International Journal of Cardiology 199 (2015) 34–37
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Successful prediction of MACE by myocardial fibrosis on CT in hypertrophic cardiomyopathy patients without obstructed coronary arteries Hiroyuki Takaoka, Nobusada Funabashi ⁎, Masae Uehara, Koya Ozawa, Yoshio Kobayashi Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
a r t i c l e
i n f o
Article history: Received 19 June 2015 Accepted 27 June 2015 Available online 9 July 2015 Keywords: Successful prediction MACE Myocardial fibrosis on CT Hypertrophic cardiomyopathy Without obstructed coronary arteries
Hypertrophic cardiomyopathy (HCM) is recognized as a high risk cardiovascular disease leading to sudden cardiac death in young people [1]. Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) are already known as useful modalities for risk stratification in HCM patients [2]. Recently there have been dramatic developments in multislice computed tomography (CT) which until now have been mainly used for the evaluation of coronary arteries [3,4]. However, multislice CT has not been used frequently in daily clinical practice for the evaluation of characteristics of left ventricular (LV) myocardium. To compare the value of non sustained ventricular tachycardia (VT) and myocardial fibrosis in LV myocardium on CT in risk stratification for major adverse cardiac events (MACE) in HCM patients without obstructed coronary arteries, using Kaplan–Meier analysis. We selected 45 consecutive symptomatic HCM patients (31 males, mean age 60 ± 14 years), who had suspected coronary artery disease, cardiac dysfunction, valvular disease or intracardiac thrombi, and who underwent cardiac CT (Aquilion one, Toshiba Medical or Light Speed ultra 16, GE Healthcare) mainly to evaluate coronary arteries, in whom no obstructed coronary arteries (N50%) were observed.
⁎ Corresponding author. E-mail address: [email protected] (N. Funabashi).
http://dx.doi.org/10.1016/j.ijcard.2015.06.139 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
On CT, retrospective ECG gated CT scans were performed on all patients to evaluate coronary arteries, myocardium, intracardiac thrombi, and cardiac function. If there was a contrast defect in LV myocardium in the early phase, a late phase acquisition was added with prospective ECG gating (320 slice CT) or thickened slice thickness (16 slice CT), both of which could achieve reduction of total radiation exposure. If abnormal late enhancement was observed in the corresponding site, we diagnosed myocardial fibrosis [5] (Fig. 1). All patients underwent TTE, 24-hour ECG monitoring and CT within a 12 month period between 2002 and 2009. No patients had previous myocardial infarction on medical record or clinical course. Diagnosis of HCM was based on TTE demonstration of an asymmetric hypertrophied LV myocardium ≥15 mm [5]. Non sustained VT was defined as ≥3 consecutive premature ventricular beats (b30 s) on 24-hour ECG monitoring or 12 lead ECG. Patients were followed for a median of 68 months after CT acquisition for occurrence of MACE. MACE included cardiac death, cardiac arrest, hospitalization for heart failure, sustained ventricular tachycardia (continued for ≥ 30 s), ventricular fibrillation and appropriate discharge of Implantable cardioverter defibrillators. Incidence of MACE was compared using Kaplan–Meier analysis and the log-rank statistic. Patient characteristics and TTE findings of 45 HCM patients were represented in Table 1. Among the 45 HCM patients, non sustained VT was detected in 23 patients (51%). HCM patients with non sustained VT had a more frequent presence of myocardial fibrosis in LV myocardium (78%) than those without (41%; P = 0.025). But there was no significant difference in occurrence of MACE between HCM patients with and without non sustained VT (17% vs 5%, P = 0.346) (Table 2). Also no significant differences between HCM patients with and without non sustained VT were seen at each time point and when the entire follow-up period was compared with Kaplan–Meier and log-rank-tests for occurrence of MACE (P = 0.188) (Fig. 2). Among the 45 HCM patients, myocardial fibrosis in LV myocardium on CT was detected in 26 patients (58%). HCM patients with myocardial fibrosis had a greater maximum LV wall thickness on TTE (21 ± 4 mm) than those without (17 ± 2 mm; P = 0.001) (Table 3). HCM patients with myocardial fibrosis had a more frequent occurrence of VT (67%) than those without (32%;
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
35
Fig. 1. Typical computed tomographic (CT) images of myocardial fibrosis in left ventricular (LV) myocardium in a Maron type 2 hypertrophic cardiomyopathy patient. AB: axial source images. CD: multiplanar reconstruction images of short axis of LV. On CT, if a contrast defect (arrows and arrowheads, AC left figure) was observed in early phase images, late phase acquisition was added at 6 min after contrast injection. If abnormal late enhancement was observed at a corresponding site (arrows and arrowheads, BD right figure), we diagnosed this site as myocardial fibrosis.
