18 Cardio-1

Cardiology I
Cardiology I
Sheryl L. Chow, Pharm.D., FCCP, BCPS
Western University of Health Sciences
College of Pharmacy
Pomona, California
ACCP Updates in Therapeutics® 2012: The Pharmacotherapy Preparatory Review and Recertification Course
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Cardiology I
Learning Objectives: 3. H.E. is a 53-year-old woman admitted to the hos-

pital after the worst headache she has ever expe-
1. Formulate evidence-based treatment strategies for rienced. Her medical history includes exertional
patients with acute decompensated heart failure. asthma, poorly controlled hypertension (HTN),
2. Describe an appropriate treatment strategy for and hyperlipidemia. She is nonadherent to her
atrial and ventricular arrhythmias using evidence- medications, and she has not taken her BP drugs,
based medicine. including clonidine, for 4 days. Vital signs include
3. Prepare a treatment strategy for a patient newly BP 220/100 mm Hg and HR 65 beats/minute. She
given a diagnosis of idiopathic pulmonary arterial receives a diagnosis of a cerebrovascular accident
hypertension. and hypertensive emergency. Which one of the fol-
4. Select appropriate pharmacologic therapy and de- lowing choices is the best management option for
velop a monitoring plan for antihypertensive drug this patient’s hypertensive emergency?
therapy for managing hypertensive crises. A. Fenoldopam 0.1 mcg/kg/minute.
B. Nicardipine 5 mg/hour.
C. Labetalol 0.5 mg/minute.
Self-Assessment Questions: D. Enalaprilat 0.625 mg intravenously every 6
Answers and explanations to these questions hours.
may be found at the end of this chapter.
4. The Sudden Cardiac Death in Heart Failure trial
1. A.A. is a 25-year-old woman with a new diagno- evaluated the efficacy of amiodarone or an implant-
sis of idiopathic pulmonary arterial hypertension able cardioverter defibrillator (ICD) versus placebo
(IPAH). Her home drugs include warfarin 5 mg/ in preventing all-cause mortality in ischemic and
day, furosemide 60 mg 2 times/day, and bosentan nonischemic NYHA class II and III patients with
62.5 mg 2 times/day. Which one of the following is HF. There was a 7.2% absolute risk reduction and
the best contraceptive strategy for this patient? a 23% relative risk reduction in all-cause mortality
A. Estrogen-progesterone oral contraceptive. at 60 months with an ICD versus placebo. Which
B. Injectable hormonal contraceptive. of the following best demonstrates the number of
C. Any hormonal contraceptive and barrier patients needed to treat with an ICD to prevent one
method. death versus placebo?
D. Barrier method only. A. 1.3.
B. 4.3.
2. R.P. is a 60-year-old woman with New York Heart C. 13.8.
Association (NYHA) class IV heart failure (HF) D. 43.4.
admitted for increased shortness of breath and dys-
pnea at rest. Her extremities appear well perfused, 5. A.D. is a 52-year-old woman with a history of wit-
but she has 3+ pitting edema in her lower extremi- nessed cardiac arrest in a shopping mall; she was
ties. R.P.’s vital signs include blood pressure (BP) resuscitated with an automatic external defibril-
125/70 mm Hg, heart rate (HR) 102 beats/minute, lator device. On electrophysiologic study, she has
and O2 saturation 89% on 100% facemask. After inducible ventricular tachycardia (VT). Which one
the initiation of an intravenous diuretic, which one of the following is best for reducing the secondary
of the following is the best intravenous drug to incidence of sudden cardiac death in patients such
treat this patient? as A.D.?
A. Dobutamine. A. Propafenone.
B. Milrinone. B. Amiodarone.
C. Nesiritide. C. ICD.
D. Metoprolol. D. Metoprolol.

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Cardiology I
6. S.V. is a 75-year-old woman with a history of D. Only severe or life-threatening ADRs need to
NYHA class III HF (left ventricular ejection frac- be reported.
tion [LVEF] 25%) and several non–ST-elevation
myocardial infarctions (MIs). She had an episode 9. Your Pharmacy and Therapeutics Committee
of sustained VT during hospitalization for pneu- wants you to perform a pharmacoeconomic analy-
monia. Her QTc interval was 380 milliseconds on sis of a new drug available to treat decompensated
the telemetry monitor, and her serum potassium HF. This drug works through a unique mechanism
(K+) and magnesium (Mg) were 4.6 mmol/L and of action. Unlike other available inotropic thera-
2.2 mg/dL, respectively. Which one of the follow- pies that can increase mortality, this drug appears
ing is the best treatment option for S.V.? to reduce long-term mortality. However, the cost is
A. Procainamide. 10 times greater than that of other available drugs.
B. Metoprolol. Your findings will be presented at the next Pharma-
C. Intravenous Mg. cy and Therapeutics Committee meeting to make a
D. Amiodarone. formulary decision. Which of the following types
of pharmacoeconomic analysis would be best to
7. You are working on a review article about newer determine whether this new drug is a better formu-
treatment strategies for hypertensive crises. You lary choice than currently available agents?
want to ensure that you retrieve all relevant clinical A. Cost-minimization analysis.
trials and related articles on your subject. Which B. Cost-effectiveness analysis.
one of the following comprehensive databases C. Cost-benefit analysis.
is best to search next to ensure that you have not D. Cost-utility analysis.
missed key articles?
A. International Pharmaceutical Abstracts. 10. A.S. is a 56-year-old African American man with
B. Iowa Drug Information Service. a long history of poorly controlled HTN secondary
C. Clin-Alert. to medication nonadherence and subsequent di-
D. Excerpta Medica. lated cardiomyopathy (LVEF 35%). He is assessed
in a community health clinic today and reports not
8. A physician on your team asks that you report an having taken his medications for the past week.
adverse drug reaction (ADR) experienced by a pa- A.S. is asymptomatic, and his examination is un-
tient taking nesiritide. The patient had severe hy- remarkable except for BP 180/120 mm Hg and HR
potension after the initial bolus dose of nesiritide, 92 beats/minute. All laboratory values are within
even though his BP was in the normal range before normal limits except for a serum creatinine (SCr)
therapy initiation. The hypotension led to reduced of 1.4 mg/dL and urinalysis with 2+ proteinuria.
renal perfusion, resulting in oliguric acute kidney Which one of the following therapeutic options
injury and subsequent hemodialysis. The patient would be best to manage A.S.’s condition in the
had no known renal insufficiency before develop- clinic?
ing this complication. Which one of the following A. Nifedipine 10 mg sublingually.
statements best describes the Joint Commission re- B. Clonidine 0.2 mg orally.
quirements for institutional ADR reporting? C. Captopril 12.5 mg orally.
A. A MedWatch form must be completed that D. Labetalol 200 mg orally.
explains the situation in which the ADR
occurred.
B. Institutions must create their own definition
of ADR with which practitioners will be
familiar.
C. Hospital staff must use the Naranjo algorithm
for assessing the severity of the ADR.
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I. ACUTE DECOMPENSATED HEART FAILURE (ADHF)
A. Hemodynamic Parameters
Table 1. Hemodynamic Values in Patients with ADHF and Sepsis

Normal Typical Typical
Parameter Value ADHF Value Sepsis Value
Mean arterial pressure (MAP) (mm Hg) 80–100 60–80 60–80
Heart rate (HR) (beats/minute) 60–80 70–90 90–100
Cardiac output (CO) (L/minute) 4–7 2–4 5–8
Cardiac index (CI) (L/minute/m2) 2.8–3.6 1.3–2 3.5–4
Pulmonary capillary wedge pressure (PCWP) (mm Hg) 8–12a 18–30 5–8
Systemic vascular resistance (SVR) (dynes•second•cm-5) 800–1200 1500–3000 300–800
Central venous pressure (CVP) (mm Hg) 2–6 6–15 2–6
a
15–18 mm Hg is often desired/optimal in patients with HF to ensure optimal filling pressures.
ADHF = acute decompensated heart failure; CI = CO/BSA (BSA = body surface area);
MAP = diastolic blood pressure + [1/3 (systolic blood pressure − diastolic blood pressure)]; SVR = [(MAP − CVP)/CO] × 80.
B. Clinical Presentation
Table 2. Signs and Symptoms of ADHF

Congestion (elevated PCWP) Hypoperfusion (reduced CO)
Dyspnea on exertion or at rest Fatigue
Orthopnea, paroxysmal nocturnal dyspnea Altered mental status or sleepiness
Peripheral edema Cold extremities
Rales Worsening renal function
Early satiety, nausea/vomiting Narrow pulse pressure
Ascites Hypotension
Hepatomegaly, splenomegaly Hyponatremia
Jugular venous distention
Hepatojugular reflux
ADHF = acute decompensated heart failure; CO = cardiac output; PCWP = pulmonary capillary wedge pressure.
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Table 3. Forester Hemodynamic Subsets and Therapy

Subset I. Subset II.
Normal Congestion
Warm and dry Warm and wet
CI
2.2 Subset III. Subset IV.
Hypoperfused Congestion + hypoperfusion
Cold and dry Cold and wet
18
PCWP
Subset I – Warm and Dry (Normal Parameters)

• (PCWP 15–18 mm Hga -AND- CI greater than 2.2 L/minute/m2)
• Optimize oral medications
Subset II – Warm and Wet (Pulmonary/Peripheral Congestion)
• (PCWP greater than 18 mm Hg -AND- CI greater than 2.2 L/minute/m 2)
• IV diuretics ± IV vasodilators (venousc)
Subset III – Cold and Dry (Hypoperfusion)
• (PCWP 15–18 mm Hga -AND- CI less than 2.2 L/minute/m 2)
• If PCWP < 15 mm Hg, IVF until PCWP 15–18 mm Hg
• If PCWP ≥ 15 mm Hg and MAP < 50 mm Hg, IV dopamine
• If PCWP ≥ 15 mm Hg, MAP ≥ 50 mm Hg and compelling reason for inotrope,b IV inotrope
• If PCWP ≥ 15 mm Hg, MAP ≥ 50 mm Hg, and no compelling reason for inotrope,b IV vasodilator (arteriald)
Subset IV – Cold and Wet (Pulmonary/Peripheral Congestion -AND- Hypoperfusion)
• (PCWP greater than 18 mm Hg -AND- CI less than 2.2 L/minute/m 2)
• If MAP < 50 mm Hg, IV dopamine
• If MAP ≥ 50 mm Hg and compelling reason for inotrope,b IV inotrope
• If MAP ≥ 50 mm Hg and no compelling reason for inotrope,b IV vasodilator (venous and/or arterialc,d)
a
Goal PCWP is 8–12 mm Hg in a normal patient and 15–18 in a patient with heart failure. If PCWP is less than 15 mm Hg in a patient with heart
failure, either remove fluid restriction or cautiously administer fluids until PCWP is 15–18 mm Hg and then reassess CI.
b
Compelling reason for inotrope = SBP < 90 mm Hg, symptomatic hypotension, or worsening renal function.
c
Venous vasodilator – reduce PCWP.
d
Arterial vasodilator – reduce SVR with compensatory increase CI.
CI = cardiac index; IV = intravenous; IVF = intravenous fluid; MAP = mean arterial pressure; PCWP = pulmonary capillary wedge pressure.
C. Chronic HF Therapy in the Setting of Acute Decompensation

