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Women and Coronary Artery Disease (CAD)

Women and Coronary Artery Disease (CAD). Module 3 Diagnosis and Prognosis. Supported by an unrestricted educational grant from Fujisawa Healthcare, Inc. Diagnosis and Management of Coronary Artery Disease in Women. Gender differences: presentation, manifestation and diagnosis of CAD

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Women and Coronary Artery Disease (CAD)

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  1. Women andCoronary Artery Disease (CAD) Module 3Diagnosis and Prognosis

  2. Supported by an unrestricted educational grant from Fujisawa Healthcare, Inc.

  3. Diagnosis and Management of Coronary Artery Disease in Women • Gender differences: presentation, manifestation and diagnosis of CAD • Gender differences in mortality • 63% of women who die suddenly from CAD had no prior warning symptoms • 42% of women vs 24 % of men will die within one year after myocardial infarction (MI) • Thus, early recognition of symptoms and accurate diagnosis of CAD is of great importance

  4. Heart Disease in Women: Lessons From the Past Decade • The importance of studying gender-specific aspects of CAD have helped in the following clinical dilemmas: • Presentation of CAD: women are older than men • Less specific clinical manifestations of CAD in women • Greater difficulty in diagnosis: women > men • More severe consequences on MI when it occurs in women

  5. Screening for Heart Disease What Tests Should I Undergo to Tell That I Have Heart Disease?

  6. Limited Representation of Women in Studies of CAD Testing Adapted from: Shaw LJ, et al. Coronary Artery Disease in Women: What All Physicians Need to Know. 1999

  7. Are There Gender Differences in Noninvasive Diagnostic Tests? Is There a Difference in Diagnostic Accuracy of Noninvasive Tests?

  8. Noninvasive Testing Options Stress ECG Stress Echo Stress MPI EBCT PET MRI

  9. Noninvasive Testing in Symptomatic Women • Stress electrocardiography (ECG) • Stress echocardiography (ECHO) • Stress nuclear

  10. Exercise ECG (Treadmill) • Despite advances in technology, the exercise ECG remains an important tool in the diagnosis and prognosis of the patient suspected of having CAD • The exercise ECG has an overall sensitivity of 68% and a specificity of 77% for the detection of CAD in men • The sensitivity and specificity of the exercise ECG in women are about 61% and 70% respectively Kwok Y, et al. Am J Cardiol. 1999.

  11. ECG Testing in WomenSensitivity and Specificity No. ofWomen Study, Year Sensitivity (%) Specificity (%) Detry et al, 1977 47 80 63 Weiner et al, 1979 580 76 64 Barolsky et al, 1979 92 60 68 Friedman et al, 1982 60 32 41 Guiteras et al, 1982 112 79 66 Hung et al, 1984 92 73 59 Adapted from Heller GV, et al. Nuclear Cardiology: State of the Art and Future Directions. 1998

  12. Gender Differences in Exercise ECG Testing •  sensitivity in women >65 years •  specificity in women on hormone replacement therapy •  false-positive results due to autonomic/hormonal influences • Digoxin like effect of estrogen Shaw LJ, et al. CAD in Women: What All Physicians Need to Know. 1999

  13. Factors Affecting Accuracy • Hormonal status/cyclic variation • Functional capacity • Onboard medications • Adequacy of flow reserve

  14. Diagnosis of Noninvasive Tests in Women • ECG • Nuclear • ECHO • Computed tomography

  15. Should All Women With Suspected CAD Have Cardiac Imaging Studies? • Nuclear • ECHO • Positron emission tomography (PET)

  16. Incremental Value of Imaging to Exercise ECG: Women With Abnormal Rest ECG Douglas PS. Coronary artery disease in women. In: Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine. 2001

