Internal Medicine

Lecture 7. CONGESTIVE HEART

FAILURE
V. Babadzhan, D.M.
Professor of Medicine,
Kharkov State Medical University
Department of Internal Medicine 2,
Clinical Immunology and Allergology
DEFINITION
“The situation when the heart is
incapable of maintaining a cardiac
output adequate to accommodate
metabolic requirements and the
venous return."
E. Braunwald
I ncidence and prevalence

Heart failure is an epidemic affecting

1-2 million Ukraineans and nearly 15
million people worldwide.
Heart failure carries worse prognosis,
as 50% of patients with heart failure
will die within 5 year, and in patient
with sever heart failure more than
50% will die within 2 year.
 DETERMINANTS OF
VENTRICULAR FUNCTION
CONTRACTILITY

PRELOAD AFTERLOAD

STROKE
VOLUME

- Synergistic LV contraction HEART

- LV wall integrity RATE
- Valvular competence

CARDIAC OUTPUT
Pathophysiology of heart failure

PUMP
DYSFUNCTION MYOCARDIAL
HORMONAL REMODELING

CIRCULATORY NEUROREGULATORY
CYTOKINE
INSUFFICIENCY

HEART FAILURE
 DIAGNOSIS

 HISTORY.
 PHYSICAL EXAMINATION.
 APPROPRIAT INVESTIGATION.
1. SYMPTOMS OF HEART FAILURE (AT REST OR DURING
EXERCISE).
2.Objective evidence of cardiac dysfunction.
3.Response to treatment directed towards heart failure.
CRITERIA FOR CONGESTIVE HEART
FAILURE

 MAJOR CRITERIA  MINOR CRITERIA

1.Paroxysmal nocturnal dyspnea 1.Ankle edema.
or orthopnea. 2.Night cough.
2.Rales. 3.Dyspnea on exertion.
3.Cardiomegaly. 4.Pleural effusion.
4.Acute pulmonary edema. 5.Vital capacity decreased 1/3
5.S3 Gallop. from maximum.
6.Increased venous pressure>16 6.Tachycardia (rate>120/min).
cm of water.
7.Circulation time>25 sec.
 MAJOR OR MINOR
Weight loss>4.5 Kg in 5 days in
8.Hepatojugular reflux.
response to treatment.
 Sym ptom atic classification of
ex ercise tolerance
New York Heart Association (NYHA)
NYHA Class I: No complaints under
heavy physical load.
NYHA Class II: Complaints under
heavy physical load.
NYHA Class III: Complaints under light
physical load.
NYHA Class IV : Complaints at rest.
 Descriptive terms
in heart failure
Acute vs Chronic heart failure.

Systolic vs Diastolic.

Right vs Left heart failure.

Types of Heart Failure
include left, right or both sides
left ventricular heart failure
most common
systolic failure: unable to contract
diastolic failure: unable to relax
right ventricular heart failure
usually occurs after left failure
less blood received causes right damage
less pumping by right side
venous pooling of blood in legs
 Causes of Chronic
Heart Failure
Systolic dysfunction:
Coronary artery disease.
Hypertension.
Dilated Cardiomyopathy.
Myocarditis.
 Causes of Chronic
Heart Failure cont.
Diastolic Dysfunction:
Coronary artery disease.
Systemic Hypertension.
Diabetis Mellitus.
Aortic stenosis.
Hypertrophic cardiomypathy.
Infiltrative cardiomypathy
Endocardial fibrosis.
Normal aging process.
Causes of worsening Heart Failure cont.
Cardiac:

 Atrial fibrillation.
 Other supraventricular or ventricular
arrhythmias.
 Bradycardia.
 Appearance or worsening mitral or ticusped
regurgitation.
 Myocardial ischaemia.
 Excessive preload reduction(diuretics,ACE
inhibitors).
Causes of w orsening Heart Failure
Non- cardiac:
 Non compliance to the prescribed
regimen(salt,liquid,medication).
 Recently co-prescribed drugs
(antiarrhythmic,beta-blockers,non steroidal
anti-inflmatory drugs,verapamil,diltiazem).
 Renal dysfunction.
 Infection.
 Pulmonary embolism.
 Thyroid dysfunction.
 Anemia.
 Alcohol abuse.
The Heart Failure Milieu
Clinical Presentation
Disease
Proccess
Ventricular
Dysfunction
Haemdynamic
Abnormalities Symptomes
And
Compansatory Metabolic
Physical
Mechanism Changes finding
M etabolic Changes

 Azotemia.
 Hyponatraemia.
 Hypokalemia.
 Hypomagnesemia.
 Hyperuricemia.
 Acidosis/Alkalosis.
 Hypoxia/O2 desaturation.
 Decreased MVO2.
Sym ptom es

 Fatigue ,weakness and decreased

exercice tolerance.
 Dyspnea and fluied retention
symptomes.
 Nocturia.

