- Email: [email protected]
Mechanisms of Late and Very Late Bioresorbable Vascular Scaffold Thrombosis
JACC VOL. 67, NO. 10, 2016
Letters
MARCH 15, 2016:1254–60
equivalents, a finding that likely plays a significant role in the reduction of AF burden and recurrences. Hypertension and obesity are key mediators of atrial electrical and structural remodeling (4,5), with
conscious chronically instrumented ovine model. Heart Rhythm 2010;7: 1282–90. 5. Mahajan R, Lau DH, Brooks AG, et al. Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol 2015;66:1–11.
blood pressure lowering and weight loss likely contributing to the improved diastolic function, perhaps in tandem with exercise-induced changes. Although we fully agree that an improvement in LV diastolic function is an important factor in the antiarrhythmogenic benefits of exercise, the alliance of other risk factor changes, most notably reductions in blood pressure, body weight, and metabolic risk factors, clearly also improves AF outcomes in
symptomatic,
obese
patients
after
Mechanisms of Late and Very Late Bioresorbable Vascular Scaffold Thrombosis Is it Only About Flow?
lifestyle
modification. Adrian D. Elliott, PhD Rajeev K. Pathak, MBBS Rajiv Mahajan, MD, PhD Dennis H. Lau, MBBS, PhD *Prashanthan Sanders, MBBS, PhD *Centre for Heart Rhythm Disorders Department of Cardiology Royal Adelaide Hospital L5 McEwin Building North Terrace Adelaide, 5000 Australia E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.12.041 Please note: Dr. Pathak is supported by a Postgraduate Scholarship from the Lion’s Medical Research Foundation, an Australian Postgraduate Award, and a Leo J. Mahar Electrophysiology Scholarships from the University of Adelaide. Dr. Mahajan is supported by the Leo J. Mahar Lectureship from the University of Adelaide. Dr. Lau is supported by a Postdoctoral Fellowship from the National Health and Medical Research Council of Australia, and the Robert J. Craig Lectureship from the University of Adelaide. Dr. Sanders is supported by Practitioner Fellowships from the National Health and Medical Research Council of Australia, and by the National Heart Foundation of Australia. Dr. Sanders has served on the advisory board of Biosense-Webster, Medtronic, and St. Jude Medical; has received lecture and/or consulting fees from Biosense-Webster, Medtronic, and St. Jude Medical; and received research funding from Medtronic, St. Jude Medical, Boston Scientific, Biotronik and Sorin. Dr. Elliott has reported that he has no relationships relevant to the contents of this paper to disclose.
REFERENCES 1. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985–96. 2. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64:2222–31. 3. Edelmann F, Gelbrich G, Dungen HD, et al. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study. J Am Coll Cardiol 2011;58: 1780–91. 4. Lau DH, Mackenzie L, Kelly DJ, et al. Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a
We read with interest the paper by Räber et al. that was published in the Journal (1). The authors have conducted a meticulous analysis of 4 cases of very late bioresorbable scaffold thrombosis. One of the assumptions is that resorption-related scaffold discontinuity (2) and malapposition activate the clotting cascade, thus inducing very late bioresorbable scaffold thrombosis. The paper makes no mention of peri-strut low intensity area, namely the nonsignal-attenuating zones around struts, which seems to be present in cases 2 and 4. Late and very late scaffold thrombosis, in the absence of salient mechanical triggers, have been observed in association with peri-strut low intensity area (3). This optical coherence tomography finding is no innocent bystander and has been associated with metallic drugeluting stent peristrut inflammation at histology as well as malapposition, evagination, strut fracture, and uncovered struts (4). It has also been observed in the vessels of bare metal stent- and drug-eluting stenttreated swine where histopathologic analysis showed a variety of underlying tissue such as fibrinoid, proteoglycans, and polymorphic response (macrophages and/or lymphocytes) (5) as well as inflammation (4). PLSIA is thought to be a surrogate marker of edema. Whether or not it is an innocuous phase of device resorption or the expression of inflammation and thus a thrombotic risk has yet to be determined. Diego Arroyo, MD *Stéphane Cook, MD Serban Puricel, MD *Department of Cardiology University and Hospital Fribourg Chemin des Pensionnats 2-6 CH-1708 Fribourg Switzerland E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.11.062
