10/22/16 Lay of the land Update on Acute Coronary Syndrome: Case - - PDF document

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Update on Acute Coronary Syndrome: Five Things Hospitalists Must Know

Dhruv S. Kazi, MD, MSc, MS Assistant Professor Department of Medicine (Cardiology), Department of Epidemiology and Biostatistics, Center for Vulnerable Populations, and Center for Health Care Value University of California San Francisco Division of Cardiology Zuckerberg San Francisco General Hospital Email: kazi@ucsf.edu Twitter: @kardiologykazi

Conflicts of Interest: None

Lay of the land

§ Case studies with an emphasis on discussions § Focus on five key take-home points § Grounded in evidence, not acronyms

Definition of ACS

§ Spectrum of clinical conditions that produce acute myocardial ischemia and/or infarction, usually due to an abrupt reduction in coronary blood flow.

Asymptomatic coronary dz à Stable angina à Unstable angina à NSTEMI à STEMI

Why do we worry about ST elevations?

§ We used to define MIs by Q waves: but those are fickle (early/transient, transient) § EKG criteria: ST elevations of ≥1mm in 2 contiguous leads or ≥2 mm in V2-V3. § ST elevation is a powerful predictor of occlusion or high- grade stenosis of epicardial coronary artery, determines management (early reperfusion), and is a marker of a higher in-hospital mortality

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Case 1:

A 62 year old woman with diabetes and hypertension presents with nausea, vomiting, 4/10 substernal discomfort, and 6/10 abdominal pain. In the ED, she is noted to be afebrile with a heart rate in the 90s, BP 155/95.

Presenting EKG:

MOC question

62yo woman with DM, HTN presenting with substernal discomfort, nausea, vomiting, and abdominal pain, with LBBB on initial EKG. What do you do next?

a. Don’t know if the LBBB is new, contact primary care doc for an old EKG b. LBBB makes the initial EKG uninterpretable, repeat EKGs every 10 minutes c. Request a stat echocardiogram for wall motion abnormalities d. Send off stat cardiac troponins, drill deeper into the history and clinical presentation e. LBBB is a STEMI-equivalent, activate the cath lab

Audience Response

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Anatomy of the conducting system

§ Right bundle is a discrete structure that is subendocardial for the proximal and distal thirds of its course (Cue: fragile) § Left bundle is a fan-like structure that quickly divides into the anterior and posterior fascicles (Cue: relatively resilient)

So why fret over LBBB?

§ 7% of patients who present with an acute MI have a LBBB on the presenting EKG § Almost half these patients did not have concomitant CP § Abnormal depolarization leads to abnormal repolarization, so ST-T changes not interpretable. § Produces delays in diagnosis and initiation of evidence- based therapies, and therefore adversely affects

• utcomes.

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§ Patients with old LBBB can occlude a coronary, we just wouldn’t see it on the EKG § Patients can have a new LBBB from causes other than ischemia § LBBB is not a STEMI equivalent – it simply makes a STEMI more challenging to diagnose.

Caveat emptor: MOC question

What do you do next?

a. Don’t know if the LBBB is new, call around for an old EKG b. LBBB makes the initial EKG uninterpretable, repeat EKGs every 10 minutes c. Request a stat echocardiogram for wall motion abnormalities d. Send off stat cardiac troponins, drill deeper into the history and clinical presentation e. LBBB is a STEMI-equivalent, activate the cath lab

MOC question

What do you do next?

a. Don’t know if the LBBB is new, call around for an old EKG b. LBBB makes the initial EKG uninterpretable, repeat EKGs every 10 minutes c. Request a stat echocardiogram for wall motion abnormalities d. Send off stat cardiac troponins, drill deeper into the history and clinical presentation e. LBBB is a STEMI-equivalent, activate the cath lab

Take-Home Point #1

The primary challenge with LBBB in the setting of acute chest pain is that it may mask an ongoing MI. In the setting of LBBB, the diagnosis of ACS comes down to a good clinical story. But even when ACS is established, cannot distinguish between an NSTEMI and a STEMI à hence the cath lab.

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Case 2:

§ 68 yo man with obesity, hypertension, and diabetes, 30 pack-year smoking history was driving home from work when he had a head-on collision with a truck operated by a drunk teenager. In the ED, he was in pain but hemodynamically stable, and noted to have multiple, displaced fractures of the pelvis and both lower

• extremities. On hospital day 4, he notes shortness of

breath and new 7/10 substernal chest pain. He is tachycardic 120s, normotensive, sating 94% on 2L nc. EKG showed sinus tachycardia and non-specific ST-T changes.

MOC question

What would you NOT do next?

