Cardiovascular manifestations of monkeypox virus outbreak: An overview of the reported cases

Abstract

Background

Monkeypox (Mpox) is a zoonotic DNA virus related to the orthopoxvirus family that causes also smallpox infection.

Objectives

In this paper, we aimed to study the cardiovascular manifestations of Mpox.

Method

A literature databases search was conducted on 20th October 2022 and limited to 2022 (the new outbreak) to collect all the relevant papers that discussed cardiovascular manifestations in Mpox.

Results

The literature included 6 cases of myocarditis, one case of pericarditis, one case of myopericarditis and one case of atrial fibrillation. Of total 6 cases with completed data, ECG results and troponin levels were abnormal in 5 cases while only three cases had abnormal ECHO and CMR results. In the four cases who undergone chest X-rays, only one patient had non-specific retro-cardiac opacities. All patients (9 cases) recovered well from their cardiovascular manifestations with no deaths and only 3 of them required ICU admission.

Conclusion

With the limited reported cases, we recommend performing cardiovascular examinations -in particular ECG and troponin levels- in order to exclude cardiovascular insult in patients with suspected Mpox -cardiovascular involvement. However, in our series the infection was mild in most patients with no mortality.

Introduction

Monkeypox (Mpox) is a zoonotic DNA virus related to the orthopoxvirus family that causes also smallpox infection, and is first diagnosed in humans in 1970.¹ From the beginning of 2022, more than 70,000 cases were reported of Mpox infection in more than 50 countries, prompting the world health organization (WHO) to declare it as a public health concern.^{2 , 3}

Mpox symptoms mainly included rash, fever, lymphadenopathy, fatigue and headache; however asymptomatic nature of the disease is reported as well.4, 5, 6 Large respiratory droplets, close or direct contact with skin lesions, and possibly contaminated fomites are the common routes of Mpox spread.^{7 , 8} Fortunately, Mpox is self-limited, and supportive treatment is sufficient based upon the reported literature.⁹ Moreover, less than 5% of hospitalized patients had fatal outcomes.¹⁰

Many viruses are related to cardiac infections.^{11 , 12} In a large population study of Thornhill et al. across 16 countries and including more than 500 Mpox cases, the authors indicated that two Mpox patients experienced myocarditis and both patients recovered well with supportive treatment.¹³ Moreover, two Mpox patients had high troponin levels and were complaining from chest pain and/or dyspnea were finally diagnosed with myocarditis.¹⁴ Therefore, we aimed to collect all available evidence regarding the cardiovascular manifestations of Mpox and the associated outcomes of those patients.

Method

Database search and search procedure

We followed the guidelines of Liberati and colleagues which known as PRISMA checklist for conducting systematic reviews.¹⁵ Five databases were searched on 20th October 2022 and limited to 2022 (the new outbreak). We used the search term “("monkeypox" OR "MPV" OR "monkeypox virus" OR "monkey pox") AND ("arrhythmia" OR "pericarditits" OR "myocardititis" OR "heart failure" OR "myocardial infarction" OR "acute coronary syndrome" OR "pericardial effusion" OR "heart")” to collect all the relevant papers from Scopus, Google Scholar, PubMed, Virtual Health Library and Web of Science. Another round of searching was performed by using each keyword alone in Google Scholar to avoid missing any relevant paper.

After transferring all the results of the database search, duplicates were excluded and the remaining records were transferred to an Excel sheet for facilitating the screening process. At least two authors scanned all papers via title and abstract then full text screening methods. A senior author revised all the screening results to ensure collecting all the available literature.

Inclusion criteria: We included all papers that discussed cardiologic manifestations of Mpox in 2022 without restriction to study design, language or country of patients.

Exclusion criteria: We excluded Mpox cases before the new pandemic in 2022, review papers and pre-print papers.

Data extraction

The extraction sheet was done by the most experienced author together with the incorporation of the senior author. The extraction sheet included: study ID, age, sex, comorbid conditions, Mpox diagnostic method, symptoms and signs at admission, laboratory, chest X-ray, electrocardiogram (ECG), echocardiography (ECHO) and cardiac magnetic resonance (CMR) findings, intensive care unit (ICU) admission, treatment, outcome of patients and the final cardiovascular diagnosis.

Quality of evidence

Based upon the study designs we found, we used two quality assessment tools to rate the quality of evidence. The National Institute of Health tool was used for the cohort and the cross-sectional studies and the Joanna Briggs Institute Critical Appraisal tool was used for the case reports studies (Table S1 and S2).