P = 0.025) (Table 3). HCM patients with myocardial fibrosis had a higher risk of MACE (19%) than those without (0%; P = 0.063) during the observation period but this difference was not statistically significant (Table 3). Table 1 Patient characteristics and transthoracic echocardiographic (TTE) findings in all 45 hypertrophic cardiomyopathy patients. Total number of patients Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE Left ventricular (LV) asynergy on TTE Hypertrophic obstructive cardiomyopathy (presence of pressure gradient ≥30 mm Hg at rest) on TTE Maximum LV wall thickness on TTE (mm) Follow up period (months) Occurrence of major adverse cardiac events
45 60 ± 14 31 (69%) 26 (58%) 37 (82%) 6 (13%) 8 (18%)
19 ± 4 60 ± 36 5 (11%)
Significant differences between HCM patients with and without myocardial fibrosis were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.049) (Fig. 3). Presence of VT is known to be a risk factor for prognosis of HCM patients [6]. Characteristic changes in LV myocardium. myocardial fibrosis, usually detected on late gadolinium enhancement on MRI [5, 7,8], are common in HCM patients and delayed enhancement and myocardial fibrosis detection on MRI have been demonstrated to be very sound prognostically [9–11] and was associated with presence of LV dysfunction [11]. However, failure to demonstrate the superiority of this parameter over non sustained VT was indicated in studies criticized as undersized [12]. In general, ventricular arrhythmia is known to originate in myocardial scarring. Furthermore, the border zone between scar tissue and normal LV myocardium is a known substrate for electrical instability [13]. Therefore, it is clinically important to detect a myocardial scar in LV myocardium in patients with myocardial diseases, which presents as myocardial fibrosis using CT or MRI.
36
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
Table 2 Comparison of patient characteristics and transthoracic echocardiographic (TTE) and computed tomographic (CT) findings between hypertrophic cardiomyopathy (HCM) patients with and without non sustained ventricular tachycardia (VT). HCM patients with non sustained VT had a more frequent presence of myocardial fibrosis in left ventricular (LV) myocardium on CT (78%) than those without (41%; P = 0.025). But there was no significant difference in occurrence of major adverse cardiac events (MACE) between HCM patients with and without non sustained VT (17% vs 5%, P = 0.346). Bold values indicate significance at P b0.05.
Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE LV asynergy on TTE Hypertrophic obstructive cardiomyopathy on TTE Maximum LV wall thickness on TTE (mm) Presence of myocardial fibrosis in LV myocardium on CT Follow up period (months) Occurrence of MACE
As contrast resolution, especially low contrast resolution, is much superior in MRI to that in CT, a small amount of myocardial fibrosis detected only with MRI (and not CT), may have little influence on prognosis of HCM patients. In other words, the degree of myocardial fibrosis detected on both CT and MRI would be expected to be greater than that detected, not with CT, but only with MRI. It is generally considered that “the larger the myocardial fibrosis, the poorer the prognosis in HCM subjects”. Therefore the myocardial fibrosis visualized on CT might be above a certain size and therefore would have revealed a poorer prognosis in this study than that of subjects who had non sustained VT. Presence of obstructed coronary arteries also influences patient prognosis including HCM patients. Cardiac CT is useful for the evaluation of coronary artery disease [14,15], especially in symptomatic cases including HCM patients. From our result, CT may also be useful for detection of myocardial fibrosis in LV myocardium in risk stratification for HCM patients without obstructed coronary arteries. This may be more important than detecting presence of non sustained VT on 24-hour ECG monitoring or using conventional TTE parameters such as those used to detect hypertrophic obstructive cardiomyopathy.
