Cardiology Intensive Board Review, 3 ed.

ANSWERS

1.c. Coronary angiography within 48 hours followed by percutaneous intervention/surgical revascularization if indicated. There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of UA and NSTEMI. A pooled analysis of randomized controlled trials with 5,467 patients compared the impact of routine invasive (RI) strategy with selective invasive (SI) strategy: Over 5 years, 14.7% of patients randomized to an RI strategy experienced CV health or nonfatal MI versus 17.9% in the SI strategy (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.71 to 0.93; P = 0.002). However, the largest absolute effect was mainly observed in higher-risk patients (11.1%).1 Another meta-analysis using data from eight trials (3,075 women and 7,075 men) compared early invasive versus conservative treatment strategies in women and men with UA and NSTEMI and reported comparable odds ratio (OR) for reducing MACE (death, MI, and rehospitalization for ACS) of 0.81 (95% CI: 0.65 to 1.01) in women and 0.73 (95% CI: 0.55 to 0.98) in men. In contrast, an invasive strategy was not associated with a significant reduction in low-risk (biomarker-negative) women.2 The 2012 ACC/AHA guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction recommend an early invasive strategy (i.e., diagnostic angiography with intent to perform revascularization) in patients who have refractory angina or hemodynamic or electrical instability, and in those initially stabilized who have an elevated risk of clinical events.3 Table 4.1 lists patients at elevated risk and in whom invasive strategy is preferred based on the ACC/AHA 2011 guidelines. Our patient has several high-risk criteria (ongoing angina, elevated biomarkers, and echocardiographic abnormalities). TIMI (Thrombolysis in Myocardial Infarction) risk score revealed 5 points (26% risk at 14 days of MACE) and GRACE (Global Registry of Acute Cardiac Events) risk score showed a high risk of mortality.

2.b. Lower rate of hospital readmission. Belardinelli et al. addressed the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS). The authors studied 118 consecutive patients with CAD (mean age 57 ± 10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for 6 months at 60% of peak VO2. Group C (n = 59) was the control group. Only patients in the active group had significant improvements in peak VO2 (26%, P <0.001) and QOL (26.8%, P = 0.001 versus C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P= not significant). However, residual diameter stenosis was lower in trained patients (–29.7%, P = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%, P <0.001). During the follow-up (33 ± 7 months), trained patients had a significantly lower event rate than controls (11.9% versus 32.2%; risk ratio [RR]: 0.71; 95% CI: 0.60 to 0.91; P = 0.008) and a lower rate of hospital readmission (18.6% versus 46%; RR: 0.69; 95% CI: 0.55 to 0.93; P <0.001). Moderate ET improved functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.4 The 2011 ACC/AHA guidelines for PCI recommend (class I, evidence A) medically supervised exercise programs to patients after PCI, particularly for moderate- to high-risk patients for whom supervised ET is warranted.5 Participation in cardiac rehabilitation is associated with significant reductions in all-cause mortality (OR 0.80; 95% CI: 0.68 to 0.93)6 in several community-based surveys and meta-analyses.6-8

3.a. Heart team discussion between the interventional cardiologist and the cardiac surgeon to select the best treatment option is the recommended approach. The 2011 AHA/ACC guidelines for PCI recommend the heart team approach (class I, evidence C) for the revascularization of patients with unprotected left main trunk disease.5 Several trials used protocols that involve a multidisciplinary approach.9,10 The heart team is composed of an interventional cardiologist and a cardiac surgeon and aims at (1) reviewing patients’ medical history, (2) determining the approach of revascularization (PCI versus CABG), and (3) discussing with the patient the options of revascularization. The guidelines endorse a heart team approach in patients with unprotected left main CAD and/or complex CAD in whom the optional strategy is not straightforward. Because the STS score and the SYNTAX score predict clinical outcomes, their use is often useful in making revascularization decisions.11,12

4.c. Drug-eluting stent (DES) implantation (stent-in-stent). In the randomized trial TAXUS V ISR (treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent trial), the slow-release, polymer-based, paclitaxel-eluting stent was found to be not only noninferior to β-source vascular brachytherapy but also superior in terms of reducing clinical and angiographic restenosis at 9 months after treatment of bare-metal ISR lesions. Because of both greater acute gain and less late loss, luminal dimensions were significantly larger with paclitaxel-eluting stents compared with brachytherapy in the injury zone, at the distal edge, and over the entire analysis segment. Proximal edge luminal dimensions were also numerically larger with the paclitaxel-eluting stent.13 Similarly, the Sirolimus-Eluting Stent with Vascular Brachytherapy for the Treatment of In-Stent Restenosis (SISR) trial demonstrated a marked reduction in target vessel failure with the sirolimus-eluting stent, driven predominantly by a reduction in the rate of target vessel revascularization.14 Based on available data and the severity of the patient’s COPD, DES implantation is the best option for this patient with BMS restenosis. Brachytherapy is no longer available except in a few research centers.15

