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CONGESTIVE HEART
FAILURE
MA. LENY ALDA G. JUSAYAN,
MD
HEART FAILURE
• Inability of the heart to pump an adequate
amount of blood to the body’s needs
• CONGESTIVE HEART FAILURE – refers
to the state in which abnormal circulatory
congestion exists a result of heart failure
CAUSES OF HEART FAILURE:
• Final common pathway of many kinds of
heart diseases
– Ischemic, alcoholic, restrictive, hypertrophic
– Optimal treatment requires identification of
primary & secondary factors leading to CHF
– HELPFUL RESULT of dilatation: increases cardiac
output
– HARMFUL RESULT of dilation: more wall tension,
more oxygen is needed to produce any given
stroke volume
CLASSIFICATION:
• SYSTOLIC DYSFUNCTION:
– Inadequate force is generated to eject
blood normally
– Reduce cardiac output, ejection fraction (<
45%)
– Typical of acute heart failure
– Secondary to AMI
– Responsive to inotropics
CLASSIFICATION:
• DIASTOLIC DYSFUNCTION
– Inadequate relaxation to permit normal
filling
– Hypertrophy and stiffening of myocardium
– Cardiac output may be reduced
– Ejection fraction is normal
– Do not respond optimally to inotropic
agents
CLASSIFICATION:
• HIGH OUTPUT FAILURE
– Increase demand of the body with
insufficient cardiac output
– Hyperthyroidism, beri-beri, anemia, AV
shunts
– Treatment is correction of underlying
cause
CLASSIFICATION:
• ACUTE HEART FAILURE
– Sudden development of a large myocardial
infarction or rupture of a cardiac valve in a
patient who previously was entirely well,
usually predominant systolic dysfunction
CLASSIFICATION:
• CHRONIC HEART FAILURE
– Typically observed in patients with dilated
cardiomyopathy or multivalvular heart
diseases that develops or progresses
slowly
PRECIPITATING CAUSES OF
HEART FAILURE:
•
•
•
•
•
•
•
•
•
Infection
Anemia
Thyrotoxicosis & pregnancy
Arrythmias
Rheumatic, viral & other forms of myocarditis
Infective endocarditis
Systemic hypertension
Myocardial infarction
Physical, dietary, fluid, environmental & emotional
excesses
• Pulmonary embolism
PULMONARY CONGESTION &
RESPIRATORY SYMPTOMS:
• Result of dilatation & increasing left
ventricular end diastolic pressure, left
atrial pressure & capillary pressures
– Results to pulmonary vascular congestion
& symptoms associated with cough with
blood tinged sputum
Cont.
• EDEMA OF THE BRONCHIAL MUCOSA
– Increases resistance to airflow producing
respiratory distress similar to asthma
(cardiac asthma)
Cont:
• DYSPNEA
– Results from reflexes initiated by vascular
distention
– Increased rigidity of lungs & impaired gas
exchange resulting from interstitial edema
– Accumulation of fluid in ALVEOLARS
SACS (pulmonary edema)
Cont.
TACHYCARDIA
An early compensatory response
mediated by increased sympathetic tone
EDEMA
compensatory response mediated by the
renin angiotensin aldosterone system & by
increased sympathetic outflow
CARDIOMEGALY
a compensatory structural response
SYMPTOMS:
• Due to inadequate perfusion of peripheral
tissues (fatigue, dyspnea)
• Elevated intracardiac filling pressures
(orthopnea, PND, peripheral edema)
PHYSICAL EXAM:
• Jugular venous
distention
• S3
• Rales
• Pleural effusion
• Edema
• Hepatomegaly
• Ascites
“All the signs of CHF are the
consequences of inadequate force of
contraction"
PATHOPHYSIOLOGY:
• STARLING’S LAW
“Within limits, the force of ventricular
contraction is a function of the enddiastolic length of the cardiac muscle,
which in turn is closely related to the
ventricular end-diastolic volume.”
