Case report
Acute coronary syndrome in the oncology patient: An avoidable event?
Read
3483
Timeswas read the article
1633
Total PDF
1850
Total HTML
Share statistics
array:25 [ "pii" => "S2174204918303076" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.04.015" "estado" => "S300" "fechaPublicacion" => "2018-09-01" "aid" => "1212" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2018" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2018;37:791.e1-791.e4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 736 "formatos" => array:3 [ "EPUB" => 100 "HTML" => 321 "PDF" => 315 ] ] "Traduccion" => array:1 [ "pt" => array:20 [ "pii" => "S0870255117300021" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.04.010" "estado" => "S300" "fechaPublicacion" => "2018-09-01" "aid" => "1212" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2018;37:791.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1126 "formatos" => array:3 [ "EPUB" => 103 "HTML" => 715 "PDF" => 308 ] ] "pt" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Caso Clínico</span>" "titulo" => "Síndrome coronária aguda em doente oncológico: um problema evitável?" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "791.e1" "paginaFinal" => "791.e4" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Acute coronary syndrome in the oncology patient: An avoidable event?" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 923 "Ancho" => 2334 "Tamanyo" => 204292 ] ] "descripcion" => array:1 [ "pt" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A ‐ Descendente anterior distal com estenose de 80%. B ‐ Circunflexa distal com estenose de 90%. D ‐ Resultado final de angioplastia da circunflexa. E ‐ Coronária direita com estenose de 90% na porção média. F ‐ Resultado final de angioplastia da coronária direita.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Afonso Félix‐Oliveira, Nélson Vale, Sérgio Madeira, Miguel Mendes" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Afonso" "apellidos" => "Félix‐Oliveira" ] 1 => array:2 [ "nombre" => "Nélson" "apellidos" => "Vale" ] 2 => array:2 [ "nombre" => "Sérgio" "apellidos" => "Madeira" ] 3 => array:2 [ "nombre" => "Miguel" "apellidos" => "Mendes" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204918303076" "doi" => "10.1016/j.repce.2017.04.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918303076?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117300021?idApp=UINPBA00004E" "url" => "/08702551/0000003700000009/v2_201810120613/S0870255117300021/v2_201810120613/pt/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2174204918303118" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.07.014" "estado" => "S300" "fechaPublicacion" => "2018-09-01" "aid" => "1254" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "Rev Port Cardiol. 2018;37:793-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 646 "formatos" => array:3 [ "EPUB" => 102 "HTML" => 331 "PDF" => 213 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Image in Cardiology</span>" "titulo" => "Left pericardial defect: A rare cause of chest pain" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "793" "paginaFinal" => "795" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Defeito do pericárdio esquerdo: uma causa rara de dor torácica" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2503 "Ancho" => 1867 "Tamanyo" => 368140 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Cardiac MRI images. (A-D) Steady-state free precession images. (A) Axial image showing left and posterior heart displacement. (B) Axial image displaying non-visualization of the pericardium and pericardial fat around the left ventricle (between the white arrows). (C) Coronal image showing absence of the pericardium and pericardial fat around the left ventricle and great vessels (between the white arrows), with lung tissue interposition in the several recesses where the pericardium is usually found. (D) Axial image showing lung tissue in the aorto-pulmonary window (white arrow), which is considered a pathognomonic sign of this condition. (E) T1-weighted axial image with no abnormalities, particularly, fat tissue deposition. (F) Delayed gadolinium-enhanced axial image with no macroscopic areas of myocardial fibrosis/necrosis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Rita Pereira, Ana Rita Almeida, Inês Cruz, Luís Rocha Lopes, Isabel João, Hélder Pereira" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ana Rita" "apellidos" => "Pereira" ] 1 => array:2 [ "nombre" => "Ana Rita" "apellidos" => "Almeida" ] 2 => array:2 [ "nombre" => "Inês" "apellidos" => "Cruz" ] 3 => array:2 [ "nombre" => "Luís Rocha" "apellidos" => "Lopes" ] 4 => array:2 [ "nombre" => "Isabel" "apellidos" => "João" ] 5 => array:2 [ "nombre" => "Hélder" "apellidos" => "Pereira" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918303118?idApp=UINPBA00004E" "url" => "/21742049/0000003700000009/v2_201911291446/S2174204918303118/v2_201911291446/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2174204918303064" "issn" => "21742049" "doi" => "10.1016/j.repce.2018.08.005" "estado" => "S300" "fechaPublicacion" => "2018-09-01" "aid" => "1219" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Rev Port Cardiol. 