HCM is the most common inherited heart condition occurring in 1:500 individuals in the
general population. Left ventricular outflow obstruction at rest or after provocation occurs in 2/3 of
HCM patients and is a frequent cause of limiting symptoms. Pharmacologic therapy is the first-line
treatment for obstruction, and should be aggressively pursued before application of invasive therapy.
Beta-blockade is given first, and up-titrated to decrease resting heart rate to between 50 and 60 beats
per minute. However, beta-blockade is not expected to decrease resting gradients; its effect rests on
decreasing the rise in gradient that accompanies exercise. For patients who fail beta-blockade the addition
of oral disopyramide in adequate dose often will decrease resting gradients and offer meaningful relief of symptoms.
Disopyramide vagolytic side effects, if they occur, can be greatly mitigated by simultaneous administration of oral
pyridostigmine. This combination allows adequate dosing of disopyramide to achieve therapeutic goals. Verapamil utility
in obstructive HCM with high resting gradients is limited by its vasodilating effects that can, infrequently, worsen gradient
and symptoms. As such, we tend to avoid it in patients with high gradients and limiting heart failure symptoms. In a
head-to-head comparison of intravenous drug administration in individual obstructive HCM patients the relative efficacy
for lowering gradient was disopyramide > beta-blockade > verapamil. Severe symptoms in non-obstructive HCM are
caused by fibrosis or severe myocyte disarray, and often by very small LV chamber size. Severe symptoms caused by
these anatomic and histologic abnormalities, in the absence of obstruction, are less amenable to current pharmacotherapy.
New pharmacotherapeutic approaches to HCM are on the horizon, that are to be evaluated in formal therapeutic trials.