==== Front BMC Cardiovasc Disord BMC Cardiovasc Disord BMC Cardiovascular Disorders 1471-2261 BioMed Central London 37380955 3351 10.1186/s12872-023-03351-3 Research Can the current monkeypox affect the heart? A systematic review of case series and case report http://orcid.org/0000-0002-4378-2714 Sayad Reem reem.17289806@med.aun.edu.eg 1 http://orcid.org/0000-0003-3826-9702 Siddiq Abdelmonem Abdelmonemalsaid555@std.mans.edu.eg 2 http://orcid.org/0000-0002-1767-5966 Hashim Ahmed ahmed.hashim.fl@gmail.com 3 http://orcid.org/0000-0002-1643-9750 Elsaeidy Ahmed Saad Ahmed.Saad.Elsaeidy@gmail.com 4 1 grid.252487.e 0000 0000 8632 679X Faculty of Medicine, Assiut University, Assiut, Egypt 2 grid.10251.37 0000000103426662 Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 3 grid.7269.a 0000 0004 0621 1570 Faculty of Medicine, Ain Shams University, Cairo, Egypt 4 grid.411660.4 0000 0004 0621 2741 Faculty of Medicine, Benha University, Benha, Egypt 28 6 2023 28 6 2023 2023 23 3288 3 2023 15 6 2023 © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Monkeypox is a zoonotic viral infection first reported in May 2022. Monkeypox cases present with prodromal symptoms, rash, and/or systemic complications. This study systematically reviews the monkeypox cases presented with any cardiac complications. Methods A systematic literature search was done to locate papers that discuss any cardiac complications associated with monkeypox; then, data were analyzed qualitatively. Results Nine articles, including the 13 cases that reported cardiac complications of the disease, were included in the review. Five cases previously had sex with men, and two cases had unprotected intercourse, which reveals the importance of the sexual route in disease transmission. All cases have a wide spectrum of cardiac complications, such as acute myocarditis, pericarditis, pericardial effusion, and myopericarditis. Conclusion This study clarifies the potential for cardiac complications in monkeypox cases and provides avenues for future research to determine the underlying mechanism. Also, we found that the cases with pericarditis were treated with colchicine, and those with myocarditis were treated with supportive care or cardioprotective treatment (Bisoprolol and Ramipril). Furthermore, Tecovirimat is used as an antiviral drug for 14 days. Keywords Monkeypox Mpox Cardiomyopathy Myocarditis Carditis Pericarditis Benha UniversityOpen access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2023 ==== Body pmcIntroduction Monkeypox (Mpox) is a viral zoonotic disease caused by the Mpox virus, a member of the Orthopoxviral genus from the Poxviridae family of viruses [1]. The first human Mpox case was detected in 1970 [2]. Mpox was mainly endemic to central and western Africa, with a few sporadic cases outside Africa. Traveling to the endemic regions and importing animals such as Squirrels and rodents from Ghana in 2003 led to the Mpox outbreak in the United States [3]. The first human case of Mpox-outbreak-2022 was reported to the WHO on May 07. In 2022 from a traveler who returned from Nigeria then, the cases started to increase, which prompted the WHO to declare the Mpox disease as a public health emergency of international concern to raise awareness about it and promote the countries' preparedness [4]. According to the Center for Disease Control and Prevention (CDC), the total number of Mpox cases is 87,078 in both the endemic and non-endemic sites of the disease [5]. The disease manifestation starts with a prodromal phase of fever, headache, myalgia, and lymphadenopathy, followed by the eruption of multiple swollen and umbilicated cutaneous lesions on the patient's face, hands, and genitalia. Anal pain and the other features last five days, a common period of Orthopoxviruses, followed by a rash. The rash proceeds over different phases, starting with macular, papular, vesicular, pustular, and finally, the crustation phase lasting from two to four weeks on common sites on the body such as the face, palm, and soles, and oral membranes. Certain complications may occur, such as cellulitis, encephalitis, corneal infection, and sepsis [6]. The above data points clearly to the diversity of the disease manifestations, but other manifestations are unknown till now, so we aim here to summarize the cardiac complications of the Mpox infection. Methods We followed the approaches for conducting the current study based on the Cochrane Handbook of