PATHOPHYSIOLOGY:
– Heart failure results in DEPRESSION of the
ventricular function curve
– COMPENSATION in the form of stretching
of myocardial fibers results
– Stretching leads to cardiac dilatation
which occurs when the left ventricle fails
to eject its normal end diastolic volume
CARDIAC FAILURE
VENOUS
PRESSURE
CARDIAC
OUTPUT
SYMPATHETIC
ACTIVITY
BLOOD
PRESSURE
RENAL
BLOOD FLOW
RENIN ANGIOTENSIN II
ALDOSTERONE
CAPILLARY
FILTRATION
SODIUM RETENTION
EDEMA
NEUROHUMORAL ACTIVATION
DURING MYOCARDIAL FAILURE
MYOCARDIAL
FAILURE
CARDIAC OUTPUT
BLOOD PRESSURE/TISSUE PERFUSION
ACTIVATION OF ADRENERGIC SYSTEM
ARTERIOLAR CONSTRICTION
INCREASED SYSTEMIC VASCULAR
RESISTANCE
INCREASED RESISTANCE TO
EJECTION
COMPENSATORY RESPONSES
DURING HEART FAILURE:
CARDIAC OUTPUT
CAROTID SINUS FIRING
SYMPATHETIC
DISCHARGE
RENAL BLOOD FLOW
RENIN RELEASE
FORCE
RATE
PRELOAD
CARDIAC OUTPUT
(VIA COMPENSATION)
AFTERLOAD
REMODELING
Pathophysiology of Cardiac Performance
Factor
1. Preload (work or stress the
heart faces at the end of
diastole)
Mechanism
Therapeutic Strategy
increased blood volume and
-salt restriction
increased venous tone--->atrial -diuretic therapy
filling pressure
-venodilator drugs
2. Afterload (resistance against increased sympathetic
which the heart must pump)
stimulation & activation of
renin-angiotensin system --->
vascular resistance --->
increased BP
- arteriolar vasodilators
-decreased angiotensin II
(ACE inhibitors)
3. Contractility
decreased myocardial
-inotropic drugs (cardiac
contractility ---> decreased CO glycosides)
4. Heart Rate
decreased contractility and
decreased stroke volume --->
increased HR (via activation of
b adrenoceptors)
CLINICAL MANAGEMENT OF
CONGESTIVE HEART FAILURE
• OBJECTIVES:
Increase cardiac contractility
Decrease preload ( left ventricular
pressure)
Decrease afterload (systemic vascular
resistance)
Normalize heart rate and rhythm
Approaches:
Reduce workload of heart
1.Limit activity level reduce weight control hypertension
2. Restrict sodium (low salt diet)
3. Give diuretics (removal of retained salt and water)
4. Give angiotensin-converting enzyme inhibitors
(decreases afterload and retained salt and water)
5. Give digitalis (positive inotropic effect on depressed
heart)
6. Give vasodilators (decreases preload & afterload)
DRUGS USED TO TREAT
CONGESTIVE HEART DISEASE:
• VASODILATORS
– Reduce the preload (through
venodilatation), or reduction in afterload
(through arteriolar dilatation) or both
– Decrease the load of the myocardium
DIURETIC AGENTS:
• Reduce salt & water retention, thereby
reducing ventricular preload
INOTROPIC AGENTS:
oIncrease the strength of
contraction of cardiac muscles
DRUGS USED TO TREAT
CONGESTIVE HEART FAILURE
VASODILATORS
-CAPTOPRIL
-ENALAPRIL
-FOSINOPRIL
INOTROPIC AGENTS
-DIGOXIN
-DIGITOXIN
-LISINOPRIL
-QUINAPRIL
-DOBUTAMINE
-HYDRALAZINE
-ISOSORBIDE
-MINOXIDIL
-SODIUM
NIITROPRUSSIDE
DIURETICS
-BUMETANIDE
-FUROSEMIDE
-HYDROCHLOROTHIAZIDE
-METALAZONE
-AMRINONE
-MILRINONE
BASIC PHARMACOLOGY OF DRUGS
USED IN CONGESIVE HEART FAILURE:
DIGITALIS
PHARMACOKINETICS:
LIPID SOLUBILITY
ORAL AVAILABILITY
HALF-LIFE
PLASMA PROTEIN BINDING
PERCENTAGE METABOLIZED
VOLUME OF DISTRIBUTION
DIGOXIN
DIGITOXIN
MEDIUM
75%
40 HRS
20-40 HRS
<20
6.3 L/KG
HIGH
>90%
168 HRS
>90 HRS
>80
0.6 L/KG
PHARMACOKINETICS:
-T1/2 is long (40 hrs)
-Therapeutic plasma concentration: 0.5-2 ng/ml
