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Acute Care Cardiology

Acute Care Cardiology

Jo E. Rodgers, Pharm.D., BCPS (AQ Cardiology)

University of North Carolina School of Pharmacy Chapel Hill, North Carolina

Acute Care Cardiology

Learning Objectives:

1. Formulate treatment strategies for patients with acute decompensated heart failure (ADHF) and formulate an appropriate pharmacotherapeutical regimen for a given case scenario (e.g., warm and wet, cold and dry, other).

2. Create an evidence-based medication regimen for a patient with acute coronary syndrome given a variety of clinical scenarios (e.g., invasive/ conservative strategy, upstream antiplatelet therapy).

3. Describe an appropriate treatment strategy for ventricular arrhythmias using evidence-based


4. Prepare a treatment strategy for a newly diagnosed patient with idiopathic pulmonary arterial hypertension (PAH).

5. Develop an appropriate pharmacological and monitoring plan for antihypertensive drug therapy for managing hypertensive emergencies.

Self-Assessment Questions:

Answers to these questions may be found at the end of this chapter.

1. A.A. is a 25-year-old woman with a new diagnosis of idiopathic PAH. Her home drugs include warfarin 5 mg/day, furosemide 60 mg 2 times/ day, and bosentan 62.5 mg 2 times/day. Which one of the following is the best contraceptive strategy for this patient?

A. Estrogen-progesterone oral contraceptive.

B. Injectable hormonal contraceptive.

C. Any hormonal contraceptive and barrier methods.

D. Barrier method only.

2. F.F. is a 64-year-old man with New York Heart Association (NYHA) class III heart failure (HF) admitted for increased shortness of breath, dyspnea on exertion, and decreased exercise tolerance. He admits to dietary noncompliance and has indulged in bacon and eggs, popcorn, and french fries in the past 72 hours. His extremities appear well perfused, but he does have 3+ pitting edema in all four extremities. F.F.’s blood pressure (BP) is 115/75 mm Hg. Which one of the following is the most appropriate intravenous

(IV) vasoactive drug to treat this patient if the IV diuretic therapy fails?

A. Dobutamine.

B. Milrinone.

C. Nesiritide.

D. IV nitroglycerin.

3. H.E. is a 53-year-old woman admitted to the hospital after the worst headache she has ever experienced. Her medical history includes exertionalasthma,poorlycontrolledhypertension, and hyperlipidemia. She is drug noncompliant and has not taken her BP drugs, including clonidine, in 4 days. Vital signs include BP 220/100 mm Hg and heart rate (HR) 65 beats/minute. She receives a diagnosis of a cerebrovascular accident and hypertensive emergency. Which one of the following choices is the best management option for this patient’s hypertensive emergency?

A. Fenoldopam 0.1 mcg/kg/minute.

B. Nicardipine 5 mg/hour.

C. Labetalol 0.5 mg/minute.

D. Enalaprilat 0.625 mg IV every 6 hours.

4. W.M. is a 69-year-old man who presents to the hospital with a 3-mm ST-elevation myocardial infarction (MI) within 2 hours of chest pain onset. He is given clopidogrel 300 mg once daily and instructed to chew aspirin 81 mg 4 times/ day. Abciximab and unfractionated heparin are initiated as he is being wheeled to the cardiac catheterization laboratory for primary percutaneous coronary intervention (PCI). Four hours after returning to the intensive care unit, a complete blood cell count shows a platelet count of 15 × 10 3 cells/mm 3 . Which one of the following choices is the most likely culprit of this patient’s thrombocytopenia?

A. Clopidogrel.

B. Aspirin.

C. Unfractionated heparin.

D. Abciximab.

5. The Sudden Cardiac Death in Heart Failure trial evaluated the ef cacy of amiodarone or internal cardioverter-de brillator (ICD) versus placebo in preventing all-cause mortality in ischemic and non-ischemic NYHA class II and III patients with

HF. There was a 7.2% absolute risk reduction and

a 23% relative risk reduction in all-cause mortality

at 60 months with an ICD versus placebo. What is the number of patients needed to treat with an ICD to prevent one death versus placebo?

A. 1.3 patients.

B. 4.3 patients.

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C. 13.8 patients.

D. 43.4 patients.

6. A.D. is a 52-year-old woman with a history of witnessed cardiac arrest in a shopping mall; she was resuscitated with an automatic external de brillator device. On electrophysiology study, she is found to have inducible ventricular tachycardia. Which one of the following has signi cantly decreased the incidence of sudden cardiac death over other therapies in a patient population such as this (secondary prevention)?

A. Propafenone.

B. Amiodarone.


D. Metoprolol.

7. S.V. is a 75-year-old woman with a history of NYHA class III HF (LV ejection fraction [LVEF] 25%) and multiple non–ST-elevation MIs. She had an episode of sustained ventricular tachycardia during hospitalization for pneumonia. Her QTc interval was 380 milliseconds on the telemetry monitor. Given her comorbidities, what is the most appropriate treatment option for S.V.?

A. Procainamide.

B. Metoprolol.

C. IV magnesium.

D. Amiodarone.

8. You are working on a review article on newer treatment strategies for antiplatelet and anticoagulant therapy during PCI. You want to ensure that you retrieve all relevant clinical trials and related articles on your subject. You have searched MEDLINE and found 42 articles, but a few that you have seen before were not pulled up in a search by Medical Subject Headings. Which one of the following comprehensive databases should be searched next to ensure that you did not miss any key articles?

A. International Pharmaceutical Abstracts.

B. Iowa Drug Information Service.

C. Clin-Alert.

D. Excerpta Medica.

9. A physician on your team wants you to “do the paperwork” regarding an adverse drug reaction (ADR) that a patient on your team experienced caused by nesiritide. The patient had severe hypotension after the initial bolus dose of nesiritide for treatment of decompensated HF, even though his BP was safely in the “normal” range before therapy initiation. The hypotension led to decreased renal perfusion, resulting in

oliguric acute renal failure and subsequent hemodialysis initiation. The patient had no known renal insuf ciency before developing this complication. Which one of the following statements is correct regarding Joint Commission on Accreditation of Healthcare Organizations requirements for institutional ADR reporting?

A. A MedWatch form explaining the scenario in which the ADR occurred must be completed.

B. I nst it ut ions must create t hei r ow n de nition of ADR and make sure that practitioners are familiar with it.

C. Hospital practitioners/staff must use the Naranjo Algorithm for assessing the severity of the ADR.

D. Only severe or life-threatening ADRs need to be reported.

10. Your Pharmacy and Therapeutics Committee wants you to perform a pharmacoeconomic analysis on a new drug available to treat decompensated HF. This drug works through a speci c mechanism of action. Unlike other available inotropics (dobutamine and milrinone), which can increase mortality over time, this drug appears to reduce mortality in the long- term setting. However, the price is 10 times higher per day than other available drugs. Your ndings will be presented at the next P and T committee meeting to make a formulary decision about which medications to stock in your hospital pharmacy. What type of pharmacoeconomic analysis should be used to determine whether this new drug would be a better formulary choice than currently available products?

A. Cost-minimization analysis.

B. Cost-effectiveness analysis.

C. Cost-bene t analysis.

D. Cost-utility analysis.

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ADHF may occur because of one of the following:

1. An acute worsening of chronic HF,

2. A new cardiac event (e.g., MI, atrial brillation), or

3. An acute massive MI whose initial presentation is severe HF.

A. Hemodynamic Monitoring

Table 1. Hemodynamic Values in Patients with ADHF and Sepsis a



Typical ADHF

Typical Sepsis




Mean arterial pressure (MAP)






Heart rate





Cardiac output (CO) (L/minute)




Cardiac index (CI) (L/minute/m 2 )




Pulmonary capillary wedge pressure (PCWP)

8–12 b





Systemic vascular resistance (SVR) (dynes/ second/cm 5 )




Central venous pressure (CVP) (mm Hg)




a MAP = DBP + 1/3(SBP DBP) (SBP = systolic blood pressure; DBP = diastolic blood pressure), CI = CO/BSA (BSA = body surface area), SVR = (MAP – CVP)(80)/CO. b 15–18 mm Hg often desired/optimal in patients with HF to ensure optimal lling pressures.

1. Hemodynamic equations

a. BP = cardiac output (CO) × systemic vascular resistance

b. CO = stroke volume (SV) × HR

2. Parameters inuencing CO

a. Heart rate

i. Also known as chronotropy

ii. Controlled by autonomic nervous system

b. Stroke volume

i. Amount of blood ejected by the heart during systole

ii. Controlled by four factors:


Inotropy—ventricular contractility or “squeezing” force.


Afterload—resistance or pressure the left ventricular (LV) pumps against to eject blood into the aorta; estimated by the systemic vascular resistance.


Preload—amount of tension applied to the LV before contraction; equivalent to

LF end diastolic volume; estimated by the pulmonary capillary wedge pressure.


Lusitropy—diastolic relaxation of the ventricle.

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3. Forrester hemodynamic classifi cation 4 Category II: Category I: Pulmonary Normal congestion 3 Warm
3. Forrester hemodynamic classifi cation
Category II:
Category I:
Warm and dry
Warm and wet
Category III:
Category IV:
Pulmonary congestion and
Cold and dry
Cold and wet
10 15
mm Hg

Figure 1. Forrester Hemodynamic Classication Reprinted with permission from the American Medical Association. Nohria A, Lewis E, Warner Stevenson L. Medical management of advanced heart failure. JAMA 2002;287:628–40.

B. Clinical Presentation of ADHF

Table 2. Signs and Symptoms of ADHF

Congestion (Elevated Pulmonary Capillary Wedge Pressure)

Hypoperfusion (Reduced CO)

Dyspnea on exertion or at rest Orthopnea, paroxysmal nocturnal dyspnea Peripheral edema Rales Early satiety, nausea/vomiting Ascites Hepatomegaly, splenomegaly Jugular venous distention Hepatojugular reux

Fatigue Altered mental status or sleepiness Cold extremities Worsening renal function Narrow pulse pressure Hypotension Hyponatremia

C. Guideline Recommendations for ADHF

Table 3. Level of Evidence and Class of Effect for ADHF Guidelines

Level of Evidence

Level A

Randomized, controlled clinical trials

Level B

Case-control or cohort studies (post hoc, subgroup analysis, meta-analysis)

Level C

Expert opinion or observational studies

Class of effect

“Recommended” for routine clinical practice in all patients

“Should be considered” for the majority of patients

“May be considered” for individual patients

“Is not recommended” for any patient

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D. Drug Therapy Recommendations

Table 4. Overview of ADHF Guideline Recommendations

Diuretic Therapy

1. Recommended as an IV loop diuretic for patients admitted with uid overload (LOE = B).

2. When response to diuretics is minimal, the following options should be considered:


a. Fluid and sodium restriction,

b. Initiation of increased doses or continuous infusion of loop diuretic,

c. Addition of a second type of diuretic (metolazone or chlorothiazide), or

d. Ultraltration.