 Gastrointestinal symptomes.

 Diminished mentation.
P hysical Findings
 Peripheral edema.
 Ascites.
 Jugular venous distension.
 Rales.
 Tachycardia.
 Hypotention.
 Cachexia.
 Disease specific findings.
Compensatory Mechanisms
System ic organ failure

Renal failure.
Hepatic failure.
Respiratory failure.
Multi-organ failure.
Pulmonary embolism.
Peripheral& cerebral embolism.
Evaluation of heart failure patient

Physical Laboratory
Examination tests
History

Diagnostic
studies
 Investigation
Laboratory
 Complete Blood Count.
 Serum electrolytes, blood urea nitrogen,serum
creatinine.
 Liver function test.
 Prothrombin time.
 Lipid profile.
 Thyroid function test.
 Anaemia evaluation.
 Arterial blood gases.
 Serum drug levels(digoxin,phenytoin).
 Atrial natriuretic peptides.
 Urin analysis.
 Chest X- ray

Chest roentgenogram of patient with heart failure. This

roentgenogram demonstrates cardiomegaly (cardiothoracic
ratio 0.77), pulmonary congestion, and bilateral pleural
effusions (note blunted costophrenic angles).
12-Leads ECG
 Other investigation

 Transthoracic Echocardiography.
 Stress Echo.
 Exercise stress testing.
 24- hour Holter monitoring.
 Nuclear imaging,thallium perfusion
scan,cardiac MRI.
 Coronary angiography
 Chronic Congestive Heart Failure
EVOLUTION OF
CLINICAL STAGES
NORMAL
No symptoms
Normal exercise
Asymptomatic
Normal LV fxn LV Dysfunction
No symptoms
Normal exercise
Compensated
Abnormal LV fxn CHF
No symptoms Decompensated
Exercise
Abnormal LV fxn CHF
Symptoms
Exercise
Refractory
Abnormal LV fxn CHF
Symptoms not controlled
with treatment
 Treatment Options
 Non-pharmacological.
General advice and measures. Exercise and exercice
training.Reduce cardiac work. Rest. Weight loss. Low Na diet.
Pharmacological therapy.
Angiotensin-converting enzyme inhibitors(ACI).
Beta-adrenoreceptor antagonists.
Cardiac glycosides.
Diuretics.
Vasodilators(nitrats,hydralazine).
Antiarrhythmic agent.
Anticoagulantion.
Oxyggen.
 Divices and surgery.
Revascularization.
Pacemaker.
Implantable cardioverter defibrillator(ICD).
Cadiac trnsplantation.
Ultrafiltration,haemodialysis.
 TREATMENT
Correction of aggravating factors

Pregnancy Endocarditis
Arrhythmias (AF) Obesity
Infections Hypertension
Hyperthyroidism Physical activity
Thromboembolism Dietary excess
MEDICATIONS
 TREATMENT
PHARMACOLOGIC THERAPY

DIURETICS
INOTROPES
VASODILATORS
NEUROHORMONAL ANTAGONISTS
OTHERS (Anticoagulants,
antiarrhythmics, etc)
Normal
TREATMENT
Asymptomatic
LV dysfunction
EF <40%
Symptomatic CHF
ACEI NYHA II Symptomatic CHF
Diuretics mild NYHA - III
Neurohormonal Symptomatic CHF
inhibitors Loop
Diuretics NYHA - IV
Digoxin?
Inotropes
Specialized therapy
Transplant
Secondary prevention
Modification of physical activity
 DIURETICS
Thiazides
Inhibit active exchange of Cl-Na
Cortex in the cortical diluting segment of the
ascending loop of Henle

K-sparing
Inhibit reabsorption of Na in the
distal convoluted and collecting tubule

Loop diuretics
Medulla Inhibit exchange of Cl-Na-K in
the thick segment of the ascending
loop of Henle

