Venu Menon • Bhuvnesh Aggarwal
1.e. All of the above. Based on data from national heart disease stroke statistics, while the incidence of overall ACS, STEMI, and NSTEMI has declined with time, the incidence of UA has been increasing in the last decade. The observed decline in the rate of UA is largely attributable to the availability of sensitive troponin assays that detect myocardial necrosis.
2.a. Plaque rupture. Plaque rupture is the dominating initiating event of acute MI. Rupture of the fibrous cap of the coronary atheroma exposes the underlying subendothelial matrix eventually leading to activation of platelets, thrombin generation, and final thrombus formation. While erosion of the plaque without rupture can lead to thrombus formation, it is not as frequent an event as plaque rupture and accounts for a third of MIs.
3.a. Age. Based on results of the large GUSTO-I trial the strongest predictor of mortality following STEMI is advanced age. In addition to age, other major predictors of poor prognosis on presentation include systolic BP <100 mmHg, heart rate >100 per minute, higher Killip classification stage, and anterior infarction.
4.e. Both b and c. Aspirin, clopidogrel, prasugrel, and ticagrelor are all antiplatelet agents. Aspirin irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. While clopidogrel and prasugrel are prodrugs that require hepatic bioactivation to their pharmacologically active metabolite, ticagrelor is phenotypically active and is not affected by hepatic metabolism.
5.e. All of the above are correct. Prasugrel has faster onset of action and potency of platelet inhibition when compared with clopidogrel. Unlike clopidogrel, prasugrel is not influenced by P-450 genetic polymorphisms. In the large, randomized TRITON-TIMI-38 trial, investigators compared prasugrel with clopidogrel in patients with ACS initiated following coronary angiography. While there was no difference in mortality, there was a reduction in composite of major adverse cardiovascular events primarily driven by reduction in nonfatal MI. A higher incidence of bleeding with prasugrel when compared with clopidogrel was noted. Post hoc analysis showed net harm in patients with prior history of TIA/stroke and prasugrel should be avoided in these patients.
6.e. Fibrinolysis; low-molecular-weight heparin (LMWH), aspirin, and clopidogrel; and transfer to hospital for possible PCI. This patient has acute STEMI. Current ACC/AHA guidelines recommend (class I) administration of fibrinolytic therapy (within 30 minutes) when there is an anticipated delay to performing primary PCI within 120 minutes of first medical contact. In addition to fibrinolysis, adjunctive antiplatelet therapy (aspirin 162 to 325 mg loading dose and clopidogrel 300 mg loading dose in patients aged <75 years) and antithrombotic therapy (weight-adjusted unfractionated heparin or LMWH) should be promptly initiated. Adjunctive LMWH in the setting of fibrinolysis was compared with heparin in the randomized ENTIRE-TIMI-23 trial. The study showed reduced ischemic events (death/recurrent MI) with LMWH when compared with unfractionated heparin at 30 days (4.4% versus 15.9%). The benefit of early routine angiography regardless of symptom status and hemodynamic stability has been confirmed in a number of clinical trials. As a result, transfer to a PCI hospital following lytic administration is encouraged.
7.a. Continue unfractionated heparin, aspirin, and clopidogrel and transfer to the nearest hospital with PCI capabilities. Repeat ECG reveals resolution of ST-segment elevation that likely indicates reperfusion. As previously stated, a significant proportion of patients receiving fibrinolysis may undergo reocclusion of the infarct artery. Therefore, it is reasonable to transfer patients to the nearest PCI-capable hospital (ACC/AHA class IIa recommendation). Angiography 3 to 24 hours after fibrinolysis is now recommended in these subjects regardless of hemodynamic status. Discharge home after stress test and referral for delayed angiography are not preferred options for patients with acute STEMI treated with fibrinolysis.
8.c. Streptokinase and aspirin each have a similar effect on outcome. Based on results of International Studies of Infarct Survival (ISIS-2) trial from the fibrinolytic era, aspirin provides as much mortality benefit as streptokinase and the combination provides additive benefit in acute MI.
