Supplementary Appendix

This appendix has been provided by the authors to give readers additional information about their work.

Supplement to: Verma S, Siu SC. Aortic dilatation in patients with bicuspid aortic valve. N Engl J Med 2014;370:1920-9. DOI: 10.1056/NEJMra1207059

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Current Concepts

Bicuspid Aortopathy

Subodh Verma, MD, PhD, FRCSC and Samuel C. Siu, MD, SM, FRCPC

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Supplementary Section

Figure S1: Bicuspid valve morphology pattern may influence aortopathy pattern

Figure S2: Long term risk of aneurysm formation, aortic dissection and need for aortic surgery

Table S 1: Summary of Recently Published Studies

Table S 2: Summary of Pregnancy Management Recommendations

Table S 3: Summary of Exercise Restriction Recommendations

References

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Figure S1: Bicuspid Valve Morphology Pattern May Influence Aortopathy Pattern

A

 

 

 

 

 

 

 

 

Coregistered steady-state free precession images (panels i-iii) define anatomic landmarks and allow for determination of the direction and propagation of systolic flow jet (panels iv and v). In the right-left (RL) bicuspid aortic valve lesion shown (panel iii), the jet would be aimed towards the right-anterior aorta wall of the ascending aorta and will impact and travel along the right-anterior aorta wall in a right-handed helical direction. (Adapted with permission from Barker AJ, et al. Circulation Cardiovascular imaging 2012;5:457-66.)1

 

B 

iii

i

ii

iii

i

ii v iv

iv v vi

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A right and noncoronary cusp (RN) fusion (panels i to iv) would yield a jetting pattern towards the posterior wall of the aorta, opposite from the fused right and noncoronary cusp. The peak wall shear stress (WSS) for this patient occurs at the RP position (black closed arrow) instead of at the RA position for right-left (RL) bicuspid aortic valve patients (panel v). The incomplete opening of the fused cusp appears to influence the direction of the velocity jet (black open arrow) and thus the position of the peak WSS eccentricity (panel vi). A, anterior; LA, left-anterior; L, left; LP, left-posterior; P, posterior and RP, right-posterior; R, right; RA, right-anterior. (Adapted with permission from Barker AJ, et al. Circulation Cardiovascular imaging 2012;5:457-66.)1

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Figure S2: Twenty five year risk of aneurysm formation, aortic dissection and need for aortic surgery in patients with bicuspid aortic valves

In the top panel, risk of aortic aneurysm 25 years after diagnosis in 384 patients (32 patients with baseline aneurysm excluded) and risk of aortic dissection 25 years after diagnosis in the entire study group of 416 patients. In the bottom panel, risk of aortic surgery 25 years after diagnosis in the entire study group. (Reprinted with permission from Michelena HI et al. JAMA 2011;306:1104-12).2 Of the 416 cohort patients, 49 patients underwent surgery of the thoracic aorta, 11 patients underwent surgery for aortic coarctation or recoarctation and 2 for ascending aortic dissection. The 25 year risk of aortic surgery after diagnosis was 25%.

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Table S 1: Selected Recently Published Studies Examining Outcomes of Aorta Surgery in Individuals with Bicuspid Aortic Valves*

Inclusion Criteria and years of operation

Number of patients (n) In hospital or 30 day mortality

Long Term Outcomes

Patients undergoing bicuspid aortic valve surgery (AoV) (1993 – 2003)3

AoV alone (n= 1449) and with

ascending aortic repair (n=361) Propensity matching of 202

pairs of AoV alone and AoV plus ascending aorta repair patients

Mortality of AoV alone (1.2%) group similar to that in AoV plus ascending aorta repair group (1.1%)

Matched cohort: AoV plus ascending aorta group had similar 10 year survival (86%) and freedom from late aortic events (97%) compared to AoV alone group (85% and 95% respectively)

Patients undergoing aorta replacement (2005 – 2009)4

n=100 16% had prior aortic valve

replacement 82% underwent concomitant

arch replacement

1% No deaths or reoperation at mean follow up of 16 months

Patients undergoing repair or replacement of ascending aorta and did not required arch replacement (1988-2007)5

n=422 1.7% 90% - 5 year survival 94% - 5 year freedom

from late reoperation None of late

reoperation was for arch dilatation

Patients undergoing AoV with replacement of ascending aorta (1979 – 1997)6

n=143 2.1% 82% - 10 year event free survival

Late outcomes not predicted by operative techniques

Patients undergoing Tirone David valve-sparing aortic root replacement and cusps repair (1997-2011)7

n=75 1.3% No late deaths at median follow up of 3 years

90% - 3 years freedom from late reoperation

Patients undergoing aortic valve preserving surgery8

Overview of 30 studies published 1994 - 2011

25 of 30 studies were of combined aortic valve repair

0 – 5% 82-100% - 5 year survival

43-100% - 5 year freedom from

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* Surgical techniques varied within each study and across studies, reflecting institutional expertise, patient selection, heterogeneity in patient’s aortopathy pattern, and different threshold for interventions on the aorta. Readers interested in further details regarding surgical decision making, perioperative management, and strategy (open vs. closed distal anastomosis), arch reconstructive options, and use of cerebral protection strategies are referred to the comprehensive 2010 Guidelines document.9

and procedures on aortic root or ascending aorta

reoperation

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Table S 2: Management of Pregnant Women with Bicuspid Aortopathy*

Prior to Pregnancy

Women with a bicuspid aortic valve should undergo imaging of the entire aorta before pregnancy10

