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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiac transplantation is a well-established therapy for selected cases of end-stage heart disease&#46; In its early stages&#44; one-year survival was only 50&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> the poor results being due to allograft rejection or infection&#46; Advances in immunosuppressive therapy with more effective regimens was crucial in improving survival at one year after heart transplantation&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">As short-term survival improved&#44; cardiac allograft vasculopathy &#40;CAV&#41; became a major limitation of long-term survival&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Because cardiac transplant recipients do not feel the classic symptoms of myocardial ischemia&#44; as a result of denervation of the allograft&#44; early diagnosis is challenging&#44; but extremely important because it enables the disease to be recognized and treated in the initial stages&#44; preventing progression and improving prognosis&#46; The disorder is primarily immune-mediated&#44; but some nonimmune factors are also of importance&#46; Once CAV is diagnosed&#44; the International Society for Heart and Lung Transplantation &#40;ISHLT&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> recommend the introduction of everolimus or sirolimus&#44; since their antiproliferative effects can delay the progression of CAV and reduce its severity&#44; on top of statin therapy&#46; In selected patients&#44; coronary revascularization should be performed and in advanced CAV&#44; retransplantation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the single-center study by Pic&#227;o et al&#46; published in this issue of the <span class="elsevierStyleItalic">Journal</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> patients with heart transplantation underwent routine coronary angiography at one&#44; three&#44; five&#44; eight&#44; 10 and 12 years after transplantation and additional exams if clinically justified&#46; The prevalence of CAV &#40;9&#46;7&#37; and 17&#46;6&#37; at five and eight years post-transplantation&#44; respectively&#41; was much lower than that described in the literature &#40;29&#37; and 40&#37; in the 2015 ISHLT report<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The diagnostic prevalence of CAV is closely linked to the method used to identify it&#46; Coronary angiography remains the recommended screening method for CAV&#44; but its sensitivity is low&#46; Conventional angiography does not assess the arterial wall and the vascular remodeling associated with CAV&#46; The pathological characteristics of CAV differ significantly from those of typical atherosclerotic coronary disease&#46; CAV involves concentric and diffuse proliferation of the arterial intima&#44; with thickening and pathological remodeling leading to progressive narrowing of the lumen&#44; particularly of small and medium-sized arteries&#46; These findings are more difficult to diagnose by conventional angiography compared to the eccentric plaque typical of atherosclerotic coronary disease&#46; In this setting&#44; intracoronary imaging tools such as intravascular ultrasound &#40;IVUS&#41; and optical coherence tomography &#40;OCT&#41; significantly improve diagnostic accuracy for coronary disease in heart transplant patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">An optimal screening test should be safe&#44; easy to perform and clinically able to either rule out disease or confirm its presence and assess its severity in order to support a valid clinical decision&#46; There is growing interest in newer non-invasive imaging techniques that can exclude CAV&#44; such as dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve of the left anterior descending artery &#40;which excludes disease with a high negative predictive value of 91&#46;1&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> positron emission tomography myocardial perfusion imaging&#44; coronary computed tomography &#40;CT&#41; angiography &#40;CCTA&#41;&#44; and cardiac magnetic resonance imaging&#46; CCTA can provide non-invasive anatomical assessment by visualizing the coronary artery lumen and wall&#46; New-generation multislice systems with dual-source technology improve spatial and temporal resolution&#44; helping to overcome the limitation of high heart rates often seen in these patients&#46; CCTA currently has excellent sensitivity&#44; specificity and negative predictive value for the detection of CAV&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> although it is less sensitive than IVUS&#59; as a screening method it can be improved if associated with non-invasive physiological assessment &#40;CCTA complemented by CT-based fractional flow reserve&#41;&#46; These non-invasive techniques are likely to become more clinically important in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">More accurate screening algorithms are needed for early detection of disease or for identification of patients at risk of developing CAV&#46; In this context&#44; identifying CAV predictors&#44; as Pic&#227;o et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> did in their study&#44; is clinically important&#46; They identified previous ischemic heart disease and carotid artery disease in the recipient&#44; as well as donor age&#44; as predictors of CAV&#46; The rising age of donors in recent decades&#44; with more comorbidities&#44; especially in Europe&#44; decreases the quality of the graft&#44; and it is thus necessary to be aware of this risk predictor&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In future studies&#44; it would be useful to analyze other possible predictors of CAV development in larger multicenter study populations&#44; such as the cause of brain death&#44; ischemia-reperfusion injury&#44; viral infection and metabolic disorders&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Based on these results&#44; changes were proposed in the authors&#8217; institutional protocol&#44; including routine coronary angiography for donors over the age of 50 years to confirm eligibility for heart transplantation&#44; and assessment with OCT at the time of the first routine angiography for recipients deemed at higher risk for CAV according to the clinician&#39;s judgment &#40;including patients with vascular disease&#41;&#44; in order to improve diagnostic accuracy and to adjust immunosuppressive therapy accordingly&#46; We agree that if the disease is to be identified early&#44; intracoronary imaging &#40;IVUS or OCT&#41; will need to be used routinely in association with invasive angiography&#44; especially in the first years after transplantation&#46; Progressive intimal thickening in the first year post-transplantation identifies patients at high risk for future cardiovascular events&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In future&#44; non-invasive imaging methods will certainly replace coronary angiography for CAV screening&#46; Invasive angiography in association with IVUS or OCT will be restricted to high-risk patients&#44; for those with inconclusive or positive results on non-invasive tests&#44; and for those needing coronary revascularization&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Cardiac allograft vasculopathy: How can it be predicted?
Doença coronária do aloenxerto cardíaco. Como podemos prevê-la?
Rita Caléa,
Autor para correspondência
ritacale@hotmail.com

Corresponding author.
