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Cardiology I
Shannon W. Finks, Pharm.D., FCCP,
BCPS (AQ Cardiology)
Associate Professor
University of Tennessee College of Pharmacy
Clinical Pharmacy Specialist-Cardiology
Veterans Affairs Medical Center Memphis
Memphis, Tennessee
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Learning Objectives
1. Distinguish between the acute coronary syndromes
ST-segment elevation myocardial infarction, non
ST-segment elevation myocardial infarction, and
unstable anginaby diagnosis and treatment.
2. Formulate evidence-based treatment strategies for
patients with acute decompensated heart failure.
3. Differentiate between goals and treatment for hypertensive emergencies and hypertension without
progressive organ damage.
4. Devise a treatment plan for patients presenting
with a life-threatening arrhythmia.
5. Provide evidence-based treatment for a patient
given a diagnosis of idiopathic pulmonary arterial
hypertension.
Self-Assessment Questions
Answers and explanations to these questions
can be found at the end of this chapter.
1. A 62-year-old man presents to the emergency department with the chief concern of chest pain that
woke him from sleep and radiates to his jaw. An
electrocardiogram (ECG) is conducted, which reveals ST-segment depression in leads V2V4. His
blood pressure (BP) is 112/62 mm Hg, and heart
rate (HR) is 90 beats/minute. Cardiac enzymes
have been drawn, and the first troponin result returned slightly positive. Preparations are under
way to take the patient to the cardiac catheterization laboratory for evaluation. Which medication
regimen represents the most appropriate treatment
for this patient at this time?
A. Aspirin (ASA) 325 mg, clopidogrel 600 mg
loading dose, and unfractionated heparin
(UFH) infusion 80-unit/kg bolus, followed
by 18 units/kg/hour and metoprolol 5 mg
intravenously x 3.
B. ASA 81 mg; prasugrel 60-mg loading dose;
UFH infusion 60-unit/kg bolus, followed by
12 units/kg/hour; and intravenous enalaprilat.
C. ASA 325 mg, ticagrelor 180-mg loading dose,
and UFH infusion 60-unit/kg bolus, followed
by 12 units/kg/hour.
D. ASA 81 mg, clopidogrel 600 mg,
nitroglycerin infusion at a rate of 10 mcg/
minute, and bivalirudin 0.75-mg/kg bolus and
1.75-mg/kg/hour infusion.
3. A 60-year-old woman with New York Heart Association (NYHA) class IV heart failure (HF) is
admitted for increased shortness of breath and dyspnea at rest. Her extremities appear well perfused,
but she has 3+ pitting edema in her lower extremities. Her vital signs include BP 125/70 mm Hg, HR
92 beats/minute, and O2 saturation 89% on 100%
facemask. After initiating an intravenous diuretic,
which is the best intravenous drug to treat this
patient?
A. Dobutamine.
B. Milrinone.
C. Nitroglycerin.
D. Metoprolol.
4. A 75-year-old woman has a history of NYHA class
III HF (left ventricular ejection fraction [LVEF]
25%) and several nonST-segment elevation myocardial infarctions (NSTEMIs). She had an episode
of sustained ventricular tachycardia (VT) during
this hospitalization for pneumonia. Her corrected
QT (QTc) interval was 380 milliseconds on the
telemetry monitor, and her serum potassium and
magnesium were 4.6 mEq/L and 2.2 mg/dL, respectively. Which intravenous agent is most appropriate for this patient?
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A. Procainamide.
B. Metoprolol.
C. Magnesium.
D. Amiodarone.
A. Propafenone.
B. Amiodarone.
C. Implantable cardioverter defibrillator (ICD).
D. Metoprolol.
Nifedipine 10 mg sublingually.
Clonidine 0.2 mg orally.
Captopril 12.5 mg orally.
Labetalol 200 mg orally.
7. A 52-year-old woman experiences a witnessed cardiac arrest in a shopping mall; she is resuscitated
with an automatic external defibrillator device.
On electrophysiologic study, she has inducible
VT. Which agent is most appropriate for reducing
the secondary incidence of sudden cardiac death
(SCD)?
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Cost-minimization analysis.
Cost-effectiveness analysis.
Cost-benefit analysis.
Cost-utility analysis.
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NonST-segment
elevation MI
(NSTEMI)
ST-segment
elevation MI
(STEMI)
Objective Findings
ST-segment depression,
T-wave inversion, or
transient or nonspecific
ECG changes may occur
Positive biomarkers
(troponin I or T elevation,
CK-MB fraction > 5% of
total CK)
ST-segment elevation of
> 1 mm above baseline
on ECG in two or more
contiguous leads
Extent of Injury
No myocardial
injury; partial
occlusion of coronary
artery
Myocardial injury;
partial occlusion of
coronary artery
Myocardial necrosis;
total occlusion of
coronary artery
Positive biomarkers
(troponin I or T elevation,
CK-MB fraction > 5% of
total CK)
Note: Up to one-half of all MIs are silent or unrecognized, and one-third present with symptoms other than chest discomfort.
ACS = acute coronary syndromes; CK = creatine kinase; CK-MB = creatine kinase myocardial band; ECG = electrocardiogram; MI = myocardial
infarction.
a
2. Therapy goals
a. Unstable angina (UA)/NSTEMI goals
i. Prevent total occlusion of the infarct-related artery.
(a) Medical management includes antiplatelet therapy (ASA plus P2Y12 receptor inhibitor
plus or minus glycoprotein IIb/IIIa inhibitors [GPIs]) and antithrombotic therapy (UFH,
low-molecular-weight heparin [LMWH], fondaparinux, or bivalirudin)
(b) Percutaneous coronary intervention (PCI):
(1) Percutaneous transluminal coronary angioplasty (i.e., balloon)
(2) Stent implantation (bare metal [BMS] or drug-eluting [DES])
(3) Arthrectomy
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Points
1
1
1
Presentation
Severe angina ( 2 episodes within 24 hours
ASA within 7 days
Elevated markers
ST-segment deviation > 0.5 mm
1
1
1
1
Risk of mortality, new or recurrent MI, or severe recurrent ischemia through 14 days. Low is 02, intermediate is 3, and > 4 is high risk.
Risk score = total points (07).
