- Email: [email protected]
Myocardial stress perfusion-fibrosis imaging pattern in sarcoidosis, assessed by cardiovascular magnetic resonance imaging
Letters to the Editor
501
Myocardial stress perfusion-fibrosis imaging pattern in sarcoidosis, assessed by cardiovascular magnetic resonance imaging Sophie Mavrogeni a,⁎, Vasilios Kouranos b, Petros P. Sfikakis c, Konstantinos Bratis a, George D. Kitas d, Efrosini Manali b, Elias Perros e, Kostas Vlasis f, Aggeliki Rapti g, Nikolaos Koulouris b, Kees van Wijk h, David Hautemann h, Johan H.C. Reiber h, Genovefa Kolovou a, George E. Tzelepis b, Elias Gialafos b a
Onassis Cardiac Surgery Center, Athens, Greece 1st Department of Pulmonology, University of Athens, Athens, Greece c First Department of PropInternal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece d Arthritis Research UK Epidemiology Unit, Manchester University, Manchester, UK e Department of Pulmonology, General Hospital of Nikaia “Agios Panteleimonas”, Athens, Greece f Department of Anatomy, University of Athens, Athens, Greece g Second Department of Pulmonology, Sotiria Hospital, Athens, Greece h Leiden University Medical Center, Leiden, The Netherlands b
a r t i c l e
i n f o
Article history: Received 4 January 2014 Accepted 8 January 2014 Available online 16 January 2014 Keywords: Sarcoidosis Cardiovascular magnetic resonance (CMR) Myocarditis Stress perfusion-fibrosis CMR Late gadolinium enhancement
Sarcoidosis (SRC) is characterized by granulomas in various organs, including the heart [1]. We hypothesized that cardiovascular magnetic resonance (CMR) may diagnose silent heart lesions in SRC. Forty five consecutive, asymptomatic patients with SRC, (14 men, 45 ± 3 years) normal echocardiogram and 24-hour ECG, underwent CMR imaging, using a 1.5 T. Steady-state, free precession cines were acquired for function evaluation and STIR T2-W for edema imaging. For SRC with T2 ratio b 2 (Group A) and T2 ratio N 2 (Group B), a stress perfusion-fibrosis (Fig. 1) and a myocarditis protocol (Fig. 2) were applied, respectively and were compared to 45 age–sex matched controls. CMR was performed in 43/45 patients (2 were excluded due to technical reasons). In 34/43 SRC with T2 ratio b 2 (Group A), a stress perfusion-fibrosis CMR revealed a significant reduction in myocardial perfusion reserve index (MPRI), compared to 34 age–sex matched controls (0.95 ± 0.3 vs 3.5 ± 0.8, p b 0.001). Although clear evidence of late gadolinium enhancement was not identified, the quantitative analysis revealed diffuse fibrosis in all patients with an extent of 4.5 ± 3.4% LV (range 2–15). Available CMR after 1 year in 18/34 patients, documented LVEF b 50% in 3 patients. Notably, in 6/9 SRC patients with T2 ratio N 2 (Group B), the myocarditis protocol was positive and steroid treatment was promptly given. Six months later, their CMR was normal. No correlation between CMR, SRC duration and/or other organs involvement was identified. Detailed CMR parameters of SRC patients are presented in Table 1. Cardiac involvement, according to pathology, may occur in 20– 30% of SRC of patients [1], and has been associated with poor prognosis [2]. Despite these findings, only 5% of SRC have clinical manifestations of cardiac disease, and only 40–50% of those with cardiac SRC at autopsy have the correct diagnosis during lifetime [2]. CMR has been recently considered as the best noninvasive tool to assess the presence of fibro-granulomatous tissue in the myocardium in SRC [3]. Smedema et al. reported that the prognosis of
⁎ Corresponding author at: 50 Esperou Street, 175-61 P. Faliro, Athens, Greece. Tel./ fax: +30 210 98 82 797. E-mail address: [email protected] (S. Mavrogeni).
