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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acromegaly is a rare endocrine disorder associated with various systemic complications&#44; cardiovascular &#40;CV&#41; disease being one of the most critical and responsible for about 60&#37; of deaths&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a> Hence the importance of increasing cardiologists&#8217; knowledge about this disease&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The main feature of its CV manifestations is acromegalic cardiomyopathy&#44; which usually begins with left ventricular &#40;LV&#41; hypertrophy and diastolic dysfunction&#44; and can progress to systolic dysfunction in advanced stages&#46; Valvular heart disease&#44; coronary artery disease and arrhythmias are other common CV manifestations in acromegaly&#44; and these patients also frequently develop CV risk factors such as hypertension&#44; diabetes and sleep apnea syndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a> It is important to note that early recognition and appropriate treatment can reverse some of these abnormalities&#44; like LV hypertrophy&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">For all these reasons there is an undeniable need for cardiologists to be involved in the surveillance and management of these patients&#46; Studies are therefore needed to increase our knowledge of acromegalic cardiomyopathy&#44; particularly regarding valvulopathy&#44; its morphological and functional impact&#44; frequency of echocardiographic follow-up and possible therapeutic implications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study by Nemes et al&#46; published in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> included 27 acromegalic patients and 38 matched healthy controls and assessed mitral annular &#40;MA&#41; size and function by three-dimensional speckle-tracking echocardiography &#40;3D-STE&#41;&#46; Their main finding was significant MA dilation with no functional impairment in acromegalic patients&#44; regardless of disease activity&#46; It should be noted that MA dimensions were based on measured end-diastolic MA diameter&#44; area and perimeter&#44; and MA functional properties were calculated based on MA fractional shortening &#40;MAFS&#41; and MA fractional area change &#40;MAFAC&#41;&#44; with only a brief and qualitative assessment of mitral regurgitation &#40;MR&#41;&#44; which was reported as insignificant and unrelated to disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">While this study adds some important information regarding mitral valve involvement in acromegaly&#44; it also raises some questions&#46; First&#44; MA size and function were assessed through a 3D-STE-derived technique&#44; which although already in use and confirmed to be capable of reproducible assessment of MA dimensions&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> is still under investigation and has some technical limitations&#44; including temporal and spatial resolution&#46; Also&#44; 3D-STE-derived MA dimensions showed somewhat lower values than full-volume real-time 3D echocardiography &#40;RT-3DE&#41;&#44; which has been validated by magnetic resonance imaging and is able to analyze the complex saddle-shaped configuration of the mitral annulus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Secondly&#44; although MA function was considered preserved despite MA dilation&#44; this was assessed through MAFS and MAFAC&#46; It would be interesting to put it into a more clinical perspective by relating it to valvular regurgitation&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">There are several published studies reporting a high prevalence of mitral and aortic valve abnormalities in acromegaly&#44; with a statistically significant higher prevalence of aortic and mitral regurgitation than in matched controls&#46; However&#44; this higher reported prevalence ranged widely&#44; from 5&#37; to 86&#37; of acromegalic patients and from only trace to moderate severity&#44; but was mainly asymptomatic and rarely clinically significant&#46; Valvular heart disease appears to be definitely correlated with the duration of active disease&#44; with a calculated 19&#37; increase in odds ratio with every year of excess growth hormone &#40;GH&#41; duration&#44; but irrespective of disease activity&#44; meaning that valvular damage is irreversible even with successful treatment of acromegaly&#44; in contrast to the observed regression of LV hypertrophy&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2&#44;6&#8211;8</span></a> These studies also demonstrated that long-term exposure to excess GH leads to accelerated degenerative valvular changes&#44; including myxomatous degeneration and calcifications of leaflets and annuli&#44; suggesting that replacement valve surgery should be considered rather than valvuloplasty if therapeutic intervention is needed&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6&#8211;8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the study by Nemes et al&#46;&#44; MR was reported as insignificant&#44; with controls apparently showing no MR at all and only 25&#37; of acromegalic patients showing trace or mild severity &#40;grade &#8804;2&#41;&#46; There was only a statistically significant predominance of MR in acromegalic individuals over controls in grade 1 severity &#40;trace&#41; and in inactive disease&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The issue at stake is why MA dilation occurs without significant functional impairment or mitral regurgitation&#44; in contrast to what is demonstrated in other cardiomyopathies&#44; such as dilated or hypertrophic cardiomyopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The authors explain this phenomenon through a compensatory increase in LV and left atrial contractility owing to an increase in LV radial strains&#44; as demonstrated in acromegaly by