2018;37:783-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1425 "formatos" => array:3 [ "EPUB" => 130 "HTML" => 989 "PDF" => 306 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review Article</span>" "titulo" => "Importance of ambulatory blood pressure monitoring in the diagnosis and prognosis of pediatric hypertension" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "783" "paginaFinal" => "789" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Importância da monitorização ambulatória da pressão arterial no diagnóstico e prognóstico da hipertensão arterial em idade pediátrica" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Helena Andrade, António Pires, Natália Noronha, Maria Emanuel Amaral, Lisete Lopes, Paula Martins, António Marinho da Silva, Eduardo Castela" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Helena" "apellidos" => "Andrade" ] 1 => array:2 [ "nombre" => "António" "apellidos" => "Pires" ] 2 => array:2 [ "nombre" => "Natália" "apellidos" => "Noronha" ] 3 => array:2 [ "nombre" => "Maria Emanuel" "apellidos" => "Amaral" ] 4 => array:2 [ "nombre" => "Lisete" "apellidos" => "Lopes" ] 5 => array:2 [ "nombre" => "Paula" "apellidos" => "Martins" ] 6 => array:2 [ "nombre" => "António" "apellidos" => "Marinho da Silva" ] 7 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Castela" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S0870255117305541" "doi" => "10.1016/j.repc.2017.09.026" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305541?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918303064?idApp=UINPBA00004E" "url" => "/21742049/0000003700000009/v2_201911291446/S2174204918303064/v2_201911291446/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Acute coronary syndrome in the oncology patient: An avoidable event?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "791.e1" "paginaFinal" => "791.e4" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Afonso Félix-Oliveira, Nélson Vale, Sérgio Madeira, Miguel Mendes" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Afonso" "apellidos" => "Félix-Oliveira" "email" => array:1 [ 0 => "afonso.felix.oliveira@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Nélson" "apellidos" => "Vale" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Sérgio" "apellidos" => "Madeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Miguel" "apellidos" => "Mendes" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Serviço de Cardiologia, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 923 "Ancho" => 2334 "Tamanyo" => 223301 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) Left anterior descending artery with 80% stenosis; (B) distal circumflex artery with 90% stenosis; (C) final result of angioplasty on the circumflex artery; (D) right coronary artery with 90% stenosis in the mid segment; (E) final result of angioplasty on the right coronary artery.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The fluoropyrimidines play an important part in cancer therapy, for which they are currently the third most used drug class.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1,2</span></a> They include 5-fluorouracil (5-FU), administered intravenously, and its orally administered prodrug capecitabine, which is subsequently metabolized to 5-FU. These drugs are antimetabolites that inhibit the action of thymidylate synthase, preventing the synthesis of nucleotides that are essential for cell survival, especially in cancer tissue.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of 5-FU-associated cardiotoxicity is reported to be 1.4-4% of the overall population treated<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3,4</span></a> and 5-15% of those with known coronary artery disease (CAD).<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5,6</span></a> However, the incidence of acute coronary syndrome (ACS) has been reported as 22-36% in smaller observational studies.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1,7</span></a> Cardiotoxicity can manifest as ACS, angina, coronary dissection, cardiomyopathy, malignant arrhythmias or sudden death.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> Mortality from 5-FU-associated cardiotoxicity is significant, ranging from 2.2%<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> to 18%,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> with higher rates in cases of re-exposure to the drug.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Risk assessment in patients eligible for treatment with 5-FU and subsequent patient care are still not standardized. We present the case of a patient who suffered an ACS after beginning 5-FU treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">We report the case of a 60-year-old man, a former smoker (seven years’ abstinence), with hypertension and dyslipidemia. He had a history of colon adenocarcinoma seven years previously and had recently been diagnosed with advanced-stage adenocarcinoma of the duodenum. He was medicated with perindopril 5 mg daily, aspirin 100 mg daily and pitavastatin 2 mg daily as primary prevention, since there was no history of atherosclerotic disease in any vascular territory. Forty-eight hours before admission, he had begun a cycle of chemotherapy using the folinic acid, 5-FU and irinotecan (FOLFIRI) regimen. He was admitted with constricting retrosternal chest pain that began suddenly while at rest, radiating to the left arm and lasting more than 30 min. He reported no previous cardiovascular symptoms. At the time of admission he was still undergoing 5-FU infusion.