asymptomatic SRC patients with cardiac involvement is better compared to SRC patients with symptomatic cardiac SRC [4]. Therefore, a positive CMR in asymptomatic SRC offers the advantage of early treatment and better prognosis [4]. Greulich et al. found that among SRC with nonspecific symptoms, myocardial LGE was the best independent predictor of potentially lethal events [5]. In contrast to LGE that detects the area already replaced by the fibrogranulomatous tissue, sarcoid infiltrates may also be visible as increased intramyocardial signal on T2-weighted images, due to edema, associated with granulomatous lesions. In our asymptomatic SRC, acute myocardial inflammation was identified by CMR in 14%, characterized by both edema and positive LGE. This was in agreement with previous studies [6] and motivated early steroid treatment; none of the steroids-treated patients developed clinically overt cardiac SRC in the next 6 months; furthermore, they normalized their CMR. Our findings are in agreement with recent data, showing that the prognosis of asymptomatic cardiac involvement in pulmonary SRC remains good [6]. Microvascular disease in SRC has been identified in different organs [7]. Reversible myocardial perfusion defects have been already described in both cardiac and noncardiac SRC, using technetium-99m SPECT [8]. This reversibility made unlikely the presence of fibrosis; in contrary, it was indicative of reversible disorders at coronary microvascular level [8]. PET documented that focal perfusion defects in SRC identified patients at higher risk of death or VT and offered prognostic value beyond Japanese clinical criteria, extra-cardiac sarcoidosis and LVEF [9]. In a CMR study of connective tissue diseases, including SRC, by our group, myocardial inflammation and microvascular disease have been also identified [10]. To our knowledge, this is the first study, in which stress perfusion fibrosis CMR was applied for the detection of silent cardiac lesions in asymptomatic SRC. Using stress perfusion-fibrosis CMR, we documented MPRI deterioration and diffuse fibrosis. Our findings were in agreement with previous studies, using nuclear techniques. However, due to better spatial resolution of CMR, a more detailed description of myocardial perfusion-fibrosis pattern was feasible. We documented that microvascular heart disease is an early lesion in SRC, unrelated to granulomas, assessed in acute cases, and can contribute to diffuse fibrosis, an independent factor for LV dysfunction [11,12]. This is in agreement with previous studies supporting that microvascular disease may contribute to LV dysfunction [13,14]. No correlation was identified between CMR and patients' clinical characteristics, other organ involvement and/or disease severity/ duration. This is in agreement with previous studies supporting that heart involvement occurs only in 20–30% of SRC [1] and is not obligatory associated with fulminant or widespread disease [2]. Our findings may have important clinical implications; the early documentation of myocardial inflammation in asymptomatic SRC
502
Letters to the Editor
Fig. 1. Stress Bulls eye (left), rest Bulls eye (middle) and fibrosis polar map (right) of a patient with sarcoidosis and T2 b 2. Evidence of diffuse fibrosis (in yellow) in the fibrosis image, on the right.
necessitates steroids treatment to avoid overt heart disease; in addition, myocardial perfusion defects and fibrosis may lead to overt heart failure, a common endpoint in 25–75% of SRC [15] and address queries about the need of early start of ACE-inhibitors according to ACC/ESC guidelines [16]. The capability of CMR to detect heart SRC, undetected by other techniques, can be potentially of value to diagnose asymptomatic first-degree relatives of SRC, who have 5 times higher risk than controls to develop SRC, according to ACCESS study [17]. Finally, the high incidence of CMR lesions in SRC should motivate the implantation of MRI-conditional pacing system in SRC with complete AV block, in order to maintain the advantage of permanent CMR evaluation [18]. The current study has the following limitations: 1) Small patients' population and lack of long term follow. 2) Lack of symptomatic patients, in order to correlate the clinical presentation with CMR. 3) For diffuse fibrosis evaluation, the QMass MR analytical software was used and not the T1 mapping that is currently considered, as the most reliable way to evaluate the presence of potential diffuse myocardial fibrosis [19]. To conclude, in sarcoidosis without cardiac symptoms and normal routine assessment, CMR can detect early cardiac involvement that may in some cases necessitate immediate treatment. However, further studies are needed to establish criteria in SRC patients' selection for CMR evaluation and to propose a therapeutic algorithm, according to CMR findings.