With NSVT N = 23
Without NSVT N = 22
P value
59 ± 15 18 (78%) 14 (61%) 18 (78%) 4 (17%) 3 (13%) 19 ± 4 18 (78%) 59 ± 37 4 (17%)
61 ± 13 13 (59%) 12 (55%) 19 (86%) 2 (9%) 5 (23%) 19 ± 4 9 (41%) 61 ± 35 1 (5%)
0.910 0.165 0.668 0.705 0.699 0.459 0.723 0.025 0.733 0.346
As the limitations of study, as CT required radiation exposure and usage of iodinated contrast material, if there were no contraindications for MRI such as presence of intracardiac devices or claustrophobia, MRI may be preferable to CT for detection of myocardial fibrosis. This was a single center, retrospective study using a small population and the number of MACE was very low. A larger study population with more endpoints and a more standardized uniform CT protocol is needed to confirm these data. In conclusion, presence of myocardial fibrosis in LV myocardium on CT is a stronger predictor of MACE than presence of non sustained VT in HCM patients without obstructed coronary arteries followed for a median of 68 months.
Acknowledgment This work is supported by a Grant from the Kao Research Council for the Study of Healthcare Science (A-31016) and the Japan Heart Foundation Research Grant. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology.
Table 3 Comparison of patient characteristics and transthoracic echocardiographic (TTE) and 24-hour ECG monitoring findings between hypertrophic cardiomyopathy (HCM) patients with and without myocardial fibrosis on computed tomography. HCM patients with myocardial fibrosis had a greater maximum left ventricular (LV) wall thickness on TTE (21 ± 4 mm) than those without (17 ± 2 mm; P = 0.001). HCM patients with myocardial fibrosis had a more frequent occurrence of non sustained ventricular tachycardia (VT) (67%) than those without (32%; P = 0.025). HCM patients with myocardial fibrosis had a higher risk of major adverse cardiac events (MACE) (19%) than those without (0%; P = 0.063) during the observation period but this difference was not statistically significant. Bold values indicate significance at P b0.05.
Fig. 2. Kaplan–Meier survival curve for the occurrence of major adverse cardiac events (MACE) between hypertrophic cardiomyopathy (HCM) patients with and without non sustained ventricular tachycardia (VT). No significant differences between HCM patients with and without non sustained VT were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.188).
Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE LV asynergy on TTE Hypertrophic obstructive cardiomyopathy on TTE Maximum LV wall thickness on TTE (mm) Occurrence of NSVT Follow up period (months) Occurrence of MACE
With myocardial fibrosis N = 26
Without myocardial fibrosis N = 19
P value
60 ± 16 17 (65%) 15 (58%) 23 (88%) 5 (19%) 6 (23%)
60 ± 12 14 (74%) 11 (58%) 14 (74%) 1 (5%) 2 (11%)
0.581 0.553 0.989 0.253 0.222 0.435
21 ± 4
17 ± 2
0.001
17 (67%) 57 ± 32 5 (19%)
6 (32%) 64 ± 40 0 (0%)
0.025 0.370 0.063
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
[5]
[6]
[7] [8]
[9]
[10]
Fig. 3. Kaplan–Meier survival curve for occurrence of major adverse cardiac events (MACE) between hypertrophic cardiomyopathy (HCM) patients with and without myocardial fibrosis on computed tomography. Significant differences between HCM patients with and without myocardial fibrosis were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.049).