systematic reviews on Interventions [7]. While drafting our manuscript, we strictly followed the recommended reporting items for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [8]. Search strategy Firstly, the following electronic databases were systematically searched: PubMed, Cochrane, Medline, Scopus, and Web of Science until December 01, 2022. We used the following search strategy in the previously mentioned databases: ((Monkeypox) AND (cardi* OR Heart OR myocarditis or cardiomyopathy)). All the included studies’ references were screened to avoid missing any studies and guarantee high-quality screening. Then, we updated the search process on April 29, 2023, during the revision round. Eligibility criteria We included any primary study (case reports, case series, cohort) with patients suffering from heart injuries after the onset of Mpox symptoms. On the other hand, we excluded non-human studies, conference abstracts, reviews, and non-English studies. Screening and study selection Using Endnote software (version X20.4.1), we collected the different records from the different databases and removed duplicates. The retrieved references were examined. The screening was done in two steps; title and abstract screening, followed by full-text screening for final eligibility. Two independent authors conducted the screening, and after comparing their findings, group discussions were used to settle any differences. Data extraction The following data were extracted from the included studies by two independent authors. Study ID, Country, Study design, Age, Male gender, Presenting symptoms (Systemic, Non-systemic, and Cardiac), History of vaccinations, History of other etiology of myocarditis or infections, Homosexual/bisexual/MSM, Route of transmission, Immunocompromised, Treatment (Mpox and Myocarditis), Duration of hospitalization, and Investigation (Mpox, Myocarditis, and Follow-up). Arguments were later resolved through group discussion. Quality assessment The quality of included studies was assessed using the National Institute of Health (NIH) quality assessment tool for case reports and case series. The tool assesses the quality of each study at the level of nine domains. Each domain, as well as the overall quality, is rated either good, fair, or poor [9]. Two independent authors assessed the quality of the included studies, and arguments were later resolved through group discussion. Data synthesis Qualitative analysis was done by collecting and summarizing non-numerical data to understand symptoms, criteria, and how to manage the cases of Mpox associated with cardiac complications. Results Search results The search strategy over the different medical databases (PubMed, Scopus, Web of Science, Medline, Cochrane) yielded 144 studies. Four studies were retrieved by manual searching, so the total number of studies became 110 after removing duplication. Screening the title and the abstract yielded 24 studies after excluding eighty-six papers because of being animal studies, out of the study criteria, and/or not primary studies. Twenty-four articles were screened for their full-text testing for eligibility. Nine case reports/case series met the study criteria [3, 10–17] and were further included in the quality assessment, as shown in Fig. 1. A summary of the included papers can be found in Table 1.Fig. 1 PRISMA flowchart of the database search and searching process Table 1 A summary of included studies Study ID Country Study design Age (Years) Male gender Presenting symptoms History of vaccinations History of other etiology of myocarditis or infections Homosexual /bisexual/MSM Systemic Non-systemic Cardiac Santaliz-Ruiz et al. 2023 [17] Puerto Rico Case Report 21 Yes Fever, Myalgia, Nausea, Vomiting, Headache, and Watery Diarrhea, Cervical Lymphadenopathy Vesiculopustules on face, trunk, suprapubic area, and Extremities Retrosternal non-radiating oppressive chest pain NO No Yes Brouillard et al. 2022 [15] Canada Case Report 34 Yes Fever, Chills A well-circumscribed, umbilicated papule on the pubis, and an ulcerated lesion on the glans penis Constant, sharp, and pleuritic non radiating chest pain, relieved when sitting upright and worse when lying down No No, but later presented positive for Chlamydia and negative for Gonorrhea NO, but stayed at a homosexual friend’s house two weeks earlier Dumont et al. 2022 [14] Case 1 France Case series 21 Yes Fever Anal pustules Acute chest pain radiating into the