1. (B) Prolonged QT interval is noted on the given ECG. The patient likely has long QT syndrome (LQTS) in the clinical scenario.

Management with intravenous magnesium sulfate is reasonable for patients who present with LQTS and few episodes of torsades de pointes. Magnesium is unlikely to be effective in patients with a normal QT interval. The other agents in the scenario tend to prolong the QT interval and therefore are not recommended.

2. (E) The patient in this scenario likely has type 3 long QT syndrome (LQT3).

Class IIb recommendation: Intravenous lidocaine or oral mexiletine may be considered in patients who present with LQT3 and torsades de pointes. The other agents in the given scenario tend to prolong QT interval and therefore are not recommended.

3. (D) In the given scenario, the patient has a bileaflet mechanical aortic valve without any additional risk factors for thromboembolism (see below). The recommendation as per the ACC/AHA 2020 guidelines is to stop warfarin 3 to 4 days prior to the procedure without any need for heparin bridging. Class 1 recommendations for perioperative anticoagulation strategy as per ACC/AHA 2020 guidelines are quoted below.

Class 1 recommendation:

1. For patients with mechanical heart valves who are undergoing minor procedures (e.g., dental extractions or cataract removal) where bleeding is easily controlled, continuation of VKA anticoagulation with a therapeutic INR is recommended.

2. For patients with a bileaflet mechanical AVR and no other risk factors for thromboembolism who are undergoing invasive procedures, temporary interruption of VKA anticoagulation, without bridging agents while the INR is subtherapeutic, is recommended.

*Risk factors: atrial fibrillation, previous thromboembolism, LV systolic dysfunction, hypercoagulable conditions, older-generation thrombogenic valves (ball-cage or tilting disc), or more than one mechanical valve.

4. (B) Please refer to class 1 recommendations from ACC/AHA 2020 guidelines quoted below for postoperative anticoagulation management following mechanical valve placement and the class 2b recommendation on the concomitant use of aspirin therapy.

Class 1 recommendations:

1. In patients with a mechanical prosthetic valve, anticoagulation with a VKA is recommended.

2. For patients with a mechanical bileaflet or current-generation single-tilting disc AVR and no risk factors for thromboembolism, anticoagulation with a VKA to achieve an INR of 2.5 is recommended.

3. For patients with a mechanical AVR and additional risk factors for thromboembolism (e.g., AF, previous thromboembolism, LV dysfunction, hypercoagulable state) or an older-generation prosthesis (e.g., ball-in-cage), anticoagulation with a VKA is indicated to achieve an INR of 3.0.

4. For patients with a mechanical mitral valve replacement, anticoagulation with a VKA is indicated to achieve an INR of 3.0.

Class 2b recommendation:

1. For patients with a mechanical surgical aortic valve replacement or mitral valve replacement who are managed with a VKA and have an indication for antiplatelet therapy, addition of aspirin 75 to 100 mg daily may be considered when the risk of bleeding is low.

5. (E) Anticoagulation with frequent monitoring needs to be continued through pregnancy in the setting of a mechanical valve and only stopped prior to delivery. The class 1 recommendations from the ACC/AHA 2020 guidelines are quoted below.

Class 1 recommendations:

1. Pregnant women with mechanical prostheses should receive therapeutic anticoagulation with frequent monitoring during pregnancy.

2. Women with mechanical heart valves who cannot maintain therapeutic anticoagulation with frequent monitoring should be counseled against pregnancy.

3. Women with mechanical heart valves and their providers should use shared decision-making to choose an anticoagulation strategy for pregnancy. Women should be informed that VKA during pregnancy is associated with the lowest likelihood of maternal complications but the highest likelihood of miscarriage, fetal death, and congenital abnormalities, particularly if taken during the first trimester and if the warfarin dose exceeds 5 mg/d.

4. Pregnant women with mechanical valve prostheses who are on warfarin should switch to twice-daily LMWH (with a target anti-Xa level of 0.8 to 1.2 U/mL at 4 to 6 hours after dose) or intravenous UFH (with an activated partial thromboplastin time [aPTT] 2 times control) at least 1 week before planned delivery.

5. Pregnant women with mechanical valve prostheses who are on LMWH should switch to UFH (with an aPTT 2 times control) at least 36 hours before planned delivery.

6. Pregnant women with valve prostheses should stop UFH at least 6 hours before planned vaginal delivery.

7. If labor begins or urgent delivery is required in a woman therapeutically anticoagulated with a VKA, cesarean section should be performed after reversal of anticoagulation.