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Barnard J, Newman LS. Sarcoidosis: immunology, rheumatic involvement, and therapeutics. Curr Opin Rheumatol 2001;13(1):84–91. [2] Sharma OP, Maheshwari A, Thaker K. Myocardial sarcoidosis. Chest 1993;103:253–8. [3] Schulz-Menger J, Wassmuth R, Abdel-Aty H, et al. Patterns of myocardial inflammation and scarring in sarcoidosis as assessed by cardiovascular magnetic resonance. Heart 2006;92:399–400. [4] Smedema JP, Snoep G, van Kroonenburgh MP, et al. Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in The Netherlands. Chest 2005;128:30–5. [5] Greulich S, Deluigi CC, Gloekler S, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 2013;6(4):501–11. [6] Chiu CZ, Nakatani S, Zhang G, et al. Prevention of left ventricular remodeling by long-term corticosteroid therapy in patients with cardiac sarcoidosis. Am J Cardiol 2005;95:143–6. [7] Vilaseca J, Guardia J, Cuxart A, et al. Granulomatous hepatitis. Etiologic study of 107 cases. Med Clin (Barc) 1979;72(7):272–5. [8] Tellier P, Valeyre D, Nitenberg A, Foult JM, Bedig G, Battesti JP. Cardiac sarcoidosis: reversion of myocardial perfusion abnormalities by dipyridamole. Eur J Nucl Med 1985;11(6–7):201–4. [9] Blankstein R, Osborne M, Naya M, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63(4):329–36. [10] Mavrogeni S, Sfikakis PP, Gialafos E, et al. Cardiac tissue characterization and the diagnostic value of cardiovascular magnetic resonance in systemic connective tissue diseases. Arthritis Care Res (Hoboken) 2014;66:104–12. [11] Mavrogeni S, Cantini F, Pohost GM. Systemic vasculitis: an underestimated cause of heart failure — assessment by cardiovascular magnetic resonance. Rev Cardiovasc Med 2013;14(1):49–55. [12] Mavrogeni S, Sfikakis PP, Gialafos E, et al. Diffuse, subendocardial vasculitis. A new entity identified by cardiovascular magnetic resonance and its clinical implications. Int J Cardiol 2013;168:2971–2. [13] Timmer SA, Germans T, Götte MJ, et al. Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury. Am J Cardiol 2011;107(10):1522–8.
Table 1 SRC patients' CMR parameters at baseline.
Fig. 2. Patchy LGE deposition located in the lateral wall of LV in a patient with sarcoidosis and T2 N 2.
CMR parameters
Group A SRC patients with T2 b 2 (n = 34)
Group B SRC patients with T2 N 2 (n = 9)
LVEDV (ml) LVESV (ml) LVEF (%) LV mass (g) RVEDV (ml) RVESV (ml) RVEF (%) MPRI T2 ratio EGE LGE (%LV)
130 ± 31.9 47.7 ± 16.9 63.6 ± 7.7 81.47 ± 25.88 115.8 ± 36.5 54.3 ± 19.37 54.7 ± 7.45 0.95 ± 0.3 1.5 ± 0.3 – 5.7 ± 3.98
126 ± 11 40 ± 12.9 63 ± 8 81.5 ± 13.8 113.6 ± 12 50 ± 8.2 54.4 ± 7.2 – 3.7 ± 0.6 10.6 ± 6.1 4.5 ± 3.4
Letters to the Editor [14] Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013;62:263–71. [15] Sekhri V, Sanal S, DeLorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: a comprehensive review. Arch Med Sci 2011;7(4):546–54. [16] Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119(14):e391–479.
503
[17] Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885–9. [18] Quarta G, Holdright DR, Plant GT, et al. Cardiovascular magnetic resonance in cardiac sarcoidosis with MR conditional pacemaker in situ. J Cardiovasc Magn Reson 2011;13:26. [19] Fang L, Beale A, Ellims AH, et al. Associations between fibrocytes and postcontrast myocardial T1 times in hypertrophic cardiomyopathy. J Am Heart Assoc 2013;2(5): e000270.
