CV Complications of Malaria Rare but Portend Poor Prognosis

Cardiovascular complications resulting from malaria are rare, but they can occur and, when they do, are associated with “considerable morbidity,” according to a new state-of-the-art review published this week in the Journal of the American College of Cardiology.

Specific complications from malaria, a mosquito-borne parasitic disease found in Asia, Oceania, South and Central America, and sub-Saharan Africa, include electrocardiogram abnormalities, myocarditis, pericarditis, pericardial effusion, ischemic disease, and heart failure. “Although the cardiovascular system isn’t the first to be affected, when it is, it is a marker of poor prognosis,” senior author Adrian Baranchuk, MD (Queen’s University/Kingston Health Sciences Center, Ontario, Canada), told TCTMD. 

The extent of cardiovascular involvement in malaria has been very difficult to discern, because there are no large registries keeping tabs on cardiac complications, say researchers. These cardiac effects may be underreported or underdiagnosed due to lack of awareness, lack of diagnostic strategies, or their overlap with other fatal complications, such as circulatory collapse or sudden cardiac death.

“There is a lack of comprehensive literature in diseases that are highly prevalent in some parts of the world, but not necessarily in developed countries,” said Baranchuk. “Now that we’ve all gotten into the epidemiology of disease with COVID-19, when you see the numbers of people infected in the last year with malaria, it’s much, much higher than people infected with COVID-19. The other thing is that this is not a new disease, it’s a very old existing disease, but it doesn’t affect the rich parts of the world and so we haven’t paid enough attention to it.”

Worldwide, malaria is found in more than 100 countries, with an incidence of 230 million cases and 405,000 deaths in 2018. The disease is commonly transmitted via a mosquito bite, although there are other infrequent causes. The most common strains of malaria are Plasmodium (P.) vivax and P. falciparum, with P. falciparum causing the majority of severe cases. As Baranchuk noted, transmission occurs frequently in areas with high levels of poverty, as well as in those with close contact to animals, areas with poor sanitation, or those in proximity to rural areas.    

NET-Heart Project From Inter-American Society of Cardiology

The new review, led by Shyla Gupta, MD (Queen’s University/Kingston Health Sciences Center), is part of the Neglected Tropical Diseases and Other Infectious Diseases Affecting the Heart (NET-Heart) project conducted by the emerging leaders’ program of the Inter-American Society of Cardiology. The main goal of the NET-Heart project is to evaluate the evidence on neglected tropical diseases and their cardiovascular effects. The working group identified 17 neglected diseases, malaria among them, and as part of the project seeks to provide recommendations and potential diagnostic/therapeutic algorithms to help physicians manage the cardiovascular complications of the diseases.   

In their review of the data, the researchers found several case reports and other reviews, as well as five prospective studies, a single case-control study, one cross-sectional study, and one retrospective study. There was one published randomized trial to date, a study testing the cardiovascular safety of extended artemether-lumefantrine treatment in 195 patients with malaria.

Travelers visiting parts of the world where malaria is more common could become infected with the disease, which is not a problem if it is diagnosed and treated early. However, on their return, their symptoms “might not turn on the alarm” for physicians unaccustomed to seeing them, said Baranchuk, leading to missed diagnoses. The most serious complications are cerebral malaria, severe anemia, respiratory failure, hypoglycemia, and acute renal failure.

Although the pathophysiological mechanisms underlying cardiovascular involvement in malaria aren’t fully understood, the investigators believe there are a number of factors at play. For example, an imbalanced pro-inflammatory cytokine response and erythrocyte sequestration, where infected erythrocytes tend to adhere to the endothelium of blood vessels, specifically smaller capillaries and venules, are two possible mechanisms. Anemia produced by hemolysis and suppressed hematopoiesis might also impair cardiac function and eventually lead to left ventricular hypertrophy due to volume overload, say investigators.  

“Anemia is one of the characteristic markers,” said Baranchuk. If the patient is located in a region where malaria is endemic, or they have just returned from the area, anemia “should prompt rapid investigation to rule out malaria as the cause if the cause isn’t otherwise right in front of you.”

The researchers also propose a novel algorithm for cardiovascular screening in patients with malaria. For patients infected with the P. falciparum strain who develop complicated malaria (such as kidney disease or anemia), high parasitemia levels, or signs or symptoms that suggest cardiac problems, they recommend blood work to assess cardiac biomarkers and an ECG. If abnormal, physicians should consider more complex testing, such as echocardiography or MRI, they suggest. Baranchuk acknowledged that endemic regions might not have access to more-complex tests, so they provide recommendations specific to those zones. Here, if myocardial dysfunction is strongly suspected after an ECG and biomarker testing, they recommend transferring the patient to another facility or treating the patient according to best clinical judgement if transfer isn’t available.    

Finally, the researchers point out that complicated malaria from P. falciparum can be resistant to oral chloroquine and may require treatment with intravenous quinidine. Baranchuk stressed that intravenous treatment requires strict monitoring because these agents can cause life-threatening arrythmias and QTc prolongation. For patients requiring this type of antimalarial treatment, Baranchuk suggested use of mobile units in endemic regions that can accept patients with severe malaria who are going to receive intravenous medications so they can be monitored for any potential cardiac complications.