-Toxic plasma concentration: >2 ng/ml
*digitalis must be present in the body in certain "saturating"
amount before any effect on congestive failure is noted
this is achieved by giving a large initial dose in a process called
"digitalization"
-after intial dosages, digitalis is given in "maintenance" amounts
sufficient to replace that which is excreted
to avoid exceeding therapeutic range during digitalization:
- the loading dose should be adjusted according to the health of
the patient
- slow digitalization (over 1 week) is the safest technique
- plasma digoxin levels should be monitored
METABOLISM & EXCRETION:
• Digoxin – not extensively metabolized,
2/3 excreted unchanged in the kidneys
• Digitoxin – metabolized in the liver and
excreted into the gut via the bile
MECHANISM OF ACTION:
• Inhibit the monovalent cation transport
enzyme coupled Na+, K+ ATPase &
increased intracellular Na+ content
increases intracellular Ca2+ through a
Na+ - Ca2+ exchange carrier mechanism.
• Increased myocardial uptake of Ca2+
augments Ca2+ release to the
myofilaments during excitation invokes
a positive inotropic response
MECHANISM OF ACTION:
• Produce alterations in the electrical
properties of both contractile cells and the
specialized automatic cells, leading to
increased automaticity & ectopic impulse
activity
• Prolong the effective refractory period of
the AV node slow ventricular rate in
atrial flutter & fibrillation
PROPERTIES OF CARDIAC
GLYCOSIDES:
OUABAIN
DIGOXIN
DIGITOXIN
Lipid solubility
(oil/water
coefficient)
Low
Medium
High
Oral availability
(% absorbed)
0
75
> 90
Half-life in the
body (hrs)
21
40
168
Plasma protein
binding (%
bound)
0
<20
>80
Volume of
distribution
18
6.3
0.6
EFFECTS IN HEART FAILURE:
•
•
•
•
•
•
Stimulates myocardial contractility
Improves ventricular emptying
Increase cardiac output
Augments ejection fraction
Promotes diuresis
Reduces elevated diastolic pressure &
volume & end –systolic volume
• Reduces symptoms resulting from
pulmonary vascular congestion & elevated
systemic venous pressure
DIGITALIS INTOXICATION:
• Serious & potentially fatal complication
• Anorexia, nausea & vomiting = earliest signs
of digitalis intoxication
• Arrythmias: ventricular premature beats,
bigeminy, ventricular & atrial tachycardia w/
variable AV block
• Chronic digitalis intoxication = exacerbations
of heart failure, weight loss, cachexia,
neuralgias, gynecomastia, yellow vision,
delirium
TREATMENT OF DIGITALIS
INTOXICATION:
Tachyarrythmias: withdrawal of the
drug, treatment with beta blocker
or lidocaine
Hypokalemia: potassium
administration by the oral route
OTHER POSITIVE INOTROPIC
DRUGS USED IN HEART FAILURE:
• BIPYRIDINES
– Amrinone & Milrinone
– Parenteral forms only
– Half-life: 2-3 hrs
– 10-40% excreted in the urine
– MOA: increase inward calcium influx in the
heart during action potential & inhibits
phosphodiesterase
– ADVERSE EFFECTS: nausea, vomiting,
thrombocytopenia, liver enzyme changes
BETA ADRENOCEPTOR
STIMULANTS:
• DOBUTAMINE
– Increases cardiac output
– Decrease in ventricular filling pressure
– Given parenterally
– CONTRAINDICATIONS:
pheochromocytoma, tachyarrythmias
– ADVERSE EFFECTS: precipitation or
exacerbation of arrythmia
DRUGS WITHOUT POSITIVE
INOTROPIC EFFECTS USED IN
HEART FAILURE:
• DIURETICS
– Reduce salt & water retention reduce
ventricular preload
– Reduction in venous pressure reduction
