Ischemia and Myocardial Infarction with Non-obstructive CAD

Transcription

1 Ischemia and Myocardial Infarction with Non-obstructive CAD Noel Bairey Merz MD, Janet Wei MD, Chrissandra Shufelt MD, Margo Minissian ACNP-BC, Saibal Kar MD, Bruce Samuels MD, Babak Azarbal MD, Tim Henry MD Women s Heart Center Cedars Sinai Heart Institute Los Angeles

2 Presenter Disclosure Bairey Merz Information DISCLOSURE INFORMATION The following relationships exist related to this presentation (*paid to Cedars-Sinai Medical Center): Grant support*: NHLBI, FAMRI, Gilead, Louis B Mayer Foundation, Erika J. Glazer Women s Heart Research Initiative, NIH-CTSI, California Institute of Precision Medicine (CIAPM), Abbott Diagnostics Consulting*: Medscape, Gilead, NIH, Sanofi Vascular Honorarium*: Practice Point, Pri-Med Stocks: None

3 Mechanisms of Myocardial Infarction: Atherosclerotic and Non-atherosclerotic Prevalence and Prognosis Pathophysiology Diagnosis Treatment Next Steps

4 MI with no obstructive CAD (MINOCA): Women have a two-fold increase in normal coronary arteries in the setting of ACS, NSTEMI and STEMI Bugiardini and Bairey Merz JAMA 2005;293:477-84

5 Prevalence of Coronary Vascular Dysfunction Approximately 50% of patients with: persistent chest pain non-obstructive coronary artery disease have physiologic evidence of coronary vascular dysfunction. Takotsubo cardiomyopathy (TCM) And spontaneous coronary artery dissection (SCAD) have 10-15% Recurrence, and frequently have persistent chest pain. Reis AHJ 2001; Pepine JACC 2008; Hasdai D et al. Mayo Clin Proc. 1998; EHJ 2016

6 What is the Prognosis? p=0.20 In-hospital outcomes: CRUSADE registry Gehrie et al AHJ % death or MI in-hospital in TIMI IIIA study with non-obstructive CAD 2% cardiac death + 2.1% MI over one year in HORIZONS with non-obs CAD 10% readmission for unstable angina over one year in TIMI meta-analysis Diver et al AJC 1994, Planer et al Circ Intervention 2014, Bugiardini R et al Arch Int Med Slide courtesy of H Reynolds

7 Mechanisms of Myocardial Infarction: Atherosclerotic and Non-atherosclerotic Prevalence and Prognosis 10% MINOCA Adverse prognosis Pathophysiology Diagnosis Treatment Next Steps

8 Mechanisms MI with non-obstructive CAD Slide courtesy of H Reynolds MD

9 How frequent is plaque disruption in MI with non-obstructive CAD? Prospective cohort studies 50 women, IVUS of 2 vessels, ~2 days 38% 68 men and women, IVUS, <24 hours 37% Only clinical correlate of plaque rupture/ ulceration in both studies: % angiographic stenosis No angiographically normal patients with plaque disruption in these small studies For comparison, plaque rupture in 49% of STEMI cases (OCT ~2 hours, OCTAVIA) Slide courtesy of H Reynolds MD Reynolds et al Circ 2011, Ouldzein H et al Ann Cardiol Angeiol 2012 Guagliumi et al JACC Interventions 2014

10 1615PC Bairey-Merz/Slide # 10

11 Morphology of Intramyocardial Emboli in Epicardial Plaque Thrombosis Women vs. men: Any emboli: 73% vs. 37%, p<.001 Mean emboli: 12 ± 3 vs. 4 ± 1, p=.02 Acute myocardial necrosis: Any emboli: 88% vs. 39%, p<.001 Mean emboli: 18 ± 5, 4 ± 1, p<.001 CD61 EM Burke and Virmani R et al, In press Fibrin II 1615PC Bairey-Merz/Slide # 11