, Manuel de Sousa Almeidab
a Cardiology Department, Hospital Garcia de Orta, Almada, Portugal
b Cardiology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Head EpiDoC Unit, Nova Medical School, Universidade Nova de Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiac transplantation is a well-established therapy for selected cases of end-stage heart disease&#46; In its early stages&#44; one-year survival was only 50&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> the poor results being due to allograft rejection or infection&#46; Advances in immunosuppressive therapy with more effective regimens was crucial in improving survival at one year after heart transplantation&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">As short-term survival improved&#44; cardiac allograft vasculopathy &#40;CAV&#41; became a major limitation of long-term survival&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Because cardiac transplant recipients do not feel the classic symptoms of myocardial ischemia&#44; as a result of denervation of the allograft&#44; early diagnosis is challenging&#44; but extremely important because it enables the disease to be recognized and treated in the initial stages&#44; preventing progression and improving prognosis&#46; The disorder is primarily immune-mediated&#44; but some nonimmune factors are also of importance&#46; Once CAV is diagnosed&#44; the International Society for Heart and Lung Transplantation &#40;ISHLT&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> recommend the introduction of everolimus or sirolimus&#44; since their antiproliferative effects can delay the progression of CAV and reduce its severity&#44; on top of statin therapy&#46; In selected patients&#44; coronary revascularization should be performed and in advanced CAV&#44; retransplantation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the single-center study by Pic&#227;o et al&#46; published in this issue of the <span class="elsevierStyleItalic">Journal</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> patients with heart transplantation underwent routine coronary angiography at one&#44; three&#44; five&#44; eight&#44; 10 and 12 years after transplantation and additional exams if clinically justified&#46; The prevalence of CAV &#40;9&#46;7&#37; and 17&#46;6&#37; at five and eight years post-transplantation&#44; respectively&#41; was much lower than that described in the literature &#40;29&#37; and 40&#37; in the 2015 ISHLT report<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The diagnostic prevalence of CAV is closely linked to the method used to identify it&#46; Coronary angiography remains the recommended screening method for CAV&#44; but its sensitivity is low&#46; Conventional angiography does not assess the arterial wall and the vascular remodeling associated with CAV&#46; The pathological characteristics of CAV differ significantly from those of typical atherosclerotic coronary disease&#46; CAV involves concentric and diffuse proliferation of the arterial intima&#44; with thickening and pathological remodeling leading to progressive narrowing of the lumen&#44; particularly of small and medium-sized arteries&#46; These findings are more difficult to diagnose by conventional angiography compared to the eccentric plaque typical of atherosclerotic coronary disease&#46; In this setting&#44; intracoronary imaging tools such as intravascular ultrasound &#40;IVUS&#41; and optical coherence tomography &#40;OCT&#41; significantly improve diagnostic accuracy for coronary disease in heart transplant patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">An optimal screening test should be safe&#44; easy to perform and clinically able to either rule out disease or confirm its presence and assess its severity in order to support a valid clinical decision&#46; There is growing interest in newer non-invasive imaging techniques that can exclude CAV&#44; such as dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve of the left anterior descending artery &#40;which excludes disease with a high negative predictive value of 91&#46;1&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> positron emission tomography myocardial perfusion imaging&#44; coronary computed tomography &#40;CT&#41; angiography &#40;CCTA&#41;&#44; and cardiac magnetic resonance imaging&#46; CCTA can provide non-invasive anatomical assessment by visualizing the coronary artery lumen and wall&#46; New-generation multislice systems with dual-source technology improve spatial and temporal resolution&#44; helping to overcome the limitation of high heart rates often seen in these patients&#46; CCTA currently has excellent sensitivity&#44; specificity and negative predictive value for the detection of CAV&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> although it is less sensitive than IVUS&#59; as a screening method it can be improved if associated with non-invasive physiological assessment &#40;CCTA complemented by CT-based fractional flow reserve&#41;&#46; These non-invasive techniques are likely to become more clinically important in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">More accurate screening algorithms are needed for early detection of disease or for identification of patients at risk of developing CAV&#46; In this context&#44; identifying CAV predictors&#44; as Pic&#227;o et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> did in their study&#44; is clinically important&#46; They identified previous ischemic heart disease and carotid artery disease in the recipient&#44; as well as donor age&#44; as predictors of CAV&#46; The rising age of donors in recent decades&#44; with more comorbidities&#44; especially in Europe&#44; decreases the quality of the graft&#44; and it is thus necessary to be aware of this risk predictor&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In future studies&#44; it would be useful to analyze other possible predictors of CAV development in larger multicenter study populations&#44; such as the cause of brain death&#44; ischemia-reperfusion injury&#44; viral infection and metabolic disorders&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Based on these results&#44; changes were proposed in the authors&#8217; institutional protocol&#44; including routine coronary angiography for donors over the age of 50 years to confirm eligibility for heart transplantation&#44; and assessment with OCT at the time of the first routine angiography for recipients deemed at higher risk for CAV according to the clinician&#39;s judgment &#40;including patients with vascular disease&#41;&#44; in order to improve diagnostic accuracy and to adjust immunosuppressive therapy accordingly&#46; We agree that if the disease is to be identified early&#44; intracoronary imaging &#40;IVUS or OCT&#41; will need to be used routinely in association with invasive angiography&#44; especially in the first years after transplantation&#46; Progressive intimal thickening in the first year post-transplantation identifies patients at high risk for future cardiovascular events&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In future&#44; non-invasive imaging methods will certainly replace coronary angiography for CAV screening&#46; Invasive angiography in association with IVUS or OCT will be restricted to high-risk patients&#44; for those with inconclusive or positive results on non-invasive tests&#44; and for those needing coronary revascularization&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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