Transcript Heart failure PHL461

Heart Failure
heart failure is characterized by inadequate blood flow from
the heart .As the heart is unable to provide adequate
perfusion of peripheral organs to meet their metabolic
requirements
Factors contributing to CHF
Ischemic Heart Disease
Coronary AD: less blood flow to heart, increased damage.
Myocardial Infarct: damaged tissue.
Hypertension: “overworked” heart.
Diabetes.
Lung Diseases.
Cardiomyopathies: heart muscle disease
dilated - enlarged chambers (ventricle/atria)
hypertrophic - thickened ventricle walls
Abnormal heart valves: inefficient pumping ,causes are genetic, infection
or disease.
Congenital heart defects: present at birth
Severe Anemia
Hyperthyroidism
Cardiac Arrhythmia.
Examples of CHF factors
Hypertrophic Cardiomyopathy
Congenital Heart Defects
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 pumping by right side
venous pooling of blood in legs
Right heart vs. Left heart failure
Left Heart failure
Pulmonary congestion
Reduced forward cardiac
output:
Fatigue
Renal insufficiency
Cool extremities
Decreased mentation
Right Heart failure
Neck vein distension
Hepatic congestion
Peripheral edema
Also may result in reduced
forward cardiac output,
but with clear lung
fields
Systolic vs. Diastolic Dysfunction
Systolic dysfunction
Decreased stroke volume
Decreased forward cardiac output
Almost always associated with diastolic
dysfunction as well
Diastolic Dysfunction
One third of patients with clinical heart failure
have normal systolic function – i.e. “pure”
diastolic dysfunction
The common causes of left-sided failure
-Ischemia (old or recent myocardial infarct, ischemic muscle
disease)
-Aortic stenosis
-Mitral valve disease
-Systemic hypertension (uncontrolled)
Myocardial disease: MI, Myocarditis ....... Specefic clinical symptomes of left-sided failure
-Dyspnea (from pulmonary edema and total-body hypoxia)
-Cough
-Fatigue
-Tachycardia
-Cold pale skin &may have cynotic extremities.
-Hypoxic encephalopathy: diziness, blurred vision &syncope.
-Sodium overload and systemic dependent edema (from
hypoperfused kidneys: why do you think?)
The common causes of right-sided failure:
Cardiac causes
Pulmonic valve stenosis
RV infarction
Parenchymal pulmonary causes
COPD
Cystic fibrosis
Pulmonary vascular disease
Pulmonary embolism
Primary Pulmonary hypertension
Specefic clinical symptomes of right-sided failure
Edema in lower limb
Dyspepsia & anorexia
Splanchnic congestion (you'll feel big livers & spleens )
Jugular venous distention
Total-body dependent edema (from increased venous hydrostatic
pressure, etc.)
Effusions (transudates, of course; notably pleural, notably more on the
right side than on the left; why?)
Impaire d Contrac tility
1. Myoc ardial Infarc tion
2. Trans ie nt myoc ardial is c he mia
3. Chronic Volume ove rload
4. Dilate d Cardiomyopathy
Pre s s ure Ove rload
1. Aortic S te nos is
2. Unc ontrolle d hype rte ns ion
L.V. Sys tolic dys func tion
Left Heart Failure
L.V. Diastolic dysfunction
1. Left ventricular hypertrophy
2. Hypertrophic cardiomyopathy
3. Restrictive cardiomyopathy
4. Transient myocardial ischemia
Pre s s ure Ove rlo a d
1 . Ao rtic S te no s is
2 . Unc o ntro lle d hype rte ns io n
Pathophysiology
In HF, the heart dose not provide tissues with adequate blood for metabolic need,
and cardiac-related elevation of pulmonary or systemic venous pressures may
result in organ congestion
In LV failuir:
CO decreases and pulmonary venous pressure increases. As pulmonary capillary ,
pressure exceeds the oncotic pressure of plasma proteins , fluid extravasates
from the capillaries into the interstitial space and alveoli, reducing pulmonary
compliance and increasing the work of breathing. Lymphatic drainage
increases but cannot compensate for the increase in pulmonary fluid. Marked
fluid accumulation in alveoli (pulmonary edema) Deoxygenated pulmonary
arterial blood passes through poorly ventilated alveoli and causing dyspnea
decreases and blood pH increases (respiratory alkalosis). respiratory failure.