(LOE = C).

Inotropic Therapy

1. May be considered to relieve symptoms and improve end-organ function in patients with diminished peripheral perfusion or end-organ dysfunction (low output syndrome), particularly if:


a. marginal systolic blood pressure (less than 90 mm Hg),

b. symptomatic hypotension despite adequate lling pressure, or

c. unresponsive to, or intolerant of, IV vasodilators (LOE = C)

2. May be considered in similar patients with evidence of uid overload if they respond poorly to IV diuretics or manifest diminished or worsening renal function (LOE = C).

Vasodilator Therapy

1. May be considered in addition to IV loop diuretics to rapidly improve symptoms in patients without symptomatic hypotension (LOE = B).

2. May be considered in patients with persistent symptoms despite maximal loop diuretics and oral drug therapy (LOE = C).

3. When adjunctive therapy is required in addition to loop diuretics, IV vasodilators should be considered over inotropic drugs (LOE = B).

Invasive Hemodynamic Monitoring


Routine use of hemodynamic monitoring with invasive IV lines (e.g., Swan-Ganz pulmonary artery catheters) is not recommended (LOE = A).

E. Diuretic Medications

1. Loop diuretics (ascending limb of loop of Henle)

a. Most widely used and most potent, effective at low glomerular ltration rate (less than 30 mL/minute)

b. Furosemide (Lasix) most commonly used

2. Thiazides (distal tubule)

a. Relatively weak diuretics when used alone, not effective at low glomerular ltration rate

b. Reserved for add-on therapy in patients refractory to loop diuretics

3. Therapy for patients with diuretic resistance

a. Increase dose rather than frequency of loop diuretic.

(Note: Ceiling effect at approximately 160–200 mg IV furosemide.)

b. Add a second diuretic with a different mechanism of action.

i. Hydrochlorothiazide 12.5–25 mg PO daily, metolazone 2.5–5 mg PO daily

ii. Chlorothiazide 250–500 mg IV daily; consider if gastrointestinal edema (poor PO


c. Continuous infusion of loop diuretic

i. Furosemide 0.1 mg/kg/hour IV doubled every 4–8 hours to a maximum of 0.4 mg/kg/ hour

4. Adverse effects: electrolyte depletion (potassium and magnesium), worsening renal function

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F. Inotropic Medications

Table 5. Inotropic Therapy for ADHF


Dobutamine (Dobutrex)

Milrinone (Primacor)


β -agonist: stimulates AC to convert ATP to cAMP to CO; slight peripheral vasodilation.


PDE inhibitor: inhibits cAMP breakdown in heart to CO and in vascular smooth muscle to SVR.

of action

Clinical effects

Positive inotropic, chronotropic, and lusitropic effects

Positive inotropic and lusitropic effects, no chronotropic effects


ADHF short-term management—effective in “cold and wet” exacerbations with hypoperfusion and congestion


Start at 2.5–5 mcg/kg/minute; may titrate up to maximum 20 mcg/kg/minute

50 mcg/kg IV bolus for 10 minutes, then 0.375–0.75 mcg/kg/minute

Typical dose


mcg/kg/minute xed infusion

No bolus, 0.1–0.5 mcg/kg/minute xed infusion




1 hour, prolonged to 2–3 hours if CrCl < 50 mL/ min


Hepatically metabolized (inactive) and renally eliminated

90% renal

Adverse effects

Proarrhythmia, tachycardia, hypokalemia, myocardial ischemia, and tachyphylaxis (> 72 hours), possible increased mortality with long- term use

Proarrhythmia, hypotension (avoid bolus), tachycardia, < 1% thrombocytopenia, possible increased mortality with long-term use

Other comments

Recommended if hypotensive.

Recommended if receiving a β-blocker.

AC = adenylate cyclase; ADHF = acute decompensated heart failure; ATP = adenosine triphosphate; cAMP = cyclic adenosine monophosphate; CO = cardiac output; CrCl = creatinine clearance; PDE = phosphodiesterase; SVR = systemic vascular resistance.

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G. Vasodilator Therapy

Table 6. Vasodilator Therapy for ADHF


Sodium Nitroprusside (Nipride)



IV Nitroglycerin


Mechanism of

Nitric oxide–induced stimulation of GC to convert GTP to cGMP.

Recombinant B-type natriuretic peptide binds to natriuretic peptide receptor A to stimulate guanylate cyclase and production of cGMP. Natriuretic mechanism unknown.

Combines with sulfhydryl groups in vascular endothelium to create s-nitrosothiol compounds, which mimic nitric oxide’s stimulation of guanylate cyclase and production of cGMP.


Clinical effects

Balanced arterial and venous vasodilator

Hemodynamic effects: PCWP and SVR, minimal changes in HR or CI Neurohormonal effects: NE, ET-1, and aldosterone Natriuretic effects: urine output and sodium excretion

Preferential venous vasodilator > arterial vasodilator, arterial vasodilation at high doses


“Warm and wet” ADHF, hypertensive crises

“Warm and wet” ADHF, alternative to inotropes in “cold and wet” ADHF

“Warm and wet” ADHF, ACS, or hypertensive crises


0.3–0.5 mcg/kg/minute, by 0.5 mcg/kg/minute up to 3 mcg/kg/minute


mcg/kg bolus, 0.01 mcg/kg/

5 mcg/minute, by 5 mcg/minute up to 200 mcg/minute

minute, by 0.005 mcg/kg/minute up to 0.03 mcg/kg/minute

Typical dose

0.5–1 mcg/kg/minute

0.01 mcg/kg/minute xed infusion May omit bolus if low SBP

25–75 mcg/minute, titrated to response


< 10 minutes

20 minutes

1–4 minutes


Cyanide hepatically

Natriuretic peptide receptor C (no renal/hepatic adjustment)

Inactive metabolites in urine


thiocyanate renally



Adverse effects

Hypotension, cyanide or thiocyanate toxicity

Primarily hypotension (up to

Hypotension, reex tachycardia,

hour), tachycardia (less than inotropes)


headache, tachyphylaxis

ACS = acute coronary syndrome; ADHF = acute decompensated heart failure; CI = cardiac index; cGMP = cyclic guanine monophosphate; ET = endothelin; GC = guanylate cyclase; guanosine triphosphate = GTP; HR = heart rate; NE = norepinephrine; PAC = pulmonary artery catheter; PCWP = pulmonary capillary wedge pressure; SBP = systolic blood pressure; SVR = systemic vascular resistance.

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Patient Cases

1. D.D. is a 72-year-old man admitted to the ward team for HF decompensation. D.D. notes progressively increased dyspnea on exertion (now 10 feet, previously 30 feet) and orthopnea (now four pillows, previously two pillows), increasing bilateral lower extremity swelling (3+), a 13.6-kg weight gain in the past 3 weeks, and dietary noncompliance. He has a history of idiopathic dilated cardiomyopathy (LVEF 25%, NYHA class III), paroxysmal atrial brillation, and hyperlipidemia. Pertinent laboratory ndings: B-type natriuretic peptide 2300 pg/mL (0–50 pg/mL), potassium+ 4.9 mEq/L, blood urea nitrogen (BUN) 22 mg/dL, serum creatinine (SCr) 1 mg/dL, aspartate aminotransferase 40 IU/L, alanine aminotransferase 42 IU/L, international normalized ratio 1.3, partial thromboplastin time 42 seconds, BP 108/62 mm Hg, and HR 82 beats/minute. Home drugs include carvedilol 12.5 mg 2 times/day, lisinopril 40 mg/day, furosemide 80 mg 2 times/day, spironolactone 25 mg/day, and digoxin 0.125 mg/day. Which one of the following is the best option for treating his ADHF?

A. Carvedilol 25 mg 2 times/day.

B. Nesiritide 2 mcg/kg bolus, then 0.01 mcg/kg/minute.

C. Furosemide 120 mg IV 2 times/day.

D. Milrinone 0.5 mcg/kg/minute.

2. After being started on IV loop diuretics and metolazone 2.5 mg with only minimal urine output and rising creatinine (CrCl now 30 mL/minute), he is transferred to the coronary care unit for further management of diuretic-refractory decompensated HF. His carvedilol dose is now 6.25 mg 2 times/day, and lisinopril and spironolactone are being withheld. His BP is 110/75 mm Hg, and his HR is 75 beats/minute. How else should his decompensated HF be treated?

A. Nesiritide 2 mcg/kg bolus, then 0.01 mcg/kg/minute.

B. Sodium nitroprusside 0.3 mg/kg/minute.

C. Dobutamine 5 mcg/kg/minute.

D. Milrinone 0.5 mcg/kg/minute.

3. D.D. initially responds with 2 L of urine output overnight and weight decreased by 1 kg the next day. However, by day 5, his urine output has diminished again, and his SCr has risen to 4.3 mg/dL. He was drowsy and confused this morning during rounds. His extremities are cool and cyanotic, BP is 102/58 mm Hg, and HR is 98 beats/ minute. It is believed that he is no longer responding to his current regimen. A Swan-Ganz catheter is placed to determine further management. Hemodynamic values are cardiac index 1.5 L/minute/m 2 , systemic vascular resistance 2650 dynes/cm 5 , and pulmonary capillary wedge pressure 30 mm Hg. Which of the following is the most appropriate medication based on his current symptoms?

A. Milrinone 0.2 mcg/kg/minute.

B. Dobutamine 5 mcg/kg/minute.

C. Nitroglycerin 20 mcg/minute.

D. Phenylephrine 20 mcg/kg/minute.


A. Guideline Recommendations for Arrhythmias

Table 7. Level of Evidence and Classication for Arrhythmia Guidelines

Level of Evidence Multiple (3–5) clinical trials or registries or meta-analyses. Limited (2–3) clinical trials or registries; generally, a single randomized clinical trial or several non-randomized trials. Few (1–2) clinical trials/registries; may be only expert opinion, case series, or standard care.

