Valvular Guidelines: The Past, the Present, the Future

Transcription

1 Valvular Guidelines: The Past, the Present, the Future Robert O. Bonow, MD, MS Northwestern University Feinberg School of Medicine Bluhm Cardiovascular Institute Northwestern Memorial Hospital Editor-in-Chief, JAMA Cardiology No Relationships to Disclose

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3 The evidence base is limited by an inadequate number of randomized clinical trials

4 Hence, virtually all of the recommendations are based on expert consensus (Level C)

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6 Stages of Valvular Heart Disease Stage A B C D Definition Risk of valve disease (BAV, MVP, RF, CHF) Mild - moderate asymptomatic disease Severe valve disease but asymptomatic C1: Normal LV function C2: Depressed LV function Severe, symptomatic valve disease

7 Mitral regurgitation Degenerative MR: primary valve disease Functional MR: primary myocardial disease

8 Mitral regurgitation Degenerative MR: primary valve disease Functional MR: primary myocardial disease

9 Mitral regurgitation Indications for mitral valve surgery for degenerative MR?

10 Mitral regurgitation Indications for mitral valve surgery for degenerative MR?

11 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? MR Severity: RV = 68 ml RF = 60% ERO = 0.48 cm 2

12 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? MR Severity: RV = 68 ml RF = 60% ERO = 0.48 cm 2 Severe MR: > 60 ml > 50% > 0.4 cm 2

13 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients class I

14 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction class I class I

15 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction LVEF <60% class I class I

16 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction LVEF <60% LVSD >40mm class I class I

17 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension class I class I class IIa

18 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension PASP >50 mmhg at rest class I class I class IIa

19 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension Atrial fibrillation class I class I class IIa class IIa

20 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension Atrial fibrillation Normal LV function, repair feasible? class I class I class IIa class IIa?

21 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension Atrial fibrillation Normal LV function, repair feasible? MV repair to improve survival? class I class I class IIa class IIa?

22 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension Atrial fibrillation Normal LV function, repair feasible? MV repair to improve survival? What is the natural history? class I class I class IIa class IIa?

23 Mitral regurgitation Indications for mitral valve surgery for degenerative MR? Symptomatic patients Asymptomatic patients LV systolic dysfunction Pulmonary hypertension Atrial fibrillation Normal LV function, repair feasible? class I class I class IIa class IIa Asymptomatic severe degenerative MR: 66% come to surgery in 5 years because of symptoms, LV dysfunction, pulmonary hypertension or AF Long-term postoperative survival is worse if surgery is performed after patients become symptomatic

24 Surgery for Acquired Cardiovascular Disease J Thorac Cardiovasc Surg 2003;125:

25 Survival (percent) Surgery for Acquired Cardiovascular Disease Mitral Regurgitation Survival After Mitral Valve Surgery n=488 J Thorac Cardiovasc Surg 2003;125: Expected 64% 20 p< Time (years) 14 David et al, J Thorac Cardiovasc Surg 2003;126:

26 Survival (percent) Surgery for Acquired Cardiovascular Disease 100 Mitral Regurgitation Survival After Mitral Valve Surgery FC I-II 81% n=488 J Thorac Cardiovasc Surg 2003;125: FC III-IV 58% 20 p< Time (years) David et al, J Thorac Cardiovasc Surg 2003;126:

27 Mitral regurgitation Indications for MV repair for asymptomatic degenerative MR: Chronic severe MR Preserved LV function Experienced surgical center Likelihood of durable repair without residual MR > 95% class IIa

28 Mitral regurgitation Indications for MV repair for asymptomatic degenerative MR: Chronic severe MR Preserved LV function Experienced surgical center Likelihood of durable repair without residual MR > 95% Preserved LV function Likelihood of durable repair and low risk for surgery, and LA dilatation >60 ml/m2 -- or -- Exercise PAP >60 mmhg class IIa class IIb