</p><p id="par0025" class="elsevierStylePara elsevierViewall">On initial observation the patient was without pain, with blood pressure 124/74 mmHg, heart rate 72 bpm and 95% oxygen saturation in room air. Physical examination was unremarkable.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The electrocardiogram (ECG) performed in hospital triage (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>) showed sinus rhythm with ST segment depression of <1 mm in V1-V3 and T-wave inversion. The ECG performed 60 min after admission revealed dynamic repolarization changes with T-wave inversion in V4-V6 and in DII, DIII and aVF (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Laboratory tests showed elevated high-sensitivity troponin T sampled one hour after symptom onset (16 ng/l; reference value 14 ng/l) compatible with ongoing ACS, and no other relevant findings.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The echocardiogram showed a non-dilated and non-hypertrophied left ventricle with preserved ejection fraction and no wall motion abnormalities, diastolic parameters within normal ranges and non-dilated right chambers, with normal right ventricular free wall longitudinal strain.</p><p id="par0045" class="elsevierStylePara elsevierViewall">A diagnosis of acute non-ST-elevation myocardial infarction was assumed and antithrombotic therapy was begun. The 5-FU infusion was immediately suspended.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The patient remained in Killip class I, with peak troponin of 27 ng/l and GRACE score of 107. Invasive risk stratification by coronary angiography (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>) was performed 36 hours after symptom onset, which showed a very distal focal 80% lesion in the left anterior descending artery, 70% lesions in the first and second diagonals, a 90% stenosis in the distal circumflex artery, and diffuse disease of the proximal and mid right coronary artery with a 90% stenosis in the mid segment. Angioplasty of the right coronary and circumflex arteries was performed and XIENCE® 3.0×38 mm and Synergy® 2.24×20 mm drug-eluting stents, respectively, were implanted, with a good final angiographic result.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">This case report presents an ACS apparently triggered by 5-FU in a patient with previously unknown CAD. Although cardiotoxicity secondary to 5-FU is relatively well documented,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> there are several unanswered questions relating to pre-chemotherapy risk assessment and the optimal therapeutic strategy to adopt following a cardiotoxic event. As stated above, estimates of the incidence of ischemic events associated with 5-FU range from 1.4% to 36%, reflecting the heterogeneity of these studies. Existing heart disease is associated with more severe events,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> a finding that is common to all the studies published on this subject.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The pathophysiological mechanisms behind ACS associated with 5-FU are not fully understood. The most commonly accepted hypothesis is that endothelial injury induced by 5-FU decreases nitric oxide-dependent vasodilation, destabilizing atherosclerotic plaque with in-situ thrombus.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8,11</span></a> Besides infarction, electrocardiographic alterations suggestive of silent ischemia are observed in 68% of patients followed prospectively.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> The clinical significance of these alterations is unclear; they may reflect changes in coronary flow and predict clinical events.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a> The mode of the drug's administration affects the incidence of cardiotoxicity, the risk being higher with administration by infusion (7.6-18%) than by bolus (1.6-3%).<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3,5</span></a> Although there are more data on cardiotoxicity under 5-FU than under capecitabine, studies have reported that the level of risk is similar for both drugs.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1,6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Conventional cardiovascular risk factors are more often found in patients who suffer an acute ischemic event associated with 5-FU.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> On the basis of his known risk factors, the patient in the case presented had an intermediate risk for cardiovascular events as estimated by a Systematic Coronary Risk Estimation (SCORE)<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> of 3 on admission, and his pre-existing CAD was only discovered subsequently. The fact that the patient was completely asymptomatic prior to the acute event, and the time relation between symptom onset and mode of 5-FU administration, suggest the existence of a causal relationship.