Original article (Clinical investigation)
Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with
impaired force-frequency relationship and enhanced poststimulation potentiation.
Takeshi Kashimura, Makoto Kodama, Komei Tanaka, Keiko Sonoda, Satoru Watanabe,
Yukako Ohno, Makoto Tomita, Hiroaki Obata, Wataru Mitsuma, Masahiro Ito, Satoru
Hirono, Haruo Hanawa, and Yoshifusa Aizawa.
Division of Cardiology, Niigata University Graduate School of Medical and Dental
Sciences, Niigata, Japan
Corresponding author:
Takeshi Kashimura, Division of Cardiology, Niigata University Graduate School of
Medical and Dental Sciences, 1-757 Asahimachi, Niigata, 951-8510 Japan
Tel: +81-25-227-2185
Fax: +81-25-227-0774
Email: kashi@med.niigata-u.ac.jp
1
Abstract
Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a
predictor of cardiac events. However there have been controversies regarding the
conditions and mechanisms of MA. In order to clarify heart rate-dependent contractile
properties related to MA, we performed incremental right atrial pacing in 17 idiopathic
dilated cardiomyopathy (DCM) patients and in 6 control patients. The maximal increase
in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force
gain in the force-frequency relationship (FG-FFR) and the maximal increase in left
ventricular dP/dt of the first post-pacing beats was examined as the force gain in
poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients
(DCM MA(+)) but not in the other 8 DCM (DCM MA(-)) and not in any of the control
patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 mmHg/sec vs.
159.4 ± 103.9 mmHg/sec, p=0.0091) and higher FG-PSP (500.0 ± 96.8 mmHg/sec vs.
321.9 ± 94.9 mmHg/sec, p=0.0017), accordingly wider gap between FG-PSP and
FG-FFR (465.3 ± 119.4 mmHg/sec vs. 162.5 ± 123.6, p=0.0001) than DCM MA(-)
patients. These characteristics of DCM MA(+) showed clear contrasts to those of the
control patients. In conclusion, MA is caused with impaired FFR despite significant PSP,
2
suggesting that MA reflects ineffective utilization of the potentiated intrinsic force
during tachycardia.
Key Words: alternans; dilated cardiomyopathy; tachycardia; contractility; calcium
3
Introduction
Heart rate dependent hemodynamic changes in heart failure are subjects of great
interest [1]. Tachycardia frequently induces mechanical alternans (MA) in patients with
heart failure [2,3] and tachycardia-induced MA has been reported to be a predictor of
cardiac events [2]. Although MA has been reported in patients with heart failure for
more than a century [4-6], the mechanism causing MA is still to be clarified. Recent
findings of cellular and computational studies suggest MA is caused by calcium
transient alternans in cardiac myocytes with impaired calcium handling [7-10].
Therefore it is considered that the calcium handling in failing hearts cannot catch up
with rapid cardiac cycles and leads to MA. But relationships between MA and slow
contractile properties have not been shown in in vivo human hearts.
Another well-known tachycardia-induced response in patients with heart failure is
the attenuated force-frequency relationship (FFR). In normal hearts, an increased heart
rate progressively enhances the force of ventricular contraction, that is, FFR. In failing
hearts, tachycardia increases the contractile force to a lesser extent or can decrease it in
some severe cases [11,12]. The mechanism of attenuated FFR is considered to be
4
impaired calcium handling and indeed, FFR and MA were induced at the same time in
rodents by manipulating calcium handling [13,14], but there has been no human data on
the relationship between MA and FFR. Poststimulation potentiation (PSP) is also a
rate-dependent increase in contractile force shown in the first beat after cessation of
pacing-induced tachycardia [15,16] and has been reported to depend on calcium
handling [17]. But again its relationship to MA has not been studied in patients with
heart failure. In this study, we examined how MA correlates with FFR and PSP in the
human heart and discussed whether it is consistent with previous clinical and recent
experimental findings.
