Coronary Artery Disease in the 21 st Century: An Integrated Approach Based on Science and Art

Transcription

1 Coronary Artery Disease in the 21 st Century: An Integrated Approach Based on Science and Art Harisios Boudoulas, MD, Dr, Dr. Hon. Professor, Honorary Professor, Academician

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3 Development of Coronary Artery Disease (CAD): Genetic and Environmental Factors Smoking Inflammatory Process Hypertension Inhibitory Genes Lack of Exercise Stress Diabetes Promotor Genes Fatty Diet Other Renal Disease Other CAD

4 CAD: Development and Progression Remodeling Progression Inflammation, neo-vessel (v-v): Unstable plaque-rupture - thrombosis Stabilization-regression Atherosclerotic plaque: Has changed over last century? Is similar in all ages?

5 CAD: Progression and Clinical Manifestations Normal Lipid Pool Plaque Rupture and Thrombosis Thrombosis/ Progression/ Angina AMI Ischemic Myopathy Asymptomatic Stable Disease (± Angina) Years Plaque rupture Chest Pain (Atypical) Thrombosis Occlusion Angina (Unstable) Death

6 CAD: A Pathophysiologic Basis for Diagnosis and Therapy Genetics Environment Progression / Chronic obstruction ± Angina Stable Plaque Early diagnosis Unstable Plaque / Rupture / Thrombosis / Acute Coronary Syndrome Loss of Myocardial Cells / LV Remodeling, Myopathy, CHF Sudden Death

7 CAD: Early Diagnosis Plaques Which May Produce MI Can Not be Detected by Stress Induced Ischemia Stress ECG Stress Echo Stress Nuclear We had the experience but missed the meaning. - T.S. Eliot

8 CAD: Diagnostic Considerations for the Individual Patient Coronary angiography Diagnosis based on other parameters Identification of plaque (MSCT, other) Detection of atherosclerotic process in other arteries Carotid Lower extremities Aorta Calcium detection in the coronary arteries (?) The role of stress testing Villines TC et al. JACC 2011; 58: 2533 (Score 0) Allison MA et al. Ath Thromb Vasc Biol 2012; 32: (Calcified atherosclerosis in different vascular beds) Ann Int Med 2012; July 31

9 CAD: A Pathophysiologic Basis for Diagnosis and Therapy Genetics Environment Progression / Chronic obstruction ± Angina Stable Plaque Early diagnosis Unstable Plaque / Rupture / Thrombosis / Acute Coronary Syndrome Loss of Myocardial Cells / LV Remodeling, Myopathy, CHF Sudden Death

10 CAD: Therapy for the Plaque To Prevent D/C Smoking Cholesterol (Statin) Antiplatelet b- Blocker ACEI ICD Inter-ve ntion Progression Rupture Thrombosis Infarction? Death Moderate exercise; Mediterranean diet; niacin? The role of vitamin D Circ Cardiovasc Genet 2012 Jan 9. JACC 2012; 59: Ross AC et al. J Clin Endocrinal Metab 2011; 96: 53-58

11 CAD: A Pathophysiologic Basis for Diagnosis and Therapy Genetics Environment Progression / Chronic obstruction ± Angina Stable Plaque Early diagnosis Unstable Plaque / Rupture / Thrombosis / Acute Coronary Syndrome Loss of Myocardial Cells / LV Remodeling, Myopathy, CHF Sudden Death

12 CAD: Clinical Significance of Left Ventricular (LV) Function LV systolic function is a stronger prognostic indicator compared to number of diseased vessels. Coronary bypass surgery and/or β-blockade therapy increased survival only in patients with abnormal left ventricular systolic function. Boudoulas, O Neil, Weissler, et al. Circulation 1981, Am J Cardiol 1981, Circulation CASS (Coronary Artery Surgery Study). Circulation 1983

13 CAD: Therapy for LV to Preserve / Improve Function Goal Therapy for plaque β- Blocker ACEI Intervention Thrombo-l ysis. Cell Stabilize Plaque, Prevent Rupture, Thrombosis, MI? Infract size Improve Function Prevent Death?

