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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Mitral regurgitation &#40;MR&#41; is one of the most common valve diseases in western countries&#46; Its frequency and severity increase with age&#44; and its presence is associated with worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> The largest European echocardiography-based study reported MR in 15<span class="elsevierStyleHsp" style=""></span>501 patients &#40;24&#37;&#41; of a total of 63<span class="elsevierStyleHsp" style=""></span>463 consecutive echocardiographic studies performed in 19 centers&#46; The incidence of MR was higher than previously described&#44; and significant MR representing 30&#37; of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Mitral regurgitation is not only a problem because of its prevalence but also because it is subject to medical inertia&#46; In a recent nationwide study&#44; 107<span class="elsevierStyleHsp" style=""></span>412 patients with MR that were admitted to French hospitals between 2014 and 2015&#44; only 8&#37; underwent surgery&#44; the remaining 92&#37; were treated under a conservative strategy&#46; Hard endpoints as in-hospital mortality and one-year mortality were determined in the conservative arm&#46; In this population&#44; one-year mortality was 14&#37;&#44; and readmission rates &#40;all-cause or heart failure&#41; were high&#44; but secondary MR &#40;SMR&#41; performed worse than primary MR &#40;PMR&#41; for one-year mortality 18&#37; vs&#46; 13&#37; &#40;p&#60;0&#46;0001&#41; and one-year heart failure hospitalization 21&#37; vs&#46; 36&#37; &#40;p&#60;0&#46;0001&#41;&#46; The mean cumulative cost of all readmissions following the index admission was 10<span class="elsevierStyleHsp" style=""></span>080&#177;10<span class="elsevierStyleHsp" style=""></span>847 euros for the first hospital stay and readmissions were higher for SMR than for PMR &#40;both p&#60;0&#46;0001&#41;&#46; In this study&#44; the annual cost was extrapolated to a value between 350 and 550 million euros &#40;390-615 million US dollars&#41;&#44; revealing a high health cost burden to society&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a> Strategies to improve overall MR management and outcomes are urgently needed&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">First&#44; we should clarify where is the inertia&#46; In the diagnosis&#63; In patient stratification&#63; In the treatment approach&#47;options&#63;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In fact&#44; diagnosis and quantification of MR is very demanding and most of the time it is not a case of inertia&#44; but of lack of high-level imaging skills&#46; Mitral valve anatomy is very complex with a variable three-dimensional &#40;3D&#41; saddle annular morphology with different dimensions according to different intravascular volume and hemodynamic status&#44; in addition to the leaflets&#44; the multiple tendinous chords and two papillary muscles&#44; together posing significant challenges for the imager&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> As treatment decisions are completely dependent on accurate diagnosis of both mechanism and severity of MR&#44; the aim is to do it correctly&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Transthoracic echocardiography is the most used imaging test for MR and transesophageal echocardiography is often needed to define morphology and MR severity better&#46; Ideally&#44; MR would be measured by quantitative parameters along a continuous scale&#46; Such parameters would include effective regurgitant orifice area &#40;EROA&#41;&#44; regurgitant volume &#40;RVol&#41;&#44; and regurgitant fraction &#40;RF&#41;&#44; which is the percentage of MR volume relative to total LV stroke volume&#46; These values interact with each other in a complex way&#46; For example&#44; a given value of EROA could have a larger or smaller RVol depending on the driving velocity of flow across the valve and the duration of MR&#44; which is often not holosystolic&#46; A given RVol could have a different RF depending on the size and systolic function of the LV&#46; Another pitfall we should beware of is that non-holosystolic MR is frequently overestimated when only single-frame measurements are used&#44; such as EROA by proximal isovelocity surface area &#40;PISA&#41;&#44; vena contracta width&#44; or vena contracta area &#40;3D&#41; and finally noncircular orifices and multiple orifices are challenging for quantification&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> Therefore&#44; there are often inconsistences between clinical and imaging findings&#44; so patients should be immediately referred to a valve center where the experience and the high volume precludes misdiagnosis of severity&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Another hallmark of inertia&#44; as previous mentioned&#44; is the undertreatment&#44; not only because in severe SMR an expressive number of patients had comorbidities and advanced age that prohibits surgical intervention&#44; but also because it is not clear that the addition of mitral valve repair to surgical coronary artery bypass grafting has survival improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> Meanwhile&#44; based on the results of the COAPT &#40;Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation&#41; trial&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> current European Society of Cardiology&#47;European Association for Cardio-Thoracic Surgery practice guidelines recommend that when revascularization is not indicated and surgical risk is not low&#44; a percutaneous edge-to-edge procedure may be considered in patients with severe secondary mitral regurgitation and left ventricle ejection fraction &#40;LVEF&#41; &#62;30&#37; who remain symptomatic despite optimal medical management &#40;including cardiac resynchronization therapy&#44; if indicated&#41; and who have a suitable valve morphology based on echocardiography&#44; always avoiding futility&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> The word futility is the cornerstone of this quest&#44; as not all the transcatheter edge-to-edge repair &#40;TEER&#41; trials were shown to be beneficial&#46; One example is the MITRA-FR &#40;Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation&#41; trial&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> in which the transcatheter mitral valve repair and guideline-directed medical therapy did not lead to superior outcomes compared with medical therapy alone&#46; The diametrically opposed results of the previous two landmark trials were the trigger for an exceptional discussion exposing the main differences and weakness of the two populations included&#46; Two main differences between the trials were exposed&#58; EROA was lower in MITRA-FR compared with COAPT &#40;31 vs&#46; 41 mm<span class="elsevierStyleSup">2</span>&#41;&#44; and mean left ventricular end-diastolic diameter at baseline in MITRA-FR was 6&#46;9 cm&#44; while it was 6&#46;2 cm in COAPT&#46; They were the main drivers behind a change in paradigm and emergence of a new concept&#58; proportionate and disproportionate MR&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> This means that not all SMR is the same&#44; and ultimately the degree of dilatation of the left ventricle and its proportionality to EROA probably dictate whether mitral valve intervention is likely to be beneficial or not&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding this change of paradigm&#44; the correct selection of patients who will benefit from TEER has become paramount&#44; in other to avoid not only futile expenses but also frivolous patient procedures&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Presume et al&#46;&#44; in the present study&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> assessed the prognostic value of two different concepts of proportionality and their ability to improve MR stratification on top of the ASE guidelines&#46; Two formulas were used&#58; one proposed by Grayburn&#44; et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> disproportionate SMR defined as EROALVEDV&#62;0&#46;14 and other by Lopes&#44; et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> disproportionate SMR whenever measured EROA &#62; theoretical EROA &#40;determined as 50&#37;&#215;LVEF&#215;LVEDVMitralVIT&#41;&#46; The agreement between the formulas in the study was different as expected&#46; The Presume et al&#46; cohort included patients with LVEF &#60; 50&#37; &#40;mean 33&#177;9&#37;&#41; and the Grayburn formula was built only for patients with an LVEF around 30&#37;&#44; in contrast to the Lopes formula which is more versatile and covers all ranges of LVEF&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The disproportionality definition proposed by Lopes et al&#46; seems to be more robust in the different spectrum of stratification as it was the only one that was able to predict all-cause mortality in the multivariate analysis &#40;hazard ratio 1&#46;5&#59; 95&#37; confidence interval 1&#46;07-2&#46;1&#44; p&#61;0&#46;018&#41; and improved the risk stratification of American Society of Echocardiography &#40;ASE&#41; SMR classification&#46; A conservative approach and critical appraisal should always guide our practice&#44; so validation studies to confirm this data are required&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">At the end of the day&#44; we should probably be discussing the validity of searching for EROA and RVol in SMR&#44; which includes itself a high range of LVEDV and LVEF&#46; The definition for severe mitral regurgitation endorsed by the American Heart Association&#47;American College of Cardiology and ESC is defined as a RVol that exceeds half of the total stroke volume in both primary and secondary MR&#46; Although derived from a volumetric measurement &#40;50&#37; of stroke volume&#41;&#44; it is a dimensionless index that does not require allometric adjustments&#44; unlike EROA or RVol&#46; As previous mentioned&#44; a value of 30 ml of RVol can be severe if the stroke volume is 60 ml or not if the stroke volume is 70 ml&#59; it is only a number&#44; which if taken out of context is of low value&#46; We should note that not only EROA has important caveats but also stroke volume measured by echocardiography is not error-proof&#46; Our question is&#58; should we not use cardiac magnetic resonance more often as it is accurate&#44; reproducible&#44; and estimates volume data more reliably&#63;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the promising new data&#44; the quest for TEER patient selection continues&#8230;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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And the quest continues…
E a busca continua…
Lígia Mendesa,b
a Hospital da Luz, Setúbal, Portugal
b Faculdade de Medicina da Universidade Católica Portuguesa, Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Mitral regurgitation &#40;MR&#41; is one of the most common valve diseases in western countries&#46; Its frequency and severity increase with age&#44; and its presence is associated with worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> The largest European echocardiography-based study reported MR in 15<span class="elsevierStyleHsp" style=""></span>501 patients &#40;24&#37;&#41; of a total of 63<span class="elsevierStyleHsp" style=""></span>463 consecutive echocardiographic studies performed in 19 centers&#46; The incidence of MR was higher than previously described&#44; and significant MR representing 30&#37; of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Mitral regurgitation is not only a problem because of its prevalence but also because it is subject to medical inertia&#46; In a recent nationwide study&#44; 107<span class="elsevierStyleHsp" style=""></span>412 patients with MR that were admitted to French hospitals between 2014 and 2015&#44; only 8&#37; underwent surgery&#44; the remaining 92&#37; were treated under a conservative strategy&#46; Hard endpoints as in-hospital mortality and one-year mortality were determined in the conservative arm&#46; In this population&#44; one-year mortality was 14&#37;&#44; and readmission rates &#40;all-cause or heart failure&#41; were high&#44; but secondary MR &#40;SMR&#41; performed worse than primary MR &#40;PMR&#41; for one-year mortality 18&#37; vs&#46; 13&#37; &#40;p&#60;0&#46;0001&#41; and one-year heart failure hospitalization 21&#37; vs&#46; 36&#37; &#40;p&#60;0&#46;0001&#41;&#46; The mean cumulative cost of all readmissions following the index admission was 10<span class="elsevierStyleHsp" style=""></span>080&#177;10<span class="elsevierStyleHsp" style=""></span>847 euros for the first hospital stay and readmissions were higher for SMR than for PMR &#40;both p&#60;0&#46;0001&#41;&#46; In this study&#44; the annual cost was extrapolated to a value between 350 and 550 million euros &#40;390-615 million US dollars&#41;&#44; revealing a high health cost burden to society&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a> Strategies to improve overall MR management and outcomes are urgently needed&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">First&#44; we should clarify where is the inertia&#46; In the diagnosis&#63; In patient stratification&#63; In the treatment approach&#47;options&#63;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In fact&#44; diagnosis and quantification of MR is very demanding and most of the time it is not a case of inertia&#44; but of lack of high-level imaging skills&#46; Mitral valve anatomy is very complex with a variable three-dimensional &#40;3D&#41; saddle annular morphology with different dimensions according to different intravascular volume and hemodynamic status&#44; in addition to the leaflets&#44; the multiple tendinous chords and two papillary muscles&#44; together posing significant challenges for the imager&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> As treatment decisions are completely dependent on accurate diagnosis of both mechanism and severity of MR&#44; the aim is to do it correctly&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Transthoracic echocardiography is the most used imaging test for MR and transesophageal echocardiography is often needed to define morphology and MR severity better&#46; Ideally&#44; MR would be measured by quantitative parameters along a continuous scale&#46; Such parameters would include effective regurgitant orifice area &#40;EROA&#41;&#44; regurgitant volume &#40;RVol&#41;&#44; and regurgitant fraction &#40;RF&#41;&#44; which is the percentage of MR volume relative to total LV stroke volume&#46; These values interact with each other in a complex way&#46; For example&#44; a given value of EROA could have a larger or smaller RVol depending on the driving velocity of flow across the valve and the duration of MR&#44; which is often not holosystolic&#46; A given RVol could have a different RF depending on the size and systolic function of the LV&#46; Another pitfall we should beware of is that non-holosystolic MR is frequently overestimated when only single-frame measurements are used&#44; such as EROA by proximal isovelocity surface area &#40;PISA&#41;&#44; vena contracta width&#44; or vena contracta area &#40;3D&#41; and finally noncircular orifices and multiple orifices are challenging for quantification&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> Therefore&#44; there are often inconsistences between clinical and imaging findings&#44; so patients should be immediately referred to a valve center where the experience and the high volume precludes misdiagnosis of severity&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Another hallmark of inertia&#44; as previous mentioned&#44; is the undertreatment&#44; not only because in severe SMR an expressive number of patients had comorbidities and advanced age that prohibits surgical intervention&#44; but also because it is not clear that the addition of mitral valve repair to surgical coronary artery bypass grafting has survival improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> Meanwhile&#44; based on the results of the COAPT &#40;Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation&#41; trial&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> current European Society of Cardiology&#47;European Association for Cardio-Thoracic Surgery practice guidelines recommend that when revascularization is not indicated and surgical risk is not low&#44; a percutaneous edge-to-edge procedure may be considered in patients with severe secondary mitral regurgitation and left ventricle ejection fraction &#40;LVEF&#41; &#62;30&#37; who remain symptomatic despite optimal medical management &#40;including cardiac resynchronization therapy&#44; if indicated&#41; and who have a suitable valve morphology based on echocardiography&#44; always avoiding futility&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> The word futility is the cornerstone of this quest&#44; as not all the transcatheter edge-to-edge repair &#40;TEER&#41; trials were shown to be beneficial&#46; One example is the MITRA-FR &#40;Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation&#41; trial&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> in which the transcatheter mitral valve repair and guideline-directed medical therapy did not lead to superior outcomes compared with medical therapy alone&#46; The diametrically opposed results of the previous two landmark trials were the trigger for an exceptional discussion exposing the main differences and weakness of the two populations included&#46; Two main differences between the trials were exposed&#58; EROA was lower in MITRA-FR compared with COAPT &#40;31 vs&#46; 41 mm<span class="elsevierStyleSup">2</span>&#41;&#44; and mean left ventricular end-diastolic diameter at baseline in MITRA-FR was 6&#46;9 cm&#44; while it was 6&#46;2 cm in COAPT&#46; They were the main drivers behind a change in paradigm and emergence of a new concept&#58; proportionate and disproportionate MR&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> This means that not all SMR is the same&#44; and ultimately the degree of dilatation of the left ventricle and its proportionality to EROA probably dictate whether mitral valve intervention is likely to be beneficial or not&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding this change of paradigm&#44; the correct selection of patients who will benefit from TEER has become paramount&#44; in other to avoid not only futile expenses but also frivolous patient procedures&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Presume et al&#46;&#44; in the present study&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> assessed the prognostic value of two different concepts of proportionality and their ability to improve MR stratification on top of the ASE guidelines&#46; Two formulas were used&#58; one proposed by Grayburn&#44; et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> disproportionate SMR defined as EROALVEDV&#62;0&#46;14 and other by Lopes&#44; et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> disproportionate SMR whenever measured EROA &#62; theoretical EROA &#40;determined as 50&#37;&#215;LVEF&#215;LVEDVMitralVIT&#41;&#46; The agreement between the formulas in the study was different as expected&#46; The Presume et al&#46; cohort included patients with LVEF &#60; 50&#37; &#40;mean 33&#177;9&#37;&#41; and the Grayburn formula was built only for patients with an LVEF around 30&#37;&#44; in contrast to the Lopes formula which is more versatile and covers all ranges of LVEF&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The disproportionality definition proposed by Lopes et al&#46; seems to be more robust in the different spectrum of stratification as it was the only one that was able to predict all-cause mortality in the multivariate analysis &#40;hazard ratio 1&#46;5&#59; 95&#37; confidence interval 1&#46;07-2&#46;1&#44; p&#61;0&#46;018&#41; and improved the risk stratification of American Society of Echocardiography &#40;ASE&#41; SMR classification&#46; A conservative approach and critical appraisal should always guide our practice&#44; so validation studies to confirm this data are required&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">At the end of the day&#44; we should probably be discussing the validity of searching for EROA and RVol in SMR&#44; which includes itself a high range of LVEDV and LVEF&#46; The definition for severe mitral regurgitation endorsed by the American Heart Association&#47;American College of Cardiology and ESC is defined as a RVol that exceeds half of the total stroke volume in both primary and secondary MR&#46; Although derived from a volumetric measurement &#40;50&#37; of stroke volume&#41;&#44; it is a dimensionless index that does not require allometric adjustments&#44; unlike EROA or RVol&#46; As previous mentioned&#44; a value of 30 ml of RVol can be severe if the stroke volume is 60 ml or not if the stroke volume is 70 ml&#59; it is only a number&#44; which if taken out of context is of low value&#46; We should note that not only EROA has important caveats but also stroke volume measured by echocardiography is not error-proof&#46; Our question is&#58; should we not use cardiac magnetic resonance more often as it is accurate&#44; reproducible&#44; and estimates volume data more reliably&#63;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the promising new data&#44; the quest for TEER patient selection continues&#8230;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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