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Background Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF). Methods Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson’s Goldner staining. Results A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p < 0.001) and the CS by 50% (p < 0.001). However, LV function was significantly better in the DOX + EMPA group, both in terms of EF (61.30 ± 11% vs. 49.24 ± 8%, p = 0.007), LS (− 17.52 ± 3% vs. − 13.93 ± 5%, p = 0.04) and CS (− 25.75 ± 6% vs. − 15.91 ± 6%, p < 0.001). Those results were not duplicated in the DOX + FURO group. Hearts from the DOX + EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p = 0.03). No significant differences were found between the DOX + FURO and the DOX group (p = 0.103). Conclusion Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.

A miniaturized hyperspectral camera, developed by integrating a linear variable band-pass filter (LVBPF) with an image sensor, was installed on the TIRSAT 3U CubeSat, launched on 17 February 2024 by Japan’s H3 launch vehicle. The satellite and its onboard hyperspectral camera conducted on-orbit experiments and successfully acquired hyperspectral data from multiple locations. The required attitude control for the hyperspectral mission was also achieved. CubeSat-based hyperspectral missions often face challenges in image alignment due to factors such as parallax, distortion, and limited attitude stability. This study presents solutions to these issues, supported by actual observational hyperspectral data. To verify the consistency of the hyperspectral data acquired by TIRSAT and processed using the proposed method, a validation analysis was conducted.

BackgroundLate gadolinium enhancement imaging (LGE) of the left ventricle (LV) by cardiac magnetic resonance (CMR) has prognostic value for patients with cardiac sarcoidosis (CS). Right ventricle (RV) dysfunction is also associated with adverse outcomes in patients with heart failure. Therefore, we sought to determine if RV LGE and dysfunction predicted adverse events in patients with suspected CS.MethodsIn 103 consecutive patients with suspected CS who underwent CMR, functional and remodeling indexes of both the LV and RV were measured and the extent and localization of LGE were also analyzed. Major adverse cardiac events (MACE) were defined as cardiovascular mortality, severe ventricular tachyarrhythmia, hospitalization with heart failure, and advanced atrioventricular block.ResultsDuring a median follow-up of 20.6 months, Kaplan–Meier analysis showed that decreased RV ejection fraction (EF) was associated with MACE (P < 0.001) and receiver operating characteristics curve (ROC) analysis indicated good predictive performance of RV EF for MACE (area under the ROC = 0.834). RV EF operated independently of LV EF or LGE extent for predicting MACE. In addition, the presence of LGE in RV was independently associated with MACE (P = 0.011), and a combined analysis of RV EF and RV LGE showed better risk stratification for MACE (P < 0.001).ConclusionsBoth RV EF and LGE were independently associated with MACE and enhanced risk stratification in patients with suspected CS. CMR may be a useful tool for detecting myocardial function and fibrosis in both the LV and RV.Graphic abstract

Transcatheter aortic valve implantation (TAVI) using the NAVITOR system has been relatively underreported due to its recent introduction in Japan. This study aimed to assess the short-term outcomes of TAVI with the NAVITOR in real-world clinical practice. Patients with severe aortic stenosis who underwent TAVI using the NAVITOR system at our institution between December 2022 and December 2023 were prospectively enrolled. We evaluated the 30-day post-TAVI outcomes using the Valve Academic Research Consortium 3 (VARC-3). Among 32 consecutive patients (mean age, 84 years; 19% female), technical success was achieved in 31 (96.8%). One patient developed a subclavian artery vascular dissection, requiring balloon angioplasty during the TAVI procedure, and another received a permanent pacemaker due to persistent advanced atrioventricular block. At the 30-day follow-up, device success was achieved in 31 (96.8%) patients, with early safety observed in 27 (84.3%). One patient experienced sudden unexplained death after discharge. None of the patients experienced myocardial infarction, valve embolisation, life-threatening bleeding, or acute kidney injury within 30 days after the procedure. Echocardiographic follow-up showed a median effective orifice area index of 1.26 ± 0.27. Contrast-enhanced computed tomography was performed in 19 patients 30 days after the procedure, revealing hypo-attenuated leaflet thickening (HALT) in 10 (52.6%). Although the 30-day outcomes of TAVI using the NAVITOR system appeared promising, a relatively high incidence of HALT was observed. Graphical Abstract

