(Circulation. 1999;99:344-347.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Changes in Left Ventricular Diastolic Function 6 Months After Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy
From the Department of Medicine, Cardiology Section, Baylor College of Medicine, Houston, Tex.
Correspondence to Sherif F. Nagueh, MD, Cardiology Section, Baylor College of Medicine, 6550 Fannin, SM1246, Houston, TX 77030. E-mail sherifn{at}bcm.tmc.edu
Abstract
Background—Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown.
Methods and Results—HOCM patients (n=29) had Doppler
echocardiography at baseline and 6 months after
NSRT to evaluate changes in LV volume, pre–A-wave pressure,
early diastolic mitral annulus velocity (Ea) by tissue
Doppler, and 
. At 6 months, a significant reduction in LVOT
gradient (from 53.6±15 to 6±5 mm Hg; P<0.001) was
accompanied by improvement in exercise duration (from 284±147 to
408±178 seconds; P=0.04) and New York Health Association
class (from III to I; P<0.001). Pre-A pressure (18±6 to
14±5 mm Hg; P<0.01) and (62±8 to 51±8 ms;
P<0.01) decreased, whereas Ea (5.8±1.8 to 8±1.8 cml/s;
P<0.01) and LV end-diastolic volume (117±16 to
130±22 mL; P<0.01) increased.
Conclusions—NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.
Key Words: diastole • cardiomyopathy • hypertrophy • echocardiography
Patients with hypertrophic obstructive cardiomyopathy (HOCM) usually have increased LV/left ventricular filling pressures and dyspnea secondary to impaired relaxation and compliance. This is related to the contraction load imposed by LVOT obstruction, reduced diastolic filling loads, and asynchrony in the load distribution and (in)activation.1 Nonsurgical septal reduction therapy (NSRT) successfully relieves the obstruction and improves symptoms in HOCM patients.2 3 4 5 However, its effects on LV diastolic function are unknown. We therefore evaluated LV global and regional diastolic function 6 months after NSRT.
Methods
Our institutional review board approved the protocol, and all
patients gave written informed consent before participation. Subjects
had a basal septal thickness 
1.5 cm, with LVOT dynamic gradient
(anterior mitral leaflet septal contract) 40 mm Hg at rest or
60 mm Hg during dobutamine (to 40 µg ·
kg-1 · min-1).
Twenty nine consecutive HOCM patients who were symptomatic
despite maximal medical therapy underwent NSRT (some patients were
included in a previous report5 ). Before NSRT,
2-dimensional and Doppler echocardiography were
performed simultaneously with LV
catheterization. LV pre-A pressure was measured before
the A-wave increase in LV pressure. This pressure relates well to
pulmonary capillary wedge pressure6 and thus was
used in lieu of it. LV systolic pressures (LVS; peak [LVSp]
and at aortic valve closure) and LVOT gradient were measured with Medex
transducers (0 at midaxillary line). After angiography, an 8F guiding
catheter was engaged in the left main artery, then a 2x10-mm balloon
was advanced over a 0.014 standard wire into the septal perforator
branch of the left anterior descending artery and inflated. Albunex was
next injected into the balloon central lumen with
simultaneous echocardiographic imaging to
target ethanol delivery to the culprit septal segments. Subsequently,
ethanol (2 to 5 mL) was injected into the inflated balloon lumen and
left for 5 minutes. With a residual gradient 16 mm Hg, other
septal branches were injected similarly.
Echocardiography and treadmill testing (n=23, Bruce
protocol) were repeated 6 months later.
Echocardiographic Studies
Parasternal and apical views were obtained by use of an Acuson
or Hewlett-Packard ultrasound system. With pulse Doppler, 5 cardiac
cycles were recorded at the mitral annulus and tips in the
4-chamber view. Isovolumic relaxation time (IVRT: between mitral valve
tips and LVOT) (Figure 1
) and LVOT peak
velocity were recorded by continuous-wave Doppler. The
velocities at the mitral annulus lateral corner and septal base (5
cycles) were recorded9 with tissue Doppler (TD)
(Figure 1).