ASA = aspirin; MI = myocardial infarction; NSTEMI = nonST-segment elevation myocardial infarction; TIMI = thrombolysis in myocardial
infarction.
a
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C. Initial Management
1. MONA plus -blocker
Table 4. Initial Management of ACS MONA plus -Blocker
M = Morphine Morphine 24 mg IV q515 minutes is reasonable if symptoms are not relieved despite NTG or
if symptoms recur
O = Oxygen
N=
Nitroglycerin
NTG spray or SL tablet 0.4 mg 3 to relieve acute chest pain (if pain is unrelieved after one dose,
call 911)
NTG IV 510 mcg/minute, titrate to chest pain relief or 200 mcg/minute if pain unrelieved by
morphine and SL NTG
- Used in first 48 hours for treatment of persistent chest pain, HF, and HTN
- Use should not preclude other mortality-reducing therapies (-blocker, ACE inhibitor)
- No mortality benefits but high placebo crossover rate
CIs: Sildenafil or vardenafil use within 24 hours or tadalafil use within 48 hours; SBP < 90 mm
Hg or 30 mm Hg below baseline, HR < 50 beats/minute, HR > 100 beats/minute in absence of
symptomatic HF or right ventricular infarction
A = Aspirin
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Indicated orally within first 24 hours if anterior MI, HF, LVEF 40%, unless CI
- IV therapy contraindicated because of risk of hypotension
Consider in all patients post-ACS unless CI
Continued indefinitely in all patients post-ACS with LVEF < 40%, HF, hypertension, or diabetes
ARB indicated if contraindication to ACE inhibitor
CIs: Hypotension, pregnancy, bilateral renal artery stenosis
Aldosterone
antagonist
Indicated in patients post-ACS already receiving ACE inhibitor and -blocker and who have
LVEF 40% and either symptomatic HF or diabetes, unless CIs
CIs: Hyperkalemia (K > 5.0), CrCl < 30 mL/minute
Statins
High-intensity statin therapy should be initiated or continued in all patients without CIs
CCBs
ACE = angiotensin-converting enzyme; ACS = acute coronary syndrome; ARB = angiotensin receptor blocker; ASA = aspirin; CAD = coronary
artery disease; CCB = calcium channel blocker; CKD = chronic kidney disease; CI= contraindication; HF = heart failure; HTN = hypertension;
ISA = intrinsic sympathomimetic activity; IV = intravenous(ly); K = potassium; LV = left ventricular; LVEF = left ventricular ejection fraction;
MAP = mean arterial pressure; MI = myocardial infarction; N/A = not available; NTG = nitroglycerin; q = every; SBP = systolic blood pressure;
SL = sublingual.
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2. Antiplatelet and anticoagulant strategies for acute coronary syndromes (ACS) (see Tables 5 and 6)
Table 5. Antiplatelet and Anticoagulant Management Strategies in UA/NSTEMI
Strategy
Invasive Strategy
Anticoagulant
therapya
Aspirin PLUS:
Aspirin PLUS:
Antiplatelet
therapy
If high risk of bleeding, fondaparinux or bivalirudin preferred. If CABG planned, UFH preferred.
Fondaparinux should not be used as the sole anticoagulant during PCI. It is given a class I recommendation in the 2012 UA/NSTEMI guidelines
and a class III or harmful recommendation in the 2011 PCI guidelines.
c
Enoxaparin or fondaparinux in preference to UFH is given a class IIa LOE B recommendation in the 2012 UA/NSTEMI guidelines.
d
If unlikely to undergo CABG, initiate prasugrel or ticagrelor at time of PCI.
e
Benefit from adding GPI to dual antiplatelet therapy (DAT) is greatest among those with highest-risk features (elevated biomarkers, diabetes,
those undergoing revascularization). GPIs were studied in those receiving UFH as anticoagulant strategy. After PCI, discontinue anticoagulation
and continue GPI for 1224 hours at the discretion of the physician.
CABG = coronary artery bypass grafting; GPI = glycoprotein IIb/IIIa inhibitor; LOE = level of evidence; NSTEMI = nonST-segment elevation
myocardial infarction; NTG = nitroglycerin; PCI = percutaneous coronary intervention; UA = unstable angina; UFH = unfractionated heparin.
a
Primary PCI
Class I agents: IV UFH or
bivalirudin
Antiplatelet therapy
Aspirin PLUS:
Fibrinolysis
Should receive anticoagulant therapy with
fibrinolysis for a minimum of 48 hours,
preferably for the duration of hospitalization or
until revascularization. Regimens include UFH,
enoxaparin, and fondaparinuxa
Aspirin PLUS:
Fondaparinux should not be used as the sole anticoagulant to support PCI. Give additional anticoagulant during revascularization if fondaparinux
was initially chosen as anticoagulant strategy.
GPI = glycoprotein IIb/IIIa inhibitor; IV = intravenous; LOE = level of evidence; PCI = percutaneous coronary intervention; SC = subcutaneous;
STEMI = ST-segment elevation myocardial infarction; UFH = unfractionated heparin.
a
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Metabolism
Half-life
Nonresponders
Drug-disease
interactions
Clopidogrel (Plavix)a
ACS managed medically
or with PCI
300-mg load 6 hours
600-mg load 2 hours
LD: 300600 mg
MD: 75 mg daily
Prodrug; converted
by two-step process
involving 2C19 and
3A4
8 hours metabolite
Exposure to active drug
affected by CYP2C19
and CYP3A4 and PGP
polymorphisms
PPIs inhibit 2C19
(concomitant use
with omeprazole
is discouraged per
package labeling;
enhanced bleeding with
NSAIDs, VKA, O3FA,
etc.
5 days
Less than PRA and TIC
with standard dosing
Box warning
Genetic polymorphisms
Study
Prasugrel (Effient)b
ACS with PCI
60-mg load ~11.5 hoursd
Ticagrelor (Brilinta)c
ACS managed medically or with
PCI
180-mg load < 1 hourd
LD: 60 mg
MD: 10 mg daily (5 mge if <
60 kg; BW 75 years)
CIs: TIA/stroke
Prodrug; converted to active
metabolite by several CYP
pathways
LD: 180 mg
MD: 90 mg twice daily
CIs: ICH, severe hepatic disease
Discontinue CLO at least 5 days before surgery. Administer CLO indefinitely if ASA allergy. Avoid LD if patient is 75 years or older in STEMI
when fibrinolysis is given.
b
Discontinue PRA at least 7 days before surgery. Avoid PRA in patients with active pathologic bleeding or a history of TIA or stroke as well as in
patients older than 75 years unless patient has DM or history of myocardial infarction.
c
Discontinue TIC at least 5 days before surgery. Avoid TIC in patients with active pathologic bleeding or a history of ICH. Avoid doses of ASA >
100 mg daily (exception: first dose of 325 mg).
d
A significant antiplatelet effect has been observed at 30 minutes. Both onset of effect and extent of platelet inhibition is greater than seen with CLO.
e
Although using 5 mg in patients weighing < 60 kg should be considered, this dose has not been prospectively studied.