  17. Nuclear Imaging in Women • Myocardial perfusion imaging (MPI) • Large body of evidence in women • Gender-specific data available for Tl-201and Tc-99m tracers • Tc-99m tracers = agent of choice for women due to decrease attenuation artifacts from breast tissue • Gated single-photon emission computed tomography (SPECT) provides post stress ejection fraction and regional wall motion  helpful to reduce false positives • IV adenosine/dipyridamole stress provides comparable overall accuracy in women and men

  18. Comparative Test Statistics on Diagnostic Accuracy in Women Kwok Y, et al. Am J Cardiol. 1999

  19. Diagnostic Specificity: Tl-201 vs Tc-99m Sestamibi • Perfusion imaging • Regional blood flow • Robust evidence in women • Gender-specific data for Tl-201 and Tc-99m sestamibi • Tc-99m sestamibi is agent of choice for women (reduced breast attenuation) • Gated SPECT • Post-stress EF and regional wall motion • Reduce false-positive tests • Pharmacologic stress helpful in older and obese women N = 115, P = .0004 21 false + 10 false + • Hachamovitch R. et al. J Am Coll Cardiol. 1996; Amanullah AM, et al. Am J Cardiol. 1997; Taillefer R, et al. J Am Coll Cardiol. 1997

  20. Pharmacologic Stress Testing in a Community Setting: Women vs Men Percent of patients referred for MPI who underwent exercise stress vs pharmacologic stress at Mission Internal Medicine Group, Mission Viejo, CA (4/21/02 to 8/29/02) Data provided by Greg Thomas, MD, Mission Internal Medicine Group

  21. Multicenter study by Shaw et al compared resource consumption between 2 patient groups with varying initial diagnostic testing strategies 11,372 men and women with stable angina Patients separated into low, intermediate, and high pretest probability of CAD risk Direct cardiac catheterization (n = 5,423) MPI (primarily Tc-99m sestamibi), then selective cardiac catheterization (n = 5,826) Economics of Noninvasive Diagnosis (END) Study Shaw LJ, et al. J Am Coll Cardiol. 1999

  22. Secondary Analysis of the END Study Population Marwick T, et al. Am J Med. 1999

  23. END Study: Ischemia as Gatekeeper to Catheterization Laboratory Invasive = cardiac catheterizationNoninvasive = initial stress SPECT plus selective catheterization Shaw LJ, et al. J Am Coll Cardiol. 1999

  24. Results of END Study • MPI with selective catheterization reduced initial and follow-up care costs at all levels of pretest clinical risk • Savings noted by decreasing resource use in patients with normal MPI results • Selective catheterization reduced cost of care while preserving/enhancing quality of care Shaw LJ, et al. J Am Coll Cardiol. 1999

  25. Stress ECHO • Ultrasound performed both at rest and during peak stress • Stress—exercise or pharmacologic • Ischemia defined by development of wall motion abnormalities Courtesy of Howard Lewin, MD, of San Vicente Cardiac Imaging Center.

  26. ECHO Testing in Women • Overall • Convenient/readily available1,2 • Avoids ionizing radiation2 • Identifies cardiac structure and left ventricular function (LVF) • Sensitivity and specificity vs ECG testing1,2 • Increased sensitivity (79%-88%) • Increased specificity (77%-86%) • 1. Williams MJ, et al. Am J Cardiol. 1994 • 2. Marwick T, et al. J Am Coll Cardiol. 1995

  27. PET Imaging for CAD in Women Positron Emission Tomography

  28. PET Case Study: Patient FF Stress Rest

  29. PET Case Study: Patient FFIschemia of Lateral Wall

  30. The Role of PET for Evaluating CAD in Women • Soft-tissue artifacts encountered in SPECT are eliminated • Improved image quality due to better resolution than SPECT • Ability to quantify coronary blood flow • Rb-82 perfusion imaging: 98% sensitivity and 95% specificity for detecting CAD in women Williams BR, et al. Am J Cardiac Imaging. 1996

