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Case report
Magnesium sulphate and 123I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease
Utilidad de la gammagrafia con 123 I-MIBG y del Sulfato de Magnesio en el diagnóstico y tratamiento del feocromocitoma
M. Vendrella,
Corresponding author
marina_vendrell@hotmail.com

Corresponding author.
, N. Martína, A. Tejedora, J.T. Ortizb, À. Muxíc, P. Tauràa
a Servicio de Anestesiología, Reanimación y Tratamiento del Dolor, Hospital Clínic Barcelona, Spain
b Servicio de Cardiología, Hospital Clínic Barcelona, Spain
c Servicio de Medicina Nuclear, Hospital Clínic Barcelona, Spain
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two particularities must be recalled&#46; Firstly&#44; and regarding therapeutic approach&#44; magnesium sulphate &#40;MgSO<span class="elsevierStyleInf">4</span>&#41; is a well-known&#44; safe agent&#44; which helps in improving cardiovascular stability&#44; as it inhibits catecholamine release&#44; blocks catecholamine receptors&#44; and has antiarrhythmic properties&#44; both atrial and ventricular&#44; related to calcium channel antagonism&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Secondly&#44; the use of <span class="elsevierStyleSup">123</span>I-metaiodobenzylguanidine &#40;<span class="elsevierStyleSup">123</span>I-MIBG&#41; scintigraphy technique is not only useful to functionally confirm tumour tissue&#44; but it can also assess severity and prognosis of cardiac failure&#46; Also&#44; it can be a helpful tool in establishing a differential diagnosis in case heart function fails to improve after pheochromocytoma removal&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 48-year-old woman with hypertension and type 2 diabetes mellitus consulted at her community hospital complaining of abdominal pain&#44; nausea and vomiting&#46; Initial exploration revealed marked hypertension &#40;180&#47;130<span class="elsevierStyleHsp" style=""></span>mmHg&#41; and acute-onset dyspnoea with pulse oximeter saturation of 88&#37; &#40;despite rebreathing mask at 40&#37; oxygen&#41;&#46; During general screening&#44; supra-ventricular paroxysmal tachycardia with haemodynamic instability occurred &#40;60&#47;40<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#44; requiring cardioversion with adenosine &#40;18<span class="elsevierStyleHsp" style=""></span>mg administered in two boluses&#41; and amiodarone &#40;bolus of 150<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; as well as treatment with 1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min norepinephrine and 10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min dopamine&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Chest X-ray compatible with pulmonary oedema&#44; electrocardiogram with sinus tachycardia of 130<span class="elsevierStyleHsp" style=""></span>bpm and ST-segment elevation in the anterolateral side&#44; and elevated troponin levels suggested acute myocardial infarction Killip IV&#46; However&#44; emergency coronary angiography showed normal coronary arteries with normal coronary flow&#46; Echocardiogram demonstrated a global hypokinesia of the heart with normal chamber size&#46; Ejection fraction &#40;EF&#41;&#44; calculated using a biplane Simpson formula&#44; was 20&#37;&#44; with an E&#47;A ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;154 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Cardiac index&#44; measured by thermodilution method with a pulmonary arterial catheter&#44; was 0&#46;9<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">&#8722;2</span>&#46; Despite vasoactive therapy with norepinephrine and dopamine&#44; she remained hemodynamically unstable and an intra-aortic balloon pump &#40;IABP&#41; was placed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In this condition&#44; she was remitted to our hospital and into the cardiology intensive care unit&#46; Due to important blood pressure swings &#40;varying from 170&#47;120<span class="elsevierStyleHsp" style=""></span>mmHg to 60&#47;35<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#44; fluctuating from need of vasoactive &#40;1&#46;8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min norepinephrine&#44; 25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min dobutamine&#41; to hypotensive drugs &#40;8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min nitroprusside&#41;&#44; as well as persistent abdominal pain&#44; pheochromocytoma was suspected&#46; A bedside abdominal echography revealed a right suprarenal tumour of 60<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>52<span class="elsevierStyleHsp" style=""></span>mm&#44; confirmed by abdominal computed tomography&#46; In order to establish the definitive diagnosis&#44; a <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy showed a low-uptaking infrahepatic image&#44; suggestive of pheochromocytoma necrosis&#46; Levels of plasma metanephrines of 352<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;normal &#60;90&#41; and normetanephrines 