International Journal of Cardiology 176 (2014) 1329–1330
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Speckle tracking echocardiography in cardiac sarcoidosis Seref Kul a,⁎, Tolga Sinan Guvenc b, Huseyin Uyarel a a b
Bezmialem Vakif University, Faculty Of Medicine, Cardiology Department, Istanbul, Turkey Umraniye Research and Training Hospital, Cardiology Department, Istanbul, Turkey
a r t i c l e
i n f o
Article history: Received 13 June 2014 Accepted 27 July 2014 Available online 1 August 2014 Keywords: Speckle tracking echocardiography Cardiac sarcoidosis Subclinical involvement
To the Editor, We have read with great interest the recent letter by Aggeli and associates that was published in the Journal (1). In their work, the authors had demonstrated reduced global longitudinal strain (GLS) in patients with newly-diagnosed extra-cardiac sarcoidosis [1]. Recently, our study group has also demonstrated a similar decrease in GLS in patients with pulmonary sarcoidosis with and without cardiac involvement, and another study group presented similar findings in a recent international conference [2,3]. We would like to comment on the possible importance of these coherent findings recently found by different study groups. Manifest cardiac involvement is found in approximately 30% of patients with sarcoidosis, as demonstrated by pathobiological studies [4]. Cardiac magnetic resonance imaging (CMRI) and 18F-fluoro-2deoxyglucose positron emission tomography (PET) had a high correlation with biopsy findings, making these modalities ideal for demonstrating cardiac involvement [5]. Both pathobiological and CMRI/PET studies rely on demonstration of macroscopic lesions compatible with classical non-caseating granulomas or structural lesions observed in sarcoidosis. Recent findings with strain imaging, however, suggest that this may not be the case in all so-called “extracardiac” sarcoidosis patients, since abnormal LV contractility is present even when patients with manifest cardiac sarcoidosis (CS) are excluded. ⁎ Corresponding author at: Bezmialem Vakif University, Faculty of Medicine,Cardiology Department, Adnan Menderes Bulvarı (Vatan cad.), 34093 Fatih, Istanbul, Turkey. Tel.: +90 505 496 49 45; fax: +90 212 621 25 80. E-mail address: [email protected] (S. Kul).
http://dx.doi.org/10.1016/j.ijcard.2014.07.148 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Abnormalities in the left ventricular contractility, as demonstrated with Tissue-Doppler (TD) echocardiography were noted before by Kaderli et al., but this study went relatively unnoticed since TD evaluation does not offer a complete assessment of LV contractility [6]. In contrast to TD, global longitudinal strain measurement represents all segments of the left ventricular wall, allowing it to be sensitive to even small changes in LV contractility [7]. Previous studies utilizing strain imaging had shown that it can be used to detect sub-clinical myocardial involvement in asymptomatic patients with systemic sclerosis, diabetes, amyloidosis, Duchenne's progressive muscular dystrophy and Kawasaki syndrome [7]. Since GLS can measure minute reductions in LV contractility, it can be hypothesized that GLS can also be more sensitive to cardiac involvement compared to pathology or CMRI/PET where demonstration of structural lesions is needed to diagnose CS. This point is important, since approximately half of the patients with CS will die due to cardiovascular complications, of which ventricular tachycardia (VT) is the most frequent (and also, preventable) cause of death [8,9]. Since only a fraction of patients with CS have cardiac symptoms such as shortness of breath and palpitations, cardiac involvement would go unnoticed in the majority of patients, which leaves them vulnerable to complications. As echocardiography is widely available and speckle-tracking strain only relies on good-quality images and relevant software for measurements, strain imaging may offer a novel way for screening patients at high risk for CS, who may benefit from life-saving therapy with ICD [8]. In