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NONINVASIVE DIAGNOSIS IN CORONARY ARTERY DISEASE Nora Goldschlager, M.D. MACP, FACC, FAHA, FHRS Cardiology - San Francisco General Hospital UCSF Disclosures: None CHEST PAIN NOT DUE TO MYOCARDIAL ISCHEMIA • • • • • • • • Pericarditis Aortic dissection Esophageal spasm/rupture/reflux Peptic ulcer disease Cervical spine disease Pulmonary embolism Musculoskeletal Mediastinitis/pneumomediastinum MYOCARDIAL ISCHEMIA NOT DUE TO CORONARY ARTERY DISEASE • Aortic valve disease (aortic stenosis) • Hypertrophic cardiomyopathy (obstructive and nonobstructive) • Dilated cardiomyopathy • Tachycardia • Hypertension • Coronary artery embolism • Syndrome X (chest pain, and positive treadmill, normal coronary arteries on angiography) • Coronary artery dissection (e.g., Ao dissection, cocaine) • Coronary arteritis • Tako-tsubo cardiomyopathy ASSESSMENT OF RISK FOR CORONARY ARTERY DISEASE • Is CAD known to be present (past angina, MI)? • If CAD is not known to be present, what is the risk profile? (lipids, blood pressure, diabetes, family history, smoking) • What are the symptoms and what brings them on? • Are there physical findings of acute ischemia? of past MI? • Are there ECG abnormalities, and are they reversible? • What is the response to sublingual nitroglycerin? ISCHEMIC CHEST PAIN SYNDROMES • Stable effort angina • Crescendo angina • Acute coronary syndromes - Unstable angina - Acute MI: ST elevation, non ST elevation WOMEN: PROBLEMS IN MANAGEMENT OF CHD • Significant gender gap in MI mortality • Women, particularly younger women, have a more adverse CHD prognosis than men • Adjustment for disease severity, comorbidity and treatment does not fully account for the gap • Women with normal or minimal CAD have an adverse prognosis that is comparable to diabetics PATHOPHYSIOLOGY OF MYOCARDIAL ISCHEMIA IN WOMEN Outcomes Following Normal/Minimal CAD at Cath Outcomes Following Significant CAD at Cath • 29% perfusion abnormality • 65% persistent symptoms at 5 years despite conventional med Rx • 10% required rehospitalization for symptoms • Less obstructive stenoses • More myocardial ischemia • More unstable angina and fewer transmural infarcts • More adverse prognosis compared to men WHY DO WOMEN HAVE A MORE ADVERSE CHD PROGNOSIS? • Not due to atypical presentation • Not due to age • Not due to comorbitidy • Not due to gender gap in medical therapy • Not due to more advanced angiographic CAD • Differences in physiological vascular function (endothelial and microvascular reactivity) are likely (?partial) explanations WISE STUDY: WOMEN’S ISCHEMIA SYNDROME EVALUATION SHORT-TERM RISK OF DEATH OR NONFATAL MI IN PATIENTS WITH UNSTABLE ANGINA - 1 HIGH INTERMEDIATE Hx Acclerating tempo of ischemic sx in 48 h Prior MI, peripheral or cerebrovascular disease, or CABG/PCI, prior ASA use Pain Prolonged ongoing (> 20 min) rest pain Prolonged (> 20 min) rest angina, resolved, with moderate or high likelihood of CAD Rest angina (<20 min) or relieved with rest or SL NTG Clinical Pulmonary Age 70 yrs edema, new or worsening MR, S3 or new/ worsening rales, hypotension, bradycardia, tachycardia Age > 75 yrs LOW New onset or progressive Class III or IV angina in 2 wks, with moderate or high likelihood of CAD SHORT-TERM RISK OF DEATH OR NONFATAL MI IN PATIENTS WITH UNSTABLE ANGINA - 2 HIGH ECG INTERMEDIATE Angina at rest T-wave inversion with transient ST-segment changes Pathological Q> 0.05 mV waves LOW Normal or unchanged during chest discomfort BBB, new or presumed new Sustained VT Cardiac Elevated markers Slightly elevated Normal TIMI RISK SCORE for UA/NSTEMI Historical POINTS Age 65 1 3 CAD risk