Usefulness of Magnetocardiography to Detect Coronary ......measured on intravascular ultrasound in...

Circulation Journal Vol.77, July 2013

Circulation JournalOfficial Journal of the Japanese Circulation Societyhttp://www.j-circ.or.jp

probability because of the ionizing radiation and cost.5Cardiac allograft vasculopathy (CAV) is the leading cause

of late mortality in recipients of heart transplantation.6 It is characterized by a diffuse, concentric, intimal thickening of both the epicardial and intramyocardial arteries. Intravascular ultrasound (IVUS) has been considered a much more sensitive method in the diagnosis of CAV,7,8 but invasiveness and cost limit its clinical application. Stress ECG and myocardial SPECT often underestimate the extent and severity of CAV due to the diffuse nature of the disease and balanced ischemia.9–11 Dy-

echniques for diagnosing and estimating the severity of coronary artery disease (CAD) are important. Ex-ercise electrocardiography (ECG) test is the most com-

mon screening test, but lower diagnostic accuracy has been reported, especially in women, in subjects with greater func-tional impairment or after revascularization procedures.1 The use of stress single-photon emission computed tomography (SPECT) or CT coronary angiography is superior to exercise ECG test,2–4 but are not indicated in unselected, asymptomatic individuals or symptomatic subjects with low pretest CAD

T

Received September 27, 2012; revised manuscript received February 12, 2013; accepted March 19, 2013; released online April 19, 2013 Time for primary review: 32 days

Cardiology Division of Cardiovascular Medical Center (Y.-W.W.), Department of Nuclear Medicine (Y.-W.W., S.-Y.W.), Far Eastern Memorial Hospital, New Taipei City; National Yang-Ming University School of Medicine, Taipei (Y.-W.W.); Department of Internal Medicine (Cardiology Division) (Y.-W.W., C.-M.L., Y.-B.L., H.-C.H., H.-Y.J., C.-C.W.), Department of Nuclear Medicine (Y.-W.W.), Department of Surgery (S.-S.W.), National Taiwan University Hospital, Taipei; Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei (H.-E.H.); Department of Physics, National Taiwan University, Taipei (H.-C.Y.); Department of Primary Care Medicine, College of Medicine, National Taiwan University, Taipei (C.-C.W.); and E-Da Hospital, Kaohsiung (W.-K.T.), Taiwan

Mailing address: Chau-Chung Wu, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital and Primary Care Medicine, College of Medicine, National Taiwan University, No. 7 Chung-Shan S. Road, Taipei 10002, Taiwan. E-mail: [email protected]

ISSN-1346-9843 doi: 10.1253/circj.CJ-12-1170All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected]

Usefulness of Magnetocardiography to Detect Coronary Artery Disease and Cardiac Allograft Vasculopathy

Yen-Wen Wu, MD, PhD; Chii-Ming Lee, MD, PhD; Yen-Bin Liu, MD, PhD; Shoei-Shen Wang, MD, PhD; Hui-Chun Huang, MD; Wei-Kung Tseng, MD;

Hsiang-Yiang Jui, PhD; Shan-Ying Wang, MD; Herng-Er Horng, PhD; Hong-Chang Yang, PhD; Chau-Chung Wu, MD, PhD

Background: Electrophysiological information as well as anatomic information are important for the detection of coronary artery lesions. The aim of this study was to assess the efficacy of resting magnetocardiography (MCG) in stable coronary artery disease (CAD) and cardiac allograft vasculopathy (CAV).

