Ralacion Adreview y Potenciales Ventriculares

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ORIGINAL ARTICLE

Relationship between late ventricular potentials

and myocardial 123I-metaiodobenzylguanidine scintigraphy

in patients with dilated cardiomyopathy with mild

to moderate heart failure: results of a prospective study

of sudden death events

Shu Kasama & Takuji Toyama & Yoshiaki Kaneko &

Toshiya Iwasaki & Hiroyuki Sumino & Hisao Kumakura &

Kazutomo Minami & Shuichi Ichikawa &

Naoya Matsumoto & Yuichi Sato &

Masahiko Kurabayashi

Received: 29 November 2011 /Accepted: 15 February 2012 /Published online: 14 March 2012# Springer-Verlag 2012

Abstract

Purpose Late ventricular potentials (LPs) are considered to

be useful for identifying patients with heart failure at risk of

developing ventricular arrhythmias. 123I-metaiodobenzyl-

guanidine (MIBG) scintigraphy, which is used to evaluate

cardiac sympathetic activity, has demonstrated cardiac sym-

pathetic denervation in patients with malignant ventricular

tachyarrhythmias. This study was undertaken to clarify the

relationship between LPs and 123I-MIBG scintigraphy find-

ings in patients with dilated cardiomyopathy (DCM).

Methods A total of 56 patients with DCM were divided into

an LP-positive group (n024) and an LP-negative group (n0

32). During the compensated period, the delayed heart/me-

diastinum count (H/M) ratio, delayed total defect score

(TDS), and washout rate (WR) were determined from 123I-

MIBG images and plasma brain natriuretic peptide (BNP)

concentrations were measured. Left ventricular end-diastolic

volume (LVEDV), left ventricular end-systolic volume

(LVESV), and left ventricular ejection fraction (LVEF) were

simultaneously determined by echocardiography.

Results LVEDV, LVESV, LVEF and plasma BNP concen-

trations were similar in the two groups. However, TDS was

significantly higher (358 vs. 286, p


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high WR, the incidence of sudden death events was higher

than that in other subgroups of DCM patients.

Keywords123I-MIBG . Late ventricular potentials .

Dilated cardiomyopathy

Introduction

Patients with idiopathic dilated cardiomyopathy (DCM) have

a high incidence of ventricular arrhythmias [1] and are at

increased risk of sudden death from ventricular tachycardia

(VT) and ventricular fibrillation [2]. The histopathological and

electrophysiological characteristics of ventricular arrhythmias

in idiopathic DCM are even less well defined than those of

coronary artery disease. A variety of factors may contribute to

the genesis of ventricular tachyarrhythmias in DCM patients.

Therefore, identification of patients with idiopathic DCM at

risk of malignant ventricular arrhythmias is very important for

optimal medical management.Late ventricular potentials (LPs) detected by signal-

averaged electrocardiography (ECG) in patients with VT are

caused by delayed and fragmented ventricular activation.

These LPs are used to identify patients at risk of life-

threatening arrhythmias, and indicate an increased risk of

malignant ventricular arrhythmias and sudden death in those

with ischaemic heart disease and congestive heart failure [3, 4].

Myocardial imaging with 123I-metaiodobenzylguanidine

(MIBG), an analogue of norepinephrine, is useful for detect-

ing abnormalities of the myocardial adrenergic nervous

system in DCM patients [57]. Cardiac sympathetic nerve

activity evaluated by 123I-MIBG scintigraphy has prognostic

value in these patients [7, 8]. Moreover, recent clinical

studies have suggested that 123I-MIBG imaging predicts

ventricular arrhythmias in patients with heart failure

[9, 10].

In the present study, we clarified the relationship between

LPs and the findings of 123I-MIBG scintigraphy in patients

with mild to moderate heart failure (i.e. patients at low risk

of sudden death events) due to DCM, and determined

whether the presence of LPs and the findings of123I-MIBG

scintigraphy are a reliable sudden death marker in these

patients.

Materials and methods

Patient population

We selected 56 patients with idiopathic DCM (left ventric-

ular ejection fraction, LVEF, 38 ms and

RMS40


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Twenty-four-hour Holter ECG

Twenty-four-hour Holter ECG monitoring with two leads was

conducted using an ambulatory ECG recorder (DMC-4502;

Nihon Koden, Tokyo, Japan). A modified Lowns classification

[16, 17] was employed to evaluate the severity of ventricular

arrhythmias, including premature ventricular contractions.

Echocardiography

Echocardiography was performed using the standard method

in a blinded manner. Two independent and experienced echo-

cardiographers who had no knowledge of the study, per-

formed all measurements. Left ventricular end-diastolic

volume (LVEDV), left ventricular end-systolic volume

(LVESV), and LVEF were calculated using the modified

method of Simpson [18].

123I-MIBG imaging

The 123I-MIBG imaging method has already been described

in detail [19, 20]. Briefly, 123I-MIBG was obtained from a

commercial source (FUJIFILM RI Pharma, Tokyo, Japan).

At 15 min and 4 h after injection, anterior planar and SPECT

images were obtained with a single-head gamma camera

(Millennium MPR; GE Medical Systems, Waukesha, WI).

The heart/mediastinum count (H/M) ratio was deter-

mined from the anterior planar delayed 123I-MIBG image.

The washout rate (WR) was calculated from early and

delayed planar images. Regional tracer uptake was assessed

semiquantitatively using a five-point scoring system (0 0

normal to 4 0 no uptake) in 17 segments on the delayed

SPECT image as recommended by the American Heart

Association [21]. The total defect score (TDS) was calcu-

lated as the sum of all defect scores.

