Ventricular Pacing With Premature Excitation for

Treatment of Hypertensive-Cardiac Hypertrophy

With Cavity-Obliteration
David A. Kass, MD; Chen-Huan Chen, MD; Maurice W. Talbot, BSN; Carlos E. Rochitte, MD;
João A.C. Lima, MD; Ronald D. Berger, MD; Hugh Calkins, MD

Background—Hypertensive left ventricular hypertrophy with supranormal systolic ejection and distal cavity obliteration
(HHCO) can result in debilitating exertional fatigue and dyspnea. Dual-chamber pacing with ventricular preactivation
generates discoordinate contraction, which can limit cavity obliteration and thereby increase potential ejection reserve.
Accordingly, we hypothesized that pacing may improve exercise tolerance long-term in this syndrome.
Methods and Results—Dual-chamber pacemakers were implanted in 9 patients with exertional dyspnea caused by HHCO.
Intrinsic atrial rate was sensed, and ventricular preactivation was achieved by shortening the atrial-ventricular delay.
Pacing was on or off for successive 3-month periods (randomized, double-blind, crossover design), followed by 6
additional pacing-on months. Metabolic exercise testing, quality-of-life assessment, and rest and dobutamine-stress
echocardiographic/Doppler data were obtained. After 3 months of pacing-on, exercise duration rose from 3246133 to
5886238 s (mean6SD; P50.001, with 7 of 9 patients improving $30%), and maximal oxygen consumption increased
from 13.662.9 to 16.763.3 mL of O2 z min21 z kg21 (P,0.02). Both parameters were little changed from baseline during
the pacing-off period. Improved exercise capacity persisted at 1-year follow-up. Clinical symptoms and activities of
daily living improved during the pacing-on period and stayed improved at 1 year, but they were little changed during
the pacing-off period. Despite similar basal values, stroke volume (P,0.001) and cardiac output (P,0.02) increased
with dobutamine stimulation 2 to 3 times more after 1 year of follow-up as compared with baseline.
Conclusions—Long-term dual-chamber pacing can improve exercise capacity, cardiac reserve, clinical symptoms, and
activities of daily living in patients with HHCO. This therapy may provide a novel alternative for patients in whom
traditional pharmacological treatment proves inadequate. (Circulation. 1999;100:807-812.)
Key Words: pacing n hypertension n exercise n hypertrophy n heart failure

H ypertension is a leading risk factor for the development

of heart failure,1–3 particularly as age increases.2 As
many as 30% to 40% of affected individuals have resting
hypertrophy with cavity obliteration.5,9 Another important
factor, however, is the loss of systolic reserve. Once a heart
ejects to very small cavity volumes at rest, it cannot reduce
ejection fractions .50%, often with varying degrees of left this volume further during stress demands, thereby limiting
ventricular (LV) hypertrophy.4 –7 A subset of these patients its reserve. Cardiac output can increase by the Frank-Starling
develop severe hypertrophy with supranormal function and mechanism, which risks diastolic pressure elevation in a
near-complete distal cavity obliteration during ejection.8 Such hypertrophied heart, or by raising heart rate, which can
patients can experience profound exertional dyspnea and compromise chamber filling time.10 Treatments that increase
fatigue and intermittent pulmonary edema requiring hospital- rest-end systolic volume, such as negatively inotropic
ization. Pharmacological therapy centers around b-receptor b-receptor and calcium-channel blockers,11 may improve
and calcium-channel blockers, diuretics, and angiotensin- reserve, as volumes can again decline under stress.
converting enzyme inhibitors, yet many patients remain Dual-chamber cardiac pacing with atrial sensing and pre-
symptomatic, and alternative approaches are needed. mature ventricular activation (VDD mode) may provide a
nonpharmacological alternative. Pacing generates discoordi-
See p 786 nate contraction and, thus, inhibits cavity obliteration by
Because heart failure symptoms occur in the absence of increasing end-systolic volume.12 To date, studies of pacing
systolic abnormalities, the investigators focused on diastolic therapy in hypertrophied hearts have almost exclusively
dysfunction to explain the pathophysiology of hypertensive targeted patients with asymmetric septal thickening, systolic