Methods and Results: MCG and coronary angiography were performed within 1 month in 75 patients with sus-pected CAD and in 26 subjects after orthotopic heart transplantation (OHT). Plaque volumes were additionally measured on intravascular ultrasound in OHT recipients. The spatially distributed QTc interval maps were con-structed with 64-channel MCG. A T-wave propagation map and QTc heterogeneity index including QTc dispersion and smoothness index of QTc (SI-QTc) were derived for ischemia detection and localization. CAD patients had higher QTc dispersion and SI-QTc. Receiver operating characteristic curve analysis identified SI-QTc ≥9 ms, QTc dispersion ≥79 ms as the optimal cut-off for detecting CAD (diagnostic accuracy, 0.7953, 0.7819), better than T-wave propagation (0.6594, P<0.05). There was no significant difference of QTc dispersion between CAD and OHT sub-jects. In OHT recipients, QTc dispersion positively correlated with plaque volume, and SI-QTc progressively increased after transplantation. Using T-wave propagation mapping, regionally increased dispersion could be demonstrated in CAD patients, but increased dispersion was noted in fewer OHT recipients.

Conclusions: MCG is clinically feasible as a non-invasive tool for diagnosis of CAD, and could be used as a sur-rogate marker of CAV. (Circ J 2013; 77: 1783 – 1790)

Key Words: Cardiac allograft vasculopathy; Coronary artery disease; Heart transplantation; Magnetocardiogram

ORIGINAL ARTICLEIschemic Heart Disease


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has not been established. The aim of the present study was therefore to assess the diagnostic efficacy of MCG in the eval-uation of subjects with suspected CAD or CAV.

MethodsSubjectsBetween November 2006 and February 2011, 75 patients with suspected CAD and 26 recipients of orthotopic heart trans-plantation (OHT) with preserved left ventricular (LV) systolic function (ejection fraction [EF] ≥50%) were enrolled. All par-ticipants had a physical examination and 12-lead resting ECG. Exclusion criteria were significant arrhythmias, known MI his-tory or Q wave on surface 12-lead ECG, unstable angina pec-toris, significant valvular heart disease, metallic prosthesis (in-cluding pacemaker and implantable cardioverter defibrillator). Patients with surgical wires in the sternum were not excluded. All OHT recipients were treated with standard immunosup-pressive therapies as previously described.29 An endomyocar-dial biopsy (EMB) was performed weekly in the first month; once every 3 months in the first 6 months; at 1 year; and then annually thereafter. Coronary angiography was performed at 1 month after transplantation, then annually. For each subject,

namic perfusion positron emission tomography (PET) has been considered superior to invasive coronary angiography and SPECT in the detection of CAV.12 The complexity of produc-tion and delivery of short-lived PET tracers, high cost and ra-diation exposure, however, hinder wide utilization. Therefore, the need for a sensitive and non-invasive surveillance diagnos-tic tool is of clinical importance.

Myocardial ischemia alters regional electrophysiological properties by depolarizing the cellular membrane, reducing membrane excitability, shortening action potential duration, slowing conduction velocity, and prolonging the refractoriness beyond repolarization.13,14 Magnetocardiography (MCG) has been proposed as a non-invasive, contact-free, non-radiation technique with high reproducibility for functional diagnosis of myocardial injury and arrhythmias. MCG in the resting state has been reported to have good diagnostic accuracy of 60–90% in subjects with prior myocardial infarction (MI),15–17 un-stable angina or non-ST segment elevation MI,18–21 and stable CAD.22–28 Despite the unique fundamental principles and high sensitivity of MCG, interpretation remains a challenge because it requires highly experienced personnel and is time-consum-ing, and the criteria of diagnosis of CAD are still controver-sial. In addition, the clinical utility of MCG in diagnosing CAV

Figure 1. (A) Example of 64-channel magnetocardiography (MCG) generated repolarization map with a 21×21 resolution by signal-averaged vector-projected electrocardiography. (B) Junctional points of QRS and T were determined automatically from the superimposed 64-channel MCG waveform). (C) A QT contour map was constructed from the repolarization map accordingly.