14 Cell Based Therapy / Biomaterial Intracoronary infusion Direct intramyocardial injection Epicardial (Surgery) Endocardial (Percutaneous) Boudoulas KD et al. Dis Model Mech 2009; 2: Rane AA et al. JACC 2011; 58: Hensch G. JACC 2011: 58; Cheng K. JACC 2012; 59: Circulation 2012; 126;

15 CAD: A Pathophysiologic Basis for Diagnosis and Therapy Genetics Environment Progression / Chronic obstruction ± Angina Stable Plaque Early diagnosis Unstable Plaque / Rupture / Thrombosis / Acute Coronary Syndrome Loss of Myocardial Cells / LV Remodeling, Myopathy, CHF Sudden Death

16 CAD: Therapy to Prevent Progression, Ischemia, and to Treat Angina To Prevent Therapy for Plaque β-blocker Nitrates Ca Blocker Intervention Progression / Ischemia / Angina Infarction, Stabilize Plaque, Prevent MI LV Dysfunction Death Other pharmacologic agents (Procoralan, Ranolazine); smoking cessation, statin. Heart rate 60 beats/min

17 CAD: A Pathophysiologic Basis for Diagnosis and Therapy Genetics Environment Progression / Chronic obstruction ± Angina Stable Plaque Early diagnosis Unstable Plaque / Rupture / Thrombosis / Acute Coronary Syndrome Loss of Myocardial Cells / LV Remodeling, Myopathy, CHF Sudden Death

18 CAD: Sudden Death Plaque rupture, Thrombosis, Ischemia, MI LV dysfunction, Myocardial scar, Fibrosis, Sympathetic innervation Sudden Death Progression Ischemia Stress, Autonomic dysfunction

19 This is my hand. I can move it, feel the blood pulsing through it. The sun is still high in the sky and I, Antonius Block, am playing chess with Death. Seventh Seal, Ingmar Bergman

20 CAD: Therapy to Prevent Sudden Death Purpose Therapy for plaque β- Blocker ACEI ICD Intervention Thrombolysis. Exercise Prevent Plaque Rupture, Thrombosis, MI? Infarct Size Improve LV Function Prevent Ischemia Improve / Treat Electrical Instability Improve Autonomic function

21 CAD: The Role of the Aorta and the Kidneys Stiff aorta: Myocardial perfusion, MVO 2 Chest pain of aortic origin Atherosclerosis stroke during coronary bypass Renal disease is associated with higher cardiovascular morbidity and mortality

22 CAD: Issues to Consider Influenza vaccination Pneumonia vaccination Stress management (shift work) The role of vitamin D Elective general surgery (hip, knee) Coexistent disease / disorders JACC 2012; 54: JACC 2012; 307: Arch Int Med 2012; July 23 Br Med J 2012; July 26 Circulation 2012;126:

23 CAD: Prognosis is Related to Overall Disease and Status of LV function Progression/ Angina AMI Ischemic Myopathy Stable Disease (± Angina) Occlusion Angina (Unstable) Death

24 CAD: Approach to the Individual Patient Pharmacologic Agents Stent Bypass The Superior Physician He is skeptical toward the data of his own profession, welcomes discoveries which upset his previous hypothesis, and still animated by human sympathy and understanding. - Alfred North Whitehead, Dialogues (Lucien Press) 1954

25 Stable CAD: Medical versus Interventional Therapy Stress testing Fractional flow reserve / IVUS / OCT / other Percutaneous - surgical intervention Total occlusion Drug eluting versus bared metal stents Syntax score Diabetes, renal disease Age and gender; the very young and the very old

26 Stable CAD: Initial Therapeutic Approach Medical therapy for most patients with chronic stable angina should be the initial approach. Revascularization: persistent symptoms - large area of myocardium at risk The greater the severity of ischemia, extent of disease and LV dysfunction the greater the benefit on survival from revascularization over medical therapy. Circ Cardiovasc Interv 2012;5:

27 CAD: Myocardium at risk Myocardium at risk

28 CAD: Viable Myocardium MRI PET Dobutamine echo Thallium Other Bonow R et al. N Engl J Med 2011; 364: (Viability) Lee WW. JACC 2012; 59: (Inflammation)

29 PCI Does not protect from lesions either proximal or distal to the site of the stent. Distal embolization Restenosis. Long term dual antiplatelet therapy. Suboptimal results in diabetes, chronic kidney disease, vein grafts. Differences Between PCI and CABG Stent Bypass CABG Protects from future cardiovascular events if lesions proximal to anastomosis develop or rupture. More complete revascularization compared to PCI. LIMA excellent long term results. Surgical mortality Problems related to vein grafts Stroke / brain damage; off pump

30 Stable CAD: Interventional Therapy Available information should apply to individual patient Left main or equivalent 3 VD with EF < 50% or large area of ischemia 3 VD (prox. LAD), normal EF especially in diabetics 2 VD (prox. LAD), EF < 50% or large area of ischemia 1-2 VD (no prox. LAD), post cardiac arrest or VT Proximal LAD Symptom control 2-3 VD (prox. LAD), normal LV, no diabetes Restenosis, large area of ischemia 1-2 VD (no prox. LAD), LV dysfunction or large area of ischemia Consider CABG Consider PCI

31 Hybrid Cardiovascular Operating Room Operating Room Catheterization Lab Vanderbilt University Hybrid OR/Lab First in USA

32 Coronary Artery Disease in the 21 st Century: An Integrated Approach based on Science and Art Concluding Remarks A plaque producing small degree of stenosis (asymptomatic) may rupture resulting in acute coronary syndrome or sudden death. Diagnosis of CAD by stress induced ischemia may be too late. Aggressive medical management may stabilize unstable plaque and prevent rupture. Prognosis is related to overall disease and status of LV function and not only to a single lesion Preservation or improvement of LV function is of great clinical significance.

