Congestive Cardiac FailureCongestive Cardiac Failure

Dr. R. Senthil Kumar

Introduction to Heart FailureIntroduction to Heart Failure

• Heart unable to provide adequate perfusion of peripheral organs to meet their metabolic requirements

• Characterized by:

1. Reduction in cardiac output

2. Increased TPR• Progressing to congestive heart failure (CHF) is

accompanied by peripheral and pulmonary edema.

Recent Advances Vs RealityRecent Advances Vs Reality

• Major advances in recent years in management of patients with CHF

• In 2000 an estimated 4.7 million people in the United States had HF

• The median survival after initial diagnosis is 1.7 years for men and 3.2 years for women.

• Sudden cardiac death is common in patients with heart failure, contributing to 50% of all 287,000 deaths in the United States last year

Acute Vs Chronic HFAcute Vs Chronic HF

• In a patient with acute heart failure, the short-term aim is stabilization by providing symptomatic treatment through intravenous interventions.

• Management of chronic heart failure is multifaceted, with the long-term aims of:• relieving symptoms• improving hemodynamics• improving quality of life and • decrease mortality.

Cardiac Vs Noncardiac targetsCardiac Vs Noncardiac targets

• Conventional belief that the primary defect in HF is in the heart

• Reality is that HF involves many other processes and organs

• Research has shown that therapy directed at noncardiac targets are more valuable than cardiac targets

Compensation in HFCompensation in HF

• Heart failure is usually accompanied by an increase in:

1. Sympathetic nervous system (SNS) 2. Chronic up-regulation of the renin-

angiotensin-aldosterone system (RAAS) and effects of aldosterone on heart, vessels, and kidneys.

• CHF should be viewed as a complex, interrelated sequence of events involving hemodynamic, and neurohormonal events.

Compensation contd..Compensation contd..

• In a failing heart, the loss of contractile function leads to a decline in CO and a decrease in arterial BP.

• Baroreceptors sense the hemodynamic changes and initiate countermeasures to maintain support of the circulatory system.

• Activation of the SNS serves as a compensatory mechanism in response to the earlier

• This helps maintain adequate cardiac output by:1. Increasing myocardial contractility and heart rate (β1-

adrenergic receptors)2. Increasing vasomotor tone (α1-adrenergic receptors)

to maintain systemic blood pressure

Consequences of hyperadrenergic Consequences of hyperadrenergic statestate• Over the long term, this hyperadrenergic state

leads to irreversible myocyte damage, cell death, and fibrosis.

• In addition, the augmentation in peripheral vasomotor tone increases LV afterload

• This places an added stress upon the left ventricle and an increase in myocardial O2 demand (ventricular remodeling).

• The frequency and severity of cardiac arrhythmias are enhanced in the failing heart

• Figure p.203 kat

PathophysiologyPathophysiology

• CHF pathophysiology animation

Therapeutic Overview Therapeutic Overview

Problem• Reduced force of contraction• Decreased cardiac output• Increased total peripheral resistance• Inadequate organ perfusion• Development of edema• Decreased exercise tolerance• Ischemic heart disease• Sudden death• Ventricular remodeling and decreased function

Goals and drug therapyGoals and drug therapy

Goals• Alleviation of symptoms, improve quality of life• Arrest ventricular remodeling• Prevent sudden death Nondrug therapy• Reduce cardiac work; rest, weight loss, low Na+ diet Drug therapy• Chronic heart failure

• ACE-I, β-blockers, ARB, aldosterone antagonists, digoxin, diuretics • Acute heart failure

• Intravenous diuretics, inotropic agents, PDE inhibitors, vasodilator

Signs and symptomsSigns and symptoms

• Tachycardia• Decreased exercise tolerance & SOB• Peripheral and pulmonary edema• Cardiomegaly

DiureticsDiuretics

• Bottom line: they decrease fluid volumes

• Four Flavours:• Carbonic anhydrase inhibitors• Loop diuretics• Thiazide diuretics• K+-sparing

