Myocarditis from immune checkpoint inhibitors linked with life-threatening arrhythmias
According to a new study, immune checkpoint inhibitor-induced myocarditis is highly associated with arrhythmias and ECG findings including new conduction blocks, decreased voltage and repolarization abnormalities.
“Immune checkpoint inhibitors (ICIs) have transformed oncology care by unleashing T-cells to achieve anti-tumor effects but can cause inflammatory adverse events including myocarditis,” the researchers wrote. “ICI-myocarditis is highly arrhythmogenic, but specific electrocardiographic manifestations and their prognostic significance are poorly understood.”
With the collaboration of 49 institutions in 11 countries, researchers built a retrospective multicenter registry using a Research Electronic Data Capture web-based platform to evaluate the ECG manifestations of immune checkpoint inhibitor-induced myocarditis.
“This study really exemplifies the power of teamwork. We have formed a true international network with cardiologists and cardio-oncologists from around the world," Cardiology Today Editorial Board Member Javid Moslehi, MD, William Grossman Distinguished Professor and section chief of cardio-Oncology and immunology at the University of California, San Francisco Heart and Vascular Center, said in a press release. “We are now excited about the next studies using the database.”
Through January 2020, 147 cases of immune checkpoint inhibitor-myocarditis were identified, of which 125 patients (median age, 67 years; 63% men) had a presenting ECG obtained within 3 days of hospital admission.
ECGs were interpreted by two cardiologists who were blinded to each case. An ECG obtained prior to immune checkpoint inhibitor-myocarditis was available in 52 cases.
The study included all nine of the approved immune checkpoint inhibitors, according to the press release, but mostly concentrated on ipilimumab (Yervoy, Bristol Myers Squibb), nivolumab (Opdivo, Bristol Myers Squibb) and pembrolizumab (Keytruda, Merck).
Median hospital stay was 11 days.
Among participants with both a baseline and presenting ECG, researchers observed the following compared with baseline:
- elevated heart rate (93.9 vs. 80.4 bpm; P = .009);
- prolonged QRS (95.3 vs. 93.2 ms; P = .02);
- prolonged QT corrected for heart rate (441.8 vs. 421 ms; P = .03);
- decreased voltage (1.39 vs. 1.69 mV; P = .006);
- increased incidence of left bundle branch block (19% vs. 6%; P = .046);
- increased incidence of sinus tachycardia (48% vs. 29%; P = .02);
- greater prevalence of conduction disorders (67% vs. 44%; P = .01); and
- greater prevalence of repolarization anomalies (52% vs. 25%; P = .008).
Arrhythmogenic effects of immune checkpoint inhibitor myocarditis
Researchers observed a cumulative incidence of 21.1% for atrial fibrillation, 1.4% for atrial flutter and 2.1% for multifocal atrial tachycardia. Approximately 15% patients experienced at least one life-threatening ventricular arrhythmia, including 10.9% who experienced sustained ventricular tachycardia, 2.7% who had ventricular fibrillation and 1.4% who experienced torsades de pointes. According to the study, concomitant complete heart block and life-threatening ventricular arrhythmia occurred in 7.5% of patients.
Among 146 patients with 30-day surveillance, 26.7% died within 30 days of presentation, of which 62% of deaths were attributed to myocarditis.
Patients with immune checkpoint inhibitor-myocarditis were more likely to die within 30 days if they developed complete heart block (HR = 2.62; 95% CI, 1.33-5.18; P = .01) or life-threatening ventricular arrhythmias (HR = 3.1; 95% CI, 1.57-6.12; P = .001), according to the researchers.
After adjustment for age and sex, all-cause mortality was associated with pathological Q waves (HR = 5.98; 95% CI, 2.8-12.79; P < .001) and was inversely associated with Sokolow-Lyon Index (HR per mV = 0.57; 95% CI, 0.34-0.94; P = .03).
“This study shows that ICI-myocarditis is highly arrhythmogenic, presenting with new conduction blocks, decreased voltage, and repolarization abnormalities that frequently degenerate to malignant arrhythmias,” the researchers wrote. “Further studies are needed to evaluate how these ECG changes can facilitate screening, prognostication, and monitoring strategies in ICI-myocarditis.”