5.d. Guideline-directed medical therapy is the first recommended approach. In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,287 patients with stable CAD were randomized to undergo PCI and medical therapy or to medical therapy alone. The primary outcome was death from any cause and nonfatal MI during a follow-up of 2.5 to 7.0 years. The cumulative event rates were 19.0% in the PCI group and 18.5% in the medical therapy group (P = 0.62). As an initial management strategy, PCI did not reduce the risk of death, MI, or other MACE in the COURAGE trial.16 About 314 patients were enrolled in the nuclear substudy of the COURAGE study to perform serial stress imaging. The addition of PCI to medical therapy improved ischemia reduction in patients with significant ischemia at baseline.17 A recent meta-analysis of 10 randomized controlled trials (6,752 patients) comparing PCI with medical therapy in stable CAD did not detect significant differences in PCI versus CABG; the relative risk (RR) for all-cause mortality was 0.97 (95% CI: 0.84 to 1.12), CV mortality RR 0.91 (95% CI: 0.70 to 1.12), MI RR 1.09 (95% CI: 0.92 to 1.29), or angina relief RR 1.10 (95% CI: 0.97 to 1.26).18 According to the AHA/ACC guidelines CABG or PCI should not be performed to improve symptoms or survival in patients with CAD with one or more coronary stenoses who do not meet anatomic (≥70% non-left main stenosis diameter), physiologic (FFR >0.80, no or mild ischemia on noninvasive testing) criteria for revascularization and involve only LCX or RCA, or subtend only a small area of viable myocardium.5 The multiple meta-analyses comparing PCI versus medical therapy in patients with SIHD showed that PCI reduced the incidence of angina, but has not been demonstrated to improve survival or lower the long-term risk of MI in stable patients.17,19 Our patient does not have criteria for coronary revascularization, and the first-line therapy should be an aggressive medical therapy.

6.c. Subendocardium. The subendocardium is most susceptible to ischemic damage. Although the mechanisms of subendocardial ischemia remain to be fully defined, they are clearly associated with the transmural distribution of intramyocardial systolic pressures. Even though almost all the myocardium is perfused in diastole, a reduction of diastolic perfusion pressure or duration will result in subendocardial ischemia.11 The abnormal subendocardial perfusion in patients with cardiac syndrome X (typical angina, abnormal exercise test results, and normal coronary arteries) has been described with CV MR imaging during the IV administration of adenosine.20

7.d. Inferior wall myocardial infarction (MI) with right ventricular infarction. The association of inferior wall MI on ECG and elevated jugular venous pressure with clear lungs is suggestive of additional right ventricular infarction. Tall c–v waves of tricuspid regurgitation may be evident in patients with necrosis or ischemia of the right ventricular papillary muscles.

8.a. Reduction in left ventricular compliance. An S4 is frequently present in patients with acute MI and is related to auricular contraction and ventricular compliance reduction during ventricular filling.21 Rapid deceleration of transmitral flow during protodiastolic filling of the left ventricle and increased inflow into the left ventricle are responsible for the third heart sound (S3). A systolic ejection murmur is suggesting for aortic sclerosis.

9.e. Hybrid revascularization mandates surgical and percutaneous revascularization during the same procedure. According to the ACC/AHA PCI guidelines, hybrid coronary revascularization is defined as the planned combination of LIMA-to-LAD artery grafting and PCI of ≥1 non-LAD coronary arteries and intended to combine the advantages of CABG (i.e., durability of the LIMA graft) and PCI. Hybrid revascularization is particularly suitable in patients with limitations to traditional CABG (e.g., heavily calcified proximal aorta, lack of graft conduits, or a non-LAD coronary artery unsuitable for bypass but amenable to PCI) and situations in which PCI of the LAD artery is not feasible (e.g., excessive tortuosity or calcification, complex bifurcation lesion, and very long lesion). The procedure may be performed in one operative setting or as a staged procedure. CABG before PCI is preferred.5Preliminary reports suggest that this approach is feasible and safe,22 but randomized data are lacking.

10.c. High-sensitive troponin T (Hs-TnT). In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 9,946 patients presented with non-ST-elevation ACS: 5,357 were revascularized and 4,589 managed conservatively. High-sensitive elevated Hs-TnT (>14.0 ng/L) have been described to predict substantial benefit (reduction rate of CV death, MI, and stroke) of ticagrelor over clopidogrel in patients who were revascularized or treated conservatively, while no apparent was observed in those who had normal Hs-TnT.23

11.e. All of the above. Patients with extensive and severe CAD are more likely to present abnormal exercise ECG results.24 Early onset of angina, ischemic ST depression ≥2 mm, downsloping ST segment starting at <5 METs, involving ≥5 leads and persisting ≥5 minutes into recovery, and fall in blood pressure at low exercise are all associated with adverse prognosis.