1. It is critical to initiate and/or continue standard HF therapies unless there is a compelling reason to
avoid or discontinue such therapies (e.g., hypotension, cardiogenic shock).
2. Angiotensin-converting enzyme inhibitors (ACEIs)
a. Caution with initiation or up-titration during aggressive diuresis
b. Increases in SCr (decrease in glomerular filtration rate of 20% or more) from ACEI use are not
associated with worse outcomes.
3. β-Blockers
a. Do not discontinue in patients who are stable on dose before admission (i.e., recent initiation or up-
titration was not responsible for decompensation).
b. Do not initiate or up-titrate until euvolemic.
c. Hold if hemodynamically unstable.
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4. Digoxin
a. Continue at dose to achieve serum digoxin concentration of 0.5–0.8 ng/mL.
b. Avoid discontinuation unless there is a compelling reason because digoxin withdrawal has been
associated with worsening of HF symptoms.
c. Caution if renal function begins to deteriorate or frequently fluctuates
D. ADHF Therapy Overview
Table 4. Overview of ADHF Guideline Recommendations

Diuretic Therapy
i. Recommended as intravenous loop diuretics for patients with fluid overload
Change to oral route on day before discharge if possible
ii. 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 diuretic with different MOA (metolazone or hydrochlorothiazide, chlorothiazide),
or
(d) Ultrafiltration.
Inotropic Therapy
i. May be considered to relieve symptoms and improve end-organ function in patients with reduced LVEF
and diminished peripheral perfusion or end-organ dysfunction (low output syndrome), particularly if:
(a) Marginal systolic BP (< 90 mm Hg),
(b) Symptomatic hypotension despite adequate filling pressure, or
(c) No response or intolerance to intravenous vasodilators.
ii. May be considered in similar patients with evidence of fluid overload if they respond poorly to intravenous
diuretics or manifest diminished or worsening renal function
Vasodilator Therapy
i. May be considered in addition to intravenous loop diuretics to rapidly improve symptoms in patients with
acute pulmonary edema or severe hypertension
ii. May be considered in patients with persistent symptoms despite aggressive diuretics and oral drug therapy
iii. When adjunctive therapy is required in addition to loop diuretics, intravenous vasodilators should be
considered over inotropic drugs
Invasive Hemodynamic Monitoringa
Routine use of hemodynamic monitoring with invasive intravenous lines (e.g., Swan-Ganz pulmonary artery
catheters) is not recommended
a
Several noninvasive methods for hemodynamic monitoring are currently available.
ADHF = acute decompensated heart failure; BP = blood pressure; LVEF = left ventricular ejection fraction; MOA = mechanism of action.
E. Diuretics are primarily used to medically manage patients with pulmonary and peripheral congestion or
“wet” (subset II or IV) HF.
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Table 5. Diuretic Therapy for ADHF

Loop diuretics (ascending limb of loop of Henle)
i. Most widely used and most potent, effective at low CrCl (< 30 mL/minute)
ii. Furosemide (Lasix) most commonly used; furosemide 40 mg PO = furosemide 20 mg IV = bumetanide 1 mg
IV/PO = torsemide 10 mg IV/PO
Thiazides (distal tubule)
i. Relatively weak diuretics when used alone, not effective at low glomerular filtration rate (CrCl < 30 mL/minute)
ii. Reserved for add-on therapy in patients refractory to loops
Diuretic resistance
i. Increase dose before increasing frequency of loop diuretic
(Note: Ceiling effect at about 160–200 mg IV furosemide)
ii. Add a second diuretic with a different mechanism of action
(a) Hydrochlorothiazide 12.5–25 mg PO daily, metolazone 2.5–5 mg PO daily (30 minutes before loop diuretic
administration)
(b) Chlorothiazide 250–500 mg IV daily; consider if gastrointestinal edema; generic is very expensive –
Reserve for NPO or refractory to other alternatives
iii. Continuous infusion of loop diuretic – Furosemide 0.1 mg/kg/hour IV doubled every 4–8 hours, maximum 0.4
mg/kg/hour
Adverse effects: Electrolyte depletion (potassium, magnesium), worsening renal function
ADHF = acute decompensated heart failure; CrCl = creatinine clearance; IV = intravenous(ly); NPO = nothing by mouth; PO = orally.
F. Inotropic therapy is primarily used to manage hypoperfusion or “cold” (subset III or IV) HF. It is
important to confirm that patients in subset III have adequate filling pressures (i.e., PCWP 15–18 mm Hg)
before administering inotropic therapy.
Table 6. Inotropic Therapy for ADHF

Dobutamine (Dobutrex) Milrinone (Primacor)
Mechanism β1-agonist: Stimulates AC to convert ATP to PDE inhibitor: Inhibits cAMP breakdown in heart
of action cAMP to ↑ CO; slight peripheral vasodilation to ↑ CO and in vascular smooth muscle to ↓ SVR
Clinical effects Positive inotropic, chronotropic, Positive inotropic and lusitropic effects,
lusitropic effects no direct chronotropic effects
Indication ADHF – Cold and wet or cold and dry exacerbations (if PCWP > 15 mm Hg)
Dosing Start 2.5–5 mcg/kg/minute IV, may 50 mcg/kg IVB; then 0.375 mcg/kg/minute IV;
titrate to maximum 20 mcg/kg/minute may titrate to maximum 0.75 mcg/kg/minute
Typical dose 5 mcg/kg/minute IV No bolus, 0.1–0.375 mcg/kg/minute IV
Half-life 2 minutes 1 hour, prolonged to 2–3 hours if HF and/or
CrCl < 50 mL/minute
Elimination Hepatically metabolized (inactive), renally 90% renal
eliminated
Adverse effects Proarrhythmia, tachycardia, hypokalemia, Proarrhythmia, hypotension (avoid bolus),
myocardial ischemia, tachyphylaxis tachycardia, < 1% thrombocytopenia, possible
(> 72 hours); possible increased mortality increased mortality with long-term use
with long-term use
Other comments Consider if hypotensive Consider 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; IV = intravenous(ly); IVB = intravenous bolus; PCWP = pulmonary capillary wedge pressure;
PDE = phosphodiesterase; SVR = systemic vascular resistance.
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G. Vasodilator therapy is primarily used to manage pulmonary congestion or “wet” (subset II or IV) HF.
Venous vasodilation results in a reduction in pulmonary capillary wedge pressure (PCWP) and acute relief
of shortness of breath while awaiting the onset of diuretic effects. Vasodilators with arterial vasodilating
properties (nitroprusside and nesiritide) may also be used as an alternative to inotropes in patients with
elevated systemic vascular resistance (SVR) and low cardiac output (CO).
Table 7. Vasodilator Therapy for ADHF

Sodium Nitroprusside Nesiritide
(Nipride) (Natrecor) IV Nitroglycerin
Mechanism of Nitric oxide–induced Recombinant B-type Combines with sulfhydryl
action stimulation of GC to natriuretic peptide binds to groups in vascular endothelium
convert GTP to cGMP natriuretic peptide receptor to create S-nitrosothiol
A to stimulate guanylate compounds that mimic
cyclase and production nitric oxide’s stimulation
of cGMP; natriuretic of guanylate cyclase and
mechanism unknown production of cGMP
Clinical Balanced arterial and Hemodynamic effects: Preferential venous vasodilator
effects venous vasodilator ↓ PCWP and SVR, ↑↑↑ CI, > arterial vasodilator, arterial
minimal changes in HR vasodilation at high doses (e.g.,
Neurohormonal effects: ↓ 100 mcg/minute)
NE, ET-1, and aldosterone
Natriuretic effects at
supratherapeutic doses
Indication Warm and wet ADHF, Warm and wet ADHF, Warm and wet ADHF, ACS, or
alternative to inotropes alternative to inotropes in hypertensive crises
in cold and wet ADHF, cold and wet ADHF
hypertensive crises
Dosing 0.3–0.5 mcg/kg/minute IV, 2 mcg/kg IVB, 0.01 mcg/kg/ 5 mcg/minute IV, ↑↑↑ by 5 mcg/
↑↑↑ by 0.5 mcg/kg/minute minute IV minute
up to 3 mcg/kg/minute up to 200 mcg/minute
Typical dose 0.5–1 mcg/kg/minute IV 0.01 mcg/kg/minute IV 25–75 mcg/minute IV, titrated
May omit bolus if low SBP to response
Half-life < 10 minutes 20 minutes 1–4 minutes
Elimination Cyanide hepatically Natriuretic peptide receptor C Inactive metabolites in urine
metabolized, thiocyanate (no renal/hepatic adjustment)
renally excreted
Adverse Hypotension or cyanide or Primarily hypotension (up Hypotension, reflex tachycardia,
effects thiocyanate toxicity to 1 hour), tachycardia (less headache, tachyphylaxis
than inotropes)
ACS = acute coronary syndrome; ADHF = acute decompensated heart failure; cGMP = cyclic guanine monophosphate; CI = cardiac index;
ET-1 = endothelin; GC = guanylate cyclase; GTP = guanosine triphosphate; HR = heart rate; IV = intravenous(ly); IVB = intravenous bolus;
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 hospital for HF decompensation. D.D. notes progressively in-
creased dyspnea when walking (now 10 ft [3 m], previously 30 ft [6 m]) and orthopnea (now four pillows,
previously two pillows), increased bilateral lower extremity swelling (3+), 13-kg weight gain in the past
3 weeks, and dietary nonadherence. He has a history of idiopathic dilated cardiomyopathy (LVEF 25%,
NYHA class III), paroxysmal atrial fibrillation (AF), and hyperlipidemia. Pertinent laboratory values are
as follows: B-type natriuretic peptide (BNP) 2300 pg/mL (0–50 pg/mL), K+ 4.9 mEq/L, blood urea nitrogen
(BUN) 32 mg/dL, SCr 2.0 mg/dL, aspartate aminotransferase (AST) 40 IU/L, alanine aminotransferase
(ALT) 42 IU/L, international normalized ratio (INR) 1.3, activated partial thromboplastin time (aPTT) 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 best 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 intravenously 2 times/day.
D. Milrinone 0.5 mcg/kg/minute.