Level A

Level B

Level C

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Table 7. Level of Evidence and Classication for Dysrhythmia Guidelines (continued)


Class of Effect

Class I

Agreement that benet strongly outweighs the risk of the procedure or treatment, and it should be performed because of its efcacy.

Class IIa

May be conicting evidence or diverging opinions, but the benet is greater than the risk; it is reasonable to consider the procedure or treatment because of its efcacy.

Class IIb

May be conicting evidence or diverging opinions, but benet outweighs the risk; procedure or treatment may be considered, but additional data are needed.

Class III

Agreement that the risk outweighs the benet; procedure or treatment is not effective and should not be performed and may be harmful.


An area of ongoing research but no denitive recommendations for or against.



Table 8. Common Arrhythmia Terms and De nitions



QT interval

Time from beginning of ventricular depolarization to end of ventricular repolarization

QTc interval

QT interval corrected for heart rate (HR)


Typically narrow QRS complex arrhythmias—atrial brillation, atrial utter, multifocal atrial tachycardia (MAT), paroxysmal supraventricular tachycardia, including atrial- ventricular nodal reentrant tachycardia (AVNRT) and AV reentrant tachycardia (AVRT)



Typically wide QRS complex arrhythmias—ventricular tachycardia (VT)



At least three consecutive premature ventricular contractions at a rate > 100 beats/minute - monomorphic ventricular tachycardia and polymorphic ventricular tachycardia (e.g., torsade de pointes)



Spontaneously terminates in less than 30 seconds



Sustained ventricular tachycardia

Lasts > 30 seconds or requires cardioversion because of hemodynamic instability

Torsade de pointes

Induced primarily when QTc interval > 500 milliseconds

Sudden cardiac death

Rapid death caused by pulseless VT or ventricular brillation (VF), pulseless electrical activity, or asystole

Proarrhythmic events

New type of arrhythmia or worsening of existing arrhythmia after initiation of an antiarrhythmic medication (drug-induced), most commonly torsade de pointes

Structural heart

HF, status post-acute myocardial infarction, valvular heart disease, left valvular (LV) hypertrophy Note: Class IA and IC medications are contraindicated because of increased proarrhythmia risk.


De brillation threshold

Energy requirement (joules) necessary for debrillation of an arrhythmia into sinus rhythm

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Table 9. Antiarrhythmic Drug Effects

Na + channel blockers Class IA Class IB Class IC


ECG Effect

Primary Effect

Quinidine, procainamide, disopyramide Lidocaine, mexiletine Propafenone, ecainide, moricizine


Slows depolarization


Slows depolarization Slows depolarization

↑↑ QRS



Slows AV nodal

Class II

Metoprolol, esmolol, atenolol



K + channel blockers Class III

Amiodarone, sotalol, dofetilide, ibutilide


Slows repolarization

Ca 2+ channel blockers Class IV

Diltiazem, verapamil


Slows AV nodal conduction

AV = atrioventricular; ECG = electrocardiography; K + = potassium plus.

Table 10. Antiarrhythmic Drug Properties


Mechanism of Action, Pharmacokinetics Adverse Effects, and Drug Interactions


Dosing by Indication


MOA: strong vagolytic and anticholinergic properties, Na + channel blockade AEs: Nausea, vomiting, diarrhea 30%, use-dependent proarrhythmia rst 72 hours (torsade de pointes), “cinchonism” (CNS symptoms, tinnitus), and HF (causes exacerbation) DI: warfarin, digoxin

Avoid use for atrial brillation cardioversion caused by GI AEs A b maintenance:

sulfate: 200–400 mg every 6 hours Gluconate: 324 mg every 8–12 hours


MOA: Na + channel blockade AEs: decrease dose in renal and liver dysfunction (active metabolite NAPA accumulates), lupus-like syndrome in 30% of patients if > 6 months treatment, hypotension (IV): 5%, and HF (causes exacerbation)

A b conversion (IV):

1 g for 30 minutes, followed by 2 mg/ minute over one hour (efcacy 51% at 1 hour) A b maintenance:

Not recommended


VT (preserved LVEF > 40%):


mg/minute loading infusion until


mg/kg, arrhythmia ceases,

or QRS widens > 50% VT maintenance: 2–4 mg/minute


MOA: potent Na + and M 2 blockade; strong negative inotropic effect AEs: anticholinergic side effects (urinary retention, constipation, tachycardia, dry eyes), heart block and HF (causes exacerbation) CI: glaucoma DI: 3A4 inhibitors

A b conversion:

200 mg PO q4h (maximum 800 mg) Maintenance:

400–600 mg/day in divided doses


MOA: inactive Na + channel blocker Dose adjust in HF, liver failure, elderly patients, renal dysfunction AEs: CNS symptoms, perioral numbness, seizures, confusion, blurry vision, tinnitus CI: third-degree AV heart block

VT/VF conversion:

pulseless VT/VF or stable VT with LVEF > 40%: 1–1.5 mg/kg IVP × 1; repeat 0.5–0.75 mg/kg every 3–5 minutes (maximum 3 mg/kg) LVEF < 40%: 0.5–0.75 mg/kg IVP; repeat 0.5–0.75 mg/kg every 3–5 minutes (maximum 3 mg/kg) VT maintenance: 1–2 mg/minute


MOA: inactive Na + channel blocker CI: third-degree AV heart block

VT maintenance: 200–300 mg every 8 hours

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Mechanism of Action, Pharmacokinetics Adverse Effects, and Drug Interactions


Dosing by Indication


MOA: Na + and Ca 2+ channel blocker, ß-blocker AEs: metallic taste, dizziness CI: HF (causes exacerbation), liver disease DI: digoxin by 70%; warfarin by 50%

A b conversion:


mg PO × 1 (ef cacy 45% at 3 hours)

A b maintenance:

150–300 mg every 8–12 hours


MOA: strong Na + channel blockade; vagolytic, anticholinergic, and negative inotropic effects AEs: dizziness, tremor CI: HF (causes exacerbation), CAD DI: digoxin by 25%

A b conversion:


mg PO × 1 (ef cacy 50% at 3 hours)

A b maintenance:

50–150 mg every 12 hours


MOA: sodium, K + , calcium channel blocker, β-blocker AEs: pulmonary brosis 3%–17%, hyperthyroidism 3%; hypothyroidism 30%–50%; neurologic toxicity 20%–40%; blue-gray skin 15%; torsade < 1%; AV block 14%; hypotension, phlebitis (IV)

A b conversion:

IV: 5–7 mg/kg over 30–60 minutes then 1.2–1.8 g/day continuous IV or in divided oral dose until 10 g PO/5gIV PO: 400 mg 3 times/day for 5–7 days (until 10 g) A b maintenance:

200–400 mg/day

CI: iodine hypersensitivity, hyperthyroidism, heart block DI: warfarin, digoxin, HMG-CoA-reductase inhibitors, phenytoin ↑ ≥ 50% (among others)

Pulseless VT/VF conversion:


mg IVP every 3–5 minutes (ARREST trial) Or 5 mg/kg IVP in 30 mL D 5 W; repeat 2.5 mg/kg (ALIVE trial)

mg IVP × 1 in 20 mL D 5 W; repeat 150

Inhibits cytochrome P450 (CYP) metabolism:

CYP2C9, CYP2D6, and CYP3A4

Stable VT: 150 mg IVP × 1 over 10 minutes

Inhibits P-glycoprotein in GI tract to increase digoxin bioavailability • Maximum simvastatin dosage 20 mg/day *Does not increase mortality in patients with HF.

VT/VF maintenance: 1 mg/minute × 6 hours, followed by 0.5 mg/minute (maximum 2.2 g/day)


MOA: K + channel blocker, also β 1 - and β 2 -receptor blocking properties AEs: HF exacerbation, bradycardia, wheezing; 3%–8% torsade within 3 days of initiation; bronchospasm CI: baseline QTc > 440 milliseconds or CrCl < 40 mL/minute in atrial arrhythmias

Not effective for conversion A b maintenance: CrCl


mg 2 times/day > 60 mL/minute


mg/day 40–60 mL/minute

Contraindicated < 40 mL/minute

VT maintenance: CrCl



mg 2 times/day > 60 mL/minute

*Double dose every 3 days; NTE QTc > 500 milliseconds; hospitalization mandatory for initiation


mg/day 30–60 mL/minute


mg every 36–48 hours 10–30 mL/minute



mg > every 48 hours < 10 mL/minute


MOA: Pure K + channel blocker only AEs: torsade (0.8%; 4% if no renal adjust), dizziness, diarrhea DI: 3A4 inhibitors or drugs secreted by kidney: cimetidine, ketoconazole, verapamil, trimethoprim, prochlorperazine, megestrol and hydrochlorothiazide CI: baseline QTc > 440 milliseconds or CrCl < 20 mL/minute

*Does not increase mortality in patients with HF.

A b conversion: CrCl


mcg PO 2 times/day > 60 mL/minute


mcg PO 2 times/day 40–60 mL/minute


mcg PO 2 times/day 20–40 mL/minute

(efcacy 12% at 1 month)

A b maintenance:

Titrate upward based on QTc NTE 500 milliseconds or > 15% in QTc after initial 5 doses (hospitalization mandatory!)

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Mechanism of Action, Pharmacokinetics Adverse Effects, and Drug Interactions


Dosing by Indication


MOA: K+ channel blocker; also Na + and β-blocking properties AEs: 8% torsade risk; requires ECG monitoring during and 4 hours after cardioversion DI: 3A4 inhibitors or QT prolonging drugs CI: receiving concomitant antiarrhythmics or QTc > 440 milliseconds before initiation


b conversion: 1 mg × 1 IV (60 kg) or

0.01 mg/kg (< 60 kg), repeat in 10 minutes



(efcacy 47% at 90 minutes)

Slightly more effective for converting atrial utter than atrial brillation

AE = adverse effect; Ab = atrial brillation; ALIVE = amiodarone versus lidocaine in prehospital refractory ventricular brillation evaluation; ARREST = amiodarone out of hospital resuscitation of refractory sustained ventricular tachycardia; CAD = coronary artery disease; CI = contraindications; CrCl = creatinine clearance; CNS = central nervous system; ECG = electrocardiogram; DI = drug interactions; GI = gastrointestinal; HF = heart failure; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; IV = intravenous; IVP = intravenous push; K+ = potassium plus; MOA = mechanism of action; NTE = not to exceed; VF = ventricular brillation; VT = ventricular tachycardia.

