Qualitative and quantitative comparison of systolic velocity
profiles between CO, HOCM, and aortic stenosis (Figures 6 and 7)
Qualitatively , the LVCO ICG spectral Doppler profile has a
similar profile to the HOCM Doppler profile (Figure 6) and hence may be
confused. The HOCM LVOT initial acceleration is slow followed by a
second phase of acceleration which is faster as also seen with the
spectral profile of the ICG associated with LVCO. In the LVCO patients
with higher gradients, however (Figure 2), the second phase of
acceleration appears steeper and faster than seen with the profile of
the HOCM associated LVOT gradient. Indeed, the second phase of
acceleration of the ICG spectral profile appears almost exponential and
can be compared to one side of an inverted half pipe skateboard ramp
(Figure 6).
To quantify the difference between the profiles, we assessed the
ratio between peak and mean gradients. Consistent with the exponential,
scooped-out appearance of the second acceleration portion of the
profile, the ratio of peak to mean gradient was significantly higher in
the LVCO than HOCM patients: 3.5 (range 2.0 to 6.1) vs 2.4 (range 1.8 to
3.25) respectively (p <0.0001). The difference between LVCO
and HOCM peak/mean gradient ratios was even more marked when comparing
the 25 patients with LVCO ICGs greater than 35 mmHg (which may be more
clinically relevant, as at that magnitude of gradient there may be more
confusion with LVOT gradients associated with HOCM) as in this subgroup
the mean ratio of peak/mean gradient was 3.85 (range 2.68 to 6.1). In
23/25 patients with HOCM the ratio was between 2 and <3; in
23/25 patients with LVCO and ICGs greater than 35 mmHg, the ratio was 3
or higher.
For comparison, we assessed this ratio in patients with severe AS, and
the ratio was significantly lower in this group at 1.68 (range 1.46 to
2.05) reflecting that the AS spectral profile is the most symmetrically
parabolic contour between LVCO, HOCM and AS. In 24/25 patients with AS
the peak/mean gradient ratio was < 2 (Figure 7).
Discussion
This is the first study, to our knowledge, to assess the quantitative
pathophysiologic mechanism of the ICG. This is also the first study to
provide a quantitative method to distinguish the LVOT spectral Doppler
profile associated with HOCM from the intracavitary gradient spectral
profile associated with cavity obliteration. We are not aware of any
major current echocardiography textbook that details the specific nature
of the intracavitary gradient associated with LVCO.
In our laboratory, approximately 1% of patients had the term “cavity
obliteration” directly entered on the report (it is not currently a
“check off” option). Most patients with LVCO, in the absence of other
significant cardiac conditions, have intracavity gradients less than 36
mmHg. The spectral profile associated with lower gradients differs from
the patients with higher gradients. The spectral profile associated with
the lower gradients is more triangular with a slow acceleration and a
relatively fast deceleration. The profile of the higher gradients has an
elongated fast acceleration tacked onto the initial slower acceleration,
followed by a similar fast deceleration to the baseline (Figure 2).
Higher ICGs are associated with greater extent of cavity
obliteration, as defined by the percentage of the end diastolic LV
cavity length obliterated in systole and more prolonged LVCO, defined as
the duration that the LV walls are apposed. It seems logical that
other factors such as the longitudinal, radial and circumferential
strain rate velocity and degree of apical twist contribute, in addition
to the extent and duration of apposition, toward determining the
magnitude of the gradient. As an analogy, consider the noise made when
you clap your hands; it is the speed of apposing the hands as well as
the surface area of hands that are apposed that correlate with the noise
produced. Thirdly, higher gradients are seen in those with smaller end
diastolic and end systolic cavity dimensions.
These correlations of extent and duration of LVCO with the
ICG are analogous to the previously demonstrated quantitative andtemporal relationships between SAM and the LVOT gradient that
showed a significant correlation between the duration and timing of SAM
septal contact and the LVOT gradient4,5. Unlike SAM
associated gradients, which represent LVOT obstruction between the body
of the LV cavity and the LVOT, the ICG gradients are presumed to arise
from the gradient between the LV apex and the body of the LV beyond the
virtually closed off apical portion of the LV. That the ICG occurs when
the LV is virtually closed suggests that in these patients, the overall
hemodynamic significance to the LV cavity is minimal, especially
compared to LVOT gradients that occur in HOCM while the LV is still
emptying 4,5. They do, however, imply high pressures
at the LV apex.