9.c. Adenosine diphosphate blockade. Ticagrelor reversibly blocks adenosine diphosphate receptors of subtype P2Y12 on platelet cell membranes eventually leading to inhibition of platelet activation. Aspirin acts by a thromboxane inhibition and abciximab is a chimeric human monoclonal antibody that works by blockade of the activated GP II/IIIa receptor on the platelet surface.
10.c. Routine GP IIb/IIIa inhibitor use is associated with increased risk of bleeding. While prior studies documented benefits of routine intravenous GP IIb/IIIa in STEMI, the emergence of potent platelet adenosine diphosphate P2Y12 receptor inhibitors sparked controversy regarding their additive benefit. Most subsequent trials demonstrated no clinical benefit with possible increased risk of bleeding with routine use of these agents in addition to dual oral antiplatelet therapy. A benefit for upstream GP IIb/IIIa inhibition was also not evident in the Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) and Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trials. Use of these agents is now reserved in the catheterization laboratory for patients undergoing high-risk PCI with high thrombus burden and for bailout.
11.a. Decrease subsequent repeat TVR. Stents decrease the rate of subsequent TVR compared with balloon angioplasty alone, but there is no favorable impact on TIMI-3 flow or mortality.
12.d. It had similar rates of mortality compared with alteplase. It had similar rates of mortality to alteplase. This noninferiority trial randomized over 15,000 patients with STEMI to intravenous alteplase or reteplase. The rates of mortality (11.20% and 11.06% at 1 year, respectively) and stroke were similar for reteplase and alteplase. The major advantage of reteplase was that it could be given as two boluses rather than as an infusion.
13.e. All of the above. Results from large TIMI registry indicate that biomarker elevation (NSTEMI) and ST-segment deviation on admission ECG carries poorer prognosis in patients with NSTE-ACS. In addition, one in five patients with NSTE-ACS may have normal or nonspecific changes on ECG.
14.c. Administer aspirin, sublingual nitroglycerin, and heparin. The patient has signs and symptoms suggestive of cocaine-induced ACS. The dominant underlying pathophysiologic factor in cocaine-induced ACS can be coronary spasm or thrombus formation caused by α-adrenergic stimulation. Atherosclerosis is also accelerated by cocaine use. This patient should be started on aspirin, sublingual nitroglycerin, and intravenous heparin. β-Blockers are contraindicated as they may allow unopposed β-adrenergic stimulation and have been associated with increased mortality.
15.a. Activate the catheterization laboratory for emergent left heart catheterization. The patient has persistent ischemia after initiation of antianginal therapy. He needs to be sent for emergent left heart catheterization. Intravenous benzodiazepine can temporarily relieve cocaine-induced chest pain but this patient has ischemic symptoms with ECG changes suggestive of ACS. Fibrinolytics have not been shown to be useful in cocaine-induced chest pain without evident thrombosis.
16.d. Clopidogrel 600 mg, bivalirudin drip, and atorvastatin 80 mg. This patient has acute MI. Current ACC/AHA guidelines mandate adjunctive medical therapy in addition to aspirin, including loading dose of P2Y12 receptor inhibitor (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg) and anticoagulant therapy (unfractionated heparin or bivalirudin). Fondaparinux (a) should not be used as a sole anticoagulant to support primary PCI as it has been shown to increase catheter thrombosis. Prasugrel is contraindicated in patients with history of stroke.
17.c. Mortality benefit with routine intravenous nitroglycerin is not established. Although widely used, no randomized trial has established a mortality benefit with intravenous nitroglycerin. Intravenous ACE-I formulations have no proven benefit and were associated with increased mortality in Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS 2). Routine intravenous β-blocker use within 24 hours also did not have any impact on mortality and led to higher rates of cardiogenic shock in the Clopidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese Cardiac Study (COMMIT/CCS-2) megatrial. No benefit with intravenous magnesium was noted in the National Heart, Lung and Blood Institute (NHLBI)-supported Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial.