  31. The Role of PET for Evaluating CAD in Women • Prognosis of a normal PET study • ACC 2001: Van Tosh, et al: • Follow-up at 30 months of 301 women with chest pain, risk factors for CAD, no prior history of CAD, and normal PET • End points: cardiac death, nonfatal MI, PTCA, or CABG • Events at 30 months: 0.74% per year

  32. Electron Beam Computed Tomography (EBCT) • Resting study only • Stationary tungsten target permits rapid scanning • Detects coronary calcification • Abnormality defined as presence of any calcium Courtesy of Howard Lewin, MD, of San Vicente Cardiac Imaging Center

  33. Diagnostic Accuracy of EBCT Coronary Calcium Scores by Gender Subsets Men Women Women Men Devries S, et al. J Am Coll Cardiol. 1995. Rumberger JA, et al. Circulation. 1995. Detrano R, et al. Am J Card Imaging. 1996.

  34. Diagnostic Accuracy of EBCT • Improved CAD detection and prognostication through visualization of • Wall motion • Perfusion • Function

  35. Prognosis of Noninvasive Tests in Women Nuclear

  36. Event Rates as Function of MPI With SPECT Results by Gender Hachamovitch R, et al. J Am Coll Cardiol. 1996

  37. Prognostic Value of Adenosine SPECT Imaging in 923 Women Amanullah AM, et al. Am J Cardiol. 1998

  38. 1.0 1.0 98.5% 0 0 Ischemia extent and survival by number of vascular territories 1 1 2 2 0.9 0.9 3 Cardiac survival 0.8 0.8 80-87% 3 0.7 0.7 Women (n = 3402) Men (n = 4500) 0.6 0.6 0 0.5 1 1.5 2 2.5 3 0 0.5 1 1.5 2 2.5 3 Years Years Technetium-99m SPECT Imaging Predicts Cardiac Mortality in Women Marwick TH, et al. Am J Med. 1999

  39. Prognostic Value of MPI • Exercise MPI provides incremental prognostic value to risk stratify women and to help in CAD management1 • Abnormal Tc99m sestamibi SPECT findings associated with adverse prognosis in both women and men2 1. Hachamovitch R, et al. J Am Coll Cardiol. 1996 2. Travin MI, et al. Am Heart J. 1997

  40. Prognosis in Women: Shifting Strategies for Early Detection • Gender differences drive outcome differences1 • Baseline characteristics • Clinical course • Relative weight of prognostic factors • Misperception: Coronary artery disease has benign prognosis in women2 • Results in less aggressive diagnosis and management • Awareness of higher morbidity/mortality in women3 • Dictates need for early diagnosis and aggressive treatment • Early aggressive management lowers risk and need for repeat intervention (eg, Evaluation of Platelet IIb/IIIa Inhibitor for Stenting) 1. Bedinghaus J, et al. Am Fam Physician. 2001 2. Welty FK. Arch Intern Med. 2001 3. Keller KB, et al. Am J Crit Care. 2000

  41. Paradigm Shift in Strategies for Screening Risk in Women • Symptom presentation1 • Varies in women • More likely atypical presentation • Diabetic women • Worse outcome, often asymptomatic on presentation1,2 • Bias toward undertreatment • 63% of women with sudden cardiac death have no prior symptoms3 • If we allow symptoms (current paradigm) to drive testing and treatment, we will be less than accurate 1. Bedinghaus J, et al. Am Fam Physician. 2001 2. Welty FK. Arch Intern Med. 2001 3. American Heart Association. Women and Cardiovascular Diseases Biostatistical Fact Sheet. 2002

  42. Prognostic Value of MPI in Women With Diabetes Kang X, et al. Am Heart J. 1999

  43. Prognostic Value of MPI in Women With Diabetes • Event rates rose significantly as a function of summed stress score (SSS) • Diabetics had significantly higher rate of hard events versus nondiabetics • Adenosine and exercise were valuable tools for risk stratification and management of patients with diabetes (N = 7133) n = 215 n = 202 n = 95 n = 128 n = 151 n = 289 SSS <4 SSS 4-8 *P < .01 SSS >8 Kang X, et al. Am Heart J. 1999