arms and jaw appeared No No Yes Case 2 25 Yes NA Pustules on the face and penis Constant chest pain and palpitations No No NA Case 3 32 Yes Fever Erosive cutaneous lesions on the penis Retrosternal chest pain radiating to the left arm No Slightly detectable Epstein-Barr virus DNA in blood < 500copies/mL No Miller et al. 2022 [16] USA Case-series In his 302 Yes NA Rash on his face, head, back, and genitals then spread, coalesced, and developed central necrosis, Phimosis, urinary retention Atrial Fibrillation NA HIV, Syphilis NA Pinho et al. 2022 [10] Portugal Case Report 31 Yes Fever, Malaise, Myalgia Eruption of multiple swollen and umbilicated cutaneous lesions on his face, hands, and genitalia Chest tightness radiating to the left upper extremity that awoke him during the night Prophylaxis against HIV NO, Paucisymptomatic SARS-CoV-2 infection 2 months before this event Yes Rodriguez-Nava et al. 2022 [11] Case 1 USA Case-series 32 Yes Viral illness, Cervical Lymphadenopathy Disseminated rash and a painful penile lesion Chest pain and dyspnea for 1 day No Syphilis treated by doxycycline Yes Case 2 37 Yes Fever, Dyspnea, Inguinal Lymphadenopathy, Decreased Exercise Tolerance Multiple skin lesions in both arms and a lesion at the base of the penis Difficulty breathing and decreased exercise tolerance without chest pain Prophylaxis against HIV Syphilis NA Shaik et al. 2022 [12] USA Case-Report 51 Yes Fever, Fatigued, Flu-like symptoms, Malaise Developed several vesiculopustular lesions on his face and extremities Retrosternal chest pain radiating to the left arm NA NA NA Tan et al. 2022 [13] Canada Case-Report 40 Yes Fever, Chills, Myalgia, headache Umbilicated maculopapular and vesicular skin lesions over his chest, arms, Libs and genitals Central, non-radiating, pressure-like chest pain but denied cough, palpitations, or shortness of breath NO Stable HIV (CD4 count = 609 cells/mm3, viral load undetectable, antiretroviral therapy) Yes Thornhill et al. 2022 [3] Case 1 NA Case-series NA NA NA NA NA NA NA NA Case 2 NA NA NA NA NA NA NA NA Study ID Route of transmission Immunocompromised Treatment Duration of hospitalization Investigation Mpox Myocarditis Mpox Myocarditis Follow-up Santaliz-Ruiz et al. 2023 [17] Sexual transmission No NA High-dose Aspirin, Oral Colchicine 0.6 mg daily Five days PCR assay of a swab sample from a skin lesion CBC, CMP, ECG, Echo, Troponin, Cardiac MRI Cardiac MRI after Eight weeks Brouillard et al. 2022 [15] Contact with soiled linens of a homosexual friend No - Prophylactic Ceftriaxone and Azithromycin - Acyclovir in negative pressure room - Tecovirimat for 14 day after confirmed diagnosis ACE inhibitors Nine days PCR assay of a swab sample from a skin lesion ECG, Echo, Cardiac MRI, Troponin, Standard labs The patient left the hospital before undergoing his control cardiac MRI Dumont et al. 2022 [14] Case 1 Sexual transmission No NA Bisoprolol and Ramipril NA PCR assay of a swab sample from a 14skin lesion ECG, Troponin, CK, TTE, CRP, contrast CT chest Cardiac MRI after four weeks Case 2 Sexual transmission No NA Bisoprolol and Ramipril NA PCR assay of a swab sample from a skin lesion ECG, Troponin, CK, CRP, TTE NA Case 3 Sexual transmission No Oral Tecovirimat for 14 day after confirmed diagnosis Bisoprolol, Ramipril and Anti-aggregation NA PCR assay of a swab sample from a skin lesion ECG, Troponin, CK, TTE, CRP, Cardiac-CT Scan Cardiac MRI after 11 days Miller et al. 2022 [16] NA Yes - Oral Tecovirimat for 14 day after confirmed diagnosis, then IV in ICU - 2 doses of VIGIV - Antimicrobials NA - 4 weeks in the 1st admission - 15-day in the 2nd admission PCR assay of a swab sample from a skin lesion NA NA Pinho et al. 2022 [10] NA NA NA Supportive care and exercise restriction One week PCR assay of a swab sample from a skin lesion ECG, Chest X-ray, TTE, CRP, CK, Troponin, Brain natriuretic peptide, urine and blood toxicology tests, Cardiac MRI NO Rodriguez-Nava et al. 2022 [11] Case 1 Sexual transmission No Oral Tecovirimat for 14 day after confirmed diagnosis No specific treatment due to the rapid resolution 10 days PCR assay of a swab sample from a skin lesion ECG, Troponin, Chest X-ray, CRP, ESR, N-terminal prohormone B-type Natriuretic Peptide Echo on hospital day2, Troponin in hospital day 6 Case 2 Sexual transmission No Supportive care Supportive care 4 days PCR assay of a swab sample from a skin lesion ECG, Troponin, Echo, B-type natriuretic peptide Cardiac