General treatment concepts of congestive heart failure

Heart Failure Pathophysiology and potential therapeutic targets

Valvular leaks(mitral valve regurgitation) leads to

Kidneys retain sodium and water, Increased BP, Increased venous return →

Increased diastolic pressure/myocardial stress: Volume overload, Eccentric hypertrophy, Ventricular dilation →

Increase in: Atrial pressure, Venous pressure, Capillary pressure, Oedema, effusion

What are the therapeutic goals in cases of systolic dysfunction?

Increase cardiac output

Onset of cardiac diseases - diastolic dysfunction

Decreased ventricular compliance →

Increased diastolic pressure →

Increased pressure transmits to Atrium, Veins, Capillary beds behind affected ventricle →

Results in: Transudation of fluid out of the capillary beds and into oedema and effusion

What are the therapeutic goals in cases of diastolic dysfunction?

Increase cardiac output

1.Reducing preload and/or afterload

Treat Hypertension →

Diuretics

Vasodilators

2) optimize cardiac performance

Antiarrhythmics

+inotropes

+lusitropes

3) use of neurohormonal modulators

Effect on kidney and heart →

Angiotensin R antagonists

ACE inhibitors

Beta blockers

Aldosterone R antagonists

Chart of Cardiac drugs

Loop diuretics - furosemide

Reduction of volume overload - increase in urine production

Thiazide diuretics - hydrochlorothiazide

Reduction of volume overload - increase in urine production

Potassium sparing diuretics - spironolactone

Reduction of volume overload - increase in urine production

Mechanism of diuretics

Positive inotropic medications

↑ strength of heart muscle contraction

↑ stroke volume

↑ cardiac output

digoxin

Cardiac glycosides

Positive inotropic medication

Pimobendan

Positive inotropic medication

Phosphodiesterase inhibitors

Calcium sensitisers

dopamine

noradrenaline

Positive inotropic medication

β-adrenoceptor agonists -

Digoxin cellular effects

1. Reversible inhibition of the sodium-potassium ATP-ase pump

2. Increased intracellular Na+

3.Inhibiting effect on the Na+-Ca2+ exchanger

4.Increase in intracellular Ca2+

5.Increased contraction force

Digoxin neurohormonal effects

1. Parasympathomimetic action on the sinoatrial(SA) node and atrioventricular (AV) node

2. Slowing conduction in SA and AV nodes

3.Increase in refractory period

Digoxin adverse effects

1. Dose-dependent

2. GI upsets - vomiting and diarrhea

3.Neurological signs

4.Arrhythmias and death

5.Dosed on lean body weight

Pimobendan

Positive inotropy - increase cardiac contractility

Increased sensitivity to calcium

Inhibition of phosphodiesterase

Inodilators effects

2. Vasodilation - balanced vasodilation

3. Positive lusitropy - increased rate of myocardial relaxation

Inodilator adverse effects

well tolerated and safe.

Contraindicated in patients with outflow tract obstruction