International Journal of Cardiology 181 (2015) 39–41
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Acute myocardial infarction in a young woman on isotretinoin treatment Natalia Lorenzo, Paula Antuña, Lourdes Dominguez, Fernando Rivero, Teresa Bastante, Fernando Alfonso ⁎ Hospital Universitario de La Princesa, Madrid, Spain
a r t i c l e
i n f o
Article history: Received 12 November 2014 Accepted 23 November 2014 Available online 25 November 2014 Keywords: Myocardial infarction Isotretinoin Optical coherence tomography
a b s t r a c t The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion. © 2014 Elsevier Ireland Ltd. All rights reserved.
Dear Editor: A 28-year-old girl was admitted for an episode of prolonged chest pain. The electrocardiogram showed ST-segment elevation in the inferior leads. She had been treated with oral isotretinoin for one year due to severe acne. She was an occasional smoker but had no other medical or family cardiovascular history. However, since isotretinoin treatment was initiated oral contraceptives were prescribed and high glycemia (up to 130 mg/dl) and cholesterol levels (total cholesterol: 210 mg/dL; low-density lipoproteins: 140 mg/dL; with normal triglyceridemia) were occasionally found. Urgent coronary angiography revealed a total occlusion of the proximal right coronary artery. The left coronary artery was completely normal with a smooth angiographic appearance. Thromboaspiration retrieved a large red thrombus and obtained a TIMI 3 anterograde coronary flow. Optical coherence tomography (OCT) (St Jude Medical, St Paul MN, USA) disclosed a complicated atherosclerotic plaque (Fig. 1). Some arterial segments showed a predominantly fibrotic plaque including some areas with a layered morphology. Close to the minimal lumen area a large lipid plaque, with a ruptured fibrous cap associated with white and red thrombi, was clearly visualized (Fig. 1). A 3.5 × 18 mm bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA) was implanted and subsequently post-dilated with a noncompliant balloon at 18 bars with an excellent final angiographic result (Fig. 2). Repeated OCT disclosed a nicely apposed and fully expanded device. The characteristic image of the BVS struts (“black-box” appearance without
⁎ Corresponding author at: Cardiac Department, Hospital Universitario de La Princesa, C/Diego de León 62, Madrid 28006, Spain. E-mail address: [email protected] (F. Alfonso).
http://dx.doi.org/10.1016/j.ijcard.2014.11.169 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
dorsal shadowing) was clearly identified against underlying residual atherosclerotic tissue. Clinical outcome was uneventful (ultrasensitive troponin T peak: 3.663 ng/L, creatinine kinase peak: 1.544 U/L) and the patient was discharged 3 days later. Isotretinoin, or 13-cis-retinoic acid, a synthetic analogue of vitamin A, is the most effective drug for the treatment of nodulocystic acne. Since isotretinoin was approved in the early 1980s, it has been used worldwide in millions of patients. The extensive experience generated has demonstrated the drug´s safety profile. However, isotretinoin use has been associated with teratogenicity. Therefore, contraceptives are routinely prescribed. Lipid abnormalities are common during treatment with 13-cis-retinoic acid: 20–45% of patients develop hypertriglyceridemia and up to 30%, develop elevated total cholesterol and lowdensity lipoprotein levels. However, lipid levels rarely require treatment discontinuation [1]. In addition, insulin-resistance and diabetes have been anecdotally reported [2]. Since its approval occasional reports have associated isotretinoin therapy with myocardial infarction, stroke and thromboembolic disorders [3]. However, information in this regard is surprisingly scarce and there are no previous reports unraveling the underlying pathophysiology of these rare cardiovascular events. In our patient OCT provided unique visualization of the culprit lesion. We found advanced atherosclerosis mainly consisting in fibrotic and lipidic fibroatheroma. Furthermore, we identified a ruptured thin-cap fibroatheroma associated with occlusive thrombus. We believe that the use of BVS is very attractive in this unique scenario, particularly in young patients. BVS have potent antirestenostic efficacy yet they eventually disappear from the vessel wall allowing the restoration of a normal vessel wall physiology [4]. Moreover, BVS appear ideally suited for patients with atherosclerosis resulting from reversible metabolic alterations. Thrombotic events occurring during treatment with 13-cisretinoic acid remain unexplained. However, our case appears to
40
N. Lorenzo et al. / International Journal of Cardiology 181 (2015) 39–41
Fig. 1. A) Coronary angiography showing a total occlusion of the proximal segment of the right coronary artery (arrow). B–E) Optical coherence tomography images. A relatively large atherosclerotic plaque was visualized in the proximal right coronary artery mainly showing a fibrotic appearance but also including areas (double small arrow) with layered morphology (B). However, other segments (C–E) showed large lipid pools (+). A confined plaque rupture (arrow) was also clearly recognized (D). Finally, small residual thrombi (T) were readily visualized (E). (*) = denotes wire artifact.
