2. Acute Coronary Syndromes

2. Acute coronary syndromes

History

Typical angina defined (N Engl J Med 1979;300:1350)

substernal chest pain
exertional
relieved by rest or NTG

Exam (Do Not Edit This Line)

Assess for hemodynamic stability, check bilateral blood pressures to assess for aortic dissection
Check for new S4, new MR murmur secondary to ischemic papillary muscle dysfunction, evidence of CHF (elevated JVP, rales, new S3), Kussmaul’s sign for RV MI

EKG (Do Not Edit This Line)

STE localize better than ST depressions/T wave inversions
Anterior (V1-V4); apical (V5,V6); lateral (I, aVL)
Inferior (II, III, aVF), III>II elevation suggests RCA as culprit rather than circumflex
Posterior (V7-9, “inverse” of V1-V3)
RV (1 mm STE in V4R most predictive of RV infarct).
Wellens’s syndrome: pre-anterior wall infarction.
Two types of Wellens’s T waves (V1-V3) indicative of critical proximal LAD stenosis:

Deeply inverted T wave

Biphasic terminal T wave inversion

Consider catheterization rather than non-invasive investigation

Cardiac biomarkers

Cardiac troponins more sensitive marker of myocardial damage than CK-MB
CK-MB more useful for assessing reinfarction and infarct size
Elevated troponin, negative CK-MB

Recent MI ~2-10 d prior

“Microinfarct.” In absence of recent MI, increased long term risk of death, MI, need for urgent revascularization even in pts with renal failure; however, unclear how to use this information; no clear increase in risk for imminent arrhythmia, no clear need for SDU/CCU monitoring

End stage renal disease; estimated that 29% of patients on dialysis have elevated troponin T without evidence of myocardial injury; portends poor prognosis

Early risk stratification

Among patients with UA/NSTEMI, there is progressive benefit with increased risk from newer, advanced therapies including LMWH, platelet GP IIb/IIIa inhibition, and early invasive strategy/PCI.

Treatment of ST elevation MI

Hemodynamic support: if evidence of cardiogenic shock, institute pressors/inotropes, optimize volume status, consider urgent IABP placement
Electrical stability:

Sustained VT (more than 30 s), consider lidocaine, amiodarone

Symptomatic bradycardia, heart block, consider pharmacologic therapy, avoid beta-blockade, institute transcutaneous pacing

Reperfusion therapy

a. Thrombolytic therapy
Indications / Contraindications
1. Angina for at least 30 min and less than 12 hrs

AND

2a. ST elevations1mm in 2 anatomically contiguous leads
or
2b. LBBB not known to be old / Absolute

Prior hemorrhagic CVA at any time, non-hemorrhagic CVA within 1 year
Known intracranial neoplasm
Active internal bleeding (not including menses)
Suspected aortic dissection

Relative

SBP >180 on presentation or chronic HTN
Prior non-hemorrhagic CVA at anytime
INR >2.0 or known bleeding diatheses
Trauma or surgery within 2-4 wks
Prolonged CPR (> 10min)
Noncompressible vascular punctures (e.g. subclavian lines)
Recent internal bleeding (2-4 wks), active PUD
If considering SK, prior SK exposure (esp within 2 yrs)
Pregnancy

Complications—“early hazards”

Bleeding

Intracranial hemorrhage: increased risk in females, African Americans, the elderly, pts with prior CVA, HTN, wt <70 kg, short stature, supratherapeutic lytic dose
Overall incidence 0.75%: 0 RF 0.26%, 1 RF 0.96%, 2 RF 1.32%, 3 RF 2.17%
70% bleeding complication at puncture sites

Other

Myocardial rupture, reperfusion injury, splenic rupture, aortic dissection, cholesterol emboli

Benefit

Overall 18% decrease in 35d mortality.
No clear mortality benefit with lysis 12-24h after onset of symptoms (LATE, EMRAS trials).