.In RV Failuir:
systemic venous pressure increases, causing fluid extravasation and consequent ,
edema, primarily in dependent tissues (feet and ankles) and abdominal viscera.
fluid accumulation in the peritoneal cavity (ascites) can occur. RV failure
commonly causes moderate hepatic dysfunction, The impaired liver breaks
down less aldosterone, further contributing to fluid accumulation.
COMPANSATORY MECHANISM IN HF
As the heart fails, the low cardiac output and inadequately filled
arteries activate the neurohormonal system leading to:
1- increased sympathetic activity and circulating catecholamines that
increase heart rate, and causes vasoconstriction. In addition to
increase in endothelin release, (neurohormone secreted primarily
by endothelial cells), may exert direct toxic effects on the heart
and result in myocardial cell proliferation.
N.B. :The effects of baroreceptors in the aortic arch and carotid sinus that
normally inhibit undue sympathetic stimulation are blunted in clients
with HF, and the effects of the high levels of circulating
catecholamines are intensified).
2-activation of the renin–angiotensin aldosterone system which
cause:
i-Arterial vasoconstriction impairs cardiac function by increase in the
resistance (afterload), this increases stretch and stress on the
myocardial wall, and predisposes to subendocardial ischemia.
N.B.: Patients with severe HF have constricted arterioles in cerebral,
myocardial, renal, hepatic, and mesenteric vascular beds. This results
in increase organ hypoperfusion and dysfunction.
ii-Venous vasoconstriction and increased diastolic ventricular filling
pressures (preload)
iii-Angiotensin II also promotes sodium and water retention by
stimulating aldosterone and the release of vasopressin (antidiuretic
hormone) .These increase blood volume and pressure in the heart
chambers, stretch muscle fibers, and produce dilation, hypertrophy,
and changes in the shape of the heart (cardiac remodeling) that make
it contract less efficiently.
Overall, the compensatory mechanisms increase preload, workload
of the heart, afterload.
General Symptoms of CHF
shortness of breath
blood pooling in pulmonary veins
fluid in lungs
occurs during activity, rest, or sleeping
persistent coughing/wheezing
produces white/bloody mucus
edema (or excess fluid buildup in body
tissues)
venous pooling
swelling in extremities
necrosis
Con. : Symptoms of CHF
tiredness/fatigue
decreased O2 supply
diversion of blood supply from limbs
lack of appetite/nausea
decreased blood supply to digestive tract
confusion/impaired thinking
increased heart rate
baroreceptor reflex
SNS output
Heart Failure Diagnosis
medical history
Any symptoms you may
have
Also,to confirm a heart
failure diagnosis:
Laboratory blood tests.
Chest X-Rays
Electrocardiogram (ECG)
Treatment
Pharmacological
Chronic heart failure
ACE inhibitors
Beta-blockers
ATII antagonists
aldosterone antagonists
digoxin
diuretics
Acute heart failure
diuretics
PDE inhibitors
vasodilators
Non-pharmacological
Reduce cardiac work
Rest
Weight loss
low Na+ diet
Prototype drugs to know for treatment of
heart failure
Inotropes:
Digoxin, inamrinone, dobutamine, dopamine
Diuretics:
Hydrochlorothiazide, furosemide, amiloride, spironolactone
ACE inhibitors:
Captopril, enalapril, lisinopril
AGII receptor blockers:
Valsartan, losartan
Sympatholytics:
Carvedilol , Bisoprolol
Vasodilators:
Glyceryl trinitrate, hydralazine, sodium nitroprusside
Cardiac Glycosides
derived from plants
Strophanus – Ouabain
Digitalis lanata - Digoxin, Digitoxin
Direct effects
-Inhibitor of Na+/K+ ATPase pump
-Increased [Na+]I
-Increased Ca2+ influx through
-Na+/Ca2+ exchangernew
-Ca2+ steady-state: increased Ca2+
release during cardiac action
potential.
Indirect effects
-Increased parasympathetic tone
-Decreased SA/AV node
automaticity
-Decreased AV node conduction
velocity and increased refractory
period
Side Effects
extremely low therapeutic index .