Abstract Background Recently, mechanical support obtained with the combination of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and an Impella device, together referred to as ECPELLA, has been shown to be effective for acute myocardial infarction with cardiogenic shock. However, methods for withdrawing VA-ECMO in acute myocardial infarction cases complicated by right ventricular dysfunction are yet to be established. Here, we report the effective use of inhaled nitric oxide during the weaning of VA-ECMO from the ECPELLA management of a patient with acute myocardial infarction with cardiogenic shock. Case summary An 81-year-old man with an acute extensive anterior wall myocardial infarction with cardiogenic shock was supported with ECPELLA to improve his haemodynamics. During ECPELLA, the Impella device could not maintain sufficient flow. Echocardiography revealed a small left ventricle and an enlarged right ventricle, indicating acute right heart failure. Inhaled nitric oxide was initiated to reduce right ventricle afterload, which decreased pulmonary artery pressure from 34/20 to 27/13 mmHg, improved right and left ventricle sizes, and stabilized the Impella support. Afterward, VA-ECMO could be withdrawn because the Impella alone was sufficient for haemodynamic support. Discussion Inhaled nitric oxide improved right ventricle performance in a patient with severe myocardial infarction with right heart failure supported by ECPELLA. Thus, we suggest that inhaled nitric oxide facilitates the weaning of VA-ECMO from patients with refractory right ventricular dysfunction who are supported by ECPELLA.

Background We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). Methods This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. Results All patients were diagnosed as having exudative PE by Light’s criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light’s criteria, was associated with malignancy ( p  = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p  = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p  = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4–26.0] vs 17.4 [IQR, 13.7–26.4], respectively; p  = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy ( p  = 0.012). Conclusions Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

Aims: The clinical impact of the type of atrial fibrillation (AF) has not been completely elucidated in non-ischemic cardiomyopathy (NICM). Although the structure and function of the left atrium (LA) provide prognostic information in patients with heart failure, the relationship of the AF type with LA structure and function in NICM is unclear. Methods: Consecutive patients with NICM who underwent cardiac magnetic resonance were evaluated and followed. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for major adverse cardiovascular events (MACE) related to the AF type, such as paroxysmal AF, chronic AF, and new-onset AF (NOAF). Results: Among 625 patients with NICM (mean age, 64.4 ± 14.2 years; women, 39.7%), 133 had a history of AF at baseline; of these, 60 had paroxysmal AF. Each baseline AF type was associated with higher LA volume and lower LA emptying fraction but not with an increased incidence of MACE ( p = 0.245). New-onset AF developed in 5.9% of patients with sinus rhythm over a median follow-up period of 609 days, and maximum LA volume was a strong and independent predictor [ p < 0.001, area under the ROC curve (AUC): 0.795]. Maximum LA volume was superior to LA emptying fraction and B-type natriuretic peptide (AUC: 0.683 and 0.680, respectively). The use of β-blocker and the age of the patient were associated with the incidence of NOAF (HR: 0.37, 95% CI: 0.16–0.84 and HR: 1.05, 95% CI: 1.01–1.09, respectively). Kaplan–Meier analysis showed that patients with NOAF had a higher incidence of MACE than those with sinus rhythm or baseline AF ( p = 0.002). NOAF and LA emptying fraction were independent predictors of MACE (HR: 2.28, 95% CI: 1.20–3.97 and HR: 0.98, 95% CI: 0.96–0.99, respectively) after adjusting for age, sex, body mass index, and diagnosis. Conclusions: Paroxysmal and chronic AF in patients with NICM were not associated with an increased incidence of MACE despite their association with LA volume and function. NOAF was independently associated with poor prognosis. Higher maximum LA volume predicted the onset and lower LA emptying fraction was independently associated with poor prognosis.

