Tavi is the evidence catching up with reality


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Tavi is the evidence catching up with reality

  1. 1. 3/13/2012 2
  2. 2. Is the Evidence Catching Up With Reality? A. Yes B. No C. Both3/13/2012 3
  3. 3. Acceptance with Pros & Cons More Judicious use & Innovations Multiple deficiencies Explosive use in Real World Excellent results in Research Settings New Idea3/13/2012 4
  4. 4. The evolution of TAVI• Henning Anderson(1992) – first transcatheter implantation of aortic valve in animal model• Philipp Bonhoeffer(2000) – first transcatheter implantation of pulmonary valve in animal model• Alain Cribier on April 16,2002 – first successful in human TAVI3/13/2012 5
  5. 5. Surgical AVR• For > 40 years Surgical AVR – The Gold standard for symptomatic AS• Relieves symptoms, prolongs life – but not for everyone• 32% of symptomatic patients with severe AS were denied surgery.• Reasons – high-risk features of the population including old age, presence of serious co-morbidities. Iung B: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24:1231–43.3/13/2012 6
  6. 6. Unmet clinical needs• These medically managed patients had a dismal prognosis (1-, 5-, and 10-year survival was 60%, 32%, and 18%, respectively)• Morbidity and mortality of valve replacement surgery remains significant in several subgroups.• Surgical mortality increases by 33% in low- volume centers3/13/2012 7
  7. 7. 3/13/2012 8
  8. 8. TAVI – simple but convincing concept• It has generated enthusiasm as – – A technique easily adopted by interventional cardiologists – A large unmet clinical need.3/13/2012 9
  9. 9. The opposite course• While SAVR, in analogy to most other medical procedures (i.e. PCI), slowly progressed from low to higher risk patient populations,• The evolution of TAVI took the opposite course, with early candidates being high risk surgical patients with relevant co-morbidities judged to be „inoperable‟.3/13/2012 10
  10. 10. • After the first in-human use in 2002, few case series were published by leaders• In 2007 the technique got approval in Europe• Since then multiple registries have cropped up• These reflect the real world status of TAVI3/13/2012 11
  11. 11. 3/13/2012 12
  12. 12. 1. The reproducible safety and efficacy2. Data of unfavourable patient populations3. Increased confidence in the technique4. Also established a novel, valuable treatment option 3/13/2012 13
  13. 13. Experience of two latest registries• Eltchaninoff et al. (France) and Zahn et al. (Germany) publish the results of two moderate to large-scale national registries on TAVI in Europe.• Have almost similar enrolment period starting in early 2009• Industry independent• Report data on both commercially available devices – – The Edwards Sapien balloon-expandable prosthesis (23 and 26 mm prosthesis with 22–24 F delivery sheath) and – The Medtronic CoreValve self-expanding device (26 and 29 mm prosthesis with 18 F delivery sheath),• Include all presently established access options• Mainly octogenarians with a high prevalence of CAD , PVD previous cardiac surgery and stroke in every 10th patient European Heart Journal(2011) 32, 133-1373/13/2012 14
  14. 14. • Both studies corroborate the results of previous reports in a real-world within their respective countries,• Demonstrating 1. Technical success rate of 98–99%, 2. Similar 30-day mortality of 12%, and 3. An incidence of stroke of 3–4%.3/13/2012 15
  15. 15. What can we learn from these studies?• TAVI is associated with a high technical success rate using both devices in appropriately selected patients, and conversion to open surgery is exceedingly rare. – But the involvement of cardiac surgeons invaluable.3/13/2012 16
  16. 16. • The 30-day mortality of 12% in both registries remains high 1. May compare favourably with expected mortality 2. More than 80% of all reported deaths in these series occurred during the first week and 3. Were largely related to severe vascular complications. 4. The smaller introducer and delivery systems3/13/2012 17