References [1] B.J. Maron, Sudden death in young athletes, N. Engl. J. Med. 349 (2003) 1064–1075. [2] K. Teraoka, M. Hirano, H. Ookubo, K. Sasaki, H. Katsuyama, M. Amino, Y. Abe, A. Yamashina, Delayed contrast enhancement of MRI in hypertrophic cardiomyopathy, Magn. Reson. Imaging 22 (2004) 155–161. [3] M. Uehara, H. Takaoka, Y. Kobayashi, N. Funabashi, Diagnostic accuracy of 320-slice computed-tomography for detection of significant coronary artery stenosis in patients with various heart rates and heart rhythms compared with conventional coronary-angiography, Int. J. Cardiol. 167 (2013) 809–815. [4] H. Takaoka, N. Funabashi, M. Uehara, Y. Fujimoto, Y. Kobayashi, Diagnostic accuracy of coronary 320 slice CT angiography using retrospective electrocardiogram gated
[11]
[12]
[13]
[14]
[15]
37
acquisition compared with virtual prospective electrocardiogram gated acquisition with and without padding, Int. J. Cardiol. 168 (2013) 2811–2815. L. Zhao, X. Ma, G.M. Feuchtner, C. Zhang, Z. Fan, Quantification of myocardial delayed enhancement and wall thickness in hypertrophic cardiomyopathy: multidetector computed tomography versus magnetic resonance imaging, Eur. J. Radiol. 83 (2014) 1778–1785. A.T. Yetman, R.M. Hamilton, L.N. Benson, B.W. McCrindle, Long-term outcome and prognostic determinants in children with hypertrophic cardiomyopathy, J. Am. Coll. Cardiol. 32 (1998) 1943–1950. J. Bogaert, I. Olivotto, MR imaging in hypertrophic cardiomyopathy: from magnet to bedside, Radiology 273 (2014) 329–348. K.Y. Kebed, R.I. Al Adham, K. Bishu, J.W. Askew, K.W. Klarich, P.A. Araoz, T.A. Foley, J.F. Glockner, R.A. Nishimura, N.S. Anavekar, Evaluation of apical subtype of hypertrophic cardiomyopathy using cardiac magnetic resonance imaging with gadolinium enhancement, Am. J. Cardiol. 114 (2014) 777–782. R.H. Chan, B.J. Maron, I. Olivotto, M.J. Pencina, G.E. Assenza, T. Haas, J.R. Lesser, C. Gruner, A.M. Crean, H. Rakowski, J.E. Udelson, E. Rowin, M. Lombardi, F. Cecchi, B. Tomberli, P. Spirito, F. Formisano, E. Biagini, C. Rapezzi, C.N. De Cecco, C. Autore, E.F. Cook, S.N. Hong, C.M. Gibson, W.J. Manning, E. Appelbaum, M.S. Maron, Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy, Circulation 130 (2014) 484–495. K. Hanneman, A.M. Crean, L. Williams, H. Moshonov, S. James, L. Jiménez-Juan, C. Gruner, P. Sparrow, H. Rakowski, E.T. Nguyen, Cardiac magnetic resonance imaging findings predict major adverse events in apical hypertrophic cardiomyopathy, J. Thorac. Imaging 29 (2014) 331–339. I. Olivotto, B.J. Maron, E. Appelbaum, C.J. Harrigan, C. Salton, C.M. Gibson, J.E. Udelson, C. O'Donnell, J.R. Lesser, W.J. Manning, M.S. Maron, Spectrum and clinical significance of systolic function and myocardial fibrosis assessed by cardiovascular magnetic resonance in hypertrophic cardiomyopathy, Am. J. Cardiol. 106 (2010) 261–267. M. Salerno, C.M. Kramer, Prognosis in hypertrophic cardiomyopathy with contrastenhanced cardiac magnetic resonance: the future looks bright, J. Am. Coll. Cardiol. 56 (2010) 888–889. W.G. Stevenson, P.L. Friedman, P.T. Sager, L.A. Saxon, D. Kocovic, T. Harada, I. Wiener, H. Khan, Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping, J. Am. Coll. Cardiol. 29 (1997) 1180–1189. N. Funabashi, M. Uehara, H. Takaoka, K. Ozawa, S. Kushida, J. Kanda, Y. Fujimoto, Y. Kobayashi, A two center 320 slice CT study for evaluating coronary arteries in subjects with chronic atrial fibrillation: a comparison of prospective and retrospective ECG-gating acquisition, Int. J. Cardiol. 177 (2014) 374–379. M. Uehara, N. Funabashi, H. Takaoka, K. Ozawa, S. Kushida, J. Kanda, Y. Fujimoto, Y. Kobayashi, CHA2DS2-VASc score is a useful-predictor of not prognosis but coronary-arteriosclerosis in chronic atrial-fibrillation compared with CHADS2 score: a two-center study of 320-slice CT, part 2, Int. J. Cardiol. 177 (2014) 368–373.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Successful prediction of MACE by myocardial fibrosis on CT in hypertrophic cardiomyopathy patients without obstructed coronary arteries Hiroyuki Takaoka, Nobusada Funabashi ⁎, Masae Uehara, Koya Ozawa, Yoshio Kobayashi Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
a r t i c l e
i n f o
Article history: Received 19 June 2015 Accepted 27 June 2015 Available online 9 July 2015 Keywords: Successful prediction MACE Myocardial fibrosis on CT Hypertrophic cardiomyopathy Without obstructed coronary arteries