2. After initiation of intravenous loop diuretics with only minimal urine output, D.D. is transferred to the coro-
nary care unit for further management of diuretic-refractory decompensated HF. His O2 saturation is now 87%
on 4-L nasal cannula, and an arterial blood gas is being obtained. His BP is 110/75 mm Hg, and his HR is 75
beats/minute. D.D.’s SCr and K+ concentrations have begun to rise; they are now 2.7 mg/dL and 5.4 mmol/L,
respectively. In addition to a one-time dose of intravenous chlorothiazide, which one of the following best
represents ways in which D.D.’s decompensated HF should be treated?
A. Nitroglycerin 20 mcg/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 his weight decreases 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 89/58 mm Hg, and HR
is 98 beats/minute. It is believed that he is no longer responding to his current regimen. A Swan-Ganz cath-
eter is placed to determine further management. Hemodynamic values are cardiac index (CI) 1.5 L/minute/
m2, SVR 2650 dynes/cm-5, and PCWP 30 mm Hg. Which one of the following is the best drug given his
current symptoms?
A. Milrinone 0.2 mcg/kg/minute.
B. Dobutamine 5 mcg/kg/minute.
C. Nesiritide 2-mcg/kg bolus; then 0.01 mcg/kg/minute.
D. Phenylephrine 20 mcg/minute.
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II. ARRHYTHMIAS
A. Drug Therapy Overview

1. Review all potential causes: Electrolyte abnormalities and thyroid function tests
2. Ensure that all electrolytes are maintained at critical levels: K+ greater than 4 mmol/L and less than 5
mmol/L, Mg++ greater than 2 mg/dL.
3. Ensure that all electrocardiogram parameters are within normal limits (e.g., QT interval less than 500
milliseconds).
4. Review all potential drug etiologies and treat appropriately.
a. Drug-induced QT prolongation (see section B.3.c .)
b. Bradycardia or atrioventricular block
i. β-Blocker, calcium channel blocker, digoxin
ii. Administer antidote if appropriate (e.g., calcium for calcium channel blocker toxicity).
Table 8. Antiarrhythmic Drug Classes

Class I IA – Quinidine, procainamide, disopyramide ↑ QRS and ↑ QT
Na+ channel blockers IB – Lidocaine, mexiletine, phenytoin ↓ QT
IC – Propafenone, flecainide, moricizine ↑ QRS
Class II Metoprolol, esmolol, atenolol ↓ HR and ↑ PR
β-Blockers
Class III Amiodarone, sotalol, dofetilide, dronedarone, or ibutilide ↑ QT
K+ channel blockers
Class IV Diltiazem, verapamil ↓ HR and ↑ PR
Ca2+ channel blockers
AV = atrioventricular; Ca2+ = calcium; K+ = potassium; Na+ = sodium; QRS = time between start of Q wave and end of S wave on an
electrocardiograph; QT = time between start of Q wave and end of T wave on an electrocardiograph.
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Table 9. Antiarrhythmic Drug Properties and Dosing (class I and III agents only)
Adverse Effects, Contraindications, Drug
Drug Interactions, Pharmacokinetics Dosing by Indication
Class IA – Na channel blockers
+
Quinidine AEs: Nausea/vomiting/diarrhea (30%), AF conversion:

(Quinidex, “cinchonism”(CNS and GI symptoms, tinnitus), Avoid use because of GI AEs
Quinaglute) TdP (first 72 hours) AF maintenance:
DIs: Warfarin, digoxin Sulfate: 200–400 mg PO every 6 hours
Gluconate (CR): 324 mg PO every 8–12 hours
Procainamide AEs: Lupus-like syndrome AF conversion:
(Pronestyl) (30% if > 6 months), hypotension 1 g IV for 30 minutes; then 2 mg/minute
(IV use, 5%), TdP (1-hour efficacy 51%)
CI: LVEF < 40% AF maintenance:
PK: Reduce dose in renal and liver dysfunction No oral agent
(active metabolite NAPA [class III effects] VT conversion:
may accumulate) 20 mg/minute IV until 17 mg/kg, arrhythmia
ceases, or QRS widens > 50%
VT maintenance:
2–4 mg/minute
Disopyramide AEs: Anticholinergic effects, TdP, ADHF AF conversion:
(Norpace, (potent negative inotropic effect) IR 200 mg (if < 50 kg) or 300 mg (if > 50 kg)
Norpace CR, CI: Cardiogenic shock, congenital long QT PO every 6 hours
Rythmodan, syndrome, second- or third-degree AV block AF maintenance:
Rythmodan- 400–800 mg/day in divided doses
LA) (Recommended adult dose 600 mg/day given as
IR 150 mg PO every 6 hours or as CR 300 mg
PO every 12 hours)
If < 50 kg, moderate renal dysfunction (CrCl
> 40 mL/minute) or hepatic dysfunction,
maximum 400 mg/day
If severe renal dysfunction (IR only avoid CR)
CrCl 30–40 mL/minute 100 mg every 8 hours
CrCl 15–30 mL/minute every 12 hours
CrCl < 15 mL/minute every 24 hours
Class IB – Na channel blockers
+
Lidocaine AEs: CNS (perioral numbness, seizures, Pulseless VT/VF conversion or VT with a pulse:
(Xylocaine) confusion, blurry vision, tinnitus) 1–1.5 mg/kg IVP; repeat 0.5–0.75 mg/kg every
CI: Third-degree AV heart block 3–5 minutes (maximum 3 mg/kg)
PK: Reduce dose in those with HF, liver (If LVEF < 40%: 0.5–0.75 mg/kg IVP)
disease, low body weight and renal (Amiodarone DOC in pulseless VT/VT –
dysfunction and in the elderly lidocaine acceptable if amiodarone not available)
DI: Amiodarone (increased lidocaine levels) VT maintenance: 1–4 mg/minute
Mexiletine AEs: CNS (tremor, dizziness, ataxia, VT maintenance: 200–300 mg every 8 hours
(Mexitil) nystagmus)
CI: Third-degree AV heart block
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Table 9. Antiarrhythmic Drug Properties and Dosing (class I and III agents only) (continued)
Class IC – Na channel blockers (Note: Avoid in patients with HF or post-MI – Increased risk of sudden death)
+
Propafenonea AEs: Metallic taste, dizziness, ADHF, AF conversion:

(Rythmol, bronchospasm, bradycardia, heart block 600 mg PO × 1 (efficacy 45% at 3 hours)
Rythmol CR) (negative inotropy and b-blocking properties) 450 mg PO x 1 (weight < 70 kg)
CIs: HF (NYHA III–IV), liver disease, AF maintenance:
valvular disease, CAD, MI HCl: 150–300 mg PO every 8–12 hours
DIs: Digoxin ↑ by 70%; warfarin ↑ by 50% as HCl (SR): 225–425 mg PO every 12 hours
well as drugs that inhibit CYP 2D6, 1A2,
3A4 (increased propafenone
Flecainide a
AEs: Dizziness, tremor, ADHF AF conversion: 300 mg PO × 1
(Tambocor) (negative inotropy) (efficacy 50% at 3 hours)
CIs: HF, CAD, valvular disease, LVH (TdP) AF maintenance: 50–150 mg PO BID
DI: Digoxin ↑ by 25%
Class III – K+ channel blockers
Amiodarone AEs: Pulmonary fibrosis 3%–17%, AF conversion:
(Cordarone) hyperthyroidism 3%, hypothyroidism IV: 5–7 mg/kg IV over 30–60 minutes; then
30%, neurologic toxicity 20%–40%, 1.2–1.8 g/day continuous IV or divided oral
photosensitivity, corneal deposits, hepatitis, doses until 10 g
blue-gray skin 15%, TdP < 1%, heart block PO: 1.2–1.8 g/day in divided doses until 10 g
14%, hypotension (IV), phlebitis (IV) (Ca2+ AF maintenance:
and β-blocking properties) 200–400 mg/day PO
CIs: Iodine hypersensitivity, hyperthyroidism, Pulseless VT/VF conversion:
third-degree AV heart block 300 mg or 5 mg/kg IVB in 20 mL of D5W or NS;
DIs: Warfarin, digoxin, HMG-CoA reductase repeat 150 mg IVB every 3–5 minutes
inhibitors (maximum simvastatin dose 10 Stable VT: 150 mg IVB in 100 mL of D5W for
mg/day), phenytoin ↑ ≥ 50%, lidocaine, 10 minutes
and others VT/VF maintenance:
(inhibits CYP3A4/2D6/2C9 and gut pgp) 1 mg/minute × 6 hours; then 0.5 mg/minute
* Does not increase mortality in patients (maximum 2.2 g/day)
with HF
PK: Half-life 58 days (average)
Sotalol AEs: ADHF, bradycardia, AV block, wheezing, AF maintenance (based on CrCl)
3%–8% TdP within 3 days of initiation, 80 mg PO BID (> 60 mL/minute)
bronchospasm (β-blocking effects) 80 mg PO QD (40–60 mL/minute)
CI: Baseline QT > 440 milliseconds or Contraindicated < 40 mL/minute
CrCl < 40 mL/minute (AF only) VT maintenance (based on CrCl)
PK: Renally eliminated 80 mg PO BID (> 60 mL/minute)
* Hospitalization mandatory for initiation, 80 mg PO QD (30–60 mL/minute)
obtain QT 2–3 hours after first 5 doses, may 80 mg PO QOD (10–30 mL/minute)
increase dose after 3 days; NTE QT > 500 80 mg PO > QOD (< 10 mL/minute)
milliseconds
Not effective for AF conversion!
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Cardiology I
Table 9. Antiarrhythmic Drug Properties and Dosing (class I and III agents only) (continued)
Dofetilide AEs: TdP (0.8%; 4% if no renal adjustment), AF conversion (based on CrCl)
(Tikosyn) diarrhea (efficacy 12% at 1 month)
DIs: CYP3A4 inhibitors and drugs secreted 500 mcg PO BID (> 60 mL/minute)
by kidney (cimetidine, ketoconazole, 250 mcg PO BID (40–60 mL/minute)
verapamil, trimethoprim, prochlorperazine, 125 mcg PO BID (20–40 mL/minute)
megestrol), HCTZ Contraindicated < 20 mL/minute
CI: Baseline QTc > 440 milliseconds or AF maintenance:
CrCl < 20 mL/minute Titrate down based on QTc NTE 500 milliseconds
PK: Renally eliminated or > 15% ↑ in QTc
* Hospitalization mandatory for initiation,
obtain QTc 2–3 hours after each of the first
5 doses, reduce 50% if QTc ↑ > 15%; NTE
QTc > 500 milliseconds
* Does not increase mortality in patients
with HF
Ibutilide AEs: TdP 8%, heart block (β-blocking AF conversion:
(Covert) properties) 1 mg IV (≥ 60 kg)
DIs: CYP3A4 inhibitors or QT-prolonging or 0.01 mg/kg IV (< 60 kg),
drugs repeat in 10 minutes if ineffective
CIs: Baseline QTc > 440 milliseconds, LVEF < (efficacy 47% at 90 minutes)
30%, concomitant antiarrhythmic drugs
* ECG monitoring during and 4 hours
after CV
Dronedarone AEs: Worsening HF, QT prolongation, AF maintenance:
(Multaq) hypokalemia or hypomagnesemia with 400 mg PO BID
potassium-sparing diuretics, hepatic failure Discontinue if QTc ≥ 500 milliseconds
DIs: CYP3A4 inhibitors, QT-prolonging drugs,
simvastatin, tacrolimus/sirolimus, warfarin,
and other CYP3A4 substrates with narrow
therapeutic range, digoxin and other pgp
substrates (dabigatran)
CIs: QTc ≥ 500 milliseconds or PR ≥ 280
milliseconds, NYHA class IV HF or NYHA
class II–III HF with recent ADHF, severe
hepatic impairment, second- or third-degree
AVB or HR < 50 beats/minute
PK: Half-life 13–19 hours
a
Indicates pill-in-pocket approach can be used for selected patients.
ADHF = acute decompensated heart failure; AE = adverse effect; AF = atrial fibrillation; AV = atrioventricular; AVB = atrioventricular block;
BID = twice daily; CAD = coronary artery disease; CI = contraindication; CNS = central nervous system; CR = controlled release; CrCl =
creatinine clearance; CV = cardioversion; CYP = cytochrome P450; D5W = dextrose 5%; DI = drug interactions; DOC = drug of choice; ECG
= electrocardiogram; GI = gastrointestinal; HCL = hydrochloride; HCTZ = hydrochlorothiazide; HF = heart failure; HMG-CoA = 3-hydroxy-
3-methylglutaryl coenzyme A; HR = heart rate; IR = immediate release; IV = intravenous; IVB = intravenous bolus; IVP = intravenous push;
LVEF = left ventricular ejection fraction; MI = myocardial infarction; MOA = mechanism of action; NS = normal saline; NTE = not to exceed;
NYHA = New York Heart Association; pgp = P-glycoprotein; PK = pharmacokinetics; PO = oral; QD = once daily; QOD = once every other
day; TdP = torsades de pointes; VF = ventricular fibrillation; VT = ventricular tachycardia.
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Cardiology I
B. Adult Cardiac Arrest
Table 10. Select Advanced Cardiovascular Life Support Algorithmsa