  17. 17. • As both registries included a considerable number of sites with no previous TAVI experience – – It is likely that results will improve further in experienced centres. – The importance of the learning curve in reducing mortality has been clearly shown3/13/2012 18
  18. 18. Thirty-day mortality as a function of learning curve: Vancouver experience. John Webb, ; Circulation 2009;119; 3009-30163/13/2012 19
  19. 19. • The need for pacemaker implantation in 12–39% of patients is notable.• The anatomic proximity of the AV node and His bundle to the valvular apparatus• Balloon- and device-mediated injury and inflammation.• Device-specific differences – – A higher incidence with the Medtronic CoreValve prosthesis.• Precautionary measures will help reduce the incidence rate3/13/2012 20
  20. 20. • Notwithstanding, the threshold for pacemaker implantation varies widely according to clinical practice, as exemplified by – – a pacemaker rate of 5% in the French and 21% in the German registry following implantation of the Edwards Sapien prosthesis,• Which shows the need for widely accepted and uniform criteria on pacemaker indications after TAVI procedures3/13/2012 21
  21. 21. • The haemodynamic short-term profiles of both prostheses are excellent and similar to surgically implanted valves in terms of – Transvalvular gradient – Effective orifice area, – Symptomatic improvement and improved left ventricular function.• Conversely, TAVI remains associated with more frequent paravalvular regurgitation as compared with SAVR whose long-term sequelae require careful study.3/13/2012 22
  22. 22. “Significant AR after TAVI is common and is associated with increased in-hospital mortality. Long-term follow-up is critical to further define the impact of residual AR on clinical outcome. Until these data become available, every effort should be made to prevent and treat this complication”. Mohamed Abdel-Wahab et al;European Heart Journal; Published Online First 12 March 20113/13/2012 23
  23. 23. • TAVI is a catheterization laboratory-based technique• With more than two-thirds of procedures performed in this environment in the French registry.3/13/2012 24
  24. 24. A favorable cost-effectiveness ratio3/13/2012 25
  25. 25. • TAVI is a highly versatile technique, can be done using various access routes - 1. Transfemoral, 2. Transapical, and 3. Trans-subclavian site, allows for a broad clinical applicability in the majority of patients.3/13/2012 26
  26. 26. 3/13/2012 27
  27. 27. • Both devices play a complementary role• Currently accommodate a valve annulus ranging from 19 to 27 mm• Largely independent of the take-off of the coronary arteries• A wider range of device sizes will allow the indications to be extended to even smaller and larger aortic annuli in the near future.3/13/2012 28
  28. 28. Limitations of Registries• The two devices as well as the access routes have been used according to the discretion of the operator.• Report only short-term clinical outcome data at 1 month, which are important to define device safety, but are clearly insufficient to delineate the efficacy profile of this technology.• In addition, the data become outdated with the advent of new device iterations.3/13/2012 29
  29. 29. • The newest generation Edwards SAPIEN XT prosthesis has a lower profile (NovaFlex delivery system) and is delivered through 18/19 F sheaths.• The next iteration of the Medtronic CoreValve device uses the Accutrak feature for improved stability upon device placement.• Finally, the lack of data monitoring, independent event adjudication, differences in event reporting as well as inconsistent outcome definitions provide additional sources of relevant bias3/13/2012 30
  30. 30. VARC – Valve Academic Research Consortium 3/13/2012 J Am Coll Cardiol 2011;57:253–69 31
  31. 31. Randomized controlled Trials 3/13/2012 32
  32. 32. PARTNER Trial Cohort B• First RCT• A total of 358, aortic stenosis candidates considered inoperable• 21 centers NEJM october 21, 2010 vol. 363 no. 173/13/2012 33
  33. 33. 3/13/2012 34
  34. 34. • In standard therapy group 83.8 % of patients underwent BAV in addition to maximal medical management.3/13/2012 35
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  47. 47. AV areas over time3/13/2012 48