Fig. 2. A) Final angiographic result. Arrows denote the site of BVS implantation. B–E) Optical coherence tomography images after the procedure. The characteristic “blackbox” appearance of the device (without posterior shadowing) is readily visualized overlying different types of plaque, including lipidic, fibrotic and layered. A wide lumen with excellent expansion and apposition of the BVS was confirmed (B–E). Interestingly, some minor-angiographically silent-dissections were also identified (arrow) (C). (*) = denotes wire artifact.
suggest that even in the presence of just mild metabolic disorders isotretinoin may potentially play a role in the development not only of accelerated atherosclerosis but also of plaque rupture leading to acute myocardial infarction.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
N. Lorenzo et al. / International Journal of Cardiology 181 (2015) 39–41
References [1] N. Rodondi, R. Darioli, A.A. Ramelet, D. Hohl, V. Lenain, J. Perdrix, V. Wietlisbach, W.F. Riesen, T. Walther, L. Medinger, P. Nicod, B. Desvergne, V. Mooser, High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis-retinoic acid therapy for acne: a pharmacogenetic study, Ann. Intern. Med. 1366 (8) (2002) 582–589. [2] I. Dicembrini, G. Bardini, C.M. Rotella, Association between oral isotretinoin therapy and unmasked latent immuno-mediated diabetes, Diabetes Care 32 (8) (2009) e99.
41
[3] A. Bérard, L. Azoulay, H. Reza, K. Moussally, Isotretinoin and the risk of cardiovascular, cerebrovascular and thromboembolic disorders, Dermatology 223 (2011) 45–51. [4] J.A. Ormiston, P.W. Serruys, Y. Onuma, R.J. van Geuns, B. de Bruyne, D. Dudek, L. Thuesen, P.C. Smits, B. Chevalier, D. McClean, J. Koolen, S. Windecker, R. Whitbourn, I. Meredith, C. Dorange, S. Veldhof, K.M. Hebert, R. Rapoza, H.M. Garcia-Garcia, First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study, Circ. Cardiovasc. Interv. 5 (5) (2012) 620–632.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Acute myocardial infarction in a young woman on isotretinoin treatment Natalia Lorenzo, Paula Antuña, Lourdes Dominguez, Fernando Rivero, Teresa Bastante, Fernando Alfonso ⁎ Hospital Universitario de La Princesa, Madrid, Spain
a r t i c l e
i n f o
Article history: Received 12 November 2014 Accepted 23 November 2014 Available online 25 November 2014 Keywords: Myocardial infarction Isotretinoin Optical coherence tomography
a b s t r a c t The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion. © 2014 Elsevier Ireland Ltd. All rights reserved.
Dear Editor: A 28-year-old girl was admitted for an episode of prolonged chest pain. The electrocardiogram showed ST-segment elevation in the inferior leads. She had been treated with oral isotretinoin for one year due to severe acne. She was an occasional smoker but had no other medical or family cardiovascular history. However, since isotretinoin treatment was initiated oral contraceptives were prescribed and high glycemia (up to 130 mg/dl) and cholesterol levels (total cholesterol: 210 mg/dL; low-density lipoproteins: 140 mg/dL; with normal triglyceridemia) were occasionally found. Urgent coronary angiography revealed a total occlusion of the proximal right coronary artery. The left coronary artery was completely normal with a smooth angiographic appearance. Thromboaspiration retrieved a large red thrombus and obtained a TIMI 3 anterograde coronary flow. Optical coherence tomography (OCT) (St Jude Medical, St Paul MN, USA) disclosed a complicated atherosclerotic plaque (Fig. 1). Some arterial segments showed a predominantly fibrotic plaque including some areas with a layered morphology. Close to the minimal lumen area a large lipid plaque, with a ruptured fibrous cap associated with white and red thrombi, was clearly visualized (Fig. 1). A 3.5 × 18 mm bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA) was implanted and subsequently post-dilated with a noncompliant balloon at 18 bars with an excellent final angiographic result (Fig. 2). Repeated OCT disclosed a nicely apposed and fully expanded device. The characteristic image of the BVS struts (“black-box” appearance without
⁎ Corresponding author at: Cardiac Department, Hospital Universitario de La Princesa, C/Diego de León 62, Madrid 28006, Spain. E-mail address: [email protected] (F. Alfonso).
http://dx.doi.org/10.1016/j.ijcard.2014.11.169 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
dorsal shadowing) was clearly identified against underlying residual atherosclerotic tissue. Clinical outcome was uneventful (ultrasensitive troponin T peak: 3.663 ng/L, creatinine kinase peak: 1.544 U/L) and the patient was discharged 3 days later. Isotretinoin, or 13-cis-retinoic acid, a synthetic analogue of vitamin A, is the most effective drug for the treatment of nodulocystic acne. Since isotretinoin was approved in the early 1980s, it has been used worldwide in millions of patients. The extensive experience generated has demonstrated the drug´s safety profile. However, isotretinoin use has been associated with teratogenicity. Therefore, contraceptives are routinely prescribed. Lipid abnormalities are common during treatment with 13-cis-retinoic acid: 20–45% of patients develop hypertriglyceridemia and up to 30%, develop elevated total cholesterol and lowdensity lipoprotein levels. However, lipid levels rarely require treatment discontinuation [1]. In addition, insulin-resistance and diabetes have been anecdotally reported [2]. Since its approval occasional reports have associated isotretinoin therapy with myocardial infarction, stroke and thromboembolic disorders [3]. However, information in this regard is surprisingly scarce and there are no previous reports unraveling the underlying pathophysiology of these rare cardiovascular events. In our patient OCT provided unique visualization of the culprit lesion. We found advanced atherosclerosis mainly consisting in fibrotic and lipidic fibroatheroma. Furthermore, we identified a ruptured thin-cap fibroatheroma associated with occlusive thrombus. We believe that the use of BVS is very attractive in this unique scenario, particularly in young patients. BVS have potent antirestenostic efficacy yet they eventually disappear from the vessel wall allowing the restoration of a normal vessel wall physiology [4]. Moreover, BVS appear ideally suited for patients with atherosclerosis resulting from reversible metabolic alterations. Thrombotic events occurring during treatment with 13-cisretinoic acid remain unexplained. However, our case appears to
40
N. Lorenzo et al. / International Journal of Cardiology 181 (2015) 39–41
Fig. 1. A) Coronary angiography showing a total occlusion of the proximal segment of the right coronary artery (arrow). B–E) Optical coherence tomography images. A relatively large atherosclerotic plaque was visualized in the proximal right coronary artery mainly showing a fibrotic appearance but also including areas (double small arrow) with layered morphology (B). However, other segments (C–E) showed large lipid pools (+). A confined plaque rupture (arrow) was also clearly recognized (D). Finally, small residual thrombi (T) were readily visualized (E). (*) = denotes wire artifact.
Fig. 2. A) Final angiographic result. Arrows denote the site of BVS implantation. B–E) Optical coherence tomography images after the procedure. The characteristic “blackbox” appearance of the device (without posterior shadowing) is readily visualized overlying different types of plaque, including lipidic, fibrotic and layered. A wide lumen with excellent expansion and apposition of the BVS was confirmed (B–E). Interestingly, some minor-angiographically silent-dissections were also identified (arrow) (C). (*) = denotes wire artifact.
suggest that even in the presence of just mild metabolic disorders isotretinoin may potentially play a role in the development not only of accelerated atherosclerosis but also of plaque rupture leading to acute myocardial infarction.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
N. Lorenzo et al. / International Journal of Cardiology 181 (2015) 39–41
References [1] N. Rodondi, R. Darioli, A.A. Ramelet, D. Hohl, V. Lenain, J. Perdrix, V. Wietlisbach, W.F. Riesen, T. Walther, L. Medinger, P. Nicod, B. Desvergne, V. Mooser, High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis-retinoic acid therapy for acne: a pharmacogenetic study, Ann. Intern. Med. 1366 (8) (2002) 582–589. [2] I. Dicembrini, G. Bardini, C.M. Rotella, Association between oral isotretinoin therapy and unmasked latent immuno-mediated diabetes, Diabetes Care 32 (8) (2009) e99.
41
[3] A. Bérard, L. Azoulay, H. Reza, K. Moussally, Isotretinoin and the risk of cardiovascular, cerebrovascular and thromboembolic disorders, Dermatology 223 (2011) 45–51. [4] J.A. Ormiston, P.W. Serruys, Y. Onuma, R.J. van Geuns, B. de Bruyne, D. Dudek, L. Thuesen, P.C. Smits, B. Chevalier, D. McClean, J. Koolen, S. Windecker, R. Whitbourn, I. Meredith, C. Dorange, S. Veldhof, K.M. Hebert, R. Rapoza, H.M. Garcia-Garcia, First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study, Circ. Cardiovasc. Interv. 5 (5) (2012) 620–632.
