Correlation of Electrocardiographic Changes and Myocardial Fibrosis ...

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Aug 31, 2012 - Results: All of the subjects showed some degree of LGE on CMR. The AP group showed .... Abbreviations: AP, apical hypertrophic cardiomyopathy; ASH, asym- metric septal ... Corrected QT interval (ms). 452.4 ± 26.9. 449.5 ± ...
Clinical Investigations Correlation of Electrocardiographic Changes and Myocardial Fibrosis in Patients With Hypertrophic Cardiomyopathy Detected by Cardiac Magnetic Resonance Imaging

Address for correspondence: Hyun Suk Yang, MD Division of Cardiology, Department of Medicine Cardiac and Vascular Center, Konkuk University Medical Center Konkuk University School of Medicine 4-12, Hwayang-Dong Gwangjin-Gu, 143-729, South Korea [email protected]

Bong Gun Song, MD; Hyun Suk Yang, MD; Hweung Kon Hwang, MD; Gu Hyun Kang, MD; Yong Hwan Park, MD; Woo Jung Chun, MD; Ju Hyeon Oh, MD Division of Cardiology (Song, Yang, Hwang), Cardiac and Vascular Center, Department of Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul; Division of Cardiology (Kang, Park, Chun, Oh), Cardiac and Vascular Center, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea

Background: Despite several electrophysiologic and pathologic studies, the cause of electrocardiographic (ECG) changes in patients with hypertrophic cardiomyopathy (HCM) remains unclear. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can detect myocardial fibrosis. We aimed to assess the relationship between ECG findings and LGE in such patients. Hypothesis: Myocardial LGE may be associated with ECG changes in HCM. Methods: Seventy consecutive patients with HCM (mean age, 55.5 ± 10.7 years; 47 males) underwent CMR and 12-lead ECG. The subjects were divided into 3 groups according to the type of hypertrophy: the asymmetric septal hypertrophy group (ASH group, n = 31), the apical hypertrophy group (AP group, n = 22), and concentric hypertrophy group (CH group, n = 17). The transmural and segmental extent, pattern, and location of myocardial LGE were assessed and analyzed in relation to ECG changes. Results: All of the subjects showed some degree of LGE on CMR. The AP group showed significantly higher prevalence of negative T-wave (P = 0.028) and deep negative T-wave inversion (P = 0.001) than the ASH and CH groups. The total volume of LGE did not show any significant association with ECG changes. LGE detected at the interventricular septum was associated with increased QRS duration (P = 0.009) and was found in 94% of the ASH group, 59% of the AP group, and 77% of the CH group. LGE at the apex of the heart was present in 32% of the ASH group, 73% of the AP group, and 35% of the CH group and was also associated with negative T-wave (P = 0.006) and deep negative T-wave inversion (P = 0.018). Multifocal LGE lesions were associated with increased QRS duration (P = 0.039) as opposed to single nodular or patchy pattern of presence. Conclusions: The location of myocardial LGE in HCM shows significant association with various ECG changes. This may be useful information for initially evaluating subjects with HCM and adds pathophysiological insight into understanding ECG changes in myocardial diseases that cannot be explained otherwise.

Introduction Hypertrophic cardiomyopathy (HCM) is a genetic disorder with various morphologic, functional, and clinical features.1,2 Patients with HCM show various abnormalities in the 12lead electrocardiogram (ECG), including left ventricular (LV) hypertrophy, abnormal Q waves, bundle branch block, and giant negative T-wave inversion.3 – 5 The mechanisms of these ECG abnormalities have been studied using

The authors have no funding, financial relationships, or conflicts of interest to disclose. Received: June 17, 2012 Accepted: August 31, 2012

echocardiography or left ventriculogram but still remain unknown.6,7 Cardiac magnetic resonance (CMR) offers high spatial resolution and 3-dimensional tomographic imaging allowing for better visualization and characterization of the pattern and distribution of LV hypertrophy.8 – 10 Recently published studies have reported that late gadolinium enhancement (LGE)-CMR is a common feature of HCM and may indicate myocardial fibrosis and necrosis.10 – 12 The purpose of this study was to assess various ECG and LGE-CMR findings according to the pattern and distribution of HCM and investigate the possible Clin. Cardiol. 36, 1, 31–35 (2013) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22062 © 2012 Wiley Periodicals, Inc.

