Congestive Heart FailureA Real Threat

EtiologySystolic Dysfunction(Decreased contractility):Reduction in muscle mass(due to ishcemia&MI)Dilated cardiomyopathies(idiopathic,viral,alcoholic)Ventricular Hypertrophy:

Pressure overload(systemic or pulmonary hypertension,

aortic or pulmonic valve stenosis)

Volume overload(valvular regurgitation,high output states)

Etiology Diastolic Dysfunction(restriction in

ventricular filling): Increased ventricular stiffness

Ventricular hypertrophy Infiltrative Myocardial disease

(endomyocardial fibrosis) Myocardial ischemia and infarction

• Mitral or Tricuspid valve stenosis• Pericardial disease(Pericarditis)

Compensatory mechanisms in heart failureCompensatory response

Benefecial effects of compensation

Detrimental effects of compensation

Increased preload(through Na&water retention)

Optimize stroke volume Pulmonary and systemic congestion and edema formationIncreased MVO2

Vasoconstrition Maintain blood pressure in face of reduced COShunt blood from nonessential organs to heart and brain

Increased MVO2

Increased afterload

Tachycardia (due to SNS activation)

Helps maintain cardiac output

Increased MVO2

Shortened diastolic filling time

ß1-receptor downregulation &desensatizationArrhthemiaMyocardial cell death

Ventricular Hypertrophy and remodeling

Helps maintain COReduces myocardial wall stressDecreased MVO2

Diastolic & systolic dysfunctionMyocardial cell death &ischemia &arrhythemia

Classification(NYHA)Functional Class

Description

I Patient w cardiac disease but wout limitation of physical activity.Ordinary activity does not cause undue fatigue, dyspnea or palpitation

II Patient w cardiac disease that results in slight limitation of physical activity.Ordinary activity results in fatigue, dyspnea or palpitation

III Patient w cardiac disease that results in marked limitation of physical activity.although patients are comfortable at rest, less than ordinary activity will lead to symptoms

IV Patient w cardiac disease that results in an inability to carry on physical activity wout discomfort.symptoms are present even at rest with any physical activity, increased discomfort is experienced.

Classification(AHA)Stage Description

A Patient is at high risk for the development of HF but has no apparent structural abnormality of the heart

B Patient has structural abnormality of the heart but wout symptoms

C Patient has structural abnormality f the heart & current or previous symptoms of HF

D Patient has end-stage symptoms of HF that are refractory to standard treatment

Treatment

Treatment (Con,t) Stage A: Treat Risk factors:

Control Glucose level Control BP Dyslipidemia Thyroid disorder Valvular disease Avoid drugs which aggravate heart failure

Class II

Wet Sx

Diuretics (loop) + ACEDry Sx

ACE + B (no diuretics)

improved

Spironolactone

didn’t improve

digoxin

improved didn’t improved

Spironolactone Plan B

Sx resolve Sx don’t resolve

Spironolactone + B

give digoxin

improved didn’t improve

Give BSpironolactone

Plan B

Class III

directly give ACE inh & Loop

Sx still exist Px responded

Digoxin B & Spironolactone

Didn’t respond Didn’t respond

Plan B Plan B

Class IV (see if you hospitalize him or not)

ACE + Loop D + digoxin(don’t start B)

If Px was already on B

Did not respond optimize it

Plan B

Plan B Stage D

worsening Stage C (II, III, IV)

not improved

Plan B Stage D or worsening Stage C Hospitalize your Px.Optimize drug therapy

if not improved

wet dryGive aggressive diuretic therapy IV (thiazide and loop) to cause profound diuresis(give IV due to diuretic resistance® Give iv high dose® give combination

Give positive inotropic agents(he is already on ACE inh, digoxin)

improve

Taper down +inotrop and go back to chronic Tx

- Tissue hypoperfusion- SBP < 80- Worsening renal

function- ↙Na

hypervolemia dilutional hyponatremia cyanosis

Þ Hemodynamic Monitoring

(monitor BP, temp., CO, T0).

Negative inotropic effect cardiotoxic Sodium &water retention

Antiarrhythmic (disopyramide,flecainide)

Calcium channel blocker(verapamil…)

Itraconazole

Terbinafine

Rosiglitazone

Doxorubicine

Daunomycin

Cyclophosphamide

NSAIDs

Cox-2 inhibitor

Glucocorticoids

Androgens

Estrogens

Salicylate(high dose

Na containing Drugs (carbenicillin, ticarcillin)

Treatment (Con,t) Stage B=Class IACE inhibitors OrBeta blocker if recent or previous MI&

reduced ejection fraction due to remodeling

Stage C Є class II,III,&IVACE inhibitors & Beta blockers In all Px If Sx still exist Or EF still low Add

DigoxinWhen symptoms resolves add

aldactone

Role of drugs in CHF

Angiotensin converting enzyme inhibitors

Cardioprotctive effect Preload & Afterload RA system less Na/water

retention bradykinin level vasodilation mortality, hypertrophy, & fibrosis

ACE inhibitor Approved for Use in HF

Generic Name

Brand Name

Usual daily dose(mg)

Dosing frequancy

Target dosing survival benefit

Prodrug Elimination T1/2

Captopril Capoten 18.75-150 tid 50tid No Renal 2

Enalapril Renitec 2.5-40 bid 10bid Yes Renal 10

Lisinopril Zestril 5-40 qd 10qd No Renal 12

Ramipril Tritace 1.25-20 qdorbid 5bid yes Renal 9-18

BETA BLOCKERS

Mortality Vasoconstriction Carvidilol alpha+beta blocker

&antioxidant effect Bisoprolol Metoprolol

DIGOXIN

+ inotropic effect sympathetic output from CNS(NE) Not mortality but improve Sx Therapeutic level: 0.5-1ng/ml for CHF Max: 1-1.5ng/ml for A fib

Clinical Pharmacokinetics of DigoxinOral bioavailability: Tablets 65% Elixir 80% Capsules 95%Onset of action: Oral 4-6hr IV 1.5-4hrTerminal half –life: Normal renal function 36hr Anuric patient 5daysVolume of distribution 7.3L/kgFraction unbound in plasma 75-80%Fraction excreted unchanged in urine 65-70%

Diuretics Sx relief of edema & pulmonary

congestion Direct vasodilation , Preload DOC: Furosamide: Na excretion 20-

25%

Thiazide: Na Excretion 5-8% Dose: 20-40mg bid

Up to 400mg as max dose

If Clcr>30ml/min dose up to 1-3g/d

Loop Diuretics Used in HF

Furosemide Bumetanide

Usual daily dose 20-160mg/day 0.5-4mg/day

Normal renal function

80-160mg 1-2mg

Clcr:20-25ml/min 160mg 2mg

Clcr<20ml/min 400mg 8-10mg

Bioavailability Average50% 80-90%

Affected by food Yes Yes

T1/20.3-3.4hr 0.3-1.5hr

Spironolactone

Aldosterone, preload,ventricular remodeling

Morbidity &mortality(Rales study) Used if Scr<2.5mg/dl & K<5meq/L Aplerenone No gynecomastia Mortality & morbiity in acute MI

ANGIOTENSIN RECEPTOR BLOCKER

Persistent cough &angioedema due to ACE inhibitors

If persistent HTN Add ARB or CaCh blocker (amlodepine)

If concomitant angina: add nitrate or amlodepine

New Drug Investigation

Natriuretic Peptides:

Atrial Natriuretic Peptides (ANP)

Brain Natriuretic Peptides (BNP

C-type Natriuretic Peptides (CNP)

Neseritide:

Recombinant BNP

New Drug Investigation

Omapatrilat:

Vasopeptidase Inhibitor

ACE inhibitor

INH neutral endopeptidas

Bradykinin & NP

SE: Angiodema

Precipitating factors in Heart failure Decompensation

Noncompliance with drugs or diet

Cardiac Ischemia

Inadequate therapy at time of admission

Cardiac arrhythmias

Uncontrolled hypertension

Thank YOU