addition, more patients at risk for development of cardiac complications might be identified with strain imaging, as suggested by these recent works. Although results of these reports are encouraging, over-emphasizing the findings from preliminary studies should be avoided. First and foremost, the reduction of GLS and therefore LV contractility does not automatically mean that cardiac involvement is the cause of this reduction, since it is known that diseases without manifest cardiac involvement can have myocardial depressant effects mediated via inflammatory cytokines such as TNF-α and IL-1β [10]. Therefore, histopathologic confirmation from patients with reduced strain but without manifest cardiac involvement is required to fully demonstrate that this reduction is actually caused by direct infiltration. Secondly, the importance of this reduction is yet to be investigated, as these patients with reduced strain may or may not be under risk for developing cardiac complications. In addition, a reliable cut-off point should be demonstrated to help the clinical risk assessment. Thirdly, the studies conducted so far are still few in number and are hampered by problems inherent to study designs. For example, Aggeli
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and associates have demonstrated that patients with extra-cardiac sarcoidosis have reduced GLS, but they did not utilize CMRI or PET to exclude patients with possible CS and relied solely on clinical/ echocardiographic assessment [1]. Although we utilized cardiac MRI to rule-out manifest cardiac involvement in our study, this work was also complicated by the low number of sarcoidosis patients [2]. Therefore, we consider that more studies are required in this field and strain imaging is not ready for prime-time in this clinical setting, despite recent encouraging results. The authors of this manuscript approves that they comply with the principles of ethical publishing in the International Journal of Cardiology. Conflicts of interest and grand support There are no conflicts of interest issues. We have no grant support. References [1] Aggeli C, Felekos I, Tousoulis D, Gialafos E, Rapti A, Stefanadis C. Myocardial mechanics for the early detection of cardiac sarcoidosis. Int J Cardiol Oct 12 2013;168(5):4820–1.
[2] Kul S, Ozcelik HK, Uyarel H, et al. Diagnostic value of strain echocardiography, galectin-3, and tenascin-C levels for the identification of patients with pulmonary and cardiac sarcoidosis. Lung 2014 Aug;192(4):533–42. [3] Orii M, Hirata K, Tanimoto T, et al. Early abnormality detected by two-dimensional speckle-tracking echocardiography in patients with extra-cardiac sarcoidosis: comparison with magnetic resonance imaging. Eur Heart J Cardiovasc Imaging 2013;14(Suppl. 2):ii1–2. [4] Yeboah J, Lee C, Sharma OP. Cardiac sarcoidosis: a review 2011. Curr Opin Pulm Med Sep 2011;17(5):308–15. [5] Wicks E, Menezes L, Pantazis A, et al. 135 novel hybrid positron emission tomography– magnetic resonance (PET-MR) multi-modality inflammatory imaging has improved diagnostic accuracy for detecting cardiac sarcoidosis. Heart Jun 2014;100(Suppl. 3):A80. [6] Aydin Kaderli A, Gullulu S, Coskun F, Yilmaz D, Uzaslan E. Impaired left ventricular systolic and diastolic functions in patients with early grade pulmonary sarcoidosis. Eur J Echocardiogr 2010;11(10):809–13. [7] Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography — basic concepts and clinical applicability. Curr Cardiol Rev 2009 May;5(2):133–48. [8] Mohsen A, Jimenez A, Hood RE, et al. Cardiac sarcoidosis: electrophysiological outcomes on long-term follow-up and the role of the implantable cardioverterdefibrillator. J Cardiovasc Electrophysiol Oct 8 2013. http://dx.doi.org/10.1111/ jce.12302. [9] Alper AT, Güngör B, Ozpamuk Karadeniz F, Erer HB. Malignant ventricular arrhythmia as the first manifestation of cardiac sarcoidosis. Turk Kardiyol Dern Ars Sep 2013;41(6):561. [10] Wang Y, Li Y, Wu Y, et al. TNF-α and IL-1β neutralization ameliorates angiotensin II-induced cardiac damage in male mice. Endocrinology 2014 Jul;155(7):2677–87.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Speckle tracking echocardiography in cardiac sarcoidosis Seref Kul a,⁎, Tolga Sinan Guvenc b, Huseyin Uyarel a a b
