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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">dic</journal-id>
<journal-title-group>
<journal-title>ABC Imagem Cardiovascular</journal-title>
<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc.</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2675-312X</issn>
<publisher>
<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">abcimg.20230094i</article-id>
<article-id pub-id-type="doi">10.36660/abcimg.20230094i</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Case Report</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Takotsubo Syndrome After Percutaneous Mitral Valve Repair With Mitraclip&#xAE;: A Case Report</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0009-0007-1710-565X</contrib-id>
<name><surname>Souza</surname><given-names>Anna Luiza</given-names></name>
<role>Conception</role>
<role>design of the research:</role>
<role>acquisition of data</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript</role>
<role>critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="c1"/>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-9832-426X</contrib-id>
<name><surname>Prudente</surname><given-names>Maur&#xED;cio Lopes</given-names></name>
<role>Conception</role>
<role>design of the research</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript</role>
<role>critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-0659-8755</contrib-id>
<name><surname>Rodrigues</surname><given-names>D&#xE9;bora</given-names></name>
<role>critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5522-0372</contrib-id>
<name><surname>Nogueira</surname><given-names>Ana Cec&#xED;lia Campos</given-names></name>
<role>Conception</role>
<role>design of the research</role>
<role>critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-8763-561X</contrib-id>
<name><surname>Gardenghi</surname><given-names>Giulliano</given-names></name>
<role>Conception</role>
<role>design of the research</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript</role>
<role>critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Hospital ENCORE</institution>
<institution content-type="orgdiv1">Aparecida de Goi&#xE2;nia</institution>
<addr-line>
<named-content content-type="state">GO</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Hospital ENCORE, Aparecida de Goi&#xE2;nia, GO &#x2013; Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><bold>Mailing Address: Anna Luiza Souza &#x2022;</bold> Hospital Encore. Rua Gurupi,R. 109 06/08 S/N, quadra 25. Postal code: <postal-code>74.823-470</postal-code>. Vila Bras&#xED;lia, Goi&#xE2;nia, GO &#x2013; Brazil E-mail: <email>annaluiza.med28@gmail.com</email></corresp>
<fn fn-type="conflict"><p><bold>Potential Conflict of Interest</bold></p>
<p>No potential conflict of interest relevant to this article was reported.</p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>21</day>
<month>12</month>
<year>2023</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2023</year></pub-date>
<volume>36</volume>
<issue>4</issue>
<elocation-id>e20230094</elocation-id>
<history>
<date date-type="received">
<day>31</day>
<month>10</month>
<year>2023</year></date>
<date date-type="rev-recd">
<day>08</day>
<month>11</month>
<year>2023</year></date>
<date date-type="accepted">
<day>10</day>
<month>11</month>
<year>2023</year></date>
</history>
<permissions>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
</license>
</permissions>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Takotsubo Cardiomyopathy</kwd>
<kwd>Mitral Valve Insufficiency</kwd>
<kwd>Case Reports</kwd>
</kwd-group>
<counts>
<fig-count count="10"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="8"/></counts></article-meta></front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Takotsubo syndrome (TTS), also known as stress cardiomyopathy or broken heart syndrome, is a condition whose pathophysiology is not well established, but which results from multiple factors that act synergistically in a setting of stress perception and cardiocirculatory response.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> It was first described in 1990, and the disproportionate and excessive increase in serum catecholamines is known to play a central role in its pathogenesis by favoring the occurrence of complications. Although rare, TTS deserves attention due to its inherent risk of decompensated heart function.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
</sec>
<sec sec-type="cases">
<title>Case report</title>
<p>An 83-year-old man was referred for elective mitral valve repair after multiple hospitalizations for cardiac decompensation, characterized mainly by dyspnea at rest (New York Heart Association [NYHA] functional class [FC] IV). He had significant mitral regurgitation (MR) due to partial rupture of pretendinous cords of the posterior leaflet (P2 segment) and mild myxomatous degeneration (<xref ref-type="fig" rid="f1">Figure 1</xref>). After discussion with the Heart Team, percutaneous mitral valve repair with Mitraclip<sup>&#xAE;</sup> was indicated.</p>
