Block2 Lecture6 Bhaskar CCF
Transcript of Block2 Lecture6 Bhaskar CCF
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Congestive Heart Failure
Dr Bhaskar H Nagaiah
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Congestive Heart Failure (CHF)
Contractility / Cardiac output (COP) is notadequate to provide blood / oxygen needed by the
body.
Lethal disease, five years mortality rate is 50%
Common cause - Coronary artery disease
Prevalence ofCHF is increasing due to increase
in survival of pts with myocardial infraction
Systolic failure reduce in myocardial contractility& ejection fraction reduced COP
Diastolic failure stiffening & inadequate relaxation
of heart during diastole reduced COP
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Force of contraction of heart mainly depends onamount of free Calcium inside the cytoplasm.
Amount of free Calcium, is proportional to amount
Calcium stored and released from sarcoplasmic
reticulum (SR) Amount Calcium stored depends on influx of Ca
through L- type of calcium channels & efflux of
Ca through NaCa Exchanger, antiport
(activation depends on Na concentration)
Na concentration is maintained by Na-K ATPase
(Sodium pump)
Congestive Heart Failure (CHF)
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Congestive Heart Failure (CHF)
Predisposing factors
HTN (increase in TPR)
Myocardial infarction / IHD
Myocarditis
Congenital abnormalities AS, AR
High output failure (because the increase
the thyroid hormone, stimulate the
myocardium, and the heart can cope withthe stimulation, also with anemia makes it
work harder)
Thyrotoxicosis
Anemia
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Neurohumoral mechanisms in CHF
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Congestive Heart Failure (CHF)
Remodeling
Proliferation of connective tissue and abnormal
myocardial cells (fetal myocytes) in place of
normal cardiac muscle.
Normal cardiac myocytes gradually die due toapoptosis.
Heart gradually loses the contractility / FOC
Signs and symptoms tachycardia, decrease in
exercise tolerance, shortness of breath
/dysnoea, peripheral and pulmonary edema,
cardiomegaly, rapid muscular fatigability
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Acute Heart Failure
Symptoms severe sudden onset,
after infart LHF pulmonaryedema
Chronic Heart Failure
Slow progression Left sided heart failure
LVF leads to RVF
Right sided heart failure
Congestive Heart Failure (CHF)
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Cardiac performance in CHF
1. Pre-load increased in CHF (due to increase inblood volume and venous tone), increase left
ventricular filling pressure. Overstretching
cardiac fibers (increased End-diastolic fiber
length) and fall in stoke volume2. After-load increased due to increase in
systemic vascular resistance / TPR
3.
Contractility of the myocardium- reduced /shortening of muscle
4. Heart rate increased
5. Cardiomegaly
Pathophysiology - CHF
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Congestive Heart Failure (CHF)
Main defect in excitation and contraction coupling in
myocardium
Other processes and organs involved are
Sympathetic NS (we must reduce this)
Kidneys
Renin-angiotensin-system & aldosterone (RAS-A)
Peptides atrial natriuretic peptide
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Congestive Heart Failure (CHF)
Pharmacotherapy is aimed at:1. Decreasing PreloadEnd diastolic
pressure / fiber length
2. Decreasing After load reduce cardiac work (stupid
kidney increase the Afterload, b/c increase in TPR)
3. Increasing cardiac Contractility increase efficiency
4. Decreasing the Remodelingof cardiac muscles- to
prevent further worsening / progress
To decrease
We got to stop this remod
stop it then they live lon
must arrest it!
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Congestive Heart Failure (CHF)
Methods of treatment Reduce the work load on heart- physical
activity, body weight & control HTN
Decrease sodium in diet
Vasodilators reduce preload & afterload
Diuretics reduce blood volume & preload
Inotropic drugs increase FOC & COP
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VASODILATORS DIURETICS INOTROPICS
ACE inhibitors
ARBs (angiotensinereceptor blockers)
Direct vasodilators:
Sodium nitroprusside
Hydralazine
Nitrates:
-Nitroglycerine
-Isosorbide dinitrate
-Loop diuretics
-Thiazides
-K Sparringdiuretics
-Spironolactone
-Eplerenone
cardiac glycosides
-Digoxin
Beta agonists
-Dopamine
-Dobutamine
Phosphodiesteraseinhibitors
-Amrinone
-Milrinone
BETA BLOCKERS
Metoprolol
Carvedilol
In chronic CHF, beta blockers have beenfound to prevent the remodeling changes
in the heart.