  48. 48. Paravalvular Regurgitation with TAVI3/13/2012 49
  49. 49. Implications of PARTNER I(Cohort B)• Standard medical therapy(including BAV) did not alter the natural history• Transfemoral TAVI was superior –In the first year, NNT = 5• Significant reduction in symptoms in TAVI group• More neurologic events, major vascular complications, and major bleeding events in the TAVI group3/13/2012 50
  50. 50. • Hemodynamic performance of the bioprosthetic valve was excellent, no evidence of deterioration in the first year.• Frequent occurrence of paravalvular regurgitation, which was - 1. Usually mild, 2. Remained stable during 1-year follow-up period, and 3. Rarely required further treatment for worsening symptoms.3/13/2012 51
  51. 51. PARTNER II (Cohort A)• 25 centers• 699 high-risk patients with severe aortic stenosis but considered operable were randomized NEJM, June 9, 2011 vol. 364 no. 233/13/2012 52
  52. 52. 3/13/2012 53
  53. 53. Results At 30 days At 1 year TAVI SAVR P- TAVI SAVR P- VALUE VALUE All 3.4% 6.5% 0.07 24.2% 26.8% 0.44CauseMortalit y Major 3.8% 2.1% 0.20 5.1% 2.4% 0.07 Stroke Major 11% 3.2% 0.001 - - -VascularComplic ations 3/13/2012 54
  54. 54. • Adverse events that were more frequent after surgical replacement included – – Major bleeding (9.3% vs. 19.5%, P<0.001) and – New-onset atrial fibrillation (8.6% vs. 16.0%, P = 0.006).• More patients undergoing TAVI had an improvement in symptoms at 30 days, but by 1 year, there was not a significant between-group difference.3/13/2012 55
  55. 55. Symptom status3/13/2012 56
  56. 56. 3/13/2012 57
  57. 57. Echocardiographic Findings• Gradients and areas improved significantly after the two procedures at both 30 days and 1 year• At 1 year, TAVI was slightly superior to SAVR with respect to – – Mean AV gradient 10.2 ±4.3 mmHg vs 11.5 ± 5.4 mmHg, p value = 0.008 and – Mean valve area (1.59 ± 0.48 cm sq. vs. 1.44 ± 0.47 cm sq., P = 0.002).3/13/2012 58
  58. 58. • Moderate or severe paravalvular regurgitation was more frequent in the TAVI group at 30 days (12.2% vs. 0.9%) and at 1 year (6.8% vs. 1.9%) (P<0.001 for both comparisons)3/13/2012 59
  59. 59. Implications of PARTNER II(Cohort A)• Affirmed the primary non-inferiority hypothesis• Procedure-specific outcomes are best revealed in early (30-day) results• The surgical outcomes in this trial were excellent, as compared with those in studies involving high-risk patients with aortic stenosis.• In the as-treated population, the ratio of observed operative mortality to predicted mortality (according to STS Score) was 0.68.3/13/2012 60
  60. 60. • The rates of death at 30 days were higher among patients who had undergone TA vs TF placement• Clinical benefits of transcatheter replacement included 1. Significantly shorter stays in ICU and Hospital, 2. NYHA functional class and 6-minute walk distance were strikingly improved at 1 year in the two study groups, although at 30 days, the benefits were greater with TAVI.3/13/2012 61
  61. 61. Major problems of TAVI• Major strokes - The approximate doubling in the rate of all new neurologic events, as compared with SAVR• Most strokes appeared to be procedure-related and embolic.• Rates of stroke were similar whether the access was Transfemoral or Transapical.• Despite this, the composite end point of death from any cause or major stroke was similar in the two study groups3/13/2012 62
  62. 62. • As expected, open surgery was associated with more frequent episodes of major bleeding and new-onset atrial fibrillation• There were more major vascular complications associated with transcatheter replacement.• A definitive assessment of the durability of the prosthetic valves used in TAVI awaits longer follow up.3/13/2012 63
  63. 63. • This study used an early version of the transcatheter device, predominantly in centers with no previous experience with the procedure• The study had insufficient statistical power to reach robust conclusions with respect to specific subgroups of patients.3/13/2012 64
  64. 64. Conclusion of PARTNER II• TAVI is an alternative to surgical replacement in a well chosen, high-risk subgroup of patients with aortic stenosis.• Additional randomized trials will be required to determine whether TAVI is equivalent to SAVR for lower-risk patients with aortic stenosis.3/13/2012 65