1259
1260
JACC VOL. 67, NO. 10, 2016
Letters
MARCH 15, 2016:1254–60
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
REFERENCES 1. Räber L, Brugaletta S, Yamaji K, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol 2015;66:1901–14. 2. Otsuka F, Pacheco E, Perkins LE, et al. Long-term safety of an everolimuseluting bioresorbable vascular scaffold and the cobalt-chromium XIENCE V stent in a porcine coronary artery model. Circ Cardiovasc Interv 2014;7: 330–42. 3. Cuculi F, Puricel S, Jamshidi P, et al. Optical Coherence tomography findings in bioresorbable vascular scaffolds thrombosis. Circ Cardiovasc Interv 2015;8: e002518. 4. Tellez A, Afari ME, Buszman PP, et al. Peri-strut low-intensity areas in optical coherence tomography correlate with peri-strut inflammation and neointimal proliferation: an in-vivo correlation study in the familial hypercholesterolemic coronary swine model of in-stent restenosis. Coron Artery Dis 2014;25:595–601. 5. Teramoto T, Ikeno F, Otake H, et al. Intriguing peri-strut low-intensity area detected by optical coherence tomography after coronary stent deployment. Circ J 2010;74:1257–9.
REPLY: Mechanisms of Late and Very Late Bioresorbable Vascular Scaffold Thrombosis Is it Only About Flow?
remains speculative in the absence of comparative studies. Dr. Arroyo and colleagues suggest an association between PLSIA and late scaffold thrombosis by referring to an article by Cuculi et al (3). Although the authors of that article state that “late scaffold thrombosis is associated with lower peristrut light intensity” and suggest this to be a “prevailing pathophysioloigcal mechanism of late scaffold thrombosis,” quantitative data as well as any convincing visual representation are not provided in support of this conclusion. PLSIA was observed in 4.3% (case 1), 4.0% (case 2), 11.9% (case 3), and 53% of scaffold struts (case 4), respectively in our case series (1). There was no frame-level correlation between PLSIA and thrombus. Accordingly, we consider PLSIA as optical coherence tomography finding without obvious association to very late scaffold thrombosis. Lorenz Räber, MD, PhD Kyohei Yamaji, MD, PhD *Stephan Windecker, MD *Department of Cardiology Bern University Hospital
We appreciate the interest of Dr. Arroyo and col-
Freiburgstrasse
leagues in our paper (1). The authors suggest that
3010 Bern
peri-low strut intensity areas (PLSIA) may play a
Switzerland
causal role in very late scaffold thrombosis. PLSIA
E-mail: [email protected]
constitute peri-strut signal-poor regions without sig-
http://dx.doi.org/10.1016/j.jacc.2015.12.040
nificant attenuation by optical coherence tomogra-
Please note: Dr. Windecker has received research grants and speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
phy and have been correlated with variety of findings such as fibrin accumulation, proteoglycan rich tissue, inflammatory reactions, and organized thrombus on histologic examinations (2). Indeed, optical coherence tomography-detected PLSIA at follow-up represent a frequent finding (Cypher 58 to 67%, Taxus 80-96%, Biomatrix 40-57%, ABSORB BVS [ABSORB Bioresorbable vascular scaffold] 40%) rendering a causal relationship in the pathogenesis of very late scaffold thrombosis unlikely. Whether ABSORB BVS is more susceptible to PLSIA than other devices
REFERENCES 1. Räber L, Brugaletta S, Yamaji K, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol 2015;66:1901–14. 2. Nakano M, Vorpahl M, Otsuka F, et al. Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging. JACC Cardiovasc Imaging 2012;5:71–82. 3. Cuculi F, Puricel S, Jamshidi P, et al. Optical coherence tomography findings in bioresorbable vascular scaffolds thrombosis. Circ Cardiovasc Interv 2015;8: e002518.
