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Background Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD). Methods In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion. Results At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m 2 ), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m 2 ) and RVESVi (29.9 ± 6.9 mL/m 2 ) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (− 0.11 g/m 2 , [95% CI − 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI − 1.4 to 2.4], p = 0.58), RVEDVi (− 1.2 mL/m 2 , [95% CI − 4.1 to 1.7], p = 0.41) and RVESVi (− 0.81 mL/m 2 , [95% CI − 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months. Conclusions In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation. Clinical Trial Registration : URL:  https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1 . Unique identifier: NCT02998970.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. Objective To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. Methods 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin ( n  = 44) or placebo ( n  = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. Results At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m 2 , minimum LA volume 11.1 ± 5.7mL/m 2 ) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m 2 , minimum LA volume 12.6 ± 5.0mL/m 2 ) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m 2 (95% CI: -1.7 to 3.7 mL/m 2 ; p  = 0.47) for indexed maximum LA volume, and 0.87 mL/m 2 (95% CI: -0.9 to 2.6 mL/m 2 ; p  = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference − 0.01 (95% CI: -0.05 to 0.03, p  = 0.59). Conclusion SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970).

There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1–59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5–55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8–56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1–58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17). In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity. ClinicalTrials.gov Identifier: NCT01022086. Date of registration: November 27, 2009.

This study proposes a semi-weakly supervised learning approach for pulmonary embolism (PE) detection on CT pulmonary angiography (CTPA) to alleviate the resource-intensive burden of exhaustive medical image annotation. Attention-based CNN-RNN models were trained on the RSNA pulmonary embolism CT dataset and externally validated on a pooled dataset (Aida and FUMPE). Three configurations included weak (examination-level labels only), strong (all examination and slice-level labels), and semi-weak (examination-level labels plus a limited subset of slice-level labels). The proportion of slice-level labels varying from 0 to 100%. Notably, semi-weakly supervised models using approximately one-quarter of the total slice-level labels achieved an AUC of 0.928, closely matching the strongly supervised model’s AUC of 0.932. External validation yielded AUCs of 0.999 for the semi-weak and 1.000 for the strong model. By reducing labeling requirements without sacrificing diagnostic accuracy, this method streamlines model development, accelerates the integration of models into clinical practice, and enhances patient care.

Background Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function. Methods We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12 months after KT. Results Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) ( p  = 0.007) and global radial strain (GRS) ( p  = 0.003), but a decline in global longitudinal strain (GLS) over 12 months ( p  = 0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4 ± 6.4% at baseline, 60.6% ± 6.9% at 12 months; p  = 0.001). For entire cohort, over 12 months, change in LVEF was significantly correlated with change in GCS (Spearman’s r  = − 0.42, p  < 0.001), GRS (Spearman’s r  = 0.64, p  < 0.001), and GLS (Spearman’s r  = − 0.34, p  = 0.002). Improvements in GCS and GRS over 12 months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p  < 0.05), but not with change in blood pressure (all p  > 0.10). Conclusions Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12 months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.

Background Cardiovascular magnetic resonance (CMR) is increasingly used in the evaluation of patients who are potential candidates for implantable cardioverter-defibrillator (ICD) therapy to assess left ventricular (LV) ejection fraction (LVEF), myocardial fibrosis, and etiology of cardiomyopathy. It is unclear whether CMR-derived strain measurements are predictive of appropriate shocks and death among patients who receive an ICD. We evaluated the prognostic value of LV strain parameters on feature-tracking (FT) CMR in patients who underwent subsequent ICD implant for primary or secondary prevention of sudden cardiac death. Methods Consecutive patients from 2 Canadian tertiary care hospitals who underwent ICD implant and had a pre-implant CMR scan were included. Using FT-CMR, a single, blinded, reader measured LV global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain. Cox proportional hazards regression was performed to assess the associations between strain measurements and the primary composite endpoint of all-cause death or appropriate ICD shock that was independently ascertained. Results Of 364 patients (mean 61 years, mean LVEF 32%), 64(17.6%) died and 118(32.4%) reached the primary endpoint over a median follow-up of 62 months. Univariate analyses showed significant associations between GLS, GCS, and GRS and appropriate ICD shocks or death (all p < 0.01). In multivariable Cox models incorporating LVEF, GLS remained an independent predictor of both the primary endpoint (HR 1.05 per 1% higher GLS, 95% CI 1.01–1.09, p = 0.010) and death alone (HR 1.06 per 1% higher GLS, 95% CI 1.02–1.11, p = 0.003). There was no significant interaction between GLS and indication for ICD implant, presence of ischemic heart disease or late gadolinium enhancement (all p > 0.30). Conclusions GLS by FT-CMR is an independent predictor of appropriate shocks or mortality in ICD patients, beyond conventional prognosticators including LVEF. Further study is needed to elucidate the role of LV strain analysis to refine risk stratification in routine assessment of ICD treatment benefit.

