Cardiology Intensive Board Review, 3 ed.


Alexander Kantorovich • Michael A. Militello • Jodie M. Fink


1.b. 1,300 mg. To determine the loading dose of a one-compartment drug, three items are needed: (a) the drug’s Vd (L/kg), (b) the desired steady-state concentration (Cpss [mg/L]), and (c) the patient’s weight. Loading dose = Vd × Cpss. Kilograms and liters cancel, and you are left with the loading dose in milligrams.

2.b. 25%. The bioavailability of digoxin tablets is 75%. Therefore, when converting from PO to IV administration (bioavailability of 100%), there is a 25% increase in bioavailability. Without altering the dose of digoxin, this patient would most likely have an increase in digoxin level to approximately 2.4 ng/mL. This could lead to potential digoxin toxicity.

3.c. Vd and clearance. Half-life is a function of both clearance (Cl) and Vd. The elimination-rate constant (kel) is determined by two independent factors: Cl and Vdkel = Cl/Vd. Half-life is determined by the equation 0.693/kel. Therefore, as the apparent Vd and Cl change, the half-life of a drug may change.

4.d. Pharmacodynamics. Pharmacodynamics has been defined as the study of the biologic effects resulting from the interaction between drugs and biologic systems. Pharmacokinetic principles consider drug distribution, metabolism, clearance, and bioavailability, whereas pharmacodynamic principles take this one step further and relate these factors to pharmacologic response. Pharmacogenetics is the study of heredity on variations in drug response among individuals and populations. Pharmacogenetic studies have established that genetics play an important role in the dose–concentration–response relationships of medications, whereas pharmacology is simply the study of drugs.

5.a. Drug A is the most potent agent. This is based on the fact that at any given concentration of this agent, the effect is greater than that of the other drugs at similar concentrations. Drug B has the same maximal effect; however, it occurs at a higher concentration. Drug C is similar to drug B; however, it is less efficacious, because its maximal effect occurs at a concentration that is 50% lower than that of drug B.

6.c. Increases warfarin metabolism, decreases warfarin metabolism. Chronic ethanol consumption can lead to increased hepatic metabolism of many medications that are cleared through the liver. Increased hepatic metabolism is related to enhanced enzyme function. Therefore, chronic ethanol users typically need higher-than-usual doses of warfarin to achieve therapeutic INRs. Acute ingestion of large amounts of ethanol at a time may inhibit warfarin metabolism. This may lead to elevated INRs and increase the risk of hemorrhagic complications. Moderate ingestion of ethanol does not seem to affect the metabolism of warfarin.

7.a. Amiodarone. Amiodarone significantly increases the levels of digoxin. Amiodarone decreases the clearance of digoxin and inhibits p-glycoprotein. Amiodarone can increase digoxin levels by 50% to 70%. This interaction can occur in the first days of therapy and a 50% dosage reduction is required immediately. Metoprolol does not increase the levels of digoxin; however, it can have synergistic effects on lowering heart rate and should be monitored closely. Simvastatin and fenofibrate do not alter the levels of digoxin.

8.c. Sodium depletion is an important factor in the development of renal insufficiency associated with ACE inhibitors. Patients with hyponatremia, dehydration, and severe HF are most dependent on the maintenance of renal perfusion by angiotensin II–mediated vasoconstriction of the efferent arteriole. Prevention of hyponatremia by decreasing diuretics can reduce such risk. Numerous studies, including the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, Veterans’ Administration Heart Failure Trial (V-HeFT) II, and Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), have shown ACE inhibitors to reduce mortality in patients with ischemic and nonischemic cardiomyopathy and mild-to-moderate HF. ACE inhibitors are considered to be associated with a class benefit; however, not all ACE inhibitors carry the FDA indication for HF. The ACE inhibitors that are approved for the treatment of HF include captopril, enalapril, lisinopril, quinapril, fosinopril, and ramipril. In 1998, the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial showed that high doses of lisinopril were superior to low doses in decreasing risk of death or hospitalization. Therefore, an effort to use target doses used in clinical trials is important (e.g., captopril 50 mg thrice daily, enalapril 10 mg twice daily, and lisinopril 20 mg daily). Potassium retention of ACE inhibitors is caused by a reduction in the feedback of angiotensin II to stimulate aldosterone release. Caution is necessary when initiating a potassium supplement in a patient on ACE inhibitor therapy.