29 Mitral regurgitation Indications for MV repair for asymptomatic degenerative MR:! Chronic severe MR Preserved LV function Experienced surgical center Likelihood of durable repair without residual MR > 95%. Repair better than mitral valve replacement Patients should be referred to centers experienced in repair class IIa class I

30 Mitral regurgitation Indications for transcatheter MV repair for severe degenerative MR: Chronic severe MR Severely symptomatic Prohibited surgical risk Reasonable life expectancy class IIb

31 Mitral regurgitation Primary MR: primary valve disease Secondary MR: primary myocardial disease

32 Mitral regurgitation Primary MR: primary valve disease Secondary MR: primary myocardial disease Diagnostic dilemmas Therapeutic dilemmas

33 Imprecision in grading severity of secondary MR What is severe secondary MR?

34 Survival (percent) 100 Survival After MI p<0.001 MI without MR ERO 1-19 ERO 20 61% 47% 29% Time (years) Grigioni et al. Circulation 2001;103:

35 Hospital-Free Survival (%) Ischemic or Nonischemic Cardiomyopathy No FMR Mild-Mod FMR 51% 20 0 p< ERO >20 Severe FMR Time (years) 24% 11% 6 7 Rossi et al. Heart 2011;97:

36 Hospital-Free Survival (%) Ischemic or Nonischemic Cardiomyopathy p< EF 34% LVSD 51 mm EF 33% LVSD 53 mm EF 29% LVSD 57 mm Time (years) No FMR Mild-Mod FMR Severe FMR 6 7 Rossi et al. Heart 2011;97: % 24% 11%

37 Mortality (percent) 800 Ischemic Cardiomyopathy p<0.001 p<0.001 Mod-Severe MR 55% Mild MR 47% No MR 30% Time (years) Deja et al. Circulation 2012;125: Deja et al. Circulation 2012

38 Mortality (percent) 800 Ischemic Cardiomyopathy p<0.001 p<0.001 EF 25% ESVI 90 ml/m 2 EF 27% ESVI 80 ml/m 2 EF 30% ESVI 73 ml/m 2 Mod-Severe MR Mild MR No MR Time (years) Deja et al. Circulation 2012;125: Deja et al. Circulation 2012

39 Prevalence of MR in Patients with LV Dysfunction N Prevalence MR Yiu et al Circulation % Grigioni et al Circulation % Koelling et al Am Heart J % Trichon et al Am J Cardiol % Robbins et al Am J Cardiol % Cleland et al N Engl J Med % Grayburn et al J Am Coll Cardiol % Bursi et al Circulation % Acker et al J Thorac CV Surg % Di Mauro et al Ann Thorac Surg % Rossi et al Heart % Deja et al Circulation % Onishi et al Circ Heart Fail % * Patients with moderate to severe MR * * *

40 Secondary mitral regurgitation: a marker of a sicker LV - or - a contributor to a sicker LV?

41 Secondary mitral regurgitation: a marker of a sicker LV - or - a therapeutic target? Therapies that produce beneficial reverse remodeling also reduce severity of functional MR

42 Secondary mitral regurgitation Guideline-directed medical therapy for heart failure, including CRT class I

43 Secondary mitral regurgitation Guideline-directed medical therapy for heart failure, including CRT Indications for mitral valve surgery: class I Patients with severe MR undergoing CABG or AVR class IIa

44 Secondary mitral regurgitation Guideline-directed medical therapy for heart failure, including CRT Indications for mitral valve surgery: class I Patients with severe MR undergoing CABG or AVR Severe MR, persistent symptoms despite optimal medical therapy, including CRT class IIa class IIb

45 Secondary mitral regurgitation Guideline-directed medical therapy for heart failure, including CRT Indications for mitral valve surgery: Patients with severe MR undergoing CABG or AVR Severe MR, persistent symptoms despite optimal medical therapy, including CRT Patients with moderate MR undergoing CABG or AVR class I class IIa class IIb class IIb