12.e. No improvement of any of the mentioned endpoints. The COURAGE trial enrolled 2,287 patients with significant CAD to an initial strategy: (1) PCI and OMT or (2) OMT only. There were no significant differences between the PCI group and the medical therapy group in the composite of death, MI, and stroke (HR: 1.05; 95% CI: 0.87 to 1.27), and hospitalization for ACS (HR: 1.07; 95% CI: 0.84 to 1.37) or MI (HR: 1.13; 95% CI: 0.89 to 1.43). The authors concluded that as initial management strategy in patients with stable CAD, PCI did not reduce the risk of death, MI, or other MACE when added to OMT.16 According to the 2011 ACC/AHA PCI guidelines, revascularization should not be performed to improve survival in patients with SIHD with one or more coronary artery stenoses that are not anatomically significant, or involve only the LCX or RCA, or subtend only a small area of viable myocardium.5

13.e. All of the above. In the COURAGE patients, 314 were enrolled in the substudy of myocardial perfusion SPECT performed before treatment and 6 to 18 months after randomization. At follow-up, the reduction in ischemic myocardium was greater with PCI + OMT than with OMT (–2.7% versus –0.5%, P <0.0001). The patients with PCI + OMT exhibited significant ischemia reduction (33% versus 19%, P= 0.0004), especially those patients with moderate-to-severe myocardial ischemia at baseline (78% versus 52%, P = 0.007).17 The 2012 AHA/ACC guidelines for PCI mentioned in patients with stable ischemic coronary heart disease a benefit of angina reduction and symptom improvement with PCI versus OMT; however, PCI has not been demonstrated to improve survival in stable patients.5

14.b. Significant absolute risk reduction of major adverse cardiovascular events (MACE) of ~2% over 5 years. The 2012 ACC/AHA guidelines for the management of SIHD recommend the prescription of moderate or high dose of a statin therapy in addition to lifestyle changes (class I, evidence A).25 The Treating to New Targets (TNT) study randomized 10,001 patients with stable coronary heart disease and LDL >130 mg/dL to receive atorvastatin 10 or 80 mg daily. The mean LDL-C was 2.0 mmol/L during the treatment with 80 mg of atorvastatin, whereas it was 2.6 mmol/L during the treatment with 10 mg of atorvastatin. About 8.7% of patients in the group with intensive lipid-lowering therapy and 10.9% in the group with moderate lipid-lowering therapy presented MACE during a median follow-up of 4.9 years, representing a significant absolute reduction in the rate of MACE of 2.2% and a 22% relative reduction in risk. There was no difference between both treatment groups in the overall mortality.26

15.e. Fondaparinux might be used as the sole anticoagulant to support PCI. The 2011 ACCF/AHA PCI guidelines made the following recommendations regarding anticoagulant therapy during the procedure. Following recommendations are class I: (1) All patients undergoing PCI should receive an anticoagulant to prevent thrombus formation during the procedure; (2) the administration of IV UFH is a useful standard therapy in patients undergoing PCI; (3) an additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients who have received fewer than two therapeutic subcutaneous doses (e.g., 1 mg/kg) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PCI; and (4) for patients undergoing PCI, bivaluridin is useful as an anticoagulant with or without prior treatment with UFH. In contrast, fondaparinux should not be used as the sole anticoagulant to support PCI.5 An additional anticoagulant with anti-IIa activity should be administered because of the risk of catheter thrombosis. Fondaparinux is an indirect factor Xa inhibitor, but no effect on thrombin (IIa). The use of fondaparinux alone was associated with thrombus catheter formation and therefore the anticoagulant with anti-IIa should be used during PCI.27

16.e. Even in the absence of symptoms, routine periodic stress testing is indicated. According to the 2011 AHA/ACC PCI and 2011 AHA/ACC secondary prevention guidelines, the following interventions and targets are strongly recommended in patients with CHD to reduce morbidity and mortality: (1) to refer to a medically supervised cardiac rehabilitation program post discharge, (2) to manage lipid-lowering treatment for an LDL-C target <70 mg/dL, (3) to control blood pressure with the goal of <140/90 mmHg, and (4) to advise patients for complete smoking cessation. Conversely, there is no proven benefit or indication for routine periodic stress testing in patients after PCI, and thus, it is not indicated.24