5
Methods
Subjects
Left ventricular contractile properties and the occurrence of mechanical alternans
(MA) were assessed by right atrial incremental pacing in 23 idiopathic dilated
cardiomyopathy (DCM) patients with sinus rhythm who underwent diagnostic cardiac
catheterization at the Niigata University Medical and Dental Hospital. The aim of this
study was to assess the link between MA and myocardial contractile properties,
therefore the patient population did not include those with significant coronary stenosis
of 75% or more according to the American Heart Association classification by coronary
angiography, those with localized left ventricular dysfunction by left ventriculography,
those with significant mitral or aortic regurgitation of second degree or more according
to the Sellor’s classification, or significant mitral or aortic stenosis by pressure
measurements, because tachycardia induced ischemia, asymmetrical wall motion, or
attenuated or enhanced left ventricular pressure development could influence the
evaluation of myocardial contractile properties. Five patients whose Wenchebach point
of atrioventricular conduction was 110 per minute or less were excluded to eliminate
patients who could show MA at a higher heart rate. Another patient was excluded
6
because of frequent premature ventricular contractions during pacing. As a consequence,
we examined the remaining 17 DCM patients.
Control data from hearts with preserved left ventricular function were taken from
patients whose left ventricular ejection fraction was 60% or more after diagnostic
catheterization for symptoms suggesting stable angina pectoris. Out of 12 patients
examined, 4 patients with Wenckebach point of atrioventricular block at 110/min or less
and 2 patients with frequent premature ventricular contractions were excluded, and data
from the remaining 6 were used. Diagnoses of those patients were stable angina pectoris
in 3 and chest pain syndrome without significant coronary artery stenosis in the other 3.
Right Atrial Incremental Pacing
After diagnostic procedures including right heart catheterization, coronary
angiography and left ventriculography, a 7-French micromanometer-tipped pig tail
catheter (Millar Instruments Incorporation, Houston, TX) was placed in the left
ventricle and a pacing catheter was placed in the right atrium. Subsequent to
measurements at a basal heart rate, the right atrium was paced at a rate just above the
basal heart rate for at least 20 seconds while the left ventricular pressure was
continuously recorded with its first derivative (dP/dt) until dP/dt became stable (Fig. 1a,
7
c, e). At least 10 seconds after cessation of pacing at a previous pacing rate, the right
atrium was paced again at a rate 10 per minute faster than the previous rate for at least
20 seconds. Thus the pacing rate was increased by the increment of 10 per minute until
the pacing rate reached 150 per minute. Other end points included patient’s complaint of
discomfort, Wenckebach point of atrioventricular conduction, remarkable decline in left
ventricular systolic pressure by 25% or down to below 70 mmHg.
All procedures in this study were approved by the ethical committee of Niigata
University Graduate School of Medical and Dental Sciences and adhered to the
principles of the declaration of Helsinki. Written informed consent was obtained from
each patient beforehand.
Definition of Terms
Mechanical Alternans (MA): We defined MA as alternans in left ventricular
systolic pressure of 4mmHg or more in our previous studies [3,18,19]. However this
study focused on the relationship between MA and FFR or PSP, which were measured
by dP/dt, therefore MA should be defined by dP/dt. Then we defined MA as a
phenomenon in which dP/dt alternans exceeded 100 mmHg/sec or more for at least 20
consecutive beats based on our previous comparison of pressure alternans and dP/dt
8
alternans [3].
Alternans Amplitude (AA) and Maximal AA (max AA): To quantify size of
alternans during a steady state, the difference between dP/dt of a beat and that of the
subsequent beat was defined as alternans amplitude (AA). The maximal AA (max AA)
of each patient was determined by incremental right atrial pacing (Fig 1b,d,f).