Received April 14, 1999; revision received May 21, 1999; accepted May 24, 1999.
From the Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Dr. Chen was a visiting fellow from the National Yang-Ming Medical College and Veterans General Hospital, Taipei, Taiwan.
Correspondence to David A. Kass, MD, Halsted 500, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287. E-mail dkass@bme.jhu.edu
© 1999 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org

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808 Circulation August 24, 1999

Figure 1. Example echocardiogram (4-chamber view, top; short-axis view, bottom) showing marked, concentric, ventricular hypertro-
phy and small distal-cavity volumes at end-systole (arrows) that typified the study population. This near-cavity obliteration without out-
flow obstruction generated higher outflow velocities detected by continuous-wave Doppler. RV and LV indicate right and left ventricle,
respectively, and RA and LA, right and left atrium, respectively.

anterior motion of the mitral valve, and outflow tract obstruc- others were white. All but one had well-documented histories of
tion.13–17 However, this specific pathophysiology is not re- long-term, treated hypertension, spanning 1867 years, with mean
systolic and diastolic arterial pressures of 157629.3 and
quired to observe functional effects from VDD pacing, as
91.9615.9 mm Hg, respectively. The only patient without a docu-
patients with symmetric hypertensive hypertrophy and distal mented hypertension history had not seen a physician for most of her
cavity obliteration (HHCO) display very similar ventricular adult life; however, she had a family history of hypertension and no
mechanical responses.12 history of familial hypertrophic disease.
Accordingly, the present study was designed to test the All patients had concentric hypertrophy, with mean septal and LV
free-wall thicknesses of 18.462.5 and 16.362.2 mm, respectively.
hypothesis that long-term VDD pacing in patients with
None of the patients had significant mitral regurgitation or systolic
HHCO improves metabolic exercise performance and activ- anterior motion of the mitral valve. Mean outflow velocity assessed
ities of daily living. As a secondary goal, we sought to by continuous-wave Doppler was 244.26114 cm/s, which is consis-
determine potential mechanisms for such change, focusing on tent with an intracavitary pressure gradient of 28.5629.7 mm Hg.
alterations in rest and adrenergic-stimulated cardiac reserve. This gradient did not reflect outflow obstruction, but rather distal
cavity obliteration18 and, thus, pressure differences between distal
and basal LV regions.12 Figure 1 shows examples of echocardiogram
Methods images demonstrating marked hypertrophy with near-obliteration of
Patient Group the distal cavity at end-systole.
A total of 10 patients were recruited for the study over a period of 1.5 Long-term medications included calcium-channel blockers (ve-
years. The sample size was set by Food and Drug Administration rapamil or diltiazem 240 to 300 mg/d; n56), b-blockers (atenolol or
guidelines for a feasibility trial. One patient was diagnosed with primary metroprolol 12.5 to 75 mg/d; n55), angiotensin-converting enzyme
hyperaldosteronism on the basis of data obtained shortly after pace- inhibitors (captopril 10 to 40 mg/d; n53), and diuretics (n56).
maker implantation and, therefore, was removed from the trial. Data
from the 9 remaining patients are presented. All patients provided Study Protocol
informed consent, and the study was approved by the Joint Committee Baseline evaluation included metabolic exercise testing, ECG, rest
on Clinical Investigation of the Johns Hopkins Medical Institutions. and dobutamine-stimulated echo/Doppler studies, and the comple-
All patients had documented exertional dyspnea (NYHA class III) tion of a quality-of-life questionnaire (Minnesota Living with Heart
despite hyperdynamic systolic function, with a mean estimated Failure [MLHF]). Patients then received a permanent dual-chamber
ejection fraction of 85.267.1%. Three patients had been previously pacemaker (Thera-DR, Medtronic). The atrial lead was used to sense
hospitalized for pulmonary edema. The mean age of the 4 male and intrinsic sinus rhythm, and the right ventricular apical lead paced the
5 female patients was 5868 years. Four patients were black, and the heart. Premature ventricular activation was achieved by setting the