<fig id="f1">
<label>Figure 1</label>
<caption>
<title>Preoperative transesophageal echocardiography. (A) and (B): Significant eccentric MR. (C): Mitral valve prolapse with myxomatous degeneration and partial rupture of pretendinous cords (flail) of the posterior leaflet (P2 segment).</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf01.tif"/>
</fig>
<p>The patient&#x27;s past medical history included systemic arterial hypertension, diabetes, chronic atrial fibrillation with oral anticoagulant therapy, pulmonary hypertension with a pulmonary artery systolic pressure of 52 mmHg, and anxiety disorder. Furthermore, coronary artery disease was detected during preoperative catheterization, and percutaneous transluminal angioplasty of the proximal third of the left anterior descending (LAD) artery was performed after identification of a type A lesion (70%), followed by stenting (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
<fig id="f2">
<label>Figura 2</label>
<caption>
<title>Coronary cineangiography. (A): Type A lesion (70%) of the proximal third of the LAD artery; (B): Angioplasty of the LAD artery with everolimus-eluting stent (3.0 &#xD7; 8.0 mm).</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf02.tif"/>
</fig>
<p>Mitraclip<sup>&#xAE;</sup> implantation was performed via the right femoral vein. After transseptal puncture guided by three-dimensional transesophageal echocardiography, the delivery catheter was advanced across the septum. Two clips were implanted: the first was placed at the A2-P2 segment, and the other was placed lateral to the first (<xref ref-type="fig" rid="f3">Figure 3</xref>). After the procedure, mild MR was identified, with a mean transmitral gradient (TMG) of 5.8 mm Hg in the orifice with the greatest TMG. There were no complications during the procedure.</p>
<fig id="f3">
<label>Figura 3</label>
<caption>
<title>Percutaneous Mitraclip<sup>&#xAE;</sup> NT implantation.</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf03.tif"/>
</fig>
<p>On postoperative day 3, the patient developed hyperactive delirium, dyspnea requiring oxygen therapy, and tight, continuous, intense chest pain (not radiating). On physical examination, the patient presented confusion, mucocutaneous pallor, diaphoresis, tachypnea, and an oxygen saturation of 98% on 2 lpm of oxygen by nasal cannula. No adventitious sounds were detected on respiratory auscultation. His blood pressure was 150/70 mm Hg and heart rate was 109 bpm, with an irregular heart rhythm. The peripheral pulses were palpable and symmetric.</p>
<p>Electrocardiography (ECG) revealed symmetrically inverted peaked T-waves in the anterolateral leads, and laboratory tests showed an elevated high-sensitivity cardiac troponin level (73.8 ng/mL; reference range &#x3C; 14 ng/mL), suggesting non ST-elevation acute coronary syndrome (ACS).</p>
<p>A transthoracic echocardiogram (TTE) revealed significantly reduced left ventricular ejection fraction (LVEF) &#x2013; from 51% to 25% (Simpson) &#x2013; and significant apical hypokinesia as well as in the mid-anterior, mid-anteroseptal, and mid-anterolateral walls.</p>
<p>In view of the complementary exams, an emergency coronary cineangiography was performed, which ruled out significant coronary lesions and reveled a patent stent in the LAD artery, but with increased systolic volume due to extensive anterior, inferior, and apical akinesia (sparing only the base) on ventriculography (<xref ref-type="fig" rid="f4">Figure 4</xref>).</p>
<fig id="f4">
<label>Figura 4</label>
<caption>
<title>Ventriculography during systole on the third day after Mitraclip<sup>&#xAE;</sup> implantation</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf04.tif"/>
</fig>
<p>Because of absence of thrombotic lesions on angiography, the patient remained hospitalized and receiving clinical treatment. On postoperative day 4, troponin levels were significantly reduced to 24.3 ng/mL. The patient was clinically improved and discharged from hospital.</p>
<p>One year after the intervention, the patient remained clinically stable (NYHA FC II). Control TTE showed LVEF recovery to 61% (Simpson), moderate MR, and mild stenosis (TMG 4.0 mm Hg and peak gradient (Gp) 17.0 mm Hg), with normal segmental LV contractility (<xref ref-type="fig" rid="f5">Figure 5</xref>).</p>
<fig id="f5">
<label>Figure 5</label>
<caption>
<title>TTE 1 year after Mitraclip<sup>&#xAE;</sup> implantation showing moderate MR.</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf05.tif"/>
</fig>