C. Acute Tachyarrhythmias

1. Tachycardia with a pulse

a. Give oxygen; assess airway, breathing, and circulation and treat reversible causes.

b. If unstable, administer immediate direct current cardioversion (DCC).

c. If stable, determine whether QRS complex is narrow or wide.

i. Narrow complex tachycardia (usually atrial arrhythmias).

(a) Regular rhythm

(1) Supraventricular tachycardia (SVT) or sinus tachycardia likely

(a) Vagal maneuvers (class I, level of evidence [LOE B]) and/or adenosine 6 mg IVP, followed by 12 mg IVP (may repeat 1 time) (class I, LOE A)

(i) Use adenosine cautiously in severe coronary artery disease (CAD) because it may produce atrial brillation and induce myocaridal ischemia.

Table 11. Management of Supraventricular Tachycardia




If converts, likely AT, AVNRT, AVRT, or WPW



Any of the following depending on clinical presentation:

Catheter ablation


Verapamil, diltiazem, β-blockers, sotalol, amiodarone


Flecainide, propafenone a


If infrequent, no therapy or pill-in-the-pocket (LOE varies depending on clinical presentation)


Same as above; however, AVOID verapamil, diltiazem, and digoxin

If persistent with AV block , likely atrial utter or AT


IV ibutilide, b procainamide, or ecainide plus AV nodal blocking agents or overdrive pacing/DCC

a Relatively contraindicated for patients with coronary artery disease, LV dysfunction, or other signicant heart disease., b Ibutilide is especially effective if atrial utter but should not be used if LVEF < 30% because of risk of polymorphic ventricular tachycardia., AT = atrial tachycardia; AV = atrioventricular; AVNRT = atrioventricular nodal reciprocating/reentrant tachycardia; AVRT = atrioventricular reciprocating/reentrant tachycardia; DCC = direct current cardioversion; SVT = supraventricular tachycardia; WPW = Wolff-Parkinson-White [syndrome].

Acute Care Cardiology

(b) Irregular rhythm

(1) Atrial brillation or atrial utter likely

(a) Rate control versus rhythm control


Rate control recommended for patients with persistent or permanent atrial brillation (class I, LOE B).


If hemodynamically unstable, DCC recommended (class I, LOE C).

Table 12. Management of Atrial Fibrillation




Newly Discovered AF


No therapy needed unless symptoms, AC as needed


If accepted as permanent, AC and RC as needed; otherwise, consider AAD with DCC


Recurrent AF


If minimal or no symptoms, AC and RC as needed


If disabling symptoms, use anticoagulation and rate control as needed with AAD (ablation if AAD fails)


Permanent AF


AC and RC as needed

AAD = antiarrhythmic drug; AC = anticoagulation; AF = atrial brillation; DCC = direct current cardioversion; RC = rate control.

Table 13. Rate Control and Rhythm Control


Rate Control

General presentation

β-blockers or nondihydropyridine calcium channel blockers (diltiazem, verapamil) (class I, LOE B)

If HF and no accessory pathway present

Digoxin a (class I, LOE B) or amiodarone (class IIa, LOE C)

If accessory pathway present

Amiodarone (class IIa, LOE C)


Rhythm Control

Unstable and known duration < 48 hours

Before DCC, IV UFH immediately beforehand


(class I, LOE C)

Unstable and duration unknown or > 48 hours

Before DCC, TEE to rule out thrombus + IV UFH before DCC if




(class I, LOE C)

Stable and duration unknown or > 48 hours

Before DCC, RC + warfarin (international normalized ratio 2–3) 3–4 weeks before and 4 weeks after (class I, LOE C) If AF for up to 7 days, either elective DCC or chemical cardioversion b


Flecainide, dofetilide, propafenone, ibutilide (class I, LOE A) or amiodarone (class IIa, LOE A)

Digoxin and sotalol may be harmful when used for pharmacological cardioversion of AF and are not recommended (class II, LOE A). If AF more than 7 days, either elective DCC or chemical cardioversion



Dofetilide (class I, LOE A), amiodarone, ibutilide (class IIa, LOE A) b

a If paroxysmal AF, avoid digoxin (class III, LOE B), b Quinidine, procainamide, disopyramide, and dofetilide should NOT be started out of hospital for conversion of AF to sinus rhythm (class III, LOE B). AF = atrial brillation; DCC = direct current cardioversion; IV = intravenous; LOE = level of evidence; RC = rate control; TEE = transesophageal echocardiograph; UFH = unfractionated heparin.

ii. Wide complex tachycardia (usually ventricular arrhythmias)

(a) Ventricular tachycardia or unknown mechanism

Acute Care Cardiology

(1) IV procainamide, amiodarone (class I, LOE B), or lidocaine (class IIb, B) (2) Amiodarone preferred if LV dysfunction or signs of HF (class I, LOE B) (3) Prepare for synchronized DCC if drug therapy fails.

(b) De nite supraventricular tachycardia (see narrow complex tachycardia) (1) If supraventricular tachycardia and bundle branch block (BBB), treat as supraventricular tachycardia (see above).

(2) If pre-excited supraventricular tachycardia, IV, ibutilide or procainamide (class I, LOE B) or DCC (class I, LOE C)

2. Premature ventricular contractions


Avoid ecainide, encainide, and moricizine (class IC) post MI due to increased mortality.


β-blockers are useful for controlling symptomatic premature ventricular contractions.

3. Ventricular tachycardia

a. Nonsustained ventricular tachycardia

i. If asymptomatic, no therapy required.

ii. If symptomatic, β-blockers.

(a) If unresponsive, use amiodarone or sotalol.

b. Sustained ventricular tachycardia (QTc not prolonged)

Table 14. Management of Sustained Ventricular Tachycardia



Stable Sustained Monomorphic VT

Stable Sustained Monomorphic VT

Stable Sustained Monomorphic VT

General presentation

Associated with AMI

Associated with CAD and idiopathic VT (Repetitive)

Associated with CAD and idiopathic VT (Repetitive)

Procainamide IV (class IIa, LOE = B)

Procainamide IV (class IIa, LOE = B)

Lidocaine IV (class IIb, LOE = C)

Lidocaine IV (class IIb, LOE = C)

Amiodarone IV, β-blockers, procainamide IV (class IIa,

Amiodarone IV, β -blockers, procainamide IV (class IIa,


C) (Note: avoid procainamide if LV disfunction)

Unstable Sustained Monomorphic VT

Unstable Sustained Monomorphic VT

Unstable Sustained Monomorphic VT

General presentation

Refractory to DCC

Recurrent with procainamide


(class I, LOE = C)

Amiodarone 150 mg IV for 10 minutes (class IIa, LOE = C)

Amiodarone 150 mg IV for 10 minutes (class IIa, LOE = C)

Amiodarone 150 mg IV for 10 minutes (class IIa, LOE = C)

Amiodarone 150 mg IV for 10 minutes (class IIa, LOE = C)

AMI = acute myocardial infarction; CAD = coronary artery disease; DCC = direct current cardioversion; IV = intravenous; LOE = level of evidence; VT = ventricular tachycardia.

c. Polymorphic ventricular tachycardia (prolonged QTc)

i. Torsade de pointes


Induced primarily when QTc interval more than 500 milliseconds


Withdrawal of any offending medications that may induce torsade de pointes and correction of electrolyte abnormalities (low Mg 2+ or potassium + ) is recommended (class I, LOE = A). (1) Class I and class III antiarrhythmic drugs (2) Drug interactions via cytochrome P450 3A4 metabolized drugs: azole antifungals, erythromycin, clarithromycin, or QT prolonging drugs:

pentamidine, haloperidol, ziprasidone, droperidol, sulfamethoxazole/ trimethoprim, promethazine.

Acute Care Cardiology

Table 15. Management of Torsade de Pointes




DCC with sedation (class I, LOE = B)

Few episodes of TdP with prolonged QT

IV Mg 2+ 1–2 g IVP (maximum 16 g/24 hours a ) (class IIa, LOE = B)

Heart block and symptomatic bradycardia

Pacemaker placement (class I, LOE A)


β-blockers (especially if ischemia suspected) (class I, LOE = B)

If associated with AMI

Lidocaine 1–1.5 mg/kg IVP (class IIb, LOE = C)

a If normal renal function. AMI = acute myocardial infarction; DCC = direct current cardioversion; IVP = intravenous push; LOE = level of evidence; TdP = torsade de pointes.

d. Pulseless ventricular tachycardia or brillation algorithm

i. De brillate and perform cardiopulmonary resuscitation.

ii. Epinephrine 1 mg IV/IO (intravenously/intraosseous) every 3–5 minutes during cardiopulmonary resuscitation (evidence = IIb) or vasopressin 40 U IV/IO × 1 dose to replace rst or second epinephrine dose during cardiopulmonary resuscitation (evidence = indeterminant).

iii. Amiodarone 300 mg IV/IO × 1 (LOE = IIb), additional 150 mg IV/IO × 1 can be administered.


Consider if pulseless ventricular tachycardia/ventricular brillation persists after

two or three shocks, cardiopulmonary resuscitation, and vasopressor therapy.


Give during cardiopulmonary resuscitation to facilitate circulation of drug before or after shock.

iv. Lidocaine 1–1.5 mg/kg intravenous push (IVP) second line to amiodarone (class indeterminant); may repeat with 0.5–0.75 mg/kg IV/IO every 5–10 minutes (maximum 3 mg/kg) and continue with 1–4 mg/minute infusion if return of spontaneous circulation with lidocaine boluses.

4. Pulseless electrical activity or asystole algorithm

a. Cardiopulmonary resuscitation (no debrillation).

b. Epinephrine 1 mg IV/IO every 3–5 minutes or vasopressin 40 U IV/IO (1 dose to replace the rst or second epinephrine doses) (class IIb).

c. Atropine 1 mg every 3–5 minutes × 3 (total 0.04 mg/kg) if HR < 60 beats/minute for asystole or slow pulseless electrical activity (class indeterminant).

D. Primary Prevention of Sudden Cardiac Death

1. ICD therapy is recommended to reduce total mortality due to sudden cardiac death in patients with LV dysfunction caused by prior MI (more than 40 days post-MI), have LVEF 30%–40% or less, are NYHA class II or III, are receiving optimal chronic medications, and have reasonable survival expectation (class I, LOE = A).