18.e. Fibrinolysis should be considered 12 hours after symptom onset in hemodynamically stable patients with signs of ongoing ischemia. Fibrinolysis has not been shown to be useful and may even lead to harm after 12 hours of symptom onset in patients with STEMI. Two large, randomized trials (Late Assessment of Thrombolytic Efficacy (LATE) and Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris (EMERAS)) investigated the utility of late fibrinolysis in patients with STEMI and found no mortality benefit beyond 12 hours of symptom onset. Primary PCI is associated with reduced rate of intracerebral hemorrhage when compared with fibrinolysis. If rapidly available, primary PCI has been convincingly shown to reduce mortality when compared with fibrinolysis. Primary PCI may be considered 12 hours after symptom onset in patients with signs of ongoing ischemia. While primary PCI should be considered in patients with signs of ongoing ischemia 12 to 24 hours after symptom onset, routine PCI of the totally occluded infarct-related artery >24 hours after presentation in hemodynamically stable patients without signs of ischemia provides no additional benefit and may even be harmful. Delayed PCI (3 to 28 days after MI) of the occluded asymptomatic Infarct Related Artery (IRA) was evaluated in the randomized Occluded Artery Trial (OAT). While PCI did not reduce the occurrence of death, reinfarction, or heart failure, there was a trend toward excess reinfarction during long-term follow-up in stable patients.
19.d. Suspected aortic dissection. Suspected aortic dissection is an absolute contraindication for use of fibrinolysis. History of stroke, pregnancy, use of warfarin, and history of seizure disorders are all relative contraindications for fibrinolysis.
20.c. Presence of collateral circulation in the infarct zone reduces risk of VSR. VSR is more likely in women and after first MI. Fibrinolytic therapy is not associated with increased risk of VSR but may accelerate rupture in vulnerable subjects. VSR is equally likely after anterior or nonanterior wall MI.
21.e. Urgent surgical repair. This patient has VSR after acute MI. Although the shunt fraction is small, the rupture may rapidly progress in an unpredictable manner and lead to hemodynamic collapse and death. Although controversial, urgent surgical closure remains the treatment of choice. Vasodilators (nitroprusside) and IABP placements can reduce shunt fraction and increase forward flow and can be utilized in hemodynamically unstable patients as bridge to surgery. This patient is hemodynamically stable with a small shunt fraction.
22.d. All of the above. Acute ventricular free wall rupture usually presents with acute onset cardiac tamponade, pulsus paradoxus, and sudden death. It accounts for approximately 10% of mortality after MI. Fibrinolysis may increase risk and this potentially accounts for the “early hazard” with thrombolytic therapy as noted in the randomized clinical trials. Type I rupture is a slit-like full-thickness rupture that is usually seen within the first 24 hours. It usually occurs in the border zone between the akinetic infarct-related segment and the adjacent hyperkinetic noninfarct zone.
23.a. Ventricular aneurysm is more common than ventricular pseudoaneurysm after MI. True ventricular aneurysm is more likely than pseudoaneurysm (contained rupture of LV free wall). While ventricular aneurysm is more likely with anterior MI, pseudoaneurysms occur more often after inferior wall MI. In contrast to patients with true aneurysms that are initially managed with medical therapy, pseudoaneurysms have a high risk of rupture and surgical therapy is recommended irrespective of size or presence/absence of symptoms.
24.e. Transthoracic echocardiogram. This patient presents with symptoms suggestive of TIA. He had a recent anterior wall MI. Persistent ST elevation in V2 to V4 suggests apical aneurysm that increases the risk of mural thrombus formation. Current symptoms suggest an embolic event secondary to LV mural thrombus. Echocardiogram must be done to confirm the diagnosis. Although the patient has persistent ST elevation on ECG, there are no clinical signs of recurrent ischemia and repeat left heart catheterization is not indicated.
25.a. Pulmonary capillary wedge pressure (PCWP) 30, confidence interval (CI) 1.6. This patient has acute STEMI complicated by cardiogenic shock. Cardiogenic shock is defined as evidence of ineffective tissue perfusion arising from cardiac dysfunction supported by the presence of a systolic BP <90 mmHg, PCWP >15 mmHg, and cardiac index <2.2 L/min/kg/m2. Classic study performed in the pre-reperfusion era by Forrester risk stratified patients with cardiogenic shock based on PCWP and CI. Patients with both elevated PCWP and low CI have worst prognosis. In the GUSTO-I trial low cardiac output (and cardiac index) remained the strongest hemodynamic predictors of death in patients with cardiogenic shock.