Force Gain in Force- Frequency Relationship (FG-FFR): The force of left
ventricular contraction was measured by the peak dP/dt. Typically, as the heart rate
increases incrementally to a certain point the force keeps increasing, and when the heart
rate increases further the force starts decreasing. This is known as the force-frequency
relationship (FFR). The maximal force was assessed by incremental atrial pacing in
each case and the increase from the force during the basal condition was defined as the
force gain in FFR (FG-FFR) (Fig. 1b, d, f). In this study, many cases showed MA during
steady-state pacing, therefore averages of two consecutive beats were used as the force.
The rationale of using the average was that during MA, extrasystole at a phase reversal
point abolishes MA and force is newly set in between that of a strong beat and that of a
weak beat [20], and clinical studies on left ventricular contractility of heart failure
patients have used the average of dP/dt, and do not mention the presence or absence of
MA [21,22].
9
Force Gain in Poststimulation Potentiation (FG-PSP): Animal and human data
have shown that the contractile force of the first beat after pacing is positively
dependent on increases in the pacing rate [15,16]. This is known as poststimulation
potentiation (PSP). In this study, PSP was assessed in the first poststimulation
spontaneous beat. The maximal force was assessed by incremental atrial pacing in each
case and the increase from the force in the basal condition was defined as the force gain
in PSP (FG-PSP) (Fig. 1b,d,f).
Statistical Analysis
Data analysis was performed with JMP 5.0.1J (SAS Institute, Cary, NC). All data
are presented as means ± standard deviation (SD). Homoscedasticity between groups
was tested by the F-test. The Shapiro-Wilk W test was used to assess whether the values
were distributed normally in each group. Differences for normally distributed values
between groups with homoscedasticity were analyzed using Student’s t-tests. Otherwise,
the Wilcoxon rank-sum test was used for values, and Pearson’s chi-square test was used
for categorical variables. P < 0.05 was considered significant.
10
Results
Induction of Mechanical Alternans (MA)
The average basal heart rate of the 17 DCM patients was 79.4 ± 16.1/min and the
maximal paced heart rate was 134.7 ± 15.9 /min. Right atrial incremental pacing was
terminated with the target heart rate of 150/min in 5 patients, with Wenchebach type
atrioventricular block in 6, with low LV systolic pressure in 5, and with atrial
tachycardia in 1. No one complained of remarkable discomfort during pacing.
Nine out of the 17 DCM patients showed mechanical alternans (MA) during
pacing at least at a pacing rate (Fig. 1a arrows) (DCM MA(+)), but the other 8 did not
(Fig. 1c arrow) (DCM MA(-)). The average heart rate at which maximal alternans
amplitude (max AA) was obtained was 122.8 ± 17.5/min for the 9 DCM MA(+) patients.
In eight out of the 9 cases, their AA reached the definition of MA (100 mmHg/sec) with
a heart rate of 120/min or less. The other had a basal heart rate of 114 /min and AA rose
over 100mmH/sec at 150/min. In 5 out of the 9 DCM MA(+) patients, AA did not reach
its peak because of a continuous AA increase even at 150/min in 3 cases and because of
Wenchebach type atrioventiricular block in 2 cases. On the other hand, the other 4 DCM
MA(+) patients showed a decline of AA with an excessive increase of heart rate (Fig. 1b
11
open circles), indeed 3 cases lost MA during the incremental pacing. One patient each
lost MA at 120/min, 130/min, and 140/min. In DCM MA(+) patients at maximal AA,
LVEDP of a strong beats, LVEDP of a weak beat, and the difference between them were
8.6 ± 6.5 mmHg, 6.3 ± 6.4, and 2.2 ± 3.5 mmHg, respectively.
The average basal heart rate of the 6 control patients was 75.5 ± 12.4/min and the
maximal paced heart rate was 131.7 ± 9.8/min. None of the control patients showed
MA.