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 Kass et al Pacing Therapy for Ventricular Hypertrophy 809

pacemaker atrial-ventricular delay shorter than the intrinsic PR

interval (mean delay, 71 ms) (VDD mode). This delay was the
longest possible that achieved full preexcitation at rest and during
ambulation. Confirmation of capture during exercise was made
during metabolic stress testing. At discharge, the pacemaker was
either programmed on (VDD) or off (DDI, with low atrial backup
rate); the choice of pacing mode was randomized and double-
blinded. After 3 months, patients underwent repeat assessment, and
pacing was then switched to the alternate mode for the ensuing 3
months. After follow-up evaluation, pacing resumed in all patients
for an additional 6 months (total, 1 year), at which time final tests
were performed. This final test included a repeat rest and dobuta-
mine-stress echo/Doppler study.
Long-term medications were continued throughout the study, and
medication adjustments by the patients’ primary care physicians
were permitted. During the initial 6 months (blinded, crossover
protocol), changes were made in only 2 patients; the diuretic dose
was increased in both and the atenolol dose was increased (75 to 100
mg/d) in one. As these changes were made shortly after pacemaker
implantation, they applied similarly during much of the protocol
(specifically for on versus off comparisons). During the second
6-month period, the b-blocker dose was doubled in 2 additional
patients, and captopril was converted to lisinopril in a third.

Testing Procedures
Metabolic testing was performed during maximal effort upright
treadmill exercise with continuous ventilatory gas-exchange moni- Figure 2. Exercise capacity in patients with HHCO is enhanced by
toring (MedGraphics). Exercise followed a Naughton protocol, with VDD-pacing therapy. Data are shown at baseline (BASE) and during 2
a fixed treadmill rate of 2.0 mph and incremental elevations of 3.5 consecutive, randomized 3-month periods of pacing on (P-ON) or off
degrees every 3 minutes. These data were used to obtain total (P-OFF). Individual data are displayed on left, and summary results to
exercise duration; the peak rate of oxygen consumption (maximal right. Randomization order of pacing-on first (Group A) or second
V̇O2), reflecting the oxygen transport capacity of the circulatory (Group B) is denoted by solid lines/circles or dashed lines/open cir-
system; and the V̇O2 at the anaerobic threshold. The anaerobic cles, respectively. Overall RMANOVA probability values are shown in
threshold is the exercise level at which energy production from parentheses to right, and results of multiple comparisons tests are
anaerobic metabolism becomes significant, and it is an endurance over brackets. With VDD pacing, exercise duration, maximal V̇O2, and
measure for exercise and activities of daily living.19 Lastly, peak peak exercise heart rate–systolic pressure product rose significantly.
exercise heart rate, systolic blood pressure, and the maximal rate- This was not observed when pacing was off. *P50.01 for paired t-test
pressure product (RPPmax) were determined. of pacing on versus pacing off.
Echocardiographic and Doppler studies were performed at base-
line and after 1 year to assess wall thickness, chamber diameter, Data after 1 year were analyzed separately because the latter 6-month
