European Heart Journal (1999) 20, 252–255
Article No. euhj.1998.1347, available online at http://www.idealibrary.com on
Clinical Perspective
Is sinus bradycardia a factor facilitating overt
heart failure?
Introduction
In patients with chronic heart failure, when episodes
of overt heart failure occur, some precipitating factors can be identified in 50 to 91% of these episodes[1,2]. These factors include lack of compliance
with drugs or diet, uncontrolled hypertension, myocardial ischaemia, systemic or pulmonary infections,
pulmonary embolism, physical, environmental and
emotional excesses, endocrine and haematological
disorders, tachyarrhythmias and complete atrioventricular block.
Sinus bradycardia is not commonly included
among the factors precipitating overt heart failure[3–6];
a low resting sinus rate even appears a protecting
factor, but a high sinus rate emerged as an independent predictor of mortality in prospective studies
carried out in the general population[7,8], and in
selected groups of patients with hypertension[9] or
myocardial infarction[10]. The reason is not completely clear. It has been suggested[11] that heart rate
has a direct effect on the development of coronary
atherosclerosis by reducing the diastolic time and
consequently myocardial perfusion. Heart rate also
reflects autonomic activity. Indeed, it has been
demonstrated that vagal stimulation increases the
electrical stability of the myocardium[12].
However, it is possible that this protective
effect does not apply to patients with very low heart
rate, namely those with sick sinus syndrome or atrioventricular block. Complete atrioventricular block is
commonly reported as a precipitating cause of heart
failure; however, it must be underlined that the
haemodynamics of complete atrioventricular block
are different from those of sinus bradycardia. In fact,
this block is characterized, besides slow ventricular
rate, by asynchronous atrioventricular contraction,
responsible for a rise in mean right and left atrial
pressures[13,14].
Revision submitted 22 September 1998, and accepted 30 September
1998.
Correspondence: Dr Paolo Alboni, Division of Cardiology,
Ospedale Civile, 44042 Cento (Fe), Italy.
0195-668X/99/040252+04 $18.00/0
Published data on the relationship between
sinus bradycardia and heart failure are inconclusive:
(1) Very little investigation has been carried out on
the haemodynamic pattern of sinus bradycardia. To
our knowledge, the cardiac index was measured by
Samet[15] in a group of 17 patients with sinus bradycardia and a low value was reported (average value,
1·9 l . min . m 2). However, the author did not report how many patients had organic heart disease
and how many heart failure and, therefore, this result
appears to be of little use.
(2) Among the patients with sick sinus syndrome the
prevalence of heart failure is high, ranging from 10%
to 20%[16–20]. However, these patients were old and
several had organic heart disease, so it was not
possible to draw conclusions about this relationship.
(3) Improvement in symptoms of heart failure, with
or without the addition of digitalis, has been reported
after pacemaker implantation in patients with sick
sinus syndrome[21,22] and pacing is commonly considered an effective treatment for patients with sinus
bradycardia and heart failure. However, this evaluation was done in retrospective and uncontrolled
studies, which do not allow definitive conclusions to
be drawn. One recent prospective trial[23] suggested
that during long-term follow-up of patients with sick
sinus syndrome, the incidence of heart failure was
lower in AAI paced patients than in those VVI
paced. However, this only suggests that physiological
pacing is haemodynamically better than ventricular
pacing.
(4) In patients with bradycardia and left ventricular
dysfunction or heart failure cardiac pacing increased
cardiac output; however, this rise was also observed
in patients with normal left ventricular function[24].
The THEOPACE study
The recently published THEOPACE study offers, in
our opinion, some knowledge on the relationship
between sinus bradycardia and overt heart failure[20].
In this study 117 patients with symptomatic sick sinus
1999 The European Society of Cardiology
Clinical Perspective
253
Table 1 THEOPACE study. Baseline characteristics of the patients in the three
groups. The values were not significant
Age (years)
Resting heart rate (beats . min 1)
Maximum exercise heart rate (beats . min 1)
Organic heart disease (patients)
NHYA class 2–3 (patients)
Episodes of overt heart failure (patients)
Left ventricular ejection fraction (%)
Medications (patients)
None
ACE inhibitors
Diuretics
Nitrates
Calcium-antagonists
Aspirin or warfarin
Others
No treatment
(35 patients)
Theophylline
(36 patients)
Pacemaker
(36 patients)
7111
446
11829
22 (63%)
18 (51%)
6 (17%)
5510
7311
466
11823
27 (75%)
22 (61%)
6 (17%)
5310
749
474
11021
29 (81%)
23 (64%)
4 (11%)
5410
18 (51%)
6
6
3
2
5
4
19 (53%)
5
4
2
3
4
5
16 (44%)
7
3
3
5
5
5
NYHA=New York Heart Association; ACE=angiotensin-converting enzyme.
syndrome (age 7311 years) were randomized to no
treatment (control group, n=35), dual-chamber rateresponsive pacemaker therapy (n=36) and oral theophylline (n=36), a drug which improves sinus node
function[25] and increases sinus rate during long-term
follow-up[26–28]. Patients were evaluated for randomization if they met all of the following criteria: (1) age
d45 years; (2) mean resting sinus rate <50
beats . min 1; (3) symptoms attributable to sinus
node dysfunction such a syncope or dizziness and/or
easy fatigue or effort dyspnoea. Patients with heart
failure refractory to treatment with ACE inhibitors
and diuretics were excluded from the study. The
baseline characteristics of the patients are reported
in Table 1. The patients were followed for up to
48 months (mean, 1914). From a clinical point of
view, no universally accepted definition of heart failure exists. Due to the design of the THEOPACE
study, overt heart failure was defined as the appearance or worsening of dyspnoea or peripheral oedema
requiring hospitalization, and during which the signs
of pump failure were present. Minor clinical manifestations of heart failure are difficult to evaluate during
a long-term clinical follow-up; therefore, they were
not taken into account.
