Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment. By activating the immune system against tumours, they offer real hope across a growing number of malignancies. But that same immune activation can sometimes be directed against the heart.
ICI myocarditis is uncommon, affecting fewer than 1 in 50 patients. When it does occur, though, it can be devastating. Mortality reaches 60% in the most serious presentations, particularly when myocarditis overlaps with skeletal muscle inflammation and respiratory failure. The flip side is that early recognition and expert management make a significant difference to outcomes.
For clinicians on the front line, including GPs, emergency physicians, and oncologists, the question is what to do when a troponin comes back elevated in someone receiving immunotherapy. Not every troponin rise means myocarditis. But missing the real thing can be fatal.
Three scenarios, one practical framework
In our new paper published in the Canadian Journal of Cardiology, my colleagues and I present a case-based approach to this increasingly common clinical problem. We walk through three scenarios spanning the full spectrum of severity, accompanied by a diagnostic and management algorithm that clinicians can follow when troponin is elevated during ICI therapy.
The incidental finding. A 71-year-old man on pembrolizumab with an asymptomatic troponin rise on surveillance. His troponin normalised rapidly, his echocardiogram was normal, and the likely explanation was a brief run of atrial fibrillation. No immunosuppression was needed. After careful monitoring and a shared decision with his oncologist, treatment was safely resumed.
The concerning presentation. A 55-year-old woman on combination immunotherapy who presented with chest pain, a markedly elevated troponin, and new left ventricular dysfunction. She met criteria for non-severe ICI myocarditis and was treated with high-dose corticosteroids. Her heart function recovered over six weeks.
The emergency. A 56-year-old man who developed complete heart block, skeletal muscle weakness, and respiratory compromise three weeks into durvalumab. This was the feared “triple-M” syndrome: myocarditis, myositis, and myasthenia. He required intensive care, temporary pacing, and combination immunosuppression with abatacept and ruxolitinib alongside steroids.
Why early cardio-oncology involvement matters
One of the most important lessons from our collective experience is that involving a cardio-oncologist early makes a meaningful difference to patient outcomes. And “early” doesn’t just mean at the point of crisis. Ideally, patients at higher risk of cardiovascular complications should be assessed before starting ICI therapy, so that baseline investigations are in place and a monitoring strategy is established from the outset.
Early involvement allows us to:
Establish baseline troponin, ECG, and cardiac imaging that give future changes clinical context
Identify patients at higher risk, such as those on combination ICIs, with pre-existing autoimmune conditions, or with prior cardiac history
Respond rapidly when complications arise, rather than starting from scratch
Make informed decisions about ICI rechallenge after a cardiac event
A few practical red flags for referring clinicians:
A rising troponin in a patient on immunotherapy warrants urgent cardio-oncology assessment. Our published algorithm helps guide the next steps.
Concurrent elevation of CK and liver enzymes alongside troponin raises concern for overlap syndromes that carry the highest mortality.
New conduction abnormalities on ECG, particularly QRS widening or heart block, should prompt immediate referral.
Most ICI myocarditis presents within 30 days of starting treatment, so vigilance matters most in the early weeks.
An evolving field
It is worth emphasising that ICI myocarditis remains an area of intense, active research. Several prospective trials are underway, including the ACHLYS trial evaluating abatacept and ruxolitinib in severe ICI myocarditis, and new evidence is expected to refine our diagnostic and treatment approaches in the coming years. Current recommendations, including those in our paper, are based largely on observational data and expert consensus, and they will evolve as higher-quality evidence emerges.
That said, this paper represents what we believe to be the best available synthesis of evidence-based practice to date. It reflects the collective clinical experience of our group across hundreds of patients and draws on the most current international position statements and registry data.
This is precisely why having a cardio-oncologist involved in these cases matters so much. The landscape is shifting, and what constitutes best practice today may look different in twelve months. Patients benefit most when their care is guided by a specialist who is embedded in this field and stays across the emerging evidence as it develops.
The bigger picture
As immunotherapy expands across cancer types, these clinical scenarios will become more common. Our role as cardio-oncologists is to protect the heart so the patient can stay on the cancer treatment that is working for them.
I provide this kind of care as a fellowship-trained cardio-oncology specialist at Premier Cardiology, The Wesley Hospital in Brisbane. If you are considering starting a patient on ICIs and want a baseline cardiovascular assessment, or you are managing an acute complication, please get in touch.
📄 Read the full paper and algorithm: Canadian Journal of Cardiology (2026)
📞 Referrals: For urgent or routine cardio-oncology referrals, please contact Premier Cardiology at The Wesley Hospital. More information at https://jonathansen.com/refer/