ACS = acute coronary syndromes; ASA = aspirin; BW = box warning; CABG = coronary artery bypass grafting; CI = contraindication; CLO =
clopidogrel; CVA = cerebrovascular accident; CYP = cytochrome P450; DM = diabetes mellitus; ICH = intracranial hemorrhage; LD = loading dose;
MD = maintenance dose; NSAID = nonsteroidal anti-inflammatory drug; O3FA = omega-3 fatty acids; PCI = percutaneous coronary intervention;
P-gp = P-glycoprotein; PPI = proton pump inhibitor; PRA = prasugrel; STEMI = ST-segment elevation myocardial infarction; TIA = transient
ischemic attack; TIC = ticagrelor; VKA = vitamin K antagonist.
a
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Table 8. Dual Antiplatelet Therapy Dosing Strategies in ACS with or without PCI
ASA
STEMI
CLO 600-mg LD or PRA 60-mg LD or TIC 180-mg LD for primary PCI
Pre-PCI after fibrinolytic therapy 300 CLO 300-mg LD if within 24 hours
of event; CLO 600-mg LD if > 24 hours after event
UA/NSTEMI
CLO 600-mg LD or PRA 60-mg LD or TIC 180-mg LD if PCI planned
CLO 600-mg LD or TIC 180-mg LD if medical management
Pre-PCI
BMS or DES:
ASA 81 mg/day indefinitely
BMS:
CLO 75 mg/day for a minimum of 1 month and ideally up to 12 monthsb
DES:
CLO 75 mg/day for a minimum of 12 months
Post-ACS (medical management; no PCI)
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Of uncertain benefit
Renal Adjustments
Renal adjustment not
necessary
Tirofiban
(Aggrastat)
Of uncertain benefit
used as above
PCI: 25-mcg/kg IV bolus over 3
minutes; then 0.15 mcg/kg/minute for
1824 hours
Enoxaparin
(Lovenox)
Fondaparinux
(Arixtra)
Classification
LMWH
Factor Xa inhibitor
UA/NSTEMI
60-unit/kg IVB
(maximum 4000 units),
12 units/kg/hour IV
(maximum 1000 units/
hour) for 48 hours or
end of PCI, goal aPTT
of 5070 seconds
Supplemental doses to
target ACTa
PCI
Bivalirudin
(Angiomax)
DTI
1 mg/kg SC bid
for 2448 hours
or until end of
PCI or throughout
hospitalization (up to
8 days)
2.5 mg SC daily
Fondaparinux
should not be
used as a sole
anticoagulant for
PCI
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Bivalirudin
(Angiomax)
0.75-mg/kg IVB, 1.75
mg/kg/hour IV
Target ACT 250300 seconds for HemoTec and 300350 seconds for Hemochron without GPI and 200250 seconds in patients given a
concomitant GPI.
ACT = activated clotting time; aPTT = activated partial thromboplastin time; bid = twice daily; CrCl = creatinine clearance; DTI = direct
thrombin inhibitor; GPI = glycoprotein IIb/IIIa inhibitor; HIT = heparin-induced thrombocytopenia; IV = intravenous(ly); IVB = intravenous
bolus; LMWH = low-molecular-weight heparin; NSTEMI = nonST-segment elevation myocardial infarction; PCI = percutaneous coronary
intervention; SC = subcutaneously; STEMI = ST-segment elevation myocardial infarction; UA = unstable angina; UFH = unfractionated heparin.
a
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Dosing
15 mg IV; then 0.75 mg/kg over 30 minutes (maximum 50 mg);
then 0.5 mg/kg (maximum 35 mg) over 60 minutes
Tenecteplase
(TNK-tPA, TNKase)
< 60 kg, 30 mg IV; 6069 kg, 35 mg IV; 7079 kg, 40 mg IV; 8089 kg, 45 mg IV,
> 90 kg, 50 mg IV (about 0.5 mg/kg)
IV = intravenously; r-PA = recombinant plasminogen activator; rt-PA = recombinant tissue plasminogen activator; tPA = tissue plasminogen
activator.
Absolute Contraindications
ANY prior hemorrhagic stroke
Ischemic stroke within 3 months (except in past 4.5 hours)
Intracranial neoplasm or arteriovenous malformation
Active internal bleeding
Aortic dissection
Considerable facial trauma or closed-head trauma in past 3
months
Intracranial or intraspinal surgery within 2 months
Severe uncontrolled hypertension (unresponsive to
emergency therapy)
For streptokinase,a treatment within previous 6 months (if
considering streptokinase again)
Streptokinase is no longer marketed in the United States but is available in other countries.
BP = blood pressure; CPR = cardiopulmonary resuscitation; CVA = cerebrovascular accident; HTN = hypertension; INR = international
normalized ratio; TIA = transient ischemic attack.
a
D. Long-term Management
1. -Blockers
a. Indicated for all patients unless contraindicated
b. Initiate within a few days of event, if not acute, and continue for at least 3 years.
c. If moderate or severe left ventricular (LV) failure, initiate with gradual titration.
2. Angiotensin-converting enzyme (ACE) inhibitors
a. Indicated for all patients even if no LV dysfunction, HTN, or diabetes mellitus (DM)
b. Give oral ACE inhibitor in low doses to all patients during the first 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.
c. Angiotensin receptor blocker if ACE inhibitor intolerant
d. Avoid intravenous ACE inhibitor post-MI to prevent hypotension.
3. Aldosterone receptor blockers: Indicated if post-MI with LVEF less than 40%, symptomatic HF or
DM, and receiving ACE inhibitors; however, contraindicated if creatinine clearance (CrCl) less than 30
mL/minute or serum potassium more than 5 mEq/L
4. Lipid management High-intensity statins are indicated with a goal of less than 70 mg/dL
5. Discontinue NSAIDs except for ASA at time of presentation. Selective COX-2 inhibitors and other
nonselective NSAIDs have been associated with increased cardiovascular death. Pain should be treated
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in a stepwise fashion, starting with acetaminophen or ASA. Small doses of narcotics or nonacetylated
salicylates are preferred to NSAIDs. Nonselective NSAIDs (i.e., naproxen) are last line if other pain control
measures are unsuccessful. In all cases, the lowest effective dose should be used for the shortest time.
6. Other goals Hemoglobin A1c less than 7%, smoking cessation, body mass index 18.524.9 kg/m2,
exercise at least five times/week
7. In patients requiring warfarin therapy with dual antiplatelet therapy (DAPT), an international normalized
ratio (INR) goal of 2.02.5 is recommended with low-dose ASA according to STEMI guidelines (class IIa,
LOE [level of evidence]: C)
Patient Cases
1. A 66-year-old, 70-kg woman with a history of MI, HTN, hyperlipidemia, and DM presents with suddenonset 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. Electrocardiography showed ST-segment depression in leads II, III, and aVF and hyperdynamic T waves and positive cardiac enzymes. Home medications are ASA 81 mg/day, simvastatin 40 mg
every night, metoprolol 50 mg two times/day, and metformin 1 g two times/day. Which regimen is the best
treatment strategy for this patient?
A. ASA 325 mg and clopidogrel 600 mg 1; then 75 mg once daily, UFH 60-unit/kg bolus; then 12 units/
kg/hour titrated to 5070 seconds immediately plus eptifibatide 180-mcg/kg bolus 2; then 2 mcg/kg/
minute at the time of PCI.
B. ASA 325 mg and enoxaparin 70 mg subcutaneously two 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 two times/day, ASA 325 mg/day, and clopidogrel 300 mg 1; then 75
mg once a day.
D. Medical management with ASA 325 mg and clopidogrel 300 mg 1; then 75 mg once a day plus UFH
70-unit/kg bolus; then 15 units/kg/hour.
2. A 45-year-old patient received an elective percutaneous transluminal coronary angioplasty and DES in her
right coronary artery. Which duration best represents the minimum time DAPT should be continued?
