2. Structural Heart Disease Update
Michael Sumners, DO
Structural Heart Disease Update

3. Disclosures

4. Topics TAVR update: Durability Mitral Valve disease
2017 Valve update
Mitral Valve disease
ASD / PFO Closure data
Corevalve for valve-in-valve disease approval for high/extreme risk. 2015
Europe corevalve and sapien approved

5. 795,000 in the US with new or recurrent CVA each year.
25% end up with dx cryptogenic cause

6. Cryptogenic stroke Atrial fibrillation Hypercoagulable state
Autoimmune or inflammatory vasculitides
Aortic arch plaque
Paradoxical embolus
ASD, VSD, PFO,

7. PFO is common in the general population, 25-30%
PFO does not increase the risk of stroke
In those with cryptogenic CVA, it is observed more frequently, up to 50%
Haeusler KG, Herm J, Hoppe B et al.
Thrombophilia screening in young patients with cryptogenic stroke. Prevalence of gene polymorphisms compared to healthy blood donors and impact on secondary stroke prevention. Hamostaseologie. 2012;32(2):147-52

8. Pre 2014.
Whether to close PFO to reduce risk of recurrent ischemic stroke
Open question for decades
Trials with slow enrollment
CLOSURE 1: Closure not superior to medical therapy
RESPECT:
At 3 years, no statistical difference in recurrent stroke rate, although cited as 50% reduction**

9. RESPECT NEJM Sept 14. FDA Approval:
980 patients. Mean age 46. 6yr follow up.
PFO and cryptogenic CVA
ITT vs As treated analysis
Dropout rate
600 at 5 years, 30 at 10 years.
FDA Approval:
Despite the overall low incidence of recurrent stroke and nonsignificant findings suggesting effectiveness, preventing recurrent stroke is of high value.

10. CLOSE
663 patients with cryptogenic CVA and atrial aneurysm or large shunt
3 treatment groups at 1:1:1 ratio
PFO closure + antiplatelet therapy
Antiplatelet therapy alone
Oral anticoagulation
Mean 5.3yr follow up

11. REDUCE NEJM sept 14/2017 Supplementary appendix
664 patients. Mean age 45. Cryptogenic CVA
2:1 ratio. PFO closure + antiplatelet vs. antiplatelet therapy.
Clinical ischemic CVA and silent infarction detected at 24 mo MRI
6/441 in Closure group (1.4%)
12/223 in medical therapy group (5.4%)
AF more common in closure group 6.6% vs. 0.4%
NNT to prevent 1 cva at 24 mo was 28
Limited by: Study device not implanted in 28 patients.
Option for medical therapy arm to have closure outside of trial.
Supplementary appendix

12. Trans-esophageal echo Rhythm monitoring
Brain MRI / CT
Rule out lacunar stroke or non cva lesions
Trans-esophageal echo
Intracardiac source or aortic atheroma
Rhythm monitoring
Workup for hypercoagulable state
Typically Anticardiolipin / hyperhomocysteine

13. Final Thoughts on PFO Closure
Defining the population to benefit
Atrial septal aneurysm
Moderate to large shunt
Is a stroke in someone with a PFO and an aneurysmal or moderate to large shunt still considered cryptogenic?
What is the longer term AF risk?

14. Pre 2014
CLOSURE 1 PC
RESPECT
AHA/ASA Class 3 recommendation for PFO closure
AA Neurology: Recommended against closure in routine settings unless recurrent cryptogenic CVA

15. RoPE Score Age Cortical stroke Diabetes Hypertension Smoking
Prior CVA or TIA
Young patients with superficial stroke and no vascular disease risk factors

16. Timeline comparison

17. AS / TAVR

18. Epidemiology
Valvular heart disease accounts for % of cardiac surgical procedures.
Two-thirds of heart valve operations are for aortic valve replacement
The most common reason for AVR is bicuspid aortic valve.
Mitral valve surgery is most often performed for MR
AVR, most commonly AS.

19. Natural History of Aortic Stenosis
Sclerosis
Valve calcification with velocity <2.5m/sec
Progression to severe AS 10% at 5 years.
Once moderate disease is detected
Increase in mean gradient 7 mmHg/yr
Decrease in valve area of 0.1 cm^2/yr
Increase velocity of 0.3 m/sec/yr

20. Aortic Stenosis Not a Passive Disease Process Risk Factors
Active lipid deposition
Inflammation
Neo-angiogenesis
Calcification
Risk Factors
Male, diabetes, dyslipidemia
Metabolic syndrome, smoking

21. Epidemiology
Worldwide rheumatic fever is the most common cause of valve disease
In industrialized areas, valvular disease of “old age” predominates
Calcific aortic stenosis
Functional Mitral Regurgitation

22. Valvular Disease is Under-detected
Post-mortem studies show approximately 50% of aortic stenosis is identified before death.
When we find undiagnosed valve disease with complications it is commonly associated with perioperative and maternal deaths.