Failed lysis

Evolving chest pain and ST elevations that persist (at >50% baseline) for 90 minutes after onset of administration of thrombolytics  rescue angioplasty

Thrombolytic agent /

Dose

Alteplase (tPA) “accelerated dosing”

/ 15 mg IV bolus  0.75 mg/kg (50 mg) over 30 min  0.5 mg/kg (up to 35 mg) over 60 min (100 mg total in average pt)
Streptokinase (SK)* / 1.5 MU IV over 30-60 min *(only lytic agent not routinely dosed with IV heparin)
Reteplase (Retavase) / 10 MU IV bolus q 30 min x 2
Tenecteplase (TNK-tPA) / 0.5 mg/kg IV bolus x 1 (max 50 mg)
b. Catheter-based reperfusion
Primary angioplasty: Consider if contraindications to lysis, anterior MI, pt is s/p CABG, diabetic, or in cardiogenic shock.

PTCA with 20% lower rate of combined cardiac endpoint, 65% lower rate of CVA v. lysis when performed at high volume centers (JAMA 1997; 278:2093).
Of note: door to balloon time in most trials 1-2h. Opting for angioplasty should not significantly increase time to revascularization.

Primary stenting. Lower rate of need for revascularization but equivalent mortality when compared with primary angioplasty alone.
Rescue angioplasty. Performed in setting of failed lysis (see above).

c. Antiplatelet and antithrombin therapy

Drug / Dose
Aspirin (ASA) / 162-325 mg po x 1 chewed (trans-buccal mucosal absorption)
Heparin IV (used in conjunction with tPA, rPA, TNK-tPA and PTCA) / Bolus 60 U/kg IV (max 4000 U); initial infusion 12 U/kg/hr (max 1000 U/h); note lower dosing compared to previous recommendations
PTT goal 50-70 (lower than DVT/PE goal of 65-80)
Use “cardiac” heparin sliding scale on order entry
GP IIb/IIIa inhibitors
Abciximab (Reopro)
Eptifibatide (Integrilin)
Tirofiban (Aggrastat) / The only data in STEMI supports abciximab (ADMIRAL, RAPPORT)
0.25 mg/kg IVB  0.125 mcg/kg/min x 12-24h
180 mcg/kg IVB  2 mcg/kg/min x 72h
0.4 mcg/kg/min x 30min  0.1 mcg/kg/min x 48-96h
4. Adjunctive therapy
Drug / Dose / Cautions

Oxygen

/ Keep oxygen sat >93%
Morphine / 2-4 mg IV boluses / Unusual to see somnolence/ decreased respiratory drive in STEMI
Beta blockers
Metoprolol (Lopressor) / 5 mg IV q5 min x 3, then 25 mg PO q6h, titrate to HR 55-60 / HR <60, SBP <100, severe CHF, 1 (PR>0.24 s), 2, 3 AVB, severe bronchospastic disease
Nitrates
IV nitroglycerin / 10-1000 mg/min, titrate to symptom relief/SBP ~100 / Idiosyncratic profound hypotension/bradycardia.
ACE-inhibitors
Captopril / 6.25 mg PO tid, titrate as tolerated to SBP ~100 / SBP <100, renal failure

Treatment of unstable angina (UA)/Non-ST elevation MI (NSTEMI)

Drug / Dose
Aspirin (ASA) / 160-325 mg PO x 1 chewed
Clopidogrel (Plavix) / 300 mg PO loading, then 75 mg PO QD
Heparin IV (unfractionated)
or
LMWH
Enoxaparin (Lovenox)
Dalteparin (Fragmin) / Bolus: 60 U/kg IV (max 4000 U), initial infusion 12 U/kg/hr (max 1000 U/h). PTT goal 50-70 (lower than DVT/PE goal of 65-80). Use “cardiac” heparin sliding scale on computer order entry.
1 mg/kg SC bid x 2-8d