Hypertrophic cardiomyopathy (HCM) is recognized as a high risk cardiovascular disease leading to sudden cardiac death in young people [1]. Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) are already known as useful modalities for risk stratification in HCM patients [2]. Recently there have been dramatic developments in multislice computed tomography (CT) which until now have been mainly used for the evaluation of coronary arteries [3,4]. However, multislice CT has not been used frequently in daily clinical practice for the evaluation of characteristics of left ventricular (LV) myocardium. To compare the value of non sustained ventricular tachycardia (VT) and myocardial fibrosis in LV myocardium on CT in risk stratification for major adverse cardiac events (MACE) in HCM patients without obstructed coronary arteries, using Kaplan–Meier analysis. We selected 45 consecutive symptomatic HCM patients (31 males, mean age 60 ± 14 years), who had suspected coronary artery disease, cardiac dysfunction, valvular disease or intracardiac thrombi, and who underwent cardiac CT (Aquilion one, Toshiba Medical or Light Speed ultra 16, GE Healthcare) mainly to evaluate coronary arteries, in whom no obstructed coronary arteries (N50%) were observed.
⁎ Corresponding author. E-mail address: [email protected] (N. Funabashi).
http://dx.doi.org/10.1016/j.ijcard.2015.06.139 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
On CT, retrospective ECG gated CT scans were performed on all patients to evaluate coronary arteries, myocardium, intracardiac thrombi, and cardiac function. If there was a contrast defect in LV myocardium in the early phase, a late phase acquisition was added with prospective ECG gating (320 slice CT) or thickened slice thickness (16 slice CT), both of which could achieve reduction of total radiation exposure. If abnormal late enhancement was observed in the corresponding site, we diagnosed myocardial fibrosis [5] (Fig. 1). All patients underwent TTE, 24-hour ECG monitoring and CT within a 12 month period between 2002 and 2009. No patients had previous myocardial infarction on medical record or clinical course. Diagnosis of HCM was based on TTE demonstration of an asymmetric hypertrophied LV myocardium ≥15 mm [5]. Non sustained VT was defined as ≥3 consecutive premature ventricular beats (b30 s) on 24-hour ECG monitoring or 12 lead ECG. Patients were followed for a median of 68 months after CT acquisition for occurrence of MACE. MACE included cardiac death, cardiac arrest, hospitalization for heart failure, sustained ventricular tachycardia (continued for ≥ 30 s), ventricular fibrillation and appropriate discharge of Implantable cardioverter defibrillators. Incidence of MACE was compared using Kaplan–Meier analysis and the log-rank statistic. Patient characteristics and TTE findings of 45 HCM patients were represented in Table 1. Among the 45 HCM patients, non sustained VT was detected in 23 patients (51%). HCM patients with non sustained VT had a more frequent presence of myocardial fibrosis in LV myocardium (78%) than those without (41%; P = 0.025). But there was no significant difference in occurrence of MACE between HCM patients with and without non sustained VT (17% vs 5%, P = 0.346) (Table 2). Also no significant differences between HCM patients with and without non sustained VT were seen at each time point and when the entire follow-up period was compared with Kaplan–Meier and log-rank-tests for occurrence of MACE (P = 0.188) (Fig. 2). Among the 45 HCM patients, myocardial fibrosis in LV myocardium on CT was detected in 26 patients (58%). HCM patients with myocardial fibrosis had a greater maximum LV wall thickness on TTE (21 ± 4 mm) than those without (17 ± 2 mm; P = 0.001) (Table 3). HCM patients with myocardial fibrosis had a more frequent occurrence of VT (67%) than those without (32%;
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
35
Fig. 1. Typical computed tomographic (CT) images of myocardial fibrosis in left ventricular (LV) myocardium in a Maron type 2 hypertrophic cardiomyopathy patient. AB: axial source images. CD: multiplanar reconstruction images of short axis of LV. On CT, if a contrast defect (arrows and arrowheads, AC left figure) was observed in early phase images, late phase acquisition was added at 6 min after contrast injection. If abnormal late enhancement was observed at a corresponding site (arrows and arrowheads, BD right figure), we diagnosed this site as myocardial fibrosis.