Results

Study selection and outcomes

We screened 2298 records in two steps. The first step was title and abstract screening at which we excluded 2264 records. The second step was full text screening which resulted in inclusion of 5 papers together with another 2 papers from manual search methods (Fig. 1 ).

Fig. 1.

PRISMA flow diagram of the study process.

We included 9 patients from 7 papers.^{13 , 14 ,} 16, 17, 18, 19, 20 Four cases were from USA, two from Canada, one from Portugal and two cases from the multicenter study.¹³ The literature included 6 cases of myocarditis, one case of pericarditis, one case of myopericarditis and one case of atrial fibrillation (Fig. 2 ). Characteristics, symptoms, examination and laboratory data of patients were reported from 5 studies (6 patients) and missed in two studies, Thornhill et al.¹³ and Miller et al.,¹⁹ (authors were emailed and did not reply to get the needed data) (Table 1 ).

Fig. 2.

The cardiovascular manifestations of Mpox patients.

Table 1.

Characteristics and outcomes of MPV cases.

Study ID	Country	Age	Sex	Comorbidities	MPV diagnosis	Symptoms and signs at admission	Laboratory findings	Chest X-ray findings	ECG findings	Echo findings	CMR	ICU admission	Treatment	Outcome	Heart abnormality
Pinho-2022	Portugal	31	M	Pre-exposure prophylaxis against HIV	PCR	Chest tightness radiating to the left upper extremity	Elevated CRP, CPK, troponin I, and brain natriuretic peptide.	Normal	Sinus rhythm with nonspecific ventricular repolarization abnormalities	Normal	Areas of increased signal intensity in the basal inferior and lateral segments were found, corresponding to myocardial edema. Subepicardial enhancement in the mid inferolateral segment and midwall enhancement in the remaining inferior and lateral segments of the LV.parametric mapping demonstrated regional increase of T2 and indicated an abnormally expanded myocardial extracellular volume in the lateral wall. Postcontrast T1 mapping confirmed myocardial gadolinium accumulation with a non-ischemic pattern in the lateral wall.	Yes	Supportive care and exercise restriction	Recovery	Myocarditis
Shaik-2022	USA	51	M	–	PCR	Severe retrosternal chest pain radiating to the left arm and chest tightness after the commencement of the pain	Elevated WBCs, CRP and ESR	Normal	Sinus tachycardia with widespread ST elevation in leads v1-v6	Mild pericardial effusion	–	Yes	1 gram of aspirin	Recovery	Pericarditis
Tan 2022	Canada	40	M	HIV	PCR	Central, nonradiating, pressure-like chest pain but denied cough, palpitations, or shortness of breath	Elevated troponin and creatine kinase		Evolution of ST-segment changes	Moderate global left ventricular dysfunction with an ejection fraction of 40%	Small pericardial effusion, and foci of late gadolinium enhancement in the basal/apical lateral segments corresponding with focal edema	–	Supportive care	Recovery	Myopericarditis
Rodriguez-Nava-2022	USA	32	M	Syphilis	PCR	Chest pain and dyspnea	Elevated troponin T and N-terminal prohormone B-type natriuretic peptide	Normal	Normal	Normal	–	–	Oral tecovirimat and doxycycline	Recovery	Myocarditis
		37	M	Syphilis and HIV preexposure prophylaxis	PCR	Difficulty breathing and decreased exercise tolerance without chest pain, dyspnea after climbing a single flight of stairs, a marked decrease from his baseline.	Elevated troponin T	–	T wave inversions in the inferior and anterolateral leads	Normal	–	–	Supportive care	Recovery	Myocarditis
Thornhill-2022	Multicenter	–	–	HIV	PCR	–	–	–	–	–	–	–	–	Recovery	Myocarditis
		–	–	–	PCR	–	–	–	–	–	–	–	–	Recovery	Myocarditis
Brouillard-2022	Canada	34	M	–	PCR	Chest pain	Elevated WBCs, CRP and troponin	Non-specific retro-cardiac opacities	Sinus tachycardia with antero-lateral concave ST elevation	reduced LV ejection fraction of 44% with reduced global longitudinal strain (14.4%), especially in the anterior and lateral walls.	LV ejection fraction was mildly reduced with mild LV dilation. Possible myocardial edema. Similarly, high extra cellular volumes values were also suggestive of myocardial edema and/or injury.	–	Antibiotics, ibuprofen, colchicine andACE inhibitor	Recovery	Myocarditis
Miller-2022	USA	30	M	HIV, Syphilis	PCR	–	–	–	–	–	–	Yes	Tecovirimat, 2 doses of VIGIV, and antimicrobials. Trifluridine and antibacterial eye drops	Recovery	Atrial fibrillation

MPV= monkeypox virus, M= male, HIV= human immunodeficiency virus, PCR= polymerase chain reaction, CRP= C-reactive protein, CPK= creatine phosphokinase, WBCs= white blood cells, ESR= erythrocyte sedimentation rate, CMR= cardio magnetic resonance, ICU= intensive care unit, (-) = not reported, VIGIV = vaccinia immune globulin intravenous.

