Download Segmental Early Relaxation Phenomenon

Segmental Early Relaxation
Phenomenon*
Incidence, Clinical Characteristics, and
Significance in Stress Echocardiography
Omar Obeidat, MD; Muhammed Arida, MD; Mouaz Al-Mallah, MD;
Mohsin Alam, MD; and Karthik Ananthasubramaniam, MD
Study objectives: To evaluate the incidence, patient characteristics, and clinical significance of
segmental early relaxation phenomenon (SERP) in stress echocardiography.
Design: Retrospective interpretation of digitized rest/stress echocardiographic images of 244
consecutive patients undergoing exercise or dobutamine echocardiography with subsequent
patient follow-up for outcomes.
Setting: Tertiary care referral center.
Patients: Two hundred forty-four consecutive patients referred for stress echocardiography
(exercise or dobutamine) for various clinical indications.
Interventions: None.
Measurements and results: SERP was diagnosed as a sudden outward motion of a portion of the
left ventricle during early diastole (using frame-by-frame analysis) after peak systole prior to
mitral valve opening at rest and after stress. Stress-associated SERP was observed in 71 patients
(29.1%), with 25 patients having SERP in more than one segment. Five patients had resting SERP,
with two persisting during stress. Ninety-six of 3,658 analyzed segments were positive for SERP.
The apical septum and midseptum were most commonly involved in 49% and 18%, respectively.
Only 5 of 96 patients (5.2%) had new hypokinesis and SERP in the same segment. No significant
differences existed in demographic, clinical, or echocardiographic variables in patients with and
without SERP. Follow-up revealed no significant differences in event rates in those with and
without SERP.
Conclusions: This is the first stress echocardiographic study demonstrating that SERP is a distinct
and relatively common stress echocardiographic phenomenon occurring in early diastole regardless of type of stress. SERP occurs predominantly in apical and midseptum in the distribution of
the left anterior descending coronary artery. It should not be mistaken for atypical septal motion,
ischemia, or dyskinesia, and does not seem related solely to the presence of underlying coronary
disease or stress-induced ischemia. No adverse long-term outcomes are seen in patients with
SERP and no inducible ischemia.
(CHEST 2004; 125:1218 –1223)
Key words: asynchronous relaxation; diastole; ischemia; segmental early relaxation; stress echocardiography
Abbreviations: ASE ⫽ American Society of Echocardiography; CAD ⫽ coronary artery disease; IVRP ⫽ isovolumic
relaxation phase; LAD ⫽ left anterior descending coronary artery; LV ⫽ left ventricular; SERP ⫽ segmental early
relaxation phenomenon
egmental abnormalities in ventricular contraction
S are
known to be associated with ischemic heart
disease and have been well studied with regards to
prognostic implications.1,2 However, regional asynergy of ventricular relaxation, although observed
during angiographic studies nearly 30 years ago,3,4
still has unclear implications. These diastolic phenomena represent a sudden localized outward motion of a portion of the left ventricular (LV) wall that
has been observed to occur during the isovolumic
relaxation phase (IVRP) of the cardiac cycle. Various
descriptive terms, such as segmental early relaxation
*From Henry Ford Heart and Vascular Institute, Detroit, MI.
This work was presented in part at the American College of
Cardiology Scientific Sessions 2002, Atlanta, GA.
Manuscript received May 20, 2003; revision accepted October 2,
2003.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:
[email protected]).
Correspondence to: Karthik Ananthasubramaniam, MD, Henry
Ford Hospital, Heart and Vascular Institute, 2799 West Grand
Blvd, K-14, Detroit MI 48202; e-mail: [email protected]
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Clinical Investigations
phenomenon (SERP),4 diastolic asynergy,5 late systolic bulge,6 preinflow relaxation,7 and asynchronous
relaxation8 have been used to describe these phenomena.