factors 1 (FHx, HTN, chol, DM, smoker) Known CAD (stenosis 50%) 1 ASA use in past 7 days 1 Presentation Recent ( 24 h) severe angina cardiac markers 0.5 mm ST 1 1 1 RISK SCORE: Total Points (0-7) 14-DAY RISK OF CARDIAC EVENTS (%) RISK SCORE 0/1 2 3 4 5 DEATH/MI DEATH/MI URGENT REVASC 3 4 5 7 12 5 8 13 20 25 TIMI RISK SCORE for STEMI Historical Age 75 65-74 DM, HTN or angina POINTS 3 2 1 RISK SCORE 30-DAY MORTALITY (%) Exam SBP < 100 mmHg HR > 100 bpm Killip II-IV Weight < 67 kg 3 2 2 1 0 1 2 6 0.8 1.6 2.2 4.4 Presentation Anterior STE or LBBB Time to Rx > 4 hrs 1 1 8 >8 27 36 RISK SCORE Total points (0-14) EVALUATION AND MANAGEMENT OF PATIENTS WITH SX SUGGESTIVE OF ACS Possible ACS Definite ACS No ST Nondiagnostic ECG Normal initial cardiac markers ST ST and/or T wave changes Ongoing pain Evaluate for + cardiac markers reperfusion Observe FU at 4-8 hours ECG, cardiac markers No recurrent pain - FU studies Recurrent ischemic pain or + FU studies: Dx confirmed Stress study to provoke ischemia Evaluate LV function if ischemia - : Potential diagnoses: nonischemic +: Dx confirmed CP, low-risk ACS OP FU ACC/AHA Guidelines 2002 Admit Rx for ACS BIOCHEMICAL CARDIAC MARKERS IN PATIENTS SUSPECTED OF HAVING AN ACS - 1 Marker Advantages Troponin Powerful tool Low sensitivity for risk in very early stratification phase of MI (< 6 h after symptom onset) Greater sensitivity and specificity Detection of MI up to 2 weeks after onset Disadvantages Limited ability to detect late minor reinfarction Recommendation Useful as a single test to diagnose NSTEMI (including minor damage) BIOCHEMICAL CARDIAC MARKERS IN PATIENTS SUSPECTED OF HAVING AN ACS - 2 Marker Advantages Disadvantages Recommendation CK-MB Rapid, costefficient, accurate assays specificity in Prior standard still setting of acceptable in most clinical skeletal muscle circumstances disease or injury Ability to detect early reinfarction low sensitivity during very early MI (< 6 h after sx onset or later (> 36 h) and for minor myocardial damage detectable by troponins) STENOSIS SEVERITY PRIOR TO MI MI patients (n) 200 160 120 Stenosis prior to MI > 70% 50-70% < 50% 80 40 0 Ambrose 1998 Little 1968 Nobuyoshi 1991 Giroud 1992 All PATHOPHYSIOLOGY OF ACUTE CORONARY SYNDROMES 2006 Plaque Disruption / Erosion Thrombus formation & Embolization Unstable Angina Non-ST Elevation MI ST Elevation MI Atherosclerosis: Traditional vs. Contemporary Model Traditional Contemporary Coronary remodeling concealing extensive disease Nissen, S. E. J Am Coll Cardiol 2003;41:103S-112S Copyright ©2003 American College of Cardiology Foundation. Restrictions may apply. CLINICAL PRESENTATION OF MYOCARDIAL ISCHEMIA • Chest pain/pressure/burning/ fullness/squeezing • Epigastric discomfort/fullness/burning • Jaw/throat/tooth pain • Shoulder/back discomfort • Breathlessness • Fatigue • Acute or worsening peripheral vascular insufficiency • Dizziness, syncope THE OLDER THE PATIENT THE LESS CLASSIC THE PRESENTATION PHYSICAL EXAMINATION DURING ACUTE MYOCARDIAL ISCHEMIA / INFARCTION • S3 gallop • • • • • • Paradoxically split S2 Soft S1 (PR interval , dP/dt) Mitral regurgitation murmur (transient) Hypotension Alterations in pulse volume Pallor, diaphoresis, anxiety, tachycardia (nonspecific) ECG FINDINGS IN ACS • ST-T abnormalities - ST elevation - ST depression - Pseudonormalization • Intraventricular conduction delay • Transient Q waves DURING PAIN AFTER PAIN Pseudonormalization of T-wave inversion during angina PITFALLS IN THE ECG DIAGNOSIS OF ACUTE MI • Nonspecific ST/T-wave abnormalities • Age of Q-waves (may not be known) • Early repolarization pattern • Paced ventricular rhythm • Left bundle branch block • Right bundle branch block: secondary ST-T abnormalities in V1-3 can mimic anterior-wall MI; tall R-waves in V1-2 can mimic posterior-wall MI • Nonspecific intraventricular conduction delay with repolarization abnormalities • Atrial flutter with flutter waves pseudo ST or • Double standardization PERICARDITIS vs EARLY REPOLARIZATION DIAGNOSIS OF ACUTE MI IN LBBB • 1 mm ST segment change in same direction as terminal QRS • More than 5 mm ST elevation in direction opposite to QRS • Sgarbossa criteria (NEJM 1996;334:481) - ST-elevation > 1 mm in lead with concordant QRS complex - ST-depression > 1 mm in leads V1, V2 or V3 - ST-elevation > 5 mm in lead with discordant QRS complex 5 points 3 points 2 points Same patient, baseline ECG obtained 6 months earlier PITFALLS IN THE ECG DIAGNOSIS OF ACUTE MI: MI MIMICS • Hyperkalemia • Myocarditis • Post-defibrillation • Pericarditis with PR depression (scooped ST segments) • Early repolarization • LVH • Wide QRS complex tachycardias • Left anterior fascicle block (poor R wave progression; q V2-3, I, aVL) • Left posterior fascicle block (q II, III, aVF) • WPW patterns • Pneumothorax with mediastinal shift WPW MIMICKING INFEROPOSTERIOR WALL MI WPW MIMICKING INFERIOR WALL MI HYPERKALEMIA vs ANTERIOR WALL MI vs BRUGADA SYNDROME Flutter - Pseudo ST elevation PR ST scoop EFFECT ON OUTCOMES OF MISSING HIGH RISK (ACUTE INJURY MI) ECG IN THE ED • Missed Dx – 12% (5–15%) • Effect on Rx (odds ratio) No ASA – 2.13 No –blocker 1.85 • Mortality 7.9% ( vs 4.9% in ECG dx made correctly) • Correlates of missed Dx Advanced age HF history No chest pain • ECG patterns in missed Dx STE 8% ST DEP 18% T inversion 14% Masoudi et al Circulation 2006; 114:1565. N = 1684, 2 yr retrospective multicenter study ESOPHAGEAL PAIN More likely to: - Continue for hours, rather than stuttering - Be retrosternal, without lateral radiation - Be nonexertional - Interrupt sleep - Be meal-related - Be relieved with antacids - Be associated with heartburn, dysphagia, regurgitation SOME REASONS TO PERFORM ECHO IN PATIENTS WITH CHEST PAIN AND SUSPECTED CAD Suggestive of CAD - Segmental wall motion abnormalities (prior MI/ischemia) - Reduced ejection fraction with WMA (ischemic cardiomyopathy) Not necessarily suggestive of CAD - LVH (hypertension, hypertrophic cardiomyopathy) - Aortic valve stenosis - Intimal flap of aortic dissection - Reduced ejection fraction - no segmental WMA - RVH CLINICAL USES OF EXERCISE TESTS • Evaluation of chest pain syndromes - Effort angina: stable, crescendo - Atypical chest pain, cardiac origin - Atypical chest pain, noncardiac origin • Assessment of effort tolerance - Post-myocardial infarction - Post-revascularization - Valve disease • Chronotropic competence • Evaluation of rate control in AF • Evaluation of Rx of CAD (medical, surgical, post-PCI) CLINICAL USES OF EXERCISE TESTS • Evaluation of blood pressure Rx in hypertension • Detection of myocardial ischemia in pts at high risk for CAD • Exercise prescription and riskstratification post-MI • Detection of exercise arrhythmias - Due to myocardial ischemia - Symptoms of cerebral hypoperfusion with exercise • Survivors of out-of-hospital cardiac arrest ACC/AHA 2007 CLINICAL EXPERT CONCENSUS DOCUMENT ON CT CORONARY ARTERY CALCIUM SCORING What is the role of coronary calcium measurement by coronary CT scanning in asymptomatic patients with intermediate CHD risk (between 10% and 20% 10-year risk of estimated coronary events)? It may be reasonable to consider use of CAC measurement based on evidence that demonstrates incremental risk prediction information in this patient group. Such patients might be reclassified to a higher risk status