Is Endomyocardial Biopsy Still Necessary if Cardiac MRI Is Available?

By Michael H. Crawford, MD, Editor

SYNOPSIS: A multicenter registry study in Europe of patients with suspected myocarditis has shown that, compared to cardiac magnetic resonance imaging, endomyocardial biopsy still is the gold standard, and lower ejection fraction and need for immunosuppressant drugs predicted a worse outcome.

SOURCE: Caforio ALP, Kaski JP, Gimeno JR, et al. Endomyocardial biopsy: Safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObsevational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. Eur Heart J 2024;45:2548-2569.

The primary aims of the European Society of Cardiology (ESC) EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry were to study the clinical and diagnostic features of patients with myocarditis using the 2013 ESC diagnostic criteria, and their outcomes over one year.¹ In 46 centers from 18 countries in Europe, consecutive patients over one year with new or previous diagnosis of clinically suspected or biopsy-proven myocarditis were included and divided into three groups: group 1 (G1), clinically suspected myocarditis confirmed by cardiac magnetic resonance (CMR) using the Lake Louise criteria; G2, endomyocardial biopsy (EMB)-proven myocarditis (Dallas criteria) with or without CMR; and G3, clinically suspected myocarditis with negative or inconclusive CMR results.

The primary combined endpoint was death or heart transplantation or hospitalization or ventricular assist device (VAD) implantation or implantable cardioverter defibrillator (ICD) implantation at one-year follow-up. A total of 581 patients were included; 68% were male, 493 were adults, the median age was 38 years, and 88 were children with a median age of 8 years. Of the 581 patients, 233 (40%) were in G1, 222 (38%) were in G2, and 126 (22%) were in G3. New cases accounted for 80% of the patients.

At baseline, adults had more hypertension and angina, and children were more likely to present with New York Heart Association class III-IV symptoms (both P < 0.001). CMR was performed in 71% of patients, but fewer were performed in children. EMB was performed in 76% of patients (fewer in children), had a low complication rate of 5% in both children and adults, and there were no deaths. The most frequent complications of EMB were pericardial effusion (n = 5) and tamponade (n = 3).

The histologic findings were active myocarditis in 53% of patients, borderline in 36% of patients, and healed in 11% of patients. The most common histologic type was lymphocytic in 83% of patients, followed by giant cell in 8% of patients. A positive viral polymerase chain reaction on EMB was found in 34% of patients and was more common in children vs. adults (76% vs. 26%; P < 0.001). At one year, 3% of patients had died, 2% of patients had a heart transplant, 1% of patients had a VAD, and 4% of patients had an ICD.

Multivariable predictors of a lower risk of these adverse outcomes were a normal left ventricular ejection fraction (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.99, P = 0.004). A higher risk of these events was predicted by the use of immunosuppressant or immunomodulatory drugs (HR, 1.92; 95% CI, 1.26-2.92; P = 0.002). The authors concluded that EMB is safe and CMR is less sensitive for diagnosing myocarditis. Also, most patients are virus-negative by EMB, and the use of immunologic therapy was low, but its use was predictive of adverse outcomes at one year.

COMMENTARY

There is increasing interest in CMR for the diagnosis of myocarditis because of the perceived higher risk and the need for experienced practitioners for EMB. Thus, this registry study from Europe is of interest. Its strengths included a relatively large population and a high frequency of EMB and CMR usage (≥ 70% of patients) and only 22% of patients had neither performed. Also, it was a homogeneous population compared to prior observational studies, since the 2013 ESC guideline criteria for clinically suspected myocarditis were employed.¹ In addition, other diagnoses, such as Takotsubo and dilated and arrhythmogenic cardiomyopathy, were systematically excluded.

The results confirm previous data showing that myocarditis is more common in younger males, most are virus-negative on EMB, and lymphocytic myocarditis predominates; few get immunosuppressant drugs, and outcomes are similar in adults and children. Finally, in those who had both studies, CMR using the Lake Louise criteria was less sensitive than EMB using the Dallas criteria.

Although virus-negative by EMB was the most common diagnosis in adults and children, suggesting that an immune-mediated pathophysiology was predominant, a post-virus immune reaction could not be excluded. In those with virus detected, the most common was parvovirus, the so-called fifth disease in children. Giant cell, sarcoid, and eosinophilic myocarditis were not seen in children and were uncommon in adults. Interestingly, giant cell and sarcoid were more frequent in those from Northern Europe, and they had worse outcomes.

The observed safety of EMB, especially in children, has to be tempered with the fact that these were tertiary centers chosen for their expertise in myocarditis management. However, those chosen for EMB tended to be the sicker patients who might be expected to do worse than what was observed. Also, the pathogenicity of virus detected by EMB is unknown. They could just be innocent bystanders. In addition, the registry was closed prior to COVID, so no data on coronavirus are available. Finally, CMR is a rapidly developing field, and improvements in the near future could improve its sensitivity.

For now, it appears EMB still is the gold standard for the diagnosis of myocarditis in adults and children.

REFERENCE

1. Caforio ALP, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2636-2648.