E. Secondary Prevention of Sudden Cardiac Death

1. ICD implantation is a reasonable treatment of recurrent sustained ventricular tachycardia in post-MI patients with normal or near-normal LVEF who are on optimal medications and have a reasonable survival expectation of more than 1 year (class IIa, LOE = C).

2. Contraindications: evolving acute MI with ventricular tachycardia, acute ventricular tachycardia after coronary artery bypass graft, ventricular brillation caused by atrial brillation, terminal illness, psychiatric disorder, severe NYHA class IV (nontransplantable) HF

Acute Care Cardiology

Table 16. Alteration of Debrillation Threshold

Threshold Alteration



Increase threshold

Amiodarone, lidocaine, and mexiletine

Reprogram ICD, increased energy (joules) required

Decrease threshold


May decrease energy needed for DCC

No change

β-blockers, class IA

DCC = direct current cardioversion; ICD = internal cardioverter-debrillator.

Patient Cases

4. C.D. is a 68-year-old man admitted after an episode of syncope with a presyncopal syndrome of seeing black spots and dizziness before passing out. Telemetry monitor shows sustained ventricular tachycardia, however


patient still has a pulse and his BP is 100/64. His medical history includes HF NYHA class III, LVEF 30%,


× 2, hypertension × 20 years, left-ventricular hypertrophy, diabetes mellitus, and diabetic nephropathy.


current drugs include lisinopril 5 mg/day, furosemide 20 mg 2 times/day, metoprolol 25 mg 2 times/day,

digoxin 0.125 mg/day, glyburide 5 mg/day, and aspirin 325 mg/day. BP 120/75 mm Hg, HR 80 beats/minute, BUN 30 mg/dL, SCr 2.2 mg/dL, 70 kg. Which one of the following is the best therapy to initiate for conversion of his sustained ventricular tachycardia?

A. Amiodarone 150 mg IV for 10 minutes, followed by 1 mg/minute × 6 hours and then 0.5 mg/minute.

B. Sotalol 80 mg 2 times/day, titrated to QTc about 450 milliseconds.

C. Dofetilide 500 mcg 2 times/day, titrated to QTc about 450 milliseconds.

D. Procainamide 20 mg/minute, maximum 17 mg/kg.

5. C.D. presents to the emergency department 3 months after amiodarone maintenance initiation (he refused ICD placement) after a syncopal episode in which he lost consciousness for 30 seconds, according to witnesses. He also complains of rapid HR episodes where he feels dizzy and lightheaded. He feels very warm all the time (he wears shorts even though it is winter), is unable to sleep, and has experienced a 3-kg weight loss. He received a diagnosis of hyperthyroidism due to amiodarone therapy. On telemetry, he shows runs of nonsustained ventricular tachycardia. With an amiodarone half-life of 50 days, how long do you expect the effects of amiodarone to be provoking hyperthyroidism in this patient?

A. Never.

B. 1 month.

C. 6 months.

D. 1 year.

F. Special Patient Populations

1. Heart failure

a. Dofetilide—neutral effect on mortality

2. Acute MI

a. Encainide, ecainide, moricizine—increases mortality when used for premature ventricular contraction control post-MI

b. Class IA medications—increase mortality in post-MI survivors

c. Dofetilide—neutral effect on mortality in LV dysfunction post-MI


A. See “Levels of Evidence and Classes of Recommendations from the Arrhythmias” section.

B. Unstable Angina and Non–ST-Elevation MI

Acute Care Cardiology

Table 17. Unstable Angina and Non–ST-Elevation MI De nitions


Acute angina at rest, typically prolonged > 20 minutes, ST-segment depression, T-wave inversion, or no ECG changes may occur, but no biomarkers for cardiac necrosis present


Same as above, only with positive cardiac enzyme biomarkers of necrosis (troponin I or T elevation, CKMB fraction > 5%–10% of total CK)

CKMB = creatine kinase myocardial band; ECG = electrocardiogram; NSTEMI = non–ST-elevation MI; UA = unstable angina.

1. Unstable angina/non–ST-elevation MI (UA/NSTEMI) goals

a. Prevent total occlusion of the infarct-related artery.

i. Glycoprotein IIb/IIIa inhibitors plus unfractionated heparin or enoxaparin (preferred).

ii. PCI can be either or both:


PCI = either percutaneous transluminal coronary angiography, (i.e., “balloon”);


Stent implantation. (1) Thrombolytics have shown no benet in NSTEMI or unstable angina and bleeding.

b. Control chest pain and associated symptoms.

2. Initial Management

a. “MONA”

Table 18. “MONA” Algorithm


= Morphine

Morphine 1–5 mg IV is reasonable for patients whose symptoms are not relieved despite NTG or if they recur (class IIa, LOE N/A).


= Oxygen

Oxygen if O 2 saturation < 90% or high-risk features for hypoxemia (class I, LOE B).


= Nitroglycerin

Nitroglycerin spray or SL tablet 0.4 mg × 3 doses to relieve acute chest pain (if pain unrelieved after 1 dose, call 911) (class I, LOE C).


Nitroglycerin IV 5 mcg/minute, titrate to chest pain relief or 200 mcg/minute if pain is unrelieved by morphine and sublingual NTG (class I, LOE C). Dose may be limited by hypotension.


Used during rst 48 hours for treatment of persistent chest pain, HF, and HTN

A = Aspirin

Aspirin chew and swallow nonenteric-coated 162–325 mg × 1 dose (class I, LOE A).

HF = heart failure; HTN = hypertension; IV = intravenous; LOE = level of evidence; N/A = not available; NTG = nitroglycerin; SL = sublingual.

b. Diagnosis

i. History of chest pain syndrome, ECG changes, serum biomarkers.

3. Early Hospital Anti-ischemic and Analgesic Therapy

a. IV nitroglycerin

i. Indicated in rst 48 hours for persistent ischemia, HF, or hypertension (class I, LOE


ii. Use should not preclude other mortality-reducing therapies (β-blocker or angiotensin- converting enzyme inhibitor [ACEI]) due to no mortality benet.

iii. Dose: 10 mcg/minute, titrate to pain relief or maximum 200 mcg/minute.

iv. Adverse effects: headache, hypotension, and tolerance.

v. Contraindications: sildenal or vardenal use within 24 hours or tadalal use within

Acute Care Cardiology

48 hours; systolic BP less than 100 mm Hg or more than 30 mm Hg below baseline, HR less than 50 beats/minute, HR less than 100 beats/minute in the absence of symptomatic HF or right ventricular infarction

b. β-Blockers

i. Indicated within rst 24 hours if no contraindications (class I-PO/class IIa–IV, LOE B)

ii. First-line therapy for reducing chest pain, infarction size, and LV wall stress.

iii. Oral (PO) route preferred.

iv. Metoprolol 5 mg IV every 5 minutes × 3 doses, then 25–50 mg PO 2 times/day uptitrated as tolerated.

v. Contraindication: signs of HF or low-output state, other risk factors for cardiogenic shock, or other relative contraindications (PR > 0.24 seconds or third-degree heart block, active asthma, or reactive airway disease)

c. Angiotensin-Converting Enzyme Inhibitors

i. Indicated PO within rst 24 hours if pulmonary congestion or LVEF 40% or less in absence of hypotension (class I, LOE A).

ii. Contraindication (IV therapy): increased risk of hypotension with exception of patients with refractory hypertension.

iii. Angiotensin receptor blocker indicated if contraindication to ACEI.

d. Nondihydropyridine calcium channel blockers—verapamil, diltiazem

i. Recommended if continuing or frequently recurring ischemia and contraindication to

β-blocker therapy (LOE I, class B) or recurrent ischemia after β-blockers and nitrates fully used (LOE IIa, class C).

(a) No real benet or detriment on mortality; primarily symptom relief effects.

ii. Contraindication: clinically signicant LV dysfunction, immediate release

dihydropyridine calcium channel blockers should not be administered in the absence of a β-blocker.

4. Early Hospital Antiplatelet Therapy

a. Aspirin

i. Indicated immediately after hospital presentation and continue indenitely (class I, LOE A).

b. Clopidogrel

i. Indicated if aspirin allergy or major gastrointestinal intolerance (class I, LOE A).

ii. Loading dose (LD) 300 mg PO followed by daily oral maintenance dose 75 mg.

iii. Higher oral LD of 600 or 900 mg more rapidly inhibits platelet aggregation with higher absolute level of inhibition, but additive clinical efcacy and safety has not been established.

Acute Care Cardiology

Table 19. Antiplatelet and Anticoagulant Therapy

Initial Invasive Strategy

Initial Conservative Strategy

Antiplatelet Therapy

Antiplatelet Therapy

ASA + CLO or IV GP IIb/IIIa inhibitor (upstream) (class I, LOE A) -OR- ASA + CLO plus IV GP IIb/IIIa inhibitor (upstream) (class IIa, LOE B) a -OR- ASA + CLO > 300 mg given > 6 hours before cath if bivalirudin used as anticoagulant (i.e., omit IV GP IIb/ IIIa inhibitor) (class IIa, LOE B)

ASA + CLO × 1 month (class I, LOE A) -OR- ASA + CLO ideally up to 1 year (class I, LOE B) -OR- ASA + CLO + epti batide or tiroban (class IIb, LOE B)

Anticoagulant Therapy

Anticoagulant Therapy

Enoxaparin or UFH (class I, LOE A) b,c -OR- Bivalirudin or fondaparinux (class I, LOE B)

Enoxaparin or UFH (class I, LOE A) d -OR- Fondaparinux (class I, LOE B) -OR- other LMWH such as dalteparin (limited evidence)

a Factors favoring administration of both clopidorel and GP IIb/IIIa inhibitor: delay to angiography, high risk features, early recurrent ischemic discomfort. b LMWH is reasonable alternative to UFH in patients with UA/NSTEMI (class IIa, LOE B) or STEMI (class IIb, LOE B) in patient undergoing PCI. c If HIT, bivalrudin or argatroban preferred (Class I, LOE B). d Enoxaparin or fondaparinux are preferable to UFH, unless CABG is planned within 24 hours (Class IIa, LOE B). ASA = aspirin; cath = catheterization; CLO = clopidogrel; GP = glycoprotein; IV = intravenous; LOE = level of evidence.