P = 0.025) (Table 3). HCM patients with myocardial fibrosis had a higher risk of MACE (19%) than those without (0%; P = 0.063) during the observation period but this difference was not statistically significant (Table 3). Table 1 Patient characteristics and transthoracic echocardiographic (TTE) findings in all 45 hypertrophic cardiomyopathy patients. Total number of patients Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE Left ventricular (LV) asynergy on TTE Hypertrophic obstructive cardiomyopathy (presence of pressure gradient ≥30 mm Hg at rest) on TTE Maximum LV wall thickness on TTE (mm) Follow up period (months) Occurrence of major adverse cardiac events
45 60 ± 14 31 (69%) 26 (58%) 37 (82%) 6 (13%) 8 (18%)
19 ± 4 60 ± 36 5 (11%)
Significant differences between HCM patients with and without myocardial fibrosis were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.049) (Fig. 3). Presence of VT is known to be a risk factor for prognosis of HCM patients [6]. Characteristic changes in LV myocardium. myocardial fibrosis, usually detected on late gadolinium enhancement on MRI [5, 7,8], are common in HCM patients and delayed enhancement and myocardial fibrosis detection on MRI have been demonstrated to be very sound prognostically [9–11] and was associated with presence of LV dysfunction [11]. However, failure to demonstrate the superiority of this parameter over non sustained VT was indicated in studies criticized as undersized [12]. In general, ventricular arrhythmia is known to originate in myocardial scarring. Furthermore, the border zone between scar tissue and normal LV myocardium is a known substrate for electrical instability [13]. Therefore, it is clinically important to detect a myocardial scar in LV myocardium in patients with myocardial diseases, which presents as myocardial fibrosis using CT or MRI.
36
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
Table 2 Comparison of patient characteristics and transthoracic echocardiographic (TTE) and computed tomographic (CT) findings between hypertrophic cardiomyopathy (HCM) patients with and without non sustained ventricular tachycardia (VT). HCM patients with non sustained VT had a more frequent presence of myocardial fibrosis in left ventricular (LV) myocardium on CT (78%) than those without (41%; P = 0.025). But there was no significant difference in occurrence of major adverse cardiac events (MACE) between HCM patients with and without non sustained VT (17% vs 5%, P = 0.346). Bold values indicate significance at P b0.05.
Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE LV asynergy on TTE Hypertrophic obstructive cardiomyopathy on TTE Maximum LV wall thickness on TTE (mm) Presence of myocardial fibrosis in LV myocardium on CT Follow up period (months) Occurrence of MACE
As contrast resolution, especially low contrast resolution, is much superior in MRI to that in CT, a small amount of myocardial fibrosis detected only with MRI (and not CT), may have little influence on prognosis of HCM patients. In other words, the degree of myocardial fibrosis detected on both CT and MRI would be expected to be greater than that detected, not with CT, but only with MRI. It is generally considered that “the larger the myocardial fibrosis, the poorer the prognosis in HCM subjects”. Therefore the myocardial fibrosis visualized on CT might be above a certain size and therefore would have revealed a poorer prognosis in this study than that of subjects who had non sustained VT. Presence of obstructed coronary arteries also influences patient prognosis including HCM patients. Cardiac CT is useful for the evaluation of coronary artery disease [14,15], especially in symptomatic cases including HCM patients. From our result, CT may also be useful for detection of myocardial fibrosis in LV myocardium in risk stratification for HCM patients without obstructed coronary arteries. This may be more important than detecting presence of non sustained VT on 24-hour ECG monitoring or using conventional TTE parameters such as those used to detect hypertrophic obstructive cardiomyopathy.
