Assessment of TAVR in Filipino Adults with Severe Bicuspid Aortic Valve

1. Assessment of Safety and Efficacy of Transcatheter Aortic Valve Replacement among Adult Filipinos with Severe Stenotic Bicuspid Aortic Valve: A St. Luke’s Medical Center Experience Dr. Fontini Christi C. Cuenca1* ,, Dr. Sheryll D. Santos2, Dr. Ofelia N. Valencia3 , Fabio Enrique Posas 4 Saint Luke’s Medical Center-Global City

2. TAVR SLMC Experience Introduction • Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation occurring in 1% to 2% of the population • Stenosis of a bicuspid aortic valve is seen to develop as early as the 3rd decade of life and is caused by progressive sclerosis and calcification leading to stenosis and/or regurgitation William DS. Bicuspid Aortic Valve. Insur Med. 2006 (1) 72-74 Chui MC, Newby DE, Panarelli M, Bloomfield P, Boon NA. Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy?. ClinCardiol. 2001 (1):52-5.

3. Cardiac Events in Adults Bicuspid Aortic Valves Reproduced with permission from Tzemos N, Therrien J, Yip J, et al. Outcomes in adults with bicuspid aortic valves. JAMA 2008;300:1317-25.

4. Survival with Transcatheter Aortic Valve Implantation Compared to Standard Therapy in Adults with Severe Symptomatic Aortic Stenosis and Prohibited Risk

5. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease • SAVR remains the intervention of choice for patients with an indication for AVR and low or intermediate operative risk (Class I) • Up to 30-40% with class I indication for SAVR do not undergo SAVR • Advanced age • LV dysfunction • Multiple co morbidities • Patient preference • Physician recommendation

6. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease • TAVR is recommended for patients with an indication for AVR, but a prohibitive surgical risk (Class I) • TAVR - reasonable alternative to surgical AVR in patients with an indication for AVR and high surgical risk (Class IIa).>> Class Ia in coming guideline! • Heart valve team should collaborate to optimize care for patients in whom TAVR or high-risk surgical AVR are being considered (Class I)  Dua A, Dang P, Shaker R et al. Barriers to surgery in severe AS patients with class I Indication for AVR. J Heart Valve Dis 2011; 20:396 Bach DS, Siao D, Girard SE et al. Evaluation of pts with severe AS who don’t undergo AVR: The potential role of subjectively over estimated operative risk. Circ CardiovascQual Outcomes. 2009;2:533

7. PARTNER IA 3 Year Follow UpAll-Cause Mortality or Strokes (ITT) • HR [95% CI] =0.98 [0.79, 1.21] • p (log rank) = 0.839 47.1% 45.9% 36.9% 28.6% 36.1% 27.4% No. at Risk TAVR AVR Landmark Analysis - ACC 2013

8. Large landmark studies did not include aortic stenosis with bicuspid aortic valve • Data on efficacy and safety of TAVR among those with bicuspid aortic valve is still limited. Mack M.J., Brennan J.M., Brindis R., et al: Outcomes following transcatheter aortic valve replacement in the United States. JAMA 2013; 310: pp. 2069-2077

9. TAVR SLMC Experience • To evaluate the safety and efficacy of TAVR among Filipino patients with severe symptomatic BAV and compare the outcome with severe symptomatic tricuspid valve stenosis (TAV) in St. Luke’s Medical Center-Global City Objective

10. Objective • Primary Objective • Safety Endpoint: All cause mortality, stroke, bleeding, vascular complications • Effectiveness Endpoint: Composite of all-cause mortality, disabling stroke, or moderate or greater paravalvular aortic regurgitation TAVR SLMC Experience

11. Secondary Objective • Follow up survival, cardiac and all cause mortality • Valve performance • Need for pacemaker • Functional status TAVR SLMC Experience

12. TAVR SLMC Experience • Subjects • Consecutive patients from February 2012 to November 2016 with severe symptomatic aortic stenosis who underwent TAVR in Saint Luke’s Medical Center-Global City were included in our study. Method

13. TAVR SLMC Experience Patient Selection and Risk Stratification • Patient selection- The Heart Team • Pre-operative stratification • Surgical Thoracic Society (STS) • Logistic EuroScore (LE)