7249<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;normal &#60;200&#41; corroborated the diagnosis&#46; Cardiac sympathetic denervation was also assessed&#44; by measuring the heart-to-mediastinum activity ratio at 4<span class="elsevierStyleHsp" style=""></span>h post <span class="elsevierStyleSup">123</span>I-MIBG injection in the anterior view&#46; The ratio of 1&#46;5 &#40;normal &#62;1&#46;8&#41; demonstrated low myocardial uptake &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At this point&#44; the anaesthesiology team was contacted in order to optimize the patient prior to surgery since&#44; despite aggressive pharmacological treatment with vasoactive drugs and IABP support&#44; persistent haemodynamic instability did not allow for introduction of &#945; blocker therapy&#46; MgSO<span class="elsevierStyleInf">4</span> infusion was considered valuable as a bridge for &#945;-blocker treatment&#46; Thus&#44; on day 3&#44; MgSO<span class="elsevierStyleInf">4</span> infused at 1<span class="elsevierStyleHsp" style=""></span>g&#47;h after priming dose of 2<span class="elsevierStyleHsp" style=""></span>g was added&#46; Twenty-four hours later&#44; the patient showed gradual stabilization &#40;blood pressure around 100&#47;70<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate 80<span class="elsevierStyleHsp" style=""></span>bpm&#41;&#44; with no further hypertensive crisis weaning off of vasoactive drugs&#44; removal of IABP&#44; and volume overload in order to refill the depleted vascular space&#46; A bedside echocardiogram demonstrated a non-dilated left ventricle &#40;LV&#41;&#44; with normal motility and no segmentary alterations&#46; Calculated EF was 45&#37;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This favourable evolution allowed for removal of the IABP and initiation of alpha blockade on day 9&#44; with phenoxybenzamine 10<span class="elsevierStyleHsp" style=""></span>mg thrice a day&#44; scheduling the patient for resection of the right adrenal mass&#46; Laparoscopic surgery was performed on day 18 after admission&#46; Prior to surgery&#44; echocardiogram showed a slightly hypertrophic LV&#44; with no dilation and normal global motility&#46; Heart valves and right side of the heart were normal&#46; Estimated EF had increased up to 60&#37; with complete restoration of left ventricular systolic function with light diastolic dysfunction &#40;Doppler transmitral flow velocity E&#47;A ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;8&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Prior to anaesthesia induction&#44; which was performed with midazolam and etomidate&#44; to avoid severe blood pressure drops and reflex tachycardia&#44; as well as fentanyl and cisatracurium&#44; invasive arterial monitorisation via left radial artery was obtained&#46; As established in our hospital&#39;s protocol&#44; a bolus &#40;4<span class="elsevierStyleHsp" style=""></span>g&#41; plus infusion &#40;1<span class="elsevierStyleHsp" style=""></span>g&#47;h&#41; of MgSO<span class="elsevierStyleInf">4</span> was initiated before anaesthesia induction and maintained throughout surgery&#44; which lasted 85<span class="elsevierStyleHsp" style=""></span>min&#46; Suprarenal gland was removed without incidences&#46; Anaesthesia was maintained with desflorane&#44; fentanyl and cisatracurium&#46; Intra-operatively&#44; a modified pulmonary arterial catheter &#40;Swan-Ganz thermodilution ejection fraction&#47;volumetric catheter&#44; continuous cardiac output&#47;continuous end diastolic volume&#47;EF and SvO<span class="elsevierStyleInf">2</span>&#44; model 777F8&#44; Baxter&#44; American Edwards L&#44; Irvine&#44; CA&#41;&#44; and invasive arterial monitorisation were used&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">No inotropes or vasoconstrictors were needed intraoperatively&#44; and the patient remained stable&#44; with blood pressure around 110&#47;70 and heart rate around 80<span class="elsevierStyleHsp" style=""></span>bpm&#46; At this time&#44; haemodynamic profile showed a significant CI increase &#40;2&#46;4&#8211;3&#46;64<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">&#8722;2</span>&#41; with normal right ventricular function &#40;end-dyastolic ventricular index&#58; 156<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">&#8722;2</span>&#59; ejection fraction index&#58; 51&#37;&#41;&#46; The patient was extubed in the operating room and transferred to the reanimation ward for 24<span class="elsevierStyleHsp" style=""></span>h-control where she made an uneventful recovery&#46; Tramadol and dexketoprophen were used for postoperative analgesia&#46; She was discharged home 4 days after surgery with no drug therapy&#46; The histopathological study confirmed the diagnosis of pheochromocytoma&#44; 85&#37; of which was necrosed&#46; At nine months follow-up&#44; the patient was clinically asymptomatic&#44; hemodynamically stable&#44; with an echocardiogram that showed normal contractility with an estimated EF of 65&#37;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">This case