Complete heart block and subsequent sudden cardiac death from immune checkpoint inhibitor–associated myocarditis

Abstract Introduction Sarcoidosis is a granulomatous disease with multiorgan involvement. Cardiac involvement may be asymptomatic or present clinically as heart failure, arrhythmias or even sudden cardiac death. Objective We compared gender differences in prevalence of arrhythmias and associated outcomes in patients with sarcoidosis without established coronary artery disease. Methods The United States Nationwide Inpatient Sample was queried from 2010 to 2014 to identify patients with sarcoidosis using ICD-9 diagnosis code in patients >18 years. We excluded patients with a prior history of myocardial infarction, percutaneous coronary intervention and coronary artery bypass graft. Chi-square test was used for statistical analysis. Results The sample consisted of 308,064 patients (Mage = 55.65±11.28 years); they were mostly women 945 (65.2%) and black 957 (46.7%). In-hospital mortality in this cohort was 1,574 (2.5%). The most common arrhythmias was atrial fibrillation 29,850 (9.7%). Prevalence of ventricular fibrillation was 669 (0.2%), ventricular tachycardia 6,184 (2%), complete heart block 1462 (0.5%) and second degree Mobitz type II 245 (0.1%). Sudden cardiac death occurred in 2,059 (0.7%). Rates of various cardiac devices implanted were: implantable cardiac defibrillator (ICD) 1,452 (0.5%), cardiac resynchronization therapy-defibrillator (CRT-D) 553 (0.2%), pacemaker 1259 (0.4%). Rates of endomyocardial biopsy (EMB), radionuclide imaging, and cardiac magnetic resonance imaging were 470 (0.2%), 879 (0.3%), and 224 (0.1%), respectively. Based on gender (male vs. female), the rates of arrhythmias, cardiac device implantation and utilization of diagnostic modalities were: atrial fibrillation (41% vs 59%; p<0.001), ventricular fibrillation (50% vs 50%; p=0.983), ventricular tachycardia (55% vs 45%; p<0.001), complete heart block (48% vs 52%; p=0.3), second degree Mobitz type II (37% vs 63%; p=0.706), sudden cardiac death (38% vs 62%; p<0.171), ICD (56% vs 44%; p<0.001), CRT-D (58% vs 42%; p<0.025), pacemaker (40% vs 60%; p=0.066), EMB (55% vs 45%; p<0.001), radionuclide imaging (32% vs 68%; p=0.403), cardiac MRI (41% vs 59%; p=0.396). In-hospital mortality was higher in females (36% vs 64%; p<0.001). Conclusion In our study, in-hospital death was more common in females. Females had higher rates of atrial fibrillation compared to males who were found to have a higher burden of ventricular tachycardia. Males had higher rates of ICD and CRT-D placement. Males also had EMB performed more commonly than females. Funding Acknowledgement Type of funding source: None

Download Full-text

Electrocardiographic Manifestations of Immune Checkpoint Inhibitor Myocarditis

10.1101/2021.02.28.21252516 ◽

2021 ◽

Author(s):

John R Power ◽

Joachim Alexandre ◽

Arrush Choudhary ◽

Benay Ozbay ◽

Salim Hayek ◽

...

Keyword(s):

Immune Checkpoint ◽

Heart Block ◽

Ventricular Arrhythmias ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Adverse Outcomes ◽

Conduction Disorders ◽

All Cause Mortality ◽

Life Threatening ◽

Related Mortality

AbstractImportanceImmune-checkpoint inhibitor (ICI)-myocarditis often presents with arrhythmias, but electrocardiographic (ECG) findings have not been well described. ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation share similarities on histopathology; however, whether they differ in arrhythmogenicity is unclear.ObjectivesTo describe ECG findings in ICI-myocarditis, compare them to ACR, and evaluate their prognostic significance.DesignCases of ICI-myocarditis were retrospectively identified through a multicenter network. Grade 2R or 3R ACR was retrospectively identified within one center. Two blinded cardiologists interpreted ECGs.Setting49 medical centers spanning 11 countries.Participants147 adults with ICI-myocarditis, 50 adults with ACR.ExposureMyocarditis after ICI exposure per European Society of Cardiology criteria for clinically suspected myocarditis, grade 2R or 3R ACR per the International Society for Heart and Lung Transplantation working formulation for biopsy diagnosis of rejection.OutcomesAll-cause mortality, myocarditis-related mortality; and composite endpoint (defined as myocarditis-related mortality and life-threatening ventricular arrhythmia).ResultsOf 147 patients, the median age was 67 years (58-77) with 92 (62.6%) men. At 30 days, ICI-myocarditis had an all-cause mortality of 39/146(26.7%), myocarditis-related mortality of 24/146(16.4%), and composite endpoint of 37/146(25.3%). All-cause mortality was more common in patients who developed complete heart block (12/25[48%] vs 27/121[22.3%], hazard ratio (HR)=2.62, 95% confidence interval [1.33-5.18],p=0.01) or life-threatening ventricular arrhythmias (12/22[55%] vs 27/124[21.8%], HR=3.10 [1.57-6.12],p=0.001) within 30 days after presentation. Compared to ACR, patients with ICI-myocarditis were more likely to experience life-threatening ventricular arrhythmias (22/147 [16.3%] vs 1/50 [2%];p=0.01) or third-degree heart block (25/147 [17.0%] vs 0/50 [0%];p=0.002). In ICI-myocarditis, overall mortality, myocarditis-related mortality, and composite outcome adjusted for age and sex were associated with pathological Q-waves on presenting ECG (hazard ratio by subdistribution model [HR(sh)]=5.98[2.8-12.79],p<.001; 3.40[1.38-8.33],p=0.008; 2.20[0.95-5.12],p=0.07; respectively) but inversely associated with Sokolow-Lyon Index (HR(sh)/mV=0.57[0.34-0.94],p=0.03; HR(sh)=0.54[0.30-0.97],p=0.04; 0.50[0.30-0.85],p=0.01; respectively). The composite outcome was also associated with conduction disorders on presenting ECG (HR(sh)=3.27[1.29-8.34],p=0.01).ConclusionsICI-myocarditis has more life-threatening arrhythmias than ACR and manifests as decreased voltage, conduction disorders, and repolarization abnormalities. Ventricular tachycardias, complete heart block, low-voltage, and pathological Q-waves were associated with adverse outcomes.NCTNCT04294771Key PointsQuestionWhat are the electrocardiographic manifestations of immune checkpoint inhibitor (ICI)-associated myocarditis? How do they compare to acute cellular rejection (ACR), which is resembling pathophysiologically to ICI-myocarditis? Which electrocardiographic features are associated with adverse outcomes?FindingsICI-myocarditis results in more frequent ventricular arrhythmias and high-degree atrioventricular blocks compared to ACR. Prolonged QRS intervals, decreased voltage, conduction disorders, and pathological Q-waves are predictors of adverse outcomes in ICI-associated myocarditis.MeaningICI-associated myocarditis is a highly arrhythmogenic cardiomyopathy. Ventricular arrhythmias, conduction disorders, low-voltage, and pathological Q-waves are associated with a poor prognosis.

Download Full-text