1785MCG in Diagnosis of CAD and CAV

left chest wall. After baseline correction, data were averaged using R-peaks to obtain a time-averaged 1-period magnetocar-diac signal. The spatiotemporal analysis of repolarization het-erogeneity was determined from the spatial distribution of the QT intervals (Figure 1A). The QT interval was automatically defined from the earliest onset of the QRS complex to the lat-est terminal portion of the T wave at each position from the time-averaged Bz-t curves by using overlapped MCG wave-forms, then visually checked and manually corrected if neces-sary (Figure 1B). The QT was used for the construction of the QT contour map, with a spatial resolution of 21×21 (Figure 1C). We derived 2 parameters from the QT contour map to repre-sent the myocardial repolarization heterogeneity. First, the QTc dispersion was derived from the difference between the lon-gest and shortest QTc interval on the QT contour map. Second, we derived the spatial smoothness index of QTc (SI-QTc), mod-ified from Van Leeuwen et al,22 from the QT contour map via:

SIQTc ≡ (1/S) ΣS {(1/n) Σn [(QTc)k – (QTc)n]},

where S is the total number of measured MCG points, ΣS is summed over the total measured MCG points, n is the num-ber of nearest neighbors for a fixed position k, and (1/n) Σn [(QTc)k − (QTc)n] is the spatially averaged QTc at a fixed mea-sured position k summed over the total number of nearest neigh-

echocardiography and MCG were performed within 1 month of the coronary angiography. The protocol was approved by the institutional review board, and written informed consent was obtained from each patient before enrollment.

12-Lead ECGAfter examining the quality of the 12-lead ECG recording, the QT interval was automatically measured from the onset of the QRS complex to the end of the T wave (defined as the return to the T-P isoelectric line). The QT was measured at the nadir of the curve between the T and U waves when a U wave was present. The QTc represented a QT interval corrected for the previous cardiac cycle length and was calculated automati-cally according to Bazett’s formula: QTc = QT / (R-R)1/2 (where the R-R interval is given in seconds).30

MCGAll MCG measurements were obtained in a magnetically shield-ed room using a 64-channel superconducting quantum inter-ference device (SQUID) system developed by the Korea Re-search Institute of Standards and Science. The MCG signals were digitally recorded for 100 s at a sampling rate of 500 Hz, with the patient in the supine position and the SQUID’s 2-D arrayed sensors positioned close to, but not in contact with, the

Figure 2. Examples of (Left) QT contour map and (Right) T-wave propagation in subjects with significant coronary stenosis. The time-dependent area ratio of positive (+) T to negative (–) T waves is analyzed. Yellow-to-red, +T waves; blue-to-black, –T waves. The earliest area of the +T waves could be located in the ischemic myocardium: (A) left anterior descending artery (LAD); (B) left circumflex artery (LCX); and (C) right coronary artery (RCA).


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antibody-mediated rejection (AMR) and acute cellular rejec-tion (ACR).32

Diagnostic coronary angiogram was performed using stan-dard techniques after pretreatment with i.c. nitroglycerin to avoid vessel spasm; multiple projections of coronary arteries were recorded digitally, and the degree of coronary stenosis was assessed using a computer-aided quantitative angiographic anal-ysis system (DCI-S Automated Coronary Analysis; Philips Medical Systems, The Netherlands). Significant CAD was de-fined as angiographic maximum lesions ≥50% luminal steno-sis in the left main (LM), or ≥70% in at least one of the primary coronary arteries and their major branches. In OHT patients, CAV status was further classified in accordance with International Society for Heart and Lung Transplantation (ISHLT) recommended nomenclature as follows: not signifi-cant, CAV0; mild, CAV1; moderate, CAV2; or severe, CAV3.32,33

In OHT subjects, additional IVUS (Atlantis SR Pro 2.5F, 40-MHz; Boston Scientific) of the left anterior descending coronary artery (LAD) was performed after the coronary an-giography5,9,33 using the resident software (Galax system; Boston Scientific). The percentage of maximum area stenosis was calculated as (maximum plaque area/vessel volume) × 100%, and percentage of atheroma volume (PAV) was defined as (total plaque volume/total vessel volume) × 100%, which normalized the individual variations of the vessel and vessel length.