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/m 2 including TPM 1.099 [95%CI 1.027–1.175] p = 0.006; HR per 10 g/m 2 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.

Fragmented QRS (fQRS) on electrocardiogram (ECG) may reflect myocardial fibrosis in both ischemic and nonischemic cardiomyopathy. Gray zone on cardiac magnetic resonance (CMR), which represents a heterogeneous interface between dense scar and viable myocardium, is a known predictor of appropriate implantable cardioverter-defibrillator (ICD) shocks or death. The relationship between fQRS and myocardial scar on CMR remains poorly studied and may improve risk stratification for ICD therapy. This study aimed to evaluate the relationship between fQRS and scar core/gray zone by CMR late gadolinium enhancement (LGE), and to determine whether fQRS predicts benefit from ICD therapy. We included 388 adults who underwent CMR followed by ICD implantation for primary or secondary prevention between 2005 and 2018 at 2 tertiary centers. ECGs were assessed for fQRS and CMR images were independently evaluated. The primary endpoint was a composite of all-cause mortality or appropriate ICD shock. Mean age was 61 ± 13 years and mean left ventricular ejection fraction (LVEF) was 32%. LGE was present in 69% and fQRS in 28%. fQRS was associated with greater scar burden on visual LGE assessment (p = 0.036), but not with quantitative LGE measures (2SD, 4SD, FWHM) or gray zone. Over a median follow-up of 61 months, 36% experienced the primary outcome. In multivariable analysis adjusting for LVEF and other prognosticators, fQRS was not independently associated with the primary outcome (HR 0.85; 95% CI: 0.67–1.08; p = 0.20). In conclusion, fQRS is associated with scar burden by visual assessment but does not provide incremental predictive value for ICD benefit.

Objectives We evaluated left atrial (LA) remodeling using cardiac MRI (CMR) in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer during and after trastuzumab therapy. Methods In this prospective 2-center longitudinal study, 41 women with HER2-positive breast cancer received adjuvant trastuzumab for 12 months, in addition to standard chemotherapy. Serial CMRs were performed at baseline, 6, 12, and 18 months after initiation of trastuzumab. LA volumes were measured by a blinded reader. Linear mixed model was used to evaluate longitudinal changes. Results Of 41 women (mean age 52 ± 11 [SD] years; 56% received anthracycline), one patient experienced trastuzumab-induced cardiotoxicity (TIC) for which trastuzumab was interrupted for one cycle. Mean baseline left ventricular ejection fraction (LVEF) was 68.0 ± 5.9% and LA ejection fraction (LAEF) was 66.0 ± 6.6%. Compared to baseline, LAEF decreased significantly at 6 months (62.7 ± 5.7%, p  = 0.027) and 12 months (62.2 ± 6.1%, p  = 0.003), while indexed LA minimum volume (LAmin) significantly increased at 12 months (11.6 ± 4.9 ml/m 2 vs 13.8 ± 4.5 ml/m 2 , p  = 0.002). At 18 months, all changes from baseline were no longer significant. From baseline to 6 months, change in LAEF correlated with change in LVEF (Spearman’s r  = 0.41, p  = 0.014). No significant interactions (all p  > 0.10) were detected between time and anthracycline use for LA parameters. Conclusions Among trastuzumab-treated patients with low incidence of TIC, we observed a small but significant decline in LAEF and increase in LAmin that persisted for the duration of therapy and recovered 6 months after therapy cessation. These findings suggest that trastuzumab has concurrent detrimental effects on atrial and ventricular remodeling. Key Points • In trastuzumab-treated breast cancer patients evaluated by cardiac MRI, left atrial ejection fraction declined and minimum volume increased during treatment and recovered to baseline after trastuzumab cessation. • Changes in left atrial ejection fraction correlated with changes in left ventricular ejection fraction in the first 6 months of trastuzumab treatment . • Trastuzumab therapy is associated with concurrent detrimental effects on left atrial and ventricular remodeling .

Aims Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM. Methods In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6 months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR). Results Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108 ml/s at baseline and did not change over 6 months (− 2.7, 95% CI − 35.6, 30.2, p  = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p  > 0.50). Conclusion In T2DM patients without HF receiving saxagliptin over 6 months, there were no significant subclinical changes in LV diastolic function as assessed by CMR.