Algorithm for Pulseless Ventricular Tachycardia or Fibrillation
CPR/DCC
Epinephrine 1 mg IV/IO every 3–5 minutes
Vasopressin 40 units IV/IO × 1 (replaces first or second epinephrine doses)
Amiodarone 300 mg IV/IO × 1, repeat 150 mg IV/IO × 1
If amiodarone is unavailable, lidocaine may be considered.
Lidocaine 1–1.5 mg/kg IV, repeat 0.5–0.75 mg/kg IV/IO every 5–10 minutes (maximum 3 mg/kg)
Reversible causes of the event should be identified and correctedb
Algorithm for Asystole or PEA
CPR (no DCC)
Epinephrine 1 mg IV/IO every 3–5 minutes
Vasopressin 40 units IV/IO × 1 (replaces first or second epinephrine doses)
Atropine has been removed from the ACLS algorithm for
asystole and PEA because of a lack of evidence supporting benefit
Reversible causes of the event should be identified and correctedb
a
If no IV/IO access, endotracheal administration of epinephrine, lidocaine, and atropine is allowed at 2–2.5 times the recommended IV/IO dose.
Dilute this dose with 5–10 mL of sterile water or normal saline.
b
Hypovolemia, hypoxia, hydrogen ion (acidosis), hypo-/hyperkalemia, hypothermia, tension pneumothorax, tamponade (cardiac), toxins,
thrombosis (pulmonary), thrombosis (coronary).
ACLS = advanced cardiovascular life support; CPR = cardiopulmonary resuscitation; DCC = direct current conversion; HR = heart rate; IO =
intraosseous; IV = intravenous; PEA = pulseless electrical activity.
C. Symptomatic Bradycardia
1. If unstable, atropine 0.5 mg every 3–5 minutes (maximal dose 3 mg or 0.04 mg/kg) (Note: Unstable =
hypotension, acutely altered mental status, signs of shock, ischemic chest discomfort, acute HF)
2. If atropine fails, transcutaneous pacing, dopamine infusion, or epinephrine infusion
D. Symptomatic Tachycardia
1. If unstable, synchronized cardioversion
2. If stable, determine whether QRS complex is narrow or wide.
a. Narrow complex tachycardia (QRS less than 120 milliseconds) – Usually atrial arrhythmias
i. Regular ventricular rhythm – Supraventricular tachycardia (SVT) or sinus tachycardia likely
(a) Vagal maneuvers and/or adenosine 6-mg intravenous push followed by a 20-mL saline
flush; then a 12-mg intravenous push (may repeat once) – Use adenosine cautiously in
severe coronary artery disease (CAD). Decrease initial dose to 2–3 mg if given through a
centrally placed line.
(1) If converts, likely atrial tachycardia, paroxysmal supraventricular tachycardia
(PSVT), or Wolff-Parkinson-White (WPW) syndrome
(2) If PSVT (not WPW) and conversion is temporary, a longer-acting agent such as
diltiazem or verapamil may be considered.
(3) If WPW syndrome, avoid verapamil, diltiazem, and digoxin.
(b) Do not give adenosine for unstable or for irregular or polymorphic wide complex
tachycardias because it may cause degeneration to VF.
ii. Irregular ventricular rhythm – AF (or possibly atrial flutter)
(a) Rate control plus anticoagulation if persistent/permanent AF
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Cardiology I
(b) If disabling symptoms, consider adding antiarrhythmic drug therapy or ablation.

(c) If hemodynamically unstable, synchronized cardioversion recommended
Table 11. Atrial Fibrillation – Rate Control and Rhythm Control

Rate Control
General presentation β-Blockers or nondihydropyridine calcium channel blockers
(diltiazem, verapamil)
If HF and no accessory pathway present Digoxina or amiodarone
If accessory pathway present Amiodarone
Rhythm Control
Unstable, duration less than 48 hours DCC, IV UFH immediately beforehand
Unstable, duration unknown or greater DCC, TEE (rule out thrombus) + IV UFH beforehand and AC for 4
than 48 hours weeks afterward
Stable, duration unknown, or more than Before DCC, RC + AC (INR 2–3) for 3–4 weeks before and for 4
48 hours weeks afterward
Dabigatran can be used (Refer to Cardiology III)
If AF up to 7 days, either elective DCC or chemical cardioversionb
– Flecainide, dofetilide, propafenone, ibutilide, or amiodaronec
– Digoxin and sotalol NOT recommended and may be harmful
If AF greater than 7 days, either elective DCC or chemical
cardioversionb
– Dofetilide, amiodarone, or ibutilidec
a
If paroxysmal AF, avoid digoxin.
b
Quinidine, procainamide, disopyramide, and dofetilide should NOT be initiated out of hospital for AF conversion.
c
Expert consultation recommended.
AC = anticoagulate; AF = atrial fibrillation; DCC = direct current cardioversion; HF = heart failure; IV = intravenous; RC = rate control; TEE
= transesophageal echocardiograph; UFH = unfractionated heparin.
b. Wide complex tachycardia (QRS greater than 120 milliseconds) – Usually ventricular
arrhythmias
i. VT or unknown mechanism
(a) Consider adenosine only if regular and monomorphic.
(b) Intravenous procainamide, amiodarone (or sotalol); lidocaine second line
(c) Avoid procainamide and sotalol if prolonged QT.
ii. Definite SVT with aberrancy – Likely transiently slowed or converted by adenosine
iii. Polymorphic (irregular) VT
(a) Induced primarily when QTc interval is greater than 500 milliseconds (torsades de
pointes)
(b) Withdrawal of QT-prolonging medications, correction of low magnesium ion (Mg2+) or K+
(1) Class I and III antiarrhythmic drugs
(2) Assess for drug interactions by cytochrome P450 (CYP) 3A4 (e.g., azole antifungals,
erythromycin).
(3) Assess for other QT-prolonging drugs such as haloperidol, ziprasidone, droperidol,
sulfamethoxazole/trimethoprim, promethazine, and tricyclic amine antidepressants.
(c) If unstable, immediate cardioversion
(d) If stable, intravenous Mg2+ 1- to 2-g intravenous bolus (maximum 16 g/24 hours)
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Cardiology I
E. Implantable Cardioverter Defibrillators

1. For primary prevention of sudden cardiac death – Indicated if nonischemic dilated cardiomyopathy
or ischemic heart disease (more than 40 days post-MI), LVEF 35% or less, NYHA class II or III,
receiving optimal chronic medications, and reasonable expectation of survival with a good functional
status for more than 1 year
2. For secondary prevention of sudden cardiac death – Indicated if recurrent sustained VT in post-MI
patients, normal or near-normal LVEF, receiving optimal chronic medications, and having survival
expectation for more than 1 year
3. Contraindications: Evolving acute MIs with VT, acute VT after coronary artery bypass grafting,
VF caused by AF, terminal illness, psychiatric disorder, and severe NYHA class IV (non-
transplantable) HF
F. Special Patient Populations

1. HF – Amiodarone and dofetilide (LV dysfunction post-MI) have a neutral effect on mortality.
2. Acute MI
a. Encainide, flecainide, moricizine – Increased mortality when used to treat post-MI premature
ventricular contractions
b. Class IA medications – Increased mortality in post-MI survivors
Table 12. Alteration of Defibrillation Threshold