Loop of Henle
Collecting tubule
 CLINICAL AND PHARMACOLOGIC PROPERTIES OF DIURETICS
Drugs Rela- Site of Onset Advantages Adverse Effects
tive Action of
poten- Action
cy
Thiazide diuretics
Hydrochlorothiazide Mode- Excreted into 1-2 h Mild, relati- K loss.
Oral: 50-200 mg/day rate proximal tu- vely nontoxic, hyperglycemia,
bule, inhibiti- oral admini- decreases platelets.
on of Na and stration, ineffective when GFR
Cl, absorption antihyperten- < 20 mL/min.
in distal sive hyperuricemia
segment
Loop diuretics
Furosemide 40-200 mg High Inhibition of Oral: 1 Rapid onset, Excessive diuresis;
1, 2. or 3 times/day; IV: Cl transport h IV: potency, hypovolemia; K loss
40 mg initially; may in ascending 10-20 independent and hypokalemia;
increase to 200-400 mg, limb of loop min of acid-base hyperuricemia;
depending on response of Henle balance, transient or
Torosimide 5-10 mg/d effective even irreversible deafness
Ethacrynic acid IV: 50 when GFR is with IV
mg initially; may reduced administration,
increase, depending on especially when used
response with aminoglycoside
antibiotic
 DIURETICS
ADVERSE REACTIONS
Thiazide and Loop Diuretics

Changes in electrolytes:
Volume
Na+, K+, Ca++, Mg++
metabolic alkalosis
Metabolic changes:
glycemia, uremia, gout
LDL-C and TG
Cutaneous allergic reactions
 POSITIVE INOTROPES

CARDIAC GLYCOSIDES

SYMPATHOMIMETICS
Catecholamines
ß-adrenergic agonists

PHOSPHODIESTERASE INHIBITORS
Amrinone Milrinone
Enoximone Piroximone
Others
 DOPAMINE AND DOBUTAMINE
EFFECTS

DA (µg / Kg / min) Dobutamine

<2 2-5 >5
Receptors DA1 / DA2 ß1 ß1 + α ß1
Contractility ± ++ ++ ++
Heart Rate ± + ++ ±
Arterial Press. ± + ++ ++
Renal perfusion ++ + ± +
Arrhythmia - ± ++ ±
 POSITIVE INOTROPES
Agent Dose and Route Comment

ADRENERGIC AGONISTS
Epinephrine 300-500mug SC or IM (0.3-0.5 mL of Nonselective alpha and beta agonist;
1/1000 solution of hydrochloride increases BP, heart rate Bronchodilation
salt); 25-50 mug IV (slowly) every 5-
15 min; titrate as needed
Norepinephrine 2-4 mug of NE base/min IV; titrate Alpha and beta1 agonist
as needed Vasoconstriction predominates
Extravasation causes tissue necrosis;
infuse through IV cannula
Dobutamine 2.5-25 (mug/kg)/min IV Selective betai agonist with greater
effect on contractility than heart rate; a
congener of dopamine but not a
dopaminergic agonist
DOPAMINERGIC AG ONLSTS
Dopamine 2-5 (mug/kg)/min IV (dopaminergic Pharmacologic effects are dose
range) 5-10 (mug/kg)/min IV dependent: renal and mesenteric
(dopaminergic and beta range) vasodilation predominate at lower
10-20 (mug/kgVmin IV (beta range) doses; cardiac stimulation and
20-50 (mug/kg)/min IV (alpha range) vasoconstriction develop as the dose is
increased
 POSITIVE INOTROPES
CONCLUSIONS

May increase mortality

Safer in lower doses
Use only in refractory CHF
NOT for use as chronic therapy
 VASODILATORS
CLASSIFICATION
VENOUS Venous
Nitrates Vasodilatation
Molsidomine
MIXED
Calcium antagonists
α-adrenergic Blockers
ACEI
Angiotensin II inhibitors
K+ channel activators
Nitroprusside
Arterial ARTERIAL
Vasodilatation Minoxidil
Hydralazine
 NITRATES
HEMODYNAMIC EFFECTS
1- VENOUS VASODILATATION
Pulmonary congestion
Ventricular size
Preload Vent. Wall stress
MVO2

2- Coronary vasodilatation
Myocardial perfusion
3- Arterial vasodilatation • Cardiac output
Afterload • Blood pressure

4- Others
 CLINICAL AND PHARMACOLOGIC PROPERTIES OF VASODILATORS

Classi- Drugs Site of Onset of Action Advantages Adverse Effects

fication Action

Nitrates Nitrogtycerin Nitrate Immediate Rapid onset; Headache; hypotension;

