Dwivedi SK
*; Sandeep Bansal
†;
Aniket Puri
†; Makharia MK
†;
Narain VS
*; Saran RK
*; Hasan M
‡; Puri
VK
§.
*Professor of Cardiology,
†Senior Resident,
‡Ex-Professor
and Head,
§Professor and Head, Department of
Cardiology, King
George's Medical University, Lucknow, India.
Address for
correspondence: Prof S K Dwivedi, Department of Cardiology, King
George's Medical University, Lucknow, India. E Mail:
aniketpuri@hotmail.com
Abstract
Background:
Cardiac dysfunction after right ventricular (RV) apical pacing is well
known but its extent, time frame of appearance and individual effect on
left ventricular (LV), RV systolic and diastolic parameters has not
evaluated in a systematic fashion.
Methods:
Patients with symptomatic bradycardia and ACC-AHA Class I indication
for permanent pacemaker implantation (PPI) were implanted a single
chamber (VVI) pacemaker. They were followed prospectively by
echocardiographic examination which was done at baseline, 1 week, 1
month and 6 months after implantation. Parameters observed were chamber
dimensions (M-line), chamber volumes, cardiac output (modified
Simpson's method), systolic functions (ejection fraction, pre-ejection
period, ejection time and ratio) and diastolic functions( isovolumic
relaxation time & deceleration time) of left and right heart.
Results:
Forty eight consecutive patients (mean age 65.6±11.8 yrs, 66.7%
males, mean EF 61.82±10.36%) implanted a VVI pacemaker were
enrolled in this study. The first significant change to appear in
cardiac function after VVI pacing was in diastolic properties of RV as
shown by increase in RV isovolumic relaxation time (IVRT) from
65.89±15.93 to 76.58±17.00 ms,(p<0.001) at 1week and
RV deceleration time (DT) from 133.84±38.13 to
153.09±31.41 ms, (p=0.02) at 1 month. Increase in RV internal
dimension (RVID) from 1.26±0.41 to 1.44±0.44, (p<0.05)
was also noticed at 1 week. The LV diastolic parameters were
significantly altered after 1 month with increase in LV-IVRT from
92.36±21.47 to 117.24±27.21ms, (p<0.001) and increase
in LV DT from 147.56±31.84 to 189.27±28.49ms,(p<0.01).
This was followed by LV systolic abnormality which appeared at 6 months
with an increase in LVPEP from 100.33±14.43 to
118.41±21.34ms, (p<0.001) and increase in LVPEP/LVET ratio
from 0.34±0.46 to 0.44±0.10, (p<0.001)]. The reduction
in LV EF was manifested at 6 months falling from 61.82±10.36%
to52.52±12.11%, (p<0.05) without any significant change in
the resting cardiac output.
Conclusion: The
present study shows that dysfunction of right ventricle is the first
abnormality that occurs in VVI paced patients, which manifests by 1
week followed by LV dysfunction which starts appearing by 1 month and
the diastolic dysfunctions precede the systolic dysfunction in both
ventricles.
Key Words: diastolic
dysfunction; systolic dysfunction; left ventricle; right ventricle; RV
apical pacing
Introduction
Single chamber right ventricular apical pacing (VVI) continues to be
the predominant pacing mode in the developing countries primarily due
to economic constraints, despite the well-known advantages of dual
chamber pacing. Pacemaker induced myocardial dysfunction has been
recognized for a long time and the effect of single chamber right
ventricular (RV) apical pacing (VVI) on left ventricular (LV) functions
has been studied previously, yet there remain some unexplored
areas such as the chronology of events to occur.
1-8 Majority of studies have looked into LV
dysfunction while effects on the right ventricle (RV) have not been
studied thoroughly. Furthermore there is little data on the extent and
the time frame in which these changes occur. We therefore, aimed to
evaluate systolic and diastolic functions of LV and RV in consecutive
patients undergoing VVI permanent pacemaker implantation (PPI) over a
period of 6 months using trans-thoracic echocardiography.
Material and Methods
All
consecutive patients undergoing VVI pacemaker implantation having a
class I indication according to AHA guidelines
9
were included in the study. A written informed consent was taken for
inclusion in the study. Patients undergoing PPI implantations with
other modes of pacing were excluded from the study.