<p>In view of the foregoing, a diagnostic hypothesis of TTS secondary to Mitraclip<sup>&#xAE;</sup> implantation was made, based on dynamic changes in ECG and echocardiography, elevation of markers of myocardial necrosis, apical &#x201C;ballooning&#x201D;, and hyperkinesia of basal segments on ventriculography, with no evidence of coronary artery obstruction on coronary cineangiography despite recent stent implantation at the LAD artery, in a setting of postoperative stress.</p>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>This case report draws attention to the presumed correlation between TTS secondary to percutaneous Mitraclip<sup>&#xAE;</sup> implantation and mitral valve repair in an older male patient at very high cardiovascular risk.</p>
<p>Studies have shown that catecholamines play a central role in the pathogenesis of TTS.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Other aspects that may be related to TTS include macro and microvascular endothelial dysfunction, vasospasm, and calcium overload in myocytes, which cause disorders of ventricular contraction and function, mostly affecting postmenopausal women.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>Clinical characteristics are usually similar to those of ACS. Patients present with chest pain, dyspnea, acute heart failure, abnormal ECG (such as ST segment elevation or depression or T wave inversion), and increased serum troponin. However, these ACS patients do not present troponin peaks, as would be expected in cases of acute myocardial infarction (AMI), nor obstructive lesions that justify the severe contractility deficit observed in TTS. Although rare, TTS is a differential diagnosis of ACS, which may be underdiagnosed given the higher prevalence of AMI due to obstructive coronary artery disease in the general population.<sup><xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>Coronary angiography combined with ventriculography is considered the gold standard for TTS diagnosis. It shows apical akinesia of the LV with normal contractility of the base, which creates a &#x201C;balloon&#x201D; appearance in its apical portion (&#x201C;apical ballooning), without evidence of obstructive coronary artery disease.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>TTS treatment involves clinical support measures. Most cases progress with spontaneous and complete remission within days or weeks. However, the acute phase, which results from complications such as cardiogenic shock, arrhythmias, and cardiac arrest, may be more severe, with high morbidity and mortality rates.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>From an epidemiological perspective, TTS is extremely rare. Despite conducting a comprehensive literature search, we found only one report of MitraClip<sup>&#xAE;</sup>-related TTS, which occurred in 2020 in the United States. Similar to our case, it was observed in an older male patient and had a favorable clinical outcome.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Another study described the case of a woman with TTS who underwent open surgery to correct severe MR triggered by an adverse reaction to protamine.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>MitraClip<sup>&#xAE;</sup> implantation is less invasive than thoracotomy valve replacement for the treatment of severe MR. It is considered effective and safe in patients refractory to clinical treatment, with excellent results reported by the COAPT study and its 5-year follow-up, in addition to being an alternative treatment for those at high surgical risk or with contraindications to surgery.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup> Despite being less invasive, the percutaneous technique may induce catecholamine release as a result of physical and emotional stress, as also happens in open surgery and hospitalization.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> The case described in this report brings attention to the fact that TTS is a potential complication of percutaneous mitral valve repair with MitraClip<sup>&#xAE;</sup>.</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="supported-by" id="fn1"><p><bold>Sources of Funding</bold></p>
<p>There were no external funding sources for this study.</p></fn>
<fn fn-type="other" id="fn2"><p><bold>Study Association</bold></p>
<p>This study is not associated with any thesis or dissertation work.</p></fn>
<fn fn-type="other" id="fn3"><p><bold>Ethics Approval and Consent to Participate</bold></p>
<p>This study was approved by the Ethics Committee of the CEP/HUGO under the protocol number 85497418.2.0000.0033. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p></fn>
<fn fn-type="other" id="fn4"><p>Editor responsible for the review: Daniela do Carmo Rassi Frota</p></fn>
</fn-group>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Lyon</surname><given-names>AR</given-names></name>