of edema & its symptoms, reduction of
cardiac size improved efficiency of
pump function
ANGIOTENSIN-CONVERTING
ENZYME INHIBITORS:
• Reduce peripheral resistance reduce
afterload
• Reduce salt & water retention ( by
reducing aldosterone secretion) reduce
preload
• Reduce the long term remodelling of the
heart vessels ( maybe responsible for the
observed reduction in the mortality &
morbidity)
VASODILATORS:
• HYDRALAZINE, ISDN
– Reduction in preload through
venodilatation or reduction in
afterload through arteriolar dilation
or both
BETA-ADRENOCEPTOR
BLOCKERS:
• BISOPROLOL, CARVEDILOL,
METOPROLOL
– Reduction in mortality in patients with
stable Class II & Class III heart failure
DIURETICS
RENAL TRANSPORT MECHANISM:
• PROXIMAL CONVOLUTED TUBULE:
– Carries out isosmotic reabsorption of
amino acids, glucose and cations
– Bicarbonate reabsorption
– 40-50% Na reabsorption
THICK PORTION OF ASCENDING LIMB
OF THE LOOP OF HENLE:
• Pumps Na, K & Cl out of the lumen into
the interstitium
• Provides the concentration gradient for the
countercurrent concentrating mechanism
• Ca & Mg reabsorption
DISTAL CONVOLUTED TUBULE:
• Actively pumps Na & Cl out of the lumen
nephron
• 10 % Na reabsorbed
• Ca & Mg reabsorption
COLLECTING TUBULE:
• Primary site of acidification of urine &
aldosterone regulated reabsorption of Na
• 2-4 % reabsorbed filtered Na
• H2O reabsorption under ADH control
DIURETICS
• Drugs that increase the rate of
urine flow
• Increase the rate of Na & Cl
excretion
• Decrease reabsorption of K, Ca &
Mg
DIURETICS
•
CLASSIFICATION:
1. CARBONIC
ANHYDRASE
INHIBITORS
2. OSMOTIC DIURETICS
3. LOOP DIURETICS
4. THIAZIDE DIURETICS
5. POTASSIUM SPARING
DIURETICS
• SITE OF ACTION:
Proximal tubule
Proimal tubule, Loop of
Henle, Collecting tubule
Ascending limb of the
loop of Henle
Distal convoluted
tubule
Collecting ducts
CARBONIC ANHYDRASE
INHIBITORS:
• CLASSIFICATION & PROTOTYPES:
ACETAZOLAMIDE (Diamox) – a
sulfonamide derivative
• MECHANISM OF ACTION:
– Inhibits carbonic anhydrase w/c slows the
ff. rxn:
H + HCO3 H2O + CO2
Necessary for maximum reabsorption of
HCO3 from the glomerular filtrate
Drug effect occurs throughout the body
PHARMACOKINETICS:
•
•
•
•
Well absorbed after oral administration
Onset of action: 30 minutes
Duration: 12 hrs
Excretion: proximal tubule
CLINICAL USES:
•
•
•
•
•
Treatment of glaucoma – major application
Urinary alkalinization
Epilepsy
Acute mountain sickness
Correction of metabolic alkalosis
TOXICITY:
•
•
•
•
Hyperchloremic metabolic acidosis
Renal stones
Renal potassium wasting
Drowsiness & paresthesias – large
doses
LOOP DIURETICS
CLASSIFICATION & PROTOTYPES:
Furosemide – prototype & sulfonamide
derivative
Bumetanide- sulfonamide
Ethacrynic Acid – phenoxyacetic acid
PHARMACOKINETICS:
• Rapidly absorbed
• Diuretic response is extremely rapid
following IV injection
• Duration of effect: 2-3 hrs
• Half life: dependent on renal function
• Excreted in the kidney
MECHANISM OF ACTION:
• Inhibit the coupled Na+/K+/2Cl transport
system in the luminal membrane of the
thick asceding limb of the loop of henle
reduce NaCl reabsorption
• Increase Mg & Ca+ excretion
CLINICAL USES:
• Treatment of edematous states (CHF & ascites)
• Acute pulmonary edema in w/c a separate
pulmonary vasodilating action may play a useful
additive role
• Sometimes used in hypertension if response to
thiazide is inadequate but their short duration of