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Pre-chemotherapy screening for CAD in patients with cardiovascular risk factors, although logical, is neither mandatory nor standardized. Non-invasive anatomical assessment, such as by calculation of the Agatston score or cardiac computed tomography angiography, may be useful in patients eligible for 5-FU therapy by identifying those at greater risk for coronary events if exposed to the drug.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The reported incidence of ischemic events in patients treated with 5-FU is up to 36%, especially in those with CAD, and so the risk of such events should not be underestimated. These patients should be closely monitored for symptoms and may undergo continuous electrocardiographic monitoring to detect silent ischemia,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> which if confirmed may justify suspension of 5-FU therapy. The occurrence of symptoms should prompt a comprehensive assessment including ECG, biomarkers of myocardial necrosis, non-invasive ischemia testing and possibly coronary angiography.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Following diagnosis of an ACS, it is essential to stop 5-FU therapy. Recurrence after reintroduction of the drug is seen in 82-100% of cases,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> and mortality following reintroduction is also higher, with rates of around 18% reported.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> As the main mechanism is vasospasm, calcium channel blockers and nitrates are the preferred drugs and have been shown to be effective in observational studies.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> However, vasodilators are ineffective in preventing coronary vasospasm after the reintroduction of 5-FU,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> and their role in primary prevention is not well established. Treatment of ACS in this context is in other respects standard, although the impact of dual antiplatelet therapy on cancer management, as well as potential drug interactions, should be borne in mind.</p><p id="par0085" class="elsevierStylePara elsevierViewall">It is essential for cardiologists and oncologists to work closely together to decide on the safest and most effective therapeutic strategy. Decisions on cancer therapy are always complex, depending on the stage of the tumor and the patient's clinical characteristics, and discontinuing 5-FU is bound to make it more difficult to define an appropriate therapeutic plan. Capecitabine is also contraindicated after an ischemic event due to cross-reactions between drugs.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> Therapeutic regimens without fluoropyrimidines have been described, although they may not be as effective. Deboever et al. published an interesting review of alternatives to fluoropyrimidines in patients with documented cardiotoxicity.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">5-FU-associated cardiotoxicity is common, frequently manifesting as ACS or silent ischemia, especially in patients with documented CAD. It is thus important to standardize the assessment, monitoring and treatment of these patients. In those with cardiovascular risk factors, non-invasive screening for CAD, such as by calculation of the Agatston score or cardiac computed tomography angiography, may help improve patient selection, thereby reducing morbidity and mortality in this clinical scenario.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1270136" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1175481" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1270137" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1175482" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-02" "fechaAceptado" => "2017-04-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1175481" "palabras" => array:3 [ 0 => "5-Fluorouracil" 1 => "Angina pectoris" 2 => "Cardiotoxicity" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec1175482" "palabras" => array:3 [ 0 => "5-FU" 1 => "Angina pectoris" 2 => "Cardiotoxicidade" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">5-Fluorouracil (5-FU) is a first-line agent in several cancer therapy regimens. Cardiotoxicity is common, especially in patients with coronary artery disease. We report the case of an acute coronary syndrome presumably induced by 5-FU in a patient with previously unknown and asymptomatic corotabelnary artery disease and with an estimated intermediate risk for cardiovascular events. Pre-chemotherapy risk assessment and optimal patient care are still not standardized in this clinical scenario.