46 Baseline Optimized Medical Therapy and Biventricular Pacing

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48 Secondary mitral regurgitation Indications for transcatheter MV repair for severe secondary MR: Severe secondary MR Severely symptomatic Prohibited or high surgical risk Reasonable life expectancy class IIb

49 Prevalence of MR in Patients with LV Dysfunction N Prevalence MR Yiu et al Circulation % Grigioni et al Circulation % Koelling et al Am Heart J % Trichon et al Am J Cardiol % Robbins et al Am J Cardiol % Cleland et al N Engl J Med % Grayburn et al J Am Coll Cardiol % Bursi et al Circulation % Acker et al J Thorac CV Surg % Di Mauro et al Ann Thorac Surg % Rossi et al Heart % Deja et al Circulation % Onishi et al Circ Heart Fail % * Patients with moderate to severe MR * * *

50 Percent Moderate-Severe Mitral Valve Disease ARIC, CHS, CARDIA (n=11,911) Lancet 2006;368: Olmstead County (n=16,501) ,412 subjects < Age Nkomo et al, Lancet 2006;368:

51 Percent Moderate-Severe Aortic Valve Disease ARIC, CHS, CARDIA (n=11,911) Lancet 2006;368: Olmstead County (n=16,501) 28,412 subjects < Age Nkomo et al, Lancet 2006;368:

52 Aortic Stenosis Rheumatic AS Congenital AS Calcific AS from Bonow and Braunwald, Valvular Heart Disease Braunwald s Heart Disease, 7th ed, 2004

53 Aortic Stenosis Rheumatic AS Congenital AS Age >60 All patients Men 47% 51% Calcific AS Roberts and Ko, Circulation 2005;111: from Bonow and Braunwald, Valvular Heart Disease Braunwald s Heart Disease, 7th ed, 2004

54 Aortic Stenosis Rheumatic AS Congenital AS Age >80 All patients Men 28% 32% Calcific AS Roberts and Ko, Circulation 2005;111: from Bonow and Braunwald, Valvular Heart Disease Braunwald s Heart Disease, 7th ed, 2004

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57 Ross and Braunwald, Am J Circulation 1968;38:V-61

58 the grave prognosis that appears to accompany the onset of certain symptoms Ross and Braunwald, Am J Circulation 1968;38:V-61

59 Ross and Braunwald, Am J Circulation 1968;38:V-61

60 Ross and Braunwald, Am J Circulation 1968;38:V-61

61 Survival (percent) Aortic Stenosis Survival of Symptomatic Patients Circ Cardiovasc 100 Qual Outcomes 2009;2: % Time (months) Bach et al, Circ Cardiovasc Qual Outcomes 2009;2:

62 Aortic Stenosis Indications for AVR Symptomatic patients with severe AS class I if it is likely that the symptoms are cardiac in origin

63 Aortic Stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR

64 Aortic Stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR

65 Aortic Stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR Are asymptomatic patients with severe AS really asymptomatic?

66 Aortic stenosis Indications for valve replacement Exercise test results: Symptoms Hypotension class I class IIa How are symptoms determined? Everyone has symptoms on stress test Are the symptoms cardiac in origin? What level of exercise? How is hypotension defined? Less than 20 mmhg increase (?)

67 Aortic stenosis Indications for valve replacement Exercise test results: Symptoms Hypotension class I class IIa Should asymptomatic patients with severe AS undergo AVR? when they are really asymptomatic?

68 Vmax: 4.6 m/s Mean Δ: 52 mmhg AVA: 0.7 sq cm Severe AS: >4.0 m/s >40 mmhg <1.0 sq cm

69 Aortic Stenosis 84 year old man with severe AS Watchful waiting? * More data (more testing)? Aortic valve replacement? * Wait until he develops symptoms in 5-6 years and then recommend TAVR?