Bezmialem Vakif University, Faculty Of Medicine, Cardiology Department, Istanbul, Turkey Umraniye Research and Training Hospital, Cardiology Department, Istanbul, Turkey
a r t i c l e
i n f o
Article history: Received 13 June 2014 Accepted 27 July 2014 Available online 1 August 2014 Keywords: Speckle tracking echocardiography Cardiac sarcoidosis Subclinical involvement
To the Editor, We have read with great interest the recent letter by Aggeli and associates that was published in the Journal (1). In their work, the authors had demonstrated reduced global longitudinal strain (GLS) in patients with newly-diagnosed extra-cardiac sarcoidosis [1]. Recently, our study group has also demonstrated a similar decrease in GLS in patients with pulmonary sarcoidosis with and without cardiac involvement, and another study group presented similar findings in a recent international conference [2,3]. We would like to comment on the possible importance of these coherent findings recently found by different study groups. Manifest cardiac involvement is found in approximately 30% of patients with sarcoidosis, as demonstrated by pathobiological studies [4]. Cardiac magnetic resonance imaging (CMRI) and 18F-fluoro-2deoxyglucose positron emission tomography (PET) had a high correlation with biopsy findings, making these modalities ideal for demonstrating cardiac involvement [5]. Both pathobiological and CMRI/PET studies rely on demonstration of macroscopic lesions compatible with classical non-caseating granulomas or structural lesions observed in sarcoidosis. Recent findings with strain imaging, however, suggest that this may not be the case in all so-called “extracardiac” sarcoidosis patients, since abnormal LV contractility is present even when patients with manifest cardiac sarcoidosis (CS) are excluded. ⁎ Corresponding author at: Bezmialem Vakif University, Faculty of Medicine,Cardiology Department, Adnan Menderes Bulvarı (Vatan cad.), 34093 Fatih, Istanbul, Turkey. Tel.: +90 505 496 49 45; fax: +90 212 621 25 80. E-mail address: [email protected] (S. Kul).
http://dx.doi.org/10.1016/j.ijcard.2014.07.148 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Abnormalities in the left ventricular contractility, as demonstrated with Tissue-Doppler (TD) echocardiography were noted before by Kaderli et al., but this study went relatively unnoticed since TD evaluation does not offer a complete assessment of LV contractility [6]. In contrast to TD, global longitudinal strain measurement represents all segments of the left ventricular wall, allowing it to be sensitive to even small changes in LV contractility [7]. Previous studies utilizing strain imaging had shown that it can be used to detect sub-clinical myocardial involvement in asymptomatic patients with systemic sclerosis, diabetes, amyloidosis, Duchenne's progressive muscular dystrophy and Kawasaki syndrome [7]. Since GLS can measure minute reductions in LV contractility, it can be hypothesized that GLS can also be more sensitive to cardiac involvement compared to pathology or CMRI/PET where demonstration of structural lesions is needed to diagnose CS. This point is important, since approximately half of the patients with CS will die due to cardiovascular complications, of which ventricular tachycardia (VT) is the most frequent (and also, preventable) cause of death [8,9]. Since only a fraction of patients with CS have cardiac symptoms such as shortness of breath and palpitations, cardiac involvement would go unnoticed in the majority of patients, which leaves them vulnerable to complications. As echocardiography is widely available and speckle-tracking strain only relies on good-quality images and relevant software for measurements, strain imaging may offer a novel way for screening patients at high risk for CS, who may benefit from life-saving therapy with ICD [8]. In addition, more patients at risk for development