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.01.006
Long-term outcome of transitory “reversible” complete atrio-ventricular block unrelated to myocardial ischemia☆ Nuria Farre, Victor Bazan ⁎, Cosme Garcia-Garcia, Lluis Recasens, Julio Marti-Almor, Soledad Ascoeta, Ermengol Valles, Oona Meroño-Dueñas, Nuria Ribas, Jordi Bruguera-Cortada Cardiology Department, Hospital del Mar, Universitat Autonoma de Barcelona, Parc de Salut Mar, Barcelona, Spain
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Article history: Received 7 January 2014 Accepted 10 January 2014 Available online 23 January 2014 Keywords: Reversible Complete atrio-ventricular block Acute coronary syndrome
The need for permanent ventricular pacing in patients with transitory “reversible” complete atrio-ventricular block (CAVB) occurring in the setting of myocardial ischemia is usually spared. Accordingly, current guidelines discourage indication for permanent pace-maker (PM) implantation when CAVB is expected to resolve once the concurring “reversible” causes are controlled [1,2]. This recommendation is mainly based on expert consensus, and little is known about the long-term outcome of transitory CAVB due to presumably reversible causes other than myocardial ischemia [3–5]. This is a relevant clinical issue, as suggested by a high number of emergency department attendances for compromising bradycardia of presumably reversible causes, in which adverse drug effect/ intoxication and electrolyte disorders are frequently reported [6]. In this study, we analyzed the long-term outcome of “reversible” CAVB when it is unrelated to myocardial ischemia. Seventy-nine consecutive patients with “reversible” CAVB not undergoing initial PM implantation were retrospectively analyzed. Our population was preliminary divided into patients with acute coronary syndrome (ACS, group A, n = 52) and those with other causes of reversible CAVB (group 2, n = 27). Group A patients were younger (p = 0.001) and had a lower prevalence of underlying structural heart disease other than coronary artery disease (20% vs. 54%, respectively; p = 0.03; Table 1). Syncope was the index symptom in 3 group A vs. 9
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Cardiology Department, Hospital del Mar, Parc de Salut Mar, Passeig Maritim, 25, 08003 Barcelona, Spain. Tel.: +34 932483118; fax: + 34 932483666. E-mail address: [email protected] (V. Bazan).
group B patients (6% vs. 33%, p b 0.001). No significant differences were noted in terms of use of isoproterenol (2/52 group A vs. 4/27 group B patients; p = 0.17) and temporary PM (28/52 and 12/27 patients, respectively; p = 0.48). Distribution and clinical outcome of the distinct pathological processes leading to “reversible” CAVB are depicted in Fig. 1. The miscellany of “other mechanisms” consisted of acute infection in 3 patients and pulmonary embolism in 1. Clinical reports did not specify the cause of CAVB in 5 additional patients, with myocardial ischemia being ruled out. Once AV node conduction was recovered, remnant intra-ventricular conduction disturbances were more frequently documented among group B patients (14/52 group A vs. 20/27 group B patients, p b 0.001), the most common consisting of complete left bundle-branch block in 16 (59%), as opposed to only in 10 (19%) group A patients (p b 0.001). An electrophysiological study was undertaken in only 7 (9%) patients and did not determine indication for PM implantation in any case. Ten (14%) patients died during hospitalization, without differences between groups (p = 0.73). During a median follow-up of 19 (P25–75: 6–43) months, 10 (14%) of the surviving 69 patients received a PM due to CAVB recurrence (time to PM implantation 9 [P25–75: 4–20] months). Nine (39%) of them belonged to group B and 1 (2%) to group A (p b 0.001, Fig. 1). Eighteen (26%) patients died during follow-up (10 group A and 8 group B patients, p = 0.39). In an adjusted Cox regression analysis including age, heart failure, hyperkalemia, remnant intra-ventricular conduction disturbances, severe dementia and ACS, the only factor associated with freedom from PM implantation during follow-up in our series was the identification of acute coronary syndrome as the mechanism of CABV (p = 0.03; odds ratio [95% confidence i nterva