26.a. Consideration for advanced mechanical support. Advanced mechanical support with IABP, ECMO, or TANDEM heart is indicated at this time. IABP reduces afterload, increases cardiac output, and reduces myocardial oxygen requirement by means of reduction in wall stress. The recently conducted Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP SHOCK-II) trial failed to show a mortality benefit in this setting with IABP counterpulsation, as a result IABP support in the setting of shock is now downgraded to a IIa indication in the most recent ACC/AHA guidelines. Other supportive devices such as the TANDEM and Impella have been shown to provide superior hemodynamic support to IABP alone, although no clear benefits with regard to mortality have been noted. The patient described achieved satisfactory mechanical reperfusion and urgent CABG or repeat angiography is not indicated and nitroprusside would not be considered in this setting.
27.c. Atorvastatin, lisinopril, carvedilol, and eplerenone. Current guidelines in post reperfusion care include medical management for optimal risk factor control and treatment of myocardial dysfunction. High-potency statins (atorvastatin or rosuvastatin) and β-blockers are indicated in the absence of contraindications in all patients with STEMI. ACEIs are indicated in all patients after MI with ejection fraction <40% or anterior wall MI and aldosterone antagonists are indicated in patients with MI and ejection fraction <40% with clinical signs of heart failure.
28.f. None of the above. This patient had a brief episode of nonsustained VT in the setting of MI. Routine antiarrhythmic therapy with amiodarone or lidocaine is not indicated in patients with MI and brief, self-limited, and hemodynamically insignificant arrhythmias within 48 hours of symptoms. This patient has low ejection fraction and warrants consideration for a primary prophylaxis ICD based largely on the Multicenter Automatic Defibrillator Implantation Trial (MADIT II) trial if ventricular function does not recover. Early use of ICD post MI was not associated with benefit in the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) and Immediate Risk Stratification Improves Survival (IRIS) trials. Patients with MI and low ejection fraction need to be reevaluated after 40 days on optimal medical therapy to determine candidacy for device therapy.
29.d. Within 30 minutes. Door in door out time in the setting of STEMI is the time from patient presentation to discharge from a non-PCI hospital to a PCI-capable hospital. A door in door out time of less than 30 minutes is associated with decrease in mortality.
30.d. Initiation of hypothermia protocol. Initiation of therapeutic hypothermia in post cardiac arrest patient has been shown to be associated with a significant mortality benefit. The patient is not in shock and administration of normal saline may lead to pulmonary edema. Prophylactic intravenous lidocaine in this setting has not been shown to have any clinical benefit and may lead to harm. The patient does not have polymorphic VT and there is no role for transvenous pacing in ischemically triggered polymorphic VT. While ECMO has been shown to be useful in patients with refractory cardiogenic shock, it is not indicated in a hemodynamically stable patient post cardiac arrest.
31.b. Treatment with clopidogrel 300 mg followed by 75 mg daily. This patient has UA and will likely rule in for an NSTEMI. Initiation of antiplatelet therapy with a bolus dose of clopidogrel 300 mg followed by 75 mg once daily is indicated based on the results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. The use of prasugrel in the elderly is associated with increased risk of bleeding. In this patient who is not undergoing revascularization, the use of bolus dose prasugrel cannot be supported. In addition to antiplatelet therapy with aspirin, the patient also needs to be started on antithrombotic therapy (with unfractionated heparin, LMWH, or fondaparinux). Lastly, since he has refused revascularization, medical antianginal therapy should be maximized. Increasing β-blocker as tolerated is indicated.
32.e. Apixaban. Bivalirudin, argatroban, and hirudin are intravenous direct thrombin inhibitors and dabigatran is an oral direct thrombin inhibitor. Apixaban is an oral factor Xa inhibitor.
33.b. Fibrinolysis reduces the incidence of pericarditis in MI. Several studies, including Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (Italian) (GISSI 1), have examined this issue and found that fibrinolysis reduces the incidence of pericarditis in the setting of acute MI. Indeed, in the era of reperfusion therapy, the rate of both early and late pericarditis has decreased. Probably, by reducing infarct size, reperfusion decreases the incidence of pericarditis, which is more common with large MIs.
34.e. All of the above are acceptable indications for IABP use.
