- Relation between preoperative tricuspid annulus diameter index mm/m2 (TADI) demonstrating a greater reduction in (A) absolute TADI and (B) percentage size reduction in TADI after pulmonary valve replacement
Figure 1
Figure 2a
Figure 2B
Figure 2c
Figure 3