A.
B.
C.
D.
At least 1 month.
At least 3 months.
At least 6 months.
At least 12 months.
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A 75-year-old (weight 65 kg) male smoker has a history of HTN, benign prostatic hypertrophy, and lower
back pain. Three weeks ago, he began to experience 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 four or five times/day; they 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 ongoing pain. Home medications are ASA 81 mg/day for 2 months,
doxazosin 2 mg/day, and ibuprofen 800 mg three times/day. Vital signs include HR 42 beats/minute (sinus
bradycardia), BP 104/48 mm Hg, and weight 61 kg. Laboratory results include blood urea nitrogen (BUN)
45 mg/dL, SCr 2.5 mg/dL, CK 277 units/L, creatine kinase myocardial band (CK-MB) 35.2 units/L, and
troponin T 1.5 mcg/L (less than 0.1 mcg/L). His ECG shows a 3-mm ST-segment elevation. Aspirin, clopidogrel, and sublingual nitroglycerin were given in the emergency department. Which regimen is best to
recommend?
A. Alteplase 15 units intravenously plus enoxaparin 30 mg intravenous bolus.
B. UFH 4000 unit intravenous bolus followed by 800 units intravenously per hour.
C. Tenecteplase 35 mg intravenously plus UFH 4000-unit intravenous bolus followed by 800 units
intravenously per hour.
D. Diagnostic cardiac catheterization for possible primary PCI.
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Normal
Value
80100
6080
47
2.83.6
812a
8001200
26
Typical
ADHF Value
6080
7090
24
1.32
1830
15003000
615
Typical
Sepsis Value
6080
90100
58
3.54
58
300800
26
B. Clinical Presentation
Table 14. Signs and Symptoms of ADHF
Congestion (elevated PCWP)
Dyspnea on exertion or at rest
Orthopnea, paroxysmal nocturnal dyspnea
Peripheral edema
Rales
Early satiety, nausea/vomiting
Ascites
Hepatomegaly, splenomegaly
Jugular venous distention
Hepatojugular reflux
ADHF = acute decompensated heart failure; CO = cardiac output; PCWP = pulmonary capillary wedge pressure.
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CI
2.2
Subset I.
Normal
Warm and dry
Subset II.
Congestion
Warm and wet
Subset III.
Hypoperfused
Cold and dry
Subset IV.
Congestion + hypoperfusion
Cold and wet
18
PCWP
Subset I Warm and Dry (Normal Parameters)
(PCWP 1518 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 1518 mm Hga AND CI less than 2.2 L/minute/m2)
If PCWP < 15 mm Hg, IVF until PCWP 1518 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)
IV diuretics +
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)
Goal PCWP is 812 mm Hg in a normal patient and 1518 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 1518 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 in CI.
CI = cardiac index; IV = intravenous; IVF = intravenous fluid; MAP = mean arterial pressure; PCWP = pulmonary capillary wedge pressure.
a
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3. -Blockers
a. Do not discontinue in patients who are stable on dose before admission (i.e., recent initiation or uptitration was not responsible for decompensation).
b. Do not initiate or up-titrate until euvolemic.
c. Hold if hemodynamically unstable.
4. Digoxin
a. Continue at dose to achieve serum digoxin concentration of 0.50.8 ng/mL.
b. Avoid discontinuation unless there is a compelling reason to do so because digoxin withdrawal
has been associated with worsening HF symptoms.
c. Caution if renal function begins to deteriorate or often fluctuates
D. ADHF Therapy Overview
Table 16. 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 a different MOA (metolazone, 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 to or intolerance of 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
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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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 1518 mm Hg)
before administering inotropic therapy.
Table 18. Inotropic Therapy for ADHF
Dobutamine (Dobutrex)
Milrinone (Primacor)
Mechanism
1-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, no direct
lusitropic effects
chronotropic effects
Indication
ADHF Cold and wet (Forester subset IV) or cold and dry exacerbations (Forester III) (if
PCWP > 15 mm Hg)
Dosing
Start 2.55 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, 0.10.375 mcg/kg/minute IV
Half-life
2 minutes
1 hour, prolonged to 23 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 -blocker
AC = adenylate cyclase; ADHF = acute decompensated heart failure; ATP = adenosine triphosphate; cAMP = cyclic adenosine monophosphate;
CO = cardiac output; CrCl = creatinine clearance; HF = heart failure; 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 19. Vasodilator Therapy for ADHF
Sodium Nitroprusside
(Nipride)
Mechanism of Nitric oxideinduced
action
stimulation of GC to
convert GTP to cGMP
Nesiritide
(Natrecor)
Recombinant B-type
natriuretic peptide binds
to natriuretic peptide
receptor A to stimulate GC
and production of cGMP;
natriuretic mechanism
unknown
Hemodynamic effects:
PCWP and SVR, CI,
minimal changes in HR
Neurohormonal effects:
NE, ET-1, and aldosterone
Natriuretic effects at
supratherapeutic doses
Warm and wet ADHF,
alternative to inotropes in
cold and wet ADHF
Clinical
effects
Indication
Dosing
Typical dose
Half-life
Elimination
Adverse
effects
IV Nitroglycerin
Combines with sulfhydryl
groups in vascular endothelium
to create S-nitrosothiol
compounds that mimic nitric
oxides stimulation of GC and
production of cGMP
Preferential venous vasodilator
> arterial vasodilator, arterial
vasodilation at high doses (e.g.,
100 mcg/minute)
ACS = acute coronary syndromes; 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
5. A 72-year-old man is admitted to the hospital for HF decompensation. The patient notes progressively increased 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 (050 pg/mL), potassium (K+) 4.9 mEq/L, BUN
32 mg/dL, SCr 2.0 mg/dL (baseline 1.9 mg/dL), aspartate aminotransferase (AST) 40 IU/L, alanine aminotransferase (ALT) 42 IU/L, INR 1.3, aPTT 42 seconds, BP 108/62 mm Hg, HR 82 beats/minute, and O2
saturation 95%. Home drugs include carvedilol 12.5 mg two times/day, lisinopril 40 mg/day, furosemide 80
mg two times/day, spironolactone 25 mg/day, and digoxin 0.125 mg/day. Which regimen is best for treating
his ADHF?
A. Carvedilol 25 mg two times/day.
B. Nesiritide 2-mcg/kg bolus; then 0.01 mcg/kg/minute.
C. Furosemide 120 mg intravenously two times/day.
D. Milrinone 0.5 mcg/kg/minute.
6. After the initiation of intravenous loop diuretics with only minimal urine output, the patient is transferred to
the coronary 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. The patients 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 regimen is
most appropriate for this patient?
A.
B.
C.
D.
7.
Nitroglycerin 20 mcg/minute.
Sodium nitroprusside 0.3 mg/kg/minute.
Dobutamine 5 mcg/kg/minute.
Milrinone 0.5 mcg/kg/minute.