12 Mechanisms of Myocardial Infarction: Atherosclerotic and Non-atherosclerotic Prevalence Pathophysiology Plaque rupture/erosion and embolization Coronary macro and microvascular spasm Takotsubo cardiomyopathy Myocarditis Non-atherosclerotic SCAD Diagnosis Treatment Next steps needed Atherosclerotic At least 50-60%

13 Scheme of the potential causes and consequences of coronary microvascular dysfunction-related MINOCA Subendocardial or Epicardial Ischemia Coronary atherosclerosis PlaqueRupture/Erosion Risk Factor Conditions Hypertension, Dylipidemia, Dysglycemia Inflammatory and prooxidative stress Accelerating Factors Early Menopause Obesity Sympathetic nervous system activation, endothelial dysfunction, changes in vascular smooth muscle activation, spasm Coronary Microvascular Dysfunction Takotsubo Cardiomyopathy Crea, Camici, Bairey Merz EHJ 12/13

14 Invasive Testing 2006

15 Indications For Invasive Coronary Reactivity Testing Evidence of ischemia (INOCA or MINOCA) + No obstructive CAD + Persistent chest pain Chest pain refractory to medical management Preference for definitive diagnosis We cite a 1/600 (IVUS)-1,000 (CRT) SAE; Wei JACC Intervention 2012

16 Catheterization Laboratory Set Up Cath Lab with facilities to perform Quantitative Coronary Angiography IVUS side-by-side with Angio Doppler Flow Wire for measurement of coronary blood velocity (IMR OK) Plug and Play digital imaging Bedside Controller at your fingertips

17 Coronary Reactivity Testing - Interpretation Non-Endothelial Dependent Endothelial Dependent Microvascular Dysfunction CFR in response to adenosine 2.5 Change in CBF in response to acetylcholine < 50% Macrovascular Dysfunction Change in coronary artery diameter in response to nitroglycerin < 20% Change in coronary artery diameter in response to acetylcholine < 0% Coronary Spasm Chest Pain + EKG changes +/- Change in coronary artery diameter in response to acetylcholine <90% CBF: CSA of coronary artery x average peak velocity /2

18 Coronary Reactivity Testing Reporting Findings 1. Nonobstructive coronary artery atherosclerosis. 2. Elevated LVEDP (23 mmhg). 3. No evidence of heightened cardiac nociception. 4. Elevated resting average peak velocity (29 cm/sec), suggesting abnormal resting coronary vasomotor tone. 5. Diffuse coronary vasospasm to high dose acetylcholine. Non-Endothelial Dependent Endothelial Dependent Microvascular Dysfunction CFR 3.9 (Abnl 2.5) CBF change -4.5% (Abnl < 50%) Macrovascular Dysfunction NTG +18% (Abnl < 20%) ACH +67% (Abnl < 0%)

19 Pursue non-invasive stress testing for objective evidence of ischemia Is patient able to exercise? Is baseline EKG ok to pursue ETT If yes, start with ETT: Elicit symptoms Detection of Ischemic EKG changes METS and functional capacity Arrhythmias Hypertensive response to exercise

20 If ETT inconclusive and/or persistent symptoms Add an imaging test Stress Echo (diastolic function, hypertrophy, pulmonary hypertension, valvular problems, WMA) Stress SPECT (rarely) PET-CT with Coronary Flow Reserve (added benefit of CAC) Adenosine Stress Cardiac Magnetic Resonance Imaging (added benefit of scar imaging and best for tissue characterization)

21 Noninvasive Testing 2008

22 CMRI LGE IMAGING: Troponin Leaks are not False Positives! Bakir JACC 2014:63:A391 and Wei et al Circulation manuscript (in press)