<name><surname>Citro</surname><given-names>R</given-names></name>
<name><surname>Schneider</surname><given-names>B</given-names></name>
<name><surname>Morel</surname><given-names>O</given-names></name>
<name><surname>Ghadri</surname><given-names>JR</given-names></name>
<name><surname>Templin</surname><given-names>C</given-names></name>
<etal/>
</person-group>
<article-title>Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review</article-title>
<source>J Am Coll Cardiol</source>
<year>2021</year>
<volume>77</volume>
<issue>7</issue>
<fpage>902</fpage>
<lpage>921</lpage>
<pub-id pub-id-type="doi">10.1016/j.jacc.2020.10.060</pub-id>
</element-citation>
<mixed-citation>Lyon AR, Citro R, Schneider B, Morel O, Ghadri JR, Templin C, et al. Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021;77(7):902-21. doi: 10.1016/j.jacc.2020.10.060.</mixed-citation>
</ref>
<ref id="B2">
<label>2</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Gariboldi</surname><given-names>V</given-names></name>
<name><surname>Jop</surname><given-names>B</given-names></name>
<name><surname>Grisoli</surname><given-names>D</given-names></name>
<name><surname>Jaussaud</surname><given-names>N</given-names></name>
<name><surname>Kerbaul</surname><given-names>F</given-names></name>
<name><surname>Collart</surname><given-names>F</given-names></name>
</person-group>
<article-title>Takotsubo Syndrome After Mitral Valve Replacement for Acute Endocarditis</article-title>
<source>Ann Thorac Surg</source>
<year>2011</year>
<volume>91</volume>
<issue>3</issue>
<fpage>e31</fpage>
<lpage>e32</lpage>
<pub-id pub-id-type="doi">10.1016/j.athoracsur.2010.10.085</pub-id>
</element-citation>
<mixed-citation>Gariboldi V, Jop B, Grisoli D, Jaussaud N, Kerbaul F, Collart F. Takotsubo Syndrome After Mitral Valve Replacement for Acute Endocarditis. Ann Thorac Surg. 2011;91(3):e31-2. doi: 10.1016/j.athoracsur.2010.10.085.</mixed-citation>
</ref>
<ref id="B3">
<label>3</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Uribarri</surname><given-names>A</given-names></name>
<name><surname>N&#xFA;&#xF1;ez-Gil</surname><given-names>IJ</given-names></name>
<name><surname>Conty</surname><given-names>DA</given-names></name>
<name><surname>Vedia</surname><given-names>O</given-names></name>
<name><surname>Almendro-Delia</surname><given-names>M</given-names></name>
<name><surname>Duran Cambra</surname><given-names>A</given-names></name>
<etal/>
</person-group>
<article-title>Short- and Long-Term Prognosis of Patients with Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature</article-title>
<source>J Am Heart Assoc</source>
<year>2019</year>
<volume>8</volume>
<issue>24</issue>
<elocation-id>e013701</elocation-id>
<pub-id pub-id-type="doi">10.1161/JAHA.119.013701</pub-id>
</element-citation>
<mixed-citation>Uribarri A, N&#xFA;&#xF1;ez-Gil IJ, Conty DA, Vedia O, Almendro-Delia M, Duran Cambra A, et al. Short- and Long-Term Prognosis of Patients with Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature. J Am Heart Assoc. 2019;8(24):e013701. doi: 10.1161/JAHA.119.013701.</mixed-citation>
</ref>
<ref id="B4">
<label>4</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Bonow</surname><given-names>RO</given-names></name>
<name><surname>O&#x2019;Gara</surname><given-names>PT</given-names></name>
<name><surname>Adams</surname><given-names>DH</given-names></name>
<name><surname>Badhwar</surname><given-names>V</given-names></name>
<name><surname>Bavaria</surname><given-names>JE</given-names></name>
<name><surname>Elmariah</surname><given-names>S</given-names></name>
<etal/>
</person-group>
<article-title>2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: a Report of the American College of Cardiology Solution Set Oversight Committee</article-title>
<source>J Am Coll Cardiol</source>
<year>2020</year>
<volume>75</volume>
<issue>17</issue>
<fpage>2236</fpage>
<lpage>2270</lpage>
<pub-id pub-id-type="doi">10.1016/j.jacc.2020.02.005</pub-id>
</element-citation>
<mixed-citation>Bonow RO, O&#x2019;Gara PT, Adams DH, Badhwar V, Bavaria JE, Elmariah S, et al. 2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: a Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;75(17):2236-70. doi: 10.1016/j.jacc.2020.02.005.</mixed-citation>
</ref>
<ref id="B5">
<label>5</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Nomura</surname><given-names>T</given-names></name>
<name><surname>Munehisa</surname><given-names>Y</given-names></name>
<name><surname>Nakashima</surname><given-names>M</given-names></name>
<name><surname>Matsumoto</surname><given-names>T</given-names></name>
</person-group>
<article-title>Takotsubo Syndrome Following MitraClip Procedure</article-title>
<source>Eur Heart J Case Rep</source>
<year>2020</year>
<volume>4</volume>
<issue>6</issue>
<fpage>1</fpage>
<lpage>2</lpage>