Table 20. Managing Anti-platelet and Anticoagulant Therapies Based on Various Scenarios

If, after stress testing, patient classied as low risk

- ASA (Class I, LOE A)

- CLO for 1 month (class I, LOE A), ideally up to 1 year (class I, LOE B)

- D/C IV GP IIb/IIIa inhibitor (class I, LOE A)


UFH for 48 hours -OR- enoxaparin or fondaparinux for hospital duration, up to 8 days (class I, LOE B)


CABG post-catheter

- ASA (Class I, LOE A)

- D/C CLO 5–7 days before elective CABG (class I, LOE B)

- D/C IV GP IIb/IIIa inhibitor 4 hours before CABG (class I, LOE C)

Continue UFH (class I, LOE B) -OR- discontinue enoxaparin 12–24 hours, fondaparinux 24 hours, or bivalirudin 3 hours before CABG and initiate UFH (class I, LOE B)


PCI post-catheter a

- ASA (Class I, LOE A)

- CLO LD if not started before diagnostic angiography (class I, LOE A)

- IV GP IIb/IIIa inhibitor if not started before diagnostic angiography (class I, LOE A)

- Discontinue anticoagulant after PCI if uncomplicated case (class I, LOE B)

Medical therapy

If no signicant CAD on cath


Antiplatelet and anticoagulant therapy at clinician discretion (class I, LOE C) If CAD on cath


- ASA (Class I, LOE A)

- CLO LD if not started before diagnostic angiography (class I, LOE A)

- Discontinue IV GP IIb/IIIa inhibitor (class I, LOE B)

- If given before angiography, continue UFH for 48 hours or until discharge -OR-

enoxaparin or fondaparinux for hospital duration, for up to 8 days (class I, LOE B)

If given before angiography, either discontinue bivalirudin or continue at 0.25 mg/kg/ hour for up to 72 hours at clinician’s discretion (class I, LOE B)


Acute Care Cardiology

a May omit IV GP IIb/IIIa inhibitor upstream if bivalirudin used as anticoagulant and > 300 mg CLO > 6 hours before catheterization (class IIa, LOE B) or if troponin () and without high-risk features. ASA = aspirin; CABG = coronary artery bypass grafting; cath = catheterization; CLO = clopidogrel; D/C = discontinue; GP = glycoprotein; LD = loading dose; LOE = level of evidence; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.

Table 21. Aspirin and Clopidogrel


Aspirin a,b

Clopidogrel c (Plavix)


Initial therapy

Initial therapy


ASA 162–325 mg nonenteric PO or chewed × 1

CLO 300 mg LD × 1 (class I, LOE A) Pre-PCI

CLO 300 mg LD at least 6 hours before PCI (class I, LOE A) No stent



(class I, LOE C) Pre-PCI


If taking long-term ASA, ASA 75-325 mg before

PCI (class I, LOE A)


If not taking long-term ASA, ASA 300-325 mg at


CLO 75 mg/day for at least 1 month

least 2 hours before PCI, preferably 24 hours (class I, LOE C) No stent

(class I, LOE A) and ideally for up to 1 year (class I, LOE B) Post-stent


ASA 75–162 mg/day indenitely (class I, LOE A)


If bare-metal stent, CLO 75 mg/day for


at least 1 month and ideally for up to 1 year (class I, LOE B)


ASA 162–325 mg/day for: at least 1 month (bare-

metal stent), at least 3 months (sirolimus-eluting stent), at least 6 months (paclitaxel-eluting stent) (class I, LOE B); then, 75–162 mg/day indenitely (class I, LOE A)

If drug-eluting stent, CLO 75 mg/day for at least 1 year (class I, LOE B)



Anaphylaxis, bronchospasm after therapy, serious bleeding

Withhold for up to 5–7 days before elective CABG

a If ASA contraindicated, CLO 75 mg/day long-term or 300 mg LD at least 6 hours prior to PCI +/- Glycoprotein IIb/ IIIa inhibitor (class I, LOE A). b If bleeding risk, reduce ASA dosage post-stent PCI 75–162 mg/day (class IIa, LOE C). c Higher oral LD of 600 or 900 mg more rapidly inhibits platelet aggregation with higher absolute level of inhibition, but additive clinical efcacy and safety have not been established. ASA = aspirin; CABG = coronary artery bypass graft; CLO = clopidogrel; LOE = level of evidence; PO = orally.

Table 22. Glycoprotein IIb/IIIa Inhibitors




PCI Dose

Renal Adjustment



Abciximab (ReoPro) GP receptor irreversible inhibitor

PCI only

Same as PCI dose if cardiac catheterization planned soon

0.25 mg/kg IV bolus, then 0.125 mcg/kg/ minute (maximum 10 mcg/kg) for 12 hours

Not necessary;


system clearance

Eptibatide (Integrelin) GP receptor competitive antagonist


180 mcg/kg IV bolus, followed by 2 mcg/kg/ minute

180 mcg/kg IV bolus × 2 (10 minutes apart), then 2 mcg/kg/minute for 18–24 hours post- PCI

If CrCl < 50 mL/minute, reduce infusion 50%; IP dialysis, contraindicated

elective PCI

Tiroban (Aggrastat) GP receptor competitive antagonist




Same as UA/NSTEMI dose, continue for 18–24 hours post-PCI

If CrCl < 30 mL/minute, reduce infusion 50%


for 30 minutes (LD infusion), followed by




Abciximab is preferred upstream agent if no appreciable delay to angiography and PCI is likely to be performed; otherwise, eptibatide or tiroban preferred.

Acute Care Cardiology

CrCl = creatinine clearance; GP = glycoprotein; LD = loading dose; NSTEMI = non–ST-elevation myocardial infarction; PCI = percutaneous coronary intervention; SCr = serum creatinine; UA = unstable angina.

Table 23. Anticoagulants


Unfractionated Heparin















Factor Xa






U/kg IV bolus,



120 IU/kg bcutaneously twice daily × 5–8 days

2.5 mg



U/kg/hour infusion



0.1 mg/kg IV bolus, then 0.25 mg/kg/hour PCI: 0.5–0.75 mg/kg IV bolus, then 1.75 mg/kg/hour for 4 hours post-PCI


twice daily

once daily


Maximum 4000 U bolus and 1000 U/ hour infusion; titrate to goal activated partial thromboplastin time 1.5–2.5× control




Not FDA approved for HIT

Useful in setting of HIT

subcutaneously once daily if CrCl < 30 mL/minute

dose 10,000

IU twice




Previous HIT, serious active bleeding

Weight > 175 kg or SCr > 2.5 not well studied


Contraindicated if CrCl < 30 mL/ minute

Adjust infusion dose in severe renal dysfunction (bolus dose same)

renal or





CrCl = creatinine clearance; DTI = direct thrombin inhibitor; FDA = U.S. Food and Drug Administration; HIT = heparin-induced thrombocytopenia; LMWH = low-molecular-weight heparin; PCI = percutaneous coronary intervention; NSTEMI = non–ST-elevation MI; SCr = serum creatinine; UA = unstable angina.

5. Additional Long-term Medical Therapy

a. β-Blockers

i. Indicated for all patients unless contraindicated (class I, LOE B).

ii. Initiate within a few days of even, if not acutely, and continue indenitely.

iii. If moderate or severe LV failure, initiate with gradual titration.

b. ACE Inhibitors

i. Indicated for all patients with HF, LVEF less than 40%, hypertension, or diabetes

mellitus (class I, LOE A).

ii. Also reasonable if no LV dysfunction, hypertension, or diabetes mellitus (class I, LOE A).

iii. Angiotensin receptor blocker if ACEI intolerant and signs of HF and LVEF less than 40% (class I, LOE A).

iv. May consider combination ACEI and angiotensin receptor blocker if persistent symptomatic HF and LVEF less than 40% despite standard therapy (class IIb, LOE B).

c. Aldosterone Receptor Blockers

i. Indicated if LVEF less than 40% and symptomatic HF or diabetes mellitus and receiving therapeutic doses of ACEI.

(a) Contraindicated if CrCl less than 30 mL/minute or potassium more than 5 mEq/L

Acute Care Cardiology

Patient Cases

6. J.D. is a 66-year-old, 70-kg woman with history of MI, hypertension, hyperlipidemia, and diabetes who presents with sudden-onset diaphoresis, nausea, vomiting, and dyspnea, followed by a bandlike upper chest pain (8/10) radiating to her left arm. She had felt well until 1 month ago, when she noticed her typical angina was occurring with less exertion. The ECG showed ST-depressions in leads II , III, and AVF, and hyperdynamic T waves. Cardiac enzymes are positive, and she receives a diagnosis of NSTEMI. Home medications: aspirin 81 mg/day, simvastatin 40 mg every night, metoprolol 50 mg 2 times/day, and metformin 1 g 2 times/day. Which one of the following is the best antiplatelet/anticoagulant strategy for this patient?

A. Epti batide 180 mcg/kg bolus × 1, then 2 mcg/kg/minute plus unfractionated heparin titrated to 50–70 seconds, aspirin 325 mg, and clopidogrel 300 mg × 1 and then 75 mg/day plus cardiac catheterization for possible PCI.

B. Aspirin 325 mg and enoxaparin 80 mg subcutaneously 2 times/day plus cardiac catheterization for possible PCI.

C. Medical management with abciximab 0.25 mg/kg bolus, then 0.125 mg/kg/minute for 12 hours plus enoxaparin

80 mg subcutaneously 2 times/day, aspirin 325 mg/day, and clopidogrel 300 mg × 1, then 75 mg/day.

D. Medical management with aspirin 325 mg and clopidogrel 300 mg × 1; then 75 mg/day plus unfractionated

heparin 70 U/kg bolus, followed by 15 U/kg/hour.

7. J.D. received a percutaneous transluminal coronary angioplasty and paclitaxel-eluting stent in her right coronary artery. What is the optimal length of time clopidogrel therapy be continued?


1 month.


6 months.






8. Which one of the following is the optimal lifelong aspirin dose once dual therapy with clopidogrel after PCI with stent implantation is completed?

A. mg.



B. mg.

C. 325 mg.

D. 650 mg.

d. Lipid Management

i. Statins indicated with low-density lipoprotein goal less than 100 mg/dL (class I, LOE A) with a goal less than 70 mg/dL reasonable (class IIa, LOE A).

ii. See “Chronic Cardiology” section for additional detail.

