CV involvement in malaria death may be area for diagnostic, therapeutic improvement
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Due to potential underreporting of CV complications in malaria infection, consistent monitoring for and treatment of CV complications may represent unmet areas in care, researchers reported.
According to a review published in the Journal of the American College of Cardiology, malaria was responsible for 400,000 deaths globally in 2018, and although CV involvement was not commonly attributed to infection mortality, complications may be unrecognized and underreported from a lack of diagnostic testing or overlap with other fatal events.
“Malaria continues to be a serious health problem in endemic regions. Cardiac involvement seems to be rare from the low reporting incidence; however, studies have shown late detection could be potentially lethal and frequent. Early detection of CV compromise is crucial to improve prognosis,” Shyla Gupta, student at the Kingston Health Sciences Center at Queen’s University in Kingston, Ontario, Canada, and colleagues wrote.
For this analysis, researchers evaluated 28 documents to assess CV involvement in malaria mortality and to report cardiac monitoring and treatment methods.
CV complications in malaria
According to the review, reported CV complications include myocarditis, pericarditis, pericardial effusion, ischemic disease and HF.
Moreover, high serum levels of parasitemia, immunocompromised states, poor nutrition and chronic heart problems may increase the severity of CV complications, the researchers wrote.
Researchers reported three potential pathophysiological causes of CV complications in malaria infection: an imbalanced proinflammatory cytokine response, endothelial dysfunction and/or the sequestration of infected red blood cells in cardiac capillaries that cause blood flow obstruction and ischemic injury.
According to the review, cardiac symptoms resolve once the malaria infection has been treated; therefore, no specific treatments for CV complications exist aside from hemodynamic support when necessary.
“The systemic stress of a severe malaria infection is thought to impact general cardiac function, as well as other general complications such as severe anemia and kidney disease,” the researchers wrote. “In addition, some antimalarial drugs have been reported to cause cardiotoxicity, presenting as CV complications in the recovery phase.”
Complications in malaria treatment
Complicated malaria is treated with IV quinidine and replaced with sulfadoxine as serum levels of parasitemia decrease and symptoms resolve; however, polymorphic ventricular tachycardia is a known life-threatening complication of quinines. The researchers reported that other CV adverse effects include angina, hypotension, circulatory failure and cardiac arrest. Quinidine can also cause long QT syndrome among high-risk patients such as children with severe anemia, Gupta and colleagues wrote.
In addition, mefloquine, another therapy for malaria, may occasionally cause sinus bradycardia and long QT syndrome, according to the researchers.
“Standardized tests, such as ECGs, should be considered for early identification and prevention of CV compromise,” the researchers wrote. “Patients diagnosed with malaria should be monitored carefully, especially when presenting with clinical findings of heart failure. Both serum levels of parasitemia and cardiac biomarkers should be monitored as they are important in determining CV involvement: Despite nonspecific findings on a physical examination, there may be elevated levels of troponin T or N-terminal pro-B-type natriuretic peptide indicating myocardial injury.”
According to the review, prior routine ECGs, follow-up appointments and early serum analyses found that most CV involvement in malaria is fully reversible; however, in cases of severe malaria, patients should be monitored immediately and routinely to prevent fatal progression.
Perspective
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Frederick Masoudi, MD, MSPH, FACC
For those of us who practice in areas where malaria is not endemic, it reminds us of the public health importance of the condition (more than 220 million cases and almost 500,000 deaths per year globally). Despite the substantial incidence of malaria, the published data on the CV effects of the condition is fairly sparse, which could mean one of two things: CV complications from malaria are rare and/or because of where malaria occurs, the capacity to ascertain for CV complications is limited, resulting in underdiagnosis. I would guess that both are relevant. Regardless, even a rare manifestation of a common infection can have important implications.
There are case reports of myocarditis and pericarditis with malaria; the more commonly reported systemic effects, specifically anemia and acute kidney injury, have secondary CV effects as well.
The toxicity of many antimalarial therapies (specifically QT prolongation and risk for polymorphic VT) is better documented and highlights the value of the capacity to monitor for this toxicity when treatment is provided.
Given the importance of malaria (and other tropical diseases), more systematic data on the clinical manifestations and outcomes would have substantial public health impact. The studies that were included in this paper enrolled around 1,000 individuals — a strikingly small number for such a common condition. While I am not aware of ongoing efforts to collect data systematically, a registry could play a critical role in better understanding malaria and its effects on multiple organ systems, including the heart.
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