Possible acute and chronic synergistic effect of
dual chamber pacing and disopyramide in
obstructive hypertrophic cardiomyopathy: a
Shintaro Haruki, Yuichiro Minami*, Katsuya Kajimoto, Bun Yashiro,
Tsuyoshi Suzuki, Masatoshi Kawana, and Nobuhisa Hagiwara
Department of Cardiology, Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
Received 9 April 2009; revised 1 October 2009; accepted 7 October 2009; online publish-ahead-of-print 25 November 2009
It remains unclear whether the combination of dual-chamber (DDD) pacing and disopyramide can achieve prolonged left ventricular outflow
tract (LVOT) gradient reduction and symptom relief in patients with obstructive hypertrophic cardiomyopathy (HCM). In an HCM patient
with a severe LVOT gradient, the combination of DDD pacing and disopyramide achieved marked improvement of gradient in the catheter
laboratory and also after medium-term follow-up. The patient’s severe dyspnoea was alleviated during the follow-up period. This combi-
nation might enable physicians to treat and manage elderly symptomatic obstructive HCM patients with a severe LVOT gradient more
effectively and less invasively.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Hypertrophic cardiomyopathy † Dual chamber pacing † Disopyramide
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease
that is characterized by marked variability of its morphological
expression and natural history. A left ventricular outflow tract
(LVOT) gradient, due to systolic anterior motion (SAM) of the
anterior mitral valve leaflet, occurs at rest in roughly 25% of
patients with HCM, and is an independent predictor of adverse
clinical consequences such as progression to severe limiting symp-
toms and cardiovascular death.1Pharmacological agents with a
negative inotropic effect are the first-line therapy for obstructive
HCM, because these drugs reduce the LVOT gradient and symp-
toms.2–4However, patients who do not respond to medical
therapy will need further intervention such as surgical septal
myectomy or percutaneous alcohol septal ablation. For some
patients, such interventions may not be feasible because of
advanced age, co-morbidities, or patient refusal. In these patients,
dual-chamber (DDD) pacing may be a less-invasive alternative
approach. Here we present an elderly HCM patient with a
severe LVOT gradient and dyspnoea, which was successfully con-
trolled by a combination of DDD pacing and disopyramide in
both the acute and chronic phases.
A 77-year-old-woman was admitted with a diagnosis of obstructive
HCM. She had suffered from exertional dyspnoea for several years,
and obstructive HCM had been diagnosed at her local hospital.
Treatment was started with a beta-blocker (atenolol at 25 mg/
day) and disopyramide (150 mg/day), but both drugs were with-
drawn because of severe drug-induced sinus bradycardia. The
patient was referred to our hospital for further management.
She did not suffer from syncope or faintness, but had persistent
dyspnoea (New York Heart Association class III). On admission,
her blood pressure was 124/60 mmHg and her heart rate was
44 b.p.m. A grade three of six systolic murmur was heard at the
left sternal border. Echocardiography revealed left ventricular
hypertrophy (the inter-ventricular septal thickness was 20 mm
and the left ventricular posterior wall thickness was 15 mm),
LVOT obstruction with a peak gradient of 159 mmHg at rest
due to SAM of the mitral valve, and mild mitral regurgitation
(Figure 1A–C). At first, oral disopyramide (150 mg/day) alone was
administered. However, the LVOT gradient was unchanged and
her symptoms were also not improved with severe sinus bradycar-
dia during disopyramide monotherapy. She did not seem to be a
* Corresponding author. Tel: þ81 3 3353 8111, Fax: þ81 3 3356 0441, Email: firstname.lastname@example.org
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: email@example.com.
European Journal of Heart Failure (2010) 12, 94–97
Figure 1 (A) On admission, transthoracic echocardiography in the parasternal long-axis view shows LVOT obstruction by SAM of the
anterior mitral valve leaflet (arrow). (B) M-mode image obtained across the mitral valve also shows SAM (arrow). (C) Continuous-wave
Doppler of the LVOT demonstrates a late peaking resting gradient of 159 mmHg. (D and E) Six months after the start of DDD pacing combined
with disopyramide, LVOT obstruction and SAM have disappeared. (F) The LVOT gradient is remarkably reduced.
Figure 2 Simultaneous measurement of aortic and left ventricular pressures. (A) The baseline pressure gradient was 127 mmHg. (B) DDD
pacing at a rate of 80/min and an atrioventricular interval of 150 ms reduced the gradient to 27 mmHg. (C) After 5 min of disopyramide infusion
(1.0 mg/kg) without DDD pacing, the gradient was 28 mmHg. (D) The combination of DDD pacing with an atrioventricular interval of 150 ms
and disopyramide reduced the gradient to 4 mmHg.