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">O 5-flurouracilo é um agente de primeira linha no tratamento de várias neoplasias. Associa-se frequentemente a toxicidade cardíaca, particularmente em doentes com doença coronária. O caso apresentado ilustra uma síndrome coronária aguda presumivelmente precipitada por 5-FU, num doente com doença coronária previamente assintomática e desconhecida e com risco estimado de eventos cardiovasculares de nível intermédio. A avaliação de risco pré-quimioterapia e a melhor abordagem para a prevenção e manejo desse cenário clínico permanecem por definir.</p></span>" ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Félix-Oliveira A, Vale N, Madeira S, Mendes M. Síndrome coronária aguda em doente oncológico: um problema evitável?. Rev Port Cardiol. 2018;37:791.</p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The authors agree on and take responsibility for the present manuscript.</p>" "identificador" => "fn0005" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 482 "Ancho" => 1584 "Tamanyo" => 92792 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Electrocardiogram on admission (A) and 60 min later (B) (25 mm/s; 10 mm/mV).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 923 "Ancho" => 2334 "Tamanyo" => 223301 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) Left anterior descending artery with 80% stenosis; (B) distal circumflex artery with 90% stenosis; (C) final result of angioplasty on the circumflex artery; (D) right coronary artery with 90% stenosis in the mid segment; (E) final result of angioplasty on the right coronary artery.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0070" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluoropyrimidine-associated cardiotoxicity: revisited" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Saif" 1 => "M. Shah" 2 => "A. Shah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1517/14740330902733961" "Revista" => array:6 [ "tituloSerie" => "Expert Opin Drug Saf" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "191" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19309247" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0075" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alternative treatment options in colorectal cancer patients with 5-fluorouracil- or capecitabine-induced cardiotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Deboever" 1 => "N. Hiltrop" 2 => "M. Cool" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clcc.2012.09.003" "Revista" => array:6 [ "tituloSerie" => "Clinical Colorectal Cancer" "fecha" => "2013" "volumen" => "12" "paginaInicial" => "8" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23102544" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0080" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiotoxicity following different doses and schedules of 5-fluorouracil administration for malignancy – a survey of 427 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Tsavaris" 1 => "C. Kosmas" 2 => "M. Vadiaka" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Sci Monit" "fecha" => "2002" "volumen" => "8" "paginaInicial" => "51" "paginaFinal" => "57" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0085" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiotoxicity of de Gramont's regimen: incidence, clinical characteristics and long-term follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Meydan" 1 => "I. Kundak" 2 => "T. Yavuzsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jjco/hyi071" "Revista" => array:6 [ "tituloSerie" => "Jpn J Clin Oncol" "fecha" => "2005" "volumen" => "35" "paginaInicial" => "265" "paginaFinal" => "270" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15855175" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0090" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Schoeber" 1 => "E. Papageorgiou" 2 => "A. Harstrick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/1097-0142(19931001)72:7<2242::aid-cncr2820720730>3.0.co;2-e" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1993" "volumen" => "72" "paginaInicial" => "2242" "paginaFinal" => "2247" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8374883" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0095" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Kosmas" 1 => "M. Kallistratos" 2 => "P. Kopterides" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Cancer Res Clin Oncol" "fecha" => "2008" "volumen" => "134" "paginaInicial" => "75" "paginaFinal" => "82" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0100" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac toxicity of 5-fluorouracil: a study on 1083 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Labianca" 1 => "G. Beretta" 2 => "M. Clerici" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Tumori" "fecha" => "1982" "volumen" => "68" "paginaInicial" => "505" "paginaFinal" => "510" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7168016" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0105" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "5-fluorouracil induced cardiotoxicity: review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.F. Sorrentino" 1 => "J. Kim" 2 => "A.E. Foderaro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5603/cj.2012.0084" "Revista" => array:6 [ "tituloSerie" => "Cardiol