Clinical
evaluation: A thorough clinical evaluation and resting 12-lead
electrocardiogram (ECG) were done at admission, on day 7 after PPI and
on follow up at 1 month and 6 months. Patients were discharged with a
programmed pacing rate of 70/mt. At follow up visits, patients were
evaluated for any evidence of a new onset dyspnea attributable to
pacemaker syndrome, in the absence of any recognizable recent
myocardial infarction, anaemia, respiratory illness and new LV ejection
fraction of less than 50%.
10,11
The left ventricular function was evaluated by 2D echocardiography. At
the end of 6 months follow up, a 24 hour ambulatory ECG was done to
document the duration of paced and sinus rhythm in the previous 24
hours. A patient with paced rhythm of more than 90% of all ventricular
complexes was considered to be on persistent pacing mode.
Echocardiography
protocol: Baseline echocardiographic evaluation was done within
24 hours of hospital admission with the temporary pacemaker rate being
kept at 70/mt. In the event of intact atrio-ventricular (AV)
conduction, echocardiography was done on right ventricular temporary
pacing at a rate 10 beats higher than the intrinsic sinus rate.
Echocardiography was repeated at day 7, 1 month and 6 months after
implantation. Each measurement was taken in three consecutive
paced beats not preceded by a sinus P wave and the average was
considered as the representative value.
LV end
diastolic and systolic volumes (LVEDV and LVESV) were calculated using
modified Simpson's method. Left ventricular internal diameter in
diastole (LVIDd) and systole (LVIDs) and fractional shortening (FS)
were measured in parasternal long axis view using the M-mode. The right
ventricular internal diameter in diastole (RVIDd) and systole
(RVIDs) were taken in the parasternal long axis view and their
mean was taken as the RVID. Left atrial size was measured in systole
(LAs) and diastole (LAd) on M-line in parasternal long axis view. Left
sided systolic time intervals; LV pre ejection period (LVPEP) and LV
ejection time (LVET) were calculated using Doppler aortic flow. Right
sided systolic time intervals, RV pre ejection period (RVPEP), and RV
ejection time (RVET) were calculated using Doppler pulmonary
flow. The LV diastolic parameters were calculated in apical 5-chamber
view keeping the Doppler cursor at a point where both aortic outflow
and mitral inflow could be obtained. The LV isovolumic relaxation time
(LV-IVRT) was taken as a period from end of aortic flow to beginning of
mitral inflow. The acceleration and deceleration time of mitral inflow
(MV-AT and MV- DT) were measured from the onset of the mitral inflow to
its peak and from peak to return to baseline respectively with the
Doppler cursor placed just beyond the mitral annulus in apical
four-chamber view. The RV isovolumic relaxation time (RV-IVRT) was
calculated using two views. First, the RV electromechanical systole was
calculated in parasternal short axis view using Doppler pulmonary flow.
This was taken as the period from Q-wave on ECG to the completion of
pulmonary flow. An average of three such readings was taken. Then the
tricupid valve Doppler inflow tracing was taken in apical four chamber
view in the manner similar to mitral inflow. The RV electromechanical
systole was marked on this. This point was taken as beginning of the RV
diastole and the period from this point to the beginning of tricuspid
inflow was taken as RV-IVRT. The tricuspid acceleration and
deceleration time (RV-AT and RV-DT) were measured in a manner similar
to mitral AT and DT. The systemic and pulmonary cardiac outputs were
calculated using velocity time integral (VTI) method across aortic and
pulmonary Doppler flow respectively. Colour Doppler was used to conform
and quantify AV valvar regurgitation, using area of the regurgitant jet
relative to the size of LA.
12
Statistical analysis: Student 't' test was used for statistical
evaluation. The paired 't' test was used to compare the baseline values
with the values at day 7, 1 month and 6 months respectively. A 'p'
value of <0.05 was considered to be significant. Parameters compared
were LVIDd, LVIDs, LVEDV, LVESV, RVID, LVEF, LVFS, LVPEP, LVET, RVPEP,
RVET, LAd, LAs, systemic and pulmonic cardiac output, LV-IVRT, LV-
AT& DT, RV-IVRT, RV- AT & DT. The effect of confounding
parameters as age (< 50 versus > 50 years), sex (male versus
female), indication (complete heart block versus Sick Sinus Syndrome),
LV dysfunction (LVEF < 50% versus > 50%) and the requirement of
pacing (intermittent versus regular) were also studied using two
way 't' test.