33 Coronary Artery Disease in the 21 st Century: An Integrated Approach based on Science and Art Concluding Remarks Medical therapy in most patients with stable angina should be the initial approach. Revascularization should be reserved for patients with persistent symptoms despite optimal medical therapy and those with large area of myocardium at risk. CABG and PCI are complementary; each approach has advantages and limitations (Hybrid approach). Left internal mammary (chest) artery gives excellent long term results; this may be the single most important factor for the superiority on survival of CABG vs PCI.

34 Coronary Artery Disease in the 21 st Century: An Integrated Approach based on Science and Art Concluding Remarks Coronary atherosclerosis is a dynamic disease process and our understanding of atherosclerosis is evolving continuously. Data from epidemiology or randomized studies should be applied to the individual patient. The greatest challenge for the clinician in the 21 st century is not in absorbing the new knowledge but rather in applying this knowledge to the individual patient. Where is the wisdom we have lost in knowledge? Where is the knowledge we have lost in information? - T.S. Eliot

35 CAD: Quo Vadis? Areas of Special Interests for Research Why patients without risk factors develop coronary atherosclerosis? Early accurate noninvasive diagnosis of atherosclerotic plaque (CT, MRI, molecular imaging, other) Define and monitor noninvasively the natural history of high risk (unstable) atherosclerotic plaque Define patients at risk for stent thrombosis Define the role of inflammation and anti-inflammatory therapy (methotrexate) Better stratify patients at high risk for sudden death Cell therapy Pharmacogenetics/pharmacogenomics Define the role of neo-vessels (vasa-vasorum) Define the role of genes promoting or inhibiting coronary atherosclerosis (genome-wide association studies) TA PANTA REI HRAKLEPOS There is nothing permanent except change.

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38 CAD: Therapy Plaque: stabilize / prevent progression rupture thrombosis acute coronary syndrome Left ventricle (LV): preserve / improve function Angina: prevent progression ischemia, treat angina Sudden death: prevent Need diagnosis before therapy

39 CAD: Therapy Plaque: stabilize / prevent progression rupture thrombosis acute coronary syndrome Left ventricle (LV): preserve / improve function Angina: prevent progression ischemia, treat angina Sudden death: prevent Need diagnosis before therapy

40 CAD: Therapy Plaque: stabilize / prevent progression rupture thrombosis acute coronary syndrome Left ventricle (LV): preserve / improve function Angina: prevent progression ischemia, treat angina Sudden death: prevent Need diagnosis before therapy

41 CAD: Therapy Plaque: stabilize / prevent progression rupture thrombosis acute coronary syndrome Left ventricle (LV): preserve / improve function Angina: prevent progression ischemia, treat angina Sudden death: prevent Need diagnosis before therapy

42 CAD: Therapy Plaque: stabilize / prevent progression rupture thrombosis acute coronary syndrome Left ventricle (LV): preserve / improve function Angina: prevent progression ischemia, treat angina Sudden death: prevent Need diagnosis before therapy

43 IV CAD: Acute versus Stable Stable CAD Intervention Intervention FC Medical Medical I IV Acute Coronary Syndrome Intervention FC Medical I Time Antithrombotic therapy (Xa inhibitor, Rwa-receptor, roxaban) N Engl J Med, Nov Eur Heart J 2012; 33: Sex/gender Differences in Cardiovascular Disease. Mosca L et al. Circulation 2011; 124:

44 Stable CAD: Medical Therapy Improves symptoms and in stable disease is not inferior to interventional therapy in regard to survival As medical therapy becomes better, interventional therapy looks better as well (free ride) Therapy with statins ( LDL, endothelial fx, anti-inflammatory, other effects): Improves survival, decreases incidence of MI, stroke and need for revascularization Therapy with antiplatelet agents (ASA, clopidogrel, other): Prolongs life, decreases incidence of MI and stroke Therapy with b-blockers / ACE inhibitors: Improves symptoms, increases survival, prevent MI mostly in patients with LV dysfunction Other