In this regard, and to show the difference between LVOT gradients
associated with HOCM and ICG gradients associated with LVCO, we studied
another 25 patients with HOCM and severe SAM. We chose to compare the
LVCO patients with gradients of 36 mmHg or greater, as that level the
size of the gradient lies within the realm of the gradients seen with
severe SAM where the confusion may arise.
The distinction in peak/mean gradient ratios between LVCO and HOCM may
be helpful to determine quantitatively the origin of a high systolic
velocity obtained from the apex when the origin is uncertain or the
shape of the spectral profile is ambiguous or unclear qualitatively as
the ICG and LVOT spectral profiles are somewhat similar with an initial
slow acceleration followed by a second faster rate of acceleration.
Meticulous placement of the continuous wave Doppler cursor through the
body of the left ventricle to separate the LVOT profile from the LCO
profile is not always possible, especially when LV cavity size is small
or the cavity is not perfectly vertically aligned to the apical acoustic
window. These different origin gradients may also be confused because of
depth ambiguity, a known phenomenon of continuous wave Doppler, where
spectral profiles from MR, LVOT and ICG may overlap (Figure 8).
Confusion may also arise as Valsalva maneuver increases both the ICG and
the LVOT gradient (Figure 9). We have noticed that some of our less
experienced sonographers may confuse LVOT spectral profiles with LVCO
ICG profiles, perhaps because, in addition to the foregoing, patients
with HCM and LVCO have similar hyperdynamic left ventricular
contraction. The obstructed LVOT gradient spectral profile in HOCM has
been likened to a dagger, presumably due to its pointed appearance.
Daggers, however, have many different shapes (Figure 6), and this is an
imprecise way of identifying a profile, especially as the ICG spectral
profile, also has a “point” and resembles a dagger. The ICG gradient,
particularly in those with a peak gradient of more than 35 mmHg,
however, has a distinctive appearance and resembles an inverted
skateboard half-pipe slope (Figure 6). The quantitative index of
separating the contours as described by the peak/mean ratio may be
especially helpful clinically when the origin of the high velocity is in
doubt. The distinction has clinical relevance, because treating the ICG
gradient as if it were an LVOT gradient associated with HOCM11, with measures such as disopyramide, septal
ablation or surgical myectomy, would be inappropriate, and potentially
harmful although there is one case report 12 of using
cibenzoline to reduce the intracavitary gradient from 65 to 35 mmHg with
improvement in dyspnea.
The lower peak/mean gradient ratio for HOCM patients (2.4) than for the
LVCO patients (especially those with peak gradients equal to or more
than 36 mmHg) (3.8) lends weight to the known hemodynamic and clinical
significance of LVOT gradients. For example, a peak HOCM LVOT gradient
of 64 mmHg translates to a mean gradient of approximately 27mmHg,
whereas a peak ICG gradient of 64 mmHg is equivalent to a mean gradient
of 17 mmHg.
As a further comparison, as a
contrast, and because depth ambiguity may overlay systolic velocity
profiles obtained from the apex simultaneously, we also looked at 25
patients with severe AS. The peak/mean gradient ratio was lowest in this
group, at 1.7, consistent with the more symmetrically shaped parabolic
contour (Figure 6) associated with the AS spectral profile. For an
equivalent peak gradient of 64 mmHg, there would be a mean gradient of
38 mmHg.
The clinical relevance of these intracavitary gradients is uncertain. It
seems plausible that the higher intracavitary gradients may have
significance, as the resulting high apical pressures, and the potential
accompanying apical ischemia 9, provide a possible
reason for the association between LVCO and adverse outcomes of the
combined end-point of sudden death and potentially lethal arrhythmic
events, in patients who also have HOCM 13. These high
apical pressures are also the presumed etiology for the development of
apical aneurysms in patients with HOCM and coexisting
LVCO14. Furthermore, intense catecholamine excess,
which may produce severely high apical pressures secondary to LVCO, may
be the cause of the apical wall motion abnormality seen in Takotsubo
cardiomyopathy 15 and the LV wall motion abnormalities
associated with subarachnoid hemorrhage 16.
Conclusion
Our study provides insight into the mechanism of the ICG in patients
with LVCO. Just as SAM is not an all-or-none phenomenon, ranging from
late and minimal septal contact which produces a small LVOT gradient, to
early and prolonged septal contact that produces a large LVOT gradient4,5, so too LVCO is not an all-or-none phenomenon.
