therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited.OBJECTIVE To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTSIn this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES Sequential therapy with anthracyclines and trastuzumab.MAIN OUTCOMES AND MEASURES Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and Ն 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCEUsing CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually.

Background Current indications for implantable cardioverter defibrillator (ICD) implantation for sudden cardiac death prevention rely primarily on left ventricular (LV) ejection fraction (LVEF). Currently, two different contouring methods by cardiovascular magnetic resonance (CMR) are used for LVEF calculation. We evaluated the comparative prognostic value of these two methods in the ICD population, and if measures of LV geometry added predictive value. Methods In this retrospective, 2-center observational cohort study, patients underwent CMR prior to ICD implantation for primary or secondary prevention from January 2005 to December 2018. Two readers, blinded to all clinical and outcome data assessed CMR studies by: (a) including the LV trabeculae and papillary muscles (TPM) (trabeculated endocardial contours), and (b) excluding LV TPM (rounded endocardial contours) from the total LV mass for calculation of LVEF, LV volumes and mass. LV sphericity and sphere-volume indices were also calculated. The primary outcome was a composite of appropriate ICD shocks or death. Results Of the 372 consecutive eligible patients, 129 patients (34.7%) had appropriate ICD shock, and 65 (17.5%) died over a median duration follow-up of 61 months (IQR 38–103). LVEF was higher when including TPM versus excluding TPM (36% vs. 31%, p < 0.001). The rate of appropriate ICD shock or all-cause death was higher among patients with lower LVEF both including and excluding TPM (p for trend = 0.019 and 0.004, respectively). In multivariable models adjusting for age, primary prevention, ischemic heart disease and late gadolinium enhancement, both LVEF (HR per 10% including TPM 0.814 [95%CI 0.688–0.962] p = 0.016, vs. HR per 10% excluding TPM 0.780 [95%CI 0.639–0.951] p = 0.014) and LV mass index (HR per 10 g/m2 including TPM 1.099 [95%CI 1.027–1.175] p = 0.006; HR per 10 g/m2 excluding TPM 1.126 [95%CI 1.032–1.228] p = 0.008) had independent prognostic value. Higher LV end-systolic volumes and LV sphericity were significantly associated with increased mortality but showed no added prognostic value. Conclusion Both CMR post-processing methods showed similar prognostic value and can be used for LVEF assessment. LVEF and indexed LV mass are independent predictors for appropriate ICD shocks and all-cause mortality in the ICD population.