Korm&#225;nyos et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> enabling adequate MA contraction and function despite dilation of the annulus&#46; However&#44; this is only seen in active disease&#44; while patients with inactive disease show no radial strain gain compared to controls&#46; But based on this argument&#44; more MR would be expected than was actually reported&#44; particularly in inactive disease&#46; On the other hand&#44; this is probably the reason for the tendency towards a slightly higher grade of MR in inactive acromegalic patients than in controls&#44; although still at a very low grade of severity&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors also found preserved MA function independent of disease activity&#46; Although this may be due to the early stage of acromegaly at which the assessment was performed&#44; this cannot be confirmed since the stage of the disease in which patients were assessed was not identified&#46; It can at least be presumed that it was not at a very advanced stage&#44; given the low grade of LV hypertrophy and the preserved ejection fraction in these acromegalic patients&#44; but this is not certain&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Besides this&#44; the study lacks information on mitral valve structural abnormalities and the pathophysiological mechanisms responsible for MR in these patients&#44; probably due to the low spatial resolution of 3D-STE&#46; MR appears to have been an undervalued issue in this study&#44; which soon became clear once the authors stated that MR severity was qualitatively rather than quantitatively graded &#40;not following the latest guidelines of the European Association of Cardiovascular Imaging and the American Society of Echocardiography&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study contrasts with previous ones by giving a clearer insight into acromegalic cardiomyopathy&#44; since it demonstrates preserved MA function without significant MR despite MA dilation&#44; highlighting a possible new mechanism for this to happen &#40;increase in LV radial strain&#41;&#46; Although it has some technical issues&#44; including the small number of patients analyzed with an echocardiographic technique that has limited resolution&#44; the authors should be congratulated for their effort to increase our knowledge of a rare but clinically significant disease&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">I believe a more clinical approach with more emphasis on MR would be welcome&#44; and the question remains whether these findings are related to an early or late stage of the disease&#46; Therefore&#44; more confirmatory studies are needed&#46; But the importance of careful and continuous cardiological follow-up and echocardiographic monitoring in this disease remains unquestioned&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Mitral annular function in acromegaly: Still a lot to learn
Função do anel mitral na acromegalia: muito para aprender…
Liliana Marta
Department of Cardiology, Hospital Beatriz Ângelo, Loures, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acromegaly is a rare endocrine disorder associated with various systemic complications&#44; cardiovascular &#40;CV&#41; disease being one of the most critical and responsible for about 60&#37; of deaths&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a> Hence the importance of increasing cardiologists&#8217; knowledge about this disease&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The main feature of its CV manifestations is acromegalic cardiomyopathy&#44; which usually begins with left ventricular &#40;LV&#41; hypertrophy and diastolic dysfunction&#44; and can progress to systolic dysfunction in advanced stages&#46; Valvular heart disease&#44; coronary artery disease and arrhythmias are other common CV manifestations in acromegaly&#44; and these patients also frequently develop CV risk factors such as hypertension&#44; diabetes and sleep apnea syndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a> It is important to note that early recognition and appropriate treatment can reverse some of these abnormalities&#44; like LV hypertrophy&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">For all these reasons there is an undeniable need for cardiologists to be involved in the surveillance and management of these patients&#46; Studies are therefore needed to increase our knowledge of acromegalic cardiomyopathy&#44; particularly regarding valvulopathy&#44; its morphological and functional impact&#44; frequency of echocardiographic follow-up and possible therapeutic implications&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study by Nemes et al&#46; published in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> included 27 acromegalic patients and 38 matched healthy controls and assessed mitral annular &#40;MA&#41; size and function by three-dimensional speckle-tracking echocardiography &#40;3D-STE&#41;&#46; Their main finding was significant MA dilation with no functional impairment in acromegalic patients&#44; regardless of disease activity&#46; It should be noted that MA dimensions were based on measured end-diastolic MA diameter&#44; area and perimeter&#44; and MA functional properties were calculated based on MA fractional shortening &#40;MAFS&#41; and MA fractional area change &#40;MAFAC&#41;&#44; with only a brief and qualitative assessment of mitral regurgitation &#40;MR&#41;&#44; which was reported as insignificant and unrelated to disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">While this study adds some important information regarding mitral valve involvement in acromegaly&#44; it also raises some questions&#46; First&#44; MA size and function were assessed through a 3D-STE-derived technique&#44; which although already in use and confirmed to be capable of reproducible assessment of MA dimensions&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> is