Results
Forty-eight
patients underwent VVI pacing. Three of the 48 patients had poor echo
window and were excluded from the final analysis. Over the 6
months follow up, 2 patients died. One patient had a haemorrhagic
stroke and the other having documented coronary artery disease died
suddenly. Two patients were lost to follow up after discharge but
postal inquiries showed that they had no fresh symptoms. Data could
therefore be obtained for all 45 patients at baseline and day 7, in 44
patients at 1 month and 41 patients at 6 months.
Baseline
characteristics of the patients are given in
Table 1. The study population
consisted of 66.7% males with a mean age of 65.6±11.8
years (range 35-90years). Thirty four (75.6%) patients had complete
heart block (CHB) and remaining (24.4%) had sick sinus syndrome (SSS).
The mean LVEF of the group was 61.8±10.4%. Seven patients had
LVEF of < 50% with 5 having dilated cardiomyopathy with normal
coronaries and 2 having coronary artery disease, 1 patient had complete
heart block secondary to inferior wall MI persisting beyond 3
weeks and 5 patients had co-existing coronary artery disease
(CAD) of varying duration.
Table
1: Baseline Clinical Characteristics of Study Patients (n=45)
( LVEF= Left Ventricular ejection fraction)
Syncope did
not recur in any patients over the 6 month period. Eight patients who
had presented on admission with dyspnoea experienced initial relief
with drug therapy but dyspnoea worsened in 4 of these patients. Over
the 6 months follow up period new onset dyspnoea occurred in 7
patients. In 4 patients, it was considered as a part of pacemaker
syndrome while in 3 it was attributed to progressive LV dysfunction.
New onset persistent atrial fibrillation developed in 9 patients, it
was noted at the end of 1 month in 2 patients and at 6 months in
remaining 7 patients. Nine patients were adjudged to be having
intermittent pacing showing <90% paced complexes on 24 hours
ambulatory ECG monitoring at 6 months.
Cardiac
dimensions, volumes, systolic functions and systolic time intervals are
shown in (
Table 2). The LVEDV
and LVESV increased significantly by 6 months over their corresponding
baseline values (p<0.05). The right ventricular dimension (RVID)
showed an earlier increase from baseline (p<0.05) at day 7 and
progressively increased in the 6 months follow up period. Significant
increase in left atrial diastolic diameter (LAd) was observed at 6
months (p<0.05). The left atrial systolic diameter (LAs) also
increased but not statistically significant (p>0.05). The LVEF
decreased progressively from baseline (61.82 ± 10.36%)
and was statistically significant at 6 months (52.52 ±
12.11%, p<0.05). Systemic and pulmonic resting cardiac output did
not change significantly over the six months follow up period. The
LVPEP increased significantly by 6 months (p<0.001) while LVET
decreased over the same period (p<0.05). The RVEP increased
significantly by 1 month (p<0.001) and continued to increase
progressively thereafter. The RVET decreased significantly by 6 months
(p<0.02).
Table
2: Changes in Cardiac Dimensions
(LAd = Left
atrial diameter in diastole, LAs = Left atrial diameter in systole,
RVID = Right ventricular internal diameter, LVIDd = End diastolic left
ventricular internal diameter, LVIDs = End systolic left ventricular
internal diameter, LVEDV = Left ventricular end diastolic volume, LVESV
= Left ventricular end systolic volume, RVPEP = Right ventricular
pre-ejection period; RVET = Right ventricular ejection time; LVPEP =
Left ventricular pre ejection period, LVET = Left ventricular ejection
time).
Among the
diastolic parameters (
Table 3),
LV-IVRT increased significantly at 1 month (p<0.001) and continued
to increase progressively till 6 months. The mitral valve DT also
increased similarly becoming statistically significant by 1 month
(p<0.01). The right ventricular parameters showed a change much
earlier than corresponding LV parameters. RV-IVRT showed a significant
increase as early as day 7 (p<0.01) and continued to do so during
the 6 month follow up period. The RV-DT also showed a significant
increase by 1 month (p<0.02). The ventricular filling
acceleration time (AT) did not change significantly during the entire
period in either of the two ventricles. New valvar regurgitation was
seen in 7 patients. Of these, 4 had mild mitral regurgitation (MR)
while 3 had mild tricuspid regurgitation (TR). Two of these patients
had both MR and TR co-existent. One patient had pre-existing MR and TR,
which worsened after pacemaker implantation.