report was performed in a university hospital setting&#44; based on patient data acquired during care-as-usual&#46; The data were analyzed retrospectively&#44; and all requirements for patient anonymity are in agreement with the regulations of the ethical committee of our hospital for publication of patient data&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">We report the case of a patient presenting with spontaneous haemorrhagic necrosis of pheochromocytoma&#44; with sudden release of catecholamines&#46; This caused what is known as a catecholamine storm or &#8220;attack&#8221;&#44; with myocardial stunning&#44; pulmonary oedema and heart failure&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The patient had to undergo surgery for tumour removal&#46; Prior to surgery&#44; it is essential to block &#945;-adrenergic receptors&#44; since emergency surgery in absence of preparation is associated to poor survival rates&#46; However&#44; the patient&#39;s unstable haemodynamic condition did not allow for introduction of alpha-blockade&#46; After ensuring there were no other treatable causes of acute-onset heart failure&#44; such as coronary artery lesions&#44; magnesium sulphate was used as bridge therapy for weaning off vasoactive drugs and initiation of alpha-blockade treatment&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The successful use of magnesium sulphate for prevention of catecholamine storms during surgical removal of pheochromocytoma has been known for quite a long time&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> However&#44; MgSO<span class="elsevierStyleInf">4</span> is also useful for treating pheochromocytoma crisis&#44; and it has been recognized as such since James et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> presented three cases of life-threatening crisis in which MgSO<span class="elsevierStyleInf">4</span> was particularly beneficial&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">MgSO<span class="elsevierStyleInf">4</span> has a generally marked anti-adrenergic effect&#44; inhibiting catecholamine release and storage and mainly blocking extra-cellular and intra-cellular sites of calcium action&#46; It is mostly well known for treatment of ventricular arrhythmias such as Torsades de Pointes because of its aforementioned action on calcium channels&#44; but it may also be used for auricular arrhythmias&#44; since it acts on sodium and potassium currents that affect membrane potentials in the heart&#39;s conductive system&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4&#44;8</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The haemodynamic behaviour observed in our patient suggested the protective cardiac effects of MgSO<span class="elsevierStyleInf">4</span>&#44; improving the contractile response of stunned myocardium with a decrease of systemic vascular resistance and an increase in cardiac index without changes in heart rate or arterial pressure&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Another interesting consideration derived from this case is the use of <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy&#46; Being a norepinephrine analogue&#44; MIBG demonstrates a high uptake in sympathetically innervated tissues&#44; and it has been in use for diagnostic assessment of tumours that arise from neural crest cells since the 1980s&#46; Its main goal is to functionally confirm tumour tissue that has been localized via computerized tomography scan or magnetic resonance imaging&#44; and to diagnose extra-adrenal pheochromocytomas and remaining tumour tissue after surgery&#44; being a useful tool for follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">However&#44; and as in our case&#44; once this was performed&#44; cardiac sympathetic denervation was also assessed&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-MIBG scintigraphy can also be used for the assessment of cardiac sympathetic function in heart failure&#46; In chronic heart failure&#44; there is a reduction in NE uptake&#44; with an accelerated spillover in the myocardial adrenergic nerve terminals &#40;increase in pre-synaptic activity&#41;&#46; MIBG&#44; with the same uptake and storage methods as NE&#44; allows for autonomic cardiac function characterization&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> This technique can also be used in acute heart failure syndromes&#46; As a direct effect of excessive catecholamines&#44; myocardial injury and myocardiocyte degeneration have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In our patient&#44; <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy showed a low myocardial uptake&#44; as demonstrated by a low heart-to-mediastinum ratio &#40;1&#46;5&#44; normal &#62;1&#46;8&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This ratio correlates with the severity of heart failure and outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> When <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy for pheochromocytoma is performed&#44; it is useful to have myocardial uptake measured