Stress echocardiography is an increasingly used,
widely available noninvasive modality for the diagnosis and prognosis of coronary artery disease (CAD).9
Atypical septal motion due to various cardiovascular
conditions and left bundle-branch block are situations that can make interpretation of wall motion
abnormalities difficult in daily practice. SERP is an
abnormal localized bulge of a portion of the ventricle
predominantly reported in the resting state.4 – 8 To
our knowledge, the prevalence and clinical significance of SERP in stress echocardiography has not
been well studied.
The objectives of this study were to retrospectively
study the prevalence, patient demographics, and
clinical and echocardiographic features of SERP in
patients undergoing stress echocardiography. We
further wanted to identify if this phenomenon had
any bearing on the presence of ischemic response on
stress echocardiography. Unless specified, we will
refer to all similar diastolic phenomena reported in
other studies as SERP.
Materials and Methods
We retrospectively evaluated 244 consecutive patients who
underwent stress echocardiography (exercise and dobutamine
stress) at our echocardiographic laboratory between September
1999 and June 2000. Chest pain (48%), screening for CAD
(14%), and miscellaneous indications (38%) were the main
reasons for referral of study patients for stress echocardiography.
Exclusion criteria included left bundle-branch block, poor baseline echocardiographic images (lack of visualization of three or
more segments), and patients in whom IV contrast enhancement
for endocardial border definition was needed. This was due to the
discretionary use of contrast at the time of stress by the sonographer; hence, some study patients did not have contrast
enhancement at rest, making comparisons of rest and stress
images suboptimal. Baseline demographics and clinical features
of all the study patients were obtained by review of their medical
records. Two American Society of Echocardiography (ASE) level
III-equivalent echocardiographers who were blinded to patient
information and study results interpreted all digitized rest and
stress images recorded on optical discs. Frame-by-frame analysis
of all baseline and post-stress cine-loops were performed with
side-by-side comparison using standard four-quadrant format.
Each segment was graded for wall motion using the ASE
16-segment model (Fig 1)10 as follows: 1 ⫽ normal, 2 ⫽ hypokinetic, 3 ⫽ akinetic, 4 ⫽ dyskinetic, and 5 ⫽ aneurysmal. SERP
was denoted as being present or absent in each segment if a
portion or segment of the LV wall demonstrated a sudden
outward bulge after peak systole prior to mitral valve opening,
which would represent IVRP. Peak systole was defined as the
frame during systole that demonstrated the maximum inward
excursion with the smallest LV cavity. Since the mitral valve was
not visualized adequately in parasternal short-axis views, SERP
was predominantly evaluated in the parasternal long-axis, apical
four-chamber and two-chamber views, although the short-axis
Figure 1. The standard 16-segment model of the left ventricle as
recommended by the ASE. Ant ⫽ anterior; AL ⫽ anterolateral;
AS ⫽ anteroseptum; Inf ⫽ inferior; IL ⫽ inferolateral; IS ⫽ inferoseptum; Lat ⫽ lateral; Sep ⫽ septum.
was also assessed. In cases where there was disagreement of ⬎ 1
score in segment evaluation, a joint review and consensus
between the two readers was obtained.
Follow-up was done by the investigators from the electronic
patient database available at our health system. Medical records
were reviewed to look for emergency department visits, office
visits, or hospitalization for cardiovascular events including angina, unstable angina, myocardial infarction, revascularization,
stroke, congestive heart failure, and death. If no follow-up was
documented in our electronic database, mortality through Michigan state vital records and health statistics and the United States
vital records and health statistics were cross-referenced. The
study protocol was approved by our Institutional Review Board.
Statistical Analysis
Baseline demographics and clinical characteristics were reported for patients with SERP and without SERP, including
means ⫾ SD and proportions as appropriate. Univariate comparisons were carried out using two-sample t test and ␹2 test. A
two-sided ␣ level of 0.05 has been used to determine clinical
significance. Bivariate statistics were performed with ␹2 test, and
odds ratios were reported with 95% confidence intervals and p
values. Multivariate statistics were performed using primarily
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conditional multiple logistic regression for the independent
relationship of different factors of interest with SERP.
Table 2—Stress Echocardiographic Variables*
SERP
(n ⫽ 71)
Variables
Results
Baseline characteristics of patients with and without SERP on stress imaging are shown in Table 1.
