Case report
Takotsubo Syndrome in a Rheumatoid Arthritis Patient Under Tofacitinib: A Case Report
Síndrome de takotsubo en un paciente con artritis reumatoide tomando tofacitinib: reporte de un caso
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"<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Georgina" "apellidos" => "Terroso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Elisabete" "apellidos" => "Martins" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Sofia" "apellidos" => "Pimenta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Lúcia" "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Miguel" "apellidos" => "Bernardes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Rheumatology Department, Centro Hospitalar de São João, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Cardiology Department, Centro Hospitalar de São João, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de takotsubo en un paciente con artritis reumatoide tomando tofacitinib: reporte de un caso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Concerns of adverse cardiovascular events with the use of tofacitinib have been raised, but no case of cardiomyopathy has been reported so far.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a rare case of Takotsubo cardiomyopathy (TKM) in a rheumatoid arthritis (RA) patient treated with tofacitinib.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical observation</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 57-year-old white woman was diagnosed with a seropositive for anti-citrullinated protein antibody RA 5 years ago. She was treated with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg daily (started one year ago) and prednisolone 5<span class="elsevierStyleHsp" style=""></span>mg daily. Initially, the patient experienced adverse events with the first 2 attempted csDMARDs (liver toxicity under methotrexate and hypertension with leflunomide) and was refractory to multiple biologic agents (etanercept, golimumab and tocilizumab, were consecutively tried) and her disease was refractory to multiple biologic agents (etanercept, golimumab and tocilizumab). She had no other cardiovascular risk factors. Previous electrocardiogram (ECG) was unremarkable.</p><p id="par0020" class="elsevierStylePara elsevierViewall">She presented to the emergency department with an acute onset tight squeezing chest pain lasting for 7<span class="elsevierStyleHsp" style=""></span>h. Upon admission, we observed the following vital signs: blood pressure of 110/60<span class="elsevierStyleHsp" style=""></span>mmHg, heart rate of 90 beats per minute, respiratory rate of 18 breaths per minute and oxygen saturation of 98% on room air with a pulse oximeter. Her heart sounds were regular with no murmurs and lung examination was normal. Her cardiac enzymes were elevated, presenting with a creatine phosphokinase-MB of 5.7<span class="elsevierStyleHsp" style=""></span>ng/mL (normal<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>ng/mL) and a troponin <span class="elsevierStyleSmallCaps">I</span> of 1.16<span class="elsevierStyleHsp" style=""></span>ng/mL (normal<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.04<span class="elsevierStyleHsp" style=""></span>ng/mL). She had a normal complete blood count. Thyroid function and cortisol levels were normal. ECG showed pathologic Q-waves in leads V1-V3 and a negative T-waves in lead V4. Cardiac catheterization was performed, demonstrating normal coronary arteries, circumferential akinesia of the apex and a poor left ventricular systolic function (LVEF) (of approximately 40%], consistent with the diagnosis of TKM. Myocardial perfusion scintigraphy performed on day 6 showed no alterations; LVEF was estimated at 38%.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient received supportive care and had an uneventful hospital stay with complete resolution of symptoms and normalization of cardiac enzymes in 48<span class="elsevierStyleHsp" style=""></span>h. Three days after, prior to hospital discharge, she performed an echocardiogram that revealed a preserved LVEF (estimated at 55%), with normal wall thickness and absence of wall motion abnormalities.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment with tofacitinib was stopped and the patient started abatacept. One year later, the patient was reassessed with a cardiac magnetic resonance, showing no abnormalities in segmental motility/contractility or areas of late gadolinium enhancement, estimating LVEF at 58%.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of TKM was made in this patient once all four Mayo Clinic diagnostic criteria were present: transient left ventricular systolic dysfunction, absence of obstructive coronary disease, new electrocardiographic abnormalities and absence of pheochromocytoma.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Several pathophysiological mechanisms have been proposed for TKM, but one of the most unanimous is a catecholamine surge, supported by a number of features, including its association with emotional stress and with the exposure to supratherapeutic doses of catecholamines.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">4–6</span></a> In a 2017 article, reviewing all the 157 drug-induced TKM cases published in the literature until then, the authors conclude that over two-thirds of drug-induced TKM cases were due to catecholamine stimulation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> Moreover, a recent study in rats, who were given tofacitinib, evaluated the relationship between cardiovascular hemodynamics and plasma norepinephrine (NE) levels, showing a dose-dependent increase in circulating NE levels, which was maintained during 14 days of tofacitinib administration. However, this increase in plasma NE concentrations presumably reflects a reflex response to direct vasodilation.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> Further studies in humans, are needed to clarify this finding. It may represent the link between tofacitinib and TKM.</p><p id="par0045" class="elsevierStylePara elsevierViewall">This is, to our knowledge, the first report of a case of TKM in a patient taking tofacitinib. A cause cannot be clarified with certainty, however the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1777443" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1560625" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1777444" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1560626" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical observation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-04-16" "fechaAceptado" => "2021-06-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1560625" "palabras" => array:4 [ 0 => "Rheumatoid arthritis" 1 => "Tofacitinib" 2 => "Takotsubo" 3 => "Cardiomyopathy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1560626" "palabras" => array:4 [ 0 => "Artritis reumatoide" 1 => "Tofacitinib" 2 => "Takotsubo" 3 => "Cardiomiopatía" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We describe a case of a 57-year-old white woman treated for rheumatoid arthritis (RA) with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg daily (started one year ago) and prednisolone 5<span class="elsevierStyleHsp" style=""></span>mg daily. She presented to the emergency department with a tight squeezing chest pain and shortness of breath for 7<span class="elsevierStyleHsp" style=""></span>h and the clinical evaluation revealed regional systolic dysfunction of the left ventricle, mimicking a myocardial infarction, in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. All changes were transient and resolved completely within 4 days. The diagnosis of Takotsubo cardiomyopathy (TKM) was established. This is, as far as we know, the first report of a case of TKM in a RA patient taking tofacitinib. Although the association has not been previously described and the precise cause cannot be identified in this patient, the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Describimos el caso de una mujer blanca de 57 años tratada por artritis reumatoide (AR) con tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg al día (iniciado hace un año) y prednisolona 5<span class="elsevierStyleHsp" style=""></span>mg al día. Acudió al servicio de Urgencias con dolor torácico opresivo y dificultad para respirar durante 7 h y la evaluación clínica reveló disfunción sistólica regional del ventrículo izquierdo, simulando un infarto de miocardio, en ausencia de evidencia angiográfica de enfermedad arterial coronaria obstructiva o aguda. rotura de placa. Todos los cambios fueron transitorios y se resolvieron por completo en 4 días. Se estableció el diagnóstico de miocardiopatía de takotsubo (TKM). Este es, hasta donde sabemos, el primer informe de un caso de TKM en un paciente con AR que toma tofacitinib. Aunque la asociación no se ha descrito previamente y no se puede identificar la causa precisa en este paciente, la asociación con tofacitinib debe considerarse dada la justificación etiopatogénica y la ausencia de cualquier otra causa identificable.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of tofacitinib for up to 9.5<span class="elsevierStyleHsp" style=""></span>years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wollenhaupt" 1 => "E.B. Lee" 2 => "J.R. Curtis" 3 => "J. Silverfield" 4 => "K. Terry" 5 => "K. 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