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cardiac transplant recipients do not experience angina because of perioperative denervation&#46; However&#44; they may present with left ventricular dysfunction as a consequence of myocardial ischemia&#46; Therefore&#44; routine surveillance for CAV is recommended by the International Society for Heart and Lung Transplantation&#44; for which coronary angiography is considered the modality of choice&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment of CAV remains a clinical challenge&#46; The options are limited and include the use of oral antiproliferative agents&#44; statins&#44; percutaneous coronary intervention &#40;PCI&#41; and&#47;or repeat OHT&#44; all with suboptimal results&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Case report</span><p id="par0070" class="elsevierStylePara elsevierViewall">We present the case of a 64-year-old male with ischemic cardiomyopathy who received an OHT from a 42-year-old male donor in 2009&#46; The patient had three-vessel disease and had undergone coronary artery bypass grafting in 1998&#59; in the pre-heart transplantation evaluation only the left internal mammary artery &#40;LIMA&#41; to left anterior descending artery &#40;LAD&#41; graft was patent&#46; Two pre-existing non-occlusive &#40;&#60;50&#37;&#41; stenoses in the mid LAD of the donor heart led to the decision to use the patient&#39;s LIMA to anastomose to the donor&#39;s LAD during the transplantation procedure&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">At five-year follow-up after transplantation&#44; the routine coronary angiography &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41; showed progression of the two mid LAD stenoses &#40;50-70&#37;&#41; and revealed that the LIMA&#8211;LAD graft was no longer patent&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The functional significance of the LAD lesions was assessed by measurement of fractional flow reserve &#40;FFR&#41; using a 0&#46;014&#8243; pressure guide wire &#40;PressureWire Aeris&#8482;&#44; St&#46; Jude Medical&#44; Uppsala&#44; Sweden&#41;&#46; The value obtained was 0&#46;78&#44; suggesting the presence of functionally significant lesions&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The pressure guide wire was then replaced by a 2&#46;7F optical coherence tomography &#40;OCT&#41; catheter &#40;Dragonfly Duo&#8482; imaging catheter&#44; St&#46; Jude Medical&#44; St&#46; Paul&#44; MN&#44; USA&#41; and OCT images &#40;Ilumien Optis&#8482; system&#44; St&#46; Jude Medical&#44; St&#46; Paul&#44; MN&#44; USA&#41; were recorded from the mid to proximal portions of the LAD at an automatic pull-back speed of 20 mm&#47;s and a frame rate of 100&#47;s&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">OCT images of the mid LAD segment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41; showed a lipid-rich plaque with atherosclerotic characteristics&#44; and OCT of the proximal LAD segment &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41; demonstrated intimal hyperproliferation compatible with CAV&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Considering these findings&#44; we decided to treat the two lesions with 3&#46;0 mm&#215;15 mm and 3&#46;0 mm&#215;12 mm Ultimaster&#8482; sirolimus-eluting stents&#46; The result was assessed by OCT and revealed malapposed struts of the distal stent &#40;maximum length of segments with malapposed struts 1&#46;5 mm&#59; maximum malapposition distance 0&#46;36 mm&#41;&#46; We therefore decided to proceed with adjunctive post-dilatation using a 3&#46;0 mm&#215;12 mm non-compliant balloon&#46; Final OCT examination showed a very good result&#44; as presented in <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>&#46; FFR was repeated&#44; indicating a good physiological result of 0&#46;89&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Heart transplant coronary artery disease represents a unique clinical challenge&#44; due to its distinctive pathogenesis&#44; diagnostic approach and treatment modalities&#46; CAV is thought to be an immunologic phenomenon that involves the entire coronary vasculature diffusely&#44; with marked intimal proliferation and concentric vascular thickening and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> This contrasts with conventional coronary atherosclerosis&#44; which is marked by focal&#44; eccentric fibrofatty atheroma&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Advances in invasive coronary imaging&#44; such as intravascular ultrasound &#40;IVUS&#41; and OCT&#44; have shown promising results in increasing knowledge of the pathophysiology of CAV&#46; Intimal thickening is typically the initial finding on IVUS&#44; and rapidly progressive CAV is defined as an increase of &#8805;0&#46;5 mm in intimal thickness within the first year post-OHT&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> More recent studies using intracoronary OCT have demonstrated higher sensitivity for early detection of CAV&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> and have provided new insights that extend beyond the traditional concept of CAV&#44; showing the development of atherosclerosis with vulnerable plaque and complicated coronary lesions such as intraluminal thrombus&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Although both IVUS and OCT are more sensitive and specific in detecting early-stage CAV than coronary angiography alone and provide additional information for risk stratification&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> routine use of these methods is limited&#46; The current recommendation for screening and surveillance of CAV remains annual coronary