Greater extent, and longer duration of obliteration are associated with
higher intracavitary gradients.
Our study also highlights the different qualitative differences between
the Doppler spectral profiles of HOCM and LVCO. For the first time, this
study reports a quantitative method of differentiation by using the
ratio of peak/mean gradient. The difference between the profiles has
clinical implications as the ICG associated with LVCO may be confused
with the LVOT gradient of HOCM, and treatment for the former as if it
were the latter would be inappropriate and potentially harmful.
Limitations of the study
This is a retrospective study. A prospective study performing
simultaneous echocardiographic and Doppler studies would provide more
insight into the pathophysiology between LVCO and the resulting ICG.
Three dimensional echocardiographic assessment of apical obliteration
might provide more accurate spatial quantification of the degree of
obliteration. In addition, strain measurements of LV shortening would
likely be illuminating.
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Figure Legends
Figure 1
2D echo apical 4 chamber frames in a LVCO patient with peak ICG of 2.1
mmHg. End diastolic (ED) frame at top left. Apical length from apex to
mitral annulus is 5.6 cm. Cavity obliteration first occurs in frame 7,
and has already ended by frame 9 (post CO) which shows a tiny gap
between the LV walls; therefore only 2 frames; 7 and 8: are obliterated.
At a frame rate of 50 Hz, this equals 20 msec per frame, and therefore
obliteration lasts 2 x 20 msec, or 40 msec. End obliteration apex to
annulus length in frame 8 is 2.9 cm. Percent obliteration = 5.6-2.9/2.9
= 48%.
Figure 2
Left panel: upper – typical spectral profile in a patient with a small
peak ICG (yellow arrow): lower – typical spectral profile in a patient
with a higher peak ICG (green arrow)
Right panel: schematic of the spectral profile in a patient with a small
ICG gradient (A) with an initial slow acceleration (1) that speeds up
(2) and then decelerates (3). For the higher gradients (B), the
acceleration continues (4) to a peak and then rapidly decelerates (5).
Figure 3
Peak ICG gradient vs peak/mean ratio for all 87 patients
Figure 4
Upper graph: Peak ICG vs % obliteration in 65 patients; Lower graph:
Peak ICG gradient vs time in obliteration in 65 patients
Figure 5
Upper panel: Apical length % obliteration in patients subgrouped into
peak gradients <36 mmHg and =/> 36 mmHg; Lower
panel: Time in obliteration in patients subgrouped into peak gradients
<36 mmHg and =/> 36 mmHg
Figure 6
Left panel: AS, HOCM, and ICG profiles. Right panel: real life images of
a parabola (inverted city arch), daggers, and inverted half pipe
skateboard ramp.
Figure 7
Comparison of peak/mean gradients between patients with AS, HOCM, and
LVCO
Figure 8
Spectral continuous wave Doppler profile in a patient (not in the study)
with overlapping (in order of peak velocity) mitral regurgitation (green
arrow), SAM associated LVOT obstruction (blue arrow), and LVCO (yellow
arrow), demonstrating depth ambiguity
Figure 9
Patient with LVCO and ICG at rest (yellow arrow - left panel) that
doubles with Valsalva maneuver (green arrow – right panel)
Figure 1
2D echo apical 4 chamber frames in a LVCO patient with peak ICG of 2.1
mmHg. End diastolic (ED) frame at top left. Apical length from apex to
mitral annulus is 5.6 cm. Cavity obliteration first occurs in frame 7,
and has already ended by frame 9 (post CO) which shows a tiny gap
between the LV walls; therefore only 2 frames; 7 and 8: are obliterated.
At a frame rate of 50 Hz, this equals 20 msec per frame, and therefore
obliteration lasts 2 x 20 msec, or 40 msec. End obliteration apex to
annulus length in frame 8 is 2.9 cm. Percent obliteration = 5.6-2.9/2.9
= 48%.
Figure 2
Left panel: upper – typical spectral profile in a patient with a small
peak ICG (yellow arrow): lower – typical spectral profile in a patient
with a higher peak ICG (green arrow)
Right panel: schematic of the spectral profile in a patient with a small
ICG gradient (A) with an initial slow acceleration (1) that speeds up
(2) and then decelerates (3). For the higher gradients (B), the
acceleration continues (4) to a peak and then rapidly decelerates (5).
Figure 3