  65. 65. • Yes ,the evidence is catching up with reality• But in our setting it is RHD that is more common• No use of this device in AS due to RHD till date• Our patients are denied surgery due to financial status• As our life expectancy is increasing, we may face scenarios similar to western countries in future3/13/2012 66
  66. 66. Special Problems with TAVI3/13/2012 67
  67. 67. Procedure related Strokes• Clinically apparent neurologic complications with TAVI has varied from 0 to 11% in series that include single institutions and registries.• The 5.5% early risk of stroke or TIA in the PARTNER trial is consistent with previous studies and is similar to the 6.7% risk in patients who were not candidates for surgery.• Despite this increased risk of stroke there was a dramatic 18.3% reduction in the combined risk of death or major stroke at 1 year3/13/2012 68
  68. 68. • TAVI has been used in patients who are at high operative risk, and the same clinical characteristics that increase the risk of stroke with any major cardiovascular intervention• Thus, the 1-in-20 occurrence of stroke or TIA - a complication that comes with the territory in treating elderly patients with multiple coexisting conditions.3/13/2012 69
  69. 69. • Such an increased rate of neurologic complications might be acceptable for surgically rejected cases• But for those who are candidates for either transcatheter or surgical replacement, a dilemma in balancing the risks of increased neurologic complications against the benefits of avoiding sternotomy and cardiopulmonary bypass.3/13/2012 70
  70. 70. • Deposits of calcification in aortic-valve cusps are usually covered by endothelium, but dilatation of the valve may lead to fracture of the calcified portion and exposure to the circulation.• Some patients have friable ulcerations of calcified cusps that are especially prone to embolization3/13/2012 71
  71. 71. A Surgically Excised Stenotic Aortic Valve.Heaped-up deposits of calcium are clearly visible on the aortic side of thethree cusps of the valve (Panel A). In one cusp, there is an area of ulcerationwith exposed friable fragments (Panel B, arrow) 3/13/2012 72
  72. 72. • Procedural stroke, often due to embolization of the friable material found in the diseased aortic valve, as demonstrated by transcranial Doppler.• The insertion of a prosthesis without removal of the diseased aortic valve creates an irregular zone around the stent that may predispose to thrombus formation3/13/2012 73
  73. 73. • Experimental approaches to mitigation include catheters designed to capture embolic material or deflect it away from the cerebral circulation• But these new devices should be evaluated in RCTs• The risk seems to be falling with smaller and less traumatic catheters, improved technique, and lower risk patients.3/13/2012 74
  74. 74. • However, not all strokes are atheroembolic.• Possible factors include – – Valve thrombosis, – Atrial fibrillation, and – Institution or discontinuation of anticoagulation.• In the absence of data the standard approach - long-term aspirin and 1–3 months of clopidogrel or, in the presence of additional risk factors such as atrial fibrillation, warfarin.3/13/2012 75
  75. 75. Embolic protection devices. The Aortic Embolic Protection Device The Embrella Embolic Deflector Device from (AEPD) from SMT Ltd. Available in Embrella Cardiovascular Inc. Available in 6F and 8F and is inserted via the transfemoral is inserted via right radial artery. The device spans arterial route. spans the three major Two major neck vessels, namely the neck vessels braciocephalic artery and the left carotid artery.3/13/2012 76
  76. 76. VASCULAR COMPLICATIONS• Vascular events - the most common complication, given the large-bore catheters• Often implicated, sometimes directly but often indirectly, in procedural mortality• Vascular complications are associated with increased in- hospital mortality (36% with vs. 10.3% without vascular complications)3/13/2012 77