angiography&#46; Nevertheless&#44; IVUS with a baseline study at 4-6 weeks and at one year after OHT&#44; in order to exclude donor coronary artery disease and to detect rapidly progressive CAV&#44; is already mentioned as an optional method&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">12</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Coronary artery disease in heart transplant recipients is often a combination of donor-transmitted atherosclerosis and de novo lesions of CAV&#46; This distinction can be difficult to make solely on the basis of the distribution and morphology of lesions on coronary angiography&#46; Though the lesions of CAV tend to be more diffuse and circumferential than donor-transmitted atherosclerosis&#44; both types of lesions have a predilection for proximal segments and bifurcation sites&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a> In the case reported&#44; the progression of pre-existing non-obstructive stenoses in the mid LAD segment of the donor heart was easily detected by angiography and their nature confirmed by OCT imaging&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The etiology of the heart failure that leads to OHT may also be an important factor in the progression of transplant coronary artery disease&#46; Guddeti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> demonstrated that ischemic cardiomyopathy patients had significantly greater plaque volume index at initial and follow-up virtual histology IVUS examinations and that this was an independent predictor of plaque progression&#44; especially within three years of transplantation&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Treatment of CAV is truly a challenge since its pathophysiology is multifactorial&#44; with a wide range of immunologic and non-immunologic contributors&#46; Furthermore&#44; patients are usually asymptomatic&#44; but their survival after documentation of CAV is significantly reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> Current immunosuppressive therapy has limited efficacy in preventing the development of CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> By contrast&#44; statins exert multiple pleiotropic effects in the transplanted heart&#44; reducing cytokine activity&#44; improving coronary endothelial function and increasing coronary flow reserve&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> and several statins have been associated with reduced CAV progression and improved survival after OHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">18&#8211;20</span></a> Repeat OHT is the only definitive therapy for CAV but it is associated with higher perioperative mortality&#44; lower long-term survival and a higher recurrence of CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> Coronary artery bypass surgery is rarely performed&#44; because CAV is associated with poor distal targets&#44; due to the diffuse nature of the disease&#44; and greater perioperative mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Hence&#44; PCI has been routinely used as a treatment alternative in patients with focal proximal CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> Although small-scale&#44; single-center studies have demonstrated excellent procedure outcomes&#44;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">24&#44;25</span></a> data on long-term mortality benefit are sparse and controversial&#46; Recently&#44; Agarwal et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> showed that among patients with at least moderate CAV on any coronary angiogram&#44; long-term survival in those amenable to PCI was greater than in those with CAV not treatable with PCI&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The assessment of cardiac transplant recipients by routine coronary angiography entails interpreting the physiological significance of focal coronary stenosis&#44; particularly of intermediate stenosis&#44; in order to guide the need for PCI&#46; FFR is an index that provides information on the degree to which epicardial artery disease is affecting myocardial perfusion and is well validated in non-OHT populations&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> Studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">27&#44;28</span></a> on the changes in coronary anatomy and physiology after heart transplantation found that soon after OHT there is a strong correlation between FFR and IVUS-determined epicardial percentage plaque volume&#46; Late after OHT&#44; increased microvascular resistance &#40;as shown by a higher index of microvascular resistance&#41; results in a decrease in the maximum achievable flow down the epicardial vessel and lessens the physiologic impact of structural abnormalities in the epicardial artery&#46; For this reason&#44; when significant microvascular dysfunction is present&#44; FFR may not provide a good representation of epicardial artery plaque burden&#46; In this case report&#44; FFR was very useful for assessing the functional significance of the two mid LAD intermediate stenoses&#44; guiding the decision whether to intervene&#46; After PCI an increase in FFR was also demonstrated&#44; proving the physiologic benefit of the PCI&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Finally&#44; PCI in heart transplant recipients is associated with a higher incidence of restenosis&#44; compared to the non-OHT population&#46; Outcomes with balloon angioplasty have been less than ideal&#44; contributing to allograft loss because of the very high incidence of restenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> PCI with drug-eluting stents &#40;DES&#41; appears to be associated with reduced