Table
3: Changes in Diastolic Parameters
(LV-IVRT =
Left ventricular isovolumic relaxation time, MV-AT = Mitral valve
acceleration time, MV-DT = Mitral valve deceleration time, RV-IVRT =
Right ventricular isovolumic relaxation time, TV-AT = Tricuspid valve
acceleration time, TV-DT = Tricuspid valve deceleration time).
The changes
observed were largely uniform and independent of age, sex, indication
for pacing and pre-existing LV dysfunction. Only persistent pacing, as
identified by >90% paced beats in a 24 hour holter, was
associated with a significantly higher decrease in LVEF (p<0.02) in
persistently paced group. This group also showed a higher LVESV
(p<0.005), greater RV dysfunction as suggested by higher RVPEP/RVET
ratio (p=0.024), and a tendency to have a larger LAd (p=0.063).
Discussion
In the present
study, the first significant change to appear in myocardial functions
following VVI pacing was in diastolic properties of RV. This was
manifest by an increase in RV-IVRT at one week, followed by an increase
in RV dimensions and the appearance of RV systolic abnormality i.e.
increased RV-PEP and RV-PEP/RV-ET ratio at one month. The LV diastolic
parameters were significantly altered at one month, which were manifest
by an increase in IVRT and DT, followed by LV systolic dysfunction
which appeared at 6 months with an increase in LV-PEP and LV-PEP/LV-ET
ratio. The reduction in LVEF also manifest at 6 months without change
in the resting cardiac output.
Our findings
suggest two inter-related sequence of events. Firstly, it appears that
changes in cardiac haemodynamics start appearing as early as one-week
after VVI pacing, which are subtle and are limited to right ventricle
only. Left ventricular dysfunction occurs later and this follows RV
dysfunction, as reported in previous studies
4,6-8. Secondly, diastolic
abnormalities are first to appear which are followed by appearance of
systolic abnormalities of the respective ventricles. Our study is
unique in highlighting the sequence in change in the LV and RV
diastolic and systolic function in a serial fashion in VVI paced
patients.
There is often
a debate whether LV dysfunction after long term ventricular pacing is
real or is dependent on pre-existing disease. Mohan et al4 in their
study found no significant difference in resting LVEF in long term
follow up of AAI and VVI paced patients of sinus node dysfunction
without structural heart disease. Similarly, Anderson et al
6, in their study of sick sinus syndrome
patients, found no difference in incidence of clinical congestive heart
failure or LV dimensions between AAI and VVI pacing modes on long
term follow up. On the other hand, Faerestrand et al
13 found an increase in end diastolic
volume in VVI paced patients after 3 months. Likewise, Fehrsson et al
7 found greater resting LV volumes and
lesser EF in patients paced on VVI rather than with physiological
pacing mode. In most of these studies, stress has been on systolic
function of LV after long term pacing while few have looked into the
serial follow up of these patients. Data regarding the diastolic
function is conflicting. LeClercq et al
14
in a study of 11 patients found that filling rates improved with AAI
pacing as compared to DDD pacing, and similar Doppler data was provided
in another report by Rosenqvist et al
15.
However data from Vardas et al
16
found no difference in the the diastolic Doppler indices between AAI
and DDD modes of pacing. Moreover, the systolic functions of right
ventricle as well as diastolic functions of both the ventricles have
not been studied comprehensively.
The true
mechanism of cardiac dysfunction is still unclear. It has been shown
that pacing from RV apex induces an electrical sequence of
depolarisation, which results in reduced stroke output of both the
ventricles.
17,18
RV apical pacing induces a left bundle branch block pattern and studies
have shown that alteration in normal activation sequence adversely
affects LV function as demonstrated by decrease in the global ejection
fraction.
19 This is
supported by finding that near normal activation sequence as seen in RV
outflow tract pacing results in a narrowed QRS and improved cardiac
output.
20 Karpawich and
Mital, in a report, have also shown a normalized LV function with
septal pacing despite a loss in atrial contribution as compared to
atrial pacing.
