A Closer Look at Cardiovascular Complications of Malaria

Malaria has many serious cardiovascular complications and typical antimalarial therapies present an increased risk for fatal cardiac side effects. This highlights the importance of these patients being evaluated for possible cardiac involvement. This perspective was stated in a review published in the Journal of the American College of Cardiology.

Studies of cardiovascular abnormalities and malaria were searched in publication databases. A total of 28 case reports, reviews, and studies, as well as 1 randomized controlled trial were included in this analysis.

Patients with malaria infection present with fever, flulike symptoms, and myalgia. Stage 1 is identified by intense shivering. Stage 2 includes fever, headache, nausea, vomiting, and myalgia for 3 to 7 hours. During stage 3, other symptoms begin to wane, but the patient has intense sweating for about 4 hours.

Prompt identification and treatment is required to avoid potentially serious complications. Pregnant women, older adults, children, and people with coexisting conditions are at increased risk for severe malarial infection.

Possible complications of malaria include reduced cardiac output, conduction disorders, myocarditis, pericarditis, arrhythmias, cardiac tamponade, and heart failure. Malaria’s direct consequences on the cardiovascular system remain poorly understood, but hypotheses involve erythrocyte sequestration and proinflammatory cytokine response.

Infected red blood cells have an increased expression of adhesion membrane proteins that can impair microcirculation, causing increased cytoadherence to endothelial cells. Proinflammatory cytokines can induce energy depletion of cardiac muscle cells and the plasmodial toxin may induce apoptosis among cardiomyocytes.

In addition, malaria is associated with profound anemia, which may cause cardiac stress or left ventricular hypertrophy. Anemia may also lead to acute renal failure.

There have been no generally accepted recommendations for diagnosing potential cardiovascular involvement among patients with malaria. In a prospective cohort of patients with malaria, an electrocardiogram detected cardiovascular involvement in 17% of participants. Another study used electrocardiograms and echocardiograms to determine that 26% of participants had evidence of cardiovascular involvement.

The review authors propose that patients with evidence of complicated malaria, high parasitemia, or signs of cardiovascular involvement be evaluated by electrocardiogram and for cardiac biomarkers, such as troponin T or N-terminal pro-B-type natriuretic peptide. If abnormalities are identified, these patients should be further evaluated with echocardiogram or magnetic resonance imaging.

In addition to the typical therapy of intravenous quinidine and continuous monitoring among patients with severe malaria, patients with cardiovascular involvement may require symptom-specific therapy. For instance, patients with myocarditis or pericarditis should be treated with anti-inflammatory therapy and possibly steroids.

In the case of heart failure or renal failure, diuretics, fluids, or transfusions may be required. Patients with evidence of arrhythmia may need additional monitoring. Some antimalarial drugs, such as mefloquine, may be poor treatment candidates because they have been associated with sinus bradycardia or QTc interval prolongation.

This study was limited by the underlying studies. Many had an observational design with a short follow-up. Cardiovascular involvement may have been under-reported, and long-term consequences remain unclear.

The review authors concluded that early detection of cardiovascular involvement among patients with malaria infection is imperative for effectively administering interventions and avoiding long-term complications.

Additional research is needed to better understand the relationship between the cardiovascular system and infection with malaria.

Reference

Gupta S, Gazendam N, Farina JM, et al. Malaria and the heart. JACC state-of-the-art review. J Am Coll Cardiol. 2021;77(8):1110-1121. doi:10.1016/j.jacc.2020.12.042