9.c. (1) ii; (2) iii; (3) i; (4) iv. Agents exhibiting α-blockade include labetalol and carvedilol. Agents with ISA are pindolol, penbutolol, carteolol, and acebutolol. Agents with membrane-stabilizing activity are propranolol, labetalol, and acebutolol. β1-Selective agents include bisoprolol, betaxolol, atenolol, acebutolol, and metoprolol.

10.a. Diltiazem and verapamil decrease conduction velocity within the AV node and increase refractory period of nodal tissue. This then causes slowing of ventricular rate.

11.d. Nimodipine. Nimodipine is the only agent indicated for patients with subarachnoid hemorrhage. Nimodipine decreases the influx of extracellular calcium, thus preventing vasospasm.

12.a. Ethacrynic acid. Ethacrynic acid is the only loop diuretic that is not a sulfonamide. It is used only in patients allergic to other either loop or thiazide diuretics. Disadvantages of ethacrynic acid include gastrointestinal intolerance and a narrower dose–response curve.

13.b. False. Conivaptan is a dual vasopressin antagonist indicated for the treatment of euvolemic and hypervolemic hyponatremia. Its predominant pharmacodynamic effect is through the V2 antagonism of vasopressin in the renal collecting ducts that results in excretion of free water. Because of the limited number of HF patients with hypervolemic hyponatremia treated with conivaptan, safety in HF patients has not been established; therefore, its use in HF patients may be considered only when the clinical benefit outweighs the risk of adverse effects.

14.a. Inhibition of the Na+/K+-adenosine triphosphatase. Digoxin inhibits the Na+/K+-adenosine triphosphatase pump on the myocardial cell surface. This inhibits the ability of the cell to exchange potassium for sodium and thus leads to an increase in intracellular sodium. This increase in intracellular sodium leads to exchange of sodium for calcium, increasing intracellular calcium concentrations. Increased intracellular calcium enhances contraction coupling.

15.b. Discontinue the digoxin and administer digoxin-specific antibodies. Digoxin-immune Fab is indicated for patients with life-threatening ventricular arrhythmias relating to digoxin toxicity. It is also indicated in patients with progressive bradyarrhythmias, such as severe sinus bradycardia or second- or third-degree heart block not responsive to atropine. It should not be used for milder forms of digoxin toxicity. Also, in the setting of hyperkalemia and digitalis intoxication, digoxin-immune Fab fragment is indicated. Digoxin-immune Fab fragment is ovine derived; there is a potential for hypersensitivity reactions, and there are no data available in regard to readministration.

16.c. Milrinone. Milrinone is a phosphodiesterase inhibitor classified as inodilator. Thus, milrinone produces positive inotropic effects and vasodilation. Milrinone inhibits the phosphodiesterase III enzyme, leading to an increase in intracellular cAMP, thus causing increased intracellular levels of calcium. In addition, milrinone will decrease pulmonary pressures and left ventricular (LV) end-diastolic pressures more predictably than the other agents listed. These combined effects lead to minimal increases in myocardial O2 consumption. Also, milrinone may be useful in this patient secondary to chronic metoprolol therapy.

17.c. IV vitamin K works faster to lower the INR than oral vitamin K at similar doses. The onset of action of IV vitamin K is 1–2 hours compared to 6–10 hours for oral vitamin K. As a result, INR values return to normal quicker with IV vitamin K. The overall reduction in INR is dose dependent and not route dependent when comparing IV and oral formulations. Subcutaneous vitamin K has variable absorption which can lead to variations in time to onset as well as INR lowering effect.

18.b. Fondaparinux. Fondaparinux, a pentasaccharide, selectively inhibits activated Xa through its binding to antithrombin. Enoxaparin and UFH bind to both thrombin (IIa) and activated Xa, whereas bivalirudin binds directly to thrombin. UFH binds to thrombin and activated factor Xa in a 1:1 ratio, whereas LMWHs vary in their binding ratios.

19.c. Warfarin, with a target goal international normalized ratio (INR) of 2.5. This patient is at high risk for a thromboembolic event. Recommendations for antithrombotic therapy include risk stratification. Risks are stratified into high, moderate, and low. High-risk patients include patients with prior stroke or transient ischemic attack or systemic embolus, history of HTN, poor LV systolic function, age older than 75 years, rheumatic mitral valve disease, and a prosthetic heart valve. Moderate risk factors include age between 65 and 75 years, DM, and CAD with preserved LV systolic function. Low-risk patients are those younger than 65 years old with no clinical or transthoracic echocardiogram evidence of cardiovascular disease.

20.c. Warfarin with a target INR of 2.5 for 3 weeks before cardioversion and continued for 4 weeks after cardioversion. Recommendations from the Sixth ACCP Consensus Conference on Antithrombotic Therapy state that patients undergoing elective cardioversion for AFib should be initiated on oral anticoagulant therapy for 3 weeks before and at least 4 weeks after elective direct current cardioversion. The grade of evidence is 1C+. Also, an alternative approach would be to initiate anticoagulation, have the patients undergo a transesophageal echocardiography, and have the cardioversion performed if no thrombi are seen. Warfarin should be continued for at least 4 weeks, as long as the patient maintains normal sinus rhythm. This is a grade 1C recommendation.

21.a. Antithrombin. Heparin must first bind to antithrombin to exert its anticoagulant effect. This complex accelerates antithrombin effect. Heparin potentiates antithrombin’s effect by binding to a glucosamine unit within a pentasaccharide sequence.

22.b. 50 mg. Every 1 mg of protamine will antagonize approximately 100 units of heparin. Because this patient just received the bolus, she would require 50 mg of protamine. If she had received the dose 30 to 60 minutes ago, then a dose of 0.50 to 0.75 mg of protamine per 100 units of heparin would be required. If she had been on a continuous infusion of heparin, then the dosing would be dependent on the time and dose of the last bolus of heparin and the rate of infusion. In this scenario, most patients require approximately 25 to 50 mg of protamine.

23.a. 90% to 100%. There have been several reports of patients who have heparin-induced thrombocytopenia being treated with LMWH. However, the cross-reactivity in vitro approaches 100%. The use of LMWH should be considered a contraindication unless there is a documented negative test for antibodies against LMWH.

24.c. Argatroban, 2 µg/kg/min. Argatroban is hepatically cleared and, therefore, does not require dosing adjustment for patients with renal dysfunction and may be a safer alternative for anticoagulation. Lepirudin is reasonable as well; however, patients with significant renal dysfunction require appropriate dosing adjustments. Continuous infusion should not be used in patients with a creatinine clearance <15 mL/min because of accumulation of drug. LMWHs have a high likelihood for in vitro and in vivo cross-reactivity of 80% to 100%, and there is a potential for an increase in thrombotic complications.

25.b. 100 mg. The Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes (PLATO) trial evaluated antiplatelet strategies in addition to aspirin post-ACS. The trial did not mandate a specific aspirin maintenance dose which was left to the discretion of the provider. After trial completion, a subset analysis was performed which favored ticagrelor use with low maintenance dose aspirin (≤100 mg) as higher doses resulted in decreased ticagrelor effectiveness. The package insert for ticagrelor recommends the maintenance dose of aspirin to be 75–100 mg daily if being used concomitantly with ticagrelor. An initial 325 mg dose of aspirin should still be given with ticagrelor in the ACS setting.

26.d. The number of days to discontinue therapy prior to CABG. The recommended number of days prior to CABG surgery to stop clopidogrel or ticagrelor is 5. Patients in both the Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes (PLATO) trial and the Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation (CURE) trial had increased bleeding if the agents were not stopped at least 5 days prior to surgery. Although the competitive antagonist property of ticagrelor at the P2Y12 receptor and its short half-life (~7 hours) would lead clinicians to believe that ticagrelor could be stopped earlier than 5 days prior to surgery, that has not proven to be true.

27.c. In the Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes (PLATO) trial, patients were more likely to experience dyspnea in the ticagrelor arm versus the clopidogrel arm (14% vs. 8 %). Also, more patients had to discontinue ticagrelor than clopidogrel because of dyspnea (0.9% vs. 0.1%). The mechanism for increased dyspnea is hypothesized to be triggered by adenosine. Ticagrelor inhibits the clearance of adenosine thereby increasing its concentration in the circulation. Although, more dyspnea results from ticagrelor use, there were no differences in forced expiratory volume in 1 second (FEV1) between ticagrelor and clopidogrel.

28.c. Neutropenia. Ticlopidine causes neutropenia in 2.4% of patients who are initiated on therapy. Nearly 1% of patients develop severe neutropenia. Therefore, a complete blood count is required every 2 weeks during initiation of therapy for the first 3 months of therapy. Both agents can cause diarrhea and rash. Structurally, these two drugs are so similar that allergic cross-reactivity is expected. Thrombotic thrombocytopenic purpura has been reported with both agents. There have been >100 cases of thrombotic thrombocytopenic purpura reported with the use of ticlopidine and clopidogrel.

29.c. Adenosine diphosphate (ADP) inhibitor. ADP is released from red blood cells, activated platelets, and damaged endothelial cells, leading to platelet adhesion and aggregation. However, the precise mechanism of its action has not been completely identified. ADP blockade decreases the expression of the glycoprotein IIb/IIIa receptor. Platelet inhibition occurs at maximal effect within 3 to 5 days and produces approximately 40% to 50% platelet inhibition. The onset and degree of platelet inhibition can be expedited with use of loading doses (300 to 600 mg).

30.b. Abciximab. All glycoprotein IIb/IIIa inhibitors may cause thrombocytopenia. However, abciximab has the highest rate of all, based on the clinical trials.

31.c. Abciximab. Abciximab has a serum half-life of 10 to 30 minutes; however, because of its high binding affinity to the glycoprotein IIb/IIIa receptor, it maintains its activity for many hours after discontinuation of therapy, and abciximab can be detected in the serum for longer than 2 weeks. The short-acting inhibitors have half-lives of approximately 2 hours, depending on renal function; however, because of their competitive inhibiting nature, once the infusion is discontinued, their effects wane relatively quickly.

32.c. NYHA class IV heart failure. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) was a mortality trial comparing dronedarone to placebo in patients with moderate to severe heart failure for rhythm control. The trial was prematurely terminated as a significantly higher mortality rate was seen in the dronedarone arm versus placebo (8.1% vs. 3.8%). The risk of death was highest in patients with severely depressed left ventricular systolic function. The package insert for dronedarone states the drug is contraindicted in patients with NYHA Class IV heart failure or symptomatic heart failure with recent decompensation requiring hospitalization because it doubles the risk of death.

33.a. Dofetalide. Structural heart failure limits the use of antiarrythmic therapies for rhythm control in atrial fibrillation due to mortality concerns. Dofetalide has not shown to increase mortality in patients with atrial fibrillation who also have heart failure unlike dronedarone, flecanide, and quinidine. The agent of choice in this situation; however, would likely be amiodarone unless the patient has other contraindications for amiodarone therapy.

34.b. Amiodarone. Although amiodarone does not carry an FDA indication for the treatment of AFib, it can convert to and maintain normal sinus rhythm. The other agents listed are only used for rate control when used for AFib.

35.b. Amiodarone. The most recent advanced cardiac life support guidelines recommend that amiodarone be the first-line agent in patients with pulseless VT/VF. This recommendation is based on the Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest due to Ventricular Fibrillation (ARREST) trial, which showed that amiodarone increased the likelihood of admission to the hospital after an out-of-hospital arrest. This is further supported by the recently presented Amiodarone versus Lidocaine in Pre-Hospital Refractory Ventricular Fibrillation Evaluation (ALIVE) trial. Lidocaine is now considered Class Indeterminate based on the lack of controlled trials supporting its use in pulseless VT/VF. Procainamide administration is prolonged and not suitable for rapid administration. Bretylium is no longer available secondary to lack of raw materials.

36.c. Loading dose of 180 µg/kg and a maintenance dose of 1 µg/kg/min. Based on product information, eptifibatide loading dose should not be changed and the maintenance infusion should be initiated at 1 µg/kg/min. Eptifibatide is contraindicated in patients on dialysis and there is limited experience using this agent in this patient population. Tirofiban is not contraindicated in patients on dialysis; however, there are limited data to support its use in dialysis patients.

37.b. Enoxaparin 1 mg/kg daily. Enoxaparin is approved for both ST-segment-elevation and non-ST-segment-elevation MI. In patients with a creatinine clearance >30 mL/min then the standard dose of 1 mg/kg every 12 hours is appropriate. However, when the creatinine clearance is <30 mL/min then the dose should be reduced to 1 mg/kg once daily. Fondaparinux is contraindicated in patients with a creatinine clearance <30 mL/min.

38.d. Loading dose of 30 mg IV once followed by 0.75 mg/kg every 12 hours. Enoxaparin was recently approved for the treatment of ST-segment-elevation MI with fibrinolysis based on the ExTRACT-TIMI 25 trial. In the older patients, lower enoxaparin doses were used to minimize bleeding. There was a lower risk of the primary endpoint in those that received enoxaparin versus those receiving UFH. There was no difference in intracranial hemorrhage; however, there was a significantly higher rate of major bleeding with enoxaparin (2.1% versus 1.4%).

39.d. Time to presentation. Time to presentation is not a risk factor for intracranial hemorrhage in patients receiving thrombolytic therapy. In clinical trials, the risks for intracranial hemorrhage included age older than 65 years, low body weight (<70 kg), HTN on hospital admission, and the use of alteplase. Also, the levels of concomitant anticoagulation can also increase the risk of intracranial hemorrhage.

40.c. 15 mg bolus; then 50 mg over 30 minutes; then 35 mg over 60 minutes. Based on the first GUSTO trial, the most effective dosing for acute ST-segment-elevation MI is front-loaded tissue plasminogen activator. The maximum dose should be 100 mg and, therefore, Answer b may increase the risk of major bleeding, specifically intracranial hemorrhage. Answer d is standard dosing of recombinant tissue-type plasminogen activator and was found inferior to front loading. Finally, Answer a is the recommended dosing for acute ischemic stroke.

41.c. Daptomycin. Daptomycin may cause elevations in creatine phosphokinase (CPK) levels. The product literature for daptomycin recommends temporary discontinuation of medications that can raise CPK levels when a patient is receiving this antibiotic. Even though this adverse reaction is rare, CPK levels should be monitored weekly in patients receiving daptomycin alone and more frequently if statin therapy is continued.

42.a. A > P > C > G. HMG-CoA reductase inhibitors decrease LDL by 18% to 55%. Atorvastatin is the most potent agent statin of the group. Bile-acid sequestrants decreased LDL by 15% to 30%. Fibrates decrease LDL by 5% to 20%.

43.b. Forced diuresis with urine alkalinization and discontinuation of gemfibrozil and atorvastatin are indicated for this patient. Rhabdomyolysis secondary to the interaction of atorvastatin and gemfibrozil is responsible for this clinical picture. Rhabdomyolysis is defined as the disintegration of muscle, associated with the excretion of myoglobin in the urine. Clinical signs and symptoms include myalgias, elevated creatine kinase, elevated urine and serum myoglobin, and dark urine. Complications of rhabdomyolysis are numerous and may include renal failure, disseminated intravascular coagulation, metabolic acidosis, and cardiomyopathy. HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) can be considered direct myotoxins and may induce rhabdomyolysis when used alone. However, the risk of toxicity increases when statins are used in combination with fibric acid derivatives (gemfibrozil or fenofibrate), nicotinic acid, cyclosporine, itraconazole, or erythromycin, to name a few. Treatment of the underlying cause, in this case discontinuation of the offending agents, is necessary. In addition, renal failure caused by products of tissue degradation must be combated with urinary alkalinization and maintenance of a high urine volume.