21 Resultant
chronic reduction in stroke output may mediate a compensatory
mechanisms leading to cardiac chamber enlargement in an effort to
maintain requisite stroke volume by Starling's law. There is evidence
that delayed depolarisation of the LV can result in augmented
intra-myocardial pressure in the septum and affect myocardial
perfusion. Kolletis et al
22
have shown that atrial or AV sequential pacing does not alter coronary
flow reserve while ventricular pacing decrease resting coronary flow
velocity in some patients. Furthermore, long term RV apical pacing also
results in myocardial perfusion defects on nuclear studies.
23 The magnitude of these defects is
shown to be proportional to the duration of pacing and are
associated with apical wall motion abnormalities and impaired global LV
function.
23
Beside this,
animal experimental studies have shown myofibrillar disarray
24, redistribution of myocardial fibre
strain and blood flow
25 and
adverse histopathological changes
26
on long term pacing in canine hearts which may also contribute to
systolic dysfunction on RV apical pacing. Since repolarization sequence
is determined by depolarization sequence, myocardial relaxation is also
likely to be non-homogeneous and diastolic abnormalities are likely to
appear. The diastolic filling parameters on radionuclide left
ventriculography, such as time to peak filling rate and negative dp/dt
are significantly altered in ventricular paced animal models
27 as well as in human hearts on
atrioventricular pacing.
28
However, these
mechanisms are not enough to explain significant reduction in systolic
performance of the left ventricle as adjudged by gross reductions of
the LVEF on long term pacing. It is hypothesized that left ventricular
diastolic and systolic functions are deranged in many conditions
secondary to involvement of right ventricle. Isolated right ventricular
infarction, atrial septal defect with right sided chronic volume over
load, cor pulmonale and chronic obstructive lung disease result in
altered LV diastolic as well as systolic functions secondary to RV
dysfunction.
29-32
LV dysfunction in paced patients may be a consequence of RV dysfunction
which occurs earlier as is shown in the present study. However, more
studies are required to have a firm explanation to this hypothesis.
Study
Limitations: Echocardiographic evaluation of RV size may not be
a reliable and reproducible method with inherent problems of inter and
intra observer variability. However, since every patient was serving as
their own control, and a change in the parameters could be attributed
to permanent pacing. The study was designed to include consecutive
patients undergoing single chamber VVI pacing and those having a
baseline ejection fraction of less than 50% were also included, however
in the final analysis on comparison with patients having ejection
fraction greater than 50% there was no difference in the observed
parameters. A critically timed atrial contraction can change the
filling characteristics of ventricle and alter the measured diastolic
and systolic parameters. Though, we chose to evaluate only paced
complexes, it may not have completely removed the impact of atrial
contribution to ventricular filling during the intervening sinus
rhythm.
In conclusion,
the present study shows that right ventricular apical pacing has a
major effect on systolic and diastolic ventricular functions. On serial
evaluation, right ventricle dysfunction is the first abnormality that
occurs in right ventricular apical paced patients, followed by LV
dysfunction which appears later and on both sides, diastolic
dysfunction precede the systolic dysfunction.
Glossary of Abbreviations
PPI= permanent pacemaker implantation
VVI= Single chamber Right ventricular apical pacemaker implantation
LV= Left ventricular
RV= Right ventricular
LAd= Left atrial diameter in diastole
LAs= Left atrial diameter in systole
LVIDd= End diastolic left ventricular internal diameter
LVIDs= End systolic left ventricular internal diameter
LVEDV= Left ventricular end diastolic volume
LVESV= Left ventricular end systolic volume
RVIDd= End diastolic right ventricular internal diameter
RVIDs= End systolic right ventricular internal diameter
RVID= Mean Right ventricular internal diameter
LVEF= Left ventricular ejection fraction
LVFS= Left ventricular fractional shortening
LVPEP= Left ventricular pre ejection period
LVET= Left ventricular ejection time
RVPEP= Right ventricular pre-ejection period
RVET= Right ventricular ejection time
LV-IVRT= LV isovolumic relaxation time
LV- AT= mitral flow acceleration time
LV- DT= mitral flow deceleration time
RV-IVRT= RV isovolumic relaxation time
RV- AT= tricuspid flow acceleration time
RV- DT= tricuspid flow deceleration time
CAD= coronary artery disease
CHB= Complete Heart Block
AHA= American Heart Association
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