Concurrent Acute Myocardial Infarction and Acute Ischemic Stroke in a Diabetic Patient Undergoing Chemotherapy for Non-Hodgkin Lymphoma:Should I administer thrombolytic therapy? A Case Report

Concurrent Acute Myocardial Infarction and Acute Ischemic Stroke in a Diabetic Patient Undergoing Chemotherapy for Non-Hodgkin Lymphoma:Should I administer thrombolytic therapy? 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A Case Report Sigfrid Casmir Shayo, Khuzeima Khanbai, Yona Gandye, Nakigunda Kiroga, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4628795/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Concurrent ST-elevation myocardial infarction (STEMI) and acute ischemic stroke (AIS) are extremely rare, and their management remains perplexing due to the absence of high-quality evidence and limited resources. For the first time, we report a rare, preventable and suboptimallymanaged case of concurrent AIS and STEMI in a patient with non-Hodgkin lymphoma (NHL) who received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy. Case Presentation A postmenopausal woman of African origin with a background history of type 2 diabetes mellitus presented to the Jakaya Kikwete Cardiac Institute with sudden onset of left-sided weakness and typical ischemic chest pain for 3 days. The patient was recently diagnosed with NHL and started CHOP chemotherapy 3 weeks prior. Physical examination revealed left-sided hemiplegia. Emergency brain computed tomography (CT) and 12-lead echocardiography (ECG) revealed AIS and STEMI, respectively. A diagnosis of concurrent AIS and STEMI was reached, and the patient was loaded with dual antiplatelets and heparin and rushed for emergency coronary angiography (GAG) and percutaneous coronary intervention (PCI). CAG revealed massive thrombotic occlusion of the mid-segment of the left anterior descending coronary artery (mLAD) and proximal segment of the right coronary artery. Revascularization was achieved in both vessels with a resultant TIMI flow grade of 3. The post-PCI period was marked bysignificant improvement inchest pain and resolution of ST-elevation, as revealed by 12-lead ECG. However, the patient remained hemiplegic. Conclusion We have described a rare case of concurrent AIS and STEMI in a postmenopausal woman who had a significant risk of thromboembolism. The patient had uncontrolled type 2 diabetes and received CHOP chemotherapy for NHL, which was diagnosed 3 weeks prior. This case underscores the need for thromboembolic prophylaxis for selected cancer patients receiving chemotherapy. The need to individualize management is also emphasized,as both PCI and thrombolysis carry therisk of serious repercussions. In our patient, if thrombolysis was attempted it would have caused myocardial ruptureand immediate death. The patient would have benefited from endovascular mechanical embolectomy for AIS;however, this practice is lacking at our institution. This calls for the establishment and strengthening of neurointerventional practices in our tertiary healthcare facilities. Cardiac & Cardiovascular Systems Ischemic Stroke ST-Elevation Myocardial Infarction Cerebral Infarction CHOP Chemotherapy Percutaneous Coronary Intervention Thrombolysis Endovascular Mechanical Embolectomy Figures Figure 1 Figure 2 Figure 3 Background There has been an alarming global increase in the incidence of cardiovascular disease and its traditional risk factors, particularly in middle- and low-income countries. 1 Traditional risk factors for cardiovascular disease include visceral obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), and smoking. All of these factors orchestrate chronic systemic low-grade inflammation that is responsible for atherosclerosis of coronary, cerebral, and peripheral arteries, which is referred to as atherosclerotic cardiovascular disease (ASCVD). 2 , 3 Acute myocardial infarction (AMI) and stroke are the two major vascular events with a significant toll on healthcare expenditure, quality-adjusted life years, morbidity, and mortality.4 These catastrophic vascular events share common triggering factors, including oxidative stress, inflammation, and endothelial dysfunction(s) 5 . Although these events share important risk factors as well as triggering factors, concurrent AMI and AIS are rare findings. In 2010, Omar and his colleagues used the term cardio-cerebral infarction to refer to simultaneous AMI and AIS. The incidence of cardio-cerebral infarction is reported to be as low as 0.009%. 