23. Aortic Stenosis – Medical therapy
Treat Hypertension
Vasodilators
Statins - Class 3
Vasodilators – Generally need hemodynamic monitoring for monitoring changes in SVR and cardiac output.
Dropping SVR may acutely reduce CO, in some individuals it may increase.

24. TAVR US FDA approval in 2011 Over 50,000 procedures
Survival, symptom status, quality of life

25. TAVR History: Extreme Risk High Risk 2014 2015
Higher rate of survival with TAVR at 2 years

26. 2017 Guideline changes High or prohibitive risk: B to A. Class 1
Mean life expectancy 11 mo to 30 mo
Intermediate risk : 2A
PARTNER 2A.
SURTAVI: Published after guideline release
Lower risk group than PARTNER 2A
Risk of stroke was lower with TAVR
AI and pacemaker need were higher.
80% of SAVR procedures are low risk pts

27. Valve in Valve
Failed prior bioprosthetic valves

28. TAVR – The Current State and What is Next?
Ongoing:
PARTNER 2A
SURTAVI : RESULTS***
Next:
PARTNER III – Low risk Sapien 3 trial.
FDA Approved

29. NOTION trial – Low risk

30. PARTNER 3 1300 severe AS patients STS low risk 3%.
SAVR vs. TAVR with Sapien 3 valve
Primary endpoint 12 mo all cause mortality, stroke and rehospitalization.
Followed for 10 years.
Results around Fall 2019.

31. Natural history / clinical course is variable
40-50% is asymptomatic.
Natural history / clinical course is variable
5-6% undergo treadmill stress due to fear of testing risk.
EARLY-TAVR Trial
1100 patients. Severe Asymptomatic AS
Started enrolling March 2017.

32. Durability Subclinical leaflet thrombosis Raj R Makkar ACC 17
TAVR 12 %, SAVR 4 %
Postulated mechanism for structural deterioration
Ongoing CT substudies to investigate.

33. Vascular Complications
20Fr to 14Fr.

34. Durability EuroPCR 2017 2343 patients. 0.2 to 1.5%
Avg 22 months, out to 9 years.
3-4 years for low and intermediate risk data
5 year performance of the Corevalve from ADVANCE study
996 patients: 5 year mortality 50%.
Mean gradient and valve area did not change over time.

35. Durability
For the followed cohort to date, 5 year mortality is high and appears to be unrelated to valve complications.
As intermediate and low risk patients are followed longer more durability data will be available.

36. Asymptomatic Severe Aortic Stenosis
Which patients with asymptomatic severe aortic stenosis should be considered for intervention.
EF < 50
Already undergoing cardiac surgery
Velocity >5m/sec, Mean gradient >60, low risk
Abnormal Exercise Treadmill
Fast progression on echo >0.3m/s/yr
Changes from 2008.

38. 2012 ESC valve guidelines

39. Major Changes to the Guideline
Restructured to help determine timing of interventions
Transcatheter therapies
Recommendations for use of heart valve team

40. 2014 2008 Update ABCD Helps to determine Timing of intervention
Assess risk
Severity of Valve Lesion
Symptoms
Response of LV and RV

42. Left Sided Valve Disease
Endovascular Therapy: TAVR, Mitraclip
Mixed Valve Disease
Prosthetic Valve Considerations

43. The Simvastatin and Ezetemibe in Aortic Stenosis Trial (SEAS)
Randomized double blind: pts
Simvastatin + Zetia or Placebo
Mild – Moderate Aortic Stenosis
Followed for average of 52 months
No difference in rate of AVR or hemodynamic progression

44. Aortic Stenosis – Timing of Intervention

45. 3815 Consecutive patients from registry data with severe AS :
3815 Consecutive patients from registry data with severe AS
300 Initial surgical Conservative
5 yr All cause death and HF hospitalization
15% - Initial surgical
26% - Conservative
Published december 2015.

46. TAVR >50% risk of death or major morbidity at 1 year with surgery
Disease affecting 3 major organ systems
Anatomic factors that increase risk of surgery

47. STS Scoring Summary

48. Mitral Regurgitation Primary (Degenerative) Secondary (Functional)
Correction of MR curative
Mitral Prolapse
Secondary (Functional)
LV dysfunction

49. Mitral Regurgitation Benefits of Mitral Repair vs. Replacement
Lower operative mortality
LV Function is better preserved
Risks with anticoagulation
Valve degeneration

50. Mitraclip
EVEREST II Trial
Reduced MR
Improved symptoms
LV remodeling

51. Bicuspid Aortic Valve Prevalence of 0.5-2% 70-80% of cases are male
Should be considered a general thoracic aortopathy.
CT or MRA

