Cintigrafia de Perfusão Miocárdica no Enfarte do Miocárdio: Impacto da elevação do segmento ST e da Diabetes mellitus

1 2020/2021 João Miguel Portugal Antas de Barros Barbosa Myocardial Perfusion Scintigraphy in Myocardial Infarction: Impact of ST segment elevation and of Diabetes mellitus Cintigrafia de Perfusão Miocárdica no Enfarte do Miocárdio: Impacto da elevação do segmento ST e da Diabetes mellitus MARÇO, 2021 2 MARÇO, 2021 Mestrado Integrado em Medicina Área: Medicina Nuclear Tipologia: Original Report Trabalho efetuado sob a Orientação de: Prof. Doutor José Pedro Lopes Nunes Trabalho organizado de acordo com as normas da revista: Journal Of Investigative Medicine João Miguel Portugal Antas de Barros Barbosa Myocardial Perfusion Scintigraphy in Myocardial Infarction: Impact of ST segment elevation and of Diabetes mellitus Cintigrafia de Perfusão Miocárdica no Enfarte do Miocárdio: Impacto da elevação do segmento ST e da Diabetes mellitus i DECLARAÇÃO DE INTEGRIDADE ii DECLARAÇÃO DE REPRODUÇÃO iii DEDICATÓRIA Há poucos anos atrás, decidi mudar de rumo, pessoal e profissionalmente. Naquilo que foi o ano mais difícil da minha vida até então, a morte do meu Avô materializou a enorme lacuna que existia no meu conhecimento da saúde humana. Até aí, tinha explorado o mundo laboral, munido do meu curso anterior – Ciências Farmacêuticas – chegando, então, à conclusão de que a minha influência na saúde do paciente teria que ser mais interventiva e mais capaz. Esta escolha levou-me à Faculdade de Medicina da Universidade do Porto. Os últimos 5 anos constituíram uma trajetória para a qual, isolado, seria sempre insuficiente. Consegui completá-la precisamente por não estar sozinho, devendo por isso agradecer e dedicar o presente trabalho: Ao Professor Doutor José Pedro Nunes, pela assídua, sábia e amável orientação durante o curso no geral, e durante a elaboração deste trabalho em particular; À minha família – em especial aos meus Pais e irmãos – por todo o apoio incondicional que me deram ao longo da minha vida; À minha Avó Maria da Graça, ao meu Avô João, e à minha Avó Nina, por me ensinarem a procurar ser sempre superior a mim mesmo; Ao Dr. Jorge Pereira, à Dra. Emília Barbosa, e à Dra. Luciana Pereira, pela importante contribuição na execução deste trabalho; Ao Armindo e à Lab52, pelo mundo de oportunidades que me ofereceram, e pela certeza que tiveram no meu improvável sucesso; À Margarida d’ “O Farol”, pela confiança que depositou em mim; Aos meus amigos, em especial aos LCR e ao Almirante, pela inabalável amizade com que me brindam todos os dias; Por fim, à Teresinha, pelo tempo, pelas palavras, pelos atos, pela (imérita) fé em mim e por tudo o que me deu, que qualquer texto será insuficiente para enumerar; Nas palavras do meu antepassado Manoel de Portugal Marreca, formado pela Escola Médico-cirúrgica do Porto em 1902, “este trabalho, […] um thesoiro que fosse, a vós pertenceria”. 1 ORIGINAL REPORT MYOCARDIAL PERFUSION SCINTIGRAPHY IN MYOCARDIAL INFARCTION - IMPACT OF ST SEGMENT ELEVATION AND OF DIABETES MELLITUS. João Miguel Portugal Antas de Barros Barbosa Rua do Padrão, 32, 2º Direito 4150-557 Porto Portugal [email protected] Word count (excluding title page, abstract, references, figures and tables): 2049 2 ABSTRACT Myocardial perfusion scintigraphy (MPS) is frequently used in the evaluation of patients with myocardial infarction (MI). The goal of the present work was to evaluate changes in MPS according to the nature of the infarction (ST elevation versus non-ST elevation status) as well as according to the presence or absence of Diabetes mellitus. A prospective study of 124 consecutive patients with MI was carried out, using MPS. Patients with ST segment elevation MI (STEMI) had significantly larger values both for percentage and absolute areas of perfusion defects, both at rest and in stress situation, when compared to patients without ST segment elevation (NSTEMI). These patients had significantly lower values for left ventricular ejection fractions (EF), in a similar comparison. The values for perfusion defects at rest for STEMI patients were more than double the values for NSTEMI patients (17.1+14.6% versus 6.5+7.8%, p <0.001). Concerning resting left ventricular EF, STEMI patients had a mean value of 47.6+13.6% and NSTEMI patients had a mean value of 53.2+12.4% (p 0.026). Regarding the comparison between patients with and without Diabetes mellitus, none of the parameters under study showed significant differences. Linear regression analysis, taking percentage of perfusion defect, as dependent variable, yielded an overall significant result, however only ST segment elevation was shown to have an individually significant result. We conclude that the presence of ST segment elevation but not the presence of Diabetes mellitus is associated to different patterns of MPS in patients with MI. What is already known about this subject? Acute myocardial infarction (MI) poses as a significant cause of death and morbidity. Myocardial perfusion scintigraphy (MPS) is frequently used in the evaluation of patients with MI. Specific electrocardiographic findings and risk factors lack correlation with MPS results. 