Layer-specific myocardial strain analysis for early detection and prevention of anthracycline-induced heart failure: the CARDIAC-STRAIN study protocol

Background

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. The problem lies in our current approach to surveillance: serial ejection fraction measurements detect damage only after significant myocardial injury has already 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 intervention.

Purpose

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 more timely cardioprotective treatment.

Methods

This prospective single-centre diagnostic cohort study will recruit 120 consecutive patients scheduled for anthracycline-based chemotherapy. Eligible participants are aged 18-75 years with preserved baseline ejection fraction (>=50%) and no prior anthracycline exposure or known cardiomyopathy. Each patient undergoes comprehensive cardiac evaluation at four defined timepoints: before treatment initiation, following the fourth chemotherapy cycle, four weeks after treatment completion, 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 imaging. We perform layer-specific strain quantification at subendocardial (0-33%), midmyocardial (33-67%), and subepicardial (67-100%) levels using dedicated feature-tracking software. Parallel assessments include three-dimensional echocardiography and serum biomarkers. Primary endpoints are defined as ejection fraction decline exceeding 10% to below 50%, decline greater than 15% with preserved function, or layer-specific strain deterioration beyond 15% from baseline values.

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 enable a shift from heart failure treatment to prevention in cardio-oncology. The study received ethics committee approval in November 2025, and patient recruitment is underway.