Patient Characteristics and MA
Table 1 shows the background characteristics of each group, and those of DCM
MA(+) and of DCM MA(-) were compared. Digoxin had been prescribed to 3 out of the
9 DCM MA(+) patients, but to none of the DCM MA(-) patients, even though there was
no statistical difference (p=0.090). The DCM MA(+) patients had lower pulmonary
capillary wedge pressure (p=0.011) and lower left ventricular end diastolic pressure
(p=0.009). Other characteristics including LVEF and basal left ventricular dP/dt did not
differ between the two DCM groups (p=0.79, and p=0.16, respectively) (Table 1, Fig. 2a,
b).
12
Force Gain in Force-Frequency Relationship (FG-FFR) and MA
Left ventricular dP/dt increased to some extent as the pacing rate increased in
most of the patients (Fig. 1a, c, e, arrows) and the force-frequency relationship (FFR)
was obtained from each patient as shown in Fig. 1b, d, and f with closed squares. The
absolute values of the maximal dP/dt during incremental pacing did not differ between
DCM MA(+) and DCM MA(-) patients (963 ± 199 vs. 973 ± 397 mmHg/sec, p=0.94)
(Fig. 2c). However the maximal increase of dP/dt (the force gain in FFR: FG-FFR) was
significantly less in DCM MA(+) patients (35 ± 41 vs. 159 ± 104 mmHg, p=0.0091)
(Fig. 2d). The average LVEDP at FG-FFR measurement was 9.2 ± 5.9 mmHg in MA(+)
patients, and 14.4 ± 8.3 mmHg in MA(-) patients (p=0.15).
Force Gain in Poststimulation Potentiation (FG-PSP) and MA
Poststimulation potentiation (PSP) (Fig. 1a, c, e, asterisks) was enhanced to some
extent as the pacing rate increased in most of the patients (Fig. 1b, d, f, open triangles).
The absolute value of maximal dP/dt did not differ between DCM MA(+) and DCM
MA(-) patients (1433 ± 263 vs. 1141 ± 367 mmHg/sec, p=0.085). But the increase from
the basal condition (the force gain in PSP: FG-PSP) was significantly elevated in DCM
MA(+) patients compared with DCM MA(-) patients (500 ± 97 vs.325 ± 131 mmHg/sec,
13
p=0.0017) (Fig. 3a). The average LVEDP at FG-PSP measurement was 11.8 ± 2.4
mmHg in MA(+) patients, and 19.4 ± 9.3 mmHg in MA(-) patients (p=0.043).
Gap between FG-FFR and FG-PSP
As shown in Fig. 1b, DCM MA(+) patients seemed to have a wider gap between a
high FG-PSP and a low FG-FFR, therefore this gap was examined. The gap was wider
in DCM MA(+) patients compared with DCM MA(-) patients (465 ± 119 vs. 163 ± 124
mmHg/sec, p=0.0001) (Fig. 3b). Fig. 3c shows that DCM MA(+) patients had both high
FG-PSP and low FG-FFR levels. These properties of DCM MA(+) patients were quite
different from those of the control patients.
The occurrence of MA at a single rapid pacing rate
We also examined whether the gap between dP/dt in PSP and dP/dt in FFR
reflected the occurence of AA at a single rapid pacing rate, because FG-FFR, FG-PSP,
and max AA were obtained separately during incremental pacing at different pacing
rates. For example, FG-FFR and FG-PSP were obtained at different heart rates in 11 out
of 17 DCM cases, and in these 11 patients dP/dt in FFR started to decline at a heart rate
during incremental pacing, while dP/dt in PSP kept increasing until a higher pacing rate
14
was reached.
The number of patients who showed MA at 110/min and 120/min were 5 and 6,
respectively, and these numbers were more than those at other heart rates. The 5 DCM
patients with MA at 110/min had a wider gap between dP/dt in PSP and dP/dt in FFR at
110/min than those without (375 ± 64 vs. 123 ± 98 mmHg/sec, p=0.0002, Fig. 4a). The
6 DCM patients with MA at 120/min had a wider gap between dP/dt in PSP and dP/dt in
FFR at 120/min than those without (423 ± 121 vs. 165 ± 133, p=0.0017, Fig. 4b).