23 TOP) 56 year-old woman with diabetes, hyperlipidemia, hypertension, persistent angina and history of NSTEMI. LGE demonstrated distal anterior subendocardial scar (6g) without significant change at one year follow-up. Coronary reactivity testing revealed LAD atherosclerosis and microvascular endothelial dysfunction. BOTTOM) 26 year old woman with recurrent MIs (recent ramus artery spasm) and miscarriages. LGE revealed regions of mid-myocardial scar (11g) in inferior, basal septal, basal lateral and basal anterior wall. She had interval MI but no significant change in scar size. Wei JACC :A399 and Circulation manuscript (in press)

24 Mechanisms of Myocardial Infarction: Atherosclerotic and Non-atherosclerotic Prevalence Pathophysiology Diagnosis Advanced imaging with: OCT/IVUS CMRI-LGE CTA Treatment Next Steps

25 Treatment ACC/AHA guidelines do not specifically discuss secondary prevention for MINOCA patients ESC guidelines indicate dual antiplatelet therapy + statin (targeting atherosclerotic plaque rupture CMD capillary obliteration mechanisms) Is this appropriate for: Takotsubo (ACE may reduce recurrence)? Epicardial vasospasm (CCB reduces recurrence)? SCAD (FMD associated media hemorrhage)? Myocarditis?

26 Potential Treatment Targets for Angina and No Obstructive CAD Coronary Endothelial Dysfunction - ACE-I, Statins, L-arginine supplementation, Aerobic Exercise, Enhanced External Counterpulsation (EECP) Abnormal Non-endothelial Dysfunction (reduced CFR)- Betablockers/ alpha-beta blockers; nitrates,?pde5-i Coronary Smooth Muscle Dysfunction - Calcium Channel Blockers; Rho-kinase inhibitors (not available), nicorandil (not available) Anti-Anginal - Anti-Ischemic Ranolazine,?Aminophylline Abnormal Cardiac Nociception - Low Dose Tricyclic Medication, Spinal Cord Stimulation (TENS unit), Cognitive Behavioral Therapy Atherosclerosis Aspirin, Statin Elevated LVEDP ACE-I, aldosterone antagonist (eplerenone) Mehta PK and Bairey Merz CN. Braunwald s The Heart 9 th Edition 2011.

27 Low use of meds and elevated 1 year MI rate following angiographic non-obstructive CAD }

28 Mechanisms of Myocardial Infarction: Atherosclerotic and Non-atherosclerotic Prevalence Pathophysiology Diagnosis Treatment Empiric atherosclerotic-ihd Rx is reasonable (ASA/DAPT, statin, ACE/ARB, BB) Evidence to advise guidelines needed Next Steps

29 HARP Study PI Janet Wei/N Bairey Merz MD Can the prevalence of plaque disruption in MI with non-obstructive CAD be higher than 45%? 3-vessel imaging OCT (optical coherence tomography) improves detection of disrupted plaque Plaque rupture Plaque erosion Calcified nodule Dissection Slide courtesy of H Reynolds MD

30 Figure 3 WISE-HFpEF Study PI CN Bairey Merz MD - Proposed cascade of events in coronary microvascular dysfunction-related MINOCA, INOCA, and HFpEF Genetic and Environmental Factors Arteriolar Remodelling Microvascular Dysfunction MINOCA HFpEF Arrhythmias Sudden Death Myocardial Fibrosis and Scar Myocardial Ischemia LV Remodeling Diastolic and Systolic Dysfunction Crea, Camici, Bairey Merz EHJ 12/13

31 Ischemia and Myocardial Infarction with Non-obstructive CAD MINOCA occurs dominantly in women and is not a false positive MI! Differential can include plaque rupture, plaque erosion, epicardial or microvascular spasm, Takotsubo, spontaneous coronary dissection (SCAD), myocarditis Additional diagnostics should be used (OCT/IVUS, CMRI, CTA) A majority involve atherosclerosis Current US guidelines do not address MINOCA ESC guidelines - DAPT and high intensity statin Next step MINOCA research needed for evidencebased guidelines