Combination of DDD pacing and disopyramide in HCM
candidate for surgical myectomy or alcohol ablation because of her
advanced age and insufficient motivation. Therefore, a pacing study
was performed in the catheterization laboratory, using the DDD
mode at atrioventricular intervals of 50, 100, and 150 ms,
without oral disopyramide. The baseline LVOT gradient was
127 mmHg, and DDD pacing at 80/min with an atrioventricular
interval of 150 ms achieved the maximal decrease of the gradient
to 27 mmHg. Subsequently, intravenous infusion of disopyramide
(1.0 mg/kg/5 min) was performed without pacing, and it was
found that disopyramide alone reduced the LVOT gradient to
28 mmHg. After assessing the gradient reduction with disopyra-
mide alone, DDD pacing was restarted with the optimal atrioven-
tricular delay (150 ms) and a lower LVOT gradient of 4 mmHg was
achieved (Figure 2). Therefore, a DDD mode permanent pace-
maker was implanted and treatment with oral disopyramide
(300 mg/day) was restarted. Soon after starting this combined
therapy, her dyspnoea was markedly improved to New York
Heart Association class I. Since discharge, she has been followed
up at our outpatient department for 6 months with no episodes
of recurrent dyspnoea, and echocardiography at 6 months
showed no residual LVOT gradient (Figure 1D–F).
Pharmacological agents are the first-line therapy for the reduction
of an LVOT gradient. Beta-adrenergic blockers, verapamil, and dis-
opyramide all decrease the LVOT gradient and improve symp-
toms.2–4Disopyramide is a potent negative inotropic agent and
it has been shown to decrease the LVOT gradient both acutely
and over the long term, with a parallel improvement of symptoms
and exercise tolerance.5–7However, a subgroup of patients is
refractory to pharmacological agents or may not be able to toler-
ate therapy. Septal myectomy has been employed with consider-
able success for over 40 years and is considered to be the
gold-standard of treatment for drug-refractory obstructive HCM
causing severe symptoms.8Successful surgery will completely
abolish the gradient and mitral regurgitation, leading to marked
improvement of symptoms. More recently, alcohol ablation has
become an increasingly common non-surgical treatment for
obstructive HCM. This procedure relies on iatrogenic myocardial
infarction to decrease septal thickness and thus reduce the
LVOT gradient.9Implantation of a DDD pacemaker has been pro-
posed as a therapeutic alternative that is less invasive than either
myectomy or alcohol ablation. The mechanism of the therapeutic
effect derived from pacing is unclear, but it has been suggested that
initiation of the electrical impulse at the apex of the right ventricle
alters the systolic contraction sequence of the basal septum and
thus reduces the LVOT gradient. Although cohort studies have
suggested that DDD pacing effectively reduces the LVOT gradient
and symptoms, randomized blinded cross-over studies have shown
less marked improvement of both the gradient and the quality of
life.10–13Therefore, pacing is not regarded as a primary therapy
Recently, we reported a synergistic effect of DDD pacing and
disopyramide on gradient reduction in patients with obstructive
HCM during acute testing in the catheter laboratory. In the
17 patients treated with both pacing and disopyramide, the
gradient decreased from 102 to 28 mmHg, a reduction of 72%
(P , 0.05 compared with the 35% reduction achieved by disopyr-
amide alone and P , 0.05 compared with the 26% reduction due
to DDD pacing alone).14However, it was unclear whether com-
bined DDD pacing and disopyramide could achieve better long-
term gradient reduction and symptom relief than either method
alone. In the present elderly HCM patient with a severe LVOT gra-
dient, we achieved marked alleviation of the gradient by a combi-
nation of DDD pacing and disopyramide, both in the catheter
laboratory and after medium-term follow-up. Severe dyspnoea
(New York Heart Association class III) was also relieved during
Although DDD pacing is not a primary treatment for obstructive
HCM, there is nevertheless evidence to support a trial of pacing in
selected elderly patients (over 65 years old) who may benefit by
alleviation of the gradient and improvement of symptoms and
exercise tolerance.12Another potential advantage of pacing is
that it permits more aggressive drug treatment by obviating
concern about drug-induced bradycardia. Although DDD pacing
alone cannot eliminate the gradient, additional aggressive medical
treatment could abolish the residual gradient and symptoms. In
the present case, we could not provide optimal medical treatment
because of drug-induced bradycardia and did not consider myect-
omy or alcohol ablation mainly because of the patient’s advanced
age. For this patient, implantation of a permanent DDD pacemaker
permitted optimal medical therapy with disopyramide, and the
combination of pacing and disopyramide eliminated the LVOT
gradient and the patient’s dyspnoea in a less invasive manner.
