Gender Differences in Valvular Heart Disease. Linda D. Gillam, MD FESC Disclosure: Core Lab services Edwards Lifesciences

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1 Gender Differences in Valvular Heart Disease Linda D. Gillam, MD FESC Disclosure: Core Lab services Edwards Lifesciences

2 Obstacles Interest in gender differences is a relatively new phenomenon Registries/RCT for valvular heart disease are under-developed Modest evidence base

3 Confounding Variables Size Longevity Treatment biases Prevalence of coronary disease Possibility that pre-menopausal women post-menopausal women

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5 Gender Differences in Valvular Heart Disease Etiology Pathophysiology (Ventricular Adaptation) Natural History Treatment Outcomes (surgical)

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7 Congenital Bicuspid Unicuspid Acquired Degenerative Other Aortic Stenosis Etiology

8 Bicuspid Aortic Valve Most common congenital heart defect Prevalence 0.5-2% Male predominance 3:1

9 In patients with bicuspid aortic valve does gender influence outcome?

10 At Diagnosis

11 Baseline Characteristics of Patients With and Without Baseline Aortic Valve Dysfunction Toronto Congenital Program Referral Population Tzemos, N. et al. JAMA 2008;300: (Toronto Series) Copyright restrictions may apply.

12 Baseline Characteristics of Patients With and Without Valve Degeneration at Diagnosis Mayo Clinic (Olmstead County) Michelena HI et al. Circulation 2008;117:

13 Following Diagnosis

14 Predictors of Primary Cardiac Events Tzemos, N. et al. JAMA 2008;300: Copyright restrictions may apply.

15 Independent Predictors of Primary Cardiac Events Gender is not predictive

16 Conclusion In patients with bicuspid valve For the same degree of valve dysfunction gender not predictive of outcome Controversy concerning impact of gender on development of dysfunction Need natural history series

17 From another perspective: Surgical Series N = 465 consecutive AS pts Bicuspid: vs. =1.85:1 Tricuspid: vs. = 0.76:1 Davies MJ et al. Heart 1996; 75:174-8 (St George s Hospital London) N = 115 (65 men, 50 women) Men: 48% bicuspid Women: 46% bicuspid Stephan BSPJ et al. Amer. J Cardiol. 1997;79: (Baylor)

18 Pathophysiology of Aortic Stenosis

19 Ventricular Adaptation Women have thicker walls, smaller ventricles Reduces wall tension and metabolic demand BUT predisposes to intraventricular and subaortic gradients Clinical significance uncertain

20 LVEF Women tend to have higher LVEF s but likely not increased contractility

21 Long term outcomes? Rat model of aortic banding: males make earlier transition to ventricular dilatation, eccentric remodeling

22 Aortic Regurgitation Inferential

23 At Surgery for AR Male predominance (4:1) Women Older (median 68 vs 55 yrs) More likely to have aortic pathology More likely to have class III/IV HF (? Vs LV dimension indication) Similar operative mortality Worse long term outcomes RR 4:1 corrected for age, LVEF, symptoms, CABG, aortic aneurysm

24 In rats (volume overload due to AV fistula) Despite same degree of hypertrophy, female rats less likely to decompensate

25 Surgery for Aortic Valve Disease

26 Short term

27 Surgical Outcomes In both STS and Euroscore risk calculators, female gender carries increased risk 1.23 (CI ) for AVR (STS) OR 1.4 cardiac surgery (Euroscore)

28 Outcomes (STS)

29 Long term

30 Surgical Outcomes Long-term Kulik et al: Ottawa Heart : Ottawa series of 2255 pts with AVR Women older ( vs ) Equally likely to receive bioprosthesis vs. mechanical valve

31 Kulik et al: Ottawa Heart :

32 Kulik et al: Ottawa Heart : Bbioprosthetic AVR

33 Surgical Outcomes Long-term Kulik et al: Ottawa Heart : Women at increased risk of stroke post mechanical AVR for same degree of anticoagulation adjusted HR 1.7; CI

34 Mitral Valve Disease

35 Rheumatic MS More common in women 72% vs. 28% of cases Exaggerated immunologic response due to estrogen binding to receptors on CD4+ and CD8+ subsets of T lymphocytes capable of producing the mitral valve damage Male gender a predictor of successful valvuloplasty

36 Mitral Regurgitation

37 Mitral Regurgitation Degenerative Overall prevalence 2-3% of population female to male 1.7 to 1 Women more likely to have benign course BUT less severe regurgitation less likely to require surgery higher mortality if they develop severe mitral regurgitation

38 Surgical Outcomes STS

39 Surgical Outcomes STS

40 Kulik et al: Ottawa Heart :

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42 Valve Disease in Pregnancy In general regurgitant lesions well tolerated Stenotic lesions less well tolerated

43 Summary Important gender differences in valvular heart disease Etiology Bicuspid aortic valve more common in men Rheumatic mitral (aortic?) disease Degenerative mitral disease more common in women

44 Summary Ventricular response (aortic stenosis) Natural history (degenerative MR) Surgical outcomes Women have poorer short term outcomes?better outcomes longterm (bioprostheses)

45 Much to be learned Are ventricular size cutoffs that have been proposed (largely derived from studies of men) suitable for women? Are there interventions for rheumatic mitral disease? How can we improve short term surgical outcomes for women? CVA CAD

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