The patient 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 SwanGanz catheter is placed to determine further management. Hemodynamic values are cardiac index (CI)
1.5 L/minute/m 2, SVR 2650 dynes/cm-5, and PCWP 30 mm Hg. Which regimen is most appropriate for his
current symptoms?
A.
B.
C.
D.
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B. Symptomatic Bradycardia
1. If unstable, atropine 0.5 mg every 35 minutes (maximal dose 3 mg). (Note: Unstable = hypotension, acutely
altered mental status, signs of shock, ischemic chest discomfort, acute HF)
2. If atropine fails, transcutaneous pacing, dopamine 210 mcg/kg/minute, or epinephrine 210 mcg/minute
C. 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)
(1) Rapid push followed by elevation of arm to increase circulation
(2) Larger doses may be needed in patients taking theophylline, caffeine, or theobromine.
(3) Initial dose should be reduced to 3 mg in patients taking dipyridamole or carbamazepine
and in patients after heart transplantation, as well as when the drug is being given by
central access.
(4) Use adenosine cautiously in severe CAD.
(5) Adenosine should not be given to patients with asthma.
(6) Do not give adenosine for unstable or for irregular or polymorphic wide complex
tachycardias because it may cause degeneration to VF.
(b) If vagal maneuvers or adenosine fails to convert paroxysmal SVT, calcium channel blockers
or -blockers can be used. If WPW (Wolff-Parkinson-White) syndrome, avoid verapamil,
diltiazem, and digoxin
ii. Irregular (narrow complex) ventricular rhythm AF (or possibly atrial flutter)
(a) General management should focus on control of the rapid ventricular rate.
(1) Usually nondihydropyridine calcium channel blockers (diltiazem, verapamil) or
-blockers; digoxin is sometimes useful
(2) Rate is acceptable if it is less than 110 beats/minute at rest in asymptomatic persistent
AF.
(b) If hemodynamically unstable, synchronized cardioversion recommended
(c) Patients with AF for more than 48 hours are at high risk of cardioembolic events and should
not be immediately cardioverted if stable.
(d) TEE (transesophageal echocardiography) before cardioversion is an alternative strategy to
ensure the absence of left atrial clot.
(e) Risk of thromboembolic event surrounding cardioversion (both pharmacologic and electrical)
is greatest within the first 10 days.
(f) Cardioversion:
(1) If AF for up to 7 days, either elective direct current conversion (DCC) or chemical
cardioversion with:
(A) Flecainide, dofetilide, propafenone, ibutilide, or amiodarone (proven efficacy)
(B) Digoxin and sotalol NOT recommended and may be harmful
(C) Disopyramide, quinidine, and procainamide are less effective or incompletely
studied.
(2) If AF greater than 7 days, either elective DCC or chemical cardioversion with
dofetilide, amiodarone, or ibutilide (proven efficacy)
b. Wide complex tachycardia (QRS greater than 120 milliseconds) Usually ventricular arrhythmias
i. VT or unknown mechanism
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Cardiology I
Class/Ion Affected
Agents
Class I/Na+ channel
blockers
IA Disopyramide
(INTERMEDIATE) Quinidine,
procainamide
IB Lidocaine,
(FAST) mexiletine,
phenytoin
IC Flecainide
(SLOW) Propafenone
Class II
-Blockers
Metoprolol,
esmolol,
atenolol
Class III
Amiodarone,a
K+ channel blockers
dronedarone,a
sotalol,b
dofetilide,
ibutilide
Class IV
Diltiazem,
Ca2+ channel blockers verapamil
a
Physiologic Effect
Result on
Electrophysiologic
Parameters
Clinical Utility
Conduction velocity
Refractory period
QRS and QT
Conduction velocity
Refractory period
QT
Ventricular
arrhythmias
Conduction velocity
Refractory period
QRS
Conduction velocity
Refractory period
HR and PR
Supraventricular
arrhythmias
and ventricular
arrhythmias
Atrial and ventricular
arrhythmias
Conduction velocity
Refractory period
QT
Conduction velocity
Refractory period
HR and PR
Amiodarone and dronedarone have Ib, II, and IV class activity in addition to class III actions.
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Cardiology I
Table 22. Antiarrhythmic Drug Properties and Dosing (class I and III agents only)
Drug
Quinidine
(Quinidex,
Quinaglute)
Procainamide
(Pronestyl)
AF conversion:
Avoid use because of GI AEs
AF and VT maintenance:
Sulfate: 200400 mg po every 6 hours
Gluconate (CR): 324 mg po every 812 hours
Decrease dose 25% if CrCl < 10 mL/minute
AF conversion:
1 g IV for 30 minutes; then 2 mg/minute
(1-hour efficacy 51%)
AF maintenance:
No oral agent available
VT conversion:
20 mg/minute IV until 17 mg/kg, arrhythmia
ceases, hypotension, or QRS widens > 50%
VT maintenance:
14 mg/minute
Lidocaine
(Xylocaine)
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Cardiology I
Table 22. Antiarrhythmic Drug Properties and Dosing (class I and III agents only) (continued)
Drug
Mexiletine
(Mexitil)
Propafenonea
(Rythmol,
Rythmol SR)
Flecainidea
(Tambocor)
Amiodarone
(Cordarone)
AF conversion:
IV: 57 mg/kg IV over 3060 minutes; then
1.21.8 g/day continuous IV or divided oral
doses until 10 g
po: 1.21.8 g/day in divided doses until 10 g
AF maintenance:
200400 mg/day po
Pulseless VT/VF conversion:
300 mg or 5 mg/kg IVB in 20 mL of D5W or NS;
repeat 150 mg IVB every 35 minutes
Stable VT: 150 mg IVB in 100 mL of D5W for
10 minutes
VT/VF maintenance:
1 mg/minute 6 hours; then 0.5 mg/minute
(maximum 2.2 g/day)
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Cardiology I
Table 22. Antiarrhythmic Drug Properties and Dosing (class I and III agents only) (continued)
Drug
Sotalol
Dofetilide
(Tikosyn)
Ibutilide
(Covert)
Dosing by Indication
AF maintenance (based on CrCl):
80 mg po bid (> 60 mL/minute)
80 mg po qd (4060 mL/minute)
Contraindicated < 40 mL/minute
VT maintenance (based on CrCl):
80 mg po bid (> 60 mL/minute)
80 mg po bid (3060 mL/minute)
80 mg po bid (1030 mL/minute)
80 mg po > qod (< 10 mL/minute)
AF conversion:
1 mg IV ( 60 kg)
or 0.01 mg/kg IV (< 60 kg);
repeat in 10 minutes if ineffective
(efficacy 47% at 90 minutes)
BW: Potentially fatal arrhythmias (e.g.,
polymorphic VT) can occur with ibutilide,
usually in association with TdP; patients with
chronic AF may not be the best candidates for
ibutilide conversion
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Cardiology I
Table 22. Antiarrhythmic Drug Properties and Dosing (class I and III agents only) (continued)
Drug
Dronedarone
(Multaq)
Dosing by Indication
AF maintenance:
400 mg orally two times/day
Discontinue if QTc is 500 milliseconds or greater
BW: The risk of death is doubled when used
in patients with symptomatic HF with recent
decompensation requiring hospitalization
or NYHA class IV symptoms; use is
contraindicated in these patients
Use in patients with permanent AF doubles the
risk of death, stroke, and hospitalization for HF.