|
Echocardiographic Analysis
A single observer blinded to all data performed the
analysis off-line using a Digisonics station (with
2-dimensional and Doppler software). Measurements included LV
volume,7 septal base thickness (parasternal views), and
septal area opacified by Albunex during NSRT. Mitral inflow was
analyzed for peak early diastolic (E) and late
diastolic (A) velocities, acceleration time of E (AT-E:
onset to peak E), and deceleration time of E and A (DT-E, DT-A, by
linear extrapolation to baseline). IVRT (aortic valve closure to
mitral flow onset) was derived as previously described.6 8
We noted in this HOCM population that early diastolic
mitral annulus velocity at (Ea) the lateral corner has a weak inverse
relation to filling pressures and is not influenced by pressure
changes. Septal base systolic, early diastolic, and
late diastolic velocities were measured. LVOT peak gradient
was derived by the modified Bernoulli equation10 : maximal
gradient=4v2, where v (m/s) is peak LVOT velocity. The time
constant of LV relaxation was derived as: =IVRT/(Ln LVS-Ln
pre-A).11 Pressures were obtained at baseline invasively.
At 6 months, they were estimated noninvasively. LVSp was derived as
systolic blood pressure+LVOT gradient. We previously noted E/Ea
to relate well to pre-A pressure (r=0.76; pre-A
pressure=3.3+[1.1(E/Ea)]; P<0.01) and to adequately
detect LV filling pressure changes (r=0.8, SEE=3
mm Hg; P<0.01) in HOCM patients. This equation was
validated in 17 additional patients with HOCM: when it performed
equally well (r=0.82; P<0.01; SEE=3
mm Hg). Accordingly, we used it for pre-A pressure estimation at 6
months. Was also calculated at baseline noninvasively (see above).
Furthermore, it was calculated assuming no change in pre-A pressure at
6 months.
Statistics
Baseline and 6-month Doppler data were compared by paired
t test, and functional class changes were evaluated with
Wilcoxon signed rank test. Regression analysis
correlated changes with changes in LV volumes, LVOT gradient,
septal thickness, New York Heart Association (NYHA) class, and exercise
duration. Significance was set at P
0.05.
Results
Mean age was 53.6±15 years (range 29 to 83) (15 women). Four
patients were in NYHA class IV, with 25 in class III; 23 had angina;
and 18 had presyncope or syncope despite maximal therapy with
ß-blockers, verapamil, disopyramide, and
amiodarone, or sotalol. All but 4 had a resting LVOT gradient
(56±29 mm Hg; range 15 to 120 mm Hg), and 4 had
dobutamine-provocable gradients. Patients had hyperdynamic
ventricles without severe mitral regurgitation.
Satisfactory mitral inflow and TD of mitral annulus and septal base
were obtained in all. At baseline, invasively derived (62±8 ms)
correlated well with noninvasive (r=0.8; SEE=9 ms).
Changes in Functional Status and Hemodynamics
AT 6 months, 24 patients were in NYHA class I, 4 were in class II,
and 1 was in class III (this patient had no change in gradient, pre-A
pressure, and ), with 14 taking ß-blockers or
verapamil (lower doses). NYHA class decreased significantly
(III to I; P<0.001). Five patients still had angina
(P<0.001 versus baseline). In those who were able or agreed
to exercise at baseline, exercise duration increased (from 284±147 to
408±179 seconds; P=0.04). There were no malignant
ventricular arrythmias or deaths in the 29 patients, and 6
were AV sequentially paced at 6 months. LVOT gradient was significantly
reduced (6±5 mm Hg; P<0.001) as were LVS and pre-A
(18±6 to 14±5 mm Hg) pressures (both P<0.01).
Was shorter at 6 months (Figure 2A)
(62±8 to 51±8 ms, P<0.01; for baseline noninvasive ,
P=0.03), with similar results observed using an unchanged
pre-A pressure at 6 months (P=0.035). Shortening of
related to LVOT gradient reduction (r=0.53;
P=0.05). The changes in functional class and exercise
duration were related to shortening (r=0.54 and -0.67,
respectively; both P=0.03) and pre-A pressure reduction
(r=0.48 and -0.58, respectively; both
P=0.04).
|
Changes in LV Structure and Filling
LV end-diastolic volume increased (from 117±16 to
130±22 mL; P<0.01), and septal base thickness decreased
(from 2.06±0.4 to 1.5±0.4 cm; P<0.001) at 6 months. IVRT
(Figure 2B
) and AT-E (Figure 2C) were significantly shorter, whereas E,
A, E/A, and DT-E were relatively unchanged
(Table). DT-A (Figure 2D) was
significantly longer at 6 months. Lateral mitral annular Ea increased
(P=0.001), and E/Ea decreased (from 12.9±5.2 to 9.8±4.7;
P<0.01) (Figure 2E). Shortening was also related to
septal thickness reduction (r=0.58; P=0.01) and
LV volume increase (r=-0.57; P=0.05).