Renin angiotensin systemRenin angiotensin system• Baroreceptor mediated activation of the SNS

leads to an increase in renin release and formation of angiotensin II

• Angiotensin II acts through AT1 and AT2 receptors (most of its actions occur through AT1 receptors)

• This causes vasoconstriction and stimulates aldosterone production

• RAS remains the most important target of chronic CHF therapy

Effects of AT-IIEffects of AT-II

MOAMOA• ACE-Inhibitors and ARB animation• Blockade of ACE• Decreased AT-II• Decreased aldosterone• Decreased fluid retention• Vasodilation• Reduced preload and afterload• Slows cardiac remodeling

Advantages Advantages

• Improves symptoms significantly• Improves exercise tolerance• Slows progression of the disease• Prolong survival in established cases

ADRADR

• What are the ADR of ACEIs?• Cough (why?)• Postural hypotention (why?)• Hyperkalemia (possible Drug interactions?)• Contraindicated in pregnant women (1st

trimester)• Rare: angioedema

Other Vasodilators:Other Vasodilators:

• Mechanism 2: • Direct smooth muscle relaxants• Nitrates

• Venous dilators• Reduce preload• Eg: sodium nitropruside

InotropesInotropes

• Increase force of contraction• All increase intracellular cardiac Ca++

concentration• Eg:

• Digitalis (cardiac glycoside)• Dobutamine (β-adrenergic agonist)• Amrinone (PDE inhibitor)

Cardiac glycosidesCardiac glycosides

• Digitalis • Sourced from foxglove plant• 1785, Dr. William Withering’s

monograph on digitalis• Has a profound effect on the cardiac

contractility

PckPck

• Two drugs (digoxin, digitoxin)• Well absorbed orally• 10% of population have bacteria in the gut,

which inactivate digoxin, needing an increased dose in such

• Beware of using antibiotics in such patients• Digoxin has a very narrow ther. Margin

PckPck

• Taken orally• Enters CNS (so what?)• Renal clearance proportional to CC• To be used with extreme caution in

patients suffering from renal impairment

MOAMOA

• Regulation of cytosolic Ca metabolism:• Reversibly combine with sodium-potassium

ATPase of the cardiac cell membrane• Results in inhibition of pump activity• This leads to in intracellular Na conc.• This favors Ca ions in the cell• Ca levels result in increased systolic force of

contraction

Digoxin MOADigoxin MOA

Na/K ATPase inhibitionNa/K ATPase inhibition

Additional MOAAdditional MOA

• Force of contraction resembles to that of the normal heart

• Improved circulation leads to reduced sympathetic activity

• This reduces PVR• All this leads to reduction in HR• Vagal tone is enhanced• Finally myocardial O2 demand is reduced

Electrophysiological effects on the Electrophysiological effects on the heart heart

Uses Uses

• Severe LV systolic dysfunction• Only after initiation of diuretics and

vasodialtor therapy• Management of patients with chronic atrial

fibrillation• Cannot arrest the progression of pathological

changes causing heart failure, and does not prolong life in patients with CHF

ADRADR

• Digitalis toxicity is one among most commonest encountered (why?)

• Therapeutic concentration- 0.5-1.5 ng/ml• Often the first step is discontinuation of Rx• Digoxin levels must be monitored closely

Signs of digoxin toxicitySigns of digoxin toxicity

• CNS: Malaise, confusion, depression, vertigo, vision (abnormalities in color vision)

• GI: Anorexia, nausea, intestinal cramping, diarrhea

• Cardiovascular: Palpitations, syncope, arrhythmias, bradycardia, AV node block, tachycardia

Factors increasing the possibility of Factors increasing the possibility of digoxin toxicitydigoxin toxicity• Pharmacological and toxic effects are greater

in hypokalemic patients.• K+-depleting diuretics are a major

contributing factor to digoxin toxicity.

Management Management Arrhythmias may be converted to normal

sinus rhythm by K+. when the plasma K+ conc. is low or within the normal range.

When the plasma K+ conc. is high, antiarrhythmic drugs, such as lidocaine, procainamide, or propranolol, can be used.

Severe toxicity treated with Digibind, an anti-digoxin antibody.

• A 96-year-old AAF was admitted from a nursing home with complaints of abdominal pain, N/V, dizziness, confusion and double vision for 5 days. She was discharged from the hospital just 4 days ago. Digoxin was started during that previous hospitalization for control of tachycardia in atrial fibrillation. One day prior to discharge, digoxin level was 1.8 mg/mL and digoxin dose was decreased to 125 mcg PO Q 48 hr.PMHHypertension, atrial fibrillation, coronary artery disease, stroke, congestive heart failure.MedicationsMetoprolol, Digoxin, ASA, lisinopril, Lasix, Coumadin, Nexium

What could it be???What could it be???

DopamineDopamine• Dopamine acts at a variety of

receptors (dose dependant)• Rapid elimination- can only be

administered as a continuous infusion

DobutamineDobutamine• Stimulates beta-adrenergic receptors and

produces a positive inotropic response • Unlike the vasoconstriction seen with high

doses of dopamine, dobutamine produces a mild vasodilatation

MOAMOA

PDE inhibitors PDE inhibitors • Inamrinone (amrinone) and Milrinone

(bipyridines)• Acts by inhibiting the enzyme Phosphodiesterase• Thus lead to increase of intracellular

concentrations of cAMP• cAMP is responsible for the conversion of

inactive protein kinase to active form• Protein kinases are responsible for

phosphorylation of Ca channels • Thus causing increased Ca entry into the cell.

MOAMOA

• Increase myocardial contractility by increasing the Ca influx during AP

• Also have vasodilating effect• Selective for PDE isoenzyme-3 (found

in cardiac and smooth muscle)

Current statusCurrent status

• Both are orally active• Only available in parenteral forms• Limited efficacy• Clinical trials- increased mortality (oral)• Still new drugs are under trial

ADRADR

• Inamrinone: nausea, vomiting, arrhythmias, thrombocytopenia and liver enzyme changes

• Withdrawn in some countries• Milrinone: arrhythmias, less likely to

cause other ADR

(BNP)-Niseritide(BNP)-Niseritide

• Brain (B-type) natriuretic peptide (BNP) is secreted constitutively by ventricular myocytes in response to stretch

• BNP binds to receptors in the vasculature, kidney, and other organs, producing potent vasodilation with rapid onset and offset of action by increasing levels of cGMP

• Niseritide is recombinant human BNP approved for treatment of acute decompensated CHF.

BNP contd..BNP contd..

• It reduces systemic and pulmonary vascular resistances, causing an indirect increase in cardiac output and diuresis.

• Effective in HF because cause reduction in preload and afterload

• ADR- hypotension

Beta blockersBeta blockers

• Overwhelming evidence to support the use of β-blockers in CHF, however

• Mechanism involved remain unclear • Part of their beneficial effects may derive

from slowing of heart rate and decrease myocardial O2consumption.

• This would lessen the frequency of ischemic events and potential for development of a lethal arrhythmia.

Beta blockersBeta blockers

• Suggested mechanisms also include reduced remodeling

• β-Blockers may be beneficial through resensitization of the down-regulated receptor, improving myocardial contractility.

• Recent studies with bisoprolol, carvedilol and metoprolol showed a reduction in mortality in patients with these drugs

• CI in unstable cases

Management of Chronic HFManagement of Chronic HF(combination of drugs) (combination of drugs)

• Limit physical activity• Reduce weight• Reduce water intake• Control HT• Na restriction• Diuretics• ACE-Is• Digitalis (ther. margin, DI with quinidine) • Beta blockers• Vasodilators

Management of acute HFManagement of acute HF

• Diuretics• Vasodilators• Inotropic drugs• Life support• Treating cause (surgery to correct

valvular disorders)