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Arrest / reversal of disease progression
and prolongation of survival
ACE inhibitors / AT1 receptor blockers (ARBs)
Beta blockers
Aldosterone antagonists
Spironolactone Eplerenone
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VASODILATORS
ACE inhibitors / ARBs
ACE inhibitors & AT1 receptor blockers
reduce
Aldosterone secretion
Salt and Water retention Reduce Vascular resistance, preload &
afterload
They reduce morbidity & mortality in ChronicHeart Failure
Are first line drugs for Chronic Heart Failure,
along with Diuretics
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ACE inhibitors
Captopril Lisinopril
Enalpril
Ramipril
Quinapril Moexipril
Perindopril
Trandolapril Fosinopril
BenzaprilNon renal elimination
Know these
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Mechanism of action of ACE inhibitors in
CHF
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Acts by inhibiting ACE(angiotensin convertingenzyme);
Decreases Angiotensin II levels Vasodilatation of both arterioles & veins and
decrease in preload & after-load Increase in cardiac output & ejection fraction
Reduce blood volume (preload) by inhibitingretention of sodium & water
Arrest/reverse the remodeling changes in the
myocardium
ACE Inhibitors
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Dry irritating cough (due to bradykinin)
Angioedema
Hypotension during initial doses
Hyperkalemia
Skin rashes, Urticaria Dysgeusia (metallic taste)
Acute renal failure contraindicated in bilateral renal
artery stenosis so if preg, give calcium blockers instead.
Adverse effects of ACE Inhibitors :
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Angiotesin II receptor blockers (ARBs)
Losartan, valsartan, Candesartan, eprosartan, Irbesartan, telmisartan
Benefits similar to ACE inhibitors
Used in pts intolerance to ACE inhibitors
Less AEs dry cough, angioedema No effect on bradykinin metabolism
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Diuretics
Loop diuertics - are preferred in acute CHF
Furosemide
Bumetanide
Thiazide diuretics
Potassium sparing diuretics
Spironolactone (an Aldosterone Antagonist)
Amiloride
Triamterene
Spironolactone aldosterone antagonist, reduces
the morbidity & mortality, Reduces myocardial &
vascular fibrosis
but
but
e
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DIURETICS
Decreases plasma volume
excretion of Na+ & H2O
Decrease Venous Return
Reduce preload and end diastolic pressure
Reduce cardiac workload (Oxygen demand)
More efficient cardiac contraction (COP)
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Aldosterone antagonist: Eplerenone
Selective aldosterone antagonist Decreases Na and water reabsorption,
decrease blood volume
More selective to aldosterone receptors blocker
than Spironolactone.
Less affinity to androgen receptors Less antiandrogenic AEs than spironolactone
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Nesiritide
Recombinant human Brain natriuretic peptide
(BNP)
Mechanism of Action
Increases cGMP
Cause relaxation of arteries and veins
Induce diuresis
Short half life IV bolus Used acute CHF
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Other Vasodilators
Hydralazine
Arteriolar dilator reduce afterload
Isosorbide dinitrate Predominantly venodilator Reduce preload
Used acute LVF
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INOTROPIC AGENTS
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Inotropic agents
Cardiac glycosides (Digitalis compounds) Digoxin
Digitoxin
Beta agonists
Dopamine
Dobutamine
Phosphodiesterase inhibitors
Inamirinone (Amrinone)
Milrinone
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Normal myocardial cell
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Cardiac glycoside digoxin
Mechanism of Action:
Inhibit Na-K pump (Na+/K+ ATPase)
Increase intracellular Na
Suppress Na+- Ca+ exchanger
Increase intracellular Ca2+
Increases FOC & Cardiac output
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Increase in ejection fraction, FOC & COP
Enhance renal perfusion
Reduces compensatory mechanisms
Reduce Sympathetic overactivity
TPR HR
Myocardial oxygen demand
Leading to more efficient contraction withoutincreasing Oxygen demand
Systole is shortened & diastole is prolonged
Cardiac glycosides
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Cardiac glycosides -
Therapeutic Uses
Congestive heart failure - Inotropic agent used in
left ventricular Systolic failure
Other uses:
In Atrial fibrillation To control the ventricular rate.
