Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes

Background Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. Methods Consecutive patients (n=315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2) and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. Results Compared to those without diabetes (n=156), the diabetes group (n=159) had a higher LGE prevalence (76 vs 60%, p<0.05), higher T1 (1285±42 vs 1269±42ms, p<0.001) and higher ECV (30.5±3.5 vs 28.8±4.1%, p<0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2 and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43-3.79], p<0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02-1.07], p=0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03-1.21], p=0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p=0.02). Conclusions Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS is a powerful and independent prognostic marker in HF patients with diabetes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The ATTRaCT study was supported by research grants from A*STAR Biomedical Research Council ATTRaCT program \[SPF2014/003, SPF2014/004, SPF2014/005\] (A*STAR, Singapore). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained from the local Centralized Institutional Review Board in Singapore, and all participants provided written informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are included in this article or available from the corresponding author upon reasonable request. * HF : heart failure GLS : global longitudinal strain CMR : cardiovascular magnetic resonance LGE : late gadolinium enhancement ECV : extraceullar volume NT-proBNP : N-terminal pro B-type natriuretic peptide hs-TnT : high-sensitivity troponin T GDF-15 : growth differentiation factor 15 sST2 : soluble ST2 Gal-3 : galectin 3 left ventricle : LV