6. (A) The patient was started on ACE inhibitor (captopril, enalapril, etc.). ACE converts angiotensin I to angiotensin II. It also inactivates or breaks down bradykinin. ACE inhibitors therefore increase bradykinin levels and decrease angiotensin II levels. Increased bradykinin levels are thought to be responsible for dry cough symptoms in patients taking ACE inhibitors. Digoxin inhibits Na⁺-K⁺ ATPase pump. CCBs inhibit calcium entry into vascular smooth muscle cells. Angiotensin II receptor blockers (ARBs) inhibit the activation of angiotensin II receptors. Dry cough is not commonly recognized as a side effect of digoxin, CCBs, or ARBs.

7. (C) In the given scenario, atrial fibrillation with preexcitation is the diagnosis. This is the most likely rhythm with an irregularly irregular wide complex tachycardia in an otherwise healthy patient. In atrial fibrillation with preexcitation, antegrade conduction would be through both the AV node and accessory pathway, and some beats are likely to be fusion beats. Any AV nodal blocking agent (adenosine, digitalis, diltiazem, β-blocker) is likely to result in unopposed ventricular activation through accessory pathway and can result in ventricular fibrillation. Thus, AV nodal blocking agents are best avoided in this scenario. Direct current cardioversion is the treatment of choice. If this is not possible, amiodarone may be given in this situation as it can restore atrial fibrillation to sinus rhythm as well as decrease accessory pathway conduction. Amiodarone is a class III antiarrhythmic agent that slows cardiac conduction (including accessory pathway conduction).

8. (A) The ECG shows sinus rhythm with varying degrees of AV block (predominately 2:1 AV block with occasional Mobitz type 1 second-degree AV block (i.e., Wenckebach). Accelerated junctional rhythm is also seen in the first part of the tracing. Of the medications given above, digoxin is the most likely culprit to produce nausea/vomiting and high-grade AV block with activation of ectopic pacemakers (junctional, ventricular, etc.).

9. (C) In CPVT patients with VT/VF storm, intravenous β-blocker therapy is considered the first line of treatment. General anesthesia can be used as a last resort if β-blocker therapy is ineffective.

10. (C) Since he does not have hemodynamically significant ASD, patient is unlikely to benefit from RSV prophylaxis. He does not meet other criteria for prophylaxis based on the 2014 AAP guidelines for palivizumab prophylaxis. According to the more recent AAP guidelines, children who are 12 months of age or younger with hemodynamically significant cyanotic and acyanotic congenital heart disease may benefit from palivizumab prophylaxis.

Children younger than 12 months of age with congenital heart disease who are most likely to benefit from immunoprophylaxis include:

The new guidelines do not provide specific recommendations for infants with palliated or unrepaired cyanotic heart disease. [Pediatrics. 2014;134(2):415-420]

11. (D) This patient is a candidate for RSV prophylaxis given the presence of acyanotic heart disease that requires therapy for congestive heart failure within the first year of life. The primary benefit of immunoprophylaxis with palivizumab is a decrease in the rate of RSV-associated hospitalization. Results from double-blinded, randomized, placebo-controlled trials with palivizumab involving 2,789 infants and children with prematurity, chronic lung disease, or congenital heart disease demonstrated a reduction in RSV hospitalization rates of 39% to 78% in different groups. None of the clinical trials have demonstrated a significant decrease in the rate of mortality attributable to RSV infection in infants who receive prophylaxis. [Pediatrics. 2014;134(2):415-420]

12. (A) Furosemide inhibits Na⁺-2Cl^–-K⁺ cotransporter in the loop of Henle and is therefore termed a loop diuretic. Thiazide diuretics inhibit Na⁺-Cl^– cotransporter. Digoxin inhibits Na⁺-K⁺ ATPase pump.

13. (D) The patient in the given scenario most likely has idiopathic/viral pericarditis. Ibuprofen and aspirin have been most commonly used and provide prompt relief of pain in most patients but they do not alter the natural history of the disease. High-dose aspirin (800 mg orally every 6 to 8 hours for 7 to 10 days followed by gradual tapering of the dose by 800 mg per week for three additional weeks) is usually recommended if aspirin is used. Although acute pericarditis appears to respond dramatically to corticosteroids, early use of corticosteroids has been associated with an increased risk of relapsing pericarditis in multiple studies.

Routine use of colchicine in the treatment of acute pericarditis has been supported by the Colchicine for Acute Pericarditis (COPE) trial that randomized patients into receiving aspirin alone versus aspirin + colchicine. A 4- to 6-week colchicine therapy may be considered in patients with acute pericarditis, especially in those who have not benefitted from NSAID therapy after 1 week. In this given scenario, ibuprofen is the best option given the side effect profile of colchicine, and it would also require a longer course than listed.