angiographic in-stent restenosis rate in transplant patients&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> Tremmel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> compared PCI with bare-metal stents &#40;BMS&#41; vs&#46; DES in cardiac transplant recipients and demonstrated that DES are safer and more effective in suppressing neointimal hyperplasia after PCI for CAV&#46; This leads to a significantly lower rate of late lumen loss and target lesion revascularization&#44; as well as to reduced rates of cardiac death and nonfatal myocardial infarction&#46; In the case presented&#44; we used two new-generation DES and then assessed the result by OCT imaging&#46; As the distal stent had an incomplete expansion&#44; which is known to be associated with an even higher restenosis rate&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> we performed a high-pressure post-dilation to obtain optimal stent expansion&#44; confirmed by another OCT examination&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">Heart transplant coronary artery disease is a complex disorder and remains a significant cause of morbidity and mortality in OHT patients&#46; Invasive coronary imaging modalities such as IVUS or OCT are crucial as they provide information on early-stage CAV and can confirm the nature of coronary stenosis and help in PCI optimization&#46; Although it is affected by microvascular dysfunction in the late stages after OHT&#44; assessment through FFR may be valuable in making therapeutic decisions&#46; Compared with BMS&#44; PCI with DES is safer and reduces the restenosis rate in patients with CAV&#46; The present case demonstrates the use of a multimodality approach and highlights its importance to achieve good outcomes in this challenging population&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Protection of human and animal subjects</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Confidentiality of data</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Right to privacy and informed consent</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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            1 => "Coronary artery disease"
            2 => "Cardiac allograft vasculopathy"
            3 => "Optical coherence tomography"
            4 => "Fractional flow reserve"
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            2 => "Vasculopatia do enxerto"
            3 => "Tomografia de coer&#234;ncia &#243;tica"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Coronary artery disease is the most important cause of late morbidity and mortality after heart transplantation&#46; It is usually an immunologic phenomenon termed cardiac allograft vasculopathy&#44; but can also be the result of donor-transmitted atherosclerosis&#46; Routine surveillance by coronary angiography should be complemented by intracoronary imaging&#44; in order to determine the nature of the coronary lesions&#44; and also by assessment of their functional significance to guide the decision whether to perform percutaneous coronary intervention&#46; We report a case of coronary angiography at five-year follow-up after transplantation&#44; using optical coherence tomography and fractional flow reserve to assess and optimize treatment of coronary disease in this challenging population&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Doen&#231;a coron&#225;ria &#233; a causa mais importante de morbimortalidade tardia ap&#243;s transplanta&#231;&#227;o card&#237;aca&#46; Habitualmente&#44; representa um fen&#243;meno imunol&#243;gico designado como vasculopatia do aloenxerto&#44; mas tamb&#233;m pode resultar da aterosclerose transmitida pelo dador&#46; A vigil&#226;ncia atrav&#233;s de coronariografia de rotina deve ser complementada pela utiliza&#231;&#227;o de imagem intracoron&#225;ria&#44; de forma a determinar a natureza das les&#245;es&#44; e tamb&#233;m atrav&#233;s de uma avalia&#231;&#227;o funcional para tomada da decis&#227;o de realizar interven&#231;&#227;o coron&#225;ria percut&#226;nea&#46; Apresentamos o caso de uma coronariografia aos cinco anos de seguimento ap&#243;s transplanta&#231;&#227;o&#44; utilizando tomografia de coer&#234;ncia &#243;tica e <span class="elsevierStyleItalic">fractional flow reserve</span> para avalia&#231;&#227;o e otimiza&#231;&#227;o do tratamento da doen&#231;a coron&#225;ria nesta popula&#231;&#227;o desafiante&#46;</p></span>"
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                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">cardiac allograft vasculopathy</p>"
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                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">optical coherence tomography</p>"
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                "termino" => "OHT"
                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">orthotopic heart transplantation</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Coronary angiography&#58; images of the left coronary artery showing two mid left anterior descending artery intermediate stenoses &#40;50-70&#37;&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Optical coherence tomography&#58; image of the mid left anterior descending artery with lipid-rich atherosclerotic plaque &#40;asterisk&#58; incomplete blood displacement&#41;&#46;</p>"
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Case report
Heart transplant coronary artery disease: Multimodality approach in percutaneous intervention
Doença coronária no transplantado cardíaco: abordagem anatomofuncional na intervenção percutânea
Luís Leitea,
Corresponding author
luispcleite@gmail.com

Corresponding author.