action is a disadvantage
• Treatment of severe hypercalcemia induced by a
carcinoma – less common
• Acute renal failure
• Hyperkalemia
TOXICITY:
• Hypokalemic metabolic alkalosis
• Hyperuricemia
• Hypovolemia & cardiovascular
complications
• Ototoxicity – important toxic effect of the
loop agents
• hypomagnesemia
THIAZIDE DIURETICS
• CLASSIFICATION & PROTOTYPE:
– HYDROCHLOROTHIAZIDE – sulfonamide
derivative
– INDAPAMIDE – new thiazide like agent with a
significant vasodilating effect than Na diuretic
effect
MECHANISM OF ACTION:
• Inhibit NaCl transport in the early segment
of the distal convoluted tubule ( a site w/c
significant dilution of urine takes place)
REDUCE THE DILUTING CAPACITY OF THE NEPHRON
EFFECTS:
• Urinary excretion
– Full doses – produce a moderate Na & Cl
diuresis hypokalemic metabolic alkalosis
– Reduced the blood pressure by reduction of
the blood volume but with continued use
these agents appear to reduce vascular
resistance
CLINICAL USE:
• Hypertension – major application, for w/c
their long duration of action & moderate
intensity of action are useful
• Chronic therapy for edematous conditions
(CHF) another common application
• Recurrent renal calcium stone formation
can sometimes be controlled with
thiazides
TOXICITY:
• Hypokalemic metabolic alkalosis &
hyperuricemia
• Chronic therapy is often associated with
potassium wasting
• hyperlipidemia
POTASSIUM SPARING DIURETICS:
• CLASSIFICATION & PROTOTYPES
o SPIRINOLACTONE – antagonist of
aldosterone in the collecting tubules
• Has a slow onset & offset of action (24-72 hrs)
o TRIAMTERENE & AMILORIDE – inhibitors
of Na flux in this portion of the tubule
ADVERSE EFFECTS:
• Decrease K & H ion excretion and may
cause hyperchloremic metabolic
acidosis
• Interfere with steroid biosynthesis
CLINICAL USE:
• Hyperaldosteronism – important indication
• Potassium wasting caused by chronic
therapy with loop diuretic or thiazide if not
controlled by dietary K supplements
• Most common use is in the form of
products that combine a thiazide with a K
sparing agent
TOXICITY:
• Hyperkalemia – most important toxic effect
• Metabolic acidosis in cirrhotic patients
• Gynecomastia & antiandrogenic effects
OSMOTIC DIURETICS
• CLASSIFICATION & PROTOTYPE:
– MANNITOL – prototype osmotic diuretic
given intravenously
MECHANISM OF ACTION:
• Holds water in the lumen by virtue of its
osmotic effect
• Major location for this action is the
proximal convoluted tubule, where the
bulk of isosmotic reabsorption takes place
• Reabsorption of H2O is also reduced in
the descending limb of the loop of henle &
the collecting tubule
EFFECTS:
• Volume or urine is increased
• Most filtered solutes will be excreted in
larger amounts unless they are actively
reabsorbed
CLINICAL USES:
• Maintain high urine flow (when renal blood
flow is reduced & in conditions of solute
overload from severe hemolysis or
rhabdomyolysis)
• Useful in reducing intraocular pressure in
acute glaucoma & increase intracranial
pressure in neurologic conditions
TOXICITY:
• Hyponatremia & pulmonary edema due to
removal of water from the intracellular
compartment
• Headache, nausea, vomiting
• dehydration
Asymptomatic
Mild to
LV Dysfubction moderate CHF
Moderate to
severe CHF
ACE inhibitor
Digoxin
Digoxin
Beta blocker
Diuretics
Diuretics
ACE inhibitor
ACE inhibitor
Beta blocker
Beta blocker
Spironolactone