120 U/kg SC bid x 5-6d

discuss with cardiology before using LMWH given lack of easy reversibility
Nitrates
IV nitroglycerin
Nitropaste / Titrate to symptom relief, SBP ~100
10-1000 mcg/min (<300 mcg/min  SDU, >300mcg/min  CCU)
Sliding scale on computer order entry
Beta blockers
Metoprolol (Lopressor)
Propranolol (Inderal) / Titrate as tolerated to HR 55-60, contraindicated in decompensated CHF
5 mg IV q5 min x 3, then 25 mg PO q6h
1 mg IV q5 min x 4, then 20 mg PO q6h
GP IIb/IIIa inhibitors
Abciximab (Reopro)
Eptifibatide (Integrilin)
Tirofiban (Aggrastat) / The best data is in favor or eptifibatide and tirofiban (PURSUIT, PRISM-PLUS), not abciximab.
0.25 mg/kg IVB  0.125 mcg/kg/min x 18-24h (max 10 mcg/min)
180 mcg/kg IVG  2 mcg/kg/min x 72h
0.4 mcg/kg/min x 30 min  0.1mcg/kg/min x 48-108h
Post-catheterization care
Complication / Finding / Imaging / Management
Bleeding groin / Overt bleeding / none / Call cards fellow ASAP, compress
Groin hematoma / Assess for neurovascular compromise of limb / ± groin US / Stable in size  observation
Rapidly expanding  cards ASAP
Retroperitoneal hematoma / Decreased Hct ± back, abd, LE pain; hypotension / I abd CT / Stabilize hemodynamically, transfuse
General surgery consult, to OR if unstable or LE neurovasc compromise
Pseudoaneurysm / Groin: pulsatile mass, tenderness, bruit / Groin US / Vascular surgery for repair
IR for graded compression (by US)
AV-fistula / Groin: continuous bruit ± thrill / Groin US / Vascular surgery  observation with repeat imaging v. OR repair
Distal embolization / Diminished distal pulses, decreased cap refill, LE neurologic compromise / LE arterial non invasives; angio / Vascular surgery consult
? anticoagulation v. urgent embolectomy
Renal insuff.
Contrast ATN / Increased Cr ± decreased urine output / ± renal u/s
if concern for obstruction / Optimize volume status
Prophylaxis with N-acetylcysteine 600 mg PO bid x 48h peri-cath if inc Cr
Chol. emboli / Livedo reticularis, rash, urine eosinophils
Post-stent care
Antithrombotics / Aspirin 325 mg PO qd
Clopidogrel 300 mg PO x 1 (in cath lab)  75 mg PO qd x 1 year, likely up to 4 yrs
Heparin IV: cont 48h post-sheath pull if poor angiographic result, otherwise discontinue
GP IIb/IIIa: usually continued 12-24h post-procedure
Statins / Lowers target vessel revascularization rate (LIPS)
Folate, B6, B12 / Lower restenosis rates independent of homocysteine levels (Swiss Heart Study)
Post-stent complications / Timing / Incidence / Findings / Pathophys / Management
Abrupt closure / Min-24h / 1% / Severe CP, STE on EKG / Dissection, thrombosis / Contact cards ASAP, urgent revascularization
Subacute thrombotic occlusion / 1-30d / 4% vs.
<1% with drug-eluting stent
In-stent restenosis / 1-6mo / ~15-36% vs. <1% to 8% with DES / Increasing angina / Endothelial proliferation / Semi-elective revascularization
Vessel rupture/perforation / Minutes-48h, rare complication, pleuritic chest pain  cardiac tamponade secondary to hemopericardium.
Do not perform pericardiocentesis / Contact cards ASAP, stat echo
Distal embolization / Minutes-48h, common complication, minor ischemic pain without ECG changes / Follow serial ECGs

Contacting cardiology: 6-9292 (cardiology page operator)

Cardiology patients covered by either “ward service” or “private attending”

re: private patients, call 6-9292 and ask for attending coverage

re: ward patients, call 6-9292 and ask for “ward cardiology fellow on call”

For post-cath complication, call 6-9292 and ask for “interventional fellow on call.”
For urgent overnight assistance, call 4-5110 (Ellison 11) and ask for “access fellow”
For stat or weekend echo, call x 6-9292 and ask for “fellow on call for echo”
Prior to instituting thrombolysis at MGH, call appropriate cardiology coverage; they may wish to mobilize cath lab instead,

MGH Medical Housestaff Manual1

3. Noninvasive testing

MGH Medical Housestaff Manual

3. Noninvasive testing

General considerations

Exercise tolerance test with MIBI imaging (ETT-MIBI) is the most commonly used noninvasive risk stratification for patients who are able to ambulate at MGH
Adenosine-MIBI, a pharmacologic stress test, is useful for patients who are unable to sufficiently ambulate for an ETT-MIBI.
Nuclear imaging (MIBI) is used in nearly all stress tests performed at MGH, though there may be variation in practice at other institutions.
In most cases, testing should be performed within 72 hours of presentation for low-risk patients.