, Vítor Matosa, Lino Gonçalvesa, João Silva Marquesa, Elisabete Jorgea, João Calistoa, Manuel Antunesb, Mariano Pegoa
a Cardiology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
b Cardiothoracic Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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cardiac transplant recipients do not experience angina because of perioperative denervation&#46; However&#44; they may present with left ventricular dysfunction as a consequence of myocardial ischemia&#46; Therefore&#44; routine surveillance for CAV is recommended by the International Society for Heart and Lung Transplantation&#44; for which coronary angiography is considered the modality of choice&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment of CAV remains a clinical challenge&#46; The options are limited and include the use of oral antiproliferative agents&#44; statins&#44; percutaneous coronary intervention &#40;PCI&#41; and&#47;or repeat OHT&#44; all with suboptimal results&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Case report</span><p id="par0070" class="elsevierStylePara elsevierViewall">We present the case of a 64-year-old male with ischemic cardiomyopathy who received an OHT from a 42-year-old male donor in 2009&#46; The patient had three-vessel disease and had undergone coronary artery bypass grafting in 1998&#59; in the pre-heart transplantation evaluation only the left internal mammary artery &#40;LIMA&#41; to left anterior descending artery &#40;LAD&#41; graft was patent&#46; Two pre-existing non-occlusive &#40;&#60;50&#37;&#41; stenoses in the mid LAD of the donor heart led to the decision to use the patient&#39;s LIMA to anastomose to the donor&#39;s LAD during the transplantation procedure&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">At five-year follow-up after transplantation&#44; the routine coronary angiography &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41; showed progression of the two mid LAD stenoses &#40;50-70&#37;&#41; and revealed that the LIMA&#8211;LAD graft was no longer patent&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The functional significance of the LAD lesions was assessed by measurement of fractional flow reserve &#40;FFR&#41; using a 0&#46;014&#8243; pressure guide wire &#40;PressureWire Aeris&#8482;&#44; St&#46; Jude Medical&#44; Uppsala&#44; Sweden&#41;&#46; The value obtained was 0&#46;78&#44; suggesting the presence of functionally significant lesions&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The pressure guide wire was then replaced by a 2&#46;7F optical coherence tomography &#40;OCT&#41; catheter &#40;Dragonfly Duo&#8482; imaging catheter&#44; St&#46; Jude Medical&#44; St&#46; Paul&#44; MN&#44; USA&#41; and OCT images &#40;Ilumien Optis&#8482; system&#44; St&#46; Jude Medical&#44; St&#46; Paul&#44; MN&#44; USA&#41; were recorded from the mid to proximal portions of the LAD at an automatic pull-back speed of 20 mm&#47;s and a frame rate of 100&#47;s&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">OCT images of the mid LAD segment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41; showed a lipid-rich plaque with atherosclerotic characteristics&#44; and OCT of the proximal LAD segment &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41; demonstrated intimal hyperproliferation compatible with CAV&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Considering these findings&#44; we decided to treat the two lesions with 3&#46;0 mm&#215;15 mm and 3&#46;0 mm&#215;12 mm Ultimaster&#8482; sirolimus-eluting stents&#46; The result was assessed by OCT and revealed malapposed struts of the distal stent &#40;maximum length of segments with malapposed struts 1&#46;5 mm&#59; maximum malapposition distance 0&#46;36 mm&#41;&#46; We therefore decided to proceed with adjunctive post-dilatation using a 3&#46;0 mm&#215;12 mm non-compliant balloon&#46; Final OCT examination showed a very good result&#44; as presented in <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>&#46; FFR was repeated&#44; indicating a good physiological result of 0&#46;89&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Heart transplant coronary artery disease represents a unique clinical challenge&#44; due to its distinctive pathogenesis&#44; diagnostic approach and treatment modalities&#46; CAV is thought to be an immunologic phenomenon that involves the entire coronary vasculature diffusely&#44; with marked intimal proliferation and concentric vascular thickening and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> This contrasts with conventional coronary atherosclerosis&#44; which is marked by focal&#44; eccentric fibrofatty atheroma&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Advances in invasive coronary imaging&#44; such as intravascular ultrasound &#40;IVUS&#41; and OCT&#44; have shown promising results in increasing knowledge of the pathophysiology of CAV&#46; Intimal thickening is typically the initial finding on IVUS&#44; and rapidly progressive CAV is defined as an increase of &#8805;0&#46;5 mm in intimal thickness within the first year post-OHT&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> More recent studies using intracoronary OCT have demonstrated higher sensitivity for early detection of CAV&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> and