During the follow-up period, six patients
(17%) in the no treatment arm, one (3%) in the
theophylline arm and one (3%) in the pacemaker arm
developed overt heart failure. The differences were
statistically significant (P=0·05). Overt heart failure
occurred after 99 months and the actuarial rates of
occurrences were 14%, 18% and 25%, respectively,
after 1, 2 and 4 years. These results demonstrate, for
the first time, that in a patient population with
symptomatic sinus bradycardia an increase in heart
rate induced by oral theophylline or DDD pacing
reduces the incidence of overt heart failure. Therefore, sinus bradycardia seems to play a role in the
genesis of heart failure. The bradycardic subjects who
developed overt heart failure were older (814
years), had a higher prevalence of underlying heart
disease, (hypertensive in three and ischaemic [not
post-infarction] in the remaining three), and showed a
more marked chronotropic incompetence than those
who did not (Table 2). Resting sinus rate, New York
Heart Association class and left ventricular ejection
fraction appeared similar in the patients who developed overt heart failure and in those who did not
(Table 2).
These results suggest that in a population of
symptomatic sick sinus syndrome patients, sinus
bradycardia can facilitate the appearance of overt
heart failure and the subjects more prone to develop
this complication are older, (about 80 years of age)
with organic heart disease and severe chronotropic
incompetence. In other patient populations, such as
those with acute myocardial infarction, age emerged
as a powerful risk factor for the development
of heart failure[29]. This is a pilot investigation which
does not allow us to define therapeutic strategies.
However, these results seem to suggest that old
patients with sinus bradycardia, severe chronotropic
incompetence and organic heart disease, even without
left ventricular dysfunction, should be periodically
checked for the possible appearance of overt heart
failure.
Eur Heart J, Vol. 20, issue 4, February 1999
254
Clinical Perspective
Table 2 The ‘no treatment group’ of the THEOPACE study. Comparison between
the baseline characteristics of the six patients who developed overt heart failure during
the follow-up period and the 29 who did not
No treatment group
(35 patients)
Age (years)
Resting heart rate (beats . nin 1)
Maximum exercise heart rate (beats . min 1)
Organic heart disease (patients)
NYHA class 2–3 (patients)
Left ventricular ejection fraction (%)
Six patients
who developed
overt heart failure
during the
follow-up
29 patients
who did not
develop overt
heart failure
P value
814
458
8612
6 (100%)
4 (67%)
5012
6910
446
12223
14 (48%)
14 (48%)
5610
<0·01
Pathophysiological relationships
between sinus bradycardia and overt
heart failure
Up to now, haemodynamic or echocardiographic
studies have not been carried out in patients with
sinus bradycardia, with or without heart failure,
apart from the above-mentioned investigation by
Samet[15], who observed a low cardiac index. Therefore, we can only speculate on the relationship
between sinus bradycardia and heart failure.
Heart rate is one of the main adaptive cardiac
mechanisms, together with ventricular dilatation
(Frank–Starling mechanism) and myocardial hypertrophy. Heart rate always acts as a compensatory
mechanism during exercise or other stressess and
sometimes while at rest, when the other compensatory mechanisms, paricularly Frank–Starling, are already fully activated. In this situation a low sinus rate
could be responsible for inadequate cardiac output.
Moreover sinus bradycardia could induce a rise in
ventricular diastolic pressures. In fact our results
suggest that among bradycardic patients, the ones
most prone to develop overt heart failure are older,
with organic heart disease, but without significant
pump function involvement. In the elderly, diastolic
function is more greatly altered than systolic function. As the myocardium undergoes structural and
biochemical changes with age, the stiffness of the
ventricular walls gradually increases[30,31]. In this
regard, many studies have shown that in elderly
patients, ventricular systolic function is relatively
preserved, dilatation less prominent and neuroendocrine activation less marked than in younger
patients[32–34]. Reduced left ventricular compliance
can potentially impair diastolic filling and cause a
marked increase in ventricular diastolic pressure, with
Eur Heart J, Vol. 20, issue 4, February 1999
<0·0001
<0·02
a small increase in ventricular volume. Consequently,
volume changes are not well tolerated in the elderly
and a slow heart rate is responsible for a marked
increase in diastolic ventricular volumes. Therefore
sinus bradycardia could facilitate the development of
overt heart failure in the elderly either through an
inadequate cardiac output or by increasing ventricular volumes, which may markedly increase left ventricular diastolic pressures to such an extent that
pulmonary congestion develops even if systolic
function is normal.
P. ALBONI*, M. BRIGNOLE†,
C. MENOZZI‡, S. SCARFO
v*
*Division of Cardiology,
Ospedale Civile,
Cento (Fe), Italy;
†Arrhythmology Center,
Department of Cardiology,
Ospedali Riuniti,
Lavagna, Italy;
‡Arrhythmology Center,
Department of Cardiology,
Arcispedale S. Maria Nuova,
Reggio Emilia, Italy
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