enzymes testing Shaik et al. 2022 [12] NA No Supportive care Nitroglycerin at presentation, 1 g aspirin/h for 2 weeks 7 days PCR assay of a swab sample from a skin lesion ECG,TEE, Chest X-ray, Troponin, CBC, ALT, AST, BUN, Cr, CRP, ESR, HbA1c High-dose aspirin, and a planned cardiac follow-up Tan et al. 2022 [13] Sexual transmission No Valacyclovir for initial diagnosis consideration of HSV 1,or 2 Supportive care NA PCR assay of a swab sample from a skin lesion ECG, CK, Echo, Cardiac Catheterization, Cardiac MRI, Troponin, Routine Chemistries, CBC Full recovery after 25 days Thornhill et al. 2022 [3] Case 1 NA NA NA self-limiting (< 7 days) NA NA NA NA Case 2 NA NA NA NA NA NA NA ALT Alanine transaminase, AST Aspartate transaminase, BUN Blood urea nitrogen, CBC Complete blood count, CK Creatine Kinase, CMP Comprehensive Metabolic Panel, Cr Creatinine level, CRP C-reactive protein, ECG Electrocardiography, Echo Ehocardiogram, ESR Erythrocyte sedimentation rate, HbA1c Hemoglobin A1C, HIV Human immunodeficiency viruse, HSV Herpes simplex virus, Mpox Monkeypox, MRI Magnetic resonance imaging, MSM Men Who Have Sex with Men, NA Not Available, PCR Polymerase chain reaction, TEE Transesophageal Echocardiography Baseline characteristics and data analysis The included studies represent 13 Mpox cases with cardiac complications. Elevn cases were male patients. Five male patients have a history of having sex with men [10, 11, 13, 14, 17]. The patients who developed pericarditis or myocarditis have evidence of systemic inflammatory response in the form of fever, myalgia, and headache. Additionally, 11 patients developed a maculopapular eruption that is sometimes umbilicated [10–17]. The location of the rash was related to the site of sexual contact, including genital, anal, or oral regions. The presentation of myocarditis in the afflicted patients was usually manifested with chest pain that sometimes radiated to the left arm. The history of pox virus vaccination was either unavailable or negative in all selected patients. Despite the absence of clear vaccination history, three patients have a syphilis history [11, 16], with one patient having a history of well-controlled HIV [13]. Other sexually transmitted infections were routinely excluded from most of the patients. However, in one study, the analysis of other sexually transmitted infections was rejected due to safety considerations [13]. ECG was routinely utilized as an initial cardiac assessment tool. Different findings have been demonstrated, including sinus tachycardia, repolarization abnormality (e.g., T wave inversion), and widespread ST-segment elevation. The treatment was usually supportive because the patients presented with mild complications. However, one patient has been prescribed doses of aspirin aiming to relieve the pericarditis [12]. Real-time Polymerase Chain Reaction (PCR) targeting the virus nucleic material from the skin lesion was surely the only method to diagnose the current infection with Mpox. Various methods are used to verify the pericarditis/myocarditis diagnosis. High-sensitivity serum troponin was used to diagnose associated myocarditis in most patients. In the included cases, we found elevated levels of High-sensitivity troponins (0.165–21.20 ng/ml) [11, 17], Creatine Kinase reached (291–740 U/L) [10, 13], and N-terminal prohormone B-type natriuretic peptide (155–1258 pg/ml) [10, 11]. In addition, a serial electrocardiogram was usually used to aid the diagnosis of pericarditis. Four patients have required cardiac magnetic resonance (CMR) imaging to confirm the myocarditis [10, 13, 15, 17]. Besides, eight patients have utilized echocardiography either (transthoracic (TTE) or transesophageal) to visualize the cardiac function and pericardial fluid collection properly [10–15, 17]. Magnetic resonance imaging occasionally demonstrated the inflammation location despite transesophageal echocardiography. In T2-weighted images, areas of increased signal intensity in the basal inferior and lateral segments were found, corresponding to myocardial edema [10]. Late gadolinium enhancement sequences revealed subepicardial enhancement in the mid inferolateral segment and mid-wall enhancement in the remaining inferior and lateral segments of the LV, findings compatible with necrosis [10]. In addition, parametric mapping demonstrated a regional increase of T1 and T1 native values, indicating an abnormally expanded myocardial extracellular