most effects caused by inhibition of Na+/K+ ATPase in extracardiac tissues:
CNS: malaise, confusion, depression, vertigo, vision
GI: anorexia, nausea, intestinal cramping, diarrhea
yellow-tinted vision or yellow corona-like spots
Cardiac: bradycardia, arrhythmias
anti-digoxin antibody in toxic emergencies
Serum Electrolytes affect Toxicity
Ca2+
hypercalcemia: increases toxicity
K+
digitalis competes for K+ binding site on Na+/K+ ATPase
contraindicated with K+ depleting diuretics or patients with
hypo/hyperkalemia
hypokalemia: increased toxicity
hyperkalemia: decrease toxicity
Phosphodiesterase Inhibitors
primarily used for management of acute heart failure
Amrinone (Inocor) and Milrinone (Primacor)
-They are inhibitors of phosphodiesterase
Increased [cAMP]
Increased PKA phosphorylation of
Ca2+ channels in cardiac muscle
increased cardiac contraction
(positive inotropic effects)
&
relaxes vascular smooth muscle
(decrease total peripheral resistance
and afterload)
Side Effects:
sudden death secondary to ventricular arrhythmia, hypotension and
thrombocytopenia
now only prescribed for acute cardiac decompensation in patients nonresponsive to diuretics or digoxin
Direct acting sympathomimetics
Dopamine:
activates prejunctional D2 dopamine receptors, inhibit NE release of sympathetic
nerves, vasodilation
activates cardiac β1-adrenergic receptors, increase cardiac output
used with furosemide in diuretic resistant patients (volume overload)
Dobutamine:
racemic mixture, stimulates β1-adrenergic receptors
peripheral vasodilation
used in patients with low cardiac output and increased left ventricular enddiastolic pressure
Side Effects:
restlessness
tremor
headache
cerebral hemorrhage
cardiac arrhythmias
used with caution in patients taking β-blockers
β-adrenergic receptor antagonists
-Antagonizes β-adrenergic receptors on cardiac myocytes
-Counterbalances increased SNS activity in CHF
-Prevents development of arrhythmias
-Reduces cardiac remodeling
-Prevents renin release
-Usually given in conjunction with other therapy (ACE
inhibitors & Digoxin)
-Effective in patients with chronic systolic heart failure in
-Prevents remodeling and cardiac damage
ACE inhibitors/AT1 receptor antagonists
ACE inhibitors
-Inhibits angiotensin converting enzyme (ACE)
-Prevents conversion of ATI to ATII
-Slows progression of left ventricular dysfunction in CHF
AT1 receptor antagonists
-Selectively inhibits ATI receptor activation.
-More effective then ACE inhibitors
-AT2 receptors still active: vasodilation, antiproliferative effects
-Used in conjunction with ACE inhibitors for increased effectiveness
Both classes are drugs of choice in heart failure
•decreased preload
•decreased afterload
•decreased cardiac remodeling
•decreased SNS effects
•Side Effects:
Cough , angioneurotic edema (with ACEI), hypotension & hyperkalemia
ACE inhibitors and ATI receptor antagonists are both teratogenic
Vasodilators
Reduce TPR without ,reduce preload & reduce
afterload
Nitroglycerin
acute ischemia or acute heart failure
orally active
also administered I.V. for peripheral vasodilation
quick onset for acute relief
Isosorbide dinitrate/hydralazine
chronic administration for long-term symptom
relief
administered I.V.
Nesiritide
recombinant brain-natriuretic peptide (BNP)
BNP is secreted from ventricular myocytes in
response to stretch
vasodilator: increases cGMP in SMCs
decrease afterload/preload
inhibits cardiac remodelling
suppresses aldosterone secretion
administered IV for acute decompensated CHF
adverse effects: hypotension, renal failure.
Diuretics
used in CHF to reduce extracellular fluid volume
primarily used in patients with acute CHF with
volume overload
IV infusion causes immediate and predictable
diuresis for immediate relief
Goal: reduce preload/afterload
overdosing can result in excessive reduction in
preload, overreduction in stroke volume
thiazide and loop diuretics (i.e. Furosemide)
commonly used as adjunct therapies in CHF
Aldosterone Antagonists
elevated AngII levels increase production of aldosterone in the adrenal cortex (~20X
increase)
aldosterone activates mineralocorticoid receptors in renal epithelial cells in kidney
aldosterone promotes
Na+ retention, Mg2+ and K+ loss
increased SNS activity
decreased PSNS activity , myocardial/vascular fibrosis.
aldosterone receptor antagonists: Spironolactone & eplerenone
both antagonists reduce mortality in patients with moderate to severe CHF
only use in patients with normal renal function and K+ levels
use with K+ sparing diuretic.
Hyperkalemia , Agranulocytosis, Hepatoxicity , Renal failure
Spironolactone: gynecomastia, sexual dysfunction
Eplerenone: arrhythmia, myocardial infarct/ischemia