<pub-id pub-id-type="doi">10.1093/ehjcr/ytaa384</pub-id>
</element-citation>
<mixed-citation>Nomura T, Munehisa Y, Nakashima M, Matsumoto T. Takotsubo Syndrome Following MitraClip Procedure. Eur Heart J Case Rep. 2020;4(6):1-2. doi: 10.1093/ehjcr/ytaa384.</mixed-citation>
</ref>
<ref id="B6">
<label>6</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Li</surname><given-names>S</given-names></name>
<name><surname>Koerner</surname><given-names>MM</given-names></name>
<name><surname>El-Banayosy</surname><given-names>A</given-names></name>
<name><surname>Soleimani</surname><given-names>B</given-names></name>
<name><surname>Pae</surname><given-names>WE</given-names></name>
<name><surname>Leuenberger</surname><given-names>UA</given-names></name>
</person-group>
<article-title>Takotsubo&#x27;s Syndrome After Mitral Valve Repair and Rescue with Extracorporeal Membrane Oxygenation</article-title>
<source>Ann Thorac Surg</source>
<year>2014</year>
<volume>97</volume>
<issue>5</issue>
<fpage>1777</fpage>
<lpage>1778</lpage>
<pub-id pub-id-type="doi">10.1016/j.athoracsur.2013.08.032</pub-id>
</element-citation>
<mixed-citation>Li S, Koerner MM, El-Banayosy A, Soleimani B, Pae WE, Leuenberger UA. Takotsubo&#x27;s Syndrome After Mitral Valve Repair and Rescue with Extracorporeal Membrane Oxygenation. Ann Thorac Surg. 2014;97(5):1777-8. doi: 10.1016/j.athoracsur.2013.08.032.</mixed-citation>
</ref>
<ref id="B7">
<label>7</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Sorajja</surname><given-names>P</given-names></name>
<name><surname>Cavalcante</surname><given-names>JL</given-names></name>
<name><surname>G&#xF6;ssl</surname><given-names>M</given-names></name>
</person-group>
<article-title>The Need for Transcatheter Mitral Valve Replacement</article-title>
<source>J Am Coll Cardiol</source>
<year>2019</year>
<volume>73</volume>
<issue>11</issue>
<fpage>1247</fpage>
<lpage>1249</lpage>
<pub-id pub-id-type="doi">10.1016/j.jacc.2018.11.062</pub-id>
</element-citation>
<mixed-citation>Sorajja P, Cavalcante JL, G&#xF6;ssl M. The Need for Transcatheter Mitral Valve Replacement. J Am Coll Cardiol. 2019;73(11):1247-9. doi: 10.1016/j.jacc.2018.11.062.</mixed-citation>
</ref>
<ref id="B8">
<label>8</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Stone</surname><given-names>GW</given-names></name>
<name><surname>Abraham</surname><given-names>WT</given-names></name>
<name><surname>Lindenfeld</surname><given-names>J</given-names></name>
<name><surname>Kar</surname><given-names>S</given-names></name>
<name><surname>Grayburn</surname><given-names>PA</given-names></name>
<name><surname>Lim</surname><given-names>DS</given-names></name>
<etal/>
</person-group>
<article-title>Five-Year Follow-Up After Transcatheter Repair of Secondary Mitral Regurgitation</article-title>
<source>N Engl J Med</source>
<year>2023</year>
<volume>388</volume>
<issue>22</issue>
<fpage>2037</fpage>
<lpage>2048</lpage>
<pub-id pub-id-type="doi">10.1056/NEJMoa2300213</pub-id>
</element-citation>
<mixed-citation>Stone GW, Abraham WT, Lindenfeld J, Kar S, Grayburn PA, Lim DS, et al. Five-Year Follow-Up After Transcatheter Repair of Secondary Mitral Regurgitation. N Engl J Med. 2023;388(22):2037-48. doi: 10.1056/NEJMoa2300213.</mixed-citation>
</ref>
</ref-list>
</back>
<sub-article article-type="translation" id="S01" xml:lang="pt">
<front-stub>
<article-id pub-id-type="doi">10.36660/abcimg.20230094</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Relato de Caso</subject></subj-group></article-categories>
<title-group>
<article-title>S&#xED;ndrome de Takotsubo Ap&#xF3;s Reparo Percut&#xE2;neo da Valva Mitral com Mitraclip<sup>&#xAE;</sup>: Relato de Caso</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0009-0007-1710-565X</contrib-id>
<name><surname>Souza</surname><given-names>Anna Luiza</given-names></name>
<role>Concep&#xE7;&#xE3;o</role>
<role>desenho da pesquisa</role>
<role>obten&#xE7;&#xE3;o de dados</role>
<role>an&#xE1;lise</role>
<role>interpreta&#xE7;&#xE3;o dos dados</role>
<role>reda&#xE7;&#xE3;o do manuscrito</role>
<role>revis&#xE3;o cr&#xED;tica do manuscrito quanto</role>
<role>conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref><xref ref-type="corresp" rid="c2"/>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-9832-426X</contrib-id>
<name><surname>Prudente</surname><given-names>Maur&#xED;cio Lopes</given-names></name>
<role>Concep&#xE7;&#xE3;o</role>
<role>desenho da pesquisa</role>
<role>an&#xE1;lise</role>
<role>interpreta&#xE7;&#xE3;o dos dados</role>
<role>reda&#xE7;&#xE3;o do manuscrito</role>
<role>revis&#xE3;o cr&#xED;tica do manuscrito quanto</role>
<role>conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-0659-8755</contrib-id>
<name><surname>Rodrigues</surname><given-names>D&#xE9;bora</given-names></name>
<role>revis&#xE3;o cr&#xED;tica do manuscrito quanto</role>
<role>conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5522-0372</contrib-id>
<name><surname>Nogueira</surname><given-names>Ana Cec&#xED;lia Campos</given-names></name>
<role>Concep&#xE7;&#xE3;o</role>
<role>desenho da pesquisa</role>
<role>revis&#xE3;o cr&#xED;tica do manuscrito quanto</role>
<role>conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-8763-561X</contrib-id>
<name><surname>Gardenghi</surname><given-names>Giulliano</given-names></name>
<role>Concep&#xE7;&#xE3;o</role>
<role>desenho da pesquisa</role>
<role>an&#xE1;lise</role>
<role>interpreta&#xE7;&#xE3;o dos dados</role>
<role>reda&#xE7;&#xE3;o do manuscrito</role>
<role>revis&#xE3;o cr&#xED;tica do manuscrito quanto</role>
<role>conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
</contrib>
<aff id="aff2">
<label>1</label>
<addr-line>
<named-content content-type="state">GO</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Hospital ENCORE, Aparecida de Goi&#xE2;nia, GO &#x2013; Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><bold>Correspond&#xEA;ncia: Anna Luiza Souza &#x2022;</bold> Hospital Encore. Rua Gurupi,R. 109 06/08 S/N, quadra 25. CEP: <postal-code>74.823-470</postal-code>. Vila Bras&#xED;lia, Goi&#xE2;nia, GO &#x2013; Brasil E-mail: annaluiza.med28@gmail.com</corresp>
<fn fn-type="conflict"><p><bold>Potencial Conflito de Interesse</bold></p>
<p>Declaro n&#xE3;o haver conflito de interesses pertinentes.</p></fn>
</author-notes>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>S&#xED;ndrome de Takotsubo</kwd>
<kwd>Insufici&#xEA;ncia da Valva Mitral</kwd>
<kwd>Relatos de Casos</kwd>
</kwd-group>
</front-stub>
<body>
<sec sec-type="intro">
<title>Introdu&#xE7;&#xE3;o</title>
<p>A s&#xED;ndrome de Takotsubo (STT), tamb&#xE9;m conhecida como cardiomiopatia de estresse ou s&#xED;ndrome do cora&#xE7;&#xE3;o partido, &#xE9; uma condi&#xE7;&#xE3;o cuja fisiopatologia n&#xE3;o &#xE9; bem estabelecida, mas que decorre de m&#xFA;ltiplos fatores que agem em sinergia num contexto de percep&#xE7;&#xE3;o de estresse e resposta cardiocirculat&#xF3;ria.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A doen&#xE7;a foi primeiro descrita em 1990, e sabe-se que o aumento desproporcional e excessivo das catecolaminas s&#xE9;ricas desempenha um papel central na sua patog&#xEA;nese ao favorecer o surgimento de complica&#xE7;&#xF5;es. Embora rara, a STT merece aten&#xE7;&#xE3;o pelo risco inerente de descompensa&#xE7;&#xE3;o da fun&#xE7;&#xE3;o card&#xED;aca.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
</sec>
<sec sec-type="cases">
<title>Relato de caso</title>
<p>Paciente do sexo masculino, 83 anos, foi encaminhado para corre&#xE7;&#xE3;o eletiva da valva mitral ap&#xF3;s m&#xFA;ltiplas interna&#xE7;&#xF5;es por descompensa&#xE7;&#xE3;o card&#xED;aca, caracterizada principalmente por dispneia em repouso (classe funcional [CF] da New York Heart Association [NYHA] IV). O paciente apresentava regurgita&#xE7;&#xE3;o mitral (RM) de grau importante devido a rotura parcial das cordas pr&#xE9;-tend&#xED;neas do folheto posterior (segmento P2) e degenera&#xE7;&#xE3;o mixomatosa discreta, conforme ilustra a <xref ref-type="fig" rid="f6">Figura 1</xref>. Ap&#xF3;s discuss&#xE3;o com o <italic>Heart Team</italic>, por tratar-se de idoso fr&#xE1;gil, foi indicado reparo percut&#xE2;neo da valva mitral com implante de Mitraclip<sup>&#xAE;</sup>.</p>
<fig id="f6">
<label>Figura 1</label>
<caption>
<title>Ecocardiograma transesof&#xE1;gico pr&#xE9;-operat&#xF3;rio. (A) e (B): RM exc&#xEA;ntrica de grau importante. (C): Prolapso da valva mitral com degenera&#xE7;&#xE3;o mixomatosa e rotura parcial de cordoalhas (flail) do folheto posterior (segmento P2).</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf01-pt.tif"/>
</fig>
<p>O paciente apresentava como antecedentes patol&#xF3;gicos hipertens&#xE3;o arterial sist&#xEA;mica, diabetes mellitus, fibrila&#xE7;&#xE3;o atrial cr&#xF4;nica em uso de anticoagulante oral, hipertens&#xE3;o pulmonar com press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar de 52 mmHg e transtorno de ansiedade. Al&#xE9;m disso, foi detectada doen&#xE7;a coronariana no cateterismo pr&#xE9;-operat&#xF3;rio, seguido de angioplastia transluminal percut&#xE2;nea do ter&#xE7;o proximal da art&#xE9;ria descendente anterior (DA) ap&#xF3;s evidenciar-se les&#xE3;o tipo A (70%), com implante de stent (<xref ref-type="fig" rid="f7">Figura 2</xref>).</p>
<fig id="f7">
<label>Figura 2</label>
<caption>
<title>Cineangiocoronariografia. (A): Les&#xE3;o tipo A (70%) no ter&#xE7;o proximal da art&#xE9;ria DA. (B): Angioplastia da art&#xE9;ria DA com tent eluidor de everolimus (3,0 &#xD7; 8,0 mm).</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf02-pt.tif"/>
</fig>