14. TAVR SLMC Experience Inclusion Criteria • Severe symptomatic aortic valve disease • High surgical risk • Life expectancy of > 1 year • Willingness to sign informed consent • Other high risk features included are the presence of the following features: • porcelain aorta • cachexia defined as BMI < 18 kg/m2 • frailty • hostile chest defined as any anatomic condition which may complicate open heart surgery such as prior open heart surgery, retrosternal LIMA grafts, prior chest radiation and morbid obesity

15. TAVR SLMC Experience • Estimated life expectancy of <1 year • Liver cirrhosis (Child Pugh C) • Sepsis or ongoing severe infectious processes • Stroke within the previous 6 months • Symptomatic untreated carotid or vertebral artery disease • Absence of feasible vascular access • Inability or refusal to sign consent • Indications prior to TAVR was carefully reviewed by the SLMC TAVR team composed of interventional cardiologist, cardiothoracic surgeon,cardiac anesthesiologist, critical care and pulmonary specialist and cardiac imaging specialists. Exclusion Criteria

16. TAVR SLMC Experience Preoperative work-up • Coronary angiogram • Revascularization if indicated • CT of thoracoabdominal aorta • Vascular access, aortic anatomy, coronary take-off height • Annular sizing-diameter and perimeter • Leaflet and annular calcification – severity and pattern • Transthoracic echcocardiography • Ventricular function, valve area and morphology and annular dimension and calcification • Dobutamineechocardiography • Low flow low gradient AS, define contractile reserve and document severity of AS

17. TAVR SLMC Experience Valve Sizing and Implantation Technique • Valve size is based on CTA perimeter measurements • Intraoperative TEE used to confirm optimal size and aid in optimization of valve placement and function • All procedure done at cardiac catheterization laboratory • General anesthesia, generally • Intra-op TEE • 5F balloon tipped temporary pacemaker • Femoral approach whenever possibe • Left subclavian, transaortic

18. TAVR SLMC Experience Implantation Technique • Balloon Aortic Valvuloplasty • Balloon sized 20% smaller than the nominal annulus • Rapid pacing-180 bpm • Valve deployment • Beating heart- pacing when necessary • Target implant depth: 2-4 mm below the annulus • 31 mm valve delivery- annular level 2 mm below the annulus • Clopidogral and Aspirin for 3 months • AF: Clopidogrel + Warfarin with a target INR of 2.0

19. TAVR SLMC Experience Data processing and Analysis • All follow-up data were collected and encoded in clinical data sheet and Microsoft Excel software • Qualitative data is expressed as numbers or percentages while quantitative variables as mean ± standard deviation (SD) • Independent sample t-test, compare quantitative variable and difference in variable distribution • Qualitative variables were compared using Chi-square or Fisher’s exact test • The survival distribution analysis with Kaplan-Meir Method and Log-Rank or Mantel-cox test to compare the difference in the survival distribution between the two groups • Logistic regression analysis was done to determine the significant factors that potentially increases the risk of mortality. Statistical significance was defined as p <0.05.

20. TAVR SLMC Experience Result & Discussion • A total of 89 consecutive patients with symptomatic severe AS who underwent TAVR in St. Luke’s Medical Center-Global City from February 2012 to November 2016 were included in the study.

21. TAVR SLMC Experience Baseline Characteristics 11 %

22. TAVR SLMC Experience Baseline Characteristics

23. TAVR SLMC Experience Access, Type and size of Implanted valve

24. TAVR SLMC Experience Procedural, Clinical and Echocardiographic outcome

25. TAVR SLMC Experience Procedural, Clinical and Echocardiographic outcome

26. TAVR SLMC Experience Clinical and Echocardiographic outcome Aortic valve area Mean Gradient P value 0.6

27. TAVR SLMC Experience Clinical and Echocardiographic outcome Paravalvar leak All cause mortality

28. 6 months Follow up

29. 12-month Follow-up

30. Predictors of Death

31. The prevalence of bicuspid aortic valve stenosis is 10% in our study population • Yoon et al, reported a prevalence of bicuspid aortic valve in Asian population to be at 5.8% to 10% which is lower than that in Northern America and Europe • 90% of patients with BAV in our study were treated with early generation self expanding valve • Perlman et al uses a new generation TAVR device which did not only less mortality rate but favorable valve performance and no cases >2 regurgitaion