fractional shortening, LV mass (area/length method),20 and LV period was unblinded and the duration of contiguous pacing varied with
outflow tract mean flow velocity, which was determined by initial randomization. For this comparison, data were assessed by a
continuous-wave Doppler. The latter provided an estimate of intra- nonparametric Wilcoxan test. Data are presented as mean6SD.
cavitary pressure gradients associated with hyperdynamic contrac-
tion.21 Dobutamine stress-echocardiography was performed to assess Results
cardiac reserve. Patients received intravenous dobutamine in incre-
mental doses to maximal tolerated levels (7.5 to 40 mg z kg21 z VDD Pacing and Exercise Performance
min21). Dobutamine stress results were compared at a matched dose Four patients were randomized to have pacing on during the first
in all but 2 patients. In these 2 patients, 1-year follow-up data were 3 months, and the remaining patients had active pacing during
recorded only at the 40 mg z kg21 z min21 dose, versus the 30 and 20
mg z kg21 z min21 doses used at baseline in each, respectively. The the second 3 months. Exercise capacity improved during the
average dose used for baseline and 1-year studies was 25612.8 pacing-on period in nearly all patients. Figure 2 provides
versus 29613.6 mg z kg21 z min21, respectively (P50.2). individual and summary data comparing exercise duration,
Chamber-diameter and wall-thickness measurements were made maximal V̇O2, and RPPmax at initial baseline to pacing-on and
under rest conditions using commercial software. The ECG was not pacing-off periods. Randomization order is coded in the figure.
displayed on the echocardiographic monitor; therefore, analysis was
blinded to pacing conditions (on versus off). All echodimension and With active pacing, total exercise duration lasted an average of
flow-gradient data were determined at the time of the procedure, and 82% longer, from 3246133 to 5886239 s (P50.001 by
the technician was blinded to prior results. Baseline and dobutamine- RMANOVA with multiple comparisons test). Although there
stimulated stroke volume and cardiac output were determined from was heterogeneity in this response, 7 of 9 subjects experienced
either aortic flow velocity3aortic root-area or cavity volumes
calculated from biplane images. These data were an average from at
$30% improvement in exercise duration. Maximal V̇O2 in-
least 3 separate cycle determinations performed by a single observer creased 24%: from 13.562.9 to 16.763.3 mL of O2 z min21 z
blinded to data source. kg21 (P50.05), with all but 2 patients experiencing at least a
10% increase. V̇O2 at the anaerobic threshold increased from
Statistical Analysis 8.660.97 to 11.461.9 mL of O2 z min21 z kg21 (P50.005).
For the randomized, blinded portion of the study (baseline, pacing on, RPPmax rose 46%, from 15.663.2 to 22.863.3 mm Hg z beats/s z
and pacing off), data were analyzed by repeated-measures analysis of
variance (RMANOVA), with protocol period and patient number 103 (P50.002), indicating that prolonged exercise duration and
treated as categorical variables. Post-hoc testing of individual mean maximal V̇O2 were associated with enhanced total cardiac work.
differences due to protocol period was performed using a Tukey test. Resting RPP was similar for all periods.

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810 Circulation August 24, 1999

TABLE 1. Metabolic Exercise Results at 1-Year Follow-Up TABLE 2. Resting Echocardiographic and Doppler Assessment
Compared With Baseline at 1-Year Follow-Up Compared With Baseline
Baseline 1 Year P Baseline 1 Year P
21
Exercise time, s 3246133 6006263 0.012 Heart rate, min 60.368.0 61.468.2 NS
Rest V̇O2, mL of O2 z min21 z kg21 3.960.7 3.360.7 0.06 End-diastolic diameter, mm 44.165.9 47.366.7 0.04
Max V̇O2, mL of O2 z min21 z kg21 13.662.9 14.764.5 NS Mean wall thickness, mm 17.963.3 15.962.3 0.03
V̇O2–AT, mL of O2 z min21 z kg21 8.660.97 10.161.5 0.05 Radius/thickness ratio 1.2960.43 1.5260.35 0.04
RPPmax, mm Hg z beats/min z 10 3
15.663.3 20.665.8 0.012 Estimated wall mass, g 273.3684.3 257.2684.7 0.015
AT indicates anaerobic threshold. Mean LV outflow velocity, cm/s 244.26114 182.9674 0.024
Estimated intracavitary pressure 28.5629.7 15.3613.5 0.05
None of these or any other exercise performance indexes gradient, mm Hg
were altered from baseline during the 3-month pacing-off Fractional shortening, % 62.769.8 58.4617.2 NS
period. All but one patient had a lower maximum V̇O2 during E:A ratio 1.1660.74 1.461.0 NS
pacing-off than pacing-on. Paired comparisons made solely E-wave deceleration time, ms 252664.6 221657.6 NS
between pacing-on versus pacing-off data revealed signifi- Stroke volume, mL 82.5624 82.5621 NS
cant differences in exercise duration (P50.024) and maxi-
Cardiac output, L/min 5.061.8 5.161.2 NS
mum V̇O2 (P50.01).
E:A ratio indicates early to late filling ratio.
Improved exercise capacity was generally sustained at the
1-year follow-up (Table 1). Exercise duration and RPPmax re-
mained substantially increased over baseline (and pacing-off (74.6 versus 42.6; P50.057). However, unlike the pacing-on
period) at 1 year. Maximal V̇O2 was not significantly elevated; period, no corresponding changes in metabolic exercise data
however, an 18% decline in resting V̇O2 existed (P50.007). In existed during the pacing-off period in these subjects.
addition, V̇O2 at the anaerobic threshold tended to increase
(P50.05). These results suggested an improvement in exertional Echocardiographic/Doppler Data
efficiency. Initially, 8 of 9 patients developed dyspnea and 3 Table 2 provides baseline and 1-year follow-up echocardio-
developed dizziness during exercise, which led to its termina- graphic/Doppler data. Resting chamber diameter at the papillary
tion. After 1 year of therapy, only 1 patient developed either muscle level increased and average midwall thickness declined;
symptom (P,0.001; x2 test), and the most common reason for thus, the radius/thickness ratio increased. These changes were
stopping exercise was leg fatigue. modest but significant. A corresponding 6.465.7% decline in
wall mass occurred (P,0.05). Resting stroke volume, cardiac
Pacing and Quality of Life Assessment output, and fractional shortening did not significantly change
Figure 3 displays the total MLHF questionnaire scores during between baseline and 1-year follow-up. Similarly, diastolic
the initial controlled crossover portion of the study. The function assessed by the early-to-late filling ratio and E-wave
baseline MLHF score was 67.7622.6 and it improved to deceleration time was not significantly altered.
33.4627.7 during the pacing-on period (P50.008). In con- In contrast to rest function, cardiac reserve assessed during
trast, the score was 47.2627.6 during the pacing-off period dobutamine stimulation was increased after 1 year of pacing
(P50.18 versus baseline by RMANOVA). Symptomatic therapy. Figure 4 displays absolute stroke volume and cardiac
improvement was also generally sustained at 1 year output at the 2 observation times: before and after receiving
(33.4623.8; P50.008). There was evidence of a substantial matched or nearly matched dobutamine doses. The 2 patients
placebo effect, as MLHF score also declined considerably in who received slightly higher doses at 1 year (see Methods) did
the 5 patients who had pacing off during the initial 3 months not display the larger changes in either parameter. At baseline,
LV stroke-volume change with dobutamine varied, and it was
not significant overall (8.1621 mL). In contrast, stroke volume
rose by 30624 mL (P50.001) after 1 year (P50.009 versus
baseline response). The improvement in dobutamine response
was not related to a change in resting stroke volume between the
initial and final studies (P50.84). Likewise, baseline cardiac
output increased more with dobutamine after 1 year of pacing
(14.865.2 L/min; P50.02) than it did during the initial study
(12.463.1 L/min, P50.04; P50.02 versus 1-year response).
Further evidence that functional reserve was altered was found
in the maximal tolerated dobutamine doses. Initially, only 3
patients tolerated a 40 mg z kg21 z min21 dose, with all 9
Figure 3. Changes in total MLHF-questionnaire score for initial, experiencing anginal-type chest pain and 6 developing dyspnea.
randomized, double-blinded study periods. Significant improve- In contrast, all patients tolerated the higher dose after 1 year of
ment (decline) occurred in scores during pacing-on period; this
was less marked during pacing-off period. Abbreviations and follow-up, with only 1 experiencing anginal-type pain and none
symbols are as in Figure 2. developing dyspnea.

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 Kass et al Pacing Therapy for Ventricular Hypertrophy 811