<p>Para implante percut&#xE2;neo do Mitraclip<sup>&#xAE;</sup>, foi realizado acesso venoso femoral direito. Ap&#xF3;s pun&#xE7;&#xE3;o transeptal guiada por ecocardiograma transesof&#xE1;gico 3D, cruzamos o septo com o dispositivo. Foram utilizados dois clips: o primeiro foi posicionado no segmento A2-P2, e o segundo lateral ao primeiro (<xref ref-type="fig" rid="f8">Figura 3</xref>). Ao final, foi verificada RM discreta com gradiente transmitral (GTM) m&#xE9;dio de 5,8 mmHg no orif&#xED;cio com o maior GTM. O procedimento foi realizado sem intercorr&#xEA;ncias.</p>
<fig id="f8">
<label>Figura 3</label>
<caption>
<title>Implante percut&#xE2;neo de dois Mitraclip<sup>&#xAE;</sup> NT.</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf03-pt.tif"/>
</fig>
<p>No terceiro dia de p&#xF3;s-operat&#xF3;rio (DPO), o paciente evoluiu com <italic>delirium</italic> hiperativo, dispneia exigindo suplementa&#xE7;&#xE3;o de oxig&#xEA;nio e dorsalgia tor&#xE1;cica, em aperto, cont&#xED;nua, de forte intensidade e n&#xE3;o irradiada. Ao exame f&#xED;sico, o paciente apresentou confus&#xE3;o, palidez cutaneomucosa, diaforese, taquipneia e satura&#xE7;&#xE3;o de oxig&#xEA;nio de 98% em cateter nasal de oxig&#xEA;nio a 2 lpm. N&#xE3;o foram identificados ru&#xED;dos advent&#xED;cios &#xE0; ausculta respirat&#xF3;ria. Al&#xE9;m disso, apresentava press&#xE3;o arterial de 150/70 mmHg e frequ&#xEA;ncia card&#xED;aca de 109 bpm, com ritmo card&#xED;aco irregular. Os pulsos perif&#xE9;ricos dos quatro membros eram palp&#xE1;veis e sim&#xE9;tricos.</p>
<p>O eletrocardiograma (ECG) mostrou invers&#xE3;o de onda T sim&#xE9;trica e apiculada na parede anterolateral, e os exames laboratoriais evidenciaram n&#xED;vel elevado de troponina ultrassens&#xED;vel (73,8 ng/mL; valor de refer&#xEA;ncia &#x3C; 14 ng/mL). Esses achados foram sugestivos de s&#xED;ndrome coronariana aguda (SCA) sem supra ST.</p>
<p>O ecocardiograma transtor&#xE1;cico (ETT) evidenciou redu&#xE7;&#xE3;o significativa da fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o do ventr&#xED;culo esquerdo (FEVE) &#x2013; de 51% para 25% (Simpson) &#x2013;, al&#xE9;m de hipocinesia apical importante e na regi&#xE3;o m&#xE9;dia das paredes anterior, anterosseptal e anterolateral.</p>
<p>Diante dos exames complementares, foi realizada cineangiocoronariografia de urg&#xEA;ncia, que descartou les&#xF5;es coronarianas significativas e evidenciou stent p&#xE9;rvio na art&#xE9;ria DA, por&#xE9;m com aumento do volume sist&#xF3;lico por extensa acinesia anterior, inferior e apical, poupando apenas as bases na ventriculografia (<xref ref-type="fig" rid="f9">Figura 4</xref>).</p>
<fig id="f9">
<label>Figura 4</label>
<caption>
<title>Ventriculografia em s&#xED;stole no terceiro DPO de implante de Mitraclip<sup>&#xAE;</sup></title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf04-pt.tif"/>
</fig>
<p>Devido &#xE0; aus&#xEA;ncia de les&#xF5;es tromb&#xF3;ticas na angiografia, a conduta m&#xE9;dica consistiu em manter o paciente internado e em tratamento cl&#xED;nico. No quarto DPO, o paciente cursou com queda significativa de troponina para 24,3 ng/mL. Evoluiu com melhora cl&#xED;nica e recebeu alta hospitalar.</p>
<p>Ap&#xF3;s 1 ano da interven&#xE7;&#xE3;o, o paciente apresentava-se clinicamente bem, em CF da NYHA II. O ETT de controle demonstrou recupera&#xE7;&#xE3;o da FEVE para 61% (Simpson), RM de grau moderado e estenose discreta (GTM 4,0 mmHg e gradiente de pico (Gp) 17,0 mmHg), sem altera&#xE7;&#xE3;o da contratilidade segmentar nas paredes do VE (<xref ref-type="fig" rid="f10">Figura 5</xref>).</p>
<fig id="f10">
<label>Figura 5</label>
<caption>
<title>ETT 1 ano ap&#xF3;s implanta&#xE7;&#xE3;o do Mitraclip<sup>&#xAE;</sup> evidenciando insufici&#xEA;ncia mitral de grau moderado.</title></caption>
<graphic xlink:href="2675-312X-dic-36-04-e20230094-gf05-pt.tif"/>
</fig>
<p>Diante do quadro exposto, foi levantada a hip&#xF3;tese diagn&#xF3;stica de STT secund&#xE1;ria &#xE0; implanta&#xE7;&#xE3;o de Mitraclip<sup>&#xAE;</sup>, caracterizada por altera&#xE7;&#xF5;es din&#xE2;micas no ECG e na ecocardiografia, eleva&#xE7;&#xE3;o dos marcadores de necrose mioc&#xE1;rdica, &#x201C;baloniza&#xE7;&#xE3;o&#x201D; apical e hipercinesia dos segmentos basais na ventriculografia, sem evid&#xEA;ncia de obstru&#xE7;&#xE3;o arterial coronariana &#xE0; cineangiocoronariografia apesar de implante recente de stent em art&#xE9;ria DA, em um contexto de estresse p&#xF3;s-operat&#xF3;rio.</p>
</sec>
<sec sec-type="discussion">
<title>Discuss&#xE3;o</title>
<p>Neste caso, o que chama a aten&#xE7;&#xE3;o &#xE9; a correla&#xE7;&#xE3;o presumida entre STT secund&#xE1;ria &#xE0; implanta&#xE7;&#xE3;o percut&#xE2;nea do Mitraclip<sup>&#xAE;</sup> e corre&#xE7;&#xE3;o da RM em um paciente do sexo masculino com idade avan&#xE7;ada, de muito alto risco cardiovascular.</p>
<p>Estudos mostram que as catecolaminas desempenham um papel central na patog&#xEA;nese da STT.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Al&#xE9;m disso, outros aspectos que podem estar relacionados &#xE0; s&#xED;ndrome incluem disfun&#xE7;&#xE3;o endotelial macro e microvascular, vasoespasmo e sobrecarga de c&#xE1;lcio nos mi&#xF3;citos, os quais promovem dist&#xFA;rbios da contra&#xE7;&#xE3;o e da fun&#xE7;&#xE3;o ventricular, afetando, em sua maioria, mulheres na p&#xF3;s-menopausa.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>Habitualmente, as caracter&#xED;sticas cl&#xED;nicas s&#xE3;o semelhantes &#xE0;s da SCA. Os pacientes cursam com dor tor&#xE1;cica, dispneia, insufici&#xEA;ncia card&#xED;aca aguda, altera&#xE7;&#xF5;es no ECG (como supra ou infradesnivelamento do segmento ST ou invers&#xE3;o de onda T) e aumento de troponina s&#xE9;rica. Entretanto, esses pacientes n&#xE3;o apresentam curva de troponina, como seria esperado nos casos de infarto agudo do mioc&#xE1;rdio (IAM), nem les&#xF5;es obstrutivas que justifiquem o d&#xE9;ficit agudo de contratilidade observado na STT. Embora rara, a STT &#xE9; um diagn&#xF3;stico diferencial de SCA, podendo ser subdiagnosticada devido &#xE0; maior preval&#xEA;ncia de IAM por coronariopatia obstrutiva ateroscler&#xF3;tica na popula&#xE7;&#xE3;o geral.<sup><xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>A angiografia de coron&#xE1;rias com ventriculografia &#xE9; considerada o padr&#xE3;o-ouro para o diagn&#xF3;stico, sendo observada acinesia do &#xE1;pice do VE com contratilidade preservada na base, conferindo aspecto de bal&#xE3;o em suas por&#xE7;&#xF5;es apicais (&#x201C;balonismo apical&#x201D;), sem les&#xF5;es obstrutivas coronarianas.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>O tratamento dessa cardiomiopatia envolve medidas de suporte cl&#xED;nico. A maioria dos casos evolui com remiss&#xE3;o espont&#xE2;nea e completa das altera&#xE7;&#xF5;es dentro de dias ou semanas. Por&#xE9;m, a fase aguda da doen&#xE7;a pode ser grave, sendo decorrente de complica&#xE7;&#xF5;es como choque cardiog&#xEA;nico, arritmias e parada card&#xED;aca, com alta morbidade e mortalidade nesses casos.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>Do ponto de vista epidemiol&#xF3;gico, a STT &#xE9; um evento extremamente raro. Ap&#xF3;s extensa busca, encontramos na literatura apenas um relato de STT associada ao MitraClip<sup>&#xAE;</sup>, publicado em 2020. O caso ocorreu nos Estados Unidos e apresentou caracter&#xED;sticas epidemiol&#xF3;gicas semelhantes &#xE0;s do nosso relato, em paciente idoso do sexo masculino com desfecho cl&#xED;nico favor&#xE1;vel.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Um outro estudo tamb&#xE9;m descreveu um caso de STT, em paciente do sexo feminino, a qual foi submetida a cirurgia aberta para corre&#xE7;&#xE3;o de RM grave ocasionada por rea&#xE7;&#xE3;o adversa a infus&#xE3;o de protamina.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>O procedimento de implanta&#xE7;&#xE3;o de MitraClip<sup>&#xAE;</sup> &#xE9; menos invasivo do que a troca valvar por toracotomia para o tratamento de RM grave. &#xC9; considerado eficaz e seguro em pacientes refrat&#xE1;rios ao tratamento cl&#xED;nico, com &#xF3;timos resultados reportados pelo estudo COAPT e seu seguimento de 5 anos, al&#xE9;m de ser um tratamento alternativo para aqueles com risco cir&#xFA;rgico alto ou com contraindica&#xE7;&#xE3;o para cirurgia.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup> Apesar de menos invasiva, a t&#xE9;cnica percut&#xE2;nea &#xE9; tamb&#xE9;m capaz de induzir a libera&#xE7;&#xE3;o de catecolaminas pelo estresse f&#xED;sico e emocional, assim como a cirurgia aberta e a pr&#xF3;pria hospitaliza&#xE7;&#xE3;o.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Este caso refor&#xE7;a que a STT &#xE9; uma complica&#xE7;&#xE3;o potencial do reparo percut&#xE2;neo da valva mitral com MitraClip<sup>&#xAE;</sup>.</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="supported-by" id="fn5"><p><bold>Fontes de Financiamento</bold></p>
<p>O presente estudo n&#xE3;o teve fontes de financiamento externas.</p></fn>
<fn fn-type="other" id="fn6"><p><bold>Vincula&#xE7;&#xE3;o Acad&#xEA;mica</bold></p>
<p>N&#xE3;o h&#xE1; vincula&#xE7;&#xE3;o deste estudo a programas de p&#xF3;s-gradua&#xE7;&#xE3;o.</p></fn>
<fn fn-type="other" id="fn7"><p><bold>Aprova&#xE7;&#xE3;o &#xC9;tica e Consentimento Informado</bold></p>
<p>Este estudo foi aprovado pelo Comit&#xEA; de &#xC9;tica do CEP/HUGO sob o n&#xFA;mero de protocolo 85497418.2.0000.0033. Todos os procedimentos envolvidos nesse estudo est&#xE3;o de acordo com a Declara&#xE7;&#xE3;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#xED;dos no estudo.</p></fn>
<fn fn-type="other" id="fn8"><p>Editor respons&#xE1;vel pela revis&#xE3;o: Daniela do Carmo Rassi Frota</p></fn>
</fn-group>
</back>
</sub-article>
</article>