6,7 There has never been a reported case of concurrent AIS and AMI occurring in a patient who received cancer chemotherapy, specifically CHOP chemotherapy. We present a rare, preventable and suboptimally managed case of concurrent AIS and AMI occurring in a postmenopausal woman who received chemotherapy for NHL. Case Presentation A 59-year-old postmenopausal woman with a 5-year history of type 2 diabetes mellitus presented to the Jakaya Kikwete Cardiac Institute with sudden onset of left-sided weakness and excruciating chest pain that had worsened over 3 days. The patient was recently diagnosed with non-Hodgkin lymphoma and started chemotherapy with CHOP 3 weeks prior. She denied prior hypertension or heart disease but reported using a menopausal supplement. Physical examination revealed a conscious patient who experienced chest pain with left-sided hemiplegia but no facial asymmetry or aphasia. She was hemodynamically stable with unremarkable vital signs. An emergency CT scan revealed early ischemic stroke features (figure 1a), which were later confirmed by a follow-up CT scan showing an extensive infarct (figure 1b). A 12-lead ECG showed significant ST-segment elevation in the inferior leads, i.e., leads II, III, and aVF, with reciprocal changes in leads I and aVL. There was also some ST-segment elevation in leads V5 and V6 (Figure 2). Blood tests revealed markedly elevated troponin I, c-reactive protein (CRP), glycated hemoglobin (HbA1c), and random blood glucose (RBG). A diagnosis of concurrent acute myocardial infarction (AMI) and acute ischemic stroke (AIS) was made. The patient was loaded with clopidogrel, aspirin, and atorvastatin and prepared for emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI). CAG revealed total thrombotic occlusion of the mid-segment of the left anterior descending coronary artery (mLAD) (figure 3a) and proximal segment of the right coronary artery (pRCA) (figure 3b). Balloon angioplasty of the mLAD and stenting of the pRCA were successfully carried out. TIMI flow grade 3 was achieved in both vessels (figure 3c, figure 3d). The patient developed ventricular fibrillation during coronary angiography, which was treated with defibrillation, but later developed bradycardia requiring temporary pacing. Following PCI, she was admitted to the coronary care unit (CCU) and received anticoagulation therapy. Her chest pain improved, but she developed a throbbing headache on the third day, which was ruled out as hemorrhagic transformation of the ischemic stroke (figure 1b). She was transferred to the high dependency unit (HDU) and continued on dual antiplatelet therapy, heparin, furosemide, and atorvastatin. She showed remarkable improvement and was discharged after 9 days in the hospital. 12-lead ECG done before the patient was discharged showed normal sinus rhythm with complete resolution of ST-segment elevation. Echocardiography revealed ischemic cardiomyopathy with reduced left ventricular systolic function (LVEF=34%). At discharge, the patient had stable vital signs but residual left-sided hemiplegia. She was advised to continue dual antiplatelet therapy, rivaroxaban, and metformin-glimepiride combination therapy and was scheduled to visit a neurology clinic. Her oncology team planned to continue chemotherapy after her discharge from the hospital. Discussion and Conclusions To the best of our knowledge, this is the first case of concurrent AMI and AIS following diagnosis of NHL and initiation of chemotherapy. According to the American Society of Hematology, the diagnosis of cancer increases the incidence of stroke and AMI. Patients with incident cancer have a substantially short-term risk of arterial thromboembolism. 8 This situation is further aggravated by the use of certain chemotherapies, such as doxorubicin, which have been shown to also increase the risk of thromboembolism. 9 Our patient had received CHOP chemotherapy with doxorubicin as one of the components approximately three weeks prior to the onset of acute cardio-cerebral infarction. As the patient’s symptoms and worsening health conditions are linked with the initiation of chemotherapy, it is more likely that in addition to uncontrolled T2DM, the initiation of chemotherapy might have contributed to acute cardio-cerebral infarction. Antithrombotic therapy is generally recommended for the prevention of both arterial and venous thromboembolism in high-risk cancer patients, particularly those treated with chemotherapy. 10 In contrast, our patient did not receive a single antiplatelet or anticoagulant prior to having a cardio-cerebral infarction. Therefore, there is a need to increase awareness among oncologists about the risk of thrombosis among cancer patients with comorbidities undergoing chemotherapy. It is worth recognizing that inflammation is at the heart of vascular endothelial dysfunction and thromboembolism. Our patient had a remarkably elevated high-sensitivity CRP (106 mg/dL) but a normal CBC at presentation. Her HbA1c and RBG levels were 11.76% and 18 mmol/L, respectively, indicating poorly controlled T2DM. This finding suggested that sterile inflammation induced by danger-associated molecular patterns (DAMPs) from killed cancer cells as well as uncontrolled T2DM contributed to the occurrence of arterial thrombosis. The diagnosis of cardio-cerebral infarction exerts significant decision-making pressure on