volume in the lateral wall. Postcontrast T1 mapping confirmed myocardial gadolinium accumulation with a nonischemic pattern in the lateral wall [10]. Quality assessment We have used the NIH quality assessment tool for case series to assess the quality of the included studies as previously described [9]. Three of the included studies have a good quality (> 6) [3, 11, 16], Five studies have a fair quality (from 3 to 6 points) [12–15], and one study has a poor quality (< 3) [10] as shown in Table 2.Table 2 The quality of included studies using the NIH tool for case series Author (YOP) Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Overall rating Santaliz-Ruiz et al. 2023 [17] Y Y U U Y Y Y U Y Fair Brouillard et al. 2022 [15] Y Y U U Y Y N U Y Fair Dumont et al. 2022 [14] Y Y Y Y U N U U Y Fair Miller et al. 2022 [16] Y Y Y Y Y Y Y U Y Good Pinho et al. 2022 [10] N N U U N N U U N Poor Rodriguez-Nava et al. 2022 [11] Y Y Y Y Y Y Y U Y Good Shaik et al. 2022 [12] Y Y U U Y U Y U Y Fair Tan et al. 2022 [13] Y Y U U Y Y Y U Y Fair Thornhill et al.2022 [3] Y Y Y U Y Y Y Y Y Good Q1: Was the study question or objective clearly stated? Yes/No/Unclear Q2: Was the study population clearly and fully described, including a case definition? Q3: Were the cases consecutive? Q4: Were the subjects comparable? Q5: Was the intervention clearly described? Q6: Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? Q7: Was the length of follow-up adequate? Q8: Were the statistical methods well-described? Q9: Were the results well-described? YOP Year of publication, Y Yes, N No, U Unclear, NIH National institute of health Discussion The declaration of Mpox as a public health emergency by the WHO on July 23, 2022, has raised awareness and alertness about the disease's manifestations and complications [18]. We included nine studies that reported possible cardiac complications of Mpox in which a total of 13 patients were presented [3, 10–17]. Five male patients had sex with men [10, 11, 13, 14, 17] and three male patients had unprotected sexual intercourses [11, 14] which reveal the importance of the sexual route in the disease transmission as it was reported by the CDC. Sexual contact with an infected Mpox patient is considered the main route of disease transmission during the current outbreak [19]. According to CDC, monkeypox infection is identified more in males [20]. In Mpox cases: The history began with typical Mpox symptoms such as fever, anal pain, and pustules on the face and penis a few days (four-seven days) after the last unprotected homosexual intercourse or with at-risk partners. Then, the Mpox diagnosis is confirmed by PCR. A few days later (two-seven days), patients presented with acute chest pain, elevated cardiac markers, and biological inflammatory syndrome. Typical electrocardiogram and TTE abnormalities associated with myocarditis were also identified [3, 10–17]. Few cases of cardiac involvement in Mpox infection have been reported. However, according to smallpox infection, genetically related to the Mpox virus but more aggressive, was associated with myocarditis. Furthermore, cardiac complications of smallpox vaccination have been reported since the initiation of vaccination in the 1950s in Europe, including post-vaccinal myocarditis and myopericarditis [21]. Both the live replicating smallpox vaccine ACAM2000 and the live non-replicating smallpox vaccine JYNNEOS, which are used to immunize people against the Mpox virus, have a high incidence of myocarditis but the exact mechanism remains unclear [22, 23]. On the other hand, some studies suggested two potential mechanisms of smallpox vaccine-related myopericarditis. The virus may affect the myocardium directly or by immune-mediated reaction, as evidenced by several studies that found a Th1-predominant cytokine profile associated with myocarditis after smallpox vaccination [24–26]. As Orthopoxviruses are closely related to the Vaccinia virus used in vaccination, it is reasonable that Mpox may also be associated with myocarditis. Extrapolating, the Mpox virus may have a tropism for myocardium tissue or cause immune-mediated injury to the heart [10]. Pericarditis is characterized by pericardial inflammation responding to various stimuli that cause an autoimmune or inflammatory response. It may result in pericardial effusion, impairing cardiac filling [27]. As most acute episodes of pericarditis are preceded by a flu-like or gastrointestinal