Patients’ characteristics, overview of cardiologic side effects and outcome

Pat-IDAge (y)Gender (m/f)Type of pathology (cardiomyopathy, heart block, etc.)Occured in week xxx after initiation of checkpoint inhibitor therapySigns and symptomsTreatment of side effectOutcome of side effect (resolved/permanent changes/other)Other immune-related AEsIpilimumab (number of doses and dosage)Nivolumab or Pembrolizumab (number of doses and dosage)Clinical response (CR, PR, MR, SD, PD)Survival in months from time of distant metastases
172Mmyocarditis and cardiomyopathyweek 22Clinical findings: edema, ascites, pleural effusion, dyspneadiuresis, steroids (1 mg/kg), life vestgood regression of symptoms under steroid therapy; slight permanent decrease in EFthyroiditis, hypophysitisIpilimumab 3 mg/kg x 4Nivolumab 1 mg/kg x 4 followed by 3 mg/kg x 6PR22
ECHO: EF from 50 % down to 15 % und up again to 40 %; dilatation of heart
Stress MRI: DCM, EF 15-23 %, no signs for ischemia
Cardiac catheterization: no signs for ischemia
Endomyocardial biopsy: interstitial inflammation mainly with lymphocytes and interstitial fibrosis
268Mcardiomyophathyweek 12Clinical findings: dyspnea, edemadiuresisresolvednoneIpilimumab 3 mg/kg x 4noPD40+
Echo: decrease of EF to 46 %; mild LV dysfunction; increased pulmonary pressures with moderate tricuspid regurgitation
Endomyocardial biopsy: Myocyte hypertrophy, interstitial and perivascular fibrosis, mild focal subendocardial myocyte vacuolization. Focal fibrous endocardial thickening.
Transmission electron microscopy: mild perinuclear accumulation of lysosomes, consistent with lipofuscin pigment deposition; increase of cytoplasmic glycogen and the number of mitochondria, without anomalous forms.
Cardiac catheterization: no evidence of coronary artery disease, however, measurements of his right heart pressures suggested an RA pressure of 16, RV pressure of 67/10, wedge of 23 and PA pressures of 68/39
361Mmyocardial fibrosisweek 4Clinical findings: no cardiologic symptomssteroids (2 mg/kg), intensive care unitfatal; massive autoimmune side effects could not be overcomeautoimmune hepatitisIpilimumab 3 mg/kg x 2nodied of side effects3
Endomyocardial biopsy: myocardial fibrosis identified at autopsy
481Mheart failureweek 22Clinical findings: dyspneadiuresispermanent decrease in EFcolitis, hypophysitisIpilimumab 3 mg/kg x 3noPR22+
ECHO: moderately-to-severely reduced left ventricular EF at 35 %; mildly dilated left ventricle; global hypokinesis with regional variation; akinetic basal inferior and inferoseptal segments
523Mmyocarditis/CHFweek 31Clinical findings: cardiogenic shock requiring dopamine and dobutamine gttHigh dose steroids 2 mg/kg methylprednisolone per day converted to 80 mg prednisone/d with taper over 1 month, ACEi and beta blockerresolved to baseline (NYHA C1)uveitisIpilimumab 3 mg/kg x 4noSD31
Endomyocardial biopsy: T cell infiltration without eosinophilia
ECHO: drop of EF to 20 %
Cardiac MRI: left ventricular dilation and moderate LV systolic dysfunction (LVEF 34 %); right ventricular dilation and moderate RV systolic dysfunction (RVEF 33 %); increased T2 signal in the mid-inferolateral wall, suggestive of underlying myocardial edema supportive of myocarditis.
664Mmyocarditisweek 5Clinical findings: fatigue, seizures, abdominal paindopamine and fentanylfatalnoneIpilimumab 10 mg/kg x 2 noNAdied of side effects
Cardiac catheterization and electrocardiogram: normal
evidence of myocarditis and LV hypertrophy upon autopsy
788Mcardiac arrestweek 20Clinical findings: collapse with cardiac arrest during shopping without any prodromiAED with defibrillation, intensice care unit, catecholamines, steroids (125 mg i.v./d)resolvednonenoPembrolizumab 2 mg/kg x 9PR8+
ECHO: akinesis of the apex
Cardiac catheterization and electrocardiogram: coronary artery disease with no culprit stenosis, reduced LV function; similar to taktsubo cardiomyopathy
880Mmyocarditisweek 5Clinical findings: dyspnea, edema, arrhythmiassteroids (10 mg dexamethasone + 4 mg every 4 h), intensive care unitfatalautoimmune hepatitisIpilimumab 3 mg/kg x 2noPRdied of side effects
EKG: atrial fibrillation, right bundle-branch block
Nuclear stress test: no stress-induced ischemia
ECHO: drop of EF to 31 %, hypokinesis
Endomyocardial biopsy: Multinucleated giant cells, lymphocytes, eosinophils