Threshold Alteration Medications Comments
Increase threshold Amiodarone, lidocaine, and Reprogram ICD, increased energy
mexiletine (joules) required
Decrease threshold Sotalol May decrease energy needed for DCC
DCC = direct current conversion; ICD = implantable cardioverter defibrillator.
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Cardiology I
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 experiencing dizziness before passing out. Telemetry monitor showed sustained VT for 45
seconds. His medical history includes HF NYHA class III, LVEF 30%, MI × 2, HTN × 20 years, LV hyper-
trophy, diabetes mellitus, and diabetic nephropathy. His 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. His laboratory tests show BP 120/75 mm Hg, HR 80 beats/minute, BUN 30 mg/dL, and SCr 2.2 mg/dL.
Which one of the following is the best therapy to initiate for conversion of his sustained VT?
A. Amiodarone 150 mg intravenously for 10 minutes; then 1 mg/minute for 6 hours; then 0.5 mg/minute.
B. Sotalol 80 mg 2 times/day titrated to QTc of about 450 milliseconds.
C. Dofetilide 500 mcg 2 times/day titrated to QTc of about 450 milliseconds.
D. Procainamide 20 mg/minute, with a maximum of 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 during which he lost consciousness for 30 seconds, according to
witnesses. He also has rapid HR episodes during which he feels dizzy and light-headed. 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 caused by amiodarone therapy. On telemetry, he shows
runs of nonsustained VT. Which of the following would best predict the duration of amiodarone-associated
tachyarrhythmia in this patient?
A. Never.
B. 1 month.
C. 6 months.
D. 1 year.
6. S.L., a 64-year-old woman, presents to the emergency department with a chief concern of palpitations. Her
medical history includes HTN controlled with a diuretic and inferior-wall MI 6 months ago. She is pale and
diaphoretic but able to respond to commands. S.L.’s laboratory parameters are within normal limits. Her
vital signs include BP 95/70 mm Hg and HR 145 beats/minute; telemetry shows sustained VT. Although
initially unresponsive to β-blockers, S.L. is successfully treated with lidocaine. Subsequent electrophysi-
ologic testing reveals inducible VT, and sotalol 80 mg orally twice daily is prescribed. Two hours after the
second dose, S.L.’s QTc is 520 milliseconds. Which one of the following changes would be best with respect
to S.L.’s antiarrhythmic regimen?
A. Continue sotalol at 80 mg orally twice daily.
B. Increase sotalol to 120 mg orally twice daily.
C. Discontinue sotalol and initiate dofetilide 125 mcg orally twice daily.
D. Discontinue sotalol and initiate amiodarone 400 mg orally 3 times/day.
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Cardiology I
III. Pulmonary ARTERIAL hypertension
A. Definition, Diagnosis, and Treatment Goals

1. Pulmonary arterial hypertension (PAH)
a. Idiopathic pulmonary arterial hypertension
i. Change in nomenclature during 2003 World Conference on Pulmonary Hypertension;
previously known as primary pulmonary hypertension
ii. Familial PAH
b. Secondary causes – Scleroderma (most common), chronic thromboembolic disease, HIV (human
immunodeficiency virus), liver disease, connective tissue diseases, medications, toxins, others
2. Symptoms
a. Dyspnea with exertion (60% of patients), fatigue, chest pain, syncope, weakness (40%) – Caused
by impaired oxygen delivery to tissues and diminished CO
b. Orthopnea, peripheral edema, liver congestion, abdominal bloating, and other signs of right
ventricular hypertrophy and failure occur when disease progresses to involve the heart.
3. Diagnosis and classification – See Tables 13 and 14.
Table 13. Diagnostic Findings of PAH

Hemodynamic alterations mPAP > 25 mm Hg (> 30 mm Hg if exercising), PCWP ≤ 15 mm Hg, and PVR > 3
Wood units on RHC
Electrocardiogram Signs of RV hypertrophy, right-axis deviation, and anterior ST- and T-wave
abnormalities consistent with RV strain pattern
Echocardiography 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; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary
wedge pressure; PVR = pulmonary vascular resistance; RHC = right heart catheterization; RV = right ventricle.
Table 14. World Health Organization Classification of Functional Status for PAH
Class Definition
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
PAH = pulmonary arterial hypertension.
4. Treatment goals
a. Relieve acute dyspnea symptoms.
b. Improve exercise capacity/quality of life and prevent death.
5. For acute vasodilator response testing:
a. Use intravenous epoprostenol, inhaled nitric oxide, or intravenous adenosine.
b. Positive response: Reduction in mean pulmonary arterial pressure (mPAP) of at least 10 mm Hg to
an absolute mPAP of less than 40 mm Hg
c. Positive response predicts mortality reduction with long-term calcium channel blocker or
vasodilator use.
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Cardiology I
B. Treatment of PAH
1. Reassessment should include functional class determination and 6-minute walk test every 3–6 months,
with right heart catheterization less often.
2. Satisfactory condition – Functional class I–II, ambulated 380 m or greater (or 1250 ft) during 6-minute
walk test, with a CI of 2.2 L/minute/m2 or greater and mPAP less than 12 mm Hg.
Table 15. Initial PAH Treatment Algorithm

Supportive Care: Treat corrective causes of hypoxemia and
avoid dehydration, pain, fatigue, high altitude, smoking, pregnancy, iron deficiency, etc.
Oxygen to maintain O2 saturation > 90%, diuretic if peripheral edema or ascites
Oral anticoagulation, warfarin (INR 1.5–2.5) if IPAH ± diuretics ± digoxin
(anticoagulation to prevent catheter thrombosis (IV prostaglandin use) and venous thromboembolism)
Immunizations for influenza and Pneumococcus
Discuss effective methods of birth control with women of childbearing potential
Positive Response to Acute Vasoreactivity Testing
Initiate oral CCB
- If sustained response, continue CCB
- If no sustained response, see Lower Risk algorithm below
Negative Response to Acute Vasoreactivity Testing
Lower Riska Higher Riskb
First line: ERAs or PDEIs (oral) Epoprostenol or treprostinil (IV)
Alternatives: epoprostenol or treprostinil (IV) Iloprost (inhaled)
Iloprost (inhaled), treprostinil (SC) ERAs or PDEIs (oral)
Treprostinil (SC)
Reassess: consider combination therapy, investigational protocols, atrial septostomy, lung transplantation
a
Low risk (good prognosis) if no RV failure, gradual progression of symptoms, WHO class II or III, 6 MW more than 400 m, peak VO2 more than
10.4 mL/kg/minute, minimal RV dysfunction, RAP less than 10 mm Hg, CI more than 2.5 L/minute/m 2, BNP minimally elevated.
b
High risk (poor prognosis) if RV failure, rapid progression of symptoms, WHO class IV, 6 MW less than 300 m, peak VO2 < 10.4 mL/kg/minute,
substantial RV enlargement/dysfunction (or pericardial effusion or right atrial enlargement), RAP greater than 20 mm Hg, CI less than 2 L/
minute/m 2, BNP significantly elevated.
BNP = B-type natriuretic peptide; CCB = calcium channel blocker; CI = cardiac index; ERA = endothelin receptor antagonist; INR = international
normalized ratio; IPAH = idiopathic pulmonary arterial hypertension; IV = intravenously; MW = molecular weight; PDEI = phosphodiesterase
inhibitor; RAP = right atrial pressure; RV = right ventricle; SC = subcutaneously; WHO = World Health Organization.
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Cardiology I
Table 16. Overview of PAH Treatment Options

Drug/Mechanism/
Indication Dose Adverse Effects Considerations
Calcium channel Varies by Hypotension, headache, Should not be used empirically without positive
blockers agent and dizziness, peripheral response to acute vasodilatory response testing!
patient edema, cardiac Diltiazem, amlodipine, nifedipine most
Class II PAH tolerance conduction delay commonly used
(diltiazem) Select agent on the basis of HR at baseline
If tachycardic, choose diltiazem
If bradycardic, choose amlodipine, nifedipine
Epoprostenol 2–40 ng/kg/ Jaw pain, nausea, Continuous IV infusion by pump
(Flolan, Veletri) minute IV vomiting, flushing, Flolan: Unstable at acidic pH and room
Prostanoid headache, muscle aches temperature (refrigerate or use ice packs before
and pain, catheter-related and during infusion)
Class III–IV PAH thrombosis, and IV line Veletri: Stable at room temperature
infections; rebound Drug requires reconstitution in sterile
worsening of symptoms if environment
abruptly discontinued Medical emergency if infusion interrupted
(half-life – 6 minutes) – Spare drug cassette and
infusion pump should be kept available
Treprostinil 1.25- to Severe erythema and Longer half-life (t1/2 – 3 hours) – Longer to seek
(Remodulin, 40-ng/kg/ induration (83%) and medical attention
Tyvaso) minute SC injection site pain Premixed, prefilled syringe easier to administer
Prostanoid infusion, IV (85%) limits use; also Local treatments (hot/cold packs or topical
Inhaled headache, nausea, analgesics) can be used to minimize infusion
Class II–IV PAH diarrhea, rash site discomfort
Moving infusion site every 3 days minimizes
irritation
Inhaled iloprost 2.5 × 1; then Mild, transient cough, Requires 6–9 inhalations daily (15 minutes each
(Ventavis) 5 mcg/ flushing, headache, with jet nebulizer)
Prostanoid inhalation syncope Prodose AAD nebulization system required
by nebulizer Inhaled form has fewer systemic adverse
Class III–IV PAH 6–9 times/ reactions
day while Use no more than every 2 hours
awake
Bosentan 62.5–125 mg Peripheral edema Severe drug interactions with glyburide
(Tracleer) PO twice 5%–14%, hypotension (increased LFTs) and cyclosporine (decreased
Nonselective daily 7%, increased LFTs efficacy of both cyclosporine and bosentan)
endothelin receptor 11%, flushing 7%–14%, Monitor LFTs monthly
antagonist palpitations 5% Monitor hemoglobin/hematocrit every 3 months
(ETA and ETB) Potential teratogen; if childbearing age, use two
contraceptive methods (reduced efficacy of
Class III–IV PAH hormonal contraceptives); monthly pregnancy
test required
Efficacy decreased with inducers and toxicity
increased with inhibitors of CYP2C8/9 and 3A4
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Cardiology I
Table 16. Overview of PAH Treatment Options (continued)

Drug/Mechanism/
Indication Dose Adverse Effects Considerations
Ambrisentan 5–10 mg PO Peripheral edema Caution with cyclosporine
(Letairis) once daily 17%, hypotension Monitor LFTs monthly
Selective 0%, increased LFTs Potential teratogen (see above comments)
endothelin receptor 0%–2.8%, flushing 4%, No CYP drug interactions documented
antagonist palpitations 5%, fluid
(ETA only) retention
Class II–III PAH