• a. Obtain serial EKGs
• b. Send off cardiac troponins

c. Request an echocardiogram

• d. Obtain a CT chest with contrast
• e. Activate the cath lab

Audience Response

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Suspicion for ACS but initial EKG non- specific:

§ Look carefully for ST elevations: – Serial EKGs every 5-10 minutes – right-sided or posterior leads Right-sided infarct

§ Infarct of the RIGHT ventricle § Complicates inferior MI or isolated event § Obtain a right-sided EKG § Look for ST elevations in V4R § Echo may help

Posterior infarct

§ infarct the LEFT ventricle § Complicates inferior MI or isolated event § Obtain a posterior EKG § Look for ST elevations in V7-9 § Echo may help

Bottom line: Suspicion for ACS, evaluation must include Right-sided + Posterior EKGs.

Detectable Tropoinin = Death of Myocytes

§ Ischemia-mediated myocardial injury: – Decreased supply due to coronary disease: Plaque rupture, coronary vasospasm, dissection, vasculitis, embolic disease, cocaine/meth use – Decreased supply due to non-coronary conditions: shock, hypoxia, pulmonary embolism – Increased demand: tachycardia or severe hypertension, cocaine/meth use § Direct myocardial injury: – Myocarditis, chest trauma, toxic meds, electrical shock, CO exposure, heart failure, malignancy § Myocardial injury from other systemic conditions: – Sepsis, stress-cardiomyopathy, infiltrative diseases, stroke, sub- arachnoid hemorrhage, acute respiratory failure.

Cath lab?

§ Patients presenting with a NSTEMI may still benefit from an early invasive therapy if there are high-risk features: – Ongoing pain despite antiplatelet + anticoagulation – Electrical or hemodynamic instability – Heart failure Note that contemporary data suggest patients with NSTEMI and those presenting with a STEMI have similar one-year mortality.

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MOC question

What would you NOT do next?

• a. Obtain serial EKGs
• b. Send off cardiac troponins

c. Request an echocardiogram

• d. Obtain a CT chest with contrast
• e. “Activate” the cath lab

MOC question

What would you NOT do next?

• a. Obtain serial EKGs
• b. Send off cardiac troponins

c. Request an echocardiogram

• d. Obtain a CT chest with contrast
• e. “Activate” the cath lab

Take-home point #2

Ask yourself: Would this person benefit from early reperfusion? § ST elevations? § LBBB? à Think it through § Neither? – Obtain serial EKGs – Obtain right-sided and posterior-EKGs – Are there high-risk features? – Consider alternative explanations for an elevated troponin level

Take-home point #3

§ Even if it’s “just a NSTE-ACS”, many patients benefit from an early-invasive approach – Evidence of ongoing injury (e.g., unrelenting pain) – Electrical or hemodynamic instability – Heart failure

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Case 3:

63 yo man with diabetes and ongoing 1pack per day cigarette use presents with chest pain that woke him up from his sleep at 6am. In the emergency room, he is hemodynamically stable and chest pain free. Presenting EKG shows 2mm ST depressions in II, III, aVF, with no ST elevations in right-sided or posterior leads. Troponin I is 0.2 ng/dL (reference value < 0.04). A diagnosis of NSTEMI is made. Aspirin, statin, heparin, and metoprolol are initiated. The next day, coronary angiography reveals a 60% lesion of the mid-RCA and 50% lesion of the left anterior descending. LV systolic function is normal on the transthoracic echocardiogram. A decision is made to “medically manage” the coronary disease with aspirin, statin, an ACE-inhibitor, and a betablocker.

MOC question

Would our patient with an NSTEMI benefit from a second antiplatelet agent, even though he did not undergo PCI? a. No, patients who present with an NSTEMI but do not undergo a PCI were not included in trials of dual antiplatelet therapy, and bleeding risk exceeds any potential benefit b. Yes, I would start clopidogrel for six months because it is the

• nly agent studied in this context

c. Yes, I would pick prasugrel for nine months because it is a more potent antiplatelet agent that is not affected by CYP2C19 polymorphisms d. Yes, I would pick ticagrelor and use it for at least one year.

Audience Response

Does a patient who presents with an NSTEMI but does not undergo PCI still benefit from dual antiplatelet therapy?

§ Yes, this has been VERY WELL studied in randomized trials and observational data § One year of DAPT after medically managed NSTEMI § Remains an enormous evidence-practice gap in ACS management.

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All these categories of patients benefit from dual antiplatelet therapy: § STEMI, s/p PCI § STEMI, s/p fibrinolytics § STEMI, unrevascularized § NSTEMI, s/p PCI § NSTEMI, medical management § Unstable angina § Stable angina s/p PCI

Dual Antiplatelet Therapy for NSTEMI: The devil is in the details

§ Clopidogrel – Most well studied – Inexpensive ($10 per month) – Pro-drug, carriers of some polymorphisms of CYP2C19 may not achieve adequate platelet inhibition.