32. It is undeniable that paravalvar leak is significantly higher compared to TAV group with moderate paravalvar leak is seen in 22% in BAV vs 0% in TAV • Results were consistent with early reports using early generation of self expanding valve In our study paravalvar leak could have been attributed to: • Uneven expansion of the prosthetic valve over the native bicuspid aortic valve • Valve under sizing might have contributed to the increased incidence of paravalvularleak which may also account for the higher mean gradient. • The trend of decreasing degree of paravalvular leak at 12 months may be attributed to the ability of the valve to expand

33. Noteworthy, paravalvular leak in both group did not influence the overall clinical outcome.

34. In our study, the 30-day mortality rate is 7.8% which is comparable to the FRANCE 2 registry and UK TAVI registry who reported a 30-day mortality rate of 9.7% and 7.1, respectively. • Our 30-day mortality is higher in the recently conducted study by Perlman et al, who reported 30-day mortality rate of only 4% with the use of a new generation bioprosthetic valve. • The overall mortality rate in 1 year is 12% and 10% among patients with bicuspid aortic valve. The mortality rate in our present study is comparable with the results done among Asian population, 10.8 vs 12% Yoon S.H. Ahn, J.M, et al, Clinical Outcome Following Transcatheter Aortic Valve Replacement in Asian population. J Am Coll, 2016; 9:926-933 Perlman G.Y , Blanke P , et al. Bicuspid aortic valve stenosis: favorable early outcomes with a next-generation transcatheter heart valve in a multicenter study. J Am CollCardiolIntv. 2016; 9:817–824 Genereux P., Head S.J., Van Mieghem N.M., et al: Clinical outcomes after transcatheter aortic valve replacement using valve academic research consortium definitions: a weighted meta-analysis of 3,519 patients from 16 studies. J Am CollCardiol 2012; 59: 2317-2326 Bauer T., Linke A., Sievert H., et al: Comparison of the effectiveness of transcatheter aortic valve implantation in patients with stenotic bicuspid versus tricuspid aortic valves (from the German TAVI registry). Am J Cardiol 2014; 113: pp. 518-521 Cribier A., Eltchaninoff H., Tron C., et al: Treatment of calcific aortic stenosis with the percutaneous heart valve: mid-term follow-up from the initial feasibility studies: the French experience. J Am CollCardiol 2006; 47: 1214-1223 Webb J.G., Pasupati S., Humphries K., et al: Percutaneous transarterial aortic valve replacement in selected high-risk patients with aortic stenosis. Circulation 2007; 116: 755-763

35. The incidence of stroke, bleeding, vascular complications of our patients in comparable to those reported previously • Multivariate analysis in this study showed the coexisting comorbidities that potentially alters the clinical outcome of TAVR. Functional capacity, STS and logistic score and age are found out to be a significant predictor of mortality. Also, frailty, presence of porcelain aorta and COPD. Genereux P., Head S.J., Van Mieghem N.M., et al: Clinical outcomes after transcatheter aortic valve replacement using valve academic research consortium definition: a weighted meta-analysis of 3,519 patients from 16 studies. J Am Coll Cardiol 2012; 59: 2317-2326

36. Though the population is limited , our study showed that TAVR is a feasible and effective treatment option in patients with bicuspid aortic valve stenosis with high procedural success, acceptable 30 days, 6 months and 1-year all cause mortality. • A year follow-up showed no significant valvular dysfunction. • Functional capacity improved significantly • Paravalvar leak though prominent among those with BAV is not associated with mortality and with noted trend of improvement in severity in midterm follow-up • Non cardiac mortality is the interplay of multiple comorbidities among these high risk and inoperable patients.

37. Conclusion • TAVR in our limited experience represents a feasible and effective treatment option in patients with BAV stenosis. • The procedural and short term and intermediate outcomes are comparable to those patients with TAV stenosis. • More research with larger population and long term follow up is needed to validate results.

38. Thank you!