still under investigation and has some technical limitations&#44; including temporal and spatial resolution&#46; Also&#44; 3D-STE-derived MA dimensions showed somewhat lower values than full-volume real-time 3D echocardiography &#40;RT-3DE&#41;&#44; which has been validated by magnetic resonance imaging and is able to analyze the complex saddle-shaped configuration of the mitral annulus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Secondly&#44; although MA function was considered preserved despite MA dilation&#44; this was assessed through MAFS and MAFAC&#46; It would be interesting to put it into a more clinical perspective by relating it to valvular regurgitation&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">There are several published studies reporting a high prevalence of mitral and aortic valve abnormalities in acromegaly&#44; with a statistically significant higher prevalence of aortic and mitral regurgitation than in matched controls&#46; However&#44; this higher reported prevalence ranged widely&#44; from 5&#37; to 86&#37; of acromegalic patients and from only trace to moderate severity&#44; but was mainly asymptomatic and rarely clinically significant&#46; Valvular heart disease appears to be definitely correlated with the duration of active disease&#44; with a calculated 19&#37; increase in odds ratio with every year of excess growth hormone &#40;GH&#41; duration&#44; but irrespective of disease activity&#44; meaning that valvular damage is irreversible even with successful treatment of acromegaly&#44; in contrast to the observed regression of LV hypertrophy&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2&#44;6&#8211;8</span></a> These studies also demonstrated that long-term exposure to excess GH leads to accelerated degenerative valvular changes&#44; including myxomatous degeneration and calcifications of leaflets and annuli&#44; suggesting that replacement valve surgery should be considered rather than valvuloplasty if therapeutic intervention is needed&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6&#8211;8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In the study by Nemes et al&#46;&#44; MR was reported as insignificant&#44; with controls apparently showing no MR at all and only 25&#37; of acromegalic patients showing trace or mild severity &#40;grade &#8804;2&#41;&#46; There was only a statistically significant predominance of MR in acromegalic individuals over controls in grade 1 severity &#40;trace&#41; and in inactive disease&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The issue at stake is why MA dilation occurs without significant functional impairment or mitral regurgitation&#44; in contrast to what is demonstrated in other cardiomyopathies&#44; such as dilated or hypertrophic cardiomyopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The authors explain this phenomenon through a compensatory increase in LV and left atrial contractility owing to an increase in LV radial strains&#44; as demonstrated in acromegaly by Korm&#225;nyos et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> enabling adequate MA contraction and function despite dilation of the annulus&#46; However&#44; this is only seen in active disease&#44; while patients with inactive disease show no radial strain gain compared to controls&#46; But based on this argument&#44; more MR would be expected than was actually reported&#44; particularly in inactive disease&#46; On the other hand&#44; this is probably the reason for the tendency towards a slightly higher grade of MR in inactive acromegalic patients than in controls&#44; although still at a very low grade of severity&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors also found preserved MA function independent of disease activity&#46; Although this may be due to the early stage of acromegaly at which the assessment was performed&#44; this cannot be confirmed since the stage of the disease in which patients were assessed was not identified&#46; It can at least be presumed that it was not at a very advanced stage&#44; given the low grade of LV hypertrophy and the preserved ejection fraction in these acromegalic patients&#44; but this is not certain&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Besides this&#44; the study lacks information on mitral valve structural abnormalities and the pathophysiological mechanisms responsible for MR in these patients&#44; probably due to the low spatial resolution of 3D-STE&#46; MR appears to have been an undervalued issue in this study&#44; which soon became clear once the authors stated that MR severity was qualitatively rather than quantitatively graded &#40;not following the latest guidelines of the European Association of Cardiovascular Imaging and the American Society of Echocardiography&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study contrasts with previous ones by giving a clearer insight into acromegalic cardiomyopathy&#44; since it demonstrates preserved MA function without significant MR despite MA dilation&#44; highlighting a possible new mechanism for this to happen &#40;increase in LV radial strain&#41;&#46; Although it has some technical issues&#44; including the small number of patients analyzed with an echocardiographic technique that has limited resolution&#44; the authors should be congratulated for their effort to increase our knowledge of a rare but clinically significant disease&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">I believe a more clinical approach with more emphasis on MR would be welcome&#44; and the question remains whether these findings are related to an early or late stage of the disease&#46; Therefore&#44; more confirmatory studies are needed&#46; But the importance of careful and continuous cardiological follow-up and echocardiographic monitoring in this disease remains unquestioned&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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