17.e. All of the above. The clinical situations associated with higher risk of BMS restenosis have been defined by the 2011 AHA/ACC PCI guidelines as follows: (1) left main disease, (2) small vessels, (3) ISR, (4) bifurcations, (5) diabetes, (6) long lesions, (7) multiple lesions, and (8) saphenous vein grafts. The ISR of BMS presented by the patient should be treated with DES,5 as sirolimus- or paclitaxel-eluting stents are superior to balloon angioplasty.28The use of DES over BMS had decreased the incidence of ISR by over 70%.13,28

18.b. Rosuvastatin 20 mg/day significantly decreased the incidence of MI. The JUPITER trial randomized 17,802 men and women without CVD presenting an LDL-C lower than 130 mg/dL, but high levels of hs-CRP, to rosuvastatin, 20 mg daily, or to placebo. Rosuvastatin reduced LDL-C levels by 50% and hs-CRP levels by 37%. The primary endpoint outcome was a composite of MI, stroke, arterial revascularization, hospitalization for UA, or death from CVD. The study was interrupted after 1.9 years at interim analyses because of a significant decrease for primary outcome (HR: 0.56; 95% CI: 0.46 to 0.69). HR for MI was 0.46, 95% CI (0.30 to 0.70), and HR for stroke was 0.52, 95% CI (0.34 to 0.79). In the adverse events section, the physician-reported diabetes was more frequent in the rosuvastatin group (n = 270) than in the placebo group (n = 216, P = 0.01); the difference in the median glycated hemoglobin value was minimal (5.9% versus 5.8%, respectively, P = 0.001).29

19.c. CABG is associated with a reduction of death and of MI, but not of stroke. The future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial randomized 1,900 patients with diabetes and multivessel CAD to a revascularization strategy with (1) CABG or (2) PCI. The primary outcome was defined as death from any cause, nonfatal MI, or nonfatal stroke. The primary outcome rate at 5 years was 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was observed in reduction of death (P = 0.049) and MI (P<0.001) rates, but stroke was more frequent in the CABG group than the PCI group (5.2% versus 2.4%, P = 0.03).30

20.c. More than 70% of patients quit smoking after ACS. About 50% to 70% of smokers continue to smoke after an ACS,31 despite the fact that smokers who quit smoking have a 36% reduction in the risk of mortality and 32% in the risk of recurrent nonfatal MI in comparison with continuing smokers over a mean follow-up of 5 years.32 Smoking cessation intervention is a major target of secondary prevention of CVD and should be one of the priorities of clinicians providing care to such patients. Given the large benefits of smoking cessation, promotion of smoking cessation is the most effective intervention to reduce morbidity and mortality in smokers with CHD.32Unfortunately smoking receives less attention from cardiologists than other CV risk factors,33 and many smokers with CHD are unable to quit smoking without assistance. Based on a systemic review, several studies found a beneficial effect on smoking cessation rates through a smoking cessation intervention that started in hospital and continued in the ambulatory setting.31

21.e. Answers b and d are correct. The leading cause of death in patients hospitalized for acute MI is cardiogenic shock. The SHOCK investigators conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. Patients with shock caused by left ventricular failure complicating MI were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either CABG or angioplasty. Intra-aortic balloon counterpulsation was performed in 86% of the patients in both groups. The primary endpoint was mortality from all causes at 30 days. Six-month survival was a secondary endpoint. The mean age of the patients was 66 ± 10 years; 32% were women and 55% were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87% underwent revascularization; only 2.7% of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days (primary endpoint) did not differ significantly between the revascularization and medical therapy groups (46.7% and 56.0%, respectively; difference, –9.3%; 95% CI for the difference, –20.5% to 1.9%; = 0.11). However, at 6 months mortality was lower in the revascularization group than in the medical therapy group (50.3% versus 63.1%, P = 0.027).34

22.a. Patients with CKD undergoing cardiac catheterization should receive adequate preparatory hydration. The 2011 ACC/AHA PCI guidelines made recommendations regarding contrast-induced AKI. Contrast-induced AKI is considered one of the most frequent causes of iatrogenic AKI. Risk factors for developing contrast-induced AKI are hypotension, intra-aortic balloon pump, congestive heart failure, CKD, diabetes, age >75 years, anemia, and volume of contrast.35 The following recommendations are of class I for the prevention of AKI: (1) Patients should be assessed for risk of contrast-induced AKI before PCI; (2) patients undergoing catheterization with contrast media should receive adequate preparatory hydration; and (3) in patients with CKD (creatinine clearance <60 mL/min), the volume of contrast media should be minimized. However, the administration of N-acetyl-cysteine is not useful for the prevention of contrast-induced AKI and is not recommended based on the results of several randomized controlled trials.36

23.a. No significant difference in the risk of stroke. Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in high-risk patients undergoing PCI in the setting of ACS compared with a regimen of aspirin and UFH. Akkerhuis et al. combined analysis of data from 8,555 patients undergoing PCI assigned to receive a bolus and infusion of abciximab (n = 5,476) or matching placebo (n = 3,079). No significant difference in stroke rate was observed between patients assigned abciximab (n = 22 [0.40%]) and those assigned placebo (n = 9 [0.29%]; P = 0.46). The rate of nonhemorrhagic stroke was 0.17% in patients treated with abciximab and 0.20% in patients treated with placebo (difference: –0.03%; 95% CI: –0.23% to 0.17%), and the rates of hemorrhagic stroke were 0.15% and 0.10%, respectively (difference: 0.05%; 95% CI: –0.11% to 0.21%). Abciximab in addition to aspirin and heparin does not increase the risk of stroke in patients undergoing PCI.39

24.d. 70 mg/dL. For patients with established CAD, LDL-lowering therapies significantly reduce the risk of MACE and yield highly favorable cost-effectiveness ratios. In high-risk persons, the recommended LDL-C goal is <100 mg/dL. An LDL-C goal of <70 mg/dL is a therapeutic option on the basis of available clinical trial evidence, especially for patients at very high risk. Diabetic patients with established advanced CAD, like the mentioned patient, should be considered at very high risk for MACE and qualify for the ambitious target of LDL <70 mg/dL.42

25.c. Additional aspirin (81 to 325 mg) is recommended in all patients on chronic aspirin therapy before PCI. The 2011 AHA/ACC PCI guidelines recommend the use of antiplatelet therapy before PCI.5Aspirin reduced ischemic CV events after PCI37,38 and should be given at least 2 hours before PCI after which aspirin has to be continued indefinitely.39 In addition to aspirin, a loading dose of P2Y12 receptor inhibitor might be given to patients undergoing PCI with stenting.40-42 Options include clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg. The duration of P2Y12 receptor inhibitor after stent implantation (BMS or DES) for ACS should be of at least 12 months.43,44 Options include clopidogrel 75 mg daily, prasugrel 10 mg daily, and ticagrelor 90 mg twice daily. In patients receiving DES for a non-ACS indication, clopidogrel 75 mg daily should be given for 12 months if patients are not at high risk for bleeding.45 In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months.44 A benefit of additional aspirin in patients on chronic aspirin undergoing PCI has never been demonstrated.

26.c. 20% to 30%. A proportion of patients who present with suspected ACS are found to have insignificant CAD during coronary angiography. Of the 5,767 patients with non-ST-segment-elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent inhospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to ≤50%), and 6% had no CAD (no stenosis identified). Overall, 12% of the patients had nonsignificant CAD.44 Patients with nonsignificant CAD were more likely to be women, non-white, younger, nondiabetic, nonhypercholesterolemic, without history of CVD, without ST-segment changes, but with more T-wave inversion compared with patients with significant CAD. Based on the profile of the patient admitted, her probability of having nonsignificant CAD is >12%.

27.b. Prothrombin complex. Bivaluridin is a naturally occurring anticoagulant secreted by the salivary glands of the leech Hirudo medicinalis. It is a potent and specific anticoagulant and exerts its action by binding directly to the active catalytic site of thrombin. Unlike heparin, it does not require a cofactor (antithrombin) and does not appear to cause immune-mediated thrombocytopenia. It is also a more potent inhibitor of platelet function than heparin, probably because of a direct inhibitory effect on thrombin. Unlike heparin, which is readily neutralized by protamine or platelet factor 4, a specific agent useful in reversing the effects of bivalirudin is unavailable. Irani et al. demonstrated the first clinical experience, suggesting benefit from prothrombin complex concentrate in neutralizing the effect of r-hirudin. Although the specific mechanism of action remains unclear, the generation of additional thrombin probably plays a role. Also, epinephrine-induced platelet aggregation in hirudinized platelet-rich plasma is restored by addition of prothrombin complex concentrate, most probably by additional thrombin generation. Adverse effects of prothrombin complex concentrate include intravascular thrombosis, particularly in patients with liver disease and possible viral hepatitis. As the product contains some activated clotting factors (II, VII, IX, and X) and has thrombogenic potential, it should be used as a last resort, especially in patients with liver disease. Clinical experience suggests that prothrombin complex concentrate in a dose of 25 to 30 UI/kg can be considered for patients with life-threatening hemorrhage caused by bivalirudin.45

28.e. The radial vascular access is more frequently performed in the United States than in Europe. Radial site access is used more frequently in Europe and Canada than in the United States.46 The 2011 AHA/ACC PCI guidelines recommend radial artery access to decrease access site complications.5 In fact, it has been demonstrated that radial access, compared with femoral access, decreases the rate of access-related bleeding and complications.47 Its utility is more pronounced in patients at higher risk for bleeding or vascular access complications such as in patients with coagulopathy, anticoagulated, or morbid obesity.