Exercise tolerance test (ETT)

Of choice when patient can ambulate
Can do without imaging if no baseline ECG abnormalities (digoxin effect, LVH, LBBB, paced, WPW, ST abnormalities associated with SVT, atrial fibrillation, mitral valve prolapse, severe anemia). RBBB okay for ECG interpretation
Advantages: inexpensive, low morbidity, estimates functional capacity, predictor of mortality
Indications: diagnosis of CAD, risk assessment and prognosis among patients with symptoms or known CAD, post-MI
In low risk patients, testing can be performed when patients have been free of active ischemic or heart failure symptoms for a minimum of 8-12 hours and have ruled out for myocardial infarction
After MI, can perform submaximal stress test at about 4-76 days post event (but not necessary in patients who have undergone cardiac catheterization).

Submaximal test is generally exercise to predetermined end point, i.e. peak heart rate 120 or 70% of predicted max heart rate, or 5 METs

Contraindications include acute coronary syndrome, MI within past 2 days, uncontrolled arrhythmia, acute CHF, severe AS, recent PE/DVT, acute infection, aortic dissection, uncontrolled hypertension (SBP >200 or DBP >110).
Sensitivity/specificity: single VD 68/77%, multi VD 81/66%, 3VD or LM 86/53%
Patient preparation: if to diagnose in CAD, hold beta-blockers if possible unless the test is solely for functional purposes, NPO within 3 hours of testing and longer if imaging is used (which is generally the case at MGH)
Data

ST segment is most sensitive for ischemia

ST depression of at least 1 mm that is horizontal or downsloping

ST depression of at least 2 mm that is upsloping

Criteria that further increase probability of ischemia: number of leads, workload at which changes occur, angle of ST slope, time to ST recovery, ventricular ectopy during recovery

Location of ECG changes does not localize area of ischemia

Age-predicted maximum heart rate (220  age): if 85% is not reached, test is non-diagnostic

SBP monitoring: failure of SBP to rise with exercise indicates CAD and test should be terminated

Functional capacity: in metabolic equivalents (METs), with >6 indicating good prognosis; failure to achieve 5 METs is associated with a worse prognosis

Symptoms: angina, shortness of breath, etc.

Data interpretation: 1. normal, 2. abnormal, 3. normal except for, 4. nondiagnostic (<85% max HR and no abnormal ECG changes or baseline ECG changes are present)
Prognosis, can use Duke treadmill score = exercise time (min) – (5  max ST deviation in any lead) – (4  angina index). Angina index is no angina = 0, non-limiting angina = 1, angina reason for stopping = 2. See N Engl J Med 1991;325:849.

Nuclear perfusion imaging

Improves sensitivity (75-90%) and specificity (65-90%) over standard ETT
Indications: assessment of physiologic importance of known CAD, pts with abnormal baseline ECG, major to intermediate clinical predictors, high risk surgeries, unable to exercise
Advantages: higher sensitivity, localizes ischemic area, can use pharmacologic agents for pts unable to exercise (see below).
Limitations: lower specificity for single vessel disease, low PPV for post-op events (~20%), attenuation from adjoining tissue
Two major radiopharmaceuticals are used: thallium-201 and technetium-99m-sestamibi (MIBI)
Thallium

Produced in cyclotron, 72 hour half life, actively transported into cells, redistributes with time to other cardiac and non-cardiac cells

MIBI (most commonly used at MGH)

Produced on site, 6 hour half life, uptake passive and thus proportional to regional myocardial blood flow, no redistribution

Tracer is excreted into the GI tract through biliary system, and appearance of tracer in GI tract can interfere with imaging of the inferior wall (this is why patients must be NPO)

Produces sufficient count densities to allow ECG gating and thus allows for calculation of EF

Defects characterized as fixed (scar), reversible (ischemic), partially reversible (mixture of scar and ischemia), artifact (breast, diaphragm), high-risk (defect in >1 distribution, increased lung thallium uptake, LV dilation)

Pharmacologic testing

Used in concert with nuclear imaging
Dipyridamole (not commonly used at MGH)

Indirect vasodilator, flow enhanced in normal vessels and much less so in stenosed vessels (which possess little flow reserve)

Side effects: headache, nausea, chest pain, hypotension, dizziness, flushing

Avoid in severe COPD, theophylline therapy, and critical carotid stenosis

Adenosine (used at MGH)