Sublingual: 0.4 mg pm receptor Immediate various methemoglobinemia;
Spray: 0.4 mg pm Immediate 30-60 routes of tolerance if not given
min 30-60 min admnistra- intermittently
IV: 10-100 μg/min tion; good for
Isosorbide dinitrate emergencies
Sublingual:2.5-10mg q 2-4 h
Oral: 20-60 mg q 4-6 h
2-5 min
20-40 min

Arterial Hydralazine Smooth 30-45 min Specific Tachycardia; lupus

vasodi- Oral: 25-100 mg q 6 h muscle arteriolar phenomenon; long-term
lators vasodilator benefit requires nitrates
Minoxidil Hypotension; thiocyanate
accumulation
Oral: 25-40 mg twice daily
Tachycardia; aggravates
angine; marked fluid
retensiot; hair growth on
Diazoxid IV: 1-3 mg/kg up to face and body, coarsening
150 mg rapidly of facial features
Nitroprusside Hyperglycemia,
10-500 (μg/min) Dilates hyperuricemia, sodium
arteries and retension
Immediately veins Cianide toxicity
 NITRATES
SURVIVAL
0.7
Placebo (273)
0.6 Prazosin (183)
Hz + ISDN (186)
0.5
PROBABILITY
0.4
OF
0.3
DEATH
0.2
0.1
0
VHefT-1 0 6 12 18 24 30 36 42
N Engl J Med 1986;314:1547 MONTHS
 NITRATES
TOLERANCE

" Decrease in the effect of a drug

when administered in a long-acting form"
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Tolerance can be avoided
- Using the least effective dose
- Creating discontinuous plasma levels
 NITRATES
CONTRAINDICATIONS

Previous hypersensitivity
Hypotension ( < 80 mmHg)
AMI with low ventricular filling pressure
1st trimester of pregnancy

WITH CAUTION:
ž Constrictive pericarditis
ž Intracranial hypertension
ž Hypertrophic cardiomyopathy
 ACE-Inhibitors
MECHANISM OF ACTION
VASOCONSTRICTION VASODILATATION
ALDOSTERONE PROSTAGLANDINS
VASOPRESSIN Kininogen tPA
SYMPATHETIC Kallikrein
Angiotensinogen
RENIN
Angiotensin I
BRADYKININ

A.C.E. Inhibitor Kininase II

ANGIOTENSIN II Inactive Fragments

 ACEI
HEMODYNAMIC EFFECTS

Arteriovenous Vasodilatation
- PAD, PCWP and LVEDP
- SVR and BP
- CO and exercise tolerance
No change in HR / contractility
MVO2
Renal, coronary and cerebral flow
Diuresis and natriuresis
 ACEI
FUNCTIONAL CAPACITY
100

No 95 Quinapril
Additional continued
n=114
Treatment 90
p<0.001
Necessary
85
(%)
Quinapril
80 stopped
Placebo
Class II-III
n=110
75
2 4 6 8 10 12 14 16 18 20
Quinapril Heart Failure Trial
JACC 1993;22:1557 Weeks
 ACEI
INDICATIONS

Clinical cardiac insufficiency

- All patients

Asymptomatic ventricular
dysfunction
- LVEF < 35 %
 ACEI
UNDESIRABLE EFFECTS
Inherent in their mechanism of action
- Hypotension - Dry cough
- Hyperkalemia - Renal Insuff.
- Angioneurotic edema
Due to their chemical structure
- Cutaneous eruptions
- Neutropenia, - Dysgeusia
thrombocytopenia - Proteinuria
- Digestive upset
 ACEI
CONTRAINDICATIONS

Renal artery stenosis

Renal insufficiency
Hyperkalemia
Arterial hypotension
Intolerance (due to side effects)
 ANGIOTENSIN II INHIBITORS
MECHANISM OF ACTION
RENIN

Angiotensinogen Angiotensin I
ACE
Other paths ANGIOTENSIN II
AT1
RECEPTOR
BLOCKERS
AT1 RECEPTORS AT2

Vasoconstriction Proliferative Vasodilatation Antiproliferative

Action Action
AT1 RECEPTOR BLOCKERS
DRUGS

Losartan
Valsartan
Irbersartan
Candersartan
Competitive and selective
blocking of AT1 receptors
 ALDOSTERONE INHIBITORS