Statistical AnalysisAll data are given as mean ± SD. Comparisons were made using Student’s t-test for continuous variables and chi-square analy-sis for categorical variables. ANOVA was performed to detect any associations between 2 or more variables. In the subgroup of cardiac transplant recipients, IVUS measurements were com-pared with MCG variables on linear regression analysis. The

bors, n. Then, the time-dependent area ratio was analyzed via

the equation of A+T(t) 1+A–T(t), where A+T and A–T denote the areas

occupied by +T and –T waves at a certain instant t, and a T-wave propagation map was then plotted, as previously de-scribed.26 The early occurrence of the +T wave could be at-tributed to the shorter action potential of ischemic myocardium, and the vascular distribution was defined by the 2-D mapping around the occurrence of the peak. The representative images of QT contour map and T-wave propagation in subjects with significant coronary stenosis are given in Figure 2. Quality evaluation and analysis of ECG and MCG were performed by an independent investigator.

EchocardiographyEchocardiography was performed with 2.5–3.75-MHz trans-ducers (Hewlett-Packard 5500; Hewlett-Packard, Palo Alto, CA, USA) according to standard criteria. Peak velocities of early filling (E), atrial filling (A), and deceleration time (DT) of early filling of transmitral flow were recorded using pulsed-wave Doppler from an apical 4-chamber view. Tricuspid re-gurgitation velocity was obtained on continuous-wave Doppler, which reflects the pressure difference during systole between the right ventricle and the right atrium (4 × tricuspid regurgita-tion velocity2). Restrictive physiology was defined as LVEF >50%, E/A ratio >2 and shorter DT (<150 ms) or restrictive hemodynamic parameters (estimated pulmonary capillary wedge pressure >25 mmHg).31

Cardiac Catheterization and EMBStarting the first or second week after transplantation, EMB were done. Histologic and immunofluorescence findings were recorded, and semi-quantitative scales were used to report an

Table 1. Subject Clinical Characteristics

With CAD (n=51) Without CAD (n=24) OHT (n=26) P-value

Age (years) 64±10 64±10 52±12 0.0174

Male 50 (94) 17 (71) 20 (77) <0.0001　Cardiovascular risk factors

Hypertension 41 (80) 17 (71) 8 (31) <0.0001　 Diabetes mellitus 18 (35) 5 (21) 10 (38) NS

Hyperlipidemia/statin 41 (80) 11 (46) 3 (12) <0.0001　UCG

IVS (mm) 11.6±2.2 11.5±1.8 11.8±1.5 NS

PW (mm) 11.3±1.7 10.1±1.7 11.0±1.4 NS

LVEDD (mm) 49.6±4.5 46.6±2.1 44.6±3.9 0.0007

LVESD (mm) 33.0±9.0 27.6±2.6 27.6±3.3 0.0060

LVEF (%) 65.6±9.0 71.0±5.1 67.2±6.0 NS

E/A ratio 0.98±0.71 0.87±0.33 1.71±0.70 <0.0001　 DT (ms) 227.8±55.0 194.9±39.5 164.5±43.4 0.002　　 TR PG (mmHg) 32.5±17.3 26.4±7.8 24.0±8.3 NS

12-lead ECG QTc (ms) 427±65 405±29 443±23 0.004　　MCG

Early TW peak 45 (88) 14 (58) 15 (58) 0.0023

QTc (ms) 383±29 377±25 435±53 <0.0001　 QTc dispersion (ms) 95.2±22.3 74.1±18.1 99.7±20.8 0.0001

SI-QTc (ms) 10.82±2.26 8.57±2.91 9.61±2.60 0.0016

Data given as mean ± SD or n (%). CAD, coronary artery disease; DT, deceleration time; EDD, end-diastolic diameter; EF, ejection fraction; ESD, end-systolic diameter; IVS, interventricular septum; LV, left ventricular; MCG, magneto-cardiography; OHT, orthotopic heart transplantation; PW, posterior wall; SI, smoothness index; TR PG, tricuspid regur-gitation pressure gradient; TW, T wave; UCG, ultrasound echocardiography.