14. (B) NIRS saturation is a good surrogate for tissue level saturation/oxygenation. NIRS saturation can be substituted for a mixed venous saturation (MVO₂). The difference between SaO₂ and MVO₂ is a surrogate for cardiac output that is likely to be low given the difference of 40 (80 – 40) in this scenario, which would explain the pH of 7.2 (acidosis).

The pulmonary venous O₂ can be assumed to be close to 100% given the FiO₂ of 21% and clear lungs. The Q_p/Q_s in this scenario is 20.

Q_p/Q_s = (SaO₂ – MVO₂)/(pulmonary venous O₂ – SaO₂) = (80 – 40)/(100 – 80) = 40/20 = 2.

Thus, the patient has a low systemic cardiac output state and his lungs are getting at least two times the systemic blood flow. Norepinephrine is a potent vasoconstrictor. Weaning norepinephrine would lower systemic vascular resistance (SVR) and improve cardiac output, making the Q_p/Q_s more balanced. This should be the first line of management in addition to giving fluids that has already been tried in this patient. IV furosemide would decrease the intravascular volume and be detrimental for the patient. IV β-blocker therapy may decrease cardiac inotropy and worsen the low output state. Decreasing the milrinone would reduce the systemic cardiac output by increasing the SVR and by decreasing the cardiac inotropy. Increasing the FiO₂ would lower the PVR and lead to more pulmonary blood flow at the expense of systemic blood flow (increase in Q_p/Q_s).

15. (E) Initial therapy for KD during the acute phase is IVIG and high-dose aspirin. Single-dose pulse methylprednisolone should not be administered with IVIG as routine primary therapy for patients with KD. Administration of a longer course of corticosteroids (e.g., tapering over 2 to 3 weeks), together with IVIG 2 g/kg and ASA, may be considered for treatment of high-risk patients with acute KD, when such high risk can be identified in patients before initiation of treatment. In the case of persistence or recurrence of fever despite one dose of IVIG, it is reasonable to administer a second dose of IVIG (2 g/kg) to patients with persistent or recrudescent fever at least 36 hours after the end of the first IVIG infusion. Administration of high-dose pulse steroids (usually methylprednisolone 20 to 30 mg/kg intravenously for 3 days, with or without a subsequent course and taper of oral prednisone) may be considered as an alternative to a second infusion of IVIG or for retreatment of patients with KD who have had recurrent or recrudescent fever after additional IVIG. Administration of a longer (e.g., 2 to 3 weeks) tapering course of prednisolone or prednisone, together with IVIG 2 g/kg and ASA, may be considered in the retreatment of patients with KD who have had recurrent or recrudescent fever after initial IVIG treatment.

16. (C) The patient has mild to moderate carditis that needs therapy with high-dose aspirin (80 to 100 mg/kg/d in four divided doses in children). Oral prednisone is indicated for more severe carditis associated with a sicker patient in the setting of heart failure, severe valvular regurgitation, significant pericarditis/myocarditis, or reduced cardiac function. There is no recommendation for combining oral steroids with aspirin for treatment of acute RF. IVIG + aspirin is used in the treatment of KD. There is no indication for a β-blocker in pericarditis.

17. (C) Sirolimus acts at a more distal site in the lymphocyte activation cascade by blocking transcription of activation genes. Sirolimus (also known as rapamycin) is not a calcineurin inhibitor. Cyclosporine and tacrolimus are calcineurin inhibitors. Cyclosporine and tacrolimus are available for intravenous use. Tacrolimus offers no survival advantage over cyclosporine in heart transplant recipients. Sirolimus may be less nephrotoxic over the long term.

18. (C) The patient had mild carditis during RF but is free of residual heart disease now. Per guidelines, she will need RF antibiotic prophylaxis for at least 10 years or until 21 years of age, whichever is longer.

As per the current guidelines,

19. (E) Please refer to the guidelines as quoted below.

Class IIa recommendations:

Prophylaxis against IE is reasonable for the following patients at highest risk for adverse outcomes from IE who undergo dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth or perforation of the oral mucosa:

IE prophylaxis is not recommended for the following dental procedures: routine anesthetic injections through noninfected tissue, dental radiographs, placement/removal of orthodontic/prosthodontic appliances, shedding of deciduous teeth, and bleeding from trauma to lips/oral mucosa. IE prophylaxis is not recommended for the following respiratory procedures: bronchoscopy without biopsy, endotracheal intubation, or myringotomy with tube insertion. IE prophylaxis is not recommended for all gastrointestinal and genitourinary procedures including EGD and colonoscopy even with biopsy.