In conclusion, this case suggests that the combination of DDD
pacing and disopyramide might enable physicians to treat and
manage elderly symptomatic HCM patients with a severe LVOT
gradient more effectively and less invasively. Further clinical
trials are needed to evaluate both the acute and chronic effects
of this combined therapy (DDD pacing and disopyramide) in
patients with obstructive HCM refractory to the best available
Conflict of interest: none declared.
1. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F,
Maron BJ. Effect of left ventricular outflow tract obstruction on clinical
outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295–303.
adrenergic blockade on the circulation with particular reference to observations in
patients with hypertrophic subaortic stenosis. Circulation 1964;29:84–98.
3. Rosing DR, Condit JR, Maron BJ, Kent KM, Leon MB, Bonow RO, Lipson LC,
Epstein SE. Verapamil therapy: a new approach to the pharmacologic treatment
of hypertrophic cardiomyopathy: III. Effects of long-term administration. Am J
4. Sherrid MV, Barac I, McKenna WJ, Elliott PM, Dickie S, Chojnowska L, Casey S,
Maron BJ. Multicenter study of the efficacy and safety of disopyramide in obstruc-
tive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;45:1251–1258.
5. Pollick C. Disopyramide in hypertrophic cardiomyopathy. II. Noninvasive assess-
ment after oral administration. Am J Cardiol 1988;62:1252–1255.
6. Pollick C, Kimball B, Henderson M, Wigle ED. Disopyramide in hypertrophic
cardiomyopathy. I. Hemodynamic assessment after intravenous administration.
Am J Cardiol 1988;62:1248–1251.
7. Sherrid M, Delia E, Dwyer E. Oral disopyramide therapy for obstructive hyper-
trophic cardiomyopathy. Am J Cardiol 1988;62:1085–1088.
8. Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE,
Shah PM, Spencer WH III, Spirito P, Ten Cate FJ, Wigle ED. American College of
Cardiology/European Society of Cardiology clinical expert consensus document
S. Haruki et al.
on hypertrophic cardiomyopathy. A report of the American College of
Cardiology Foundation Task Force on Clinical Expert Consensus Documents
and the European Society of Cardiology Committee for Practice Guidelines.
J Am Coll Cardiol 2003;42:1687–1713.
9. Nagueh SF, Ommen SR, Lakkis NM, Killip D, Zoghbi WA, Schaff HV,
Danielson GK, Quinones MA, Tajik AJ, Spencer WH. Comparison of ethanol
septal reduction therapy with surgical myectomy for the treatment of hyper-
trophic obstructive cardiomyopathy. J Am Coll Cardiol 2001;38:1701–1706.
results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopa-
thy. Evidence for progressive symptomatic and hemodynamic improvement and
reduction of left ventricular hypertrophy. Circulation 1994;90:2731–2742.
11. Kappenberger L, Linde C, Daubert C, McKenna W, Meisel E, Sadoul N,
Chojnowska L, Guize L, Gras D, Jeanrenaud X, Ryden L. Pacing in hypertrophic
obstructive cardiomyopathy. A randomized crossover study. PIC Study Group.
Eur Heart J 1997;18:1249–1256.
12. Maron BJ, Nishimura RA, McKenna WJ, Rakowski H, Josephson ME, Kieval RS.
Assessment of permanent dual-chamber pacing as a treatment for drug-refractory
randomized, double-blind, crossover study (M-PATHY). Circulation 1999;99:
13. Nishimura RA, Trusty JM, Hayes DL, Ilstrup DM, Larson DR, Hayes SN,
Allison TG, Tajik AJ. Dual-chamber pacing for hypertrophic cardiomyopathy: a
randomized, double-blind, crossover trial. J Am Coll Cardiol 1997;29:435–441.
14. Minami Y, Kajimoto K, Kawana M, Hagiwara N, Sherrid MV. Synergistic effect of
dual chamber pacing and disopyramide in obstructive hypertrophic cardiomyopa-
thy. Int J Cardiol; doi:10.1016/j.ijcard.2008.11.088. Published online ahead of print
20 December 2008.
Combination of DDD pacing and disopyramide in HCM