Parasympathomimetic effects of digilatis
(stimulate central Vagal N) Decreases AV conduction by increasing
refractory period of AV node & PR interval
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Cardiac glycosides PK
Digoxin
Plasma half life is short compared to
digitoxin
Fast onset of action
Excreted unchanged in urine Digitoxin(not available in US)
Extensive extra-vascular binding
Metabolized in liver Excreted in feces
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Digoxin Digitoxin
Half-Life (hours) 36 40 hrs 180 hrs
Protein Binding 20-40% 70 - 90%
Route of elimination Renal
(60%)
Hepatic
Vagal Stimulation +++ +
Cardiac glycosides
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Cardiac glycosides DigoxinAdverse effects: are more due to narrow TI
Extra cardiac: Stimulation of vagus nerve causes increase in GI
effects common, anorexia, diarrhea nausea,
vomiting (stimulation of CTZ centre),
Gynecomastia
visual disturbances (diplopic, aberration in color
perception)
Cardiac AE: Can induce all types of cardiac arrhtythmias
ventricular bigeminy, ventricular arrhythmias,
AV block, bradycardia,
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Digitalis toxicity
Hypokalemia enhance digitalis toxicity -
Signs/Symptoms of Digitalis toxicity
GIT: nausea, vomiting, diarrhea
CNS : headache, hallucinations, fatigue,
confusion
Vision disturbances - blurred vision, alteration of
color perception, haloes
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Signs/Symptoms of Digitalis toxicity.
On Heart: Ectopic beats/ premature ventricular beats
Delayed after depolarization (due increased
intracellular Ca2+ concentration)
Ectopic beats,
Ventricular arrhythmias
Sinus bradycardia
First-degree AV block
Complete heart block
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Digitalis toxicity
Predisposing factors Hypokalemia - binding of digoxin to Na-K ATPase
Drugs
Loop diuretics or thiazide - induce Hypokalemia
Quinidine- decreases digoxin renal clearance
& displace digoxin from plasma protein binding
- toxicity
Hypomagnesemia
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Rx of digitalis toxicity:
Treatment
Stop Digoxin treatment Correct the Potassium & magnesium deficiency:
K sparing diuretic or KCl
For arhythmia: give antiarrhythmic drugs lidocaine or Phenytoin to control Ventricular
fibrillation
Anti digoxin antibodies (Digibind) in severe
toxicity / other therapies are not effective (not
perferred, only in severe toxicities)
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Beta agonists
Dopamine
Dobutamine Used in acute CHF
Disadvantage ofDopamine over Dobutamine
and digoxin Dopamine increase heart rate & oxygen
demand
Dobutamine increases contractility more than
HR
Preferred in acute CHF than other inotropic
agent
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Phosphodiesterase Inhibitors (Bipyridines)
Inamrinone (Amrinone) and Milrinone
Mechanism of Action:
Inhibits phosphodiesterase (PDE) enzyme &
increase in cAMP level
Increase cytoplasmic Ca2+ concentration &
cardiac contractility
Dilates the blood vessels -
Used in acute cardiac failure
Not used in chronic CHF
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Drugs contraindicated in CHF
Drugs contraindicated in CHF:
Ca2+ channel blockers(verapamil, diltiazem)
Beta blockersin high dosage (we now only
admin in small doses) Antiarrhythmic drugs
Combination of Verapamil & diltiazem with Beta
blockers
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Role of Beta-receptor antagonists
Beta blockers like Metoprolol, Carvedilol Reduce progression ofChronic Heart Failure. By increasing the Ventricular ejection fraction
& exercise tolerance and reduce mortality rate.
May by Up-regulation of receptors & reducesremodeling
Not beneficial/ no value in Acute failure detrimental if systolic dysfunction is marked
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Treatment
Acute CHF Most common cause isAcute MI
Treat with inotropics, loop diuretics,
vasodilators
Chronic CHF
Reduce work load Restrict Na & water (if require but rarely)
Give diuretics
ACE inhibitors / ARBs Digoxin
Beta blockers & vasodilators