or MCG (P=0.25) between subjects with CAD and those with-out. Patients with significant CAD had significantly larger LV dimensions, higher prevalence of early occurrence of time-de-pendent area ratio of +T-wave propagation and increased het-erogeneity (QTc dispersion and SI-QTc) on MCG (all P<0.05). ROC curve analysis identified SI-QTc ≥9 ms, QTc dispersion ≥79 ms as the optimal cut-off for detecting CAD. There were no significant differences between areas under the ROC curve (AUC) when using a single criterion or a combination of QTc dispersion and SI-QTc criteria (Figure 3).

Although the heterogeneity indicators were consistently more

strength of associations was estimated with the Pearson cor-relation coefficient (r). Diagnostic criteria of CAD using QTc on 12-lead ECG and MCG, the presence of early peaking of T-wave propagation, QTc dispersion and SI-QTc on MCG were developed based on receiver operating characteristic (ROC) analysis. Logistic regression was used to evaluate the statisti-cal significance of different cut-offs of QTc dispersion and SI-QTc in predicting CAD. All analyses were performed using STATA (release 10.0; StataCorp LP). All statistical tests were 2-sided, and P<0.05 was considered statistically significant.

ResultsA total of 75 subjects with known or suspected CAD and 26 OHT recipients were included in the study. The clinical char-acteristics are summarized in Table 1.

Of 75 subjects with known or suspected CAD, there were 51 patients with significant CAD based on coronary angiogram; 16 had single-vessel disease, 17 had 2-vessel disease, and the remaining 18 patients had LM or 3-vessel disease. There was good correlation between QTc dispersion and SI-QTc (r=0.70, P<0.0001). The early occurrence of +T-wave propagation was also correlated with higher SI-QTc (P=0.049), but not QTc dispersion. There was no significant association between clin-ical characteristics (including age, gender and cardiovascular risk factors) and these MCG parameters. Only QTc dispersion was positively correlated with LV end-systolic dimensions (P=0.038).

There was no significant difference of QTc on ECG (P=0.14)

Figure 3. Receiver operating character-istic (ROC) curve of QTc dispersion and smoothness index of QTc (SI-QTc) crite-ria using magnetocardiography (P=NS). CI, confidence interval.

Table 2. MCG Parameters in Detection of Significant CAD

Early TW peak QTc dispersion ≥79ms or SI-QTc ≥9 ms

ROC area (95% CI) 0.6594±0.0562 (0.5393–0.7597)

0.7855±0.0533 (0.6811–0.8900)

Sensitivity (%) 88 86

Specificity (%) 42 71

PPV (%) 76 86

NPV (%) 63 71

Diagnostic accuracy (%)

73 81

CI, confidence interval; NPV, negative predictive value; PPV, posi-tive predictive value; ROC, receiver operating characteristic; SI, smoothness index. Other abbreviations as in Table 1.


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mined on IVUS agrees well with myocardial perfusion reserve assessed on PET in OHT recipients,12 it can be used as a mark-er of inducible ischemia burden and disease severity. In the present study, QTc on ECG and MCG was significantly high-er in OHT patients than in those with patent coronary angio-gram (both P<0.0001), but did not correlate well with any IVUS parameters. In contrast, only QTc dispersion derived from MCG was positively correlated with PAV (r=0.49, P=0.021) and max-imum area stenosis (r=0.37, P=0.049). The OHT recipients with QTc dispersion ≥79 ms or SI-QTc ≥9 ms, the criteria for de-tecting significant CAD, had significantly higher PAV than those with lower QTc dispersion or SI-QTc (27.8±10.8%, n=15 vs. 16.9±9.8%, n=11, P=0.014). Although SI-QTc was not cor-related well with plaque volume in OHT patients, it still mar-ginally increased with the post-transplantation time (P=0.05; Figure 4).

