Letter to the editor - To conclude that BNT162b2 does not worsen echocardiographic indices, well-powered multicenter studies are required

Sep 29, 2026

Uploaded by Riley

Letter to the editor evaluating a preliminary prospective study on echocardiographic findings in 25 adolescent vaccinees after the second BNT162b2 dose. The correspondent discusses limitations including small sample size, unclear reasons for steady increases in systolic function, omission of autonomic function measures, and inadequate explanation of sex-specific changes in LVIDs. The letter asks how sympathetic activation and peri-vaccination symptoms were assessed and argues that larger, well-powered multicenter studies are needed before concluding no worsening.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages1

Reading Time3 min

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Letter to the editor

Study overview and interpretation

Key limitations and discussion points

Autonomic function and measurement questions

Sex-specific findings and symptom explanations

Conclusion and call for further studies

J Chin MedAssoc Letter to the editor To conclude that BNT162b2 does not worsen echocardiographic indices, well-powered multicenter studies are required Josef Finsterera,* , Claudia Stollbergerb aNeurology and Neurophysiology Center, Vienna, Austria; bSecond Medical Department, Klinik Landstrasse, Vienna, Austria DEAR EDITOR, We read with interest Hsu et al’s1 article on the echocardiographic findings in 25 adolescent vaccinees who received the second dose of the BNT162b2 vaccine. Serial echocardiographic examinations were performed on days −7, 2, 7, 14, and 28 before/ after vaccination.1 Ejection fraction increased from 73.8% at baseline to 77.8 on day 28.1 Likewise, fractional shortening increased from 42.4% at baseline to 46.7% on day 28 postvaccination.1 In females (n = 11), left ventricular assist devices (LVIDs) decreased from baseline to day 2 postvaccination.1 It was concluded that adolescents vaccinated with BNT162b2 often experience transient discomfort after the second dose, but serial echocardiography does not detect significant deterioration until day 28 postvaccination.1 The study is impressive, but some points require discussion. The major limitation of the study is the small group size. Because cardiac complications following severe, acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccinations are reported to be rare,2 it would be imperative to convert the design to multicenter and international to increase the group size and increase the likelihood that some of the included vaccinees will become manifest with cardiac side effects. No final conclusions can be drawn before expanding the study cohort. A second limitation is that there is no comprehensible explanation as to why systolic function increased steadily from baseline to day 28 postvaccination.1 Was the increase in systolic function a compensatory mechanism for myocardial damage not visible on echocardiography or due to increased sympathetic tone? In a study of isolated rat cardiomyocytes, both messenger ribunucleic acid (mRNA)-1273 (Moderna) and BNT162b2 led to the expression of the spike protein in cardiomyocytes 48 hours after vaccination, mRNA-1273 induced arrhythmic and completely irregular contractions associated with irregular and localized calcium transients, suggesting dysfunction of the cardiac ryanodine receptor (RyR2), and BNT162b2 increased cardiomyocyte contractility via increased protein kinase-A (PKA) activity on the cellular level.3 A third limitation is that autonomic function was not included in the analysis. Because systolic function depends on the balance between sympathetic and parasympathetic drive, we should know how the level of sympathetic activation was measured and included in the assessment. Vaccinees in whom sympathetic tone predominates may have higher systolic function than vaccines in whom parasympathetic tone predominates. Were urinary catecholamines or serum norepinephrine levels measured before echocardiography was performed?4 A fourth limitation is that the decreased LVIDs in femaleson day 2 were not adequately explained. Were the decreased LVIDs in females attributable to the significantly increased LVIDat baseline in males compared to women? How was chest pain within 2 days of vaccination explained in “most vaccinees”? Was there elevated blood pressure, coronary spams, pulmonary embolism, or systolic dysfunction on the first-day postvaccination that could not be detected in the study because the first echocardiography was not performed until the second day after vaccination? In conclusion, the interesting study has limitations that put the results and their interpretation into perspective. Clarifying these weaknesses would strengthen the conclusions and could improve the study. Before concluding that echocardiographic parameters do not worsen after vaccination with BNT162b2, well-powered multicenter studies must be performed. REFERENCES 1. Hsu WF, Hsu CH, Jeng MJ. Echocardiogr

FAQs

What is the main conclusion the letter challenges regarding BNT162b2 and echocardiographic indices?

The letter argues that concluding BNT162b2 does not worsen echocardiographic indices requires well-powered multicenter studies and that the current findings should be interpreted with caution due to multiple limitations.

What limitations does the letter identify in the referenced study?

The correspondent highlights small sample size, lack of a clear explanation for steadily increasing systolic function, absence of autonomic function analysis, and insufficient explanation for decreased LVIDs in females on day 2.

What additional analyses or measurements does the letter request to strengthen conclusions?

The letter asks how sympathetic activation was measured and included, whether urinary catecholamines or serum norepinephrine were assessed, and how early chest pain and related cardiovascular events after vaccination within the first 2 days were explained.

Sep 29, 2026

Uploaded by Riley