44.b. Metoprolol. The American College of Cardiology (ACC) and American Heart Association (AHA) recommend the use of β-blockers in patients after surviving an MI to decrease mortality, sudden death, and reinfarction. Therefore, if this patient is not already on a β-blocker, one would be indicated, not only for HTN but also for secondary prevention.

45.d. Clonidine. Abrupt withdrawal of an α2-agonist is the most likely cause of severe rebound HTN. Typically, this is seen within 24 to 48 hours of discontinuation of clonidine and typically occurs in patients taking large doses for longer than 3 months. The best treatment for this is to restart clonidine. β-Blockers could make the situation worse by causing unopposed α1-stimulation.

46.b. Initiate nitroprusside drip and give IV fluids. Hypertensive emergencies are defined by the presence of end-organ damage in the face of high BP. This patient was dehydrated from diarrhea and had uncontrolled BP because of the medication change that occurred. Use of nitroprusside would be most appropriate in this patient because of the emergent situation of the renal insufficiency and possible cerebrovascular involvement exhibited by the headache. Typically, parenteral antihypertensive agents are initiated for hypertensive emergencies. In addition, it is necessary to correct the underlying cause of the hypertensive episode, if it can be identified; therefore, rehydration in this patient is prudent. Nitroprusside is the drug of choice because it has a quick onset of action yet is easily titratable. Sublingual nifedipine is no longer advocated because of the precipitous drop in BP and the subsequent adverse effects.

47.d. Lisinopril 5 mg daily. Because the patient is not already receiving ACE inhibitor therapy, an ACE inhibitor is indicated in patients with HF and a reduced ejection fraction (less than 35% to 45%) to decrease morbidity and mortality, as shown in the SOLVD, V-HeFT, and CONSENSUS trials. The patient has no contraindications to such therapy. If the patient’s renal function were changing, thereby making an ACE inhibitor inappropriate, then hydralazine plus a nitrate would be indicated, because V-HeFT I showed mortality benefit compared with placebo and an α-blocker. An angiotensin receptor blocker (ARB), like valsartan, would be indicated if the patient were intolerant to ACE inhibitors in the past. Both ACE inhibitors and ARB should be initiated at low doses, and titrated (as tolerated) to doses proven in clinical trials to reduce cardiovascular events.

48.a. Admit her to the hospital for IV furosemide therapy and hemodynamic monitoring. Nesiritide is contraindicated for use in patients with systolic BP <90 mmHg. However, based on meta-analyses that raised questions of increased renal dysfunction and mortality associated with nesiritide, the FDA convened a panel to assess available data and provide recommendations regarding appropriate use of nesiritide. These recommendations state that nesiritide should be limited to hospitalized patients with decompensated HF with dyspnea at rest and it should not be used to replace diuretics. Furthermore, because of insufficient evidence, nesiritide should not be used for intermittent outpatient infusions, for scheduled repetitive use, to improve renal function, or to enhance diuresis. A large-scale clinical trial to assess outcomes and further assess the risks of nesiritide versus standard therapy is currently being conducted.

49.b. Carvedilol 3.125 mg twice daily. All patients with stable, class II or III HF should be initiated on a β-blocker, unless a contraindication (bronchospastic disease, symptomatic bradycardia, or advanced heart block) or intolerance is exhibited. Initiation of β-blocker therapy is recommended in stable patients with mild-to-moderate HF and a low ejection fraction (less than 35% to 40%). The mortality benefit of β-blocker use was seen when added to a preexisting regimen of an ACE inhibitor and diuretic, with or without digoxin. It should be noted that β-blockers must be initiated at very low doses and only gradually increased if low doses have been well tolerated.