70 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Vmax > 4.0 m/s Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Otto Time (years) Otto et al. Circulation 1997;95:

71 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Vmax > 4.0 m/s Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Otto Rosenhek Time (years) Otto et al. Circulation 1997;95: Rosenhek et al. N Engl J Med 2000;343:

72 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Vmax > 4.0 m/s Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Otto Rosenhek Pellikka Time (years) Otto et al. Circulation 1997;95: Rosenhek et al. N Engl J Med 2000;343: Pellikka et al. Circulation 2005;111:

73 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Vmax > 4.0 m/s Average hospital mortality: 8.8% Low volume centers: 13.0% Stewart High volume centers: 6.0% Otto Rosenhek Pellikka Time (years) Otto et al. Circulation 1997;95: Rosenhek et al. N Engl J Med 2000;343: Pellikka et al. Circulation 2005;111: Stewart et al. Eur Heart J 2010;31:

74 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Vmax > 4.0 m/s Average hospital mortality: 8.8% Low volume centers: 13.0% Rosenhek High n=128 volume centers: 6.0% Time (years) Rosenhek et al. N Engl J Med 2000;343:

75 Event-Free Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Average hospital mortality: 8.8% Low volume centers: 13.0% High n=198 volume centers: 6.0% p<0.001 Vmax m/s Vmax m/s Vmax >5.5 m/s Time (years) Rosenhek et al. Circulation 2010;121:

76 Aortic Stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR What is the risk of death while waiting for symptoms to trigger AVR?

77 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Pai Time (years) Pai et al. Ann Thorac Surg 2006;82:

78 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Kang Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Pai Time (years) Pai et al. Ann Thorac Surg 2006;82: Kang et al. Circulation 2010;121:

79 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Kang Average hospital mortality: 8.8% Low volume centers: 13.0% High volume centers: 6.0% Nistri Pai Time (years) Pai et al. Ann Thorac Surg 2006;82: Kang et al. Circulation 2010;121: Nistri et al. Am J Cardiol 2012;109;

80 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Kang Average hospital mortality: 8.8% 60 Taniguchi Low volume centers: 13.0% High volume centers: 6.0% Nistri Pai Time (years) Pai et al. Ann Thorac Surg 2006;82: Kang et al. Circulation 2010;121: Nistri et al. Am J Cardiol 2012;109; Taniguchi et al. J Am Coll Cardiol 2105;66:

81 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Average hospital mortality: 8.8% 60 Taniguchi Low volume centers: 13.0% High volume centers: 6.0% Time (years) Taniguchi et al. J Am Coll Cardiol 2105;66:

82 Survival (%) Natural History of Severe Asymptomatic AS Medicare 80 data Average hospital mortality: 8.8% AVR (n=291) Low volume centers: 13.0% Conservative (n=291) High volume centers: 6.0% 85% 74% Taniguchi 31% of patients who developed symptoms did not have AVR 17 deaths Time (years) Taniguchi et al. J Am Coll Cardiol 2105;66:

83 Asymptomatic Aortic Stenosis Indications for valve replacement: Very severe AS: Vmax 5 m/s class IIa

84 Asymptomatic Aortic Stenosis Indications for valve replacement: Very severe AS: Vmax 5 m/s Rapid progression and low surgical risk class IIa class IIb

85 Asymptomatic Aortic Stenosis Indications for valve replacement: Very severe AS: Vmax 5 m/s Rapid progression and low surgical risk class IIa class IIb Very severe AS: Vmax >5.5 m/s class IIa

86 Asymptomatic Aortic Stenosis Indications for valve replacement: Very severe AS: Vmax 5 m/s Rapid progression and low surgical risk class IIa class IIb Very severe AS: Vmax >5.5 m/s Severe valve calcification and rate of progression 0.3 m/s / year class IIa class IIa

87 Asymptomatic Aortic Stenosis Indications for valve replacement: Very severe AS: Vmax 5 m/s Rapid progression and low surgical risk class IIa class IIb Very severe AS: Vmax >5.5 m/s Severe valve calcification and rate of progression 0.3 m/s / year Markedly elevated BNP Increase in gradient with exercise >20 mmhg Excessive LVH class IIa class IIa class IIb

88 Asymptomatic Aortic Stenosis Indications for valve replacement: The ACC/AHA and ESC/EACTS guidelines have lowered the threshold for surgery in asymptomatic patients with AS Severity of AS Severity of calcification Left ventricular function Exercise response

89 Asymptomatic Aortic Stenosis Indications for valve replacement: The ACC/AHA and ESC/EACTS guidelines have lowered the threshold for surgery in asymptomatic patients with AS Severity of AS Severity of calcification Left ventricular function Exercise response BNP?