Kazi, el al. Annals of Internal Medicine, 2014

Dual Antiplatelet Therapy for NSTEMI:

§ Prasugrel – Potent antiplatelet agent, once a day dosing – Expensive ($400 per month) – Only indicated for ACS patients who have undergone PCI – Contraindicated in patients with a history of stroke or TIA § Ticagrelor – Potent, “reversible”, twice a day – Expensive ($350 a month) – Indicated for ACS patients, regardless of PCI – Ticagrelor-related dyspnea: usually self-limited

MOC question

Would our (NSTEMI) patient benefit from a second antiplatelet agent, even though he did not undergo PCI? a. No, patients who present with an NSTEMI but do not undergo a PCI were not included in the dual antiplatelet therapy studies, and bleeding risk likely exceeds any potential benefit b. Yes, I would start clopidogrel for six months because it is the

• nly agent studied in this context

c. Yes, I would pick prasugrel for nine months because it is a more potent antiplatelet agent that is not affected by CYP2C19 polymorphisms d. Yes, I would pick ticagrelor and use it for at least one year.

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MOC question

Would our (NSTEMI) patient benefit from a second antiplatelet agent, even though he did not undergo PCI? a. No, patients who present with an NSTEMI but do not undergo a PCI were not included in the dual antiplatelet therapy studies, and bleeding risk likely exceeds any potential benefit b. Yes, I would start clopidogrel for six months because it is the

• nly agent studied in this context

c. Yes, I would pick prasugrel for nine months because it is a more potent antiplatelet agent that is not affected by CYP2C19 polymorphisms d. Yes, I would pick ticagrelor and use it for at least one year.

Take-Home Point #4:

§ Patients with medically managed NSTE-ACS still benefit from one year of dual antiplatelet therapy. § Individualize the decision: choose clopidogrel when cost

• r adherence are important considerations and ticagrelor
• therwise. Prasugrel is not approved in this setting

(NSTE-ACS without PCI).

MOC question:

Which of the following statements is NOT true:

• a. CKD is common among patients presenting with ACS
• b. Patients with CKD are more likely to present with

atypical complaints with ACS, resulting in diagnostic delays c. Cardiac troponins are useful in diagnosing ACS in patients with CKD

• d. CKD is associated with increased cardiovascular and

all-cause mortality after ACS

• e. PCI and CABG are clinically equivalent in CKD patients

with multivessel coronary disease

Audience Response

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§ CKD is common among patients presenting with ACS § Patients with CKD are more likely to present with atypical complaints with ACS, resulting in diagnostic delays.

Cardiac troponins in CKD

§ Typically, we use 99th percentile of the troponin levels in the general population as the cut-off for diagnosing ACS § But CKD patients may have higher baseline levels (more so for Troponin T than Troponin I) § This compromises accuracy of a single lab value – high sensitivity but lower specificity § But serial labs still helpful, with a 20% change (increase

• r decrease) consistent with recent myocardial injury.

CKD and multivessel disease

§ PCI – increased risk of in-stent restenosis and need for repeat revascularization § CABG – increased risk of periop complications On balance, patients with CKD and multivessel disease appear to have better clinical outcomes with CABG than PCI, with at least two large observational studies showing lower all-cause mortality in community-dwelling populations

• f CKD.

MOC question:

Which of the following statements is NOT true:

• a. CKD is common among patients presenting with ACS
• b. Patients with CKD are more likely to present with

atypical complaints with ACS, resulting in diagnostic delays c. Cardiac troponins are useful in diagnosing ACS in patients with CKD

• d. CKD is associated with increased cardiovascular and

all-cause mortality after ACS

• e. PCI and CABG are clinically equivalent in CKD patients

with multivessel coronary disease

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Take-Home Point #5

§ CKD is a high-risk marker among patients presenting with

• ACS. Troponins are still useful in diagnosis if serial

values are used. Patients with multivessel coronary disease likely have better outcomes with CABG than with PCI.

Summary:

1. LBBB may mask a STEMI, so diagnosis of ACS must rely on the clinical story. 2. Before diagnosing a NSTEMI, exclude right-sided or posterior ST elevations, and rule out non-ACS causes of elevated troponin levels. 3. Patients with an NSTEMI and ongoing pain, or hemodynamic

• r electrical instability may benefit from urgent coronary

angiography 4. Medically managed patients with NSTEMI should receive one year of dual antiplatelet therapy: clopidogrel when cost, adherence are concerns, else ticagrelor. 5. CKD is a high-risk marker among patients with ACS. Optimize medical therapy, and consider surgical revascularization for multi-vessel disease. “Off hand, I’d say you’re suffering from an arrow through your head, but just to play it safe, let’s get an angiogram.” Thank you! Email: Kazi @ucsf.edu Twitter: @kardiologyKazi