attending clinicians. This is because urgent action is needed to restore perfusion to the myocardium as well as the brain. Concurrent AMI and AIS are very rare clinical conditions for which there is no high-quality evidence or clinical guidelines for management. This patient landed on the best facility for cardiovascular care in the country with a state-of-the art catheterization laboratory and highly experienced interventional cardiologists. We were therefore biased to serve the myocardium first. According to the European Society of Cardiology 2023 guidelines for the management of acute coronary syndrome (ACS), an invasive strategy should be undertaken to reperfuse the myocardium in cancer patients presenting with ACS with an expected survival of > 6 months. 11 The decision to perform PCI in this patient was reached but with significant worries about hemorrhagic transformation following the administration of anticoagulation and a high dose of dual antiplatelets, which is a requirement for performing PCI. Although the patient did not develop hemorrhagic transformation of the AIS, the infarct size increased, and she remained hemiplegic. Owing to the risk of myocardial rupture, our patient was not eligible for thrombolytics that would concurrently help to reperfuse the brain and myocardium. The patient would likely benefit from endovascular mechanical embolectomy for AIS; however, this practice is lacking at our institution. This calls for the establishment and strengthening of neurointerventional practices in our tertiary hospitals. Upon discharge, the patient presented with hemiplegia, remained hemodynamically stable, and exhibited a significant reduction in left ventricular systolic function (EF = 34%). Two days later, she proceeded with the second cycle of chemotherapy. The patient's prognosis is guarded, with favorable outcomes reliant upon patient-centered multidisciplinary collaboration among oncologists, cardiologists, and neurologists. Additionally, the patient's ability to cover healthcare expenses and adhere to prescribed therapy is crucial. In conclusion, heightened awareness is necessary among oncologists regarding the importance of administering prophylactic antithrombotic medications to high-risk newly diagnosed cancer patients undergoing chemotherapy due to the increased risk of arterial thrombosis. Managing cardio-cerebral infarction in patients with comorbidities poses significant challenges, particularly in resource-limited settings. In the absence of robust evidence and guidelines, treatment approaches must be highly individualized. Thus, it is imperative to establish and maintain advanced multidisciplinary practices and foster collaboration among experts to achieve optimal treatment outcomes. Abbreviations CHOP- Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone ASC-Acute coronary syndrome AIS-Acute Ischemic Stroke AMI-Acute Myocardial Infarction STEMI-ST-elevation myocardial infarction CAG-Coronary Angiography PCI- Percutaneous coronary intervention CT-Computed Tomography ECG-Electrocardiography TIMI-Thrombolysis in Myocardial Infarction T2DM-Type 2 Diabetes Mellitus ASCVD- atherosclerotic cardiovascular disease LAD-Left anterior descending coronary artery RCA- Right coronary artery CCU-Coronary Care Unit LVEF-Left ventricular ejection fraction DAMP-Damage-Associated Molecular Patterns CRP- C-reactive protein CBC-complete blood count RBG-Random blood glucose HbA1c- Glycated hemoglobin Declarations Ethical approval and consent to participate Not applicable Consent for Publication Written informed consent was obtained from the patient for their anonymized information to be published in this article. Availability of data and materials Not applicable Competing interests The authors declare that they have no competing interests. Funding Not applicable Author Contributions SCS took history, performed physical examination and cardiac imaging, FL helped in the acquisition and interpretation of brain CT scan images, KK, YG, TW, and PK performed coronary angiography/percutaneous coronary intervention and contributed to the acquisition and interpretation of associated data, SCS, KK, YG, NK, and PK participated in clinical management and counseling of the patient during hospitalization, and SCS wrote the initial draft of the manuscript. All authors reviewed and contributed to the final version of this case report. Acknowledgment The authors would like to express their heartfelt gratitude to the patient and her caring daughter for their cooperation toward publication of this important work. References Koon KT, Talha R. Cardiovascular Risk Factors and Prevention; A Perspective from Developing Countries.CJC 2021,37:733-743.http://doi.org/10.1016/j.cjca.2021.02.009 Daniel GH,Sonia SA.Emerging Risk Factors for Atherosclerotic Vascular Disease; A critical overview of evidence.JAMA 2003(7):932-940.doi:10.1001/jama.290.7.932 Libby P, Buring JE, Badimon L, et al.Atherosclerosis. Nat Rev Dis Primers 2019, 5,56. https://doi.org/10.1038/s41572-019-0106-z Thomas AG. Reducing the Growing Burden of Cardiovascular Disease in Developing World. Health Aff (Millwood) 2007,26(1):13-24. https://doi.org/10.1377/hlthaff.26.1.13 Partha D, Gabriel C, Ying W, et al. Myocardial Infarction accelerates atherosclerosis. Nature 2012, 487(7407): 325-329.doi:10.1038/nature11260. Omar HR, Fathy A, Rashad R, et al. Concommitant acute right ventricular infarction and ischemic cerebrovascular stroke; possible explanations.Int Arch Med 2010, 3:25. doi:10.1186/1755-7682-3-25 Yeo L, Andersson T, Yee KW, et al. Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first. J Thromb Thrombolyisis 2017, 44(1):104-111. doi:10.1007/s11239-017-1484-2. Navi BB, Reiner AS, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. Jam Coll Cardiol 2017; 70(8): 926-938. doi:10.1016/j.jacc.2017.06.047. Haichen Lv, Roupeng T, Jiawei L, et al. Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function.Am J Physiol Heart Circ Physiol2020,319: H133-H143.doi:10.1152/ajpheart.00456.2019. Falanga A, Leader A, Ambaglio C, et al. EHA guidelines on management of antithrombotic treatment in thrombocytopenic patients with cancer. HemaSphere 2022, 6(8): e 750.doi:10.1097/HS9.0000000000000750. ESC. 2023 ESC Guidelines for Management of Acute Coronary Syndromes. European Heart Journal 2023, 44:3720-3826. https://doi.org/10.1093/eurheartj/ehad191 Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4628795","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":318192049,"identity":"a034f01f-2a3e-4747-8b98-8edacd40557d","order_by":0,"name":"Sigfrid Casmir Shayo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACCSjJ3sDYIPGBgSGBeC08BxgbJGeQoIUBqIWBQZqHGC3ys5ufSXz4Y2HXI3248bZtm10eP9CJHz7m4NZicOeYmeTMNonkHr7EZuvctuRiyZ4DzJIzt+HRIpFgJs3bIJFsz8PYJp3bxpy44UYCGzMvHi3yM9K/SfP8kUjmAWmxbKsnrIXhRo6ZNA+bhB1YC2PbYcJaDG7kFFsC/ZIA1NJs2XPueOLMnoPNeP0CdNjGGx/+1Nnz8LA/vPGjrDqxn7354IeP+BzGwMACiprEBhCTkQ1MNuBVDwTMwGTCYA9h/yGkeBSMglEwCkYiAAAr8U+gcmE7cQAAAABJRU5ErkJggg==","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":true,"prefix":"","firstName":"Sigfrid","middleName":"Casmir","lastName":"Shayo","suffix":""},{"id":318192050,"identity":"c5c111c3-eb88-4fdb-80f7-91d8f60ec597","order_by":1,"name":"Khuzeima Khanbai","email":"","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":false,"prefix":"","firstName":"Khuzeima","middleName":"","lastName":"Khanbai","suffix":""},{"id":318192051,"identity":"ea439653-4d46-4137-ba56-6a9ab24c8f4a","order_by":2,"name":"Yona Gandye","email":"","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":false,"prefix":"","firstName":"Yona","middleName":"","lastName":"Gandye","suffix":""},{"id":318192052,"identity":"7b0da123-48f2-4eba-9a6b-bfbc386fd1cd","order_by":3,"name":"Nakigunda Kiroga","email":"","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":false,"prefix":"","firstName":"Nakigunda","middleName":"","lastName":"Kiroga","suffix":""},{"id":318192053,"identity":"cd250670-8a39-4e8b-bf87-a8173f0564cc","order_by":4,"name":"Tatizo Waane","email":"","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":false,"prefix":"","firstName":"Tatizo","middleName":"","lastName":"Waane","suffix":""},{"id":318192054,"identity":"5dff6871-b458-4b8f-af8e-f79aaab51f79","order_by":5,"name":"Peter Kisenge","email":"","orcid":"","institution":"Jakaya Kikwete Cardiac Institute","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Kisenge","suffix":""}],"badges":[],"createdAt":"2024-06-24 08:51:54","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4628795/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4628795/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59031427,"identity":"bebcc524-617a-4288-8547-f877a10a37c7","added_by":"auto","created_at":"2024-06-25 14:11:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":245063,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Brain CT scan taken 8 hours after left-sided hemiplegia; the arrow indicates early ischemic changes.\u003c/p\u003e\n\u003cp\u003e(b) Control brain CT scan taken 72 hours after left-sided hemiplegia; arrows indicate extensive cortical infarct\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4628795/v1/cff1ee8d8d09bd670c3a8f34.png"},{"id":59031428,"identity":"e424d17e-8fea-490a-8e67-f80d1cc603f0","added_by":"auto","created_at":"2024-06-25 14:11:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1526238,"visible":true,"origin":"","legend":"\u003cp\u003ePatient 12-lead ECG at presentation\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4628795/v1/d339b544861db2a0b5778827.png"},{"id":59031429,"identity":"c02eae61-e1ca-4037-974f-be6ebe999f88","added_by":"auto","created_at":"2024-06-25 14:11:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":698425,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Coronary angiography of a patient at presentation; the arrow indicates an occluded mLAD\u003c/p\u003e\n\u003cp\u003e(b) Coronary angiography of the patient at presentation; arrow shows a completely occluded pRCA.\u003c/p\u003e\n\u003cp\u003e(c) Coronary angiography of the patient afterballoon angioplasty of the mLAD; the arrow depicts good distal flow\u003c/p\u003e\n\u003cp\u003e(d) Coronary angiography of the patient afterstenting of the pRCA. Arrows indicate good flow to the middle and distal segments of the RCA.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4628795/v1/a71b517f269a3e6e64fa4696.png"},{"id":59032116,"identity":"d7541a63-7ad8-423c-b320-90a5cf885db8","added_by":"auto","created_at":"2024-06-25 14:19:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3221177,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4628795/v1/7f5e5590-9da9-4890-b8e4-cfc461eff0a2.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eConcurrent Acute Myocardial Infarction and Acute Ischemic Stroke in a Diabetic Patient Undergoing Chemotherapy for Non-Hodgkin Lymphoma:Should I administer thrombolytic therapy? A Case Report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eThere has been an alarming global increase in the incidence of cardiovascular disease and its traditional risk factors, particularly in middle- and low-income countries.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Traditional risk factors for cardiovascular disease include visceral obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), and smoking. All of these factors orchestrate chronic systemic low-grade inflammation that is responsible for atherosclerosis of coronary, cerebral, and peripheral arteries, which is referred to as atherosclerotic cardiovascular disease (ASCVD).\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAcute myocardial infarction (AMI) and stroke are the two major vascular events with a significant toll on healthcare expenditure, quality-adjusted life years, morbidity, and mortality.4 These catastrophic vascular events share common triggering factors, including oxidative stress, inflammation, and endothelial dysfunction(s)\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough these events share important risk factors as well as triggering factors, concurrent AMI and AIS are rare findings. In 2010, Omar and his colleagues used the term cardio-cerebral infarction to refer to simultaneous AMI and AIS. The incidence of cardio-cerebral infarction is reported to be as low as 0.009%.\u003csup\u003e\u003cb\u003e6,7\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThere has never been a reported case of concurrent AIS and AMI occurring in a patient who received cancer chemotherapy, specifically CHOP chemotherapy. We present a rare, preventable and suboptimally managed case of concurrent AIS and AMI occurring in a postmenopausal woman who received chemotherapy for NHL.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 59-year-old postmenopausal woman with a 5-year history of type 2 diabetes mellitus presented to the Jakaya Kikwete Cardiac Institute with sudden onset of left-sided weakness and excruciating chest pain that had\u0026nbsp;worsened\u0026nbsp;over 3 days. The patient was recently diagnosed with\u0026nbsp;non-Hodgkin\u0026nbsp;lymphoma\u0026nbsp;and started chemotherapy with CHOP 3 weeks prior. She denied prior hypertension or heart disease but reported using a\u0026nbsp;menopausal\u0026nbsp;supplement.\u003c/p\u003e\n\u003cp\u003ePhysical examination revealed a conscious patient who experienced chest pain with left-sided hemiplegia but no facial asymmetry or aphasia. She was hemodynamically stable with unremarkable vital signs.\u003c/p\u003e\n\u003cp\u003eAn emergency\u0026nbsp;CT scan revealed early ischemic stroke features (figure 1a), which were later confirmed by\u0026nbsp;a follow-up CT scan showing\u0026nbsp;an extensive infarct (figure 1b). A 12-lead ECG showed significant ST-segment elevation in\u0026nbsp;the inferior leads,\u0026nbsp;i.e.,\u0026nbsp;leads II, III, and aVF,\u0026nbsp;with reciprocal changes in leads I and aVL.\u0026nbsp;There\u0026nbsp;was also some ST-segment elevation in leads V5 and V6 (Figure\u0026nbsp;2). Blood tests revealed markedly elevated troponin I, c-reactive protein (CRP), glycated hemoglobin (HbA1c), and random blood glucose (RBG).\u003c/p\u003e\n\u003cp\u003eA diagnosis of concurrent acute myocardial infarction (AMI) and acute\u0026nbsp;ischemic\u0026nbsp;stroke (AIS) was made. The patient was loaded with clopidogrel, aspirin, and atorvastatin and prepared for emergency coronary\u0026nbsp;angiography\u0026nbsp;(CAG) and percutaneous coronary intervention (PCI). CAG revealed total thrombotic occlusion of the mid-segment of the left anterior descending coronary artery (mLAD) (figure 3a) and proximal segment of the right coronary artery (pRCA) (figure 3b). Balloon angioplasty of the mLAD and stenting of the pRCA were successfully carried out. TIMI flow grade 3 was achieved in both vessels (figure 3c, figure 3d).\u003c/p\u003e\n\u003cp\u003eThe patient developed ventricular fibrillation during coronary angiography, which was treated with defibrillation, but later developed bradycardia requiring temporary pacing. Following PCI, she was admitted\u0026nbsp;to\u0026nbsp;the coronary care unit (CCU) and received anticoagulation therapy. Her chest pain improved, but she developed a throbbing headache on the third day, which was ruled out as hemorrhagic transformation of the ischemic stroke (figure 1b).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;She was transferred to\u0026nbsp;the high dependency unit (HDU) and continued on dual antiplatelet therapy, heparin, furosemide, and atorvastatin. She showed remarkable improvement and was discharged after 9 days in\u0026nbsp;the hospital. 12-lead ECG done before the patient was discharged showed normal sinus rhythm with complete resolution of ST-segment elevation. Echocardiography revealed\u0026nbsp;ischemic\u0026nbsp;cardiomyopathy with reduced left ventricular systolic function (LVEF=34%).\u003c/p\u003e\n\u003cp\u003eAt discharge, the patient had stable vital signs but residual left-sided hemiplegia. She was advised to continue dual antiplatelet therapy, rivaroxaban, and metformin-glimepiride combination therapy and was scheduled to visit a neurology clinic. Her oncology team planned to continue chemotherapy after her discharge from the hospital.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eTo the best of our knowledge, this is the first case of concurrent AMI and AIS following diagnosis of NHL and initiation of chemotherapy. According to the American Society of Hematology, the diagnosis of cancer increases the incidence of stroke and AMI. Patients with incident cancer have a substantially short-term risk of arterial thromboembolism.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e This situation is further aggravated by the use of certain chemotherapies, such as doxorubicin, which have been shown to also increase the risk of thromboembolism. \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Our patient had received CHOP chemotherapy with doxorubicin as one of the components approximately three weeks prior to the onset of acute cardio-cerebral infarction. As the patient\u0026rsquo;s symptoms and worsening health conditions are linked with the initiation of chemotherapy, it is more likely that in addition to uncontrolled T2DM, the initiation of chemotherapy might have contributed to acute cardio-cerebral infarction. Antithrombotic therapy is generally recommended for the prevention of both arterial and venous thromboembolism in high-risk cancer patients, particularly those treated with chemotherapy.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e In contrast, our patient did not receive a single antiplatelet or anticoagulant prior to having a cardio-cerebral infarction. Therefore, there is a need to increase awareness among oncologists about the risk of thrombosis among cancer patients with comorbidities undergoing chemotherapy.\u003c/p\u003e \u003cp\u003eIt is worth recognizing that inflammation is at the heart of vascular endothelial dysfunction and thromboembolism. Our patient had a remarkably elevated high-sensitivity CRP (106 mg/dL) but a normal CBC at presentation. Her HbA1c and RBG levels were 11.76% and 18 mmol/L, respectively, indicating poorly controlled T2DM. This finding suggested that sterile inflammation induced by danger-associated molecular patterns (DAMPs) from killed cancer cells as well as uncontrolled T2DM contributed to the occurrence of arterial thrombosis.\u003c/p\u003e \u003cp\u003eThe diagnosis of cardio-cerebral infarction exerts significant decision-making pressure on attending clinicians. This is because urgent action is needed to restore perfusion to the myocardium as well as the brain. Concurrent AMI and AIS are very rare clinical conditions for which there is no high-quality evidence or clinical guidelines for management. This patient landed on the best facility for cardiovascular care in the country with a state-of-the art catheterization laboratory and highly experienced interventional cardiologists. We were therefore biased to serve the myocardium first. According to the European Society of Cardiology 2023 guidelines for the management of acute coronary syndrome (ACS), an invasive strategy should be undertaken to reperfuse the myocardium in cancer patients presenting with ACS with an expected survival of \u0026gt;\u0026thinsp;6 months.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The decision to perform PCI in this patient was reached but with significant worries about hemorrhagic transformation following the administration of anticoagulation and a high dose of dual antiplatelets, which is a requirement for performing PCI. Although the patient did not develop hemorrhagic transformation of the AIS, the infarct size increased, and she remained hemiplegic. Owing to the risk of myocardial rupture, our patient was not eligible for thrombolytics that would concurrently help to reperfuse the brain and myocardium. The patient would likely benefit from endovascular mechanical embolectomy for AIS; however, this practice is lacking at our institution. This calls for the establishment and strengthening of neurointerventional practices in our tertiary hospitals.\u003c/p\u003e \u003cp\u003eUpon discharge, the patient presented with hemiplegia, remained hemodynamically stable, and exhibited a significant reduction in left ventricular systolic function (EF\u0026thinsp;=\u0026thinsp;34%). Two days later, she proceeded with the second cycle of chemotherapy. The patient's prognosis is guarded, with favorable outcomes reliant upon patient-centered multidisciplinary collaboration among oncologists, cardiologists, and neurologists. Additionally, the patient's ability to cover healthcare expenses and adhere to prescribed therapy is crucial.\u003c/p\u003e \u003cp\u003eIn conclusion, heightened awareness is necessary among oncologists regarding the importance of administering prophylactic antithrombotic medications to high-risk newly diagnosed cancer patients undergoing chemotherapy due to the increased risk of arterial thrombosis. Managing cardio-cerebral infarction in patients with comorbidities poses significant challenges, particularly in resource-limited settings. In the absence of robust evidence and guidelines, treatment approaches must be highly individualized. Thus, it is imperative to establish and maintain advanced multidisciplinary practices and foster collaboration among experts to achieve optimal treatment outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCHOP- Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone\u003c/p\u003e\n\u003cp\u003eASC-Acute\u0026nbsp;coronary syndrome\u003c/p\u003e\n\u003cp\u003eAIS-Acute\u0026nbsp;Ischemic\u0026nbsp;Stroke\u003c/p\u003e\n\u003cp\u003eAMI-Acute Myocardial Infarction\u003c/p\u003e\n\u003cp\u003eSTEMI-ST-elevation myocardial infarction\u003c/p\u003e\n\u003cp\u003eCAG-Coronary Angiography\u003c/p\u003e\n\u003cp\u003ePCI- Percutaneous\u0026nbsp;coronary intervention\u003c/p\u003e\n\u003cp\u003eCT-Computed Tomography\u003c/p\u003e\n\u003cp\u003eECG-Electrocardiography\u003c/p\u003e\n\u003cp\u003eTIMI-Thrombolysis in Myocardial Infarction\u003c/p\u003e\n\u003cp\u003eT2DM-Type 2 Diabetes Mellitus\u003c/p\u003e\n\u003cp\u003eASCVD-\u0026nbsp;atherosclerotic cardiovascular disease\u003c/p\u003e\n\u003cp\u003eLAD-Left\u0026nbsp;anterior descending coronary artery\u003c/p\u003e\n\u003cp\u003eRCA- Right\u0026nbsp;coronary artery\u003c/p\u003e\n\u003cp\u003eCCU-Coronary Care Unit\u003c/p\u003e\n\u003cp\u003eLVEF-Left\u0026nbsp;ventricular ejection fraction\u003c/p\u003e\n\u003cp\u003eDAMP-Damage-Associated Molecular Patterns\u003c/p\u003e\n\u003cp\u003eCRP- C-reactive protein\u003c/p\u003e\n\u003cp\u003eCBC-complete blood count\u003c/p\u003e\n\u003cp\u003eRBG-Random\u0026nbsp;blood glucose\u003c/p\u003e\n\u003cp\u003eHbA1c- Glycated hemoglobin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for their anonymized information to be published in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSCS took history, performed physical examination and cardiac imaging, FL helped in the acquisition and interpretation of\u0026nbsp;brain\u0026nbsp;CT\u0026nbsp;scan images, KK, YG, TW, and PK performed coronary angiography/percutaneous coronary intervention and contributed to the acquisition and interpretation of associated data, SCS, KK, YG, NK, and PK participated in clinical management and\u0026nbsp;counseling\u0026nbsp;of the patient during hospitalization,\u0026nbsp;and\u0026nbsp;SCS wrote the initial draft of the manuscript. All authors reviewed and contributed to the final version of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their heartfelt gratitude to the patient and her caring daughter for their cooperation toward publication of this important work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKoon KT, Talha R. Cardiovascular Risk Factors and Prevention; A Perspective from Developing Countries.CJC 2021,37:733-743.http://doi.org/10.1016/j.cjca.2021.02.009\u003c/li\u003e\n \u003cli\u003eDaniel GH,Sonia SA.Emerging Risk Factors for Atherosclerotic Vascular Disease; A critical overview of evidence.JAMA 2003(7):932-940.doi:10.1001/jama.290.7.932\u003c/li\u003e\n \u003cli\u003eLibby P, Buring JE, Badimon L, et al.Atherosclerosis. Nat Rev Dis Primers 2019, 5,56. https://doi.org/10.1038/s41572-019-0106-z\u003c/li\u003e\n \u003cli\u003eThomas AG. Reducing the Growing Burden of Cardiovascular Disease in Developing World. Health Aff (Millwood) 2007,26(1):13-24. https://doi.org/10.1377/hlthaff.26.1.13\u003c/li\u003e\n \u003cli\u003ePartha D, Gabriel C, Ying W, et al. Myocardial Infarction accelerates atherosclerosis. Nature 2012, 487(7407): 325-329.doi:10.1038/nature11260.\u003c/li\u003e\n \u003cli\u003eOmar HR, Fathy A, Rashad R, et al. Concommitant acute right ventricular infarction and ischemic cerebrovascular stroke; possible explanations.Int Arch Med 2010, 3:25. doi:10.1186/1755-7682-3-25\u003c/li\u003e\n \u003cli\u003eYeo L, Andersson T, Yee KW, et al. Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first. J Thromb Thrombolyisis 2017, 44(1):104-111. doi:10.1007/s11239-017-1484-2.\u003c/li\u003e\n \u003cli\u003eNavi BB, Reiner AS, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. Jam Coll Cardiol 2017; 70(8): 926-938. doi:10.1016/j.jacc.2017.06.047.\u003c/li\u003e\n \u003cli\u003eHaichen Lv, Roupeng T, Jiawei L, et al. Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function.Am J Physiol Heart Circ Physiol2020,319: H133-H143.doi:10.1152/ajpheart.00456.2019.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Falanga A, Leader A, Ambaglio C, et al. EHA guidelines on management of antithrombotic treatment in thrombocytopenic patients with cancer. HemaSphere 2022, 6(8): e 750.doi:10.1097/HS9.0000000000000750.\u003c/li\u003e\n \u003cli\u003eESC. 2023 ESC Guidelines for Management of Acute Coronary Syndromes. European Heart Journal 2023, 44:3720-3826. https://doi.org/10.1093/eurheartj/ehad191\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"JAKAYA KIKWETE CARDIAC INSTITUTE","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ischemic Stroke, ST-Elevation Myocardial Infarction, Cerebral Infarction, CHOP Chemotherapy, Percutaneous Coronary Intervention, Thrombolysis, Endovascular Mechanical Embolectomy","lastPublishedDoi":"10.21203/rs.3.rs-4628795/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4628795/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcurrent ST-elevation myocardial infarction (STEMI) and acute ischemic stroke (AIS) are extremely rare, and their management remains perplexing due to the absence of high-quality evidence and limited resources. For the first time, we report a rare, preventable and suboptimallymanaged case of concurrent AIS and STEMI in a patient with non-Hodgkin lymphoma (NHL) who received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA postmenopausal woman of African origin with a background history of type 2 diabetes mellitus presented to the Jakaya Kikwete Cardiac Institute with sudden onset of left-sided weakness and typical ischemic chest pain for 3 days. The patient was recently diagnosed with NHL and started CHOP chemotherapy 3 weeks prior. Physical examination revealed left-sided hemiplegia. Emergency brain computed tomography (CT) and 12-lead echocardiography (ECG) revealed AIS and STEMI, respectively. A diagnosis of concurrent AIS and STEMI was reached, and the patient was loaded with dual antiplatelets and heparin and rushed for emergency coronary angiography (GAG) and percutaneous coronary intervention (PCI). CAG revealed massive thrombotic occlusion of the mid-segment of the left anterior descending coronary artery (mLAD) and proximal segment of the right coronary artery. Revascularization was achieved in both vessels with a resultant TIMI flow grade of 3. The post-PCI period was marked bysignificant improvement inchest pain and resolution of ST-elevation, as revealed by 12-lead ECG. However, the patient remained hemiplegic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have described a rare case of concurrent AIS and STEMI in a postmenopausal woman who had a significant risk of thromboembolism. The patient had uncontrolled type 2 diabetes and received CHOP chemotherapy for NHL, which was diagnosed 3 weeks prior. This case underscores the need for thromboembolic prophylaxis for selected cancer patients receiving chemotherapy. The need to individualize management is also emphasized,as both PCI and thrombolysis carry therisk of serious repercussions. In our patient, if thrombolysis was attempted it would have caused myocardial ruptureand immediate death. The patient would have benefited from endovascular mechanical embolectomy for AIS;however, this practice is lacking at our institution. This calls for the establishment and strengthening of neurointerventional practices in our tertiary healthcare facilities.\u003c/p\u003e","manuscriptTitle":"Concurrent Acute Myocardial Infarction and Acute Ischemic Stroke in a Diabetic Patient Undergoing Chemotherapy for Non-Hodgkin Lymphoma:Should I administer thrombolytic therapy? A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 14:11:04","doi":"10.21203/rs.3.rs-4628795/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1cb4d2f-4d57-4d0c-a127-b6586913d506","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33643573,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2024-06-25T14:11:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-25 14:11:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4628795","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4628795","identity":"rs-4628795","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}