No significant differences in baseline characteristics
were seen except for a trend toward lesser incidence
of hypertension in patients with stress-induced
SERP (p ⫽ 0.058). Also, there were a trend toward
decreased incidence of previous coronary artery
disease and hyperlipidemia in patients with stressinduced SERP. Table 2 outlines the comparison of
stress echocardiographic variables in patients with
and without SERP. No significant differences were
noted in both patient groups.
A total of 3,658 segments were systematically
analyzed in 244 patients. Figure 2 shows the distribution of SERP segments (percentage of total segments). Stress-associated SERP was observed in 96
segments in 71 patients (29.1%). Multiple segments
were involved with SERP in 25 of 71 patients (35%).
Only five patients had resting SERP (2%). The
resting ECG in these five patients only revealed
normal sinus rhythm with nonspecific ST-T wave
abnormalities, except one patient who had also nonspecific intraventricular conduction delay. None of
the five patients had a positive ECG finding suggestive of ischemia with stress. SERP persisted during
stress only in two of five patients. The distal (apical)
septum was the most commonly involved (49%)
segment with the midseptum in 20% (Fig 2). Six
patients had estimated ejection fraction ⬍ 40%, and
none of them had SERP. Only 5 of 96 segments
(5.2%) with SERP had stress-induced ischemia in
the same segment. On the contrary, 15 of 71 patients
(21%) had inducible ischemia in segments other than
SERP segments and 55 of 173 patients (32%) had
inducible ischemia without any SERP.
Table 1—Patient Demographics*
Variables
Age, yr
Male gender
Hypertension
Diabetes
Hyperlipidemia
History of CAD
Smoking
History of CHF
Mitral regurgitation
Ejection fraction
SERP (n ⫽ 71) No SERP (n ⫽ 173) p Value
54 ⫾ 13
56
45
17
38
13
27
2.8
7.0
52
58 ⫾ 14
50
58
17
51
20
28
3.4
5.7
52
0.4
0.58
0.058
NS
0.068
0.20
NS
NS
NS
NS
*Data are presented as mean ⫾ SD or %. NS ⫽ not statistically
significant; CHF ⫽ congestive heart failure.
No SERP
(n ⫽ 173)
Exercise stress test
61 (86)
133 (77)
Dobutamine stress test
10 (14)
40 (23)
Mean ejection fraction
52
52
Exercise time, min
8.5 ⫾ 3
7.5 ⫾ 3
Double product
26,684 ⫾ 6,649 23,258 ⫾ 5,690
%PMHR
90 ⫾ 11
87 ⫾ 9
Positive EKG
18
12
Positive echo
28
32
p Value
NS
NS
NS
0.06
0.12
0.10
0.16
0.68
*Data are presented as No. (%), mean ⫾ SD, or %. PMHR ⫽
predicted maximum heart rate; positive EKG ⫽ ⱖ 1 mm of new
horizontal or downsloping ST depression at 80 ms beyond the J
point in three consecutive QRS complexes; Positive echo ⫽ new or
worsening regional wall motion abnormality in any ventricular
segment except resting akinetic wall segments. See Table 1 for
expansion of other abbreviation.
Patient follow-up was completed for 89% of the
study subjects through our health system database,
and no mortality data were available for the other
11% from the State of Michigan and US vital records
and health statistics. The mean follow-up time was
29 ⫾ 9 months (mean ⫾ SD). Only one patient died
because of sepsis from the group without SERP.
There was no statistical difference of event occurrence between both groups (Table 3).
Angiographic data were available in only 25 of 244
patients (10%). Only 6 of 25 patients had SERP, and
all SERP was observed in the distal septal segment.
The left anterior descending coronary artery (LAD)
had significant atherosclerosis in four of six patients.
The other two patients had nonobstructive epicardial CAD.
