Block2 Lecture6 Bhaskar CCF

7/31/2019 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)



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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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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



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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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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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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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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

Block2 Lecture6 Bhaskar CCF

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