l] : 0.0 02 [0.001–0.118]). In this study we demonstrate that the long-term need for permanent ventricular pacing in the setting of “reversible” transitory CAVB is strongly linked to its underlying pathological mechanism. Patients with underlying conditions other than myocardial ischemia are much more prone to develop CAVB recurrences (39% vs. 2%, p b 0.001). Such patients more frequently had older age, increased creatinine levels and higher incidence of heart failure and intraventricular conduction disturbances. These variables have been associated with a higher risk of CAVB recurrences, although in our series this risk was essentially linked to the identification of pathological mechanisms other than myocardial ischemia as the
501
Myocardial stress perfusion-fibrosis imaging pattern in sarcoidosis, assessed by cardiovascular magnetic resonance imaging Sophie Mavrogeni a,⁎, Vasilios Kouranos b, Petros P. Sfikakis c, Konstantinos Bratis a, George D. Kitas d, Efrosini Manali b, Elias Perros e, Kostas Vlasis f, Aggeliki Rapti g, Nikolaos Koulouris b, Kees van Wijk h, David Hautemann h, Johan H.C. Reiber h, Genovefa Kolovou a, George E. Tzelepis b, Elias Gialafos b a
Onassis Cardiac Surgery Center, Athens, Greece 1st Department of Pulmonology, University of Athens, Athens, Greece c First Department of PropInternal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece d Arthritis Research UK Epidemiology Unit, Manchester University, Manchester, UK e Department of Pulmonology, General Hospital of Nikaia “Agios Panteleimonas”, Athens, Greece f Department of Anatomy, University of Athens, Athens, Greece g Second Department of Pulmonology, Sotiria Hospital, Athens, Greece h Leiden University Medical Center, Leiden, The Netherlands b
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i n f o
Article history: Received 4 January 2014 Accepted 8 January 2014 Available online 16 January 2014 Keywords: Sarcoidosis Cardiovascular magnetic resonance (CMR) Myocarditis Stress perfusion-fibrosis CMR Late gadolinium enhancement
Sarcoidosis (SRC) is characterized by granulomas in various organs, including the heart [1]. We hypothesized that cardiovascular magnetic resonance (CMR) may diagnose silent heart lesions in SRC. Forty five consecutive, asymptomatic patients with SRC, (14 men, 45 ± 3 years) normal echocardiogram and 24-hour ECG, underwent CMR imaging, using a 1.5 T. Steady-state, free precession cines were acquired for function evaluation and STIR T2-W for edema imaging. For SRC with T2 ratio b 2 (Group A) and T2 ratio N 2 (Group B), a stress perfusion-fibrosis (Fig. 1) and a myocarditis protocol (Fig. 2) were applied, respectively and were compared to 45 age–sex matched controls. CMR was performed in 43/45 patients (2 were excluded due to technical reasons). In 34/43 SRC with T2 ratio b 2 (Group A), a stress perfusion-fibrosis CMR revealed a significant reduction in myocardial perfusion reserve index (MPRI), compared to 34 age–sex matched controls (0.95 ± 0.3 vs 3.5 ± 0.8, p b 0.001). Although clear evidence of late gadolinium enhancement was not identified, the quantitative analysis revealed diffuse fibrosis in all patients with an extent of 4.5 ± 3.4% LV (range 2–15). Available CMR after 1 year in 18/34 patients, documented LVEF b 50% in 3 patients. Notably, in 6/9 SRC patients with T2 ratio N 2 (Group B), the myocarditis protocol was positive and steroid treatment was promptly given. Six months later, their CMR was normal. No correlation between CMR, SRC duration and/or other organs involvement was identified. Detailed CMR parameters of SRC patients are presented in Table 1. Cardiac involvement, according to pathology, may occur in 20– 30% of SRC of patients [1], and has been associated with poor prognosis [2]. Despite these findings, only 5% of SRC have clinical manifestations of cardiac disease, and only 40–50% of those with cardiac SRC at autopsy have the correct diagnosis during lifetime [2]. CMR has been recently considered as the best noninvasive tool to assess the presence of fibro-granulomatous tissue in the myocardium in SRC [3]. Smedema et al. reported that the prognosis of
⁎ Corresponding author at: 50 Esperou Street, 175-61 P. Faliro, Athens, Greece. Tel./ fax: +30 210 98 82 797. E-mail address: [email protected] (S. Mavrogeni).