Mechanisms of Improved Functional Reserve

In a recent study of patients with HHCO or familial hypertrophic
cardiomyopathy, apical pacing generated discoordinate wall
motion at the pacing site, shifting the end-systolic pressure-
volume relation rightward.12 The result was an increase in LV
end-systolic volume at any given arterial or volume load, which
exceeded that normally obtainable by these hearts in the absence
of pacing. Sympathetic activation of the heart during stress
decreases end-systolic volumes, shifting the end-systolic
pressure-volume relation leftward. By increasing basal end-sys-
tolic volumes and not directly inhibiting sympathetic drive,
VDD pacing may restore some of this reserve capacity.
Reduction of distal cavity compression may also improve
mechanoenergetics, because once the distal chamber is at
near-zero volume, subsequent systolic force contributes little
to ejection but can increase cardiac internal work. Preventing
cavity obliteration can reduce this wasted energy12 and might
Figure 4. Cardiac reserve assessed by dobutamine stress- underlie reported declines in blood flow and flow heteroge-
echocardiography (Dob) at baseline and after 1 year of VDD neity.22 We could not directly demonstrate increased end-sys-
pacing. Data for stroke volume are shown in top panels, and for
cardiac output, in bottom panels. Data are paired at each
tolic volumes in our patients given the complex end-systolic
observation time, before and after a matched (or near-matched) geometry. However, end-diastolic dimension increased and
dose of dobutamine. Basal values for stroke volume and cardiac stroke volume (derived by Doppler flow) remained un-
output were similar between initial study and 1-year follow-up. changed, suggesting this increase occurred. Additional evi-
However, greater rise in both parameters occurred with dobuta-
mine stimulation after 1 year of pacing. The probability values
dence was provided by the decline in mean outflow flow
are for paired comparisons at each time point. Differences in the velocity, indicating reduced cavity obliteration. Lastly, exer-
response between the 2 time points are provided in the text. cise duration remained considerably prolonged at 1 year,
despite little change in maximal V̇O2. This is consistent with
Discussion enhanced exercise efficiency that could reflect better condi-
This study demonstrates for the first time that long-term VDD tioning, and/or more effective cardiovascular reserve.
pacing can improve exercise capacity, clinical symptoms, and The effects of VDD pacing on diastolic function remain
the daily living activity of patients with severe exertional unclear. We previously reported chamber compliance was
dyspnea and fatigue due to HHCO. In two-thirds of the unchanged by acute VDD pacing,12 but no data exist regard-
patients, exercise duration increased substantially after 1 year ing long-term pacing. If anything, relaxation prolongs with
(.50% in each; mean, 162%), and all but one improved at discoordinate contraction from pacing23 and, given the role of
least 15%. The data further supports the hypothesis that VDD diastolic dysfunction in hypertrophic disorders, this has raised
pacing increases systolic ejection reserve, and this may concerns.17,24 Yet, we found VDD pacing improved exercise
contribute to enhanced exercise capacity. function and symptoms without a demonstrable benefit (or
worsening) of diastolic function. This suggests that while
Study Limitations diastolic abnormalities undoubtedly contribute to exercise
This study was designed as a feasibility trial and was, therefore, intolerance in patients with HHCO, they are not the only
limited in sample size. Although clearly a limitation, the ran- factor. As noted, these patients also had limited systolic
domized, blinded, crossover design enhanced the power of the reserve capacity associated with basal hyperejection, and this
study, enabling delineation of changes beyond those from a may play a greater role in their symptoms.
Our study targeted patients with increased basal LV outflow
placebo effect. We also intentionally restricted the entry criteria
velocity consistent with modest intracavitary pressure gradients
to generate a fairly homogeneous population. Although mean
from distal-wall compression. It is important to emphasize again
changes were often large, not every patient benefited similarly,
that none of the patients had outflow obstruction. Rather, the
and some had only modest gains. Confirmation of the present
velocities and estimated gradients reflected a small resting
results in a much larger cohort is needed, particularly to define
end-systolic volume that limited any further reduction with
which patients are mostly likely to benefit. Lastly, 4 patients had
exercise. It remains possible, if not likely, that patients who only
their b-blocker and/or diuretic dose increased between the initial cavity-obliterate during exercise would still benefit from VDD
and final studies, and some effect on the results cannot be ruled pacing. Lastly, the same pathophysiology occurs in elderly
out. However, it could not have altered comparisons between individuals with hypertrophic disease,8 many of whom have
randomized pacing on and off periods because the medication systolic hypertension. VDD pacing in individuals with refractory
changes occurred either very early or after this period was exertional dyspnea might also prove useful.
completed. Furthermore, the 3 patients on higher b-blocker
doses after 1 year displayed negligible differences in basal heart Comparison with Pacing Therapy for Familial
rate or cardiac output and did not have discernibly improved Hypertrophic Cardiomyopathy
symptoms, exertional capacity, or dobutamine-stimulated re- The usefulness of pacing to treat familial hypertrophic car-
serve compared with other patients. diomyopathy with asymmetric septal hypertrophy and intra-
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812 Circulation August 24, 1999