20. (B) The child is ≥10 years old and meets criteria for pharmacologic lipid-lowering therapy per the 2011 AAP guidelines since his LDL remained ≥190 mg/dL after a 6-month trial of diet and exercise modifications. Statin therapy is considered the first-line LDL lowering agent. A bile acid sequestrant or cholesterol absorption inhibitor may be added as a second agent if statin therapy alone is insufficient in lowering the LDL.

21. (D) The traditional therapeutic medication for HCM is β-blocker. If CCBs are used, then preferred medications would be diltiazem and verapamil. Dihydropyridine CCBs like nifedipine would cause peripheral vasodilation and reflex tachycardia that are both detrimental in an HCM patient with obstruction. Furosemide by reducing preload and therefore left ventricular filling (through its diuretic effect) could worsen the degree of obstruction in an HCM patient. ICD is not indicated at present as the patient has no clearly established sudden death risk factors (i.e., personal history of cardiac arrest or sustained VT, LV wall thickness of ≥30 mm, family history of sudden death in a first-degree relative, or unexplained syncope).

22. (B) Sirolimus can inhibit smooth muscle proliferation and may have the advantage of inhibiting coronary vasculopathy. Sirolimus is not a calcineurin inhibitor and may be used in combination with, or in lieu of, calcineurin inhibitors. Sirolimus may be less nephrotoxic over the long term.

23. (C) Lidocaine is considered a first-line agent in the acute treatment of ventricular tachycardia. It is a class Ib antiarrhythmic and is available IV. Lidocaine has a narrow therapeutic window and toxicity can occur at slightly higher levels. The most common side effects from lidocaine involve the central nervous system and include tremors, light-headedness, ataxia, dysarthria, mood/personality changes, hallucinations, and seizures. Lidocaine levels should be monitored, and dosing adjusted accordingly. Esmolol, verapamil, and amiodarone can be used in acute treatment of VT but generally do not have acute side effects of CNS toxicity. Adenosine effects on the AV node are short lived and except in very rare cases, adenosine has no role in the treatment of VT.

24. (A) All of the signs and symptoms listed can result from rabbit ATG infusion. The most common reported side effect is fever (over 60%). Other common side effects include rash (<25%), hyperkalemia (25% to 30%), abdominal pain (35% to 40%), myalgia (up to 40%), and shivering (55% to 60%).

25. (E) Both adenosine and β-blockers have the potential to exacerbate bronchospasm in this patient. Although the electrophysiologic effects of adenosine are temporary, the bronchospasm may persist for a long period of time. Heart transplant recipients are particularly sensitive to adenosine, and one-quarter to one-half the dose should be used initially as long periods of AV block may be noted with higher doses. Adenosine has a half-life of <2 seconds and is metabolized quickly in the blood. It therefore must be given as rapidly as possible in a large-bore IV as close to the heart as possible. Flushing and hypotension are common side effects. The bradycardia caused by adenosine may precipitate other arrhythmias including atrial fibrillation or ventricular tachycardia, so an external defibrillator should be readily available. The typical dose is 100 to 400 µg/kg in children.

26. (C) Combination therapy is increasingly used in children to treat severe pulmonary arterial hypertension despite the lack of published evidence. Ambrisentan is a selective endothelin A receptor antagonist. It does not induce or inhibit cytochrome P450 enzymes and is metabolized through glucuronidation. Therefore, it is much less hepatotoxic than bosentan. Treprostinil is a prostacyclin (PGI2) analogue and is not a prostaglandin (PGE2) analogue. It is favored over epoprostenol for long-term prostacyclin therapy due to its longer half-life. Sildenafil works through nitric oxide-cyclic GMP cascade, but it is a phosphodiesterase 5 inhibitor and not a phosphodiesterase 3 inhibitor. Milrinone is a phosphodiesterase 3 inhibitor.

27. (D) The ECG changes in Brugada syndrome can be dynamic and thus missed on a single ECG screening. Since the characteristic ECG hallmark may be concealed, drug challenge with sodium channel blockers (which may exacerbate the sodium channel dysfunction) to bring out the typical ECG changes has been proposed as a useful tool for the diagnosis of Brugada syndrome. Drugs employed for this purpose have included ajmaline, flecainide, procainamide, pilsicainide, disopyramide, and propafenone although the specific diagnostic value for all of them has not yet been systematically studied. Epinephrine challenge can be helpful in identifying concealed LQTS. Cardiac MRI may be used in the diagnosis of patients with arrhythmogenic right ventricular cardiomyopathy. Isoproterenol testing is commonly used in the EP lab to bring out arrhythmias. Exercise testing may be helpful in the diagnosis of CPVT.