Use is contraindicated in patients with AF who
will not or cannot be converted to normal sinus
rhythm
Cardiology I
c. Can be used in combination with -blockers to decrease firing of ICD (defibrillator storm)
3. Sotalol
a. No mortality advantage
b. Can suppress VT and be used to decrease frequency of ICD firing
c. Greater proarrhythmic potential; avoid in patients with severely depressed LVEF or significant
HF; renal dosing required
Table 23. Alteration of Defibrillation Threshold
Threshold Alteration
Increase threshold
Decrease threshold
Medications
Amiodarone, lidocaine, and
mexiletine
Sotalol
Comments
Reprogram ICD, increased energy
(joules) required
May decrease energy needed for DCC
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Patient Cases
8.
A 68-year-old man is 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 hypertrophy, diabetes mellitus, and diabetic nephropathy. His drugs include lisinopril 5 mg/day, furosemide 20 mg
two times/day, metoprolol 25 mg two times/day, digoxin 0.125 mg/day, glyburide 5 mg/day, and aspirin 81 mg/
day. His BP is 120/75 mm Hg, HR 80 beats/minute, BUN 30 mg/dL, and SCr 2.2 mg/dL. Which is the best
therapy to initiate for conversion of his sustained VT?
A.
B.
C.
D.
Amiodarone 150 mg intravenously for 10 minutes; then 1 mg/minute for 6 hours; then 0.5 mg/minute.
Sotalol 80 mg two times/day titrated to QTc of about 450 milliseconds.
Dofetilide 500 mcg two times/day titrated to QTc of about 450 milliseconds.
Procainamide 20 mg/minute, with a maximum of 17 mg/kg.
9. The patient 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 duration would best predict the duration of amiodarone-associated
hyperthyroidism in this patient?
A. Never.
B. 1 month.
C. 6 months.
D. 1 year.
10. 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. The patients 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 -blockers, the patient is successfully treated with lidocaine. Subsequent electrophysiologic testing reveals inducible VT, and sotalol 80 mg orally twice daily is prescribed. Two hours after
the second dose, the patients QTc is 520 milliseconds. Which regimen change would be most appropriate
for this patient?
A.
B.
C.
D.
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Cardiology I
Hypertensive Emergency
Severe elevations in BP (usually greater than
180/110 mm Hg) with the presence of acute
or ongoing target-organ damage
Hypertensive Urgency
Accelerated, malignant, or perioperative
hypertension in the absence of symptoms
or new or progressive target-organ damage
Short-term risk is not as high, so BP reduction
occurs over several days, not immediately.
1. Look for acute target-organ damage (e.g., hypertensive encephalopathy, intracranial hemorrhage, or
other acute neurologic deficit; UA or acute MI; acute HF; pulmonary edema (shortness of breath);
aortic dissection; retinopathy or papilledema; decreased urine output or acute renal failure; eclampsia)
2. Presence of acute target-organ damage determines the treatment approach.
B. Goals
1. Hypertensive emergency Lower mean arterial pressure (MAP) by no more than 25% or diastolic BP
to 100110 mm Hg within 3060 minutes.
a. Intravenous medications used
b. No one drug of choice. Agents are chosen on the basis of patient characteristics (see Table 25).
c. Patients are usually admitted for intensive care unit (ICU) care and close follow-up.
2. Hypertensive urgency Short-term risk not as high as in emergency; oral medications can be used and
BP lowered over several days.
a. No proven benefit exists from rapid reduction in BP in patients with severe asymptomatic
hypertension.
b. The choice of agent used in this setting varies, and in many cases, adjusting chronic oral therapy
(increasing doses), reinitiating therapy in the nonadherent, or adding new agent (i.e., diuretic) to
chronic therapy is appropriate.
c. In some situations, shorter-acting agents may be chosen.
d. All patients with hypertensive urgency should be reevaluated within and no later than 7 days
(preferably after 13 days).
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Cardiology I
C. Treatment Options
Table 24. Commonly Used Intravenous Drugs for Hypertensive Emergencies
Drug (onset, duration)
Sodium nitroprusside
(Nipride)
(immediate, 23 minutes)
Intravenous Dose
Adverse Effects
Vasodilators
0.250.5 mcg/kg/minute,
maximum 3 mcg/kg/minute
Nitroglycerin
510 mcg/minute,
(25 minutes, 510 minutes) maximum 100 mcg/minute
Hydralazine
(Apresoline)
10 minutes, 14 hours)
Enalaprilat
(Vasotec)
(within 30 minutes, 1224
hours)
Fenoldopam
(Corlopam)
(< 5 minutes, 30 minutes)
Nicardipine
(Cardene)
(15 minutes, 1530
minutes Up to 4 hours if
prolonged infusion)
Clevidipine
(Cleviprex)
(24 minutes, 515 minutes)
0.1 mcg/kg/minute,
maximum 1.6 mcg/kg/minute
515 mg/hour,
maximum 15 mg/hour
12 mg/hour
maximum 16 mg/hour
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Oral Dose
Onset (minutes)
Adverse Effects
Captopril
(Capoten)
Clonidine
(Catapres)
6.550 mg
1530
Nifedipine
1020 mg
(not
sublingual)
Labetalol
200400 mg repeated
(Normodyne, every 23 hours
Trandate)
1520
1530
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Cardiology I
Patient Cases
11. 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-segment 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), CK 227 units/L, and
CK-MB 22 units/L. Which medication is best to manage this patients hypertensive emergency?
A.
B.
C.
D.
12. A 56-year-old white woman, with a long history of HTN because of nonadherence and recently diagnosed
HF (EF 35%), presents to the local emergency department with a BP 210/120 mm Hg and HR 105 beats/
minute. She states that she felt a little light-headed, but that now, she is feeling okay. She ran out of her BP
medications (including HCTZ, carvedilol, and lisinopril) 3 days ago. Current laboratory values are within
normal limits. Which medication is best to manage this patient?
A.
B.
C.
D.
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Cardiology I
mPAP = mean pulmonary arterial pressure; PA = pulmonary artery; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary
wedge pressure; PVR = pulmonary vascular resistance; RHC = right heart catheterization; RV = right ventricle/ventricular.
Table 28. World Health Organization Classification of Functional Status for PAH
Class
Definition
I
No symptoms (dyspnea, fatigue, syncope, chest pain) with normal daily activities
II
Symptoms with strenuous normal daily activities that slightly limit functional status and activity level
III
Symptoms of dyspnea, fatigue, syncope, and chest pain with normal daily activities that severely limit
functional status and activity level
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.
B. Treatment of PAH
1. Reassessment should include functional class determination and 6-minute walk test every 36 months,
with right heart catheterization less often.
2. Satisfactory condition Functional class III, 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 a mPAP less than 12 mm Hg
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Cardiology I
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.
b
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 = intravenous(ly); MW = minute walk; PDEI = phosphodiesterase
inhibitor; RAP = right atrial pressure; RV = right ventricular; SC = subcutaneous; WHO = World Health Organization.
Epoprostenol
(Flolan, Veletri)
Prostanoid
Class IIIIV PAH
240 ng/kg/
minute IV
Adverse Effects
Hypotension, headache,
dizziness, peripheral
edema, cardiac
conduction delay
(diltiazem)
Considerations
Should not be used empirically without positive
response to acute vasodilatory response testing.
Diltiazem, amlodipine, nifedipine most commonly
used
Select agent on the basis of HR at baseline
If tachycardic, choose diltiazem
If bradycardic, choose amlodipine, nifedipine
Continuous IV infusion by pump
Flolan: Unstable at acidic pH and room
temperature (refrigerate or use ice packs before
and during infusion)
Veletri: Stable at room temperature
Drug requires reconstitution in sterile environment
Medical emergency if infusion interrupted
(half-life 6 minutes) Spare drug cassette and
infusion pump should be kept available
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Inhaled iloprost
(Ventavis)
Prostanoid
Class IIIIV PAH
Bosentan
(Tracleer)
Nonselective
endothelin
receptor
antagonist
(ETA and ETB)
Class IIIIV PAH
Ambrisentan
(Letairis)
Selective
endothelin
receptor
antagonist
(ETA only)
Class IIIII PAH
Sildenafil
(Revatio)
Phosphodiesterase
inhibitor
Class IIIV PAH
Considerations
Longer half-life (t1/2 3 hours) Longer to seek
medical attention
Premixed, prefilled syringe easier to administer
Local treatments (hot/cold packs or topical
analgesics) can be used to minimize infusion site
discomfort
Moving infusion site every 3 days minimizes
irritation
Requires 69 inhalations daily (15 minutes each
with jet nebulizer)
Prodose AAD nebulization system required
Inhaled form has fewer systemic adverse reactions
Use no more than every 2 hours
20 mg po
three times/
day
Headache, epistaxis,
facial flushing, bluish
or blurry vision, light
sensitivity, dyspepsia,
insomnia
Half-life 45 hours
May augment effects of other vasodilators when
used in combination (especially prostacyclin)
Contraindicated in patients receiving nitrates
Avoid combined use with strong CYP3A4
inhibitors (e.g., ritonavir, cimetidine,
erythromycin) and inducers (rifampin)
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Considerations
Half-life 17.5 hours
May augment effects of other vasodilators when
used in combination (especially prostacyclin)
Contraindicated in patients receiving nitrates
If CrCl 3180 mL/minute, initiate 20 mg po 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; Hct = hematocrit; Hgb= hemoglobin; HR = heart rate; IV = intravenous; LFT = liver function test; PAH = pulmonary
arterial hypertension; po = orally; SC = subcutaneous.
Patient Cases
13. A 38-year-old obese woman presents with increasing symptoms of fatigue and shortness of breath. She
could walk only 1020 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 partial thromboplastin time 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
two times/day, and diltiazem 480 mg/day. Her diagnosis is IPAH. Which regimen is the best evidence-based
management strategy?
A.
B.
C.
D.
14. A 48-year-old man with IPAH is admitted to the medical ICU for severe respiratory distress. Medications
before admission included bosentan and sildenafil. His vital signs include BP 97/45 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. Echocardiography reveals EF 60%
with significant right ventricular dilation. Which regimen is most appropriate?
A.
B.
C.
D.
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REFERENCES
Acute Coronary Syndromes
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patients with ADHF; increasing the -blocker dose before reaching euvolemia may acutely worsen his clinical picture. In patients admitted with volume overload
without substantial signs of reduced CO, it is reasonable
to try intravenous loop diuretics initially. As gut edema
increases, oral loop diuretics (notably furosemide) become less effective because of decreased absorption.
Nesiritide is a vasodilatory drug that can be initiated if
intravenous loop diuretic therapy fails, but because of
its adverse effects and substantial cost, it is not recommended before a trial of intravenous diuretics and other
potential therapies. Milrinone is an inotropic drug. Because of their adverse effects, inotropes are recommended in cold and wet exacerbations only after vasodilatory
medications have failed.
6. Answer: A
Intravenous vasodilators such as nitroglycerin and sodium nitroprusside are reasonable options if intravenous
diuretics fail and the patient progresses to acute pulmonary edema. Both agents rapidly cause venous vasodilation and reduce pulmonary filling pressures, which can
relieve acute shortness of breath. Nitroglycerin is the
optimal choice for this patient given the declining renal
function and concern about increased risk of thiocyanate
toxicity in this setting. Dobutamine is typically used in
states of low CO decompensation and is counteracted by
concomitant -blocker therapy, making it a poor choice
in patients receiving -blockers. Although milrinone is
a more acceptable inotropic agent in a patient receiving -blockers, the dosing strategy is inappropriate as an
initial dose. Finally, inotropes are generally reserved for
patients when other therapies have failed.
7. Answer: A
Signs of a decreased CO state in HF (e.g., increased
SCr, decreased mental status, cool extremities) suggest
a cold and wet state, and adjunctive therapy is indicated.
Positive inotropic agents such as milrinone will increase
CO to maintain perfusion to vital organs. Milrinone will
also vasodilate the peripheral vessels to unload the heart
(lower SVR). Again, although dobutamine would be a
potential choice in this patient, it is not recommended in
patients receiving -blockers. Although this patient has
low BP, his elevated SVR suggests that he will tolerate
the vasodilatory effects of milrinone. Although nesiritide would provide venous and arterial vasodilation, it is
relatively contraindicated in patients with a systolic BP
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11. Answer: A
Hypertensive emergency should be treated immediately by a 25% reduction in MAP, followed by a slow
reduction to goal for 57 days. The patients comorbidities guide the optimal therapy. His dialysis and SCr of
11.4 mg/dL are a contraindication to sodium nitroprusside caused by possible thiocyanate toxicity. Labetalol
(-blockers in general) is controversial in patients who
have taken cocaine, but its nonselective nature makes it
an option; however, a reduction of 50% initially is too
rapid a decrease in BP for safety. Clonidine is not an appropriate drug for hypertensive emergency because its
unpredictable oral nature is difficult to titrate and can
lead to precipitous drops in BP beyond the goal 25% reduction and possibly stroke or worsening MI. Nitroglycerin is an optimal choice, considering the patients lack
of contraindications to this therapy and his evolving MI.
14. Answer: A
Epoprostenol is now warranted to manage this patients
underlying disease because he has not responded to two
oral PAH therapies and is now considered high risk because of the presence of right ventricular dysfunction
and low CI. The patient has normal filling pressures for
a patient with right ventricular dysfunction, and diuresis 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 pressures should correct the low CI; thus, dobutamine is not
indicated at this time, and it would likely only worsen
his tachycardia.
12. Answer: C
In the setting of asymptomatic hypertensive crisis (without acute target-organ damage), intravenous medications, as in Answer A and Answer B, plus admission to
the hospital are unnecessary. This patient is likely presenting because of a history of nonadherence. Resuming
her home medications (Answer C) at this time would be
most appropriate, with close follow-up to ensure that her
prescribed regimen is working. Adding a fourth agent
(Answer D) at this time is unnecessary, considering that
she could be controlled on her current drug regimen if
she were adherent. Follow-up should occur within the
first few days, rather than wait 7 days.
13. Answer: C
This patient is already receiving therapy with calcium
channel blockers to control her HR caused by AF. She
is taking a considerable dose of diltiazem, and her HR
is unlikely to tolerate further increases in therapy. Sildenafil is indicated for functional class I patients to improve symptoms or for patients whose other therapies
have failed. Although bosentan is an attractive oral option to manage her PAH, her liver enzymes are elevated
more than 3 times the upper limit of normal. In this setting, administering bosentan is not recommended. If
liver transaminases are elevated transiently because of
hepatic congestion, bosentan may be reconsidered later.
Because this patient is currently in functional class IV
with symptoms at rest, epoprostenol is indicated for a
survival benefit.
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2. Answer: B
Given that this patient experienced a significantly low
platelet count with his last recent heparin exposure and
suspected HIT, the use of any GPI would be unwise for
ACS treatment because these agents need to be combined with UFH. Thrombolytic therapy is not recommended for the treatment of UA/NSTEMI and would
not be appropriate in this patient. Bivalirudin, a direct
thrombin inhibitor, would be the treatment of choice in
patients with HIT undergoing PCI.
3. Answer: C
This patient is well perfused and can be classified as
Forrester hemodynamic subset II (warm and wet). Because the patient is congested (shortness of breath, dyspnea at rest), intravenous diuretics are first-line therapy.
Nitroglycerin is the best choice in this setting because
vasodilatory agents can be used in conjunction with intravenous diuretics to improve acute pulmonary edema
or severe HTN. When adjunctive therapy is required
in addition to loop diuretics, intravenous vasodilators
should be considered over inotropic agents. Dobutamine and milrinone primarily increase CO, which is
not a considerable problem in warm and wet exacerbations. In addition, the adverse effects of these agents (increased mortality, proarrhythmia) limit their use. Intravenous metoprolol should be used extremely cautiously
because of its negative inotropic effects and because this
patient is not in a euvolemic state.
4. Answer: D
This patient has a depressed LVEF less than 40%, so her
drug therapy options are limited. Procainamide is indicated only in secondary prevention of sustained VT in
patients with a normal LVEF greater than 40%; if given
to this patient, it could worsen her HF. Metoprolol is
indicated only for treating patients with asymptomatic
nonsustained VT and SVT associated with CAD. This
patient had an episode of sustained VT. Her QTc interval is not prolonged at 380 milliseconds, and her serum
magnesium level is within normal limits, so she does
not require intravenous Mg therapy. Amiodarone is firstline treatment of patients without contraindications because of its efficacy and safety in patients with an LVEF
less than 40%.
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5. Answer: B
This patient shows target-organ damage from poorly
controlled HTN in the form of a cerebrovascular accident. Although fenoldopam is indicated for treating
hypertensive emergency, its use is cautioned in patients
with stroke symptoms because its dopamine agonist
activity can cause cerebral vasodilation and potentially
reduced blood flow to the ischemic areas of the brain.
Nicardipine is an appropriate choice for this patient because its calcium channel blocking effects will reduce
BP and potentially decrease vasospasm in the cerebral
arteries, which may lead to further ischemia or seizure
activity. Although labetalol is an effective option for
treating this patients hypertensive emergency, she has a
history of asthma and a low HR, making labetalol a lessthan-ideal option for treating her symptoms. The antihypertensive effects of enalaprilat depend on a patients
renin activity, which is unknown in this case. Therefore,
the BP-reducing effects may be more difficult to control than with a drug having a more consistent effect in
individuals. In addition, the bolus nature of the drug is
not ideal for tightly controlling BP with a 25% reduction in MAP. Continuous-infusion drugs are preferable
for easier titration to effect in a hypertensive emergency.
6. Answer: C
This patient is experiencing hypertensive urgency, considering that he has no evidence of target-organ damage.
Thus, his BP may be reduced over 24 hours using oral
medications. Given this patients concomitant comorbidities, HF, and microalbuminuria, an ACE inhibitor
would be indicated. Sublingual nifedipine is no longer
recommended for management of hypertensive urgency
because of acute BP lowering and association with lifethreatening adverse events such as MI and stroke. Clonidine and labetalol are acceptable options; however, the
patient has compelling indications for an ACE inhibitor.
Although the patient should receive a -blocker in addition to an ACE inhibitor for HF management, labetalol is not one of the three -blockers recommended for
chronic HF management.
7. Answer: C
The Cardiac Arrest Study Hamburg trial compared ICD
with antiarrhythmic therapy in survivors of cardiac arrest for secondary prevention of SCD. The propafenone
study arm was discontinued early because of a significantly (61%) higher mortality rate compared with ICDs.
Although this trial had a small sample size that prevented a statistically significant difference in total mortality from being shown in ICD-treated patients versus
patients treated with either amiodarone or metoprolol,
the incidence of sudden death was significantly reduced
in patients with an ICD (33% vs. 13%, p=0.005). The
AVID (Antiarrhythmics Versus Implantable Defibrillators) trial also evaluated ICD implantation versus antiarrhythmic drug therapy (primarily amiodarone) in
survivors of SCD. Patients with ICDs had a significantly higher rate of survival than those treated with drug
therapy (89% vs. 82%, p<0.02).
8. Answer: C
The number needed to treat can be calculated by 1/absolute risk reduction. Because the absolute risk reduction in
mortality at 60 months was 7.2% with ICD versus placebo, 1/0.072 would be used to calculate the number of
patients needed to treat to prevent one death during this
time. About 14 patients would need to be treated with
ICD to prevent one death in 60 months versus placebo.
Other calculations in this fashion, including relative risk
reduction and 100% minus the absolute or relative risk
reduction, do not provide useful information for interpreting the trial results and yield an incorrect number of
patients.
9. Answer: D
International Pharmaceutical Abstracts is a database of
primarily pharmaceutical abstracts in more than 750
journals, including foreign and state pharmacy journals,
in addition to key U.S. medical and pharmacy journals.
Many of the citations are not included on MEDLINE,
so a broader search can be performed; however, subject descriptors are not consistently defined in a uniform
way, and multiword terms are often cited backward. The
Iowa Drug Information Service database offers fulltext articles from 1966 to present in about 200 medical
and pharmacy journals (primarily based in the United
States). It is updated monthly, so it may take longer to
access newly available articles from this service. The
Clin-Alert database contains more than 100 medical and
pharmacy journals focused on adverse events, drug interactions, and medical-legal issues. It is used primarily
to look up adverse events (especially recent reports) associated with medications. Excerpta Medica is a comprehensive database of more than 7000 journals from
74 countries dating from 1974 to present. Recently pub-
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