ventricular cavity gradients has been the focus of several 4. Kessler KM. Heart failure with normal systolic function: update of prev-
recent studies and reviews.13–17,24,25 The primary hypothesis alence, differential diagnosis, prognosis, and therapy. Arch Intern Med. 1988;
148:2109–2111.
is that by altering the ventricular activation sequence, pacing 5. Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Con-
limits septal motion, reducing outflow gradients and improv- gestive heart failure with normal systolic function. Am J Cardiol. 1984;54:
ing symptoms.24 Initial, non-placebo– controlled studies 778–782.
suggested consistent success,16,25 whereas subsequent trials 6. Soufer R, Wohlgelernter D, Vita NA, Amuchestegui M, Sostman HD, Berger
HJ, Zaret BL. Intact systolic left ventricular function in clinical congestive
using controlled/crossover designs similar to that used in the heart failure. Am J Cardiol. 1985;55:1082–1086.
present study have been less consistent. For example, 7. Savage DD, Garrison RJ, Kannel WB, Levy D, Anderson SJ, Stokes JI,
Nishimura et al13 reported only modest changes in exercise Feinleib M, Castelli WP. The spectrum of left ventricular hypertrophy in a
duration (414 versus 342 s), no change in maximal V̇O2, and general population sample: the Framingham Study. Circulation. 1987;75:I-
26–I-33.
no clinical improvement in .30% of patients. Exercise 8. Topol EJ, Traill TA, Fortuin NJ. Hypertensive hypertrophic cardiomyopathy
capacity was also unchanged in the recent, larger Pacing in of the elderly. N Engl J Med. 1985;312:277–283.
Hypertrophic Cardiomyopathy trial,15 although it rose 21% in 9. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis
those patients with ,10 minutes of exercise time at baseline. of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol.
1995;26:1565–1574.
With this background, the current study is intriguing in that 10. Liu CP, Ting CT, Lawrence W, Maughan WL, Chang MS, Kass DA.
exercise capacity improved in most patients and generally was Diminished contractile response to increased heart rate in intact human left
associated with objective improvement in metabolic and hemo- ventricular hypertrophy: systolic versus diastolic determinants. Circulation.
dynamic performance. Furthermore, reduced symptoms and 1993;88:1893–1906.
11. Kass DA, Wolff MR, Ting CT, Liu CP, Lawrence W, Chang MS, Maughan
enhanced exercise capacity were sustained with long-term treat- WL. Diastolic compliance of hypertrophied ventricle is not acutely altered by
ment, which makes it less likely to reflect a placebo effect. The pharmacologic agents influencing active processes. Ann Intern Med. 1993;
difference may lie in particular characteristics of the study 119:466–473.
population. In the present study, all patients had substantial 12. Pak PH, Maughan WL, Baughman KL, Kieval RS, Kass DA. Mechanism of
acute mechanical benefit from VDD pacing in hypertrophied heart: similarity
baseline exertional disability, with an exercise duration ,6 of responses in hypertrophic cardiomyopathy and hypertensive heart disease.
minutes and maximal V̇O2,14 mL of O2 z kg21 z min21, and none Circulation. 1998;98:242–248.
had outflow tract obstruction, mitral regurgitation, malignant 13. Nishimura RA, Trusty JM, Hayes DL, Ilstrup DM, Larson DR, Hayes SN,
arrhythmias, or cavity distortion caused by asymmetric disease. Allison TG, Tajik AJ. Dual-chamber pacing for hypertrophic cardiomyopa-
thy: a randomized, double-blind, crossover trial. J Am Coll Cardiol. 1997;
Echocardiograms in these individuals were generally similar, 29:435–441.
with symmetric hypertrophy and distal cavity obliteration. Ven- 14. Slade AKB, Sadoul N, Shapiro L, Chojnowska L, Simon J-P, Saumarez RC,
tricular pacing generates regional discoordinate motion at the Dodinot B, Camm AJ, McKenna WJ, Aliot E. DDD pacing in hypertrophic
pacing site, thereby limiting cavity compression.12 In patients cardiomyopathy: a multicenter clinical experience. Heart. 1996;75:44–49.
15. Kappenberger L, Linde C, Daubert C, McKenna W, Meisel E, Sadoul N,