Prepregnancy evaluation in women with bicuspid aortic valve and aortopathy should be performed by practitioners with expertise in the management of pregnant women with heart disease

Women with ascending aorta and/or root dimension >45 mm should be advised against pregnancy11,12

Women with mildly dilated ascending aorta/root (40-45 mm) likely represent an intermediate risk group for which pregnancy is relatively contraindicated and who will require close medical surveillance during pregnancy12

Threshold for surgery prior to pregnancy is similar to that of the general population of individuals with bicuspid aortopathy without concomitant valvular dysfunction (50-55 mm) 10,12

Body surface area should be taken into account in small women. Aortic diameter to body surface area index has been proposed as an alternative threshold for pre-pregnancy surgical consideration but the suggested threshold was extrapolated from women with Turner’s syndrome10

Antepartum and Peripartum

Women with bicuspid aortopathy should receive their ante- and peripartum care by multi-disciplinary health care team with expertise in heart disease in pregnancy

Women with dilated aorta should have strict blood pressure control10 Repeated echocardiographic imaging every 4–12 weeks during pregnancy should be

performed in women with bicuspid aortopathy10 MRI (without gadolinium) is recommended if there is an indication for imaging of distal

ascending aorta, aortic arch or descending aorta during pregnancy10 Tranesophageal echocardiography is an alternative to MRI for imaging of aorta during

pregnancy 9 Beta adrenergic blockers, to reduce shear stress on the aorta, may be considered during

pregnancy in women with dilated aorta Women with bicuspid aortopathy or history of dissection should deliver in a centre where

cardiothoracic surgery is available10 Cesarean delivery should be considered for aorta > 45 mm10 For women with aorta < 40 mm, Cesarean delivery is reserved for obstetric or fetal

indications 10 Regional anesthesia and assisted 2nd stage should be considered for vaginal delivery of

women with aortopathy10

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Repeat cardiac imaging should be performed around the 6th postpartum month, in order to evaluate for progression of aortopathy

* The risk of pregnancy in women with bicuspid aortic valve and dilated aorta has not been systemically examined. Recommendations from guidelines are primarily based on small series, extrapolations from studies of nonpregnant individuals, and expert opinion.9,10,12,13

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Table S 3: Exercise Considerations In Individuals with Bicuspid Aortopathy

1. Patients with aortic aneurysm (>50% of expected dimension) or previously repaired

aortic dissection should avoid strenuous lifting, pushing, or straining that would require

a Valsalva maneuver9,12,14,15

2. The above restriction would also apply to those individuals in whom aortic diameters are

approaching the threshold for intervention.

3. Individuals with bicuspid aortopathy can undergo aerobic or endurance exercise as these

exercise is beneficial for blood pressure lowering.16

4. If patients wish to engage in vigorous aerobic exercise, such as running or basketball, one

might consider performing a symptom-limited stress test to ensure that the patient does

not have a hypertensive response to exercise.

5. Heavy weight lifting or competitive athletics involving isometric exercise may trigger

aortic dissection and that such activities should be avoided.

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References  

1. Barker AJ, Markl M, Burk J, et al. Bicuspid aortic valve is associated with altered wall shear stress in the ascending aorta. Circ Cardiovasc Imaging 2012;5:457-66. 2. Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA 2011;306:1104-12. 3. Svensson LG, Kim KH, Blackstone EH, et al. Bicuspid aortic valve surgery with proactive ascending aorta repair. J Thorac Cardiovasc Surg 2011;142:622-9, 9 e1-3. 4. Lima B, Williams JB, Bhattacharya SD, et al. Individualized thoracic aortic replacement for the aortopathy of biscuspid aortic valve disease. J Heart Valve Dis 2011;20:387-95. 5. Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt TM, 3rd. Should the proximal arch be routinely replaced in patients with bicuspid aortic valve disease and ascending aortic aneurysm? J Thorac Cardiovasc Surg 2011;142:602-7. 6. Nazer RI, Elhenawy AM, Fazel SS, Garrido-Olivares LE, Armstrong S, David TE. The influence of operative techniques on the outcomes of bicuspid aortic valve disease and aortic dilatation. Ann Thorac Surg 2010;89:1918-24. 7. Kari FA, Liang DH, Escobar Kvitting JP, et al. Tirone David valve-sparing aortic root replacement and cusp repair for bicuspid aortic valve disease. J Thorac Cardiovasc Surg 2013;145:S35-40 e1-2. 8. Vohra HA, Whistance RN, De Kerchove L, Punjabi P, El Khoury G. Valve-preserving surgery on the bicuspid aortic valve. Eur J Cardiothorac Surg 2013;43:888-98. 9. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010;121:e266-369. 10. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147-97. 11. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation 2008;118:e714-833. 12. Boodhwani M, Andelfinger G, Leipsic J, et al. Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol 2014 (in press). 13. McKellar SH, MacDonald RJ, Michelena HI, Connolly HM, Sundt TM, 3rd. Frequency of cardiovascular events in women with a congenitally bicuspid aortic valve in a single community and effect of pregnancy on events. Am J Cardiol 2011;107:96-9. 14. Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight lifting and aortic dissection: more evidence for a connection. Cardiology 2007;107:103-6.

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15. Williams MA, Haskell WL, Ades PA, et al. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2007;116:572-84. 16. Cornelissen VA, Buys R, Smart NA. Endurance exercise beneficially affects ambulatory blood pressure: a systematic review and meta-analysis. J Hypertens 2013;31:639-48.