35.c. CT abdomen without contrast. The patient has signs and symptoms suggestive of massive retroperitoneal bleeding after left heart catheterization. Retroperitoneal bleeding is a common complication after left heart catheterization through femoral access. Patients present with anemia that may be hard to detect on clinical examination. CT abdomen without contrast is the test of choice to confirm bleeding. He has no signs of recurrent ischemia on ECG and as such repeat catheterization to look for stent thrombosis (a) is not indicated. Lack of elevated jugular venous pulse makes pulmonary embolism (b) or cardiac tamponade/acute mitral regurgitation (e) unlikely.
36.b. Performance of a gated CT of the aorta. This patient has acute aortic regurgitation and performance of gated CT aorta is urgently indicated. Development of a new diastolic murmur at the base of the heart that accentuates with expiration should raise suspicion of acute aortic regurgitation. Acute aortic regurgitation is usually secondary to endocarditis or acute ascending aortic dissection. Ascending aortic dissection can involve the coronary cusps leading to acute coronary dissection that can present with chest pain and ST elevations on ECG. Cocaine use is a major risk factor for acute aortic dissection. While nongated CT with pulmonary embolus protocol can often detect acute aortic detection, it is often associated with motion artifacts in the aortic root and is not the ideal test. The patient has a suspected acute aortic dissection, and activation of catheterization laboratory for revascularization or antiplatelet therapy is not indicated. Confirmation by the performance of a CT aorta followed by immediate surgical consultation appears warranted. While two-dimensional echo can often detect an aortic dissection flap, absence of the same does not rule out aortic dissection.
37.d. Recent exposure to a phosphodiesterase 5 inhibitor. This patient developed immediate hypotension after administration of nitroglycerin. Administration of nitrates in patients who have recently taken phosphodiesterase 5 inhibitors such as sildenafil acetate can lead to severe hypotension, circulatory collapse, and death. The patient is unlikely to develop massive hemorrhage within 5 minutes of aspirin load, and anaphylaxis in this setting is extremely uncommon. Administration of nitrates can cause profound hypotension in RV infarction but this patient has ST elevations in V1 to V4, suggesting anterior-apical wall MI.
38.b. Her prognosis will likely be excellent with full recovery of LV function. This patient has Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome. This transient weakening of LV apex is often triggered by emotional stress, such as the death of a loved one, a breakup, or constant anxiety, and is most often seen in middle-aged women. Most patients achieve complete recovery within few months. There is no indication for ICD and there is no increased risk of atherosclerosis or malignancy. Routine anticoagulation with warfarin is not indicated in the absence of apical thrombus.
39.a. Discussion with the family explaining his poor prognosis and the near futility of escalating care is the ideal next step in this scenario. The patient presents with acute STEMI complicated by cardiogenic shock. The large randomized SHOCK trial did not show any benefit for a revascularization strategy in patients >75 years with cardiogenic shock. Data from multiple registries suggest that aggressive measures (IABP, heart catheterization, and revascularization) should be considered in patients with good baseline functional status, and such efforts are likely to be futile in this patient with poor functional status, extensive history of coronary artery disease, and multiple medical comorbidities.
40.b. Diagonal. The culprit infarct-related artery is the diagonal branch of LAD.
41.c. Initiate intravenous heparin and assess the risks and benefits of fibrinolysis. The echo shows a linear density in the main PA extending into the left PA. Findings are most consistent with a hemodynamically significant pulmonary embolism. Starting intravenous heparin and assessment for fibrinolysis are urgently indicated.
42.d. Mid RCA in dominant RCA. The echo shows a VSR in the basal inferoseptum. This area is usually supplied by the PDA. As a result, a dominant RCA infarction likely accounts for these changes.
43.d. Initiate fibrinolytic therapy with reteplase with adjunctive treatment with aspirin and intravenous heparin. The ECG shows significant anterior ST depression with upright T waves consistent with a true posterior current of injury. Although no benefit is noted with fibrinolytic therapy over placebo in randomized clinical trial, a benefit was noted in patients with true posterior injury defined as ST depression >2 mm in the anterior precordial leads. This patient is in the golden hour. Transfer to a remote location for PCI 4 hours later would be inappropriate.