Letters
MARCH 15, 2016:1254–60
equivalents, a finding that likely plays a significant role in the reduction of AF burden and recurrences. Hypertension and obesity are key mediators of atrial electrical and structural remodeling (4,5), with
conscious chronically instrumented ovine model. Heart Rhythm 2010;7: 1282–90. 5. Mahajan R, Lau DH, Brooks AG, et al. Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol 2015;66:1–11.
blood pressure lowering and weight loss likely contributing to the improved diastolic function, perhaps in tandem with exercise-induced changes. Although we fully agree that an improvement in LV diastolic function is an important factor in the antiarrhythmogenic benefits of exercise, the alliance of other risk factor changes, most notably reductions in blood pressure, body weight, and metabolic risk factors, clearly also improves AF outcomes in
symptomatic,
obese
patients
after
Mechanisms of Late and Very Late Bioresorbable Vascular Scaffold Thrombosis Is it Only About Flow?
lifestyle
modification. Adrian D. Elliott, PhD Rajeev K. Pathak, MBBS Rajiv Mahajan, MD, PhD Dennis H. Lau, MBBS, PhD *Prashanthan Sanders, MBBS, PhD *Centre for Heart Rhythm Disorders Department of Cardiology Royal Adelaide Hospital L5 McEwin Building North Terrace Adelaide, 5000 Australia E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.12.041 Please note: Dr. Pathak is supported by a Postgraduate Scholarship from the Lion’s Medical Research Foundation, an Australian Postgraduate Award, and a Leo J. Mahar Electrophysiology Scholarships from the University of Adelaide. Dr. Mahajan is supported by the Leo J. Mahar Lectureship from the University of Adelaide. Dr. Lau is supported by a Postdoctoral Fellowship from the National Health and Medical Research Council of Australia, and the Robert J. Craig Lectureship from the University of Adelaide. Dr. Sanders is supported by Practitioner Fellowships from the National Health and Medical Research Council of Australia, and by the National Heart Foundation of Australia. Dr. Sanders has served on the advisory board of Biosense-Webster, Medtronic, and St. Jude Medical; has received lecture and/or consulting fees from Biosense-Webster, Medtronic, and St. Jude Medical; and received research funding from Medtronic, St. Jude Medical, Boston Scientific, Biotronik and Sorin. Dr. Elliott has reported that he has no relationships relevant to the contents of this paper to disclose.
REFERENCES 1. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985–96. 2. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64:2222–31. 3. Edelmann F, Gelbrich G, Dungen HD, et al. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study. J Am Coll Cardiol 2011;58: 1780–91. 4. Lau DH, Mackenzie L, Kelly DJ, et al. Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a
We read with interest the paper by Räber et al. that was published in the Journal (1). The authors have conducted a meticulous analysis of 4 cases of very late bioresorbable scaffold thrombosis. One of the assumptions is that resorption-related scaffold discontinuity (2) and malapposition activate the clotting cascade, thus inducing very late bioresorbable scaffold thrombosis. The paper makes no mention of peri-strut low intensity area, namely the nonsignal-attenuating zones around struts, which seems to be present in cases 2 and 4. Late and very late scaffold thrombosis, in the absence of salient mechanical triggers, have been observed in association with peri-strut low intensity area (3). This optical coherence tomography finding is no innocent bystander and has been associated with metallic drugeluting stent peristrut inflammation at histology as well as malapposition, evagination, strut fracture, and uncovered struts (4). It has also been observed in the vessels of bare metal stent- and drug-eluting stenttreated swine where histopathologic analysis showed a variety of underlying tissue such as fibrinoid, proteoglycans, and polymorphic response (macrophages and/or lymphocytes) (5) as well as inflammation (4). PLSIA is thought to be a surrogate marker of edema. Whether or not it is an innocuous phase of device resorption or the expression of inflammation and thus a thrombotic risk has yet to be determined. Diego Arroyo, MD *Stéphane Cook, MD Serban Puricel, MD *Department of Cardiology University and Hospital Fribourg Chemin des Pensionnats 2-6 CH-1708 Fribourg Switzerland E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.11.062