with HHCO, the symmetry and more distal distribution of Chojnowska L, Guize L, Gras D, Jeanrenaud X, Rydén L, PIC Study Group.
hypertrophy could, thereby, enhance the efficacy of apical Pacing in hypertrophic obstructive cardiomyopathy: a randomized crossover
pacing. In contrast, patients with proximal septal hypertrophy study. Eur Heart J. 1997;18:1249–1256.
may depend more on a timing delay between an apical pacing 16. Fananapazir L, Cannon ROI, Tripodi D, Panza JA. Impact of dual-chamber
permanent pacing in patients with obstructive hypertrophic cardiomyopathy
stimulus and septal shortening, and such timing could vary with symptoms refractory to verapamil and b-adrenergic blocker therapy.
considerably among patients. Circulation. 1992;85:2149–2161.
17. Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of
Conclusions hypertrophic cardiomyopathy. N Engl J Med. 1997;336:775–785.
Congestive failure is a leading cause of cardiovascular 18. Criley JM. Unobstructed thinking (and terminology) is called for in the
understanding and management of hypertrophic cardiomyopathy. J Am Coll
morbidity and mortality in older adults, yet nearly 40% of Cardiol. 1997;29:741–743.
these individuals have preserved ejection fraction.9 In a 19. Pashkow FJ, Dafoe WA, eds. Clinical Cardic Rehabilitation: A Cardiolo-
subset of individuals with hypertensive, supranormal ejection gist’s Guide. Baltimore: Williams & Wilkins; 1993:82–83.
and near-cavity obliteration, VDD pacing may offer a useful 20. Reichek N, Helak J, Plappert T, Sutton MS, Weber KT. Anatomic validation
of left ventricular mass estimates from clinical two-dimensional echocardi-
adjunct to pharmacological therapies. Further multicenter ography: initial results. Circulation. 1983;67:348–352.
trials are needed to confirm the present findings and define 21. Sasson Z, Yock PG, Hatle LK, Alderman EL, Popp RL. Doppler echocar-
the criteria for predicting patients most likely to benefit. diographic determination of the pressure gradient in hypertrophic cardiomy-
opathy. J Am Coll Cardiol. 1988;11:752–756.
22. Posma JL, Blanksma PK, van der Wall EE, Vaalburg W, Crijns HJGM, Lie
Acknowledgements KI. Effects of permanent dual chamber pacing on myocardial perfusion in
Supported by grants from the National Public Health Clinical symptomatic hypertrophic cardiomyopathy. Heart. 1996;76:358–362.
Research Center (RR00052), Medtronic, Inc (to D.A.K.), and the 23. Betocchi S, Losi M-A, Piscione F, Boccalatte M, Pace L, Golino P, Perrone-
National Aging Institute (AG-12249; to D.A.K.) Filardi P, Briguori C, Franculli F, Pappone C, Salvatore M, Chiariello M.
Effects of dual-chamber pacing in hypertrophic cardiomyopathy on left ven-
References tricular outflow tract obstruction and on diastolic function. Am J Cardiol.
1. Vasan RS, Levy D. The role of hypertension in the pathogenesis of heart 1996;77:498–502.
failure: a clinical mechanistic overview. Arch Intern Med. 1996;156: 24. Nishimura RA, Symanski JD, Hurrell DG, Trusty JM, Hayes DL, Tajik AJ.
1789–1796. Dual-chamber pacing for cardiomyopathies: a 1996 clinical perspective.
2. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KKL. The progression from Mayo Clin Proc. 1996;71:1077–1087.
hypertension to congestive heart failure. JAMA. 1996;275:1557–1562. 25. Fananapazir L, Epstein NE, Curiel RV, Panza JA, Tripodi D, McAreavey D.
3. Iriarte M, Murga N, Sagastogoitia D, Molinero E, Morillas M, Salcedo A, Long-term result: evidence for progressive symptomatic and hemodynamic
Estella P, Extebeste J. Congestive heart failure from left ventricular diastolic improvement and reduction of left ventricular hypertrophy. Circulation.
dysfunction in systemic hypertension. Am J Cardiol. 1993;71:308–312. 1994;90:2731–2742.

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 Ventricular Pacing With Premature Excitation for Treatment of Hypertensive-Cardiac
Hypertrophy With Cavity-Obliteration
David A. Kass, Chen-Huan Chen, Maurice W. Talbot, Carlos E. Rochitte, João A. C. Lima,
Ronald D. Berger and Hugh Calkins

Circulation. 1999;100:807-812
doi: 10.1161/01.CIR.100.8.807
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