90 Survival (percent) Asymptomatic AS with Normal EF n=562 p<0.001 BNP ratio 83% <1.0 66% % % Time (years) Clavel et al, J Am Coll Cardiol 2014;63:

91 Aortic stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR

92 Low Gradient Aortic Stenosis LV Dysfunction Normal LV Function Diastole Dobutamine: Echocardiography or Catheterization Treat hypertension Catheterization Valve calcification Advanced imaging Clinical skills Systole from Pibarot and Dumesnill, J Am Coll Cardiol 2012:60:

93 Low Flow, Low Gradient Aortic Stenosis Indications for valve replacement: Reduced EF: Dobutamine study showing: Vmax >4 m/s or Mean Δ >40 mmhg or AVA 1 sq cm class IIa Reduced EF: With contractile reserve class IIa

94 Low Flow, Low Gradient Aortic Stenosis Indications for valve replacement: Reduced EF: Dobutamine study showing: Vmax >4 m/s or Mean Δ >40 mmhg or AVA 1 sq cm Normal EF: Only if clinical, anatomic and hemodynamic data support severe AS Reduced EF: With contractile reserve class IIa class IIa class IIa

95 Low Flow, Low Gradient Aortic Stenosis Indications for valve replacement: Reduced EF: Dobutamine study showing: Vmax >4 m/s or Mean Δ >40 mmhg or AVA 1 sq cm Normal EF: Only if clinical, anatomic and hemodynamic data support severe AS Reduced EF: With contractile reserve Normal EF: Only after thorough confirmation of severe AS class IIa class IIa class IIa class IIa

96 Aortic stenosis Management challenges: The asymptomatic patient with severe AS Low-flow, low gradient severe AS Indications for TAVR

97 Intervention for Severe AS Indications for TAVR vs surgical AVR: Evaluation by a Heart Team class I

98 Intervention for Severe AS Indications for TAVR vs surgical AVR: Evaluation by a Heart Team Surgical AVR for patients at low or intermediate risk class I class I

99 Intervention for Severe AS Indications for TAVR vs surgical AVR: Evaluation by a Heart Team Surgical AVR for patients at low or intermediate risk TAVR for patients with prohibitive surgical risk and life expectancy >12 months class I class I class I

100 Intervention for Severe AS Indications for TAVR vs surgical AVR:?? Evaluation by a Heart Team Surgical AVR for patients at low or intermediate risk TAVR as alternative? TAVR for patients with prohibitive surgical risk and life expectancy >12 months TAVR alternative for patients at high surgical risk class I? class I class I class I class IIa

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102 TAVR Now TAVR has been truly transformative Surgical AVR remains the standard with proven durability and safety for most patients TAVR provides treatment options for patients who previously had no options other than a predictably very poor short term outcome TAVR is an alternative to SAVR in patients at high or intermediate surgical risk The threshold for TAVR is declining in clinical trials, registries and clinical practice All patients want this Determining when to withhold TAVR is difficult

103 TAVR in the Future Guidelines will need to adapt to the rapidly evolving TAVR evidence base TAVR in intermediate and low risk surgical patients Availability of TAVR is likely to inform new indications for valve replacement Moderate AS in primary cardiomyopathy Asymptomatic severe AS? Judgment of the Heart Team remains essential in patient selection for TAVR Appropriate use criteria and performance measures are needed to define quality

104 Aortic stenosis is a simple mechanical fault which, if severe enough, imposes a heavy burden on the left ventricle and sooner or later overcomes it. it s not simple any more Wood P, Am J Cardiol 1958;1:

105 Valvular heart disease: Have the guidelines filled the gap?