1259
1260
JACC VOL. 67, NO. 10, 2016
Letters
MARCH 15, 2016:1254–60
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
REFERENCES 1. Räber L, Brugaletta S, Yamaji K, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol 2015;66:1901–14. 2. Otsuka F, Pacheco E, Perkins LE, et al. Long-term safety of an everolimuseluting bioresorbable vascular scaffold and the cobalt-chromium XIENCE V stent in a porcine coronary artery model. Circ Cardiovasc Interv 2014;7: 330–42. 3. Cuculi F, Puricel S, Jamshidi P, et al. Optical Coherence tomography findings in bioresorbable vascular scaffolds thrombosis. Circ Cardiovasc Interv 2015;8: e002518. 4. Tellez A, Afari ME, Buszman PP, et al. Peri-strut low-intensity areas in optical coherence tomography correlate with peri-strut inflammation and neointimal proliferation: an in-vivo correlation study in the familial hypercholesterolemic coronary swine model of in-stent restenosis. Coron Artery Dis 2014;25:595–601. 5. Teramoto T, Ikeno F, Otake H, et al. Intriguing peri-strut low-intensity area detected by optical coherence tomography after coronary stent deployment. Circ J 2010;74:1257–9.
REPLY: Mechanisms of Late and Very Late Bioresorbable Vascular Scaffold Thrombosis Is it Only About Flow?
remains speculative in the absence of comparative studies. Dr. Arroyo and colleagues suggest an association between PLSIA and late scaffold thrombosis by referring to an article by Cuculi et al (3). Although the authors of that article state that “late scaffold thrombosis is associated with lower peristrut light intensity” and suggest this to be a “prevailing pathophysioloigcal mechanism of late scaffold thrombosis,” quantitative data as well as any convincing visual representation are not provided in support of this conclusion. PLSIA was observed in 4.3% (case 1), 4.0% (case 2), 11.9% (case 3), and 53% of scaffold struts (case 4), respectively in our case series (1). There was no frame-level correlation between PLSIA and thrombus. Accordingly, we consider PLSIA as optical coherence tomography finding without obvious association to very late scaffold thrombosis. Lorenz Räber, MD, PhD Kyohei Yamaji, MD, PhD *Stephan Windecker, MD *Department of Cardiology Bern University Hospital
We appreciate the interest of Dr. Arroyo and col-
Freiburgstrasse
leagues in our paper (1). The authors suggest that
3010 Bern
peri-low strut intensity areas (PLSIA) may play a
Switzerland
causal role in very late scaffold thrombosis. PLSIA
E-mail: [email protected]
constitute peri-strut signal-poor regions without sig-
http://dx.doi.org/10.1016/j.jacc.2015.12.040
nificant attenuation by optical coherence tomogra-
Please note: Dr. Windecker has received research grants and speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
phy and have been correlated with variety of findings such as fibrin accumulation, proteoglycan rich tissue, inflammatory reactions, and organized thrombus on histologic examinations (2). Indeed, optical coherence tomography-detected PLSIA at follow-up represent a frequent finding (Cypher 58 to 67%, Taxus 80-96%, Biomatrix 40-57%, ABSORB BVS [ABSORB Bioresorbable vascular scaffold] 40%) rendering a causal relationship in the pathogenesis of very late scaffold thrombosis unlikely. Whether ABSORB BVS is more susceptible to PLSIA than other devices
REFERENCES 1. Räber L, Brugaletta S, Yamaji K, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol 2015;66:1901–14. 2. Nakano M, Vorpahl M, Otsuka F, et al. Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging. JACC Cardiovasc Imaging 2012;5:71–82. 3. Cuculi F, Puricel S, Jamshidi P, et al. Optical coherence tomography findings in bioresorbable vascular scaffolds thrombosis. Circ Cardiovasc Interv 2015;8: e002518.