3 What are the new findings? The goal of the present work was to evaluate specific changes in MPS according to the nature of the infarction (ST elevation versus non-ST elevation status) as well as according to the presence or absence of Diabetes mellitus. The presence of ST segment elevation was associated to different patterns of MPS in patients with MI. The presence of DM was not associated either to differences in importance of perfusion defects or in the values of left ventricular ejection fraction. How might these results change the focus of research or clinical practice? The presence of ST segment elevation in the electrocardiogram was shown to be associated to a decreased cardiac contractility and to an increased perfusion defect, when compared to the absence of this electrocardiographic feature. Therefore, the present paper translates an important and innovative correlation of the presence of ST segment elevation and the myocardial damage extent. Key words: myocardial perfusion scintigraphy, myocardial infarction, Diabetes mellitus 4 INTRODUCTION Acute myocardial infarction (MI) poses as a significant cause of death and morbidity 1,2, and is defined as the loss of functional cardiac tissue, due to a cardiac ischemic event 1. Although the incidence of this type of event has declined steadily over the last decades, it still affects about 7 million individuals around the world annually, of which many occur in Europe, with the economic issues it entails 3. Risk factors for MI include male gender, smoking, arterial hypertension, dyslipidaemia, Diabetes mellitus and obesity, among others 1,4,5. MI can have different causes and be characterized in very different ways. One of the most used classifications is based on the presence of an elevation of the STsegment in the electrocardiogram (ECG), thus allowing us to categorize the event as acute myocardial infarction with ST-segment elevation (STEMI) or without STsegment elevation (NSTEMI) 1,3. Furthermore, the fourth universal classification of MI takes into account aetiology and clinical differences, and is divided into 6 types: type 1 (due to atherosclerotic plaque rupture), type 2 (due to a mismatch between supply and demand), type 3 (causing sudden death), type 4 (a - if related with percutaneous coronary intervention, PCI - and b - if related with thrombosis of a coronary stent), and type 5 (related with coronary artery bypass grafting, CABG) 1. Regarding MI presentation and diagnosis, although up to 40% of all MI are unrecognized in assessment through ECG upon admission 6, first line MI diagnosis relies primarily on ECG findings, such as the already mentioned ST-segment elevation, together with symptoms and physical exam 3,4. Second line diagnosis concerns biochemical findings, namely cardiac troponin elevation (CT), a biomarker that is elevated in this context, allowing an early confirmation, as it presents high sensitivity for myocardial necrosis 3,4. In the study of patients with suspected or confirmed ischaemic heart disease (e.g. on the aftermath of an MI), patients are frequently required to perform a myocardial perfusion scintigraphy (MPS), to assess ischemic areas of the heart, and potential loss of cardiac function 7-9. MPS relies on the differential uptake of a radioisotope by the cardiac tissue, with further quantification/imaging, thus resulting in a myocardial perfusion map 1,8,9. Decreased perfusion in certain cardiac areas (shown as one or more perfusion defects) can result from the narrowing of one of 11 DISCUSSION In the present report, MPS data obtained in patients with a previous MI were under study. The presence of ST segment elevation in the electrocardiogram was shown to be associated to a decreased cardiac contractility and to an increased perfusion defect, when compared to the absence of this electrocardiographic feature. The presence of ST segment elevation in patients with MI is frequently associated to