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associations between various ECG abnormalities and LGE-CMR findings.

Methods Study Patients This study included 70 patients who were diagnosed with HCM at Konkuk University Medical Center and Samsung Changwon Hospital, South Korea, between January 2009 and December 2011. HCM was diagnosed by the presence of a nondilated and hypertrophied LV (maximal wall thickness ≥15 mm) in the absence of another cardiac or systemic disease that may produce LV hypertrophy.13 – 15 Medical history was assessed from each patient’s medical records. Patients with hypertension, coronary artery disease, chronic renal failure, and valvular heart disease of more than a trivial degree were excluded. The protocol was approved by the institutional research ethics committee, and the ethical recommendations of the revised version of the Declaration of Helsinki were met. Electrocardiogram Standard 12-lead ECG was performed before CMR in all patients and analyzed by 2 experienced cardiologists blinded to the clinical data of patients. The criteria of abnormal Q wave were ≥0.04 seconds in duration, ≥25% of the R wave in depth, or 3 mm in depth in at least 2 contiguous leads except aVR.3,5,15,16 The criteria of deep T-wave inversion were ≥0.5 mV in at least 2 contiguous leads.3,4,6,15,16 Bundle branch block, QRS duration, and corrected QT interval were also analyzed. CMR Imaging Magnetic resonance images were obtained with 2 different 1.5 T magnetic scanners (Achieva 1.5 T; Philips Medical Systems, Best, the Netherlands; and Magnetom Avanto 1.5 T; Siemens Medical Solutions, Erlangen, Germany) with a phased array cardiac coil and electrocardiogram gating. Cine magnetic resonance imaging was obtained using steady-state, free precession breath-hold cines in 3 longaxis planes and sequential 10-mm short-axis slices from the atrioventricular ring to apex. In LV short-axis cine datasets, the LV endocardial and epicardial borders manually were traced at end diastole and end systole, respectively. LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, stroke volume, and LV mass were automatically calculated using standard ventricular analysis software (ARGUS; Siemens Medical Solutions). LV mass index (LVMI) was defined as LV mass divided by body surface area. Magnetic resonance delayed enhancement imaging was performed with a contrast-enhanced (gadolinium-DPTA 0.2 mmol/kg bodyweight [Gadovist 1.0; Bayer Schering Pharma, Berlin, Germany]) TrueFISP or 2-dimensional turboFLASH sequence with coverage of the entire LV. LGE was considered present when the signal intensity of any area within the myocardium was highly hyperintense in a sequence performed with a nonselective inversion pulse adjusted to null the myocardium and acquired up to 10 minutes after injection of contrast medium. The summed LGE area was rendered to LGE volume and the percentage

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Clin. Cardiol. 36, 1, 31–35 (2013) B.G. Song et al: ECG changes in HCM patients by CMR Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22062 © 2012 Wiley Periodicals, Inc.

against total myocardium volume was calculated. The patterns of LGE were defined, as apical involvement when LGE was detected in apical segments, septal involvement when LGE was detected in septal segments, and multifocal involvement when LGE was detected in other segments in addition to apical or septal segments. The data of CMR were transferred to a satellite workstation and analyzed using validated software (ARGUS; Siemens Medical Solutions) by 2 experienced radiologists. The patterns of LV hypertrophy by CMR were defined as asymmetric septal when a ratio ≥1.3 of septum to free wall was present, apical when both an apical wall thickness ≥15 mm and a ratio ≥1.3 of maximal LV short-axis thickness at the apical level to the basal level were present, and concentric when LV short-axis thickness ≥15 mm from the apical to the basal level were present.15,17,18 Statistical Analysis Statistical analyses were performed using SPSS statistic software version 17.0 (IBM, Armonk, NY). Continuous variables were expressed as mean ± standard deviation and categorical variables as number and percentage. The Student t test or analysis of variance was used to compare the mean values between groups, and the χ2 test was used to compare the categorical variables. Spearman correlation analysis was used to verify the correlation between continuous variables. Differences were considered statistically significant when P values were