J" "fecha" => "2012" "volumen" => "19" "paginaInicial" => "453" "paginaFinal" => "458" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23042307" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0110" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. de Forni" 1 => "M.C. Malet-Martino" 2 => "P. Jaillais" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.1992.10.11.1795" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1992" "volumen" => "10" "paginaInicial" => "1795" "paginaFinal" => "1801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1403060" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0115" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Rezkalla" 1 => "R. Kloner" 2 => "J. Ensley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.1989.7.4.509" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1989" "volumen" => "7" "paginaInicial" => "509" "paginaFinal" => "514" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2466960" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0120" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Capecitabine-induced cardiotoxicity: more evidence or clinical approaches to protect the patients’ heart?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Fontanella" 1 => "M. Aita" 2 => "M. Cinausero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/OTT.S65653" "Revista" => array:6 [ "tituloSerie" => "Onco Targets Ther" "fecha" => "2014" "volumen" => "7" "paginaInicial" => "1783" "paginaFinal" => "1791" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25302025" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0125" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Silent ischemia: clinical relevance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.R. Conti" 1 => "A.A. Bavry" 2 => "J.W. Petersen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2011.07.050" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2012" "volumen" => "59" "paginaInicial" => "435" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22281245" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0130" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Guidelines on Cardiovascular Disease Prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts), Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.F. Piepoli" 1 => "A.W. Hoes" 2 => "S. Agewall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehw106" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2016" "volumen" => "37" "paginaInicial" => "2315" "paginaFinal" => "2381" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27222591" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21742049/0000003700000009/v2_201911291446/S2174204918303076/v2_201911291446/en/main.assets" "Apartado" => array:4 [ "identificador" => "9919" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21742049/0000003700000009/v2_201911291446/S2174204918303076/v2_201911291446/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918303076?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 5 | 10 |
| 2024 October | 28 | 32 | 60 |
| 2024 September | 43 | 24 | 67 |
| 2024 August | 34 | 31 | 65 |
| 2024 July | 45 | 30 | 75 |
| 2024 June | 28 | 19 | 47 |
| 2024 May | 26 | 20 | 46 |
| 2024 April | 21 | 24 | 45 |
| 2024 March | 31 | 22 | 53 |
| 2024 February | 27 | 31 | 58 |
| 2024 January | 25 | 26 | 51 |
| 2023 December | 23 | 31 | 54 |
| 2023 November | 23 | 22 | 45 |
| 2023 October | 16 | 17 | 33 |
| 2023 September | 29 | 25 | 54 |
| 2023 August | 22 | 31 | 53 |
| 2023 July | 35 | 8 | 43 |
| 2023 June | 22 | 20 | 42 |
| 2023 May | 38 | 32 | 70 |
| 2023 April | 29 | 3 | 32 |
| 2023 March | 47 | 19 | 66 |
| 2023 February | 29 | 19 | 48 |
| 2023 January | 24 | 19 | 43 |
| 2022 December | 55 | 31 | 86 |
| 2022 November | 38 | 27 | 65 |
| 2022 October | 32 | 22 | 54 |
| 2022 September | 20 | 28 | 48 |
| 2022 August | 15 | 29 | 44 |
| 2022 July | 30 | 41 | 71 |
| 2022 June | 18 | 27 | 45 |
| 2022 May | 20 | 34 | 54 |
| 2022 April | 26 | 27 | 53 |
| 2022 March | 30 | 42 | 72 |
| 2022 February | 44 | 27 | 71 |
| 2022 January | 25 | 43 | 68 |
| 2021 December | 24 | 32 | 56 |
| 2021 November | 31 | 29 | 60 |
| 2021 October | 34 | 41 | 75 |
| 2021 September | 27 | 23 | 50 |
| 2021 August | 17 | 23 | 40 |
| 2021 July | 18 | 20 | 38 |
| 2021 June | 21 | 19 | 40 |
| 2021 May | 21 | 39 | 60 |
| 2021 April | 34 | 48 | 82 |
| 2021 March | 40 | 20 | 60 |
| 2021 February | 23 | 14 | 37 |
| 2021 January | 27 | 11 | 38 |
| 2020 December | 22 | 13 | 35 |
| 2020 November | 17 | 17 | 34 |
| 2020 October | 25 | 14 | 39 |
| 2020 September | 19 | 6 | 25 |
| 2020 August | 23 | 9 | 32 |
| 2020 July | 22 | 14 | 36 |
| 2020 June | 15 | 6 | 21 |
| 2020 May | 15 | 9 | 24 |
| 2020 April | 9 | 12 | 21 |
| 2020 March | 27 | 8 | 35 |
| 2020 February | 33 | 82 | 115 |
| 2020 January | 15 | 8 | 23 |
| 2019 December | 9 | 19 | 28 |
| 2019 November | 12 | 8 | 20 |
| 2019 October | 13 | 6 | 19 |
| 2019 September | 8 | 6 | 14 |
| 2019 August | 19 | 9 | 28 |
| 2019 July | 15 | 7 | 22 |
| 2019 June | 19 | 24 | 43 |
| 2019 May | 27 | 11 | 38 |
| 2019 April | 21 | 18 | 39 |
| 2019 March | 11 | 15 | 26 |
| 2019 February | 15 | 8 | 23 |
| 2019 January | 10 | 13 | 23 |
| 2018 December | 12 | 17 | 29 |
| 2018 November | 26 | 20 | 46 |
| 2018 October | 63 | 39 | 102 |
| 2018 September | 8 | 8 | 16 |
Show all
