Thioredoxin-1 and its mimetic peptide improve systolic cardiac function and remodeling after myocardial infarction.

Myocardial infarction (MI) is characterized by a significant loss of cardiomyocytes (CMs), and it is suggested that reactive oxygen species (ROS) are involved in cell cycle arrest, leading to impaired CM renewal. Thioredoxin-1 (Trx-1) scavenges ROS and may play a role in restoring CM renewal. However, the truncated form of Trx-1, Trx-80, can compromise its efficacy by exerting antagonistic effects. Therefore, a Trx-1 mimetic peptide called CB3 was tested as an alternative way to restore CMs. This study aimed to investigate the effects of Trx-1, Trx-80, and CB3 on mice with experimental MI and study the underlying mechanism of CB3 on CMs. Mouse cardiac parameters were quantified by echocardiography, and infarction size and fibrosis determined using Trichrome and Picro-Sirius Red staining. The study found that Trx-1 and CB3 improved mouse cardiac function, reduced the size of cardiac infarct and fibrosis, and decreased the expression of cardiac inflammatory markers. Furthermore, CB3 polarized macrophages into M2 phenotype, reduced apoptosis and oxidative stress after MI, and increased CM proliferation in cell culture and in vivo. CB3 effectively protected against myocardial infarction and could represent a new class of compounds for treating MI.

BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways.

Introduction: Diabetic nephropathy (DN), a chronic kidney disease, is a major cause of end-stage kidney disease worldwide. Mesenchymal stem cells (MSCs) have become a promising option to mitigate several diabetic complications. Methods: In this study, we evaluated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of STZ-induced DN. After the confirmation of diabetes, rats were treated with BM-MSCs and sacrificed at week 12 after treatment. Results: Our results showed that STZ-induced DN rats had extensive histopathological changes, significant upregulation in mRNA expression of renal apoptotic markers, ER stress markers, inflammatory markers, fibronectin, and intermediate filament proteins, and reduction of positive immunostaining of PCNA and elevated P53 in kidney tissue compared to the control group. BM-MSC therapy significantly improved renal histopathological changes, reduced renal apoptosis, ER stress, inflammation, and intermediate filament proteins, as well as increased positive immunostaining of PCNA and reduced P53 in renal tissue compared to the STZ-induced DN group. Conclusion: In conclusion, our study indicates that BM-MSCs may have therapeutic potential for the treatment of DN and provide important insights into their potential use as a novel therapeutic approach for DN.

DELIVER: Extending the benefits of SGLT-2 inhibitors.

The DELIVER trial investigated the efficacy and safety of dapagliflozin in patients with heart failure and preserved or mildly reduced ejection fraction. The trial demonstrated that dapagliflozin significantly reduced the risk of worsening heart failure or cardiovascular death compared to placebo. The benefit was mainly driven by a decrease in heart failure hospitalizations, with no significant impact on mortality. Patients with different ejection fractions and diabetes status showed similar treatment effects. Dapagliflozin also improved functional capacity and quality of life. These findings support the use of SGLT-2 inhibitors in HFpEF and HFmrEF, potentially influencing clinical practice and future guidelines.

Contrast-Induced Sialadenitis: A Forgotten Complication of Coronary Angiography.

Contrast-induced sialadenitis is an adverse reaction following iodine-based investigations, including coronary angioplasty. Unfamiliarity with this adverse reaction may explain its underreporting. We herein describe a case series of 4 patients to help increase awareness of this condition among interventionists. (Level of Difficulty: Advanced.).

EMPEROR-Preserved: SGLT2 inhibitors breakthrough in the management of heart failure with preserved ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease which accounts for more than half of all HF hospital admissions with high prevalence and lack of effective evidence-based management. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new antidiabetic drug that recently gained a new role in the management of heart failure with reduced ejection fraction but its role in HFpEF had yet to be studied. Study and results: EMPEROR-Preserved trial set out to evaluate the effects of SGLT2 inhibition with empagliflozin on major heart failure outcomes in patients with HFpEF. The patients were randomized in a 1:1 fashion into two groups; to receive either empagliflozin 10 mg per day (n = 2, 997) or placebo (n = 2, 991) in addition to usual therapy. Empagliflozin led to a 21% risk reduction of the composite of cardiovascular death or hospitalization for heart failure, which was mainly related to a 29% lower risk of hospitalization for heart failure rather than effect on cardiovascular death empagliflozin. The effects SGLT2 inhibitors were consistent in all patients. What we have learnt: The EMPEROR-Preserved trial is the first randomized controlled trial testing the efficacy and safety of SGLT2 inhibitor (empagliflozin) in patients with HFpEF. The trial proves that SGLT2 inhibitors (empagliflozin) can significantly reduce HF hospitalization with neutral effect on cardiovascular (CV) death.

Veno-arterial Loop Aiding Mitral Valve Crossing for Balloon Mitral Valvuloplasty in a Patient With a Huge Left Atrium.

Veno-arterial loop is a feasible and safe technique to facilitate mitral valve crossing for balloon mitral valvuloplasty in mitral stenosis patients.

A novel method to measure mitral valve area in patients with rheumatic mitral stenosis using three-dimensional transesophageal echocardiography: Feasibility and validation.

