Dr. Philip McMillan, John McMillan

On a routine visit to her local clinic, 78-year-old Mrs. Nakamura received a third COVID-19 vaccine dose (mRNA-1273) after previously receiving two doses of BNT162b2. Four days later, she began experiencing palpitations and shortness of breath, which gradually worsened over the next week. Eleven days post-vaccination, Mrs. Nakamura was rushed to hospital with symptoms of heart failure, including severe shortness of breath, rapid heartbeat, and swelling in her legs.

Upon admission, Mrs. Nakamura’s condition was concerning. Her heart rate was elevated at 120 beats per minute, and her oxygen saturation was low at 90% in room air. Physical examination revealed signs of acute heart failure, including jugular vein distention, bilateral leg edema, and abnormal heart sounds. Initial tests showed cardiomegaly on chest X-ray, abnormal ECG findings, and elevated cardiac biomarkers.

Diagnosis and STORM Mechanism

Further diagnostic imaging, including echocardiography and cardiac magnetic resonance imaging, revealed severe left ventricular dysfunction, cavity enlargement, and other abnormalities suggestive of inflammatory dilated cardiomyopathy (iDCM). An endomyocardial biopsy confirmed the diagnosis, showing inflammatory infiltrates and other characteristic features of iDCM.

Mrs. Nakamura’s condition had all the characteristics of a proposed mechanism called STORM (spike-triggered autoimmune response mechanism). This theory suggests that the immune response triggered by the infection or vaccine’s spike protein can lead to inflammation in the heart. The STORM mechanism may explain the development of vaccine-associated myocarditis (VAM) in this case.

Understanding STORM and Its Effects

STORM is thought to occur when the immune system overreacts to spike protein produced by infection or the vaccine, leading to an autoimmune response that targets heart tissue. This can result in myocarditis and, in severe cases like Mrs. Nakamura’s, progress to inflammatory dilated cardiomyopathy (iDCM). The process begins with the vaccine’s spike protein triggering an immune response in the body. In some individuals, this immune response may become misdirected, causing the immune system to attack heart tissue due to cross-reactivity between antibodies against the SARS-CoV-2 spike protein and structurally similar cardiac antigens.

The autoimmune reaction triggers an influx of inflammatory cells, specifically CD68+ macrophages and CD3+ T-lymphocytes, into the heart muscle, as revealed by the biopsy. This cellular infiltration causes myocarditis, potentially damaging cardiac tissue and impairing heart function. Consequently, patients may experience symptoms such as shortness of breath, palpitations, and signs of heart failure. In severe cases like Mrs. Nakamura’s, prolonged inflammation can progress to dilated cardiomyopathy (DCM), characterized by an enlarged and weakened heart.

Treatment, Recovery, and Significance

Mrs. Nakamura was treated with a combination of therapies, including oxygen therapy, intravenous nitroglycerine, loop diuretics, anti-heart failure medications, and oral prednisolone. Her condition improved steadily with treatment, and she was discharged after 16 days with a reduced dose of prednisolone.

At the 6-month follow-up, Mrs. Nakamura’s cardiac function had significantly improved. Echocardiography showed normalized left ventricular size and function, and the ECG abnormalities had resolved. The patient remained clinically stable without recurrence during the one-year follow-up period.

This case is significant for several reasons. It’s the first reported case of biopsy-proven iDCM following mRNA-1273 immunization in an older female patient. It occurred after a heterologous vaccination schedule, which may be associated with a higher risk of VAM. The case demonstrates the importance of considering vaccine-associated myocarditis in patients presenting with heart failure symptoms after COVID-19 vaccination, regardless of age or gender.

Mrs. Johnson’s case reminds us that while vaccine-related iDCM is rare, it is treatable if diagnosed early. It underscores the need for clinicians to be aware of this possibility in patients presenting with heart failure symptoms following COVID-19 vaccination, and to consider performing an endomyocardial biopsy when necessary for accurate diagnosis and appropriate treatment. The STORM mechanism provides a potential explanation for these rare adverse events and may guide future research and treatment strategies.