syndrome, the etiological agents behind pericarditis are predominantly viruses [27, 28]. Myocarditis is an inflammatory myocardium disease diagnosed by established histological, immunological, and immune-histochemical criteria. It is considered a challenging diagnosis because of its heterogeneity in clinical presentation and histological forms [29]. A combination of clinical presentation and noninvasive diagnostic findings, including typical CMR abnormalities, may be used to diagnose clinically suspected myocarditis [30, 31]. The three diagnostic criteria of pericardial inflammation (chest pain, a friction rub, and diffuse ECG changes, including ST elevation) may be used to diagnose clinically suspected pericarditis [28]. The history and clinical presentation may suggest a specific etiology in patients with clinically suspected and confirmed myocarditis, but a definitive cause is often difficult to identify. As mentioned in Table 1, five cases presented without any history of potential etiology of myocarditis or pericarditis. So, Mpox infection may be the etiology of heart injuries in those patients [10, 13, 14, 17]. The management of viral myocarditis depends on the presenting symptoms, and the patient must be initially diagnosed appropriately by rolling out any other causes of the presenting symptoms [32]. Regarding our scope of cardiac complications, we will focus on managing pericarditis and myocarditis. Pericarditis can be managed by using Colchicine 1–2 mg as an initial dose that will be decreased gradually, acetylsalicylic acid, and a lower dose of nonsteroidal anti-inflammatory drugs (NSAIDs) can be used as symptomatic treatment [33, 34]. Patients who were given aspirin (1.2 g) twice daily for two weeks showed significant improvement. These patients displayed signs of recovery within eight days [12, 34]. Randomized controlled trials demonstrate colchicine's efficacy and rapid recovery in pericarditis patients [35] and significantly reduce the rate of subsequent recurrences of pericarditis in patients with multiple recurrences [36]. Patients who do not respond to colchicine and NSAIDs receive low-dose steroids as a second line of treatment [34]. Our included myocarditis cases received supportive care, exercise restriction, and the initiation of ibuprofen and colchicine if the case was combined with pericarditis (myopericarditis). However, they did not receive any directed therapy for myocarditis. The patients had a full clinical recovery in one to two weeks. They were discharged with normal cardiac enzymes and sustained electric and hemodynamic stability [10, 11, 13, 15]. Three myocarditis cases received cardioprotective treatment (Bisoprolol and Ramipril) [10, 11, 13]. This treatment resulted in no recurrence of pain, and high-sensitivity troponin T decreased [14]. According to Miller et al. 2022 (newly included study), four cases received Tecovirimat as an antiviral drug for the 14-day duration with supportive treatment [11, 14–16], as recommended by the CDC guidelines [37]. Because those cases evolved rapidly, one of the cases left the hospital early before the assessment of the effect of Tecovirimat on myocardial inflammation without a follow-up CMR [15]. Early implementation of supportive care and pain control is recommended. The effectiveness of this measure is based on the patient's immune system. Usually, these treatments are sufficient for immunocompetent patients. Nevertheless, the illness outcome is determined by several factors, including the patient's initial health condition, existing diseases, immunization record, and co-morbidity. Thus, supportive care and pain control may not be enough for some people with weakened immune systems, and Tecovirimat should be considered [14, 16]. Tecovirimat is a drug that suppresses the activity of the VP37 envelope-wrapping protein of Orthopoxviruses, thus hindering the production of enveloped virions and diminishing the amount of viral DNA in the blood of a non-human primate organism [37]. While there is no data available on the effectiveness of Tecovirimat for treating people with Mpox, experiments conducted with a variety of animal species have yielded positive results regarding its ability to lessen the likelihood of death from Orthopoxviruses if it is taken early in the disease [38]. Furthermore, FDA declared that the indiscriminate usage of Tecovirimat might induce viral resistance making Tecovirimat ineffective for orthodox-infected