AIMS: Neither two- nor three-dimensional (3D) planimetry of the mitral valve (MV) orifice takes the mitral commissures into account. Thus, if the commissures are not completely fused, the MV orifice will not be planar, and MV area (MVA) will be underestimated. The study aimed to validate a novel method for measurement of the MVA using a software that traces the MV orifice including the commissures. METHODS AND RESULTS: The study included 30 patients undergoing percutaneous balloon mitral valvuloplasty for severe rheumatic mitral stenosis. All performed 3D transesophageal echocardiography (TEE) immediately before the procedure. MVA was measured using the mitral valve navigation (MVN) software of the Philips Q-Lab 10.2 in a diastolic frame with maximum diastolic opening of the MV. Regular 3D planimetry of the MV orifice was also performed. Before balloon dilation, the MVA was calculated invasively using the Gorlin's formula. No significant difference was detected between MVN-derived MVA and Gorlin-derived MVA (0.98 cm2 vs. 1.0 cm2 , P = .33). A statistically significant difference was detected between Planimetry-derived MVA and Gorlin-derived MVA (0.8 cm2 vs. 1.0 cm2 , P < .001). There were significant linear correlations between MVN-derived MVA and Gorlin-derived MVA (r = .84, P < .001). Using Bland-Altman analysis, Gorlin-derived MVA showed better and relatively narrower limits of agreement with MVN-derived MVA than planimetry-derived MVA. CONCLUSION: Measurement of the MVA using the MVN method is feasible and is more correlated to the invasively measured MVA than the 3D planimetry method. This is the most accurate method of measuring the MVA that takes MV commissures into account.

Validation of Noninvasive Measurement of Cardiac Output Using Inert Gas Rebreathing in a Cohort of Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Cardiac output (CO) is a key indicator of cardiac function in patients with heart failure. No completely accurate method is available for measuring CO in all patients. The objective of this study was to validate CO measurement using the inert gas rebreathing (IGR) method against other noninvasive and invasive methods of CO quantification in a cohort of patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: The study included 97 patients with heart failure and reduced ejection fraction (age 42±15.5 years; 64 patients (65.9%) had idiopathic dilated cardiomyopathy and 21 patients (21.6%) had ischemic heart disease). Median left ventricle ejection fraction was 24% (10%-36%). Patients with atrial fibrillation were excluded. CO was measured using 4 methods (IGR, cardiac magnetic resonance imaging, cardiac catheterization, and echocardiography) and indexed to body surface area (cardiac index [CI]). All studies were performed within 48 hours. Median CI measured by IGR was 1.75, by cardiac magnetic resonance imaging was 1.82, by cardiac catheterization was 1.65, and by echo was 1.7 L·min-1·m-2. There were significant modest linear correlations between IGR-derived CI and cardiac magnetic resonance imaging-derived CI (r=0.7; P<0.001), as well as cardiac catheterization-derived CI (r=0.6; P<0.001). Using Bland-Altman analysis, the agreement between the IGR method and the other methods was as good as the agreement between any 2 other methods with each other. CONCLUSIONS: The IGR method is a simple, accurate, and reproducible noninvasive method for quantification of CO in patients with advanced heart failure. The prognostic value of this simple measurement needs to be studied prospectively.

An interatrial tunnel: a rare form of atrial septal defects.

Atrial septal defects (ASDs) account for approximately 6%-10% of congenital heart defects. The well-known types of atrial septal communications are the ostium secundum, ostium primum, sinus venosus types, and coronary sinus defects. A 50-year-old female was referred for TEE for better assessment of MR severity and mechanism. 2D/3D-TEE showed a rare combination of different abnormalities; bi-leaflet mitral valve prolapse, cleft P2, cor triatriatum sinister, and a tunnel-shaped IAS communication. To the best of our knowledge, this is a very rare case with a rare form of atrial septal defect that was not described before. We named this defect an interatrial tunnel.

Giant left atrial appendage aneurysm compressing the left anterior descending coronary artery.

Left atrial appendage aneurysm (LAAA) is a rare congenital structural heart disease. It is often diagnosed by echocardiography; however, other imaging modalities can add to its diagnosis and its potential effects on the surrounding structures. A 16-year-old boy presented with dyspnea and palpitation. Transthoracic echocardiography showed a large LAAA communicating with the LA through a narrow neck with impaired left ventricular (LV) systolic function. Multidetector cardiac tomography showed that the LAAA is compressing the left anterior descending artery. The LAAA was surgically resected followed by improvement of the LV systolic function.

ASGR1 - a new target for lowering non-HDL cholesterol.

Non-HDL cholesterol (non-HDL-C) has been introduced as an alternative cardiovascular (CV) risk marker and a secondary therapeutic target in patients with combined hyperlipidemia, diabetes mellitus, metabolic syndrome, or chronic kidney disease. An important genetic study on the Icelandic population has recently identified a strong link between a new gene - ASGR1 (for asialoglycoprotein receptor) - mutation, plasma non-HDL-C levels, and coronary heart disease (CHD). Heterozygous carriers of a rare noncoding 12-base-pair (bp) deletion (del12 deletion) in intron 4 of ASGR1 had a 13.6 mg/dl lower level of non-HDL-C and a 34% lower risk of CHD than non carriers. The cardioprotective effect of ