1. Congestive Heart Failure
A Real Threat

2. Etiology Systolic 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)

3. 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)

4. Compensatory mechanisms in heart failure
Compensatory response
Benefecial effects of compensation
Detrimental effects of compensation
Increased preload(through Na&water retention)
Optimize stroke volume
Pulmonary and systemic congestion and edema formation
Increased MVO2
Vasoconstrition
Maintain blood pressure in face of reduced CO
Shunt blood from nonessential organs to heart and brain
Increased afterload
Tachycardia (due to SNS activation)
Helps maintain cardiac output
Shortened diastolic filling time
ß1-receptor downregulation &desensatization
Arrhthemia
Myocardial cell death
Ventricular Hypertrophy and remodeling
Helps maintain CO
Reduces myocardial wall stress
Decreased MVO2
Diastolic & systolic dysfunction
Myocardial cell death &ischemia &arrhythemia

7. 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.

8. Classification(AHA) Stage Description A B C D
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

9. Treatment

10. Treatment (Con,t) Stage A: Treat Risk factors: Control Glucose level
Control BP
Dyslipidemia
Thyroid disorder
Valvular disease
Avoid drugs which aggravate heart failure

11. Class II Wet Sx Diuretics (loop) + ACE Dry Sx
ACE  + B  (no diuretics)
Sx resolve
Sx don’t resolve
improved
didn’t improve
give digoxin
Spironolactone + B
digoxin
Spironolactone
improved
didn’t improve
improved
didn’t improved
Give B
Spironolactone
Plan B
Spironolactone
Plan B

12.  directly give ACE inh & Loop
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

13. (see if you hospitalize him or not)
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)

14. if not improved Plan B Stage D or worsening Stage C
Hospitalize your Px.
Optimize drug therapy
if not improved
wet
dry
Give 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
not improved
Tissue hypoperfusion
SBP < 80
Worsening renal function
↙Na  hypervolemia dilutional hyponatremia cyanosis
Hemodynamic Monitoring
(monitor BP, temp., CO, T0).

15. 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)

16. Treatment (Con,t) Stage B=Class I ACE inhibitors Or
Beta blocker if recent or previous MI& reduced ejection fraction due to remodeling
Stage C Є class II,III,&IV
ACE inhibitors & Beta blockers In all Px
If Sx still exist Or EF still low Add Digoxin
When symptoms resolves add aldactone

17. Role of drugs in CHF

18. Angiotensin converting enzyme inhibitors
Cardioprotctive effect
Preload & Afterload
RA system less Na/water retention
bradykinin level vasodilation
mortality, hypertrophy, & fibrosis

20. 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
tid
50tid No
Renal 2
Enalapril
Renitec
2.5-40
bid
10bid
Yes 10
Lisinopril
Zestril
5-40 qd
10qd 12
Ramipril
Tritace
qdorbid
5bid
yes
9-18

21. BETA BLOCKERS Mortality Vasoconstriction
Carvidilol alpha+beta blocker &antioxidant effect
Bisoprolol
Metoprolol

22. 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

23. Clinical Pharmacokinetics of Digoxin
Oral bioavailability:
Tablets %
Elixir %
Capsules %
Onset of action:
Oral hr
IV hr
Terminal half –life:
Normal renal function hr
Anuric patient days
Volume of distribution L/kg
Fraction unbound in plasma %
Fraction excreted unchanged in urine %

24. 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

25. 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
T1/2 hr hr

26. 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

27. 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

28. New Drug Investigation
Natriuretic Peptides:
Atrial Natriuretic Peptides (ANP)
Brain Natriuretic Peptides (BNP
C-type Natriuretic Peptides (CNP)
Neseritide:
Recombinant BNP

29. New Drug Investigation
Omapatrilat:
Vasopeptidase Inhibitor
ACE inhibitor
INH neutral endopeptidas
Bradykinin & NP
SE: Angiodema

30. Precipitating factors in Heart failure Decompensation
Noncompliance with drugs or diet
Cardiac Ischemia
Inadequate therapy at time of admission
Cardiac arrhythmias
Uncontrolled hypertension

31. Thank YOU