based on high CAC score, and subsequent patient managementmay be modified. What is the role of coronary calcium measurement by CT scan in patients with low CHD risk (below 10% 10-year risk of estimated CHD events)? Use of CAC measurement not recommended. This patient group is similar to the “population screening” scenario; screening of the general population is not recommended. ACC/AHA 2007 What is the role of coronary calcium measurement by fast CT scan in asymptomatic patients with high CHD risk (greater than 20% estimated 10-year risk of estimated CHD events, or established coronary disease, or other high-risk diagnoses)? The Committee does not advise CAC measurement as they are already candidates for intensive risk reducing therapies. ACC/AHA 2007 Is the evidence strong enough to reduce treatment intensity in patients with calcium score = 0 in patients who are intermediate risk before coronary calcium score? No evidence is available that allows a consensus. Current standard recommendations for treatment of intermediate risk patients should apply. ACC/AHA 2007 Is there evidence that coronary calcium measurement is better than other potentially competing tests in intermediate risk patients for modifying risk estimate? CAC measurement has not been compared to alternative approaches to risk assessment in head-to-head studies. This question cannot be adequately answered from available data. ACC/AHA 2007 Should there be additional cardiac testing when a patient is found to have high coronary calcium score (e.g., greater than 400)? Current practice guidelines indicate that patients at high risk (e.g., diabetes) are candidates for intensive preventive medical treatments. There is no clear evidence that additional non-invasive testing in this population will result in more appropriate selection of treatments. ACC/AHA 2007 Is there a role of CAC testing in patients with atypical cardiac symptoms? Patients at low risk of coronary disease by virtue of atypical cardiac symptoms may benefit from CAC testing to help in ruling out presence of obstructive coronary disease. Other approaches are available, and most of these have not been compared head-tohead with CAC. ACC/AHA 2007 Can coronary calcium data collected to date be generalized to specific patient populations? CAC data are strongest for Caucasian, non-Hispanic men. The Committee recommends caution in extrapolating CAC data derived from studies in white men to women and to ethnic minorities. ACC/AHA 2007 What is the appropriate follow-up when an incidental finding in the lungs or other non-cardiac tissues is found on a fast coronary CT study? Current radiology guidelines should be considered when determining need for follow-up of incidental findings. ACC/AHA 2007 PRE TEST PROBABILITY OF CAD • Patient population – Asymptomatic (Framingham Risk Score) • Low risk - < 10% event rate in 10 years • Intermediate risk – 10-20% event rate • High risk - > 20% event rate – Symptomatic (Diamond and Forrester – NEJM 1979) • Non anginal chest pain • Atypical angina • Definite angina CORONARY ARTERY CALCIUM SCREENING: ESTIMATED RADIATION DOSE AND CANCER RISK • Median dose from a single scan – 2.3 mSv Approx 250 chest x-rays • 10 fold variation between scans 0.8 – 10.5 mSv • Cancer risks for serial scans (q 5 years) for middle aged persons (45 – 75 yrs) 42 excess cancers per 100,000 men 62 excess cancers per 100,000 women LIMITATIONS OF CURRENT CORONARY CALCIUM DATA • Highly selected populations, – All patients referred to cath lab for coronary angio – High pre-test probability • Excluded technically inevaluable patients from denominator – Falsely inflates accuracy • No outcomes data