15
Discussion
Background characteristics of patients with MA
Although MA has been reported in patients with severe heart failure or LV
dysfunction [2-6], a recent study of DCM patients showed no statistical difference in
LVEF between patients with MA and those without [2]. Our data also showed no
correlation between LVEF and MA in DCM patients (Fig. 2a). It was obvious that
among patients with low LVEF some had MA and some did not, and low LVEF was not
sufficient to cause MA. In the present study, PCWP and LVEDP were significantly
lower in DCM MA(+) than in DCM MA(-) patients. This seems inconsistent with the
concept that MA is caused by heart failure and in fact other studies have shown that
patients with MA had higher PCWP and LVEDP [2,3]. However, MA is also known to
be induced by the standing posture [23] or by inferior vena caval occlusion [24] and can
disappear with exacerbation of heart failure [5,6]. Thus far, the effect of preload on MA
is still controversial. Effects of inotropic agents on MA are also controversial. Digoxin
had been prescribed only for patients with MA in this study and dobutamine has been
reported to increase the occurrence of MA [3,25]. On the other hand, attenuation or
elimination of MA with digoxin and isoproterenol has been reported in patients and in
16
dogs in the 1950’s and 1960’s [5,26,27]. These results show that inotropic agents affect
MA but their effects are not straightforward. Considering that MA is induced by
tachycardia, we can expect that heart rate-dependent parameters are more likely to
correlate with MA than those basal hemodynamics or patient characteristics.
Rate-dependent contractile parameters of patients with MA
We showed that DCM MA(+) patients had smaller FG-FFR, larger FG-PSP, and a
wider gap between them than DCM MA (-) patients did. The relationship between
FG-FFR and FG-PSP in patients with MA showed a clear contrast compared with the
control cases (Fig. 3c). This implies that not only each of the two rate-dependent
contractile properties, but also the balance between them play important roles in the
occurrence of MA. This may explain why the conditions that cause MA are not
straightforward.
One may say that the smaller FG-FFR and the larger FG-PSP in MA(+) patients
might have been caused by insufficient baseline preload, indicated by their
significantly lower LVEDP and PCWP, and although not statistically significant, by
their smaller LVEDV and LVESV than those of MA(-) patients. However, LVEDP at
baseline and at FG-FFR measurement were 5.3 ± 1.9 mmHg and 9.2 ± 5.9 mmHg in
17
MA(+) patients, and 13.5 ±10.6 mmHg and 14.4 ± 8.3 mmHg in MA(-) patients. The
larger increase in LVEDP could not explain the smaller FG-FFR. LVEDP at FG-PSP
measurement were 11.8 ± 4.2 mmHg (6.4 ± 4.6 mmHg increase from baseline) in
MA(+) patients and 19.4 ± 9.3 mmHg (5.9 ± 4.6 mmHg increase from base line) in
MA(-) patients. The similar increases could not explain the larger FG-PSP in MA(+)
patients. For precise evaluation of preload, left ventricular volume measurement is
required in future studies.
One advantage of using the gap between the two types of FGs is that it offsets
influences of the basal heart rate. When the basal heart rate is low, there will be a higher
chance to increase the force before incremental pacing reaches its endpoint, and as a
result, to increase both FG-PSP and FG-FFR. But this bias is offset by using the gap.
Furthermore as shown in Fig. 4, the gap between dP/dt in PSP and dP/dt in FFR at a
single rapid pacing rate can reveal a contractile property prone to cause MA without the
need of incremental pacing.
While FFR is known to be attenuated in patients with heart failure [12], this study
is the first to show enhanced PSP in heart failure patients. It is noteworthy that even
hearts with left ventricular dysfunction and MA can respond to tachycardia and enhance
its potential contractile force but simply cannot use the force effectively during
18
tachycardia. This finding will offer new insights into the pathophysiology and
therapeutics of heart failure and cardiac alternans.