Vasoactive end product of dipyridamole and has much shorter half-life

Side effects: chest pain, headache, nausea, flushing, dyspnea, AV block

Avoid in settings similar to dipyridamole

Dobutamine (used at MGH)

Simulates exercise by increasing heart rate

Side effects: ectopy, headache, flushing, dyspnea, parasthesias, hypotension

Stress echocardiography

To screen for CAD and localize coronary lesions, with sens and spec similar to nuclear imaging
Can use exercise or dobutamine. At MGH, exercise imaging is done with nuclear techniques, and stress echo is limited to dobutamine studies
Advantages: provides EF, rule out valvulopathy, images not attenuated (useful in women)
Limitations: severe mitral or aortic regurgitation and dilated cardiomyopathy may make interpretation difficult
Dobutamine echo is especially helpful in evaluating pts with LV dysfunction and severe aortic stenosis to quantify the extent of AS

Myocardial viability

Key is to differentiate dysfunctional yet viable myocardium from necrosed and scarred myocardium in order to determine which patients may benefit from revascularization
Stunned myocardium—viable, occurs after acute episode, can last days to weeks, may recover with or without revascularization
Hibernating myocardium—viable, caused by repetitive ischemic injury or chronic reduction in blood flow, needs revascularization for recovery
PET is the current standard for assessment, but is not typically used at MGH
Rest-redistribution thallium imaging—redistribution of tracer can only occur in viable myocardium
MIBI is less accurate in detecting viability

MGH Medical Housestaff Manual

4. Complications of myocardial infarction

Pump failure

Rales, S3, cardiogenic shock (occurs in 7% patients with MI)

Treatment

Na restriction
Diuretics
Digoxin for symptomatic relief
Afterload reduction (ACE-I or hydralazine and nitrates)
Hemodynamic stabilization and look for reversible causes
Consider PA catheter, aortic balloon pump or ventricular assist device

Mechanical complications

Accounts for 15% mortality after MI

Myocardial free wall rupture

Accounts for 10% of post MI deaths
Typically occurs in first 5 days of MI (can occur day 1-21)
Occurs in small infarcts and commonly anterolateral MI
Single vessel MI with poor collaterals
Elderly females with first MI or few prior MIs
Leads to death or PEA
Associated with less pulmonary edema, more hypertension
Not associated with murmur
Increased risk after thrombolysis
May lead to false aneurysm

Ventricular septal defect

Occurs in 1-3% of post MI patients, 1-10 days post MI
Causes 5% peri-infarct deaths
If anterior MI, VSD usually in apical septum
If inferior MI, defect located on basal inferior septum (worse outcome/more difficult to repair)
Associated with new pansystolic murmur and occasionally thrill
Can detect shunt with step-up
Usually seen in elderly females with few prior MIs and lack of collaterals
Highest overall mortality, but not acutely fatal
Class I indication for IABP

Acute disruption of the mitral valve with severe mitral regurgitation

Accounts for 5% post MI deaths; occurs 2-7 days post MI; rarest of mechanical complications
Associated with inferior MI (due to posterior-medial papillary muscle supplied by PDA) and/or true posterior MI
Rarely seen with ALMI
Females > male; less likely to have STE; EF> in end
LV function becomes hyperdynamic
May hear thrill on exam

Right ventricular infarct

Common sequela of inferior MI
Typical triad of hypotension, increased JVD, clear lungs
Kussmaul’s sign from pseudoconstriction
1 mm STE in R sided leads, particularly V4R
RV wall motion abnormal, RV dilatation
Elevated right atrial pressure
Increased incidence of high grade AV block
Volume load and add vasopressors

Infarct expansion

Thinning and dilatation of infarct segment without pain or CK leak

Infarct extension

Recurrent pain and CK-MB leak

Left ventricular aneurysm

Occurs days to weeks post MI
Begins with infarct expansion, necrosis, removal of debris, replace with scar
Risk factors include large infarcts, uncontrolled hypertension, receiving steroids or NSAIDs
Apical dyskinesis/aneurysm predisposes to thrombus
Can compromise pump function and cause VT

Left ventricular thrombus

Observed in 10-40% of anterior wall infarcts
Usually in LV apex
Increased risk of embolization during first 3-6 months post MI
Prevent with anticoagulation in patients with:

Large anterior MI