29.c. A 65-year-old man known for CAD complaining of progressive shortness of breath since 1 week. At admission, no ongoing chest pain with stable hemodynamic status but bibasilar rales at lung auscultation. The ECG revealed ST-segment elevation as well as Q waves in the anterior leads. The 2011 AHA/ACC PCI guidelines elaborated indication of PCI in patients with STEMI.5 Primary PCI should be performed in patients within 12 hours of onset of STEMI, within 90 minutes of the first medical contact in patients presenting to a hospital with PCI capabilities and within 120 minutes of the first medical contact in patients presenting to a hospital without PCI capabilities (“systems goal”).4850 Primary PCI should be performed in patients with STEMI who are candidates for primary PCI, who develop severe heart failure or cardiogenic shock irrespective of time delay,34,51 and who had clinical and/or ECG evidence for ongoing ischemia between 12 and 24 hours after symptom onset.52 Delayed PCI in patients with STEMI is reasonable in patients with infarct artery reocclusion or demonstrating ischemia on invasive testing.53 PCI of hemodynamically significant stenosis in patent infarct artery greater than 24 hours after STEMI might be considered as part of an invasive strategy (class of recommendations IIb).54,55 PCI of a totally occluded infarct artery greater than 24 hours after STEMI should not be performed in asymptomatic patients with one- or two-vessel disease if patients are hemodynamically stable and do not present evidence of severe ischemia (class III).56

30.d. Right ventricular infarction. Rupture of the interventricular septum is one of the mechanical complications of MI, less frequent than left free wall rupture.57 It occurs in general 3 to 5 days after acute MI. An increase in risk is observed in patients with occlusion of LAD wrapping the distal inferior wall and inferior septum (inferior MI with large anterior MI). The ECG findings of the interventricular septum rupture are typical for ST elevation and Q waves in the inferior leads II, III, and aVF.58 Clinically, the patients present a rapid onset of hemodynamic compromise characterized by hypotension, biventricular failure, and a new harsh, loud, holosystolic murmur best heard at the lower left sternal border.59

31.d. Immediate coronary angiography. The septal defect and the associated turbulent transseptal flow can be visualized by a transthoracic echocardiography using color flow Doppler imaging.60 The addition of Doppler to echocardiography improves significantly the sensitivity of the examination demonstrating the transseptal turbulent flow and diastolic–systolic turbulences in the right ventricle.

32.c. Mechanical ventilation with positive end-expiratory pressure. The timing of surgical repair with post-MI ventricular septal rupture is controversial. In patients with cardiogenic shock, a fatal prognosis is inevitable in the absence of urgent surgical treatment. First, stabilization with an intra-aortic balloon pump counterpulsation, inotropic agents, diuretics, and, if tolerated, vasodilators is attempted.61 This is followed by cardiac catheterization to define the coronary anatomy and then surgical repair.

33.e. All of the above. The 2011 ACC/AHA PCI guidelines assessed the risk–benefit profile for the use of BMS versus DES. DES is preferred to BMS when high risk of stent restenosis is present with BMS. The clinical situations associated with higher risk of restenosis are (1) left main disease, (2) small vessels, (3) ISR, (4) bifurcations, (5) diabetes, (6) long lesions, (7) multiple lesions, and (8) saphenous vein grafts. All the criteria mentioned above increased the risk of restenosis, suggesting the use of DES over BMS.5

34.a. Low-dose aspirin daily. The patient will have coronary angiography for a high suspicion of SIHD. Until the angiogram is performed, he should be treated with optimal medical treatment including aspirin, statins, control of blood pressure (β-blockers/angiotensin converting), and additional medical therapy for the relief of symptoms (β-blockers, calcium channel blockers, long-acting nitrates, or sublingual nitroglycerin).25 The efficacy of clopidogrel pretreatment compared with the administration in the catheterization laboratory is controversial.62 There is no evidence to give prasugrel or ticagrelor in patients with SIHD.

35.c. Pharmacologic stress with nuclear myocardial perfusion imaging if able to exercise and interpretable ECG. Patients with intermediate pretest probability of CAD are those who most benefit from stress testing to improved diagnostic accuracy. The choice of stress test depends on two questions: Is the patient able to exercise? Is the resting ECG interpretable?25 The ACC/AHA SIHD guidelines recommend standard exercise ECG testing for interpretable ECG and at least moderate physical functioning or no disabling comorbidity (level of evidence A, class I).63 Exercise with nuclear myocardial perfusion imaging or echocardiography is recommended for patients with an intermediate to high pretest probability of ischemic heart disease who have an uninterpretable ECG and at least moderate physical activity functioning or no disabling comorbidity.64,65 Pharmacologic stress with cardiac MR can be useful for patients with an intermediate to high pretest probability who have an uninterpretable ECG and at least moderate physical functioning or no disabling comorbidity.66 Pharmacologic stress with nuclear myocardial perfusion imaging, echocardiography, or cardiac MR is not recommended for patients who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidities.67

36.c. Severe ostial and moderate distal left main trunk stenosis. The coronary angiography shows severe ostial and moderate distal left main trunk stenosis.