  44. BARI-2D Clinical Trial • First BARI trial showed diabetics with CAD survive longer after initial CABG than after initial PCI • BARI-2D evaluates early revascularization vs aggressive medical therapy in patients with type 2 diabetes and CAD • Multicenter, multidisciplinary, randomized study • Stress tests (eg, adenosine SPECT) and arteriograms determine eligibility • Trial to enroll 2800 patients from 40 centers • 5-year follow-up • Repeat stress testing and heart evaluations every 12 months • VA Cooperative Study / UAB-Iskandrian Core Lab Feit F, et al. Circulation. 2000 Brooks RC, et al. Curr Opin Cardiol. 2000

  45. Diabetes: Prevalence of Subclinical CAD in Women Barzilay JI, et al. Diabetes Care. 2001

  46. SNM Guidelines for Evaluating Women With Suspected CAD Symptom evaluation, abnormal rest ECG, intermediate likelihood of CAD Caution: age <45, evaluate comorbidity Optimize ETT Consider catheterization if high risk Gated SPECT, assess functional status No functional limitations, 5 METS Functional limitations Pharmacologic stress Stratify by EF EF <50% Diagnostic EF EF <50% No ischemia, consider noncardiac origin Ischemia No defects Catheter Catheter Evaluate valvular disease (via ECHO) Primary prevention, modify risk factors Ischemia Adapted from: Shaw LJ, et al. Outcomes and Technology Assessment in Nuclear Medicine. 1999

  47. Clinical evaluation Low likelihood of CAD (<15%) Intermediate/high likelihood of CAD (15% to 85%) Risk factor modification Interpretable rest ECG Uninterpretable rest ECG Low post-ETT likelihood ETT Intermed.-high post-ETT likelihood Stress myocardial perfusion SPECT Moderately to severely abnormal Normal or mildly abnormal with normal LV function Cardiac catheterization Prognostic Evaluation of Women With Suspected CAD Adapted from: Cacciabaudo JM, et al. J Nucl Med. 1998

  48. New Paradigm for CAD Testing Detection of Subclinical CAD:Global CAD Burden Detection of Obstructive CAD High probability Cardiac catheterization Asymptomatic with risk factors Symptom onset PCI/CABS Intermediate probability Low probability: asymptomatic screening Stress ECG/Echo/SPECT • Subclinical measures: • A-B index • Carotid IMT • EBT-CT Anti-ischemic Rx and risk factor modification Shaw LJ. ACC 2002

  49. Risk factor modification +/or anti-ischemic Rx Exercise or pharmacologic stress gated SPECT Exercise treadmill (TM) testing Ex capacity >5 METs Ex capacity <5 METs Low post-ETTlikelihood Intermediate risk TM Pharmacologic stress gated SPECT Good exercise tolerance and normalrest ECG Diabetes, abnormalrest ECG, or max exercise capacity <5 METs Exercise stress gated SPECT Moderate- severelyabnormal or reduced EF Normal or mildlyabnormal withnormal LV function Cardiac catheterization Intermediate – High Likelihood Women With Atypical or Typical Chest Pain Symptoms, Dyspnea, or Reduced Activities Mieres JH, et al. ASNC VII 2003

  50. Beyond Research • Society educational programs/guideline updates • Synthesizing research • Medical literature is immense and changing rapidly—need strategies for effective/quick dissemination of research • Create opportunities for clinician education/awareness/ intervention • Training and educational programs for primary care physicians including generalists, gynecologists, and cardiovascular specialists • Health policy • Strategies for targeting screening of at-risk women •  representation of women in NIH-funded/FDA-sponsored trials—first step • Should we have a reimbursable/recommended screening test post-menopause (eg, mammogram)?

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