patients [37]. Alternate treatment options have a less safety profile than Tecovirimat. So, when Tecovirimat is needed, it is important to be aware of the lack of evidence on its effectiveness for Mpox patients and the possibility of viral resistance. Tecovirimat is accessible from the Strategic National Stockpile of the United States and should be given out under the rigid guidelines of the CDC Institutional Review Board. As per the CDC's advice, the medication should be considered for patients with intense illness, those in danger of developing a serious disease, and those whose body parts are at risk of being affected by the virus (such as the genitals) [37]. Strengths and limitations The small number of the reported Mpox cases with cardiac complications limits the study. All the available studies are case reports or case series. Additionally, we had to include some studies despite missing data due to the lack of these cases. Some of the included cases have a history of HIV and syphilis which may impact the patients' immunity. These limitations reduce the evidence quality of this study. The strong points of this study: this systematic review is novel to aggregate cardiac complications in monkeypox. Also, this study illustrates the importance to diagnose cardiac complications early which can improve patient outcomes. Conclusion and recommendations This study suggests the possibility of cardiac complications in Mpox patients. So, we advise doing cardiovascular investigations for the Mpox patients with suspected cardiovascular affectionNo mortality was associated with the documented mild myocarditis and/or pericarditis sequelae. Further research is needed to identify the pathological mechanism underlying Mpox-associated heart injury. Also, we recommend conducting clinical trials to evaluate Tecovirimat's efficacy and safety in managing Mpox patients presented with cardiac complications. Abbreviations CMR Cardiac magnetic resonance CDC Center for Disease Control and Prevention ECG Electrocardiography MSM Men Who Have Sex with Men Mpox Monkeypox NSAIDs Nonsteroidal anti-inflammatory drugs PCR Polymerase Chain Reaction TTE Transthoracic echocardiography WHO World Health Organization Acknowledgements None. Authors’ contributions ASE and RS: Conceptualization, Methodology. RS, AS, and AH: Data curation, Writing- Original draft preparation. RS, AS, and AH: Visualization, Investigation. ASE: Supervision. ASE and RS: Software, Validation. ASE: Writing—Reviewing and Editing. Funding Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials Data will be provided upon request from Reem Sayad (reem.17289806@med.aun.edu.eg). Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ==== Refs References 1. McCollum AM Damon IK Human monkeypox Clin Infect Dis 2014 58 2 260 267 10.1093/cid/cit703 24158414 2. Ladnyj ID Ziegler P Kima E A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo Bull World Health Organ 1972 46 5 593 4340218 3. Thornhill JP Monkeypox virus infection in humans across 16 countries—April–June 2022 N Engl J Med 2022 387 8 679 691 10.1056/NEJMoa2207323 35866746 4. WHO Director-General declares the ongoing monkeypox outbreak a Public Health Emergency of International Concern. https://www.who.int/europe/news/item/23-07-2022-who-director-general-declares-the-ongoing-monkeypox-outbreak-a-public-health-event-of-international-concern (Accessed 01 May 2023). 5. 2022 Mpox Outbreak Global Map | Mpox | Poxvirus | CDC. https://www.cdc.gov/poxvirus/mpox/response/2022/world-map.html (Accessed 01 May 2023). 6. Webb E Availability, scope and quality of monkeypox clinical management guidelines globally: a systematic review BMJ Glob Heal 2022 7 8 e009838 10.1136/bmjgh-2022-009838 7. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook. 8. Page MJ The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ 2021 372 n71 10.1136/bmj.n71 33782057 9. National Institutes of Health. National Heart Lung, and Blood Institute. Study Quality Assessment Tools. Bethesda: National Institutes of Health; 2018. 10 Pinho AI Acute myocarditis–a new manifestation of Monkeypox infection? JACC Case Rep 2022 4 1424 1428 10.1016/j.jaccas.2022.08.033 36249878 11. Rodriguez-Nava G Myocarditis attributable to Monkeypox virus infection in 2 patients, United States, 2022 Emerg Infect Dis 2022 28 12 2508 2512 10.3201/eid2812.221276 36179413 12. Shaik TA Monkeypox-associated pericarditis: a Maiden case Cureus 2022 14 9 e29638 36320991 13. Tan DHS Atypical clinical presentation of monkeypox complicated by myopericarditis Open Forum Infect Dis 2022 9 8 ofac394 10.1093/ofid/ofac394 36043183 14. Dumont M, Guilhou T, Gerin M, Frémont-Goudot G, Nivose PL, Koubbi A, Joly V, Bouadma L, Yazdanpanah Y, André MH, de La Porte des Vaux C. Myocarditis in monkeypox-infected patients: a case series. Clin Microbiol Infect. 