ronit.zadikany@cshs.org
Corresponding author
Dr Charles Pollick
Smidt Heart Institute, Cedars Sinai Medical Center, 127 S San Vicente
Blvd, Los Angeles, CA, 90048
Phone: 310 985 2220
charles.pollick@cshs.org
This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.
Abstract
Controversy surrounds the cause of the pressure gradient in patients
with hypertrophic obstructive cardiomyopathy (HOCM). Left ventricular
cavity obliteration (LVCO) was first described as the cause of the
gradient but subsequently systolic anterior motion (SAM) of the mitral
valve has been established as the cause.
Nevertheless, the two gradients, though different in origin and
significance, share similar characteristics. They both have a similar
“dagger” profile, are obtained from the cardiac apex, are associated
with a hyperdynamic left ventricle, and the gradients are worsened by
Valsalva. The distinction has clinical relevance, because treating the
intra cavitary gradient (ICG) of LVCO as if it were a SAM associated
gradient associated with HOCM would be inappropriate and possibly
harmful.
To clarify the cause and characteristics of the ICG in patients with
LVCO in patients without HOCM we assessed the extent and duration of
cavity obliteration and for differentiation we compared the spectral
profiles with patients with HOCM and severe aortic stenosis (AS).
Higher ICG is associated with greater extent and more prolonged
apposition of LV walls, and smaller left ventricular cavity size. The
spectral profile of patients with AS, HOCM and LVCO are differentiated
by the peak/mean gradient ratios of 2 or less, 2-3, and 3 or greater,
respectively in > 90% of patients.
Most patients with LVCO without HOCM or severe LVH have an ICG
< 36 mmHg. The magnitude of ICG is quantitatively associated
with extent and duration of LVCO. Spectral profiles of severe AS, HOCM,
and LVCO can be differentiated by the peak/mean gradient ratio.
Introduction
Left ventricular cavity obliteration (LVCO), defined as obliteration of
the apex in systole on angiography, was first described1 in 1965 and proposed as the cause of the
intraventricular pressure gradient accompanying hypertrophic
cardiomyopathy. It was subsequently documented 2 that
cavity obliteration can be seen in states other than hypertrophic
cardiomyopathy. Another school of thought 3 opined
that the pressure gradient in hypertrophic cardiomyopathy was due to
left ventricular outflow tract (LVOT) obstruction. Following decades of
study, it is now generally agreed that the characteristic gradient in
hypertrophic obstructive cardiomyopathy (HOCM) is a dynamic subaortic
pressure gradient due to LVOT obstruction from systolic anterior motion
of the mitral valve (SAM) 4,5. These LVOT gradients,
when high, are accompanied by exercise intolerance which can be
mitigated by pharmacologic or interventional methods to ameliorate the
gradient 6. At first, the intracavitary gradients
(ICG) accompanying LVCO were dismissed as either not obstructive1 and therefore not important, or possibly an artifact
of “catheter entrapment” 3, and therefore also not
clinically relevant. Intracavitary gradients with cavity obliteration
have been demonstrated during dobutamine stress echocardiography and
have, paradoxically, been associated with favorable, rather than
adverse, outcomes 7,8. More recently, however, apical
cavity obliteration has been associated with adverse outcomes, and has
been implicated in the pathogenetic mechanisms of apical aneurysm in
hypertrophic cardiomyopathy 9. Despite
such studies focusing on cavity obliteration, there is a lack of data
studying the temporal and quantitative relationship between the 2D
echocardiographic occurrence of obliteration and the magnitude of the
ICG.
In addition to the controversy between the mechanism and significance of
the gradient associated with LVCO and that of HOCM, the two gradients
may be confused for a variety of reasons. They share a similar
“dagger” profile, the gradients are both obtained from the cardiac
apex, both are associated with a hyperdynamic left ventricle, and the
gradients are both worsened by Valsalva. In patients with challenging
echocardiographic windows it may not always be possible to distinguish
the origin of the gradient. Furthermore, they can coexist in patients
with HOCM. The distinction has clinical relevance, because treating the
ICG gradient as if it were an LVOT gradient associated with HOCM would
be inappropriate and possibly harmful.
Methods
Patients
We studied the most recent 100 patients in our echocardiography
laboratory database search with the phrase “cavity obliteration”
(LVCO) entered on a transthoracic echocardiogram report. Out of those
there were 87 patients without severe valve disease, severe
pulmonary hypertension (PA systolic pressure > 65 mmHg),
hypertrophic cardiomyopathy (HCM) (non-obstructive or obstructive),
significant LV hypertrophy (defined as 15 mm or greater wall thickness)
or SAM (moderate or greater) with clearly defined spectral profiles of
intra cavitary gradients. Of these 87 patients, there were 65 patients
(female 48; mean age 74: range 40-101) who also had a well-defined,
non-foreshortened and quantifiable LV cavity demonstrated on apical 4
chamber views. In all patients, cavity obliteration was defined as
obliteration of the LV apical cap with variable extension into the mid
LV cavity. Of these 65 patients; 49 were inpatients, 17 were on
intravenous inotropes, 5 patients had sepsis; there were a variety of
other diagnoses including chest pain, pneumonia, sclerosing cholangitis,
GI bleed etc.
For comparison, the spectral profiles of 25 patients with HOCM and
severe systolic anterior motion of the mitral valve (SAM), and 25
patients with severe AS were assessed and compared with the spectral
profile associated with the ICG seen with LVCO in a subset of 25 of the
65 patients with intracavitary gradients of 36 mmHg or greater.
Transthoracic Echocardiography
Standard transthoracic echocardiographic (TTE) studies were performed,
using standard American Society of Echocardiography guidelines10, in all patients using a commercially available
ultrasound system with phased array transducers (Phillips Medical
Systems)
Echocardiographic measurements
In the standard apical 4 (Ap4) chamber view (Figure 1), the following
measurements were made from one clear representative cardiac cycle: 1.
The end-diastolic length (Ap4d) of the left ventricle from apex
endocardium to the mitral annulus (mm). 2. The length of the obliterated
cavity (Ap4s) from the most basal point of obliteration to the annulus
(mm). 3. The number of frames during which the LV cavity was obliterated
was converted into msec. Frame duration was calculated from the frame
rate in Hz. For example, if the frame rate was 50 Hz, this means that
each frame is 20 msec. If the LV cavity was obliterated for 4 frames at
50 Hz, then that translates to 80 msec of obliteration. Measurements
were made by 2 observers blinded to the ICG mmHg measurements.
Doppler measurements
For the LVCO patients, the intracavitary spectral continuous wave
Doppler profiles were identified. Peak and mean gradients were measured
from one clear representative cycle. For the HOCM and AS patients, one
clear representative spectral aortic and LVOT spectral profile was
identified, and the mean and peak gradients were measured. Measurements
were made by 4 observers blinded to the 2D measurements.
Statistical methods
Standard t-tests for unpaired variables were performed. Standard
Pearson’s correlation coefficients were determined.
Permission to access the echocardiographic images and patient data was
approved by our institutional review board.
Results