Regarding the 6 patients, all of them were male, diagnosed with PCR, presented with chest pain ± dyspnea, chest tightness and decreased exercise tolerance. An elevated troponin was found in 5 cases (Fig. 3 ). ECG results were abnormal in 5 cases while only three cases had abnormal ECHO and three cases had abnormal CMR results (total tested 3). In the four cases who undergone chest X-ray, only one patient had non-specific retro-cardiac opacities. All patients (9 cases) recovered well from their cardiovascular manifestations with no deaths and only 3 of them required ICU admission.

Fig. 3.

laboratory, examination and outcomes data of Mpox patients.

Discussion

Our results showed that six Mpox patients suffered from myocarditis, one patient suffered from pericarditis, one from myopericarditis and one from atrial fibrillation. Moreover, three out of nine patients were admitted to ICU. Most of the patients were male with comorbidities such as HIV and syphilis. These comorbidities made them more susceptible to infections.²¹ However, all the patients recovered from their cardiovascular manifestations, indicating the mild nature of the disease across the cardiovascular system without severe or life-threatening complications in most cases.

According to investigations, elevated troponin levels were reported in five cases, and also five cases had abnormal ECG findings, such as nonspecific ventricular repolarization abnormalities, sinus tachycardia with widespread ST elevation, evolution of ST-segment changes, sinus tachycardia with antero-lateral concave ST elevation and T wave inversions in the inferior and anterolateral leads. Finally, the cardiac magnetic resonance (CMR) and ECHO showed abnormalities in three cases.

Mpox is a viral infection endemic in Africa, especially in the Democratic Republic of the Congo and Nigeria.^{22 , 23} Furthermore, on July 2022 the World Health Organization (WHO) declared Mpox as a global emergency.² Most of the cases were men who had sex with men (MSM). For instance, 98% of the patients in a study conducted on 528 confirmed cases of monkeypox infection in 16 countries were MSM.²⁴ The symptoms of Mpox were: rash, fever, headache, vomiting, conjunctivitis, oral ulceration, lymphadenopathy, sepsis, encephalitis and upper respiratory tract symptoms. In addition, the average hospitalization period was 13.3, and the mean treatment duration was five days.^{25 , 26} Therefore, efforts were made to repurpose the smallpox vaccination to prevent Mpox cases.^{27 , 28}

Myocarditis was associated with many viral infections.^{29 , 30} The most typical pathogenesis of viral myocarditis is lymphocytic myocarditis, which develops 10–14 days after infection and is accompanied by myonecrosis. This condition may be self-limited or culminate in fulminant myocarditis.³⁰ At the same time, the most common form of pericardial affection is pericarditis. It could progress to pericardial effusion, with tamponade in severe cases. Currently, the pathogenicity of how Mpox affects the cardiovascular system remains an area for further investigation. However, the immune-mediated cascade serves as the most accepted theory -until now-, derived from the fact that many cases of cardiac involvement were reported after smallpox vaccination.³¹

Despite being a rare entity, appropriate diagnosis –by the exclusion of other life-threatening conditions such as coronary ischemia- and close monitoring of Mpox patients who encounter cardiovascular complications are necessary to avoid clinical deterioration and to prevent the long-term sequelae. Furthermore, cardiovascular involvement should become one of the most important differential diagnoses when Mpox patients manifested with sudden onset chest pain and/or dyspnea. Moreover, further research is still needed to highlight the true prevalence, pathologic mechanisms, high risk patients, diagnostic algorithms and appropriate treatment agents for cardiovascular involvement in Mpox patients.

Conclusion

With the limited reported cases, we recommend performing cardiovascular examinations -in particular ECG and troponin levels- in order to exclude cardiovascular insult in patients with suspected Mpox -cardiovascular involvement. However, in our series the infection was mild in most patients with no mortality.

Authors’ contribution

AEE was responsible for the study design. All authors extracted the data, wrote the manuscript and approved the final version. All steps were supervised by HME.

Funding

None.

Declaration of Competing Interest

None.