HEART FAILURE
Clinical Overview

Investigational Pharmacological Strategies

 

Calcium sensitizers⁹

• increase myocardial contractility by increasing intracellular calcium levels
• clinical trial VEST (vesnarinone) have shown increased mortality rates with active treatment
• may impair myocardial relaxation and contribute to diastolic dysfunction

Sodium channel activators⁹

• inhibit the deactivation of the fast sodium channel --> increase intracellular sodium --> activation of the Na+/Ca++ exchanger
• no down-regulation observed
• potential for proarrhythmia

Digoxin-like compounds⁹

• inhibits the Na+/K+-ATPase pump, increasing intracellular sodium concentration, activating the Na+/Ca++ exchange mechanism, increasing intracellular calcium
• currently in phase I and II trials

Neutral endopeptidase inhibitors⁹

• promotes diuresis and opposes RAAS activity through vasodilation
• nesiritide is a genetically engineered form of naturally occurring b-type natriuretic peptide (BNP) which is naturally secreted by a failing heart. Nesiritide has been recommended for approval by FDA advisory commitee.

   

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