  77. 77. • Imaging techniques such as fluoroscopic / CT and MR angiography can provide objective information of the peripheral arterial system• salient features include – Vessel diameter, – Degree of calcification and atherosclerosis, – Obstruction, – Tortuousity and – Ulceration3/13/2012 78
  78. 78. • The 18F CoreValve Safety and Efficacy trial reported a vascular complication rate of 12% whereas the Edwards PARTNER EU trial (22F and 24F device) reported a rate of 27%.• Cautious pre-procedural screening e.g. excluding patients with circumferential calcification of ilio-femoral vessels, is essential to reduce these complications.3/13/2012 79
  79. 79. • More recent experience - vascular complication rates are falling and, that when vascular complications do occur, they are better managed and less likely to be associated with mortality• It appears that with the availability of smaller delivery systems, such as the newer CoreValve and NovaFlex SAPIEN XT catheter systems, better screening and expertise, that vascular complications, and the associated risk of morbidity and mortality, will continue to fall.3/13/2012 80
  80. 80. Conduction system• Surgical AVR is associated with a need for permanent pacing in 3– 18%.• Reportedly TAVI is associated with new pacemaker implantation in 3–36% of patient• Nevertheless the 9–36% rate of new pacemaker implantation with the CoreValve device is clearly higher than the 3–12% rate reported with the Edwards Lifesciences device, presumably as this device often extends further into the left ventricular outflow tract3/13/2012 81
  81. 81. • Additional risk factors for new heart block may include – 1. Advanced age, 2. Pre-existing right bundle branch block or 3. Atrio-ventricular delay and 4. Oversizing3/13/2012 82
  82. 82. Coronaries• Placing the open cells of a THV over a coronary ostium appears to be generally well tolerated, at least acutely• Obstruction may rarely occur as a consequence of THV displacement of the native valve leaflet over the left main ostium• Risk factors for left main occlusion include a low origin of the coronary ostium, a shallow sinus of Valsalva, a bulky native valve and design characteristics of the prosthesis3/13/2012 83
  83. 83. Valve-in-valve• Reoperation for degenerated surgical bioprostheses carries significant risk.• Early reported experience with valve-in-valve implantation in aortic degenerated surgical bioprostheses with both the SAPIEN and CoreValve devices has been favourable.3/13/2012 84
  84. 84. Kidneys• Acute renal injury post-TAVI occurs in 12– 28% of cases.• Renal function may often improve in response to increased cardiac output following relief of aortic stenosis.• The reported risk is lower with percutaneous than transapical procedures.• ARF - generally mild and reversible and less common than in matched surgical patients3/13/2012 85
  85. 85. Current generation devices3/13/2012 86
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  89. 89. Three novel percutaneous aortic valve prosthesis designs.On the left is the Direct Flow valve. The device is positioned in the aortic annulus with aninflatable cuff. After a test with the cuff inflated using contrast or saline, anepoxy can be used to permanently implant the device.In the middle is the Sadra Lotus self-expanding prosthesis. The valve can be recaptured andRepositioned before finally being released.On the right is the AorTx valve, which has a collapsible metal frame that also has the potentialto 3/13/2012 be recaptured and repositioned. 90
  90. 90. Medtronic Engager3/13/2012 91
  91. 91. Summary1. SAVR remains standard therapy for symptomatic severe aortic stenosis due to a long and established track record.2. Arguably TAVI is becoming the standard of care for symptomatic patients who are not operative candidates.3. An option for selected patients who are eligible for surgery, but at high risk of morbidity.3/13/2012 92
  92. 92. Summary4. Where this line is drawn is a moving target and remains controversial.5. Careful and responsible patient selection, high- quality facilities, formal training, multidisciplinary collaboration, and concentration of expertise are fundamental to optimal outcomes.3/13/2012 93
  93. 93. 3/13/2012 94