asymptomatic SRC patients with cardiac involvement is better compared to SRC patients with symptomatic cardiac SRC [4]. Therefore, a positive CMR in asymptomatic SRC offers the advantage of early treatment and better prognosis [4]. Greulich et al. found that among SRC with nonspecific symptoms, myocardial LGE was the best independent predictor of potentially lethal events [5]. In contrast to LGE that detects the area already replaced by the fibrogranulomatous tissue, sarcoid infiltrates may also be visible as increased intramyocardial signal on T2-weighted images, due to edema, associated with granulomatous lesions. In our asymptomatic SRC, acute myocardial inflammation was identified by CMR in 14%, characterized by both edema and positive LGE. This was in agreement with previous studies [6] and motivated early steroid treatment; none of the steroids-treated patients developed clinically overt cardiac SRC in the next 6 months; furthermore, they normalized their CMR. Our findings are in agreement with recent data, showing that the prognosis of asymptomatic cardiac involvement in pulmonary SRC remains good [6]. Microvascular disease in SRC has been identified in different organs [7]. Reversible myocardial perfusion defects have been already described in both cardiac and noncardiac SRC, using technetium-99m SPECT [8]. This reversibility made unlikely the presence of fibrosis; in contrary, it was indicative of reversible disorders at coronary microvascular level [8]. PET documented that focal perfusion defects in SRC identified patients at higher risk of death or VT and offered prognostic value beyond Japanese clinical criteria, extra-cardiac sarcoidosis and LVEF [9]. In a CMR study of connective tissue diseases, including SRC, by our group, myocardial inflammation and microvascular disease have been also identified [10]. To our knowledge, this is the first study, in which stress perfusion fibrosis CMR was applied for the detection of silent cardiac lesions in asymptomatic SRC. Using stress perfusion-fibrosis CMR, we documented MPRI deterioration and diffuse fibrosis. Our findings were in agreement with previous studies, using nuclear techniques. However, due to better spatial resolution of CMR, a more detailed description of myocardial perfusion-fibrosis pattern was feasible. We documented that microvascular heart disease is an early lesion in SRC, unrelated to granulomas, assessed in acute cases, and can contribute to diffuse fibrosis, an independent factor for LV dysfunction [11,12]. This is in agreement with previous studies supporting that microvascular disease may contribute to LV dysfunction [13,14]. No correlation was identified between CMR and patients' clinical characteristics, other organ involvement and/or disease severity/ duration. This is in agreement with previous studies supporting that heart involvement occurs only in 20–30% of SRC [1] and is not obligatory associated with fulminant or widespread disease [2]. Our findings may have important clinical implications; the early documentation of myocardial inflammation in asymptomatic SRC
502
Letters to the Editor
Fig. 1. Stress Bulls eye (left), rest Bulls eye (middle) and fibrosis polar map (right) of a patient with sarcoidosis and T2 b 2. Evidence of diffuse fibrosis (in yellow) in the fibrosis image, on the right.
necessitates steroids treatment to avoid overt heart disease; in addition, myocardial perfusion defects and fibrosis may lead to overt heart failure, a common endpoint in 25–75% of SRC [15] and address queries about the need of early start of ACE-inhibitors according to ACC/ESC guidelines [16]. The capability of CMR to detect heart SRC, undetected by other techniques, can be potentially of value to diagnose asymptomatic first-degree relatives of SRC, who have 5 times higher risk than controls to develop SRC, according to ACCESS study [17]. Finally, the high incidence of CMR lesions in SRC should motivate the implantation of MRI-conditional pacing system in SRC with complete AV block, in order to maintain the advantage of permanent CMR evaluation [18]. The current study has the following limitations: 1) Small patients' population and lack of long term follow. 2) Lack of symptomatic patients, in order to correlate the clinical presentation with CMR. 3) For diffuse fibrosis evaluation, the QMass MR analytical software was used and not the T1 mapping that is currently considered, as the most reliable way to evaluate the presence of potential diffuse myocardial fibrosis [19]. To conclude, in sarcoidosis without cardiac symptoms and normal routine assessment, CMR can detect early cardiac involvement that may in some cases necessitate immediate treatment. However, further studies are needed to establish criteria in SRC patients' selection for CMR evaluation and to propose a therapeutic algorithm, according to CMR findings.