DiscussionSpatial electrical heterogeneity within the ventricular myocar-dium has been demonstrated in previous studies.34,35 The spa-tial heterogeneity of repolarization could be amplified during pathological condition. Increased repolarization heterogeneity of the diseased heart can be either anatomic, due to infarction, fibrosis, or structural remodeling; or electrophysiological, due to electrical remodeling, drugs, genetic defects, or heteroge-neous autonomic innervations.36 Chronic myocardial disease could result in both electrophysiological and structural remod-eling of the heart, and both could affect the repolarization het-erogeneity of ventricular myocardium.

Many MCG studies investigated repolarization abnormali-

effective than the time-dependent area ratio of T-wave propa-gation for detecting CAD (P=0.036), the early occurrence of +T waves can be used to localize the shorter action potential of ischemic myocardium. The 6 patients who had increased abnormal QTc heterogeneity but who lacked early +T-wave peak had multivessel disease. The sensitivity, specificity, pos-itive predictive value and negative predictive value are sum-marized in Table 2.

There were no significant correlations between parameters of ECG and MCG, and their clinical characteristics (including immunosuppressive regimen, echocardiographic parameters, ACR and CAV grades) for OHT subjects, except for a nega-tive association between SI-QTc and pre-transplant diagnosis of CAD (r=–0.40, P=0.039). After adjustment for covariates of hypertension (r=0.44, P=0.024) and hyperlipidemia (r=0.44, P=0.032), only an insignificant correlation between SI-QTc and ischemic cardiomyopathy before OHT remained.

EMB was performed 12±4 times (range, 3–21 times) and angiography 10±3 times (range, 1–16 times) in each OHT re-cipient within 4.3±3.5 years (range, 1–12 years) after heart transplantation. Only 4 of 298 EMB (1.3%) were classified as ≥grade II ACR but none as AMR. None of the OHT recipients had an acute rejection of ISHLT grade II or higher based on the concurrent EMB findings (only 1A in 6 patients). There were no significant differences in ECG and MCG parameters between subjects with or without acute rejection.

Five OHT subjects had angiographic coronary stenosis (all <50% of luminal stenosis: 3 with 1-vesssel disease and 2 with 2-vessel disease). No significant difference of clinical charac-teristics between subjects with normal coronary angiograms and those without was noted. Because plaque burden deter-

Figure 4. Correlation between magnetocardiography parameters and (A) percentage of atheroma volume (PAV) and (B) time after heart transplant. SI-QTc, smoothness index of QTc.



heterogenous interstitial fibrosis may exist. It is possible that not only myocardial ischemia but also increased interstitial cellularity or extracellular matrix accumulation could affect repolarization heterogeneity. Other methods such as delayed enhanced magnetic resonance imaging could be considered for comparison. Furthermore, we performed IVUS only in the LAD vessel, but the real extent and severity of CAV in these pa-tients cannot be assessed in vivo.

To the best of our knowledge, this is the first study to evalu-ate the efficacy of using MCG in the resting state as a non-invasive assessment of CAD and CAV. The present study sug-gests that MCG is clinically feasible as a diagnostic tool in the detection of CAD. A negative or stable MCG may obviate the necessity for invasive coronary angiography and IVUS sur-veillance in transplant recipients.

The limitations of this study include the following factors: the subject group was small and heterogeneous, and the study was cross-sectional in design. Variable factors, especially in the OHT group (including donor demographic factors, donor ischemic time, immunosuppressive regimen and history of acute rejection), may weaken the association between the study vari-ables and the MCG results. Little information on the relation-ship with arrhythmia was addressed due to study design. Also, the predictive value of MCG for long-term clinical outcome is not available. A large-scale prospective longitudinal follow-up study is warranted to further elucidate at what point the elevat-ed QTc heterogeneity is associated with significant CAD or CAV, complex arrhythmias or LV dysfunction.