52. Bicuspid Aortic Valve Aortopathy
No medical therapy has proven to reduce the rate of progression of aortopathy associated with a bicuspid valve.
>4.5cm at least annual evaluation

53. Bicuspid Aortic Valve Aortopathy
>4.5 cm:
5-5.5 cm:
>5.5cm:

54. Aortic Insufficiency
Medical Treatment

55. Aortic Insufficiency: AVR
Symptomatic
LV Dysfunction
Undergoing surgery
LV Dilation

56. Mitral Stenosis Natural history:
Rate of progression is highly variable.
Avg rate of decrease in area of 0.1cm

57. Review
Treatment for valve disease is becoming progressively more complex with increasing treatment options and a heart team approach is recommended for complex decisions.

58. Review
Trans-catheter treatments for valve disease with TAVR or Mitra-clip are becoming more common and ongoing trials assessing utility in lower risk patients are ongoing.

59. References
Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves. NEJM 2013; 369:
Makkar RR, Fontana GP, Jilaihawi H, et al. Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis. NEJM 2012; 366:
Mauri L, Foster E, Glower DD et al. 4-Year Results of a Randomized Controlled Trial of Percutaneous Repair Versus Surgery for Mitral Regurgitation. JACC 2013;62:
Nishimura RA, Carabello BA, Faxon DP, et al Focused Update Incorporated into the ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease. Circulation 2008;118:e
Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. JACC 2014; 63: e57-185
Reardon MJ, Adams DH, Kleiman NS, et al. 2-Year Outcomes in Patients Undergoing Surgical or Self- Expanding Transcatheter Aortic Valve Replacement. JACC 2015; 66:
Rossebo AB, Pedersen TR, Boman K, et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. NEJM 2008; 359:
Tadros TM, Klein MD, Shapira OM. Ascending Aortic Dilatation Associated with Bicuspid Aortic Valve: Pathophysiology, Molecular Biology and Clinical Implications. Circulation 2009; 119:
Taniguchi T, Morimoto T, Shiomi H, et al. Initial Surgical Versus Conservative Strategies in Patients with Asymptomatic Severe Aortic Stenosis. JACC 2015;66:

62. Mixed Valve Disease
64yo M presents to establish care after not having a physician for the past 10 years. Reports slowly progressive exertional fatigue for the past 6 months.
Echo
Moderate mitral regurgitation.
Moderate mitral stenosis.

63. Mixed Valve Disease
Symptoms and routine treatment follow the predominant lesion
Require more frequent evaluation than isolated disease of the same severity
May require intervention despite the lack of ‘severe quantification’

64. Prosthetic Valves Mechanical or Bio-prosthetic
How long will a bio-prosthetic valve last
Inversely related to age.
Deterioration rate at years
10% if age 70
90% if age 20
Individualized decision.

65. Prosthetic Valves Anticoagulation Mechanical:
Thrombogenicity and alteration of flow.
Aortic Valve goal INR 2.5 if low risk.
Mitral Valve or AVR with higher risk goal INR 3.0.
ASA 81mg for all.
ReAlign trial stopped prematurely due to increased thromboembolic events.

66. Mechanical Valve Anticoagulation
Mechanical Aortic
INR 2-3
Aortic Additional Risk
INR
Mitral
INR

67. Mechanical Valve Bridging Anticoagulation
Atrial Fibrillation
Prior VTE
Hypercoagulable
Older Mechanical Valve
EF < 30
>1 Mechanical Valve

68. Mild: 3-5 years Moderate: 1-2 years Severe: 6mo to 1 year
Re-iterate the natural progression of AS and of bicuspid aortic valve stenosis.
Natural history progression of mitral stenosis. Is there a natural history of MR.

69. Review
Patients with mixed valve disease of moderate severity requires closer follow- up and may require intervention despite lack of ‘severe’ quantification.

70. Review
Bicuspid Aortic Valve should be considered a global thoracic aortopathy and imaged in its entirety with routine follow up.

73. Aortic Stenosis – Low-flow low-gradient
Dose
Ao velocity
Gradient
Area
Lvef
EAE / ASE guidelines
Velocity >4m/s with Area <1.0cm2.

74. 3 Outcomes 1 - Severe Aortic Stenosis 2 - Moderate Aortic Stenosis
3 - Lack of contractile or flow reserve
Failure to increase stroke volume by >20%
Poor prognosis with medical or surgical tx.

75. Pregnancy and Valvular Heart Disease

78. TAVR for Aortic Insufficiency

80. Prosthetic Valves Dysfunction New or louder murmur Hemolysis
Thrombosis
Pannus
Endocarditis

82. How is risk determined?

83. Fellow MR
TAVR AI
Aortic
Stenosis TR MS
Testing

84. Aortic Insufficiency
Testing