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Barnard J, Newman LS. Sarcoidosis: immunology, rheumatic involvement, and therapeutics. Curr Opin Rheumatol 2001;13(1):84–91. [2] Sharma OP, Maheshwari A, Thaker K. Myocardial sarcoidosis. Chest 1993;103:253–8. [3] Schulz-Menger J, Wassmuth R, Abdel-Aty H, et al. Patterns of myocardial inflammation and scarring in sarcoidosis as assessed by cardiovascular magnetic resonance. Heart 2006;92:399–400. [4] Smedema JP, Snoep G, van Kroonenburgh MP, et al. Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in The Netherlands. Chest 2005;128:30–5. [5] Greulich S, Deluigi CC, Gloekler S, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 2013;6(4):501–11. [6] Chiu CZ, Nakatani S, Zhang G, et al. Prevention of left ventricular remodeling by long-term corticosteroid therapy in patients with cardiac sarcoidosis. Am J Cardiol 2005;95:143–6. [7] Vilaseca J, Guardia J, Cuxart A, et al. Granulomatous hepatitis. Etiologic study of 107 cases. Med Clin (Barc) 1979;72(7):272–5. [8] Tellier P, Valeyre D, Nitenberg A, Foult JM, Bedig G, Battesti JP. Cardiac sarcoidosis: reversion of myocardial perfusion abnormalities by dipyridamole. Eur J Nucl Med 1985;11(6–7):201–4. [9] Blankstein R, Osborne M, Naya M, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63(4):329–36. [10] Mavrogeni S, Sfikakis PP, Gialafos E, et al. Cardiac tissue characterization and the diagnostic value of cardiovascular magnetic resonance in systemic connective tissue diseases. Arthritis Care Res (Hoboken) 2014;66:104–12. [11] Mavrogeni S, Cantini F, Pohost GM. Systemic vasculitis: an underestimated cause of heart failure — assessment by cardiovascular magnetic resonance. Rev Cardiovasc Med 2013;14(1):49–55. [12] Mavrogeni S, Sfikakis PP, Gialafos E, et al. Diffuse, subendocardial vasculitis. A new entity identified by cardiovascular magnetic resonance and its clinical implications. Int J Cardiol 2013;168:2971–2. [13] Timmer SA, Germans T, Götte MJ, et al. Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury. Am J Cardiol 2011;107(10):1522–8.
Table 1 SRC patients' CMR parameters at baseline.
Fig. 2. Patchy LGE deposition located in the lateral wall of LV in a patient with sarcoidosis and T2 N 2.
CMR parameters
Group A SRC patients with T2 b 2 (n = 34)
Group B SRC patients with T2 N 2 (n = 9)
LVEDV (ml) LVESV (ml) LVEF (%) LV mass (g) RVEDV (ml) RVESV (ml) RVEF (%) MPRI T2 ratio EGE LGE (%LV)
130 ± 31.9 47.7 ± 16.9 63.6 ± 7.7 81.47 ± 25.88 115.8 ± 36.5 54.3 ± 19.37 54.7 ± 7.45 0.95 ± 0.3 1.5 ± 0.3 – 5.7 ± 3.98
126 ± 11 40 ± 12.9 63 ± 8 81.5 ± 13.8 113.6 ± 12 50 ± 8.2 54.4 ± 7.2 – 3.7 ± 0.6 10.6 ± 6.1 4.5 ± 3.4
Letters to the Editor [14] Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013;62:263–71. [15] Sekhri V, Sanal S, DeLorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: a comprehensive review. Arch Med Sci 2011;7(4):546–54. [16] Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119(14):e391–479.
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[17] Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885–9. [18] Quarta G, Holdright DR, Plant GT, et al. Cardiovascular magnetic resonance in cardiac sarcoidosis with MR conditional pacemaker in situ. J Cardiovasc Magn Reson 2011;13:26. [19] Fang L, Beale A, Ellims AH, et al. Associations between fibrocytes and postcontrast myocardial T1 times in hypertrophic cardiomyopathy. J Am Heart Assoc 2013;2(5): e000270.