the presence of a coronary artery thrombus in the acute setting 11,12. Patients with MI with no elevation of the ST segment are believed usually not to have coronary artery thrombotic acute occlusion 13. MI is a known health and economic burden, and is associated with risk factors such as obesity, hypertension and Diabetes mellitus. MI can often lead to tissue and functional changes in the heart, which may be evaluated through MPS. As a functional imaging technique, MPS is widely used, in ischemic heart disease assessment and prognosis. Regarding Diabetes mellitus, current literature indicates that this condition is a risk factor for coronary artery disease (CAD), due to its association with greater and more significant vascular disease 10. A previous report showed that when STEMI and NSTEMI patients were compared, the former was associated to higher mean values of troponin release, however no differences were seen in the angiographic importance of CAD 14. This lack of correlation between the apparent importance of myocardial necrosis and the importance of CAD may be an explanation for the present results concerning patients with Diabetes mellitus. These latter patients are known to often have diffuse coronary artery disease 15, however the present results show that the presence of this clinical condition is not associated either to differences in importance of perfusion defects or in the values of left ventricular ejection fraction. Limitations The number of patients is relatively small, limiting the power of the conclusions reached. All consecutive patients with a diagnosis of MI were under study, regardless of MI type or date of the event. Additionally, post-event revascularization procedure, as well as medication information, were not included in data collection, and could influence MPS data. 12 CONCLUSIONS We conclude that the presence of ST segment elevation but not the presence of Diabetes mellitus is associated to different patterns of MPS in patients with MI. The presence of ST segment elevation in the electrocardiogram was shown to be associated to a decreased cardiac contractility and to an increased perfusion defect, when compared to the absence of this electrocardiographic feature. CONFLICT OF INTEREST The author certifies that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. FUNDING No funding received for this report. 13 REFERENCES 1. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;72:2231-64. 2. Lobo MF, Azzone V, Azevedo LF, et al. A comparison of in-hospital acute myocardial infarction management between Portugal and the United States: 2000– 2010. International Journal for Quality in Health Care 2017;29:669-78. 3. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet 2017;389:197-210. 4. Anderson JL, Morrow DA. Acute Myocardial Infarction. N Engl J Med 2017;376:2053-64. 5. Dzubur A, Gacic E, Mekic M. Comparison of Patients with Acute Myocardial Infarction According to Age. Med Arch 2019;73:23-7. 6. Dorr M. Silent myocardial infarction: the risk beyond the first admission. Heart 2010;96:1434-5. 7. Nudi F, Biondi-Zoccai G, Schillaci O, et al. Prognostic accuracy of myocardial perfusion imaging in octogenarians. J Nucl Cardiol 2018;25:1342-9. 8. Notghi A, Low CS. Myocardial perfusion scintigraphy: past, present and future. Br J Radiol 2011;84 Spec No 3:S229-36. 9. Ziessman H, O'Malley J. Nuclear Medicine: The Requisites. 4th ed2013. 10. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction. New England Journal of Medicine 1998;339:229-34. 11. Fröbert O, Lagerqvist B, Olivecrona GK, et al. Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction. New England Journal of Medicine 2013;369:1587-97. 12. Meneguz-Moreno RA, Costa RA, A A, Ribamar Costa J, Jr., Abizaid A. Thrombus aspiration in ST-segment elevation myocardial infarction. Minerva Cardioangiol 2015;63:563-75. 13. Mizuno K, Satomura K, Miyamoto A, et al. Angioscopic Evaluation of Coronary-Artery Thrombi in Acute Coronary Syndromes. New England Journal of Medicine 1992;326:287-91. 14 14. Nunes JPL, Faria Mdo S, Garcia JM, Gonçalves FR. Glomerular filtration rate and coronary artery disease burden in patients with acute coronary syndrome. Clin Cardiol 2007;30:464-8. 15. Jin C, Lu L, Zhang RY, et al. Association of serum glycated albumin, Creactive protein and ICAM-1 levels with diffuse coronary artery disease in patients with type 2 diabetes mellitus. Clinica Chimica Acta 2009;408:45-9. 15 TABLES Table 1.