Sildenafil 20 mg PO Headache, epistaxis, Half-life 4–5 hours
(Revatio) 3 times/day facial flushing, bluish May augment effects of other vasodilators when
Phosphodiesterase or blurry vision, light used in combination (especially prostacyclin)
inhibitor sensitivity, dyspepsia, Contraindicated in patients receiving nitrates
insomnia Avoid combined use with strong CYP3A4
Class II–IV PAH inhibitors (e.g., ritonavir, cimetidine,
erythromycin) and inducers (rifampin)
Tadalafil 40 mg PO Headache, flushing, Half-life 17.5 hours
(Adcirca) once daily indigestion, nausea, May augment effects of other vasodilators when
Phosphodiesterase backache, myalgia, used in combination (especially prostacyclin)
inhibitor nasopharyngitis, Contraindicated in patients receiving nitrates
respiratory tract If CrCl 31–80 mL/minute, initiate 20 mg PO
Class II–IV PAH infection once daily and titrate as tolerated
If CrCl < 30 mL/minute or hemodialysis, avoid
use
If Child-Pugh class A or B, initiate 20 mg PO
once daily and titrate as tolerated
If Child-Pugh class C, avoid use
Avoid use with potent CYP3A4 inhibitors/
inducers
AAD = antiarrhythmic drug; CCBs = calcium channel blockers; CrCl = creatinine clearance; CYP = cytochrome P450; ET-1 antagonists =
endothelin-1 antagonists; FDA = U.S. Food and Drug Administration; IV = intravenous; LFT = liver function test; PAH = pulmonary arterial
hypertension; PO = orally; SC = subcutaneous.
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Cardiology I
Patient Cases
7. R.W. is a 38-year-old obese woman who presents with increasing symptoms of fatigue and shortness of
breath. She could walk only 10–20 ft at baseline and is now short of breath at rest. Her arterial blood gas is
pH 7.31/Pco2 65/Po2 53/85% O2 saturation. She has three-pillow orthopnea and 3+ pitting edema in her lower
extremities. Medical history is significant only for AF. Computerized tomographic angiography shows that
her pulmonary artery trunk is substantially enlarged, with a mean pressure of 56 mm Hg. Echocardiography
shows right atrial and ventricular hypertrophy. Chest radiography detects prominent interstitial markings.
Pertinent laboratory test values are BUN 21 mg/dL, SCr 1.2 mg/dL, AST 145 IU/L, ALT 90 IU/L, INR 2.1,
and PTT 52 seconds; vital signs include BP 108/62 mm Hg and HR 62 beats/minute. Home medications are
warfarin 2.5 mg/day, ipratropium 2 puffs every 6 hours, salmeterol 2 puffs 2 times/day, and diltiazem 480
mg/day. Her diagnosis is IPAH. From the options below, which one of the following is the best evidence-
based management strategy?
A. Increase diltiazem to 600 mg/day.
B. Start sildenafil 20 mg 3 times/day.
C. Start epoprostenol 2 ng/kg/minute.
D. Start bosentan 62.5 mg 2 times/day.
8. L.S., a 48-year-old man with IPAH, is admitted to the medical intensive care unit for severe respiratory
distress. Medications before admission include bosentan and sildenafil. His vital signs include BP 87/45
mm Hg, HR 130 beats/minute, and respiratory rate 24 breaths/minute, and his oxygen requirements are
increasing. Recently, during a previous hospital admission, pulmonary artery catheter placement revealed
an mPAP of 40 mm Hg, right atrial pressure 16 mm Hg, CI 1.2 L/minute, and PCWP 15 mm Hg. Echocar-
diography reveals EF 60% with significant right ventricular dilation. Which one of the following is the best
therapy?
A. Epoprostenol and add phenylephrine if needed for BP support.
B. Furosemide and add norepinephrine if needed for BP support.
C. Nitroprusside and add epinephrine if needed for BP support.
D. Dobutamine to increase CO.
IV. Hypertensive CRISES (Urgency and Emergency)
A. Definitions
1. Hypertensive urgency – Acutely elevated BP, particularly diastolic BP greater than 110 mm Hg (and
systolic BP greater than 180 mm Hg), without evidence of target organ damage
2. Hypertensive emergency – HTN with evidence of target organ damage (may be preexisting) to brain,
heart, kidneys, eyes (e.g., hypertensive encephalopathy, intracranial hemorrhage, or other acute
neurologic deficit; unstable angina or acute MI; acute HF; pulmonary edema [shortness of breath];
aortic dissection; retinopathy or papilledema; decreased urine output or acute renal failure; eclampsia)
B. Goals
1. Hypertensive urgency – Lower MAP to goal or near goal within 24 hours; oral medications can be used.
2. Hypertensive emergency – Lower MAP by 25% or diastolic BP to 100–110 mm Hg within 30–60 minutes.
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Cardiology I
C. Treatment Options
Table 17. Commonly Used Intravenous Drugs for Hypertensive Emergencies

Drug (onset, duration) Intravenous Dose Adverse Effects
Sodium nitroprusside 0.25–0.5 mcg/kg/minute, Cyanide/thiocyanate toxicity, nausea, vomiting,
(Nipride) maximum 3 mcg/kg/minute methemoglobinemia
(immediate, 2–3 minutes) CIs: Renal, hepatic failure
Caution: Increased ICP
Esmolol 250-400 mcg/kg/min IVB; Bronchospasm, HF exacerbation, bradycardia/
(Brevibloc) then 50-100 mcg/kg/min heart block
(1–2 minutes, 10–30 minutes) infusion, maximum 300 mcg/ Caution: Acute HF, asthma, heart block
kg/minute
Labetalol 20–80 mg every 15 minutes Same as esmolol
(Normodyne, Trandate) OR 0.5–2 mg/minute
(5–10 minutes, 3–6 hours) maximum 300 mg/24 hours
Nicardipine 5–15 mg/hour, Reflex tachycardia, nausea, vomiting, headache,
(Cardene) maximum 15 mg/hour flushing
(1–5 minutes, 15–30 Caution: Angina/MI, acute HF, increased ICP
minutes – Up to 4 hours if
prolonged infusion)
Nitroglycerin 5–10 mcg/minute, Headache, nausea, vomiting, tachyphylaxis,
(2–5 minutes, 5–10 minutes) maximum 100 mcg/minute methemoglobinemia
Caution: Increased ICP
Hydralazine 5–10 mg every 4–6 hours Reflex tachycardia, headache, flushing
(Apresoline) (not to exceed 20 mg/dose) Caution: Angina/MI, increased ICP, aortic
10 minutes, 1–4 hours) dissection
Enalaprilat 0.625–1.25 mg every 4–6 hours, Renal insufficiency/failure, hyperkalemia
(Vasotec) maximum 5 mg every 6 hours CIs: Pregnancy, renal artery stenosis
(within 30 minutes, 12–24 (Note: Long half-life)
hours)
Fenoldopam 0.1 mcg/kg/minute, Headache, flushing, tachycardia, cerebral
(Corlopam) maximum 1.6 mcg/kg/minute ischemia
(< 5 minutes, 30 minutes) Caution: Glaucoma
Clevidipine 1–2 mg/hour Patients with renal failure and hepatic failure
(Cleviprex) maximum 16 mg/hour and geriatric patients not specifically studied
(2–4 minutes, 5–15 minutes) CIs: Soy/egg product allergy, severe aortic
stenosis, defective lipid metabolism
Caution: HF, concomitant β-blocker use, reflex
tachycardia, rebound hypertension
CI = contraindication; HF = heart failure; ICP = intracranial pressure; LD = loading dose; MI = myocardial infarction.
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Cardiology I
Table 18. Commonly Used Oral Drugs for Hypertensive Urgencies

Drug Oral Dose Adverse Effects
Captopril 6.5–50 mg Renal insufficiency/failure, hyperkalemia
(Capoten) CIs: Pregnancy, renal artery stenosis
Clonidine 0.2 mg; then 0.1 mg/hour Sedation, dry mouth, dizziness
(Catapres) up to 0.8 mg total Caution: Altered mental status
CIs: Severe carotid artery stenosis
Minoxidil 5–20 mg Tachycardia, edema
(Loniten) CIs: Angina, HF
Nifedipine 10–20 mg Flushing, headache, edema
CIs: Severe aortic stenosis, coronary artery or cerebrovascular disease
Labetalol 200–400 mg repeated Bronchospasm, especially in patients with asthma
(Normodyne, every 2–3 hours HF exacerbation; bradycardia/heart block
Trandate) Caution: Acute HF
CI = contraindication; HF = heart failure.
Table 19. Agents Preferred for Hypertensive Crises Based on Comorbidities