C. ST-elevation MI

1. De nition

a. Complete occlusion of epicardial coronary artery (red blood cells plus platelets, brin).

b. Clinical chest pain syndrome lasting more than 20 minutes with good angina history, plus ST-elevation of more than 1 mm above baseline on ECG, plus positive cardiac enzyme biomarkers of necrosis (troponin I or T, creatine kinase, myocardial bound fraction more than 5%–10% of total creatine kinase).

2. STEMI Goals

a. Restore patency of the infarct-related artery and minimize infarct size.

i. Thrombolytic medications or “Door-to-Needle” within 30 minutes.

ii. PCI or “Door-to-Balloon” within 90 minutes.


Either percutaneous transluminal coronary angioplasty i.e., “balloon,”


Stent implantation, or both.

Acute Care Cardiology

b. Prevent complications such as arrhythmias or death.

c. Control chest pain and associated symptoms.

3. Acute Symptom Relief

a. “MONA” plus β-blocker.

Table 24. “MONA” Plus β-Blocker for AMI


= Morphine

Morphine 1–5 mg IV is reasonable for patients whose symptoms are not relieved despite NTG or if they recur (class I, LOE C)


= Oxygen

Oxygen 4 L/minute by nasal cannula if O 2 saturation < 90%


= Nitroglycerin

Nitroglycerin spray or SL tablet 0.4 mg × 3 doses to relieve acute chest pain (if pain unrelieved after one dose, call 911) (class I, LOE C) Nitroglycerin IV 5 mcg/minute, titrate to chest pain relief or 200 mcg/minute if pain unrelieved by morphine and sublingual NTG (class I, LOE C)


- No mortality benets but high placebo crossover rate.

- Used in rst 48 hours for treatment of persistent chest pain, HF, and hypertension.

A = Aspirin

Aspirin chew and swallow nonenteric-coated 162–325 mg × 1 dose (class I, LOE A/C)


Oral or IV β-blocker (class I, LOE A—oral, class IIa, LOE B—IV)


Mortality benet in early phases of acute MI (metoprolol 5.7% vs. placebo 8.9%).

AMI = acute myocardial infarction; HF = heart failure; IV = intravenous; LOE = level of evidence; MI = myocardial infarction; NTG = nitroglycerin.

4. Reperfusion

a. If presenting to a facility without the capability for expert, prompt intervention with primary PCI within 90 minutes of rst medical contact, patient should undergo brinolysis unless contraindicated (class I, LOE A).

b. Facilitated PCI might be performed as a reperfusion strategy in high-risk patients when PCI is not immediately available and bleeding risk is low (class IIb, LOE B).

i. Facilitated PCI refers to a strategy of planned immediate PCI after an initial pharmacological regimen such as full-dose brinolysis, half-dose brinolysis, a glycoprotein IIb/IIIa inhibitor, or a combination of reduced-dose brinolytic therapy and a platelet glycoprotein IIb/IIIa inhibitor.

c. Rescue PCI or PCI following failed thrombolysis is indicated in select patients if the following develops: shock, severe HF and/or pulmonary edema, hemodynamic or electrical instability, evidence of persistent ischemia.

Table 25. Thrombolytic Therapy



Alteplase (TPA)


mg IVP and then 0.75 mg/kg for 30 minutes (maximum 50 mg), followed by 0.5

mg/kg (maximum 35 mg) for 60 minutes

Reteplase (r-PA)


U IVP, repeat 10 U IVP in 30 minutes

Tenecteplase (TNKase)

< 60 kg to 30 mg, 60–69 kg to 35 mg, 70–79 kg to 40 mg, 80–89 kg to 45 mg, > 90 kg to 50 mg *about 0.5 mg/kg

Streptokinase (Streptase)

1.5 MU IV for 60 minutes

Thrombolytic therapy is preferred within six hours of the onset of chest pain. UFH should be given to patients undergoing reperfusion with thrombolytic therapy. (Class I, B/C)

Acute Care Cardiology

Table 26. Contraindications to Thrombolytic Therapy

Relative Contraindications

Absolute Contraindications

BP > 180/110 mm Hg on presentation

ANY prior hemorrhagic stroke

History of TIA or CVA > 3 months prior

Ischemic stroke within 3 months (except in past 3 hours)

History of chronic poorly controlled HTN

INR 2–3 on warfarin

Intracranial neoplasm or arteriovenous malformation

Active internal bleeding

Recent trauma, major surgery, CPR, internal bleeding in 2–4 weeks

Streptokinase exposure > 5 days prior or prior allergic reaction (if given streptokinase again)

Active peptic ulcer

Aortic dissection

Signicant facial trauma or closed-head trauma in past 3 months

Age > 75 years


Known intracranial pathology (dementia)

CPR = cardiopulmonary resuscitation; CVA = cerebrovascular accident; HTN = hypertension; INR = international normalized ratio; TIA = transient ischemic attack.

Patient Cases

9. R.V. is a 52-year-old man with a history of hypertension and hypertriglyceridemia who presents to a major university teaching hospital with a cardiac catheterization laboratory. He has 3 hours of crushing 10/10 substernal chest pain radiating to both arms that began while he sat eating his lunch, accompanied by nausea, diaphoresis, and shortness of breath. He has never experienced chest pain of this character or intensity before. He usually can walk several miles without dif culty and is a 1.5 pack/day smoker. Home medications: lisinopril 2.5 mg/day, gem brozil 600 mg 2 times/day. Current vital signs: HR 68 beats/minute and BP 178/94 mm Hg; weight 100 kg. An ECG shows 3-mm ST-elevation in leads V 2 –V 4 , I, and AVL. Serum chemistry values are within normal limits. First set of cardiac enzymes showed positive myoglobin levels, creatine kinase 175 U/L, myokinase 17.4 U/L, and troponin T 0.8 mcg/L (less than 0.1 mcg/L). Which one of the following should be done to treat this patient’s STEMI?

A. Cardiac catheterization with primary PCI (stent) of occluded artery together with abciximab, clopidogrel, aspirin, and unfractionated heparin.

B. Reteplase 10 U bolus twice, 30 minutes apart, plus unfractionated heparin 60 U/kg bolus and 12 U/kg/ hour infusion.

C. Abciximab 0.25 mg/kg IVP and 0.125 mg/kg/minute for 12 hours plus enoxaparin 100 mg subcutaneously 2 times/day plus tenecteplase 25 mg IVP 1 time.

D. Tiroban 0.04 mcg/kg/minute × 30 minutes, followed by 0.01 mcg/kg/minute plus unfractionated heparin 60 U/kg bolus and 12 U/kg/hour infusion.

10. W.F. is a 70-year-old male smoker with a history of hypertension, benign prostatic hypertrophy, and lower back pain. Three weeks ago, he started experiencing substernal chest pain with exertion (together with dyspnea), which radiated to both arms and was associated with nausea and diaphoresis. Episodes have increased in frequency to 4–5 times/day and are relieved with rest. He has never had an ECG. Today, he awoke with 7/10 chest pain and went to the emergency department of a rural community hospital 2 hours later. He was acutely dyspneic and had continuing pain. Home medications: aspirin 81 mg/day for 2 months, doxazosin 2 mg/day, ibuprofen 800 mg 3 times/day. Vital signs include HR 42 beats/minute (bradycardic with complete heart block); BP 104/48 mm Hg; weight 61 kg. Laboratory results include BUN 45 mg/dL, SCr 1.7 mg/dL, creatine kinase 277 U/L, creatine kinase, myocardial bound 35.2 U/L, troponin T 1.5 mcg/L (less than 0.1 mcg/L). ECG showed a 3-mm ST-elevation. Aspirin, clopidogrel, and sublingual nitroglycerin were given in the emergency department. Which one of the following best describes how he should be managed?

A. Alteplase plus enoxaparin.

B. Unfractionated heparin.

C. Tenecteplase plus unfractionated heparin.

D. Diagnostic cardiac catheterization for possible primary PCI.

Acute Care Cardiology

5. Mortality-reducing Medications

a. Aspirin

i. See dosing under “UA/NSTEMI” (class I, LOE A).

b. β-Blockers

ii. Shown to reduce mortality in both early and late phases of STEMI.

iii. See dosing under “UA/NSTEMI.”

iv. Oral β-blocker therapy should be administered promptly to those patients without a contraindication, irrespective of concomitant brinolytic therapy or performance of primary PCI (class I, LOE A).

v. IV β-blockers are reasonable for patients without contraindications, especially if a tachyarrhythmia or hypertension is present (class IIa, LOE B).

vi. β-blockers should be used cautiously or not at all in patients with symptoms of heart failure.

c. Thrombolytics

i. Mechanism of action: Plasminogen is a proenzyme and is converted to the active enzyme plasmin by plasminogen activators (endogenous or exogenous alteplase [TPA] derivatives); plasmin digests brin to soluble degradation products.

ii. Administer within 12 hours of symptom onset (preferably within 6 hours, and ideally within 30 minutes of arrival to hospital).

iii. Primary PCI preferred over thrombolytics in hospitals with cardiac catheterization laboratories.

iv. Alteplase, reteplase, and tenecteplase require concomitant unfractionated heparin administration of 60 U/kg bolus (maximum 4000 U) and 12 U/kg/hour (maximum 1000 U/hour), adjusted for activated partial thromboplastin time of about 50–70 seconds (class I, LOE C).


Low-molecular-weight heparins can be used in combination with thrombolytics if the patient is younger than 75 years without signicant renal dysfunction; SCr less than 2.5 mg/dL in men and less than 2 mg/dL in women (class IIb, LOE B). (1) Enoxaparin 30-mg IV bolus, followed by 1 mg/kg subcutaneously every 12 hours until discharge.


In patients with known heparin-induced thrombocytopenia, it is reasonable to

consider bivalirudin a useful alternative to heparin to be used in conjunction with streptokinase (class IIa, LOE B).

v. No added mortality benet at 30 days or 1 year when thrombolytics administered in

half-dose, together with full-dose unfractionated heparin or enoxaparin and full-dose glycoprotein IIb/IIIa inhibitor.


Increased risk of major bleeding events by 3 times (i.e., intracranial hemorrhage), particularly in patients older than 75 years.