⎯ Descriptive statistics for the variables collected in 124 patients with myocardial infarction. N – number; STD – standard deviation. PShown are levels of significance, Mann-Whitney U test, when patients with or without Diabetes mellitus and patients with or without ST segment elevation are compared, respectively. Total number of patients 124 Male/ female N (%) 94 (75.8%)/ 30 (24.2%) Age, years (Mean+ STD) Overall Patients without Diabetes mellitus (n=78) Patients with Diabetes mellitus (n=46) Patients with STEMI (n=58) Patients with NSTEMI (n=66) 68.2±11.4 67.8±12.1 68.9±10.0 (p=0.51) 66.7±10.0 69.5±12.4 (p=0.19) Age, range (years) 36 – 93 Age group, years (n) 30-49 50-69 70-89 Over 90 6 67 48 3 Table 2.⎯ Data from myocardial perfusion scans in 124 patients with myocardial infarction (MI), according to ST elevation status (Mean + standard deviation). EF – left ventricular ejection fraction. PPD – Percentage of perfusion defect. APD - Area of perfusion defect. Pprobability, Mann Whitney U test. N - number. ST segment elevation MI N=58 Non-ST segment elevation MI N=66 p EF/ rest 47.6+13.6 53.2+12.4 0.026 EF/ stress 46.8+13.5 51.7+12.0 0.047 PPD/ rest (%) 17.1+14.6 6.5+7.8 <0.001 PPD/ stress (%) 21.3+14.7 11.3+9.2 <0.001 APD/ rest (cm2) 26.18+26.68 9.39+12.87 <0.001 APD/ stress (cm2) 32.90+28.18 15.53+14.58 <0.001 16 Table 3⎯ Data from myocardial perfusion scans in 124 patients with myocardial infarction (MI), according to presence or absence of Diabetes mellitus (Mean + standard deviation). EF – left ventricular ejection fraction. PPD – Percentage of perfusion defect. APD - Area of perfusion defect. Pprobability, Mann Whitney U test. N - number. No Diabetes mellitus N = 78 Diabetes mellitus N= 46 p EF/ rest (%) 50.7+13.8 50.4+12.3 0.63 EF/ stress (%) 49.7+13.9 49.9+11.1 0.38 PPD/ rest (%) 11.6+12.6 11.1+12.8 0.75 PPD/ stress (%) 16.1+12.9 15.8+13.4 0.75 APD/ rest (cm2) 18.0+23.3 15.9+19.9 0.65 APD/ stress (cm2) 24.2+24.4 22.8+22.3 0.76 Table 4⎯ Linear regression analysis, taking percentage of perfusion defect (at rest) as dependent variable and several independent variables, as measured in 124 patients with myocardial infarction. Psignificance level. Dependent variable - percentage of perfusion defect, at rest. Overall ANOVA p - <0.001 p Age 0.50 Gender 0.11 ST segment elevation <0.001 Diabetes mellitus 0.21 Arterial hypertension 0.12 Dyslipidemia 0.27 Left bundle branch block 0.42 Type 2 myocardial infarction 0.82 17 ANEXO 1 – NORMAS DE PUBLICAÇÃO NO JOURNAL OF INVESTIGATIVE MEDICINE BMJ Journals Formatting your paper These are general formatting guidelines across BMJ, please always refer to journalspecific instructions for authors for article type specifications. You can browse the titles on our Journals website. You can also refer to our formatting checklist to make sure you have covered everything on submission. Title page The title page must contain the following information: Title of the article Full name, postal address and e-mail of the corresponding author Full name, department, institution, city and country of all co-authors Word count, excluding title page, abstract, references, figures and tables Keywords Authors can usually opt to (or are required to) choose keywords relevant to the content of the manuscript during the submission process. This assists in the identification of the most suitable reviewers for the manuscript. The selected keywords should also be included in the abstract itself. Authors and Institutions On submission of your article through our submission system you will be asked to provide a name, email address and institutional affiliation for all contributing authors. In the final published article author names, institutions and addresses will be taken from these completed fields and not from the submitted Word document. Refer to the BMJ policy on authorship for more information. 18 Manuscript format The manuscript must be submitted as a Word document (BMJ Case Reports and Veterinary Record Case Reports request that authors submit using a template which should also be in Word format). PDF is not accepted. The manuscript should be presented in the following order: Title page Abstract, or a summary for case reports (Note: references should not be included in abstracts or summaries) Main text separated under appropriate headings and subheadings using the following hierarchy: BOLD CAPS, bold lower case, Plain text, Italics Tables should be in Word format and placed in the main text where the table is first cited. Tables should also be cited in numerical order Acknowledgments, Competing Interests, Funding and all other required statements References. All references should be cited in the main text in numerical order We have added a “submission prefill” tool to all of our journals, which typically reduces time taken to submit a paper by 25 percent. Just upload your manuscript and the system will automatically extract and populate the following submission fields: Title, Abstract, Authors, Institutions, Funders. Figures must be uploaded as separate files (view further details under the Figures/illustrations section). All figures must be cited within the main text in numerical order and legends should be provided at the end of the manuscript. Online Supplementary materials should be uploaded using the File Designation “Supplementary File” on the submission site and cited in the main text. Please remove any hidden text headers or footers from your file before submission. Style Acronyms and abbreviations should be used sparingly and fully explained when first used. Abbreviations and symbols must be standard. SI units should be used throughout, except for blood pressure values which should be reported in mm Hg. 19 Whenever possible, drugs should be given their approved generic name. Where a proprietary (brand) name is used, it should begin with a capital letter. To ensure a consistent approach, submitted articles should not include Trademark or Registered trademark symbols in the main text, tables or figures. Figures and illustrations Images must be uploaded as separate files. All images must be cited within the main text in numerical order and legends must be provided (ideally at the end of the manuscript). Video: How to improve your graphs and tables Journal of Investigative Medicine: Submission Guidelines for Original research Original research should not exceed 5,000 words and six figures or tables (not including supplementary material) — articles must be fully documented reports of original research but should be as concise as possible without compromising the data. Articles should be organized as follows: Title page, Unstructured Abstract (250 words max), Introduction, Materials & Methods, Results, Discussion, Conflict of Interest, Acknowledgments, References, Tables, Figure Legends, Supplementary Material. The abstract should be followed by three sentences which outline the significance of the study: What is already known about this subject? What are the new findings? How might these results change the focus of research or clinical practice? Please include a box summarizing in three or four bullet points “what are the new findings?”. 20 ANEXO 2 – REPORTING GUIDELINES PARA ESTUDOS OBSERVACIONAIS DE COORTE (EQUATOR NETWORK) STROBE Statement—Checklist of items that should be included in reports of cohort studies Item No Recommendation Page No Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract; (b) Provide in the abstract an informative and balanced summary of what was done and what was found; “A prospective study of 124 consecutive patients with MI was carried out, using MPS”. 2 “Patients with ST segment elevation MI (STEMI) had significantly larger values both for percentage and absolute areas of perfusion defects, both at rest and in stress situation, when compared to patients without ST segment elevation (NSTEMI)”. 2 Introduction Background/rationale 2 Explain the scientific background and rationale for the investigation being reported “MPS relies on the differential uptake of a radioisotope by the cardiac tissue, with further quantification/imaging,...”. 4 Objectives 3 State specific objectives, including any prespecified hypotheses “The goal of the present work was to evaluate specific changes in MPS according to the nature of the infarction (ST elevation versus non-ST elevation status) as well as according to the presence or absence of Diabetes mellitus”. 5 Methods Study design 4 Present key elements of study design early in the paper “The present study was a prospective, longitudinal study”. 6 Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection “Patients enrolled in the project were given a written version of the protocol for a full evaluation, and later signed an informed consent form, prior to data collection. Inclusion criteria involved: age greater than 18, indication for MPS from September 2019February 2020 (inpatient or outpatient), and a history of MI”. 6 Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up (b) For matched studies, give matching criteria and number of exposed and unexposed “Inclusion criteria involved: age greater than 18, indication for MPS from September 2019February 2020 (inpatient or outpatient), and a history of MI”. 6