Hypothetical mechanisms of MA
Left ventricular pressure-volume loops during MA of isolated canine hearts and
of a DCM patient have shown that MA is caused both by alternating preload and by
alternating contractility [28,29]. In MA(+) patients at maximal AA, LVEDP of a strong
beats, LVEDP of a weak beat, and the difference between them were 8.6 ± 6.5 mmHg,
6.3 ± 6.4 mmHg, and 2.2 ± 3.5 mmHg, respectively. The difference in preload seems to
have partially contributed to MA, but MA was not always accompanied by apparent
alternation of LVEDP, as have shown in isolated canine hearts [28].
The contractile force of cardiac myocytes is produced by a systolic rise of the
cytoplasmic calcium concentration, known as calcium transient [30], and recent
experimental studies have shown that MA is caused by calcium transient alternans
[7-10]. It is still speculative whether frequency- or coupling interval-dependent change
in contractile force is ruled by calcium kinetics, because calcium transient cannot be
recorded directly in the hearts of patients. However, assuming that the contractile force
is controlled mainly by the size of calcium transient, we can further discuss the
19
relationship between MA and FFR or PSP.
The underlying mechanism of FFR is considered as following: during rapid
stimulation more calcium ions enter the cardiac myocytes, and the more the cells are
loaded with calcium the stronger the heart contracts. Attenuated FFR along with
impaired calcium handling has been proven with ventricular muscle strips from patients
with heart failure [13,31]. In this study we have shown for the first time that MA
occurred in in-vivo patients’ hearts with impaired FFR. At first sight, MA seemed to
occur in hearts with an impaired calcium loading mechanism. If impaired calcium
loading had been the only mechanism of attenuated FFR, the hearts would have
received no extra force even with longer intervals after tachycardia. However, patients
with MA had far larger MFG-PSP than MFG-FFR. This suggests that the mechanism
which stores additional calcium during tachycardia is still working during MA, but the
heart with MA cannot effectively employ this mechanism during tachycardia.
The next question is why the contractile force during tachycardia did not reach
the level of PSP in patients with MA. Calcium is loaded mainly in the sarcoplasmic
reticulum in the cardiac myocytes, and the loaded calcium is released through the
ryanodine receptor, which is the calcium releasing channel of the sarcoplasmic
reticulum. According to this concept, the contractile force during tachycardia will be
20
smaller than PSP when the refractory period of the ryanodine receptor is prolonged or
when transport of the loaded calcium inside the sarcoplasmic reticulum to the ryanodine
receptor is delayed. Indeed, inhibition of the ryanodine receptor [8-11,32] and enhanced
buffering of calcium inside sarcoplasmic reticulum [14,33] have been shown to cause
alternans in experimental and computational studies. These experimental findings are
consistent with what really happens in in-vivo human hearts as shown in this study; MA
is caused with impaired FFR and enhanced PSP.
Study Limitations
This study included only 19 DCM cases and 6 control cases. MA is known to
occur in a variety of cardiac diseases and conditions and it remains unknown whether
the findings in this study are applicable to MA in other specific heart diseases.
Furthermore, 3 out of the 6 control cases had stable angina. Although none of the 3
control cases with stable angina showed MA in this study, MA is reported to be caused
by ischemia [31]. All the control cases, therefore should have been without coronary
stenosis.
PSP in this study was obtained from the first spontaneous beat which had various
coupling intervals. It may raise a suspicion that DCM MA(+) patients might have had
21
longer coupling intervals of PSP to obtain larger force gain in PSP compared to DCM
MA(-) patients.. However the mean coupling interval of PSP in DCM MA(+)
patients was rather shorter than that of DCM MA(-) patients even though
the difference was not statistically significant ( 812 ± 146 ms vs 916 ± 137ms,
p=0.15). The mean coupling interval of control patients was 1010 ± 148 ms.
Preferably these beats should have had the same coupling interval for precise
comparison among different heart rates and patients.
Acknowledgments
This study was supported in part by the Grants-in-Aid for Scientific Research
(18590763, 22590805) from the Ministry of Education, Science, Sports, Culture and
Technology of Japan.
22
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Legends to Figures
Fig. 1. Mechanical alternans, force-frequency relationship, and poststimulation
potentiation by incremental pacing.
a: A 52-year-old male with idiopathic dilated cardiomyopathy, whose LVEF was 34%,
showed mechanical alternans during pacing (arrows) and dP/dt of the first beat after
pacing (asterisk) was larger than those during pacing. b: Data from the same patient
with a. Closed squares show dP/dt at the basal heart rate and at each pacing rate. Open
triangles show left ventricular dP/dt of poststimulation potentiation at each pacing rate.
Open circles show alternans amplitude at each pacing rate.
c: A 56-year-old female with idiopathic dilated cardiomyopathy, whose LVEF was 22%,
did not show mechanical alternans and had relatively small rises in dP/dt during and
after pacing (arrow, asterisk). d: Data from the same patient with c. e: A 54-year-old
female control patient with angina pectoris, whose LVEF was 73%, showed an increase
in dP/dt during pacing without mechanical alternans (arrow). The first beat after pacing
showed smaller dP/dt (asterisk) than those during pacing. f: Data from the same patient
with e.
dP/dt: left ventricular dP/dt, ECG: electrocardiogram, FG-FFR: force gain in force
30
frequency relationship, FG-PSP: force gain in poststimulation potentiation. LVP: left
ventricular pressure. max AA: maximal alternans amplitude,
Fig. 2. Mechanical alternans and LVEF, basal left ventricular dP/dt, maximal dP/dt in
FFR, and force gain in FFR.
a: Plots show the maximal alternans amplitude (max AA) and LVEF of each patient.
The dashed bar divides patients with max AA of 100mmHg/sec or more (MA(+)) from
those with max AA less than 100mmHg/sec (MA(-)). Statistical difference between
MA(+) and MA(-) was analyzed among DCM patients only (closed squares). Data from
control patients are shown with “x” marks. b, c and d: Plots show max AA and basal
dP/dt, maximal dP/dt in FFR, and force gain in FFR, respectively.
Fig. 3. Mechanical alternans and poststimulation potentiation.
a: Plots show the maximal alternans amplitude (max AA) and force gain in
poststimulation potentiation (MFG-PSP) of each patient. The dashed bar divides
patients with a max AA of 100mmHg/sec or more (MA(+)) from those with a max AA
of less than 100mmHg/sec (MA(-)).Statistical difference between MA(+) and MA(-)
was analyzed among DCM patients only (closed squares). Data from control patients
31
are shown with “x” marks. b: Plots show alternans amplitude and the gap between
FG-PSP and FG-FFR of each patient. c: Plots show FG-FFR and FG-PSP of each
patient. Solid triangles show data from DCM MA(+) patients, open triangles from DCM
MA(-) patients, and “x” marks from control patients.
Figure 4. Mechanical alternans and the gap between dP/dt in PSP and dP/dt in FFR at
110/min and 120/min.
a,b: Plots show alternans amplitude and the gap between dP/dt in PSP and dP/dt in FFR
of each patient at 110/min (a), and at 120/min (b). The dashed bar divides patients with
alternans amplitude of 100mmHg/sec or more (MA(+)) at each pacing rate and those
with alternans amplitude of less than 100mmHg/sec (MA(-)). The arrow in b shows a
plot taken from a patient who showed MA at 110/min and lost MA at 120/min.
Statistical difference between MA(+) and MA(-) was analyzed among DCM patients
only (closed squares). Data from control patients are shown with “x” marks.
32