37.e. All of the above. The 2012 AHA/ACC guidelines on SIHD25 recommend using a nomogram to predict the risk of death in patients with SIHD.68 This score is based on following clinical and exercise testing variables: age, male gender, typical angina, diabetes, cigarette smoking, hypertension, proportion of predicted METs achieved, ST-segment depression, test-induced angina, abnormal heart rate recovery, and frequent ventricular ectopy during recovery.

38.b. Arteriovenous fistula. The coronary angiography reveals large coronary AV fistula involving the RCA. Patient underwent surgical ligation of the fistula with resolution of her symptoms.

39.e. All of the above. The coronary angiography shows a bifurcation lesion involving the distal left main trunk as well as the ostium of the left anterior descending and left circumflex coronary arteries.

40.c. Perforation of the RCA. The coronary angiography demonstrates extravasation of contrast caused by perforation of the RCA.

41.e. All the mentioned clinical situations do not justify coronary angiography in the initial phase of patient management. According to 2012 AHA/ACC SIHD guidelines,25 coronary angiography is not recommended as an initial testing strategy to assess risk in the following clinical situations (class III, no benefit): (1) patients with SIHD who elect not to undergo revascularization or who are not candidates for revascularization because of comorbidities or individual preferences; (2) patients with SIHD who have preserved left ventricular function and low-risk criteria on noninvasive testing; (3) low risk according to clinical criteria and who have not undergone noninvasive risk testing; and (4) asymptomatic patients with no evidence of ischemia on noninvasive testing.

42.b. Calcified coronary arteries. Patients with long-standing terminal nephropathy have frequently severely calcified vessels including the coronary arteries.69 Qualitative analysis of the coronary arteries showed significantly more calcified plaques of coronary arteries in patients with end-stage renal failure. Plaques of nonuremic patients were mostly fibroatheromatous, while coronary plaques in patients with end-stage renal failure were characterized by increased media thickness and marked calcification. Deposition of calcium within the plaques may contribute to the high event rate in uremic patients.

43.e. Acupuncture might be used for the purpose of improving symptoms of patients with SIHD. According to 2012 AHA/ACC SIHD guidelines,25 acupuncture should not be used for the purpose of improving symptoms or reducing CV risk in patients with SIHD (class III, no benefit). Smoking cessation and avoidance of exposure to environmental tobacco smoke at work and home should be encouraged (class I), dipyridamole is not recommended as antiplatelet therapy for patients with SIHD (class III, no benefit), treatment with clopidogrel is reasonable when aspirin is contraindicated in patients with SIHD (class I), and it is reasonable to consider screening SIHD patients for depression and to refer or treat when indicated (class IIa).

44.e. PCI does not reduce the occurrence of death, reinfarction, or heart failure. The Occluded Artery Trial (OAT) study showed high rates of procedural success with PCI and sustained patency but no clinical benefit during an average 3-year follow-up with respect to death, reinfarction, or heart failure.56 There was, in fact, a trend toward excess nonfatal reinfarction when routine PCI was performed in stable patients who were found to have occlusion of the infarct-related artery 3 to 28 days after MI. A strategy of CABG was not tested in the OAT.

45.e. Answers a and d are correct. In the CHARISMA trial of 15,603 patients with established stable atherothrombotic disease or at high risk for such disease, there was no significant benefit associated with clopidogrel plus aspirin as compared with placebo plus aspirin in reducing the incidence of the primary endpoint of MI, stroke, or death from CV causes. Clopidogrel was associated with a significant increase in the rate of moderate bleeding.70

46.b. Significant survival advantage. A cohort study of approximately 1,400 patients demonstrated that the use of combination evidence-based medical therapies was independently and strongly associated with lower 6-month mortality in patients with ACSs.71 Furthermore, there was a gradient of benefit across the different TIMI risk groups with higher-risk patients obtaining higher absolute benefit.72 The 2013 AHA/ACCA STEMI guidelines73recommend (1) indefinitely aspirin 81 to 325 mg daily maintenance dose after PCI (class I), (2) β-blockers should be continued after hospitalization for all patients with STEMI and with no contraindications to their use (class I), (3) angiotensin-converting enzyme inhibitors are reasonable for all patients with STEMI and no contraindications to their use (class IIa and class I if presence of reduced LVEF), and (4) high-intensity statin therapy should be initiated or continued in all patients with STEMI and no contraindications to its use.