by an experienced radiologist&#44; in order to assess the influence of catecholamines on the heart&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">After pheochromoytoma removal&#44; catecholamine over-stimulation is discontinued&#46; Accordingly&#44; tumour removal prompts a reversal of cardiomyopathy and associated symptoms&#46; Heart function should improve&#44; with the myocardium returning to normal within months&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">If heart function fails to improve&#44; again <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy proves useful&#46; A continued heart-to-mediastinum ratio alteration may be due to a permanent remaining lesion on the heart after the insult&#59; but it may also be because of persistent adrenergic influence on the heart&#44; due to incomplete tumour removal&#44; contra-lateral pheochromocytoma&#44; or extra-adrenal paragangliomas&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In conclusion&#44; we believe that the use of these two well-known &#8216;devices&#8217; &#8211; magnesium as a therapeutic one and <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy as a diagnostic and prognostic one &#8211; is a relatively simple and extremely useful approach to keep in mind when facing pheochromocytomas&#44; helping us to better manage cardiovascular alterations caused by this tumour&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">None of the authors have declared conflict of interest related to the case&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical responsibilities</span><p id="par0125" class="elsevierStylePara elsevierViewall">The information in this case was collected during the usual process of diagnosis and treatment of a patient&#46; The authors have followed the protocols established by the Hospital Clinic of Barcelona to access data from medical records&#46; The patient gave permission by informed consent for the usage of such data&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pheochromocytoma is a tumour of the chromaffin tissue&#46; It may&#44; through catecholamine release&#44; have deleterious effects on myocardial structure&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A 48-year-old woman with a history of hypertension and type II diabetes mellitus &#40;ASA II&#41; was diagnosed of pheochromocytoma-induced myocarditis&#44; which caused severe cardiogenic shock&#44; with an ejection fraction of 20&#37;&#46; Extreme blood pressure swings required aggressive therapy with vasoactive drugs &#40;norepinephrine and dopamine&#41; and an intra-aortic balloon pump&#44; despite which severe haemodynamic instability persisted&#46; Finally&#44; the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue&#44; but also to assess severity and prognosis of cardiac failure&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Prognosis of pheochromocytoma-induced heart failure can be very poor&#46; The use of these two well-known and relatively simple &#8216;tools&#8217; for treatment and prognosis is a helpful option to keep in mind&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los feocromocitomas son tumores del tejido cromaf&#237;n&#46; Pueden&#44; a trav&#233;s de la secreci&#243;n de catecolaminas&#44; causar efectos delet&#233;reos sobre el miocardio&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Una mujer de 48 a&#241;os&#44; con antecedentes de hipertensi&#243;n arterial y diabetes mellitus tipo II &#40;ASA II&#41; fue diagnosticada de feocromocitoma&#44; con miocardiopat&#237;a&#44; y shock cardiog&#233;nico con fracci&#243;n de eyecci&#243;n del 20&#37;&#46; Las extremas oscilaciones hemodin&#225;micas requirieron tratamiento con f&#225;rmacos vasoactivos &#40;noradrenalina y dopamina&#41; as&#237; como el uso de un bal&#243;n de contrapulsaci&#243;n intra-a&#243;rtico&#44; a pesar de lo cual persist&#237;a la inestabilidad&#46; Finalmente&#44; el uso de sulfato de magnesio permiti&#243; la estabilizaci&#243;n de la paciente&#44; pudi&#233;ndose retirar las drogas vasoactivas previo a la cirug&#237;a&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El uso de la gammagraf&#237;a con 123-metayodobenzilguanidina sirve no s&#243;lo para la clasificaci&#243;n funcional del tejido tumoral&#44; sino tambi&#233;n para evaluar la severidad y pron&#243;stico del fallo card&#237;aco&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El pron&#243;stico de la insuficiencia card&#237;aca inducida por feocromocitoma puede ser grave&#46; El uso de estas conocidas y relativamente sencillas &#8216;herramientas&#8217; para el tratamiento y el pron&#243;stico son una opci&#243;n &#250;til a tener en cuenta&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Transmitral flow Doppler shows the early ventricular filling &#40;E&#41; and atrial contraction &#40;A&#41;&#46; Basal E&#47;A relationship shows an E&#47;A ratio of 2&#46;154&#46; &#40;b&#41; M mode echocardiography in the left ventricle reveals the improvement of heart contractility&#46;</p>"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos