REPLY

We thank the authors of all 3 letters for their thoughtful engagement with our study and for underscoring the shared priority that motivated this work: improving the early diagnosis and management of immune checkpoint inhibitor (ICI)–related cardiotoxicity.¹ We are encouraged by the recognition that pragmatic, real-world data are needed to inform how surveillance strategies can be implemented in routine clinical practice.

We are particularly grateful to Drs Dziewierz and Wiśniowski for their balanced assessment and highlighting our central contribution of real-world troponin monitoring data integrated with a symptom-based triage framework. As they note, this approach provides a pragmatic means of identifying patients who warrant closer evaluation while helping avoid unnecessary interruptions to cancer therapy. Our intent was to describe how troponin elevations were interpreted and acted upon in practice, showing the feasibility of surveillance at our center and the avoidance of indiscriminate escalation of care.

Drs Dziewierz and Wiśniowski, as well as Dr Zhang and colleagues, raise questions regarding the choice of cardiac troponin I (cTnI) vs cardiac troponin T (cTnT). We agree that both biomarkers play important roles in the diagnosis and prognostication of ICI myocarditis. However, the focus of our study was not on assay-level differences at low levels of elevation but on clinically significant troponin increases that prompt further evaluation. In this range, differences between isoforms are unlikely to meaningfully alter management, and both cTnT and cTnI have been reported at dramatic multiples of the upper limit of normal within 72 hours of admission of ICI myocarditis.² In our experience, ICI myocarditis cases identified through surveillance were associated with marked cTnI elevation (median initial cTnI 1,181 ng/L; Q1-Q3: 760-1,582 ng/L), and we did not observe cases of clinically meaningful myocarditis with normal cTnI.¹ We also emphasize that our study focused on cardiovascular outcomes rather than skeletal muscle involvement, and none of our myocarditis patients during the reported period had concurrent myositis. Although cTnT may be elevated in “triple M” overlap syndromes with myositis, cTnI remains highly specific for myocardial injury. From a practical standpoint, most institutions use a single troponin assay, making it essential that any surveillance framework be feasible regardless of assay choice.

Concerns regarding the feasibility of troponin surveillance and the need for a cardio-oncology response infrastructure are well taken, and we agree that this is a critical consideration. Importantly, we are not advocating for the indiscriminate adoption of troponin monitoring in settings without the capacity to interpret and act on abnormal results. Rather, our data demonstrate that when such infrastructure exists or is intentionally implemented, this approach is feasible and can be executed without widespread escalation of care. One of our key findings was that symptom-based triaging improved specificity, allowing many asymptomatic patients with troponin elevation to be evaluated safely in the outpatient setting and to continue immunotherapy without major adverse cardiovascular events.

Drs Dziewierz and Wiśniowski, as well as Dr Lei, highlight the observational, single-center nature of the study and the absence of randomized trial evidence for biomarker screening. We concur that a randomized clinical trial would be more definitive evidence, but we have no doubt that the letter authors would agree that observational studies are an important first step to laying the groundwork for a larger multicenter clinical trial. Similarly, cost-effectiveness analyses were beyond the scope of this study and represent an area of potential future investigation. Nonetheless, we note that the direct cost of troponin testing is modest, particularly when compared with the financial and clinical costs associated with hospitalization for severe myocarditis that might otherwise go unrecognized.

In summary, we sincerely appreciate the engagement of the letter authors and their shared commitment to advancing the field. We hope these data provide a transparent view of how troponin surveillance can function in real-world practice, while also highlighting the need for prospective studies to define its role more definitively. We agree that randomized trials represent the next critical step and view this work as contributing to the foundation upon which such studies can be built.