With NSVT N = 23
Without NSVT N = 22
P value
59 ± 15 18 (78%) 14 (61%) 18 (78%) 4 (17%) 3 (13%) 19 ± 4 18 (78%) 59 ± 37 4 (17%)
61 ± 13 13 (59%) 12 (55%) 19 (86%) 2 (9%) 5 (23%) 19 ± 4 9 (41%) 61 ± 35 1 (5%)
0.910 0.165 0.668 0.705 0.699 0.459 0.723 0.025 0.733 0.346
As the limitations of study, as CT required radiation exposure and usage of iodinated contrast material, if there were no contraindications for MRI such as presence of intracardiac devices or claustrophobia, MRI may be preferable to CT for detection of myocardial fibrosis. This was a single center, retrospective study using a small population and the number of MACE was very low. A larger study population with more endpoints and a more standardized uniform CT protocol is needed to confirm these data. In conclusion, presence of myocardial fibrosis in LV myocardium on CT is a stronger predictor of MACE than presence of non sustained VT in HCM patients without obstructed coronary arteries followed for a median of 68 months.
Acknowledgment This work is supported by a Grant from the Kao Research Council for the Study of Healthcare Science (A-31016) and the Japan Heart Foundation Research Grant. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology.
Table 3 Comparison of patient characteristics and transthoracic echocardiographic (TTE) and 24-hour ECG monitoring findings between hypertrophic cardiomyopathy (HCM) patients with and without myocardial fibrosis on computed tomography. HCM patients with myocardial fibrosis had a greater maximum left ventricular (LV) wall thickness on TTE (21 ± 4 mm) than those without (17 ± 2 mm; P = 0.001). HCM patients with myocardial fibrosis had a more frequent occurrence of non sustained ventricular tachycardia (VT) (67%) than those without (32%; P = 0.025). HCM patients with myocardial fibrosis had a higher risk of major adverse cardiac events (MACE) (19%) than those without (0%; P = 0.063) during the observation period but this difference was not statistically significant. Bold values indicate significance at P b0.05.
Fig. 2. Kaplan–Meier survival curve for the occurrence of major adverse cardiac events (MACE) between hypertrophic cardiomyopathy (HCM) patients with and without non sustained ventricular tachycardia (VT). No significant differences between HCM patients with and without non sustained VT were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.188).
Age (years) Male Apical hypertrophy on TTE Septal hypertrophy on TTE LV asynergy on TTE Hypertrophic obstructive cardiomyopathy on TTE Maximum LV wall thickness on TTE (mm) Occurrence of NSVT Follow up period (months) Occurrence of MACE
With myocardial fibrosis N = 26
Without myocardial fibrosis N = 19
P value
60 ± 16 17 (65%) 15 (58%) 23 (88%) 5 (19%) 6 (23%)
60 ± 12 14 (74%) 11 (58%) 14 (74%) 1 (5%) 2 (11%)
0.581 0.553 0.989 0.253 0.222 0.435
21 ± 4
17 ± 2
0.001
17 (67%) 57 ± 32 5 (19%)
6 (32%) 64 ± 40 0 (0%)
0.025 0.370 0.063
H. Takaoka et al. / International Journal of Cardiology 199 (2015) 34–37
[5]
[6]
[7] [8]
[9]
[10]
Fig. 3. Kaplan–Meier survival curve for occurrence of major adverse cardiac events (MACE) between hypertrophic cardiomyopathy (HCM) patients with and without myocardial fibrosis on computed tomography. Significant differences between HCM patients with and without myocardial fibrosis were seen at each time point and when the entire follow-up period was compared by Kaplan–Meier analysis and log rank test (P = 0.049).
References [1] B.J. Maron, Sudden death in young athletes, N. Engl. J. Med. 349 (2003) 1064–1075. [2] K. Teraoka, M. Hirano, H. Ookubo, K. Sasaki, H. Katsuyama, M. Amino, Y. Abe, A. Yamashina, Delayed contrast enhancement of MRI in hypertrophic cardiomyopathy, Magn. Reson. Imaging 22 (2004) 155–161. [3] M. Uehara, H. Takaoka, Y. Kobayashi, N. Funabashi, Diagnostic accuracy of 320-slice computed-tomography for detection of significant coronary artery stenosis in patients with various heart rates and heart rhythms compared with conventional coronary-angiography, Int. J. Cardiol. 167 (2013) 809–815. [4] H. Takaoka, N. Funabashi, M. Uehara, Y. Fujimoto, Y. Kobayashi, Diagnostic accuracy of coronary 320 slice CT angiography using retrospective electrocardiogram gated
[11]
[12]
[13]
[14]
[15]
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