50.b. Carvedilol, metoprolol succinate, bisoprolol. Overwhelming mortality benefit in patients with chronic HF has been proven in clinical trials for carvedilol, metoprolol succinate, and bisoprolol when added to standard HF therapy. These agents are specifically recommended in the ACC/AHA guidelines for the management of chronic heart failure. Despite survival benefit with each of these β-blockers, a class effect with all β-blockers should not be assumed as demonstrated by the Carvedilol or Metoprolol European Trial (COMET). The COMET compared carvedilol with metoprolol tartrate in HF patients and concluded that carvedilol exhibited superior mortality benefit. β-Blockers with ISA should not be used on patients with HF. Pindolol and others with ISA (such as penbutolol, carteolol, and acebutolol) are partial β-agonists and can maintain normal sympathetic tone. This activity prevents the benefits seen with the reduced heart rate, cardiac output, and peripheral blood flow caused by other β-blockers.

51.c. Initiate isosorbide dinitrate and hydralazine. The ACC/AHA guidelines recommend the initiation of isosorbide dinitrate and hydralazine as a reasonable addition to standard therapy in blacks with New York Heart Association class III/IV HF. The A-HeFT trial evaluated a proprietary drug combination (hydralazine 37.5 mg and isosorbide dinitrate 20 mg per tablet) in African Americans with HF along with standard treatment; because of significant mortality benefit, the study was prematurely discontinued.

52.c. The benefit of long-term IV inotropic therapy may outweigh the increased mortality risk in refractory patients unable to be weaned from IV inotropic support. Because long-term IV positive inotropic therapy may cause an increased risk of death, such therapy is not regularly recommended. This risk, however, may be outweighed in patients who cannot be weaned from continuous support. Such patients with refractory HF may experience an improved quality of life because of the relative clinical stability afforded by the inotrope; therefore, IV positive inotropic therapy may be considered as a palliative measure in end-stage HF. The DIG (Digitalis Investigation Group) trial showed that digoxin’s benefit in HF was the alleviation of symptoms and improvement in clinical status. These findings were associated with a decreased morbidity (fewer hospitalizations) but not mortality. Because digoxin has negligible effect on survival, it is recommended that digoxin be used in conjunction with diuretics, ACE inhibitors, and β-blockers to decrease the clinical symptoms of HF. Furthermore, little evidence supports the practice of dosing digoxin according to serum levels. This is because of the lack of data exhibiting a relationship between digoxin serum concentrations and therapeutic effect. In the RALES trial, spironolactone was shown to be associated with reduced mortality and morbidity. However, the patients who were included in this trial were patients with class IV HF. Therefore, it would only be prudent to consider spironolactone in patients with recent or current severe HF symptoms. Efficacy and safety of spironolactone’s use in patients with mild-to-moderate HF is yet to be determined.

53.d. No prophylaxis is recommended in this patient. The recommendations according to the 2007 Guidelines for Prevention of Infective Endocarditis no longer recommend prophylactic antibiotics prior to dental procedures for people with mitral valve prolapse, rheumatic heart disease, bicuspid valve disease, calcified aortic stenosis, or congenital heart conditions such as ventricular septal defect, atrial septal defect, and hypertrophic cardiomyopathy.

54.b. Ampicillin, 2 g IV every 4 hours for 4 to 6 weeks, plus gentamicin, 1 mg/kg IV every 8 hours for 4 to 6 weeks. Treatment of enterococcal endocarditis is complicated because of the high levels of resistance to penicillin, extended-spectrum penicillins, and vancomycin. However, penicillin, ampicillin, or vancomycin in combination with an aminoglycoside causes synergistic bactericidal effect on these organisms. Treatment with an aminoglycoside for the full 4 to 6 weeks at a synergistic dose (1 mg/kg IV every 8 hours) in addition to the penicillin agent or vancomycin is required.


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