2023;29(3):390.e5-390.e7. 10.1016/j.cmi.2022.12.001. 15. Brouillard P Monkeypox associated myocarditis: a case report IDCases 2022 30 e01628 10.1016/j.idcr.2022.e01628 36345425 16. Miller MJ, et al. Severe Monkeypox in hospitalized patients — United States, August 10–October 10, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(44):1412–7. 10.15585/mmwr.mm7144e1 10.15585/mmwr.mm7136a1|10.15585/mmwr.mm7132e3|10.1093/cid/ciaa143|10.1016/S1473-3099(19)30294-4|10.15585/mmwr.mm7142e1|10.15585/mmwr.mm7138e1|10.1056/NEJMoa2207323. Available: https://stacks.cdc.gov/view/cdc/123141. 17. IV Santaliz-Ruiz LE Pabón-González F Colón-Fontánez F Monkeypox induced acute myocarditis in a young healthy adult JAAD Case Rep 2023 34 5 6 10.1016/j.jdcr.2023.01.018 36776939 18. Sah R Public Health Emergency of International Concern declared by the World Health Organization for Monkeypox Glob Secur Heal Sci Policy 2022 7 1 51 56 10.1080/23779497.2022.2124185 19. Science brief: Detection and transmission of Mpox virus. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. 2023. Available at: https://www.cdc.gov/poxvirus/monkeypox/about/science-behind-transmission.html (Accessed: F. 20. Monkeypox Cases by Age and Gender, Race/Ethnicity, and Symptoms | Monkeypox | Poxvirus | CDC. Accessed 31 Oct 2022. https://www.cdc.gov/poxvirus/monkeypox/response/2022/demographics.html. 21. Cassimatis DC Atwood JE Engler RM Linz PE Grabenstein JD Vernalis MN Smallpox vaccination and myopericarditis: a clinical review J Am Coll Cardiol 2004 43 9 1503 1510 10.1016/j.jacc.2003.11.053 15120802 22. Keinath K Church T Kurth B Hulten E Myocarditis secondary to smallpox vaccination BMJ Case Rep 2018 2018 bcr-2017-223523, 2018 23. Halsell JS Department of Defense Smallpox Vaccination Clinical Evaluation TeamMyopericarditis following smallpox vaccination among vaccinia-naive US military personnel J Am Med Assoc 2003 289 3283 3289 10.1001/jama.289.24.3283 24 McNalley MC Qamar Y Cardiac complications of progressive generalized vaccinia: report of a case Dis Chest 1966 49 3 333 335 10.1378/chest.49.3.333 25. Bengtsson E Lundström R Postvaccinal myocarditis Cardiology 1957 30 1 1 8 10.1159/000165631 26. Cohen JI Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine J Infect Dis 2010 201 8 1183 1191 10.1086/651453 20214479 27. Chiabrando JG Management of acute and recurrent pericarditis: JACC state-of-the-art review J Am Coll Cardiol 2020 75 1 76 92 10.1016/j.jacc.2019.11.021 31918837 28. Adler Y 2015 ESC Guidelines for the diagnosis and management of pericardial diseases Kardiol Pol (Polish Hear. Journal) 2015 73 11 1028 1091 10.5603/KP.2015.0228 29. Richardson P Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomypathies Circulation 1996 93 841 10.1161/01.CIR.93.5.841 8598070 30. Caforio ALP Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases Eur Heart J 2013 34 33 2636 2648 10.1093/eurheartj/eht210 23824828 31. Rroku A Kottwitz J Heidecker B Update on myocarditis–what we know so far and where we may be heading Eur Hear J Acute Cardiovasc Care 2021 10 4 455 467 10.1177/2048872620910109 32. Olejniczak M Schwartz M Webber E Shaffer A Perry TE Viral myocarditis—incidence, diagnosis and management J Cardiothorac Vasc Anesth 2020 34 6 1591 1601 10.1053/j.jvca.2019.12.052 32127272 33. Sarda L Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms J Am Coll Cardiol 2001 37 3 786 792 10.1016/S0735-1097(00)01201-8 11693753 34. Chetrit M Imaging-guided therapies for pericardial diseases Cardiovasc Imaging 2020 13 6 1422 1437 35. Imazio M A randomized trial of colchicine for acute pericarditis N Engl J Med 2013 369 16 1522 1528 10.1056/NEJMoa1208536 23992557 36. Imazio M Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial Lancet 2014 383 9936 2232 2237 10.1016/S0140-6736(13)62709-9 24694983 37. C. for D. Control and Prevention. Guidance for tecovirimat use under expanded access investigational new drug protocol during 2022 US monkeypox outbreak. 2022. 38. Grosenbach DW Oral tecovirimat for the treatment of smallpox N Engl J Med 2018 379 1 44 53 10.1056/NEJMoa1705688 29972742