47.b. PCI may reduce the episodes of angina in the presence of moderate-to-severe ischemia at stress single-photon emission computed tomography (SPECT) but not the risk of death, MI, or other major CV events when added to optimal medical therapy. The COURAGE trial compared OMT alone or in combination with PCI as an initial management strategy in patients with stable CAD. Although the addition of PCI to OMT reduced the prevalence of angina, especially in case of moderate-to-severe ischemia detected by SPECT, it did not reduce long-term rates of death, nonfatal MI, and hospitalization for ACSs.16

48.d. Severe RCA stenosis. Coronary angiography shows severe mid-RCA stenosis explaining the inferior ischemia.

49.d. 12 months. The 2011 AHA/ACC PCI guidelines recommend the continuation of aspirin indefinitely (class I) and the duration of P2Y12 inhibitor after stent implantation as follows: (1) BMS or DES during PCI for ACS, at least 12 months; (2) DES for a non-ACS indication, at least 12 months if patients are not at high risk for bleeding; and (3) BMS for a non-ACS indication, a minimum of 1 month, and ideally up to 12 months (unless the patient is at increased risk for bleeding).5

50.a. Severe LCX stenosis. The coronary angiography of the left circulation shows severe mid-left circumflex coronary artery stenosis.

51.e. Discontinuation of dual antiplatelet therapy followed by surgery in the first few weeks following stent implantation is problematic with DES but not BMS. In patients scheduled for noncardiac surgery in the year following PCI, the implantation of DESs should be avoided. Accordingly, one of the most frequent predisposing conditions to DES thrombosis is the (partial or complete) discontinuation of dual antiplatelet therapy because of urgent or elective noncardiac surgery.74 Although preliminary data suggest that continuation of dual antiplatelet therapy during surgery, if feasible, may be protective of DES thrombosis, no recommendation can be made at this time. Conceptually, the potential for stent thrombosis remains because of the intrinsic prothrombotic state related to surgery. Perioperative thrombosis of BMS implanted shortly prior to noncardiac surgery have been described and associated with prohibitive morbidity and mortality. Therefore, whenever possible, noncardiac surgery should be postponed for at least 6 weeks following implantation of a BMS and 6 to 12 months following DES implantation.

52.d. In patients who have already suffered a stent thrombosis dual antiplatelet therapy may be extended long term, although currently there are no data to support this strategy. Currently, there are no data to support an extension of dual antiplatelet therapy beyond 12 months. Nevertheless, in selected patients at high risk for stent thrombosis, aspirin and clopidogrel may be administered for a longer period of time. The CHARISMA trial70 did show a benefit of prolonged aspirin and clopidogrel therapy over aspirin only in the secondary prevention setting, but did not specifically address the PCI population. According to the 2011 AHA/ACC PCI, continuation of P2Y12 inhibitor after stent implantation for ACS should be at least 12 months.5

53.e. Occlusion of the first diagonal branch. The ECG showed inferoposterolateral STEMI. Coronary angiography showed a thrombotic occlusion of mid-portion of the dominant RCA.

54.a. Thrombotic occlusion of the left main trunk. The coronary angiography shows thrombotic occlusion of the left main trunk artery. This lesion has been treated with thromboaspiration and implantation of a DES.

55.c. Anterior subacute MI. ECG reveals ST elevation of anterolateral fields. Due to persisting chest pain, the patient has been investigated with angiography. The ventriculography showed occlusion of the mid-portion of the left anterior descending coronary artery treated with thromboaspiration and implantation of a BMS. The image of the thrombus extracted is shown in Figure 4.14.

Figure 4.14

56.b. Occlusion of the left anterior descending coronary artery. The coronary angiography showed an occlusion of the proximal left anterior descending coronary artery. The fact that the vessel perfused the apex including the inferoapical portion of the left ventricles explains the ST elevations in the anterior and inferior leads.

57.d. Visible thrombus in the mid-portion of the RCA. The coronary angiography showed a subtotal stenosis of the mid-RCA followed by a filling defect compatible with a large thrombus. The thromboaspiration was successfully performed and the lesion was subsequently treated with stenting.

58.a. Subtotal occlusion of the left main trunk. Coronary angiography showed subtotal occlusion of the left main trunk and the lesion was treated with stenting. Ventriculography showed a severely reduced LVEF (15%) under a mechanical chest compression system. The patient did not recover and subsequently died.

59.a. ISR of the left descending coronary artery. Coronary angiography shows a ISR of the mid-left anterior descending coronary artery.

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