Spironolactone ALDOSTERONE
Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)

Retention Na+ Collagen

Edema deposition
Retention H2O

Fibrosis
Excretion K+ Arrhythmias - myocardium
Excretion Mg2+ - vessels
CLINICAL AND PHARMACOLOGIC PROPERTIES OF VASODILATORS
Classifi- Drugs Site of Onset Advantag Adverse Effects
cation Action of es
Action
Inhibitors of Captopril 6.25 mg Angiotensin 60-90 Proven Impaired renal
Angiotensin bid. up to 200 mg/d converting min symptomat function; proteinuria;
converting Enalapril 2.5-40 enzyme 60 min ic relief dysgeusia;
enzyme mg/d (ACE) 60 min and glomerulonephritis;
(ACE) Lisinopril 5-40 mg/d [inhibition improved leukopenia; cough
of] 60-90 survival
Quinapril 10-80 mg/d min Contraindications:
pregnancy,
Ramipril 2.5-20 mg/d 60-90
min bilateral renal artery
Quinapril 10-30 mg stenosis
bid;
Fosinopril 5-30 mg
qd;
Angiotensin Losartan 25-50 mg 2-4 h Proven Hypotension, ocute
e receptor once or twice daily symptomat renal failure in
antagonists Irbesartan 5-10 mg 60-90 ic relief bilateral renal artery
once or twice daily min and stenosis,
improved hyperkalemia
survival Contraindications:
pregnancy,
bilateral renal artery
stenosis
 ALDOSTERONE INHIBITORS
INDICATIONS

FOR DIURETIC EFFECT

• Pulmonary congestion (dyspnea)
• Systemic congestion (edema)
FOR ELECTROLYTE EFFECTS
• Hypo K+, Hypo Mg+
• Arrhythmias
• Better than K+ supplements
FOR NEUROHORMONAL EFFECTS
• ? Pending the RALES results
CLINICAL AND PHARMACOLOGIC PROPERTIES OF DIURETICS
Drugs Relative Site of Action Onset of Advantages Adverse Effects
Potency Action

Potassium-sparing diuretics
Spironolactone Moderate Aldosterone 2-3 days Useful in Hyperkalemia
Oral: 25-50 mg to low homolog, for combination when K salts are
bid to qid competitive maximum with more given
inhibition for effect proximal- concomitantly or
receptor site in acting diuretic renal function is
distal tubule. to spare K reduced markedly
Secondary:
inhibition of
aldosterone
biosynthesis
ALDOSTERONE INHIBITORS
CONTRAINDICATIONS

• Hyperkalemia

• Severe renal insufficiency

• Metabolic acidosis
 ß-ADRENERGIC BLOCKERS
POSSIBLE BENEFICIAL EFFECTS

Density of ß1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonal activation
HR
Antihypertensive and antianginal
Antiarrhythmic
Antioxidant
Antiproliferative
 BETA-ADRENERGIC RECEPTOR BLOCKERS
Drugs Site of Action Precautions and Side effects
special
considerations
Carvedilol 3.125 mg bid; Noncardioselectiv Should not be used in Bronchospasm,
titrate to target dose 25 mg bid. e β- and α1- patients with asthma, peripheral arterial
adrenergic chronic obstructive insufficiency,
receptor block, pulmonary disease fatigue, insomnia,
without ISA (COPD) with sexual dysfunction,
Bisoprolol 1.25 mg bid; Noncardioselectiv bronchospasm, exacerbation of
titrate to target dose 10 mg bid. e, without ISA congestive congestive heart
heart.failufe, heart failure, may mask
block (greater than symptoms of
Metoprolol tartrate 6.25 mg bid; Cardioselective, first degree), sick hypoglycemia;
titrate to target dose 50 mg bid. without ISA sinus syndrome. Use hyperglycemia;
with caution in insulin- hypertriglyceridemi
Metoprolol succinate (extended Cardioselective, dependent diabetics a, decreased high-
release) 12.5- 25 mg bid; without ISA and patients with density lipoprotein
titrate to target dose 200 mg bid. peripheral vascular (HDL) cholesterol
disease. Should not be (except for drugs
discontinued abruptly with ISA and
in patients with labetalol)
ischemic heart
disease. ISA = intrinsic sympathomimetic activity.
 ß-ADRENERGIC BLOCKERS
IDEAL CANDIDATE?

Suspected adrenergic activation

Arrhythmias

Hypertension

Angina
ß-ADRENERGIC BLOCKERS
CONTRAINDICATIONS

Hypotension: BP < 100 mmHg

Bradycardia: HR < 50 bpm
Clinical instability
Chronic bronchitis, ASTHMA
Severe chronic renal insufficiency
CALCIUM ANTAGONISTS
POTENTIAL EFFECTS

Antiischemic
Peripheral Vasodilatation
Inotropy
 CALCIUM ANTAGONISTS
POSSIBLE UTILITY

Diltiazem contraindicated
Verapamil and Nifedipine
not recommended

Vasoselective (amlodipine, nisoldipine),

may be useful in ischemia + CHF

Amlodipine may be useful in nonischemic CHF

 DIGOXIN

Na-K ATPase
Na-Ca Exchange
Na+ K+ Na+ Ca++

Myofilaments Ca++
K+ Na+

CONTRACTILITY
 DIGOXIN
PHARMACOKINETIC PROPERTIES
Oral absorption (%) 60 - 75
Protein binding (%) 25
Volume of distribution (l/Kg) 6 (3-9)
Half life 36 (26-46) h
Elimination Renal
Onset (min)
i.v. 5 - 30
oral 30 - 90
Maximal effect (h)
i.v. 2-4
oral 3-6
Duration 2 - 6 days
Therapeutic level (ng/ml) 0.5 - 2
 DIGOXIN
DIGITALIZATION STRATEGIES

Maintenance
Loading dose (mg) Dose

i.v oral 12-24 h oral 2-5 d (mg)

0.5 + 0.25 / 4 h 0.75 + 0.25 / 6 h 0.25 / 6-12 h 0.125-0.5 / d

ILD: 0.75-1 1.25-1.5 1.5-1.75 0.25 / d

ILD = average INITIAL dose required for

digoxin loading
 DIGITALIZATION SCHEDULE+
Digoxin Digitoxin Ouabain
Oral. 24 h 0 h: 0.5 mg 0 h: 0.6 mg
8 h: 0.25 mg 8 h: 0.3 mg
16 h: 0.25 mg 16 h: 0.2 mg
24 h: 0.25 mg 24 h: 0.1 mg
Thereafter, daily Thereafter, daily
maintenance dose++ maintenance dose
Oral. 48 h 0.25 mg q 8 h x 6 0.2 mg q 8 h x 6
Thereafter, daily Thereafter, daily
maintenance dose++ maintenance dose
Oral, gradual 0.25 mg/day 0.1 mg/day
(digitalization achieved (digitalization achieved
in in
5-7 days)++ 10-14 days)
IV. 24 h 0 h: 0.5 mg 0 h: 0.6 mg 0 h: 0.3 mg
6 h: 0.25 mg 8 h: 0.3 mg 4 h: 0.2 mg
12 h: 0.125 mg 16 h: 0.2 mg 8 h: 0.1 mg
18 h: 0.125 mg 24 h: 0.1 mg 12 h: 0.1 mg++
Thereafter, daily Thereafter, daily
maintenance dose++ maintenance dose
Daily maintenance 0.25-0.375 mg/day 0.1 mg 5 times/wk to 1.5
dose, oral mg/day
+ Doses are designed to produce effective but prudent plasma and tissue concentrations (see text for details).
++ Abnormal renal function prolongs plasma half-life, necessitating reduction in suggested dosage.DigoxinDigitoxinOuabainPreferred
route*Oral. IV
 DIGOXIN
HEMODYNAMIC EFFECTS

Cardiac output
LV ejection fraction
LVEDP
Exercise tolerance
Natriuresis
Neurohormonal activation
 OVERALL MORTALITY
50

40

30
% Placebo
20 n=3403 p = 0.8

10 DIGOXIN
n=3397
0
DIG 0 12 24 36 48
N Engl J Med 1997;336:525 Months
 DIGOXIN
LONG TERM EFFECTS

Survival similar to placebo

Fewer hospital admissions
More serious arrhythmias
More myocardial infarctions
 DIGOXIN
CLINICAL USES

AF with rapid ventricular response

CHF refractory to other drugs
Other indications?
Can be combined with other drugs
 DIGOXIN
CONTRAINDICATIONS

ABSOLUTE:
- Digoxin toxicity

RELATIVE
- Advanced A-V block without pacemaker
- Bradycardia or sick sinus without PM
- PVC’s and TV
- Marked hypokalemia
- W-P-W with atrial fibrillation
 DIGOXIN TOXICITY
CARDIAC MANIFESTATIONS

ARRHYTHMIAS :
- Ventricular (PVCs, TV, VF)
- Supraventricular (PACs, SVT)

BLOCKS:
- S-A and A-V blocks

CHF EXACERBATION
 TREATMENT OF DIGITALIS INTOXICATION
 Discontinue the drug
 ECG monitoring
 If serum K is low, 80 mEq of potassium chloride IV should be given
in 1 L 5% D/W at a rate of 6 mL/min (0.5 mEq/min). Potassium
must not be employed in the presence of atrioventricular block or
hyperkalemia
 Administration of specific antibody fragments to digoxin (digoxin
immune fab, Digibind®)
 Ventricular arrhythmias are treated with a 50- to 100-mg rapid IV
injection of lidocaine, repeated in 3 to 5 min until a therapeutic
effect is obtained, a total of 300 mg is given, or CNS toxicity occurs.
When the arrhythmia is controlled, a continuous infusion of 2 to 4
mg/min should be started
 Alternatively, phenytoin 100 mg q 3 to 5 min can be given slowly up
to a total of 1000 mg
 Heart block is best treated with a temporary perivenous pacemaker
 Electrical conversion may be lifesaving in digitalis-induced
ventricular fibrillation
 Isoproterenol is contraindicated in digitalis intoxication because of
the increased tendency to ventricular arrhythmia
 Phosphodiesterase Inhibitors

primarily used for

management of acute heart
failure

positive inotropic effects

increase rate of
myocardial relaxation

decrease total peripheral

resistance and afterload
 Mechanism of Action
inhibitor of type III cAMP
phosphodiesterase
increased [cAMP]
increased PKA
phosphorylation of Ca2+
channels in cardiac muscle
increased cardiac contraction
relaxes vascular smooth
muscle
 Therapeutic Use

Amrinone (Inocor) and Milrinone (Primacor)

administered IV
milrinone is ~1o fold more potent
T 1/2 = 2.5 h for amrinone and 30-60 min for
milrinone
effective in patients taking Beta-blockers
does not stop disease progression or prolong life
in CHF patients
prescribed to patients non-responsive to other
therapies
 Side Effects
sudden death secondary to ventricular
arrhythmia
hypotension
thrombocytopenia
long term clinical trials associated with
increased adverse effects and increased
mortality
now only prescribed for acute cardiac
decompensation in patients non-
responsive to diuretics or digoxin
 ANTICOAGULANTS

PREVIOUS EMBOLIC EPISODE

ATRIAL FIBRILLATION
Identified thrombus
LV Aneurysm (3-6 mo post MI)
Class III-IV in the presence of:
- EF < 30
- Aneurysm or very dilated LV
Phlebitis
Prolonged bed rest
 ANTIARRHYTHMICS

Sustained VT, with/without symptoms

- ß Blockers
- Amiodarone
Sudden death from VF
- Consider
implantable
defibrillator
Risk factors for increased mortality in heart
failure include all of the following,except:

1. Anaemia (Hgb 8.0 g/dl).

2. Sleep apnea.
3. Chronic renal insufficiency.
4. Elevated BNP level.
5. Sustained VT.
Indications for anticoagulation with
warfarin in heart failure patients
include:

1. AF with controlled ventricular

response.
2. LV thrombus.
3. Protein C or protein S deficiency.
4. Previous cardioembolic stroke.
5. All of the above.
EMERGENCY THERAPEUTIC MEASURES IN
PATIENTS WITH PULMONARY EDEMA
 Morphine is administered intravenously repetitively, as
needed, in doses from 2 to 5 mg
 100% oxygen should be administered, preferably under
positive pressure
 The patient should be maintained in the sitting position, with
the legs dangling along the side of the bed
 Intravenous loop diuretics, such as furosemide or ethacrynic
acid (40 to 100 mg), or bumetanide (1 mg)
 Intravenous sodium nitroprusside at 20 to 30 ug/min in
patients whose systolic arterial pressures exceed 100 mmHg
 Inotropic support should be provided by dopamine or
dobutamine
 Patients with systolic heart failure who are not receiving
digitalis should receive 1.0 mg digoxin intravenously
 Aminophylline (theophylline ethylenediamine), 240 to 480 mg
intravenously
 Rotating tourniquets should be applied to the extremities
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