- Systolic ejection murmur with characteristic changes during
- Marked asymmetric left ventricular hypertrophy on echocardiogram.
- Normal or hyperkinetic left ventricular systolic function.
The term “hypertrophic cardiomyopathy (HCM)” can best be defined as a condition characterized by idiopathic or unexplained
myocardial hypertrophy that is associated with small or normal ventricular
cavity size, hyperdynamic ventricular function, and diastolic dysfunction.
The qualifier unexplained is used to suggest that
this condition may coexist with hypertension or aortic valve disease,
although the extent and distribution of hypertrophy are disproportionate
to these associated disorders. Therefore, mild-to-moderate hypertension
and mild or moderate aortic valve disease cannot be implicated in
massive asymmetric hypertrophy with hyperdynamic ventricular function.
(The definition also requires hyperdynamic systolic function, a
feature that is rarely absent even in the late stages of HCM.)
Although the condition has also been called idiopathic hypertrophic subaortic stenosis, which connotes a condition characterized by
myocardial hypertrophy without underlying cause, HCM is a more accurate
term because it describes the major feature of idiopathic hypertrophy,
especially in patients with no evidence of subaortic stenosis or intraventricular
HCM can be classified as nonobstructive or obstructive, based on the presence and the location (midventricle or outflow tract)
of intraventricular obstruction. Other classifications may relate
to the distribution of the hypertrophy: asymmetric septal hypertrophy,
disproportionate upper septal thickening, apical asymmetric hypertrophy,
and the like. Such approaches are generally not fruitful except
when apical hypertrophy is localized.
The underlying cause and pathogenesis of this disease are largely unknown. The asymmetric type of HCM is commonly transmitted genetically,
but sporadic cases are also recognized. An abnormal response of
the myocardium to normal catecholamines has been postulated as a
pathogenetic mechanism. The clinical association between HCM and
pheochromocytoma, neurofibromatosis, and lentiginosis suggests a genetic
disorder of neural crest tissue. More recent studies have linked
familial HCM to the cardiac myosin heavy-chain genes on chromosome
14 in some—but not all—families, indicating genetic
heterogeneity. The presence of different disease genes or mutations
within a given gene may account for differences in the clinical
expression of familial HCM.
The pathologic findings at autopsy are remarkably uniform and include massive and generally asymmetric hypertrophy. Both the atria
and the ventricles are affected, with the left ventricle most commonly
involved. The interventricular septum is generally far more massively hypertrophied
than the free wall, a peculiar asymmetric septal hypertrophy that may
provide the necessary hemodynamic conditions to cause a dynamic outflow
obstruction. In this situation, the condition is referred to as
hypertrophic obstructive cardiomyopathy (HOCM). Localization of
such hypertrophy in the midlateral wall may result in midventricular
obstruction and distribution of the hypertrophy in the right ventricular infundibulum
in subpulmonic stenosis. Asymmetric localization of hypertrophy can
involve virtually any segment of the left ventricle, except for
the posterobasal region.
In some patients, the hypertrophy involves primarily the apical portion of the left ventricle (asymmetric apical hypertrophy) rather
than the outflow tract. Such patients exhibit none of the clinical
features of intraventricular obstruction.
Striking pathologic features common to most patients with left ventricular outflow obstruction include fibrous thickening of the
anterior mitral leaflet and plaques in the upper interventricular
septum. The thickening of the anterior mitral leaflet is thought
to represent the result of frequent contact with the interventricular septum.
The endocardial plaques in the septum may be the result of jet lesions distal
to the obstruction. The epicardial coronary arteries are large and
Microscopically, a bizarre and disorderly array of muscle fibers is a striking feature associated with increased connective tissue
that interrupts and crisscrosses the muscle bundles.
At times, the hypertrophied septum assumes a peculiar catenoid shape—convex to the left in the apex-to-base plane, but
concave on its left ventricular surface in the cross sections. This bizarre
and characteristic shape is thought to be responsible for the adynamic
nature of the septum. It is hypothesized that fiber disarray and
local hypertrophy could result from isometric contraction of a catenoid
The integrity of overall systolic function is rather well preserved even in advanced cases; indeed, hypercontractility is a hallmark
of the disorder. The cardiac output is generally normal or mildly
increased; the ejection fraction is often supernormal. Although
global function is well preserved, regional abnormalities may occur;
the upper interventricular septum is often hypodynamic and shows reduced
thickening during systole. The free walls are generally hyperdynamic.
Left ventricular outflow obstruction is dynamic and variable. The variability can be observed within the same cardiac cycle, from
one beat to the next and from one physiologic state to another.
When present, the outflow obstruction begins sometime after the
onset of early uninterrupted ejection. The obstruction is caused
by a sharp systolic anterior motion (SAM) of the anterior mitral
leaflet, which obliterates the outflow space. The actual mechanism
is not clear, although it is likely to be the result of a Venturi
effect from the rapid ejection of a jet of blood through an anatomically narrowed
outflow space. The degree of left ventricular outflow obstruction
can be accentuated by factors that reduce preload (end-diastolic
volume), diminish afterload (arterial pressure), or increase contractility
or heart rate. Echocardiographic recordings have demonstrated that
a sharp systolic anterior motion of the mitral valve is both accentuated
and prolonged by interventions that exacerbate the outflow obstruction,
and vice versa (ie, it is diminished and shortened by interventions
that reduce the outflow obstruction). Some investigators interpret
intraventricular pressure gradients as not indicative of true obstruction
because left ventricular emptying is normal or exaggerated and because
early emptying is unimpeded. These gradients have been attributed
to cavity obliteration. Echocardiographic techniques have elucidated
differences between true gradients resulting from obstruction and
those from cavity obliteration.
Mitral regurgitation is shown by color-flow Doppler echocardiography in more than 90% of patients with HOCM and ...