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.01.006
Long-term outcome of transitory “reversible” complete atrio-ventricular block unrelated to myocardial ischemia☆ Nuria Farre, Victor Bazan ⁎, Cosme Garcia-Garcia, Lluis Recasens, Julio Marti-Almor, Soledad Ascoeta, Ermengol Valles, Oona Meroño-Dueñas, Nuria Ribas, Jordi Bruguera-Cortada Cardiology Department, Hospital del Mar, Universitat Autonoma de Barcelona, Parc de Salut Mar, Barcelona, Spain
a r t i c l e
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Article history: Received 7 January 2014 Accepted 10 January 2014 Available online 23 January 2014 Keywords: Reversible Complete atrio-ventricular block Acute coronary syndrome
The need for permanent ventricular pacing in patients with transitory “reversible” complete atrio-ventricular block (CAVB) occurring in the setting of myocardial ischemia is usually spared. Accordingly, current guidelines discourage indication for permanent pace-maker (PM) implantation when CAVB is expected to resolve once the concurring “reversible” causes are controlled [1,2]. This recommendation is mainly based on expert consensus, and little is known about the long-term outcome of transitory CAVB due to presumably reversible causes other than myocardial ischemia [3–5]. This is a relevant clinical issue, as suggested by a high number of emergency department attendances for compromising bradycardia of presumably reversible causes, in which adverse drug effect/ intoxication and electrolyte disorders are frequently reported [6]. In this study, we analyzed the long-term outcome of “reversible” CAVB when it is unrelated to myocardial ischemia. Seventy-nine consecutive patients with “reversible” CAVB not undergoing initial PM implantation were retrospectively analyzed. Our population was preliminary divided into patients with acute coronary syndrome (ACS, group A, n = 52) and those with other causes of reversible CAVB (group 2, n = 27). Group A patients were younger (p = 0.001) and had a lower prevalence of underlying structural heart disease other than coronary artery disease (20% vs. 54%, respectively; p = 0.03; Table 1). Syncope was the index symptom in 3 group A vs. 9
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Cardiology Department, Hospital del Mar, Parc de Salut Mar, Passeig Maritim, 25, 08003 Barcelona, Spain. Tel.: +34 932483118; fax: + 34 932483666. E-mail address: [email protected] (V. Bazan).
group B patients (6% vs. 33%, p b 0.001). No significant differences were noted in terms of use of isoproterenol (2/52 group A vs. 4/27 group B patients; p = 0.17) and temporary PM (28/52 and 12/27 patients, respectively; p = 0.48). Distribution and clinical outcome of the distinct pathological processes leading to “reversible” CAVB are depicted in Fig. 1. The miscellany of “other mechanisms” consisted of acute infection in 3 patients and pulmonary embolism in 1. Clinical reports did not specify the cause of CAVB in 5 additional patients, with myocardial ischemia being ruled out. Once AV node conduction was recovered, remnant intra-ventricular conduction disturbances were more frequently documented among group B patients (14/52 group A vs. 20/27 group B patients, p b 0.001), the most common consisting of complete left bundle-branch block in 16 (59%), as opposed to only in 10 (19%) group A patients (p b 0.001). An electrophysiological study was undertaken in only 7 (9%) patients and did not determine indication for PM implantation in any case. Ten (14%) patients died during hospitalization, without differences between groups (p = 0.73). During a median follow-up of 19 (P25–75: 6–43) months, 10 (14%) of the surviving 69 patients received a PM due to CAVB recurrence (time to PM implantation 9 [P25–75: 4–20] months). Nine (39%) of them belonged to group B and 1 (2%) to group A (p b 0.001, Fig. 1). Eighteen (26%) patients died during follow-up (10 group A and 8 group B patients, p = 0.39). In an adjusted Cox regression analysis including age, heart failure, hyperkalemia, remnant intra-ventricular conduction disturbances, severe dementia and ACS, the only factor associated with freedom from PM implantation during follow-up in our series was the identification of acute coronary syndrome as the mechanism of CABV (p = 0.03; odds ratio [95% confidence i nterva l] : 0.0 02 [0.001–0.118]). In this study we demonstrate that the long-term need for permanent ventricular pacing in the setting of “reversible” transitory CAVB is strongly linked to its underlying pathological mechanism. Patients with underlying conditions other than myocardial ischemia are much more prone to develop CAVB recurrences (39% vs. 2%, p b 0.001). Such patients more frequently had older age, increased creatinine levels and higher incidence of heart failure and intraventricular conduction disturbances. These variables have been associated with a higher risk of CAVB recurrences, although in our series this risk was essentially linked to the identification of pathological mechanisms other than myocardial ischemia as the