|
Changes in Septal Base Function
The systolic velocity was lower after NSRT (6.5±1
to 4.5±1 cm/s; P<0.01) and was related to LVOT gradient
reduction (r=0.35; P=0.05). Early (5.3±1.4 to
5.2±1.5 cm/s; P=0.2) and late (7.8±2 to 8±2.5
cm/s; P=0.8) diastolic velocities were
unchanged. Septal Ea change was directly related to risk area
(r=0.57; P=0.05).
Discussion
HOCM patients frequently have dyspnea, largely resulting from
diastolic dysfunction (a nearly universal feature), with
myocardial ischemia contributing some to the
diastolic dysfunction and dyspnea.1
Symptomatic HOCM patients are usually treated first with
verapamil or ß-blockers. These drugs may favorably modify
LV diastolic function through their anti-ischemic
actions. However, their benefit is present only in a select group
of patients, with verapamil prolonging and increasing
filling pressures in some patients. Accordingly, some patients remain
symptomatic despite maximal medical therapy, with the only
options left being pacemaker therapy or septal myectomy with its
attendant morbidity and mortality. NSRT was recently introduced as an
alternative therapy for such patients, and as shown by us and
others,2 3 4 5 it significantly reduces the LVOT gradient and
improves cardiac symptoms. This improvement is probably related to the
diastolic function changes, LVOT gradient reduction,
decrease in severity of mitral regurgitation, and a
decrease in the frequency or severity of ischemia. The
present study explores the effects of NSRT on LV
diastolic function. NSRT favorably influences a number of
factors that impair relaxation in HOCM. First is the systolic
contraction load incurred with obstruction, which delays and slow
relaxation.1 By relieving the obstruction, NSRT results in
an improvement in relaxation. In fact, the shortening of in our
patients was directly related to the LVOT gradient reduction. The
shorter IVRT and AT-E and the higher lateral annular Ea reflect this
improved relaxation, given the shorter and the lower pre-A
pressure. The lengthening load that operates in early
diastole is another factor. It enhances filling by
promoting myocardial fiber lengthening. In HOCM patients, this
load (and tension, where tension=pressurexradius/2xthickness) is
reduced because of LV hypertrophy and the small
ventricular dimensions that are frequently
present.1 After NSRT, septal thickness decreases and
LV end-diastolic volume increases. Accordingly, wall
tension increases, promoting LV filling. Furthermore, outflow
obstruction relief results in a higher aortic diastolic
pressure along with a lower LV end-diastolic pressure. Both
changes increase coronary perfusion pressure and blood flow,
thus possibly minimizing ischemia and increasing the
coronary filling load, a load that aids relaxation during IVRT.
DT-A is a measure of LV end-diastolic pressure and shortens
with higher pressure8 ; this parameter became
significantly longer after NSRT, suggesting lower
end-diastolic pressures after the procedure. Interestingly,
lower filling pressures were observed after surgical myectomy, a
procedure that reduces septal thickness and increases LV
dimensions.12 NSRT also appears to alter the regional load
differences in HOCM. By ameliorating LVOT gradient and increasing
ventricular volume, NSRT decreases the contraction load and
increases the lengthening load applied to the LV inflow territory,
minimizing the inflow and outflow tract asynchrony and possibly
contributing to the improvement in global LV relaxation. This occurs at
the expense of reduced systolic function (and
diastolic function) of the septal base afterward. In
addition, NSRT increases LV compliance. This conclusion is supported by
lower filling pressures in the face of the end-diastolic
volume increase and may be the result of the mass volume ratio decrease
and improvement in LV relaxation after NSRT.5
Acknowledgments
This study was supported by grants from the T.L.L. Temple Foundation, Lufkin, Dunn Foundation, and Methodist Hospital Foundation, Houston, Tex.
We thank Anna Zamora for expert secretarial assistance and Eula Landry for help with the graphs.
Footnotes
Guest Editor for this article was William H. Gaasch, MD, Lahey Clinic, Burlington, Mass.
Received July 13, 1998; revision received October 22, 1998; accepted November 3, 1998.
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