Immune checkpoint inhibitor therapy: Heart complaints, myocarditis, cardiovascular mortality? Insights from real-world melanoma patients treated at a German university hospital.

Background: Immune checkpoint inhibitors (ICI) are known for adverse cardiovascular effects including myocarditis. Due to their revolutionary impact on therapy of melanoma and consequently increasing prescription, cardiologists need to be aware of the side effects of ICIs. But how severe are cardiac complications associated with ICI therapy and how many findings can be objectively confirmed? We thought, it would be interesting to descriptively determine number and severity of cardiac side effects in patients treated with ICIs at our university hospital.

Methods and results: This is a retrospective, single-centre, observational study. We enrolled 261 patients, who were treated with ICIs between 2018 and 2024 at our hospital. All patients were assessed by cardiologists at our department before therapy initiation and/or for various heart complaints. Overall, 47 patients deceased (18.0%). Out of these 47 patients, 2 patients (4.2%) died due to myocarditis and 1 patient due to myocardial infarction (2.1%). Suspected myocarditis was diagnosed in 56 patients (21.4%) based on clinical findings including dyspnoea and chest pain. However, definitive myocarditis based on MRI and cardiac biomarkers was found in 15 patients (5.7%). Baseline and follow-up echocardiography were available in 146 patients. In 28 (19.2%) of these patients, left ventricular ejection fraction (LVEF%) declined over time. In patients with worsening LVEF%, mean decline was -9.2% (SD 13.6%). 13 patients developed ventricular and/or supraventricular tachycardia (5.0%). Troponin I was measured in 122 patients. 34 patients showed elevated troponin I levels (27.9%). NT-proBNP was determined in 101 patients and was elevated in 83 patients (80.6%). Finally, in 14 patients (5.4%) surveillance at the chest pain unit was deemed necessary.

Conclusion: These data show real-word, preselected patients, treated for melanoma at a German university hospital. A considerable number of patients showed symptoms suggestive for myocarditis. However, myocarditis was confirmed in only a fraction of patients. Furthermore, several patients showed decline of ejection fraction and elevated cardiac biomarkers, indicating both acute myocardial damage and heart failure. Although all-cause mortality was high in our collective, cardiovascular death accounted for a minority of the observed endpoints. In conclusion, cardiac affection in patients with ICI therapy seems frequent and may be objectively confirmed. On the other hand, the majority of patients in our collective deceased due to their underlying disease instead of cardiovascular causes implying that cessation of ICIs due to myocarditis or worsening LVEF should always be carefully considered.