of cardiac complications might be identified with strain imaging, as suggested by these recent works. Although results of these reports are encouraging, over-emphasizing the findings from preliminary studies should be avoided. First and foremost, the reduction of GLS and therefore LV contractility does not automatically mean that cardiac involvement is the cause of this reduction, since it is known that diseases without manifest cardiac involvement can have myocardial depressant effects mediated via inflammatory cytokines such as TNF-α and IL-1β [10]. Therefore, histopathologic confirmation from patients with reduced strain but without manifest cardiac involvement is required to fully demonstrate that this reduction is actually caused by direct infiltration. Secondly, the importance of this reduction is yet to be investigated, as these patients with reduced strain may or may not be under risk for developing cardiac complications. In addition, a reliable cut-off point should be demonstrated to help the clinical risk assessment. Thirdly, the studies conducted so far are still few in number and are hampered by problems inherent to study designs. For example, Aggeli
1330
S. Kul et al. / International Journal of Cardiology 176 (2014) 1329–1330
and associates have demonstrated that patients with extra-cardiac sarcoidosis have reduced GLS, but they did not utilize CMRI or PET to exclude patients with possible CS and relied solely on clinical/ echocardiographic assessment [1]. Although we utilized cardiac MRI to rule-out manifest cardiac involvement in our study, this work was also complicated by the low number of sarcoidosis patients [2]. Therefore, we consider that more studies are required in this field and strain imaging is not ready for prime-time in this clinical setting, despite recent encouraging results. The authors of this manuscript approves that they comply with the principles of ethical publishing in the International Journal of Cardiology. Conflicts of interest and grand support There are no conflicts of interest issues. We have no grant support. References [1] Aggeli C, Felekos I, Tousoulis D, Gialafos E, Rapti A, Stefanadis C. Myocardial mechanics for the early detection of cardiac sarcoidosis. Int J Cardiol Oct 12 2013;168(5):4820–1.
[2] Kul S, Ozcelik HK, Uyarel H, et al. Diagnostic value of strain echocardiography, galectin-3, and tenascin-C levels for the identification of patients with pulmonary and cardiac sarcoidosis. Lung 2014 Aug;192(4):533–42. [3] Orii M, Hirata K, Tanimoto T, et al. Early abnormality detected by two-dimensional speckle-tracking echocardiography in patients with extra-cardiac sarcoidosis: comparison with magnetic resonance imaging. Eur Heart J Cardiovasc Imaging 2013;14(Suppl. 2):ii1–2. [4] Yeboah J, Lee C, Sharma OP. Cardiac sarcoidosis: a review 2011. Curr Opin Pulm Med Sep 2011;17(5):308–15. [5] Wicks E, Menezes L, Pantazis A, et al. 135 novel hybrid positron emission tomography– magnetic resonance (PET-MR) multi-modality inflammatory imaging has improved diagnostic accuracy for detecting cardiac sarcoidosis. Heart Jun 2014;100(Suppl. 3):A80. [6] Aydin Kaderli A, Gullulu S, Coskun F, Yilmaz D, Uzaslan E. Impaired left ventricular systolic and diastolic functions in patients with early grade pulmonary sarcoidosis. Eur J Echocardiogr 2010;11(10):809–13. [7] Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography — basic concepts and clinical applicability. Curr Cardiol Rev 2009 May;5(2):133–48. [8] Mohsen A, Jimenez A, Hood RE, et al. Cardiac sarcoidosis: electrophysiological outcomes on long-term follow-up and the role of the implantable cardioverterdefibrillator. J Cardiovasc Electrophysiol Oct 8 2013. http://dx.doi.org/10.1111/ jce.12302. [9] Alper AT, Güngör B, Ozpamuk Karadeniz F, Erer HB. Malignant ventricular arrhythmia as the first manifestation of cardiac sarcoidosis. Turk Kardiyol Dern Ars Sep 2013;41(6):561. [10] Wang Y, Li Y, Wu Y, et al. TNF-α and IL-1β neutralization ameliorates angiotensin II-induced cardiac damage in male mice. Endocrinology 2014 Jul;155(7):2677–87.