Comorbidity Preferred Intravenous Agent(s)
Acute aortic dissection Labetalol, esmolol alone or in combination with nicardipine, clevidipine,
or nitroprusside
(β-blocker must precede other agents)
(Avoid hydralazine)
Acute heart failure Nitroprusside, nitroglycerin, nesiritide, or ACE inhibitors in combination
with diuretics if pulmonary edema
(Note: Avoid β-blockers)
Acute intracerebral hemorrhage/acute Labetalol, nicardipine
ischemic stroke
Acute myocardial infarction β-Blocker in combination with nitroglycerin
If heart rate < 70 beats/minute, consider nicardipine or clevidipine
Acute pulmonary edema Nesiritide, nitroglycerin, nitroprusside
Acute renal failure Fenoldopam, nicardipine, clevidipine
Eclampsia or preeclampsia Hydralazine, labetalol, nicardipine
Hypertensive encephalopathy Nitroprusside, labetalol, fenoldopam, nicardipine
Perioperative hypertension Clevidipine, esmolol, nicardipine, nitroglycerin, nitroprusside
Sympathetic crisis Nicardipine, fenoldopam, clevidipine, phentolamine
(Note: Avoid unopposed β-blockade)
ACE = angiotensin-converting enzyme.
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Cardiology I
Patient Cases
9. A.W., a 68-year-old man with a history of chronic kidney disease stage V on hemodialysis, HTN, CAD post-
MI, moderately depressed LVEF, and gastroesophageal reflux disease, presents with acute-onset shortness
of breath and chest pain. After his recent dialysis, he had a large barbecue meal with salt and smoked some
marijuana laced with cocaine. He was nonadherent to medical therapy for 2 days and noticed he had gained
2 kg in 24 hours. His baseline orthopnea worsened to sleeping sitting up in a chair for the 2 nights before
admission. He developed acute-onset chest tightness with diaphoresis and nausea, pain 7/10. He went to the
emergency department, where a BP of 250/120 mm Hg was noted. He had crackles halfway up his lungs on
examination, and chest radiography detected bilateral fluffy infiltrates with prominent vessel cephalization.
Electrocardiography showed sinus tachycardia HR 122 beats/minute and ST depressions in leads 2, 3, and
aVF. He was admitted for hypertensive emergency. Laboratory results are as follows: BUN 48 mg/dL, SCr
11.4 mg/dL, BNP 2350 pg/mL, troponin T 1.5 mcg/L (less than 0.1 mcg/L), creatine kinase 227 units/L, and
creatine kinase-MB 22 units/L. Which one of the following medications is best to manage A.W.’s hyperten-
sive emergency?
A. Intravenous nitroglycerin 5 mcg/minute titrated to a 25% reduction in MAP.
B. Labetalol 2 mcg/minute titrated to a 50% reduction in MAP.
C. Sodium nitroprusside 0.25 mcg/kg/minute titrated to a 25% reduction in MAP.
D. Clonidine 0.1 mg orally every 2 hours as needed for a 50% reduction in MAP.
10. M.R., a 56-year-old white woman with a long history of HTN because of nonadherence and recently diag-
nosed HF (EF 35%), presents to the local emergency department with the sudden onset of severe, sharp, and
diffuse chest pain that radiates to her back. A physical examination reveals BP 210/120 mm Hg and HR 105
beats/minute but otherwise within normal limits. Current laboratory values are also within normal limits,
except for a toxicology screen positive for cocaine. A chest radiograph reveals a widened mediastinum, and
a subsequent chest computed tomography scan reveals aortic arch dissection. Which one of the following
medications is best to manage M.R.’s hypertensive emergency?
A. Esmolol 25 mcg/minute.
B. Esmolol 25 mcg/minute followed by sodium nitroprusside 0.5 mcg/kg/minute.
C. Sodium nitroprusside 0.5 mcg/kg/minute.
D. Labetalol 2 mg/minute followed by sodium nitroprusside 0.5 mcg/kg/minute.
2-189
Cardiology I
References
Acute Decompensated Heart Failure and the European Society of Cardiology Com-
1. Hunt SA, Abraham WT, Chin MH, et al. 2009 mittee for Practice Guidelines. J Am Coll Cardiol
focused update incorporated into the ACC/AHA 2003;42:1493–531.
2005 guidelines for the diagnosis and management 5. American Heart Association. 2010 guidelines for
of heart failure in adults: a report of the American cardiopulmonary resuscitation and emergency car-
College of Cardiology Foundation/American Heart diovascular care. Circulation 2010;122:S729–S767.
Association Task Force on Practice Guidelines
developed in collaboration with the International
Pulmonary Arterial Hypertension
Society for Heart and Lung Transplantation. J Am
Coll Cardiol 2009;53:1343–82. 1. McLaughlin VV, Archer SL, Badesch DB, et al.
ACCF/AHA 2009 expert consensus document
2. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA
on pulmonary hypertension. J Am Coll Cardiol
2010 comprehensive heart failure practice guide-
2009;53:1573–619.
line. J Card Fail 2010;16:e1–194.
2. Badesch DB, Abman SH, Simonneau G, et al.
Medical therapy for pulmonary arterial hyperten-
Acute Dysrhythmias sion: updated ACCP evidence-based clinical prac-
1. Fuster V, Ryden LE, Cannom DS. ACC/AHA/ tice guidelines. Chest 2007;131:1917–28.
ESC 2006 guidelines for the management of pa- 3. McLaughlin VV, McGoon MD. Pulmonary arte-
tients with atrial fibrillation – executive summary: rial hypertension. Circulation 2006;114:1417–31.
a report of the American College of Cardiology/
American Heart Association Task Force on Prac-
tice Guidelines and the European Society of Car- Hypertensive Emergency
diology Committee for Practice Guidelines. J Am 1. Rhoney D, Peacock WF. Intravenous therapy for
Coll Cardiol 2006;48:854–906. hypertensive emergencies, part 1. Am J Health
2. Wann LS, Curtis AB, January CT, et al. 2011 Syst Pharm 2009;66:1343–52.
ACCF/AHA/HRS focused update on the manage- 2. Rhoney D, Peacock WF. Intravenous therapy for
ment of patients with atrial fibrillation (updating hypertensive emergencies, part 2. Am J Health
the 2006 guideline): a report of the American Col- Syst Pharm 2009;66:1448–57.
lege of Cardiology Foundation/American Heart 3. Haas AR, Marik PE. Current diagnosis and man-
Association Task Force on Practice Guidelines. agement of hypertensive emergency. Semin Dial
Circulation 2011;123:104–23. 2006;19:502–12.
3. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/ 4. Marik PE, Varon J. Hypertensive crises: challenges
AHA/ESC 2006 guidelines for the management of and management. Chest 2007;131:1949–62.
patients with ventricular arrhythmias and the pre-
vention of sudden cardiac death – executive sum-
mary: a report of the American College of Car-
diology/American Heart Association Task Force
and the European Society of Cardiology Com-
mittee for Practice Guidelines. J Am Coll Cardiol
2006;48:1064–108.
4. Blomström-Lundqvist C, Scheinman MM, Aliot
EM, et al. ACC/AHA/ESC 2003 guidelines for the
management of patients with supraventricular ar-
rhythmias – executive summary: a report of the
American College of Cardiology/American Heart
Association Task Force on Practice Guidelines
2-190
Cardiology I
Answers and Explanations to Patient Cases
1. Answer: C indicated. Positive inotropic agents, such as milrinone,

This patient, who has ADHF, is receiving a β-blocker. will increase CO to maintain perfusion to vital organs.
Although long-term β-blockers can improve HF symp- Milrinone will also vasodilate the peripheral vessels
toms and reduce mortality, β-blockers can worsen to unload the heart (lower SVR). Again, although do-
symptoms in the short term. It is recommended to keep butamine would be a potential choice in this patient, it
the maintenance β-blocker therapy at the same or a is not recommended in patients receiving β-blockers.
slightly reduced dose compared with outpatient ther- Although this patient has low BP, the elevated SVR
apy in patients with ADHF; increasing the β-blocker suggests that he will tolerate the vasodilatory effects
dose before reaching euvolemia may acutely worsen of milrinone. Although nesiritide would provide venous
his clinical picture. In patients admitted with volume and arterial vasodilation, it is relatively contraindicat-
overload without substantial signs of reduced CO, it is ed in patients with systolic BP less than 100 mm Hg
reasonable to try intravenous loop diuretics initially. and absolutely contraindicated in patients with systolic
As gut edema increases, oral loop diuretics (notably fu- BP less than 90 mm Hg. Phenylephrine has no posi-
rosemide) become less effective because of decreased tive beta effects, so it will not augment contractility. In
absorption. Nesiritide is a vasodilatory drug that can be addition, it will cause vasoconstriction through alpha
initiated if intravenous loop diuretic therapy fails, but stimulation, which will further increase SVR and likely
because of its adverse effects and substantial cost, it is worsen CO. Vasoconstrictors are reserved for patients
not recommended before a trial of intravenous diuretics in cardiogenic shock. Even though this patient shows
and other potential therapies. Milrinone is an inotropic signs of significant hypoperfusion, the BP is not so low
drug. Because of their adverse effects, inotropes are that it warrants vasopressor therapy.
recommended in cold and wet exacerbations only after
vasodilatory medications have failed. 4. Answer: A
Treatment options for sustained VT are dependent on
2. Answer: A concomitant disease states, particularly LVEF (40%
Intravenous vasodilators such as nitroglycerin and so- cutoff). In a patient with LV dysfunction, class I agents
dium nitroprusside are reasonable options if intrave- such as procainamide are contraindicated. In a patient
nous diuretics fail and the patient progresses to acute whose creatinine clearance (CrCl) is less than 60 mL/
pulmonary edema. Both agents rapidly cause venous minute, sotalol requires a considerable dosage reduction
vasodilation and reduce pulmonary filling pressures, to avoid excess torsades de pointes. Sotalol is not an ef-
which can relieve acute shortness of breath. Nitroglyc- fective cardioversion drug but is more useful for prevent-
erin is the optimal choice for this patient given the de- ing future episodes of arrhythmias (maintaining sinus
clining renal function and concern about increased risk rhythm) once sinus rhythm is achieved. Dofetilide is
of thiocyanate toxicity in this setting. Dobutamine is indicated only for AF, not for ventricular arrhythmias;
typically used in states of low CO decompensation and similarly, cardioversion rates with dofetilide are low.
is counteracted by concomitant β-blocker therapy, mak- Amiodarone is first-line therapy for sustained VT in
ing it a poor choice in patients receiving β-blockers. Al- patients with severe renal insufficiency, HF, and struc-
though milrinone is a more acceptable inotropic agent tural heart disease.
in a patient receiving β-blockers, the dosing strategy is
not appropriate as an initial dose. Finally, inotropes are 5. Answer: C
generally reserved for patients in whom all other thera- With the prolonged half-life of amiodarone and exten-
pies have failed. sive fat tissue volume of distribution, it would be ex-
pected that hyperthyroid adverse effects would last for
3. Answer: A at least 3–5 half-lives of the drug, which is anywhere
Signs of a decreased CO state in HF, such as increased from 5 to 8 months. Although therapeutic levels may
SCr, decreased mental status, and cool extremities, fall off substantially by then, 1 month is too soon to
suggest a cold and wet state, and adjunctive therapy is expect the effects to subside. Even though some iodine
2-191
Cardiology I
and amiodarone molecules will likely remain absorbed

in fat stores for years, if not for life, therapeutic levels 9. Answer: A
should not exist for longer than what is predicted by the Hypertensive emergency should be treated immedi-
half-life. ately by a 25% reduction in MAP, followed by a slow
reduction to goal for 5–7 days. The patient’s comorbidi-
6. Answer: D ties guide the optimal therapy. His dialysis and SCr of
This patient is experiencing QT prolongation with so- 11.4 mg/dL are a contraindication to sodium nitroprus-
talol, placing the patient at an increased risk of develop- side caused by possible thiocyanate toxicity. Labetalol
ing life-threatening torsades de pointes. Sotalol should (β-blockers in general) is controversial in patients who
be immediately discontinued. Given the QT prolon- have taken cocaine, but its nonselective nature makes
gation that occurred with sotalol, the same will likely it an option; however, a reduction of 50% initially is
occur with dofetilide. Amiodarone is associated with too rapid a decrease in BP for safety. Clonidine is not an
minimal risk of QT prolongation and thus would be an appropriate drug for hypertensive emergency because its
appropriate alternative agent to prevent ventricular ar- unpredictable oral nature is difficult to titrate and can
rhythmias. lead to precipitous drops in BP beyond the goal 25%
reduction and possibly stroke or worsening MI. Nitro-
7. Answer: C glycerin is an optimal choice, considering the patient’s
This patient is already receiving therapy with calcium lack of contraindications to this therapy and his evolv-
channel blockers to control her HR caused by AF. She ing MI.
is taking a considerable dose of diltiazem, and her HR
likely will not tolerate further increases in therapy. 10. Answer: D
Sildenafil is indicated for functional class I patients to In the setting of cocaine-induced HTN, a dual β- and
improve symptoms or for patients whose other therapies α-blocking drug is preferable to a β-blocker alone. In
have failed. Although bosentan is an attractive oral op- the setting of aortic dissection, sodium nitroprusside
tion to manage her PAH, her liver enzymes are elevated should not be used before using β-blocker therapy first
more than 3 times the upper limit of normal. In this to prevent reflex tachycardia. Thus, the optimal regi-
setting, administering bosentan is not recommended. If men for a patient with cocaine-induced HTN resulting
liver transaminases are elevated transiently because of in aortic dissection is labetalol followed by sodium ni-
hepatic congestion, bosentan may be reconsidered later. troprusside.
Because this patient is currently in functional class IV
with symptoms at rest, epoprostenol is indicated for a
survival benefit.
8. Answer: A
Epoprostenol is now warranted to manage this patient’s
underlying disease because he has not responded to
two oral PAH therapies and is now considered high
risk because of the presence of right ventricle (RV)
dysfunction and low CI. The patient has normal filling
pressures for a patient with RV dysfunction, and diure-
sis with furosemide may only worsen his low CI. The
underlying cause of his low CI is not elevated arterial
resistance; thus, nitroprusside would likely worsen his
hypotension. Correcting the elevated pulmonary pres-
sures should correct the low CI; thus, dobutamine is not
indicated at this time, and it would likely only worsen
his tachycardia.
2-192
Cardiology I
Answers and Explanations to Self-Assessment Questions
1. Answer: C hypertensive emergency, its use is cautioned in patients

Bosentan is an inducer of CYP3A4 and CYP2C9 isoen- with stroke symptoms because its dopamine agonist
zymes. Bosentan decreases the plasma concentrations activity can cause cerebral vasodilation and potentially
of all hormonal contraceptive medications, including reduced bloodflow to the ischemic areas of the brain. Ni-
both estrogen- and progesterone-containing formula- cardipine is an appropriate choice for this patient because
tions, because of its effects on CYP metabolism. No its calcium channel blocking effects will reduce BP and
hormonal contraceptive, including oral, injectable, potentially decrease vasospasm in the cerebral arteries,
topical (patch), and implantable formulations, should which may lead to further ischemia or seizure activity.
be used as the only means of contraception because Although labetalol is an effective option for treating this
it may not effectively prevent pregnancy in patients patient’s hypertensive emergency, she has a history of
taking bosentan. Use of a double-barrier method with asthma and a low HR, making labetalol a less-than-ideal
a condom and diaphragm plus spermicide is indicated option for treating her symptoms. The antihypertensive
in patients receiving bosentan and hormonal contracep- effects of enalaprilat depend on a patient’s renin activ-
tives. Because bosentan is also a known teratogen, a ity, which is unknown in this case. Therefore, the BP-
barrier method alone may not be a sufficient form of reducing effects may be more difficult to control than
contraception. with a drug having a more consistent effect in individu-
als. In addition, the bolus nature of the drug is not ideal
2. Answer: C for tightly controlling BP with a 25% reduction in MAP.
The patient is well perfused, and his CO has not changed Continuous-infusion drugs are preferable for easier titra-
substantially (i.e., his disease has not progressed). The tion to effect in a hypertensive emergency.
patient is now experiencing shortness of breath/dyspnea
at rest (NYHA IV). From his presentation, the patient 4. Answer: C
can be classified as Forrester hemodynamic subset II The number needed to treat can be calculated by 1/abso-
(warm and wet). Because the patient is congested, intra- lute risk reduction. Because the absolute risk reduction
venous diuretics are indicated as first-line therapy. Ad- in mortality at 60 months was 7.2% with ICD versus
junctive therapy can be recommended as second-line placebo, 1/0.072 would be used to calculate the number
therapy. Dobutamine and milrinone primarily increase of patients needed to treat to prevent one death during
CO, which is not a considerable problem in warm and this time. About 13.8 patients would need to be treated
wet exacerbations. In addition, the adverse effects of with ICD to prevent one death in 60 months versus pla-
these agents (increased mortality, proarrhythmia) limit cebo. Other calculations in this fashion, including rela-
their use. Intravenous metoprolol should not be used in tive risk reduction and 100% minus the absolute or rela-
patients with ADHF because of potent negative inotro- tive risk reduction, do not provide useful information
pic effects. However, oral metoprolol may be used once for interpreting the trial results and yield an incorrect
the patient is stabilized, and it should be initiated before number of patients.
patient discharge. Nesiritide is a balanced arterial and
venous dilator that decreases afterload and preload, re- 5. Answer: C
spectively. It is useful in patients with acute pulmonary The Cardiac Arrest Study Hamburg trial compared
edema, rapidly reducing the PCWP by causing acute ICD implantation with antiarrhythmic therapy in survi-
venous dilation. The ASCEND-HF trial showed a mod- vors of cardiac arrest for secondary prevention of sud-
est but nonsignificant improvement in dyspnea without den cardiac death. The propafenone study arm was dis-
an increased risk of short-term mortality. continued early because of a significantly (61%) higher
mortality rate compared with ICDs. Although this trial
3. Answer: B had a small sample size that prevented a statistically sig-
This patient shows target organ damage from poorly nificant difference in total mortality from being shown
controlled HTN in the form of a cerebrovascular ac- in ICD-treated patients versus patients treated with ei-
cident. Although fenoldopam is indicated for treating ther amiodarone or metoprolol, the incidence of sudden
2-193
Cardiology I
death was significantly reduced in patients with an ICD Recently published articles appear in the system within
(33% vs. 13%, p=0.005). The AVID (Antiarrhythmics 10 days of article publication, and it often contains data
Versus Implantable Defibrillators) trial also evaluated not found in a typical MEDLINE search.
ICD implantation versus antiarrhythmic drug therapy
(primarily amiodarone) in survivors of sudden cardiac 8. Answer: B
death. Patients with ICDs had a significantly higher rate MedWatch is a post–U.S. Food and Drug Administra-
of survival than those treated with drug therapy (89% tion (FDA) approval program established by the FDA
vs. 82%, p<0.02). for health care professionals to report the adverse
events that occur after a drug is approved. Although it
6. Answer: D is commonly used only for reporting serious reactions
This patient has a depressed LVEF less than 40%, so to the FDA, it can be used to report any adverse event.
her drug therapy options are limited to prevent the de- Information recorded on these forms is reported to the
velopment of worsening HF, which could occur if she manufacturer and is used to determine whether black
were administered procainamide for treatment of her box warnings are necessary or whether new adverse ef-
arrhythmia. Procainamide is indicated only in second- fects are seen with a drug. The Joint Commission re-
ary prevention of sustained VT in patients with a nor- quires that all institutions have a definition of an ADR
mal LVEF greater than 40%. Metoprolol is indicated for the institution that all health care professionals can
only for the treatment of patients with asymptomatic understand and remember. In addition, the Joint Com-
nonsustained VT and SVT associated with CAD. This mission requires that each drug dose administered be
patient had an episode of sustained VT. Her QTc inter- monitored for adverse effects, that each institution have
val is not prolonged at 380 milliseconds, and her serum a system in place for reporting ADRs, and that the in-
magnesium level is within normal limits, so she does stitution ensure that the reporting mechanism identifies
not require intravenous magnesium therapy. She quali- all key ADRs.
fies for treatment with either amiodarone or lidocaine.
Amiodarone is first-line treatment of patients without 9. Answer: B
contraindications because of its efficacy. Because the Pharmacy and Therapeutics Committee
wants to discover whether the new drug is worth the
7. Answer: D extra cost for the added mortality benefits it can pro-
International Pharmaceutical Abstracts is a database vide for patients with decompensated HF compared
of primarily pharmaceutical abstracts in more than 750 with available therapies, a cost-effectiveness analysis is
journals, including foreign and state pharmacy journals, the best pharmacoeconomic analysis to perform. Cost-
in addition to key U.S. medical and pharmacy journals. minimization analysis is used to determine whether a
Many of the citations are not included on MEDLINE, therapeutically equivalent drug within a class that pro-
so a broader search can be performed; however, subject vides a therapeutic outcome the same as others avail-
descriptors are not consistently defined in a uniform able can be used for less cost. Cost-utility analysis is
way, and multiword terms are often cited backward. used to determine whether a drug can improve the qual-
The Iowa Drug Information Service database offers ity of a patient’s life more than other available therapies.
full-text articles from 1966 to present in about 200 Cost-benefit analysis is used to evaluate new programs
medical and pharmacy journals (primarily based in the or services to determine whether they provide enough
United States). It is updated monthly, so newly avail- benefit to justify the cost of running the program.
able articles may take longer to be accessed from this
service. The Clin-Alert database contains more than 10. Answer: C
100 medical and pharmacy journals focused on adverse This patient is experiencing hypertensive urgency, con-
events, drug interactions, and medical-legal issues. It sidering that he has no evidence of target organ dam-
is used primarily to look up adverse events (especially age. Thus, his BP may be reduced over 24 hours us-
recent reports) associated with medications. Excerpta ing oral medications. Given this patient’s concomitant
Medica is a comprehensive database of more than 7000 comorbidities, HF, and microalbuminuria, an ACEI
journals from 74 countries dating from 1974 to present. would be indicated. Sublingual nifedipine is no longer
2-194
Cardiology I
recommended for management of hypertensive urgen-

cy because of acute BP lowering and association with
life-threatening adverse events such as MI and stroke.
Clonidine and labetalol are acceptable options; howev-
er, the patient has compelling indications for an ACEI.
Although the patient should receive a β-blocker in ad-
dition to an ACEI for HF management, labetalol is not
one of the three β-blockers recommended for chronic
HF management.
2-195
Cardiology I
2-196

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Cardiology I

Learning Objectives: 3. H.E. is a 53-year-old woman admitted to the hos-

I. ACUTE DECOMPENSATED HEART FAILURE (ADHF)

Table 1. Hemodynamic Values in Patients with ADHF and Sepsis

Table 2. Signs and Symptoms of ADHF

Table 3. Forester Hemodynamic Subsets and Therapy

Subset I – Warm and Dry (Normal Parameters)

C. Chronic HF Therapy in the Setting of Acute Decompensation

D. ADHF Therapy Overview

Table 4. Overview of ADHF Guideline Recommendations

Table 5. Diuretic Therapy for ADHF

Table 6. Inotropic Therapy for ADHF

Table 7. Vasodilator Therapy for ADHF

A. Drug Therapy Overview

Table 8. Antiarrhythmic Drug Classes

Quinidine AEs: Nausea/vomiting/diarrhea (30%), AF conversion:

Propafenonea AEs: Metallic taste, dizziness, ADHF, AF conversion:

B. Adult Cardiac Arrest

Table 10. Select Advanced Cardiovascular Life Support Algorithmsa

(b) If disabling symptoms, consider adding antiarrhythmic drug therapy or ablation.

Table 11. Atrial Fibrillation – Rate Control and Rhythm Control

E. Implantable Cardioverter Defibrillators

F. Special Patient Populations

Table 12. Alteration of Defibrillation Threshold

III. Pulmonary ARTERIAL hypertension

A. Definition, Diagnosis, and Treatment Goals

Table 13. Diagnostic Findings of PAH

Table 15. Initial PAH Treatment Algorithm

Table 16. Overview of PAH Treatment Options

Table 16. Overview of PAH Treatment Options (continued)

Class II–III PAH

IV. Hypertensive CRISES (Urgency and Emergency)

Table 17. Commonly Used Intravenous Drugs for Hypertensive Emergencies

Table 18. Commonly Used Oral Drugs for Hypertensive Urgencies

Table 19. Agents Preferred for Hypertensive Crises Based on Comorbidities

Answers and Explanations to Patient Cases

1. Answer: C indicated. Positive inotropic agents, such as milrinone,

and amiodarone molecules will likely remain absorbed

Answers and Explanations to Self-Assessment Questions

1. Answer: C hypertensive emergency, its use is cautioned in patients

recommended for management of hypertensive urgen-

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