Discussion
The results of our study suggest that SERP is a
commonly observed early diastolic stress echocardiographic phenomenon with a predominant occurrence in the distal and midseptal distribution supplied by the LAD. There seems to be no unique
patient profile demonstrating this phenomenon during stress, and in particular there seems to be no
definite relation between detection of SERP and
stress-induced ischemia in the underlying segment
or coronary distribution. Furthermore, the presence
of SERP does not by itself seem to predict increased
incidence of adverse outcomes (Table 3). Although
75% of patients with SERP in the distal septum had
angiographic evidence of LAD disease (four of six
patients) given the small patient numbers with angiographic correlation, firm conclusions with regards
to occurrence of SERP during stress echocardiogra-
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Clinical Investigations
Figure 2. The distribution of SERP segments. Distal and midseptum were most commonly involved.
The apex and distal septum were analyzed as one segment (distal septum) when interpreting for
presence or absence of SERP. Also, note the very low prevalence of SERP in basal LV segments.
% ⫽ percentage of total SERP segments. See Figure 1 for expansion of other abbreviations.
phy as a sign of underlying CAD (in the absence of
an ischemic response) cannot be made from current
study although the possibility does exist (see discussion below).
Gooch et al3 initially described SERP in patients
with mitral valve prolapse and attributed it to functional cardiomyopathy. They noticed sudden outward movement of the anterior wall during IVRP
and believed that this was due to mitral valve
prolapse. Altieri et al4 studied 100 consecutive patients with chest pain undergoing cardiac catheterization. SERP was found in 83 patients, with 29 of 83
patients showing concomitant inward movements in
other segments. Only 30 of 59 patients with obstructive coronary artery disease (CAD) had SERP, with
SERP occurring predominantly in normally contracting segments of the left ventricle. They concluded that SERP was a normal variation of the LV
relaxation pattern.
Table 3—Clinical Outcomes After 29 ⴞ 9 Months of
Follow-up*
Variables
Atypical chest pain
Typical chest pain
Myocardial infarction
Congestive heart failure
Cerebrovascular accident
Death
SERP
(n ⫽ 71)
6
1
0
1
0
0
*See Table 1 for expansion of abbreviation.
No SERP
(n ⫽ 173)
p Value
22
6
1
1
1
1
NS
0.38
NS
NS
NS
NS
SERP and CAD
Prior studies with angiograpic6,11 and LV wall
motion12 correlations during experimental ischemia
have suggested that SERP-like phenomena was seen
frequently in the distribution of arteries subtending
significant stenosis. Hamby and colleagues6 suggested that SERP was probably related to LAD
disease, as 15 of 21 patients in their series had
significant LAD disease in segments demonstrating
SERP. Abe and Tomotsune8 studied various subgroups of patients with mitral valve disease and CAD
with and without history of myocardial infarction.
They found a high incidence of SERP in the subgroup of patients with angina pectoris and myocardial infarction, and concluded that localized myocardial ischemia definitely plays an etiologic role in
SERP, which could be an early manifestation of
ischemia.
Our study confirms and extends previous observations regarding SERP. The distribution of SERP was
noted predominantly in normal segments and was
absent in severely hypokinetic or akinetic segments.
Furthermore, SERP was observed in patients with
and without underlying CAD; although statistically
insignificant, there was actually a trend toward a less
prevalence of previous history of CAD in patients
with SERP (Table 1). Unlike the study by Gibson et
al,12 we did not observe a significant inward motion
of the left ventricle in ischemic segments during
stress echocardiography.
New contributions from our study include the
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Figure 3. Left, A: peak systole. Right, B: SERP of distal septum after peak systole during IVRP prior
to mitral valve opening.
incidence, segmental distribution, and significance
of SERP in the setting of stress echocardiography,
which to our knowledge has not been reported so far.
Since only 5% of patients had stress-induced SERP
and ischemia in the same segment, SERP is probably
not unique to CAD. Our study also indicates that
SERP by itself in the absence of ischemia does not
predict high cardiac event rates. Interestingly, despite the fact that firm conclusions cannot be made
from our angiographic data due to small numbers,
SERP as a phenomenon linked to CAD cannot be
excluded, as four of six patients with stress-induced
SERP who had angiographic data had significant
underlying LAD.
Diastolic Function in Patients With SERP
Previous angiographic studies have suggested that
alteration of viscoelastic properties of the left ventricle due to ischemia may be a cause of SERP. Alam et
al5 noted prolongation of isovolumic relaxation phase
in patients with SERP. Other studies13,14 have described significant correlation between SERP (identified angiographically) and disturbed echo-Doppler
ventricular filling dynamics.
Proposed Etiologies for SERP
The exact etiology precipitating SERP has still not
been clarified, but CAD with underlying ischemia,8,11 loss of erectile effect associated with early
coronary blood flow,15 noncoronary causes such as
valvular disease, atrial septal defect and nonischemic
cardiomyopathy,11 ventricular pacing,16 and regional
fibrosis or regional autonomic denervation have all
been implicated.
Limitations
Given that our study was retrospective, it has its
inherent limitations. Correlation of occurrence of
SERP to diastolic LV indexes changes was not
possible, as a complete diastolic study was not done
in many patients as a part of the initial resting study.
Furthermore angiographic correlation was not possible for the obvious reasons in those patients with
normal stress echo findings and SERP did not
undergo angiography, and not all patients with abnormal stress echocardiographic findings and SERP
underwent cardiac catheterization. Nevertheless, to
our knowledge ours is the first stress echocardiographic study to address SERP with patient followup, thus contributing more to the existing literature
that is largely angiographic, with most patients being
assessed in resting state. The very low incidence of
SERP in resting images in our study (2%) contrary to
all previous angiographic studies is unclear, but
could be related to different patient demographics,
neurohormonal and hemodynamic alterations at
time of identification of SERP (angiography vs echocardiography), unknown effect of cardiac medications in modifying this phenomenon, and different
methodologies and definitions used in identifying
this phenomenon in different studies.
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Clinical Investigations
Clinical Implications
Identifying SERP might be important for correct
interpretation of exercise and pharmacologic stress
echocardiograms (Fig 3). SERP might be confused
with segmental dyskinesis, which is a paradoxical
systolic outward motion of the LV wall. This is more
likely if quick outward movements of apex and distal
septum are not re-evaluated by frame-by-frame analysis. Frame-by-frame assessment with QRS reference or mitral valve visualization will clarify that
dyskinesis occurs earlier than SERP during systole,
and either involves segments with previously severely impaired contraction or severely ischemic
segments. In contrast, stress-induced SERP almost
exclusively occurs in normal or hypokinetic segments
as shown in our study (95% of patients with SERP
had normal underlying wall motion with stress).
Furthermore, dyskinesia occurs during inward excursion of the rest of the ventricular wall, whereas
SERP is seen after maximum systolic excursion is
completed and prior to mitral valve opening, indicating occurrence during IVRP.
SERP may also be confused with atypical or
paradoxical septal motion. These are usually seen in
conditions associated with conduction abnormalities
such as left bundle-branch block, right ventricular
volume overload, or after cardiothoracic surgery.
Again, frame-by-frame analysis identifies normal
septal thickening and motion pattern in systole with
localized outward bulging of septum during IVRP in
segments with SERP in contrast to systolic motion
abnormalities in the above conditions. Based on
existing literature,5,13,14 identification of SERP
should prompt more thorough analysis of diastolic
function particularly in patients with normal systolic
function.
Conclusion
SERP is a distinct diastolic phenomenon frequently seen in the early phase of relaxation by stress
echocardiography regardless of the type of the stress.
It is predominantly seen in middistal septal distribution of the LAD, and is not seen in severely hypokinetic or akinetic segments. It should not be mistaken
for atypical septal motion or ischemic response to
stress, does not seem to be solely related to previous
history of coronary disease or active ischemia, and is
not associated with adverse patient outcomes. A
prospective angiographic evaluation of patients dem-
onstrating this phenomenon with stress echocardiography and correlation with diastolic parameters
and/or flow reserve indexes is needed to firmly
address its relation to CAD and diastolic function.
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