have provided new insights that extend beyond the traditional concept of CAV&#44; showing the development of atherosclerosis with vulnerable plaque and complicated coronary lesions such as intraluminal thrombus&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> Although both IVUS and OCT are more sensitive and specific in detecting early-stage CAV than coronary angiography alone and provide additional information for risk stratification&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> routine use of these methods is limited&#46; The current recommendation for screening and surveillance of CAV remains annual coronary angiography&#46; Nevertheless&#44; IVUS with a baseline study at 4-6 weeks and at one year after OHT&#44; in order to exclude donor coronary artery disease and to detect rapidly progressive CAV&#44; is already mentioned as an optional method&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">12</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Coronary artery disease in heart transplant recipients is often a combination of donor-transmitted atherosclerosis and de novo lesions of CAV&#46; This distinction can be difficult to make solely on the basis of the distribution and morphology of lesions on coronary angiography&#46; Though the lesions of CAV tend to be more diffuse and circumferential than donor-transmitted atherosclerosis&#44; both types of lesions have a predilection for proximal segments and bifurcation sites&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a> In the case reported&#44; the progression of pre-existing non-obstructive stenoses in the mid LAD segment of the donor heart was easily detected by angiography and their nature confirmed by OCT imaging&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The etiology of the heart failure that leads to OHT may also be an important factor in the progression of transplant coronary artery disease&#46; Guddeti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">14</span></a> demonstrated that ischemic cardiomyopathy patients had significantly greater plaque volume index at initial and follow-up virtual histology IVUS examinations and that this was an independent predictor of plaque progression&#44; especially within three years of transplantation&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Treatment of CAV is truly a challenge since its pathophysiology is multifactorial&#44; with a wide range of immunologic and non-immunologic contributors&#46; Furthermore&#44; patients are usually asymptomatic&#44; but their survival after documentation of CAV is significantly reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> Current immunosuppressive therapy has limited efficacy in preventing the development of CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> By contrast&#44; statins exert multiple pleiotropic effects in the transplanted heart&#44; reducing cytokine activity&#44; improving coronary endothelial function and increasing coronary flow reserve&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> and several statins have been associated with reduced CAV progression and improved survival after OHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">18&#8211;20</span></a> Repeat OHT is the only definitive therapy for CAV but it is associated with higher perioperative mortality&#44; lower long-term survival and a higher recurrence of CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> Coronary artery bypass surgery is rarely performed&#44; because CAV is associated with poor distal targets&#44; due to the diffuse nature of the disease&#44; and greater perioperative mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Hence&#44; PCI has been routinely used as a treatment alternative in patients with focal proximal CAV&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> Although small-scale&#44; single-center studies have demonstrated excellent procedure outcomes&#44;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">24&#44;25</span></a> data on long-term mortality benefit are sparse and controversial&#46; Recently&#44; Agarwal et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> showed that among patients with at least moderate CAV on any coronary angiogram&#44; long-term survival in those amenable to PCI was greater than in those with CAV not treatable with PCI&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The assessment of cardiac transplant recipients by routine coronary angiography entails interpreting the physiological significance of focal coronary stenosis&#44; particularly of intermediate stenosis&#44; in order to guide the need for PCI&#46; FFR is an index that provides information on the degree to which epicardial artery disease is affecting myocardial perfusion and is well validated in non-OHT populations&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> Studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">27&#44;28</span></a> on the changes in coronary anatomy and physiology after heart transplantation found that soon after OHT there is a strong correlation between FFR and IVUS-determined epicardial percentage plaque volume&#46; Late after OHT&#44; increased microvascular resistance &#40;as shown by a higher index of microvascular resistance&#41; results in a decrease in the maximum achievable flow down the epicardial vessel and lessens the physiologic impact of structural abnormalities in the epicardial artery&#46; For this reason&#44; when significant microvascular dysfunction is present&#44; FFR may not provide a good representation of epicardial artery plaque burden&#46; In this case report&#44; FFR was very useful for assessing the functional significance of the two mid LAD intermediate stenoses&#44; guiding the decision whether to intervene&#46; After PCI an increase in FFR was also demonstrated&#44; proving the physiologic benefit of the PCI&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Finally&#44; PCI in heart transplant recipients is associated with a higher incidence of restenosis&#44; compared to the non-OHT population&#46; Outcomes with balloon angioplasty have been less than ideal&#44; contributing to allograft loss because of the very high incidence of restenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> PCI with drug-eluting stents &#40;DES&#41; appears to be associated with reduced angiographic in-stent restenosis rate in transplant patients&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> Tremmel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> compared PCI with bare-metal stents &#40;BMS&#41; vs&#46; DES in cardiac transplant recipients and demonstrated that DES are safer and more effective in suppressing neointimal hyperplasia after PCI for CAV&#46; This leads to a significantly lower rate of late lumen loss and target lesion revascularization&#44; as well as to reduced rates of cardiac death and nonfatal myocardial infarction&#46; In the case presented&#44; we used two new-generation DES and then assessed the result by OCT imaging&#46; As the distal stent had an incomplete expansion&#44; which is known to be associated with an even higher restenosis rate&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> we performed a high-pressure post-dilation to obtain optimal stent expansion&#44; confirmed by another OCT examination&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">Heart transplant coronary artery disease is a complex disorder and remains a significant cause of morbidity and mortality in OHT patients&#46; Invasive coronary imaging modalities such as IVUS or OCT are crucial as they provide information on early-stage CAV and can confirm the nature of coronary stenosis and help in PCI optimization&#46; Although it is affected by microvascular dysfunction in the late stages after OHT&#44; assessment through FFR may be valuable in making therapeutic decisions&#46; Compared with BMS&#44; PCI with DES is safer and reduces the restenosis rate in patients with CAV&#46; The present case demonstrates the use of a multimodality approach and highlights its importance to achieve good outcomes in this challenging population&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Protection of human and animal subjects</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Confidentiality of data</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Right to privacy and informed consent</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Case report"
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          "titulo" => "Ethical disclosures"
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              "titulo" => "Protection of human and animal subjects"
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              "identificador" => "sec0035"
              "titulo" => "Confidentiality of data"
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              "identificador" => "sec0040"
              "titulo" => "Right to privacy and informed consent"
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    "fechaRecibido" => "2015-06-22"
    "fechaAceptado" => "2015-09-13"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec821228"
          "palabras" => array:6 [
            0 => "Heart transplantation"
            1 => "Coronary artery disease"
            2 => "Cardiac allograft vasculopathy"
            3 => "Optical coherence tomography"
            4 => "Fractional flow reserve"
            5 => "Percutaneous coronary intervention"
          ]
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      ]
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec821227"
          "palabras" => array:6 [
            0 => "Transplante card&#237;aco"
            1 => "Doen&#231;a coron&#225;ria"
            2 => "Vasculopatia do enxerto"
            3 => "Tomografia de coer&#234;ncia &#243;tica"
            4 => "<span class="elsevierStyleItalic">Fractional flow reserve</span>"
            5 => "Interven&#231;&#227;o coron&#225;ria percut&#226;nea"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Coronary artery disease is the most important cause of late morbidity and mortality after heart transplantation&#46; It is usually an immunologic phenomenon termed cardiac allograft vasculopathy&#44; but can also be the result of donor-transmitted atherosclerosis&#46; Routine surveillance by coronary angiography should be complemented by intracoronary imaging&#44; in order to determine the nature of the coronary lesions&#44; and also by assessment of their functional significance to guide the decision whether to perform percutaneous coronary intervention&#46; We report a case of coronary angiography at five-year follow-up after transplantation&#44; using optical coherence tomography and fractional flow reserve to assess and optimize treatment of coronary disease in this challenging population&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Doen&#231;a coron&#225;ria &#233; a causa mais importante de morbimortalidade tardia ap&#243;s transplanta&#231;&#227;o card&#237;aca&#46; Habitualmente&#44; representa um fen&#243;meno imunol&#243;gico designado como vasculopatia do aloenxerto&#44; mas tamb&#233;m pode resultar da aterosclerose transmitida pelo dador&#46; A vigil&#226;ncia atrav&#233;s de coronariografia de rotina deve ser complementada pela utiliza&#231;&#227;o de imagem intracoron&#225;ria&#44; de forma a determinar a natureza das les&#245;es&#44; e tamb&#233;m atrav&#233;s de uma avalia&#231;&#227;o funcional para tomada da decis&#227;o de realizar interven&#231;&#227;o coron&#225;ria percut&#226;nea&#46; Apresentamos o caso de uma coronariografia aos cinco anos de seguimento ap&#243;s transplanta&#231;&#227;o&#44; utilizando tomografia de coer&#234;ncia &#243;tica e <span class="elsevierStyleItalic">fractional flow reserve</span> para avalia&#231;&#227;o e otimiza&#231;&#227;o do tratamento da doen&#231;a coron&#225;ria nesta popula&#231;&#227;o desafiante&#46;</p></span>"
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        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0025">List of abbreviations</span>"
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          0 => array:1 [
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                "termino" => "BMS"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">bare-metal stents</p>"
              ]
              1 => array:2 [
                "termino" => "CAV"
                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">cardiac allograft vasculopathy</p>"
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              2 => array:2 [
                "termino" => "DES"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">drug-eluting stents</p>"
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                "termino" => "FFR"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall">fractional flow reserve</p>"
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                "termino" => "IVUS"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">intravascular ultrasound</p>"
              ]
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                "termino" => "LAD"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">left anterior descending artery</p>"
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              6 => array:2 [
                "termino" => "LIMA"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">left internal mammary artery graft</p>"
              ]
              7 => array:2 [
                "termino" => "OCT"
                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">optical coherence tomography</p>"
              ]
              8 => array:2 [
                "termino" => "OHT"
                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">orthotopic heart transplantation</p>"
              ]
              9 => array:2 [
                "termino" => "PCI"
                "descripcion" => "<p id="par0050" class="elsevierStylePara elsevierViewall">percutaneous coronary intervention</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Coronary angiography&#58; images of the left coronary artery showing two mid left anterior descending artery intermediate stenoses &#40;50-70&#37;&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Optical coherence tomography&#58; image of the mid left anterior descending artery with lipid-rich atherosclerotic plaque &#40;asterisk&#58; incomplete blood displacement&#41;&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Optical coherence tomography &#40;OCT&#41;&#58; image showing distal mid left anterior descending artery &#40;LAD&#41; stent with malapposed struts&#59; &#40;B&#41; OCT image of the distal mid LAD stent after post-dilatation&#44; revealing well-expanded and well-apposed stent struts&#46;</p>"
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      "titulo" => "References"
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                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46;J&#46;V&#46; McMurray"
                            1 => "S&#46; Adamopoulos"
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                          ]
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                    0 => array:2 [
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                            0 => "M&#46;R&#46; Mehra"
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                          "etal" => true
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                            0 => "B&#46; Syeda"
                            1 => "S&#46; Roedler"
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                        0 => array:2 [
                          "etal" => true
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                            0 => "S&#46; Agarwal"
                            1 => "A&#46; Parashar"
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ISSN: 21742049
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