From HITS to misses - aspirin’s effect on TCD-detected cerebral microemboli in Chagas cardiomyopathy - Editorial

Sep 29, 2026

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A editorial discusses a pilot randomized PROBE trial assessing whether acetylsalicylic acid (aspirin) reduces transcranial Doppler (TCD)–detected cerebral microembolic signals in Chagas cardiomyopathy. Chagas disease from Trypanosoma cruzi is linked to higher thromboembolic risk and ischemic stroke, with HITS/microembolic signals marking subclinical embolic activity. In 22 Chagas HF patients with HITS, aspirin 300 mg daily for seven days eliminated persistent HITS versus controls, suggesting a possible short-term biological effect, while highlighting small sample size and brief follow-up limitations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Background: Chagas disease and cerebral microemboli

Why TCD-detected HITS matter

Trial design and endpoints

PROBE randomized controlled pilot

Results in Chagas HF patients with HITS

Persistence after one week

Mechanistic and contextual evidence

Platelet inhibition and anti-inflammatory pathways

Limitations and clinical implications

Article published online: 2025-12-02 Editorial 1 From HITS to misses: aspirin’s effect on TCD-detected cerebral microemboli in Chagas cardiomyopathy Brandon J. Bond 1,2 Victoria Grau Kazmieczak 1 José Biller 1,2 1 Loyola University Health System, Loyola University Chicago, Stritch School of Medicine, Department of Neurology, Maywood, Illinois, United States 2 Loyola University Health System, Loyola University Chicago, Stritch School of Medicine, Department of Neurological Surgery, Maywood, Illinois, United States Arq. Neuro-Psiquiatr. 2025;83(10):s00451812885 . Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health challenge in LatinAmerica and is increasingly recognized in non-endemic regions due to migration.1 Affecting over 7 million people globally, it is a leading cause of non-ischemic cardiomyopathy and heart failure (HF) in endemic countries, with up to one-third of infected individuals developing cardiac involvement. 1,2 Chagas cardiomyopathy carries a substantial risk of arrhythmias, sudden death, and thromboembolic events, particularly stroke. 1,3 Epidemiologic studies identify Chagas disease as an independent predictor of ischemic stroke—HR 2.54 (95% CI 1.01–6.42) in a heart-failure cohort, and OR 7.17 (95% CI 1.50–34. 19) in a case–control study.3,4 Proposed mechanisms include chronic inﬂammation, endothelial dysfunction, and a prothrombotic state contributing to intracardiac thrombus—particularly in patients with a left ventricular apical aneurysm or reduced left ventricular ejection fraction (LVEF).1 Transcranial Doppler (TCD) ultrasonography enables the detection of cerebral microembolic signals—high-intensity transient signals (HITS), also termed microembolic signals (MES)—which are considered markers of subclinical embolic phenomena traversing the cerebral circulation.5 These signals have been correlated with elevated early stroke risk inpatients with carotid stenosis and occlusion.6 TCD-detected microembolic signals are more frequent in Chagas cardiomyopathy than in other causes ofHF(12.9%vs1.2%)and this association is independent of LVEF, suggesting additional mechanisms—including chronic inﬂammation—may contribute to cerebral embolic activity.7 Yet, whether this microembolic activity is modiﬁable through antithrombotic therapy in Chagas cardiomyopathy has remained unclear. In this context, the pilot randomized controlled trial by Castello-Branco and colleagues offers compelling prelimi- Address for correspondence Brandon J. Bond (email: [brandon.bond@lumc](brandon.bond@lumc). edu) . received October 10, 2025 accepted October 13, 2025 DOI [https://doi.org/](https://doi.org/)[ ](https://doi.org/)10.1055/s-0045-1812885 . ISSN 0004-282X. nary evidence that acetylsalicylic acid (ASA, or aspirin) may mitigate cerebral microembolism in Chagas HF.8 Conducted using a prospective, randomized, open-label, blinded-endpoint (PROBE) design, the study enrolled patients with Chagas HF and HITS on baseline TCD, randomizing them 2:1 to receive ASA 300 mg daily for seven days plus standard therapy or standard therapy alone. The cohort reﬂected a relatively low thromboembolic risk proﬁle: all were in sinus rhythm (atrial ﬁbrillation [AF] excluded), had no prior stroke, and were not anticoagulated at baseline, though some were taking antiplatelet agents. The primary endpoint was the persistence of HITS after one week, assessed by a blind investigator. Of 373 HF patients screened (190 with Chagas disease), HITS were identiﬁed in 11%, without signiﬁcant difference between Chagas (12%) and non-Chagas (8%) groups after multivariable adjustment for age, sex, and LVEF (odds ratio 1.33, 95% CI 0.60–2.95). Among the 22 Chagas patients with HITS,12were randomized(8toASA, 4to control). After7 days, none of the ASA-treated patients exhibited persistent HITS, whereas two of four controls (50%) continued to do so (p ¼0.028). Median HITS decreased from 3.5 to 0 in the AS

FAQs

What do TCD-detected HITS (microembolic signals) represent in this article?

HITS are high-intensity transient signals detected by transcranial Doppler and are considered markers of subclinical embolic phenomena traveling through cerebral circulation.

How was aspirin tested, and what was the primary endpoint?

A pilot prospective randomized open-label blinded-endpoint (PROBE) trial randomized Chagas HF patients with baseline HITS 2:1 to aspirin 300 mg daily for seven days plus standard therapy versus standard therapy alone; the primary endpoint was persistence of HITS after one week assessed by a blinded investigator.

What were the main findings regarding persistent HITS after seven days?

None of the aspirin-treated patients showed persistent HITS, while two of four controls (50%) continued to do so. Aspirin also reduced median HITS from 3.5 to 0, supporting a possible short-term effect despite limited statistical significance overall and small sample size.

Sep 29, 2026

Uploaded by Eliana