Can be used to prevent reinfarction if anterior MI in patients younger than 75 years with no risk of bleeding.

d. ACE Inhibitors

i. Give oral ACEIs in low doses to all patients during rst 24 hours of anterior STEMI, HF signs (pulmonary congestion), or LVEF less than 40%, provided no hypotension exists (systolic BP less than 100 mm Hg) or other contraindication, to reduce mortality and remodeling (class I, LOE A).

ii. Consider oral ACEIs even if the above indications are not present (class IIa, LOE B)—benet less (ve lives saved per 1000 treated) than if LV dysfunction is present.

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iii. Angiotensin receptor blocker if ACEI intolerant (class I, LOE C).

iv. Administer after β-blockers and sublingual nitroglycerin to avoid excess hypotension, but in rst 24 hours.

v. Avoid IV ACEIs as it may cause hypotension (class III, LOE B).

e. Statin Therapy

i. Lipid panel should be drawn within the rst 24 hours of admission to prevent

checking during acute-phase reaction (low-density lipoprotein falsely low for up to 2 months post-MI).

ii. All patients should be discharged on statin therapy unless a contraindication exists.

f. Insulin

i. During the rst 24–48 hours after STEMI, control hyperglycemia with insulin infusion (class I, LOE B).

(c) After 48 hours, manage patients with diabetes with individualized regimens.

D. Post-MI Medical Care and Secondary Prevention

1. Antiplatelet medications

a. Aspirin 75–162 mg/day (class I, LOE A).

b. Clopidogrel 75 mg/day if PCI or medical management (see dosing under “UA/ NSTEMI”).

2. BP control

a. See Joint National Committee VII recommendations in outpatient section for goals.

b. β-Blocker therapy (class I/class IIa if low risk, LOE A)

i. Begin within a few days of the event, if not initiated acutely.

ii. If moderate or severe LV failure, use gradual titration scheme.

c. ACEI therapy (class I, LOE A) or angiotensin receptor blocker if ACEI intolerant (class I, LOE B)

i. Should be initiated at discharge if not already prescribed.

d. Aldosterone antagonist (class I, LOE A)

i. Recommended after STEMI in patients with normal renal function (SCr 2.5 mg/dL or lower in men and 2 mg/dL or lower in women) if:


Already receiving therapeutic dose of ACEI.


LVEF 40% or less.


Symptomatic HF or diabetes.

3. Lipid-lowering therapy: statins

a. Goal low-density lipoprotein less than 100 mg/dL (class I, LOE A), consider low-density lipoprotein less than 70 mg/dL in high-risk patients.

b. Goal non–high-density lipoprotein-cholesterol* less than 130 mg/dL (class I, LOE B).

i. After low-density lipoprotein-cholesterol–lowering therapy, consider adding brate or niacin (class IIa, LOE B).

4. Diabetes management

a. Goal glycosylated hemoglobin less than 7%.

5. Smoking cessation in all patients

6. Weight management

a. Goal body mass index 18.5–24.9 kg/m 2 ; begin diet program if above goal weight.

7. Exercise

a. Minimum goal 3–4 times/week.

Acute Care Cardiology


A. De nition and Treatment Goals

1. Pulmonary arterial hypertension

a. Idiopathic PAH

i. Change in nomenclature during 2003 World Conference on Pulmonary Hypertension; used to be known as primary pulmonary hypertension.

ii. Familial PAH.

b. Pulmonary artery hypertension

i. Secondary causes

(a) Scleroderma (most common), chronic thromboembolic disease, human immunodeciency virus disease, liver disease, connective tissue diseases, medications, toxins, and others.

2. Symptoms

i. Dyspnea with exertion (60% of patients), fatigue, chest pain, syncope, and weakness


(a) Caused by impaired oxygen delivery to tissues and diminished CO.

ii. Orthopnea, peripheral edema, liver congestion, abdominal bloating, and other signs of right ventricular hypertrophy and failure occur when disease progresses to the heart.

3. Diagnosis

Table 27. Diagnostic Findings of PAH

Hemodynamic alterations

MPAP > 25 mm Hg with a PCWP < 15 mm Hg on PA catheterization with failed vasodilator challenge


Signs of RV hypertrophy, right-axis deviation, and anterior ST- and T-wave abnormalities consistent with RV strain pattern


Estimated RV systolic pressure elevation, enlarged RV, RV dysfunction

Chest radiography

Enlarged pulmonary arteries and diminished peripheral pulmonary vascular markings, RV enlargement

Physical examination

Cool and/or cyanotic extremities, jugular venous distension, pulsatile hepatomegaly, peripheral edema, ascites

MPAP = mean pulmonary artery pressure; PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; RV = right ventricle.

4. World Health Organization functional assessment classication

Table 28. World Health Organization Classication for PAH


De nition

Class I

No symptoms (dyspnea, fatigue, syncope, chest pain) with normal daily activities

Class II

Symptoms with strenuous normal daily activities that slightly limit functional status and activity level

Class III

Symptoms of dyspnea, fatigue, syncope, and chest pain with normal daily activities that severely limit functional status and activity level

Class IV

Symptoms at rest; cannot conduct normal daily activities without symptoms

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5. Guideline Recommendations for PAH

Table 29. Levels of Evidence and Grades of Recommendations for PAH Guidelines

Levels of Evidence


Well-designed randomized controlled clinical trials or meta-analyses


Other controlled trials or randomized controlled trials with minor aws


Non-randomized trials, case-control studies, or observational studies

Expert opinion

Consensus opinion of a panel of experts in the topic eld; no clinical trials meet the criteria for inclusion

Grades of Recommendation

Grade A

Strong recommendation

Grade B

Moderate recommendation

Grade C

Weak recommendation

Grade D

Negative recommendation

Grade I

No recommendation possible (inconclusive)

Grade E/A

Strong recommendation based on expert opinion

Grade E/B

Moderate recommendation based on expert opinion

Grade E/C

Weak recommendation based on expert opinion

6. Treatment goals

a. Relieve acute dyspnea symptoms.

b. Improve exercise capacity/quality of life and prevent death.

i. Acute vasodilator response testing (evidence: fair, grade A for idiopathic PAH; evidence: expert opinion, grade E/C for other PAH causes).


Use IV epoprostenol, inhaled nitric oxide, or IV adenosine.


Positive response: reduction in mean pulmonary artery pressure by 10–40 mm Hg. (1) Positive response predicts mortality reduction with long-term calcium channel blocker or vasodilator use.

A. Treatment of PAH

1. Supportive care

a. Supplemental oxygen to maintain O 2 saturation more than 90% at all times (evidence:

expert opinion, grade E/A).

b. Loop diuretics if symptoms of peripheral edema or ascites.

c. Warfarin anticoagulation: goal international normalized ratio 1.5–2.5 in patients with idiopathic PAH (evidence: fair, grade B for idiopathic PAH; evidence: expert opinion, grade E/C for other PAH).

i. Prevents catheter thrombosis in patients on epoprostenol, clot formation caused by venous stasis, or right ventricular failure.

d. Immunizations for inuenza and pneumococcus.

2. Calcium channel blockers

a. First-line drug for all patients with PAH with positive acute vasodilator response (evidence: low, grade B for idiopathic PAH; evidence: expert opinion, grade E/B for other PAH causes).

i. If cannot use or calcium channel blocker therapy fails, consider use of other vasodilatory medications as second-line alternative.

b. Should not be used empirically without acute vasodilatory response testing or without a positive response to testing (evidence: expert opinion, grade E/A).

i. Diltiazem, amlodipine, and nifedipine are most commonly used.

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(a) Choose on the basis of HR at baseline.

(1) If relatively bradycardic, choose amlodipine or nifedipine. (2) If relatively tachycardic, choose diltiazem.

c. Functional class II patients who are not candidates or for whom calcium channel blocker

treatment failed may benet from other therapies, but no specic drugs are recommended because of a lack of evidence (evidence: expert opinion, grade: E/B).

3. Bosentan

a. Mechanism of action: endothelin-1 types A (ET-A) and B (ET-B) receptor antagonist

i. ET-A produces vasoconstriction and increases vascular smooth muscle.

ii. ET-B clears endothelin-1 from vasculature in kidneys and lungs; produces vasodilation.

b. Treatment effect: improves cardiac index, reduces mean pulmonary artery pressure and pulmonary capillary wedge pressure as well as mean right atrial pressure, and improves functional class.

c. Place in therapy:

i. First-line therapy for patients with PAH in functional class III who cannot take calcium channel blockers (evidence: good; grade A).

ii. Alternative option in patients in functional class IV who cannot take calcium channel blockers or IV epoprostenol (evidence: fair, grade B).

4. Epoprostenol

a. Mechanism of action: prostacyclin analogue

i. Potent vasodilator of pulmonary and systemic vessels.

b. Treatment effect: improved survival by 3–5 years, increased 6-minute walk time and

distance, increased quality of life and cardiac index, and symptomatic improvement.

c. Place in therapy:

i. First-line therapy for patients with PAH in functional class IV who experience failure with or cannot take calcium channel blockers (evidence: good, grade A).

ii. Second-line therapy for patients with PAH in functional class III who experience

failure with or cannot take calcium channel blockers or rst-line vasodilators (bosentan) (evidence: good, grade A).

d. Contraindications: inability to keep drug refrigerated before and during infusion; requires ice packs to keep stable; unable to reconstitute drug in sterile environment.

e. Other considerations: costs $100,000/year or more; if infusion is abruptly discontinued, because of the short half-life (t 1/2 less than 6 minutes); acute symptomatic decompensation and possibly death may occur if medical attention is not sought immediately.

5. Subcutaneous treprostinil

a. Mechanism of action: prostacyclin analogue: potent vasodilator of pulmonary and systemic vessels.

b. Treatment effect: dose-related symptomatic improvement and effect on exercise tolerance; more effective in functional class III and IV patients but is an alternative therapy (minimal/no effect in functional class II patients or patients with congenital heart disease) (evidence: fair, grade B).

c. Other considerations: If subcutaneous infusion is abruptly discontinued because of the longer half-life (t 1/2 = 3 hours), patients have more time to seek medical attention than with epoprostenol.

i. Premixed, prelled syringe is easier to administer than epoprostenol.

6. Inhaled iloprost

a. Mechanism of action: potent pulmonary vasodilator.

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b. Treatment effect: symptomatic improvement of functional class, quality of life for functional classes III or IV but is an alternative therapy.

i. Functional class III patients (evidence: fair, grade B).

ii. Functional class IV patients (evidence: low, grade C).


c. Other considerations: must be used with Prodose AAD nebulization system. Sildenal