Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m 2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m 2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092.

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Background-T2-Weighted MRI reveals myocardial edema and enables estimation of the ischemic area at risk and myocardial salvage in patients with acute myocardial infarction (MI). We compared the diagnostic accuracy of a new bright-blood T2-weighted with a standard black blood T2-weighted MRI in patients with acute MI. Methods and Results-A breath-hold, bright-blood T2-weighted, Acquisition for Cardiac Unified T2 Edema pulse sequence with normalization for coil sensitivity and a breath-hold T2 dark-blood short tau inversion recovery sequence were used to depict the area at risk in 54 consecutive acute MI patients. Infarct size was measured on gadolinium late contrast enhancement images. Compared with dark-blood T2-weighted MRI, consensus agreements between independent observers for identification of myocardial edema were higher with bright-blood T2-weighted MRI when evaluated per patient (PϽ0.001) and per segment of left ventricle (PϽ0.001). Compared with bright-blood T2-weighted MRI, dark-blood T2-weighted MRI underestimated the area at risk compared with infarct size (PϽ0.001). The 95% limits of agreement for interobserver agreements for the ischemic area at risk and myocardial salvage were wider with dark-blood T2-weighted MRI than with bright-blood T2-weighted MRI. Bright blood enabled more accurate identification of the culprit coronary artery with correct identification in 94% of cases compared with 61% for dark blood (PϽ0.001). Conclusions-Bright-blood T2-weighted MRI has higher diagnostic accuracy than dark-blood T2-weighted MRI.Additionally, dark-blood T2-weighted MRI may underestimate area at risk and myocardial salvage. (Circ Cardiovasc Imaging. 2011;4:210-219.)

We analyzed feature-tracking derived circumferential and longitudinal strain in healthy volunteers who underwent cardiac magnetic resonance imaging (CMR) at 3.0 T. 88 healthy adults (44.6 ± 18.0 years old, 49% male), without prior cardiovascular disease, underwent CMR at 3.0 T including cine, and late gadolinium enhancement in subjects >45 years. LV functional analysis and feature-tracking strain analyses were carried out. Global strain had better reproducibility than segmental strain. There was a sex specific difference global longitudinal strain (mean ± SD, −18.48 ± 3.65% (male), −21.91 ± 3.01% (female), p < 0.001), but not global circumferential strain (mean ± SD, −25.41 ± 4.50% (male), −27.94 ± 3.48% (female), p = 0.643). There was no association of strain with ageing after accounting for sex for both global longitudinal and circumferential strain. Feature-tracking strain analysis is feasible at 3.0 T. Healthy female volunteers demonstrated higher magnitudes of global longitudinal strain when compared to male counterparts. Whilst global cine-strain has good reproducibility, segmental strain does not.