The initial outcomes of transcatheter aortic valve replacement in patients with left ventricular outflow tract calcification are poor. Furthermore, balloon-expandable transcatheter aortic valve replacement is associated with an increased risk of annular rupture, and self-expandable transcatheter aortic valve replacement is associated with worse post-operative residual paravalvular leakage grades. Therefore, developing an optimal method for transcatheter aortic valve replacement for patients with left ventricular outflow tract calcification is desirable. We present two cases of successful balloon-expandable transcatheter aortic valve replacement, wherein the transcatheter heart valve was implanted above the left ventricular outflow tract calcification to avoid annular rupture and paravalvular leakage, and one case each of balloon-expandable and self-expandable transcatheter aortic valve replacements, wherein the transcatheter heart valve was implanted at a normal height. Although annular rupture did not occur in any of the cases, more-than-mild paravalvular leakage persisted post-operatively in cases where the transcatheter heart valve was placed at a normal height. Annular rupture is more likely to occur in areas with high calcification at the joint than in noncalcified areas. Furthermore, the greater the calcification in the landing zone of the transcatheter heart valve, the more the paravalvular leakage persists. Therefore, high implantation of transcatheter heart valves above the left ventricular outflow tract calcification can be an effective method to avoid annular rupture and paravalvular leakage.

BackgroundCoaptation gap (CG) is one of the challenging anatomies of mitral transcatheter edge-to-edge repair (TEER), but its impact on patient outcomes is unclear. This study aimed to evaluate the impact of CG on procedural and clinical outcomes in patients with functional mitral regurgitation (MR).MethodsData from 2140 patients undergoing TEER for functional MR were analysed, focusing on the presence of CG, which is a missing leaflet coaptation between the anterior and posterior leaflets during systole. The primary outcome was a composite of death, heart failure hospitalisation and mitral valve reintervention.ResultsOf the 2140 patients, 219 (10%) had CG and 1921 (90%) did not, as assessed by baseline transoesophageal echocardiography. In patients with CG, baseline MR grade and New York Heart Association (NYHA) functional class were more severe, and long/wide clip types were used more frequently. Post-TEER, patients with CG had significantly lower achievement of MR grade ≤2+ (93%) and ≤1+ (65%) compared with patients without CG (97%, p<0.01; 82%, p<0.01, respectively). NYHA functional class at 1 year was similar in both groups. The cumulative incidence of the primary outcome was comparable between CG and non-CG groups (51% vs 53% at 3 years, p=0.71). While residual MR grade 2+ was associated with the higher primary outcome incidence compared with ≤1+ in patients without CG (p<0.01), no significant difference was found in patients with CG (p=0.51).ConclusionCG was associated with less MR reduction but with no clear difference in adverse clinical outcomes after TEER. Similar outcomes between residual MR grade 2+ and ≤1+ in CG patients highlight the importance of procedural endpoint in anatomically challenging cases.Trial registration numberUMIN000023653.

The vascular system is largely exposed to the effect of changing flow conditions. Vascular cells can sense flow and its changes. Flow sensing is of pivotal importance for vascular remodeling. In fact, it influences the development and progression of atherosclerosis, controls its location and has a major influx on the development of local complications. Despite its importance, the research community has traditionally paid scarce attention to studying the association between different flow conditions and vascular biology. More recently, a growing body of evidence has been accumulating, revealing that ncRNAs play a key role in the modulation of several biological processes linking flow-sensing to vascular pathophysiology. This review summarizes the most relevant evidence on ncRNAs that are directly or indirectly responsive to flow conditions to the benefit of the clinician, with a focus on the underpinning mechanisms and their potential application as disease biomarkers.