Layer-specific myocardial strain for early detection of anthracycline-induced cardiotoxicity: the CARDIAC-STRAIN prospective diagnostic study protocol

Abstract

Anthracyclines remain cornerstone agents in oncology, yet their cardiotoxic potential poses a substantial clinical challenge. Up to 30% of treated patients develop some degree of cardiac dysfunction, with overt heart failure occurring in 2–5% of cases. Current surveillance relies on serial ejection fraction measurements, which detect damage only after significant myocardial injury has occurred. Histopathological evidence consistently shows that the subendocardial layer suffers earliest and most severely from anthracycline exposure—often weeks before any decline in global ventricular function becomes apparent. This temporal gap represents a missed opportunity for timely cardioprotective intervention. We designed the CARDIAC-STRAIN study to determine whether layer-specific strain analysis by cardiac magnetic resonance can identify subclinical cardiotoxicity substantially earlier than conventional echocardiographic surveillance, potentially enabling earlier initiation of cardioprotective treatment. This prospective single-centre diagnostic cohort study will recruit 120 consecutive patients scheduled for anthracycline-based chemotherapy (sample size calculated to detect 20% sensitivity difference, power 80%, α=0.05). Eligible participants are aged 18–75 years with preserved baseline ejection fraction (≥50%) and no prior anthracycline exposure or known cardiomyopathy. Each patient undergoes blinded comprehensive cardiac evaluation at four timepoints: baseline, after the fourth chemotherapy cycle, four weeks post-treatment, and at six months' follow-up. The protocol includes 1.5T cardiac MRI with cine sequences, native and post-contrast T1 mapping, T2 mapping, and late gadolinium enhancement. Layer-specific strain is quantified at subendocardial, midmyocardial, and subepicardial levels using dedicated feature-tracking software. Parallel assessments include three-dimensional echocardiography and cardiac biomarkers (troponin, NT-proBNP). Primary endpoints: ejection fraction decline >10% to below 50%, decline >15% with preserved function, or layer-specific strain deterioration >15% from baseline. Study hypothesis: We hypothesize that layer-specific strain analysis will detect subclinical myocardial injury approximately 2–4 weeks earlier than conventional ejection fraction monitoring, with significantly improved diagnostic sensitivity compared to standard surveillance protocols. Expected outcomes: If layer-specific strain analysis proves capable of reliably identifying subclinical cardiotoxicity before irreversible damage occurs, this approach may help shift clinical practice from heart failure treatment to early prevention in cardio-oncology. The study received ethics committee approval in November 2025, and patient recruitment is underway.