Plasma BNP concentrations

Blood samples were collected into test tubes containing

EDTA after the subject had rested in the supine position

for at least 30 min. Plasma was separated by centrifugation

and then frozen at84C. Then the plasma BNP was mea-

sured with a specific immunoradiometric assay for human

BNP using a commercially available kit (Shionogi, Osaka,

Japan), as previously reported [22, 23].

Statistical analysis

Statistical analyses were performed using SPSS 16.0 for Win-

dows (SPSS, Chicago, IL). Numerical results are expressed as

means (SD). In all analyses, p


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difference was not statistically significant. The H/M ratio was

significantly lower in the LP-positive than that in the LP-

negative group (1.570.23 vs. 1.780.20, p


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the LP-positive and high WR group was significantly higher

than those in the LP-positive and low WR group (p


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LPs in 43% of their patients with DCM [31]. Similarly, LPswere seen in 24 of our 56 patients (42.9%). Furthermore,

based on Lowns classification, the incidences of ventricular

arrhythmias was significantly higher in the LP-positive than in

the LP-negative group.

Patients with DCM have been found to show impairment of

presynaptic catecholamine reuptake, which can be assessed

using the norepinephrine analogue 123I-MIBG and either planar

scintigraphy or SPECT [58]. Moreover, 123I-MIBG uptake is

reportedly reduced in patients with malignant ventricular

tachyarrhythmias [32, 33]. Schafers et al. reported that patients

with right ventricular outflow tract tachycardia exhibit reduced123I-MIBG uptake in the posterior left ventricular wall, which

indicates presynaptic dysfunction [32]. On the other hand, in

our study, segmental analysis of SPECT images showed im-

paired uptake in the inferior wall in both groups and this wasworse, though not significantly, in the LP-positive group.

Further studies are necessary to clarify the relationship be-

tween segmental denervation and malignant ventricular

tachyarrhythmias.

Yukinaka et al. found that defect scores, as evaluated by123

I-

MIBG scintigraphy after myocardial infarction, were signifi-

cantly greater in LP-positive than in LP-negative patients [34].

In their study, however, perfusion evaluated by99m

Tc perfusion

imaging did not differ between the two groups. Therefore, the

presence of LPs may be more closely related to the denervated

but viable myocardium (i.e. the mismatch area) in patients with

myocardial infarction. In this study, we evaluated the 99mTcperfusion imaging in about half of the patients. However, the

presence of LPs did not relate to the mismatch area (data not

shown). Moreover, there were no relationships between perfu-

sion defects and denervated myocardium in our DCM patients.

Therefore, our findings demonstrate that the mechanisms asso-

ciated with the presence of LPs in patients with myocardial

infarction may be different from those in DCM patients.

Incidenceofsuddendeath(%)

**

*

**

*:p


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In our study, 123I-MIBG scintigraphic parameters (TDS,

H/M ratio and WR) overlapped between the LP-positive and

LP-negative groups, and it was difficult to utilize these

parameters. Tamaki et al. reported that WR is the most

powerful predictor of sudden cardiac death in the failing

human heart, and this parameter may be associated with a

change in arrhythmia mechanisms of re-entry, automaticity,

which triggers activity that provokes lethal arrhythmias

[35]. In this study, the difference in WR between the two

groups was more marked than that of both TDS and H/M

ratio, and this parameter was also the most significant factor

predicting sudden death in our DCM patients. Furthermore,

in the LP-positive patients with high WR, the incidence of

sudden death events was higher than in other subgroups, and

this finding was confirmed by logistic regression analysis.

Accordingly, DCM patients who are both LP-positive and

have WR50% should receive with the most careful med-

ical management.

Study limitations

The small number of DCM patients in this study limited the

statistical power. In addition, signal-averaged ECG is

known to be useful for prognostic evaluation of serious

arrhythmic complications in patients with acute myocardial

infarction [13]. However, LPs are not used widely in

patients with nonischaemic congestive cardiomyopathy, as

its positive predictive value has been shown not to be high

enough [36]. Another study has shown that 123I-MIBG

scintigraphy, but not LPs, is a powerful predictor of sudden

cardiac death in patients with cardiomyopathy [35]. Our

findings demonstrate for the first time that LP positivity

together with a high WR could be the incremental predictor

of sudden death in DCM patients, but further studies are

required to confirm this hypothesis in a larger group of

patients. It is still unclear whether the presence of LPs

impairs cardiac sympathetic nerve activity, or whether im-

paired cardiac sympathetic nerve activity leads to the pres-

ence of LPs in patients with nonischaemic heart failure.

Therefore, further studies are necessary to clarify the rela-

tionship between the presence of LPs and impaired123

I-

MIBG uptake.

Conclusion

The TDS, H/M ratio and WR determined by cardiac 123I-

MIBG scintigraphy were worse in LP-positive than in LP-

negative DCM patients. However, echocardiographic

parameters, plasma BNP concentrations and NYHA func-

tional class were similar in the two groups. Furthermore, in

LP-positive patients with high WR, the incidence of sudden

death events was higher than in other subgroups. These

findings indicate that DCM patients who are LP-positive

and have a high WR as evaluated by 123I-MIBG scintigra-

phy must be followed especially carefully during medical

management.

BA

Fig. 5 Delayed anterior planar 1123I-MIBG image (a) and signal-

averaged electrocardiogram (b) from an LP-negative patient. The

delayed H/M ratio and WR, as evaluated by 123I-MIBG, were 1.84%

and 42%, respectively. The f-QRS, LAS40 and RAM40 values were

98 ms, 29 ms and 84 V, respectively

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Conflicts of interest None.

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