ConclusionWe have developed a new method for quantitative estimation of repolarization heterogeneity using MCG, which had good diagnostic accuracy in significant CAD and good correlation with plaque volume on IVUS in CAV. The repolarization het-erogeneity index determined on MCG is clinically feasible as a diagnostic tool for the non-invasive examination of signifi-cant CAD, and could be used as a surrogate marker for CAV.

AcknowledgmentsWe thank Yu-Hui Huang, Tsai-Tzu Wu, Yu-Chi Lin, Guan-Hong Wu and Jun-You Ou for their technical assistance. This work was partly supported by the National Science Council of Taiwan under Grant NSC 96-2314-B-002-150-MY3 and 99-2314-B-002-141-MY3.

DisclosuresConflict of Interest: None declared.

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ties in subjects with acute chest pain,17–21 or stable CAD after stress36,37 or at rest.22–28 Those studies have focused either on exercise-induced ischemia or on ischemia and the infarct scar at rest. Different parameters have been developed based on signal intensity/vector, time intervals, or magnetic field map analysis. In a previous study, we have also utilized a 64-chan-nel MCG system to detect the time-dependent area ratio of T-wave propagation that is spatially distributed over the heart, for screening and localizing the myocardial ischemia.26 There was no clear separation, however, of patients with CAD from those with patent coronary arteries using these MCG param-eters. Even with a combination of multiple MCG parameters, the sensitivity was approximately 75–85% and the specificity was approximately 70–80% for diagnosis of CAD based on post-hoc analysis. The evaluation of spatial QT dispersion on MCG, reflecting regional heterogeneity of repolarization, may improve the identification of CAD patients.18,38 In this study, we demonstrated not only that the patients with significant CAD had significantly higher prevalence of early occurrence of +T-wave propagation and increased heterogeneity (QTc disper-sion and SI-QTc), but also that the repolarization heterogeneity index has superior diagnostic accuracy to T-wave propagation mapping in the patients with suspected CAD (0.79 vs. 0.65; P=0.036).

The ECG of a transplanted or native heart are different which may be due to anatomically different position. Most grafts develop right ventricular distension and tricuspid insuf-ficiency, and changes in QRS morphology and T-wave con-figuration may be diffuse, non-specific or absent. A progres-sive increase in the QT interval is considered to be a prognostic indicator after heart transplantation associated with allograft rejection or CAV,39–41 and can be reversed after statin treat-ment.42 In the present study, none of the OHT subjects had a history of acute rejection. This study has shown that QTc dis-persion determined on MCG correlated well with coronary morphological changes on IVUS, suggesting that the develop-ment of CAV is associated with an increase in QTc dispersion. This suggests that QTc dispersion may be a useful marker or predictor of cardiovascular events due to ischemia or arrhyth-mia. These findings imply that CAV is a progressive process. The SI-QTc scores in OHT patients increased gradually over time, similar to the progression of inhomogeneity scores on SPECT.6

The present study has a practical implication in that the ad-dressed MCG heterogeneity scores for CAD would be useful for distinguishing the patients with significant CAD in rest state, and the best cut-off values for these criteria was established. In addition, 2-D T-wave propagation could be used to identify the most ischemic zones, and QTc dispersion may be a useful marker for the development of CAV after OHT. All of the pres-ent patients, however, were in sinus rhythm and none had left bundle branch block, so it should be stressed that the present observations are limited to patients with sinus rhythm and with-out left bundle branch block.

Due to the low prevalence of higher grade of acute rejection at the time of MCG, the relationship between severity of acute rejection and MCG parameters was not clear. Also, CAV, dia-stolic dysfunction due to increased interstitial fibrosis, is an-other main prognostic factor after heart transplantation. The present OHT recipients had preserved LV systolic function, but significantly higher E/A ratio and shorter DT compared to subjects with known or suspected CAD (Table 1). Overall, 19% (5/26) were classified as restrictive physiology status on echocardiography criteria. Although we did not find the as-sociations between episodes of ACR or AMR, progressive and


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