Heart Rate Recovery in association with exercise stress testing Daniel E. Forman, M.D. Director, Exercise Laboratory Brigham and Women s Hospital April 21, 2006
Stress Testing Historical Rationale for Exercise Testing Test sensitive and specific to diagnose CAD Symptoms and ECG changes Has this rationale for testing changed? Diagnosis is often not the question Shifting emphasis on prognosis What constitutes meaningful endpoints?
Limitations of Stress Test for CAD: Progression lumen may be patent Compensatory expansion maintains constant lumen Normal vessel Minimal CAD Expansion overcome: lumen narrows Moderate CAD Adapted from Glagov et al. N Engl J Med. 1987;316:1371 1375. Severe CAD
Limitation of Stress Test for CAD: Cardiac Cath is a flawed Gold Standard 3.1 mm 3.1 mm We ve based our diagnostic standards on 2D imaging Courtesy of Steven Nissen
Limitations of Stress Test for CAD: No assessment of plaque stability
Bottom Line It is often hard to detect ischemia And even when ischemia is detected, it is difficult to discern the implications Prognosis is more important than diagnosis
Prognostic Endpoints Functional capacity Prognostic Scores HR indices: heart rate recovery
Heart Rate Exercise Heart Rate Responses Rest Vagal Reactivation Vagal withdrawal Sympathetic increase Exercise Recovery Peak Heart Rate Recovery 1 minute
Heart Rate Recovery Biological rationale Seminal research Confounding, interactions External validation Clinical applications
Heart Rate Recovery Biological rationale Seminal studies Confounding, interaction External validation Clinical applications
Log Heart Rate HR Recovery: After Atropine 5.4 5.3 5.3 5.2 5.2 5.1 5.1 5.0 5.0 4.9 4.9 4.8 Athlete Normal Heart Failure 0.0 0.5 1.0 Recovery Time (minutes) Imai JACC 24;1529;1994 1.5 2.0
Autonomic Function and Mortality Sympathetic Tone Vagal Tone Chronotropic Incompetence HR Recovery Increased Risk of Death
Heart Rate Recovery Biological rationale Seminal studies Confounding, interaction External validation Clinical applications
Heart Rate Recovery and Mortality 1.00 Normal (93/1789) 0.95 0.90 Abnormal (120/639) 0.85 Abnormal < 12 bpm Log rank χ2=115, P<0.0001 Hazard Ratio 4.0 (95% CI 3.0 5.2) 0.80 0.75 0 2 4 Years of Follow up Cole, Lauer. N Engl J Med 1999;341:1351 6 8
HRR and Duke Exercise Score Both normal 1.00 Abnormal HRR Survival 0.95 Abnormal Treadmill Score 0.90 0.85 Both Abnormal 0.80 0.75 Log rank χ2 = 383, P < 0.0001 0 1 2 3 4 Years of Follow up Nishime, Lauer, JAMA 2000;284:1392 1398 5 6 7
Heart Rate Recovery Biological rationale Seminal studies Confounding, interaction External validation Clinical applications
Demographic Subsets Abnormal 6 Year Mortality (%) 35 30 25 Normal P<0.001 P<0.001 P<0.001 20 P<0.001 P<0.001 15 P<0.001 10 5 0 Men Women >65 Cole, Lauer. N Engl J Med 1999;341:1351 <65 CAD No CAD
Test Subsets Abnormal 6 Year Mortality (%) 35 P<0.001 30 25 Normal P<0.001 20 P<0.001 15 P<0.001 10 5 0 Exercise HR abnormal Exercise HR normal Cole, Lauer. N Engl J Med 1999;341:1351 Thallium abnormal Thallium normal
35 30 25 20 15 10 5 0 Abnormal P<0.001 Normal P<0.001 P<0.001 P=0.15 P<0.001 P<0.001 N o B bl oc ke rs C a bl oc ke rs N o C a bl oc ke rs Va so di la to N rs o Va so di la to rs B bl oc ke rs 6 Year Mortality (%) Medication Subsets Cole, Lauer. N Engl J Med 1999;341:1351
Relative Risk 10 9 8 7 6 5 4 3 2 1 0 0 5 10 15 20 25 Heart Rate Recovery (BPM) Cole, Lauer. N Engl J Med 1999;341:1351 30 35
Stress Echocardiography Survival 1.00 Normal heart rate recovery (N=4633, 115 deaths) 0.95 Abnormal heart rate recovery, (N=805, 75 deaths) 0.90 Log rank χ2 = 99, P < 0.0001 0.85 0 1 Cut off = 18 bpm 2 Years After Test Watanabe, Lauer. Circulation 2001;104:1911 1917 3 4
HR Recovery and LVEF Both Normal 1.00 Abnormal HRR only Survival 0.95 0.90 Abnormal LV only 0.85 0.80 Both Abnormal 0.75 0.70 Log rank χ23 = 170, P<0.0001 0 1 2 Years After Test Watanabe, Lauer. Circulation 2001;104:1911 1917 3 4
HR Recovery and Angiography 1 Both Normal Survival 0.9 Severe CAD 0.8 Abnormal HR Recovery 0.7 Both Abnormal 0.6 0.5 0 1 2 3 4 5 6 Years After Stress Test Vivikenathan D and Lauer MS, J Am Coll Cardiol 2003;42:831 8 7 8
Heart Rate Recovery Biological rationale Seminal studies Confounding, interaction External validation Clinical applications
External Validation: Stanford % Survival 100 Two minutes post 22 bpm drop 75 Two minutes post < 22 bpm drop 50 25 0 0 3.5 7.0 10.5 Years Follow up Shetler K. J Am Coll Cardiol. 2001;38:1980 1987. 14.0
Technical differences 1 minute vs. 2 minute recovery Cool down vs. supine recovery protocol
Ventricular Ectopic Activity 1.00 Neither Exercise 0.90 0.80 0.70 Both Recovery 1862 deaths Log rank χ32 = 133, P < 0.0001 0.0 2.0 4.0 Years After Test Frolkis JP, Lauer MS, N Engl J Med 2003;781 90. 6.0 8.0
Heart Rate Recovery Biological rationale Seminal studies Confounding, interaction External validation Clinical applications
Combining Prognostic Indices: Function and HR recovery Shetler et al. JACC.2001;38:1980 7
Risk for CV death according to FRS categories and HRR/METs groups Mora, S. et al. Circulation 2005;112:1566 1572
Clinical Implications Does this supplant the emphasis on diagnostic testing with imaging?
Adjusted Predicted 8 Year Mortality Treatment Implications of HRR 0.35 N=8861 508 revascularization 929 deaths 0.30 0.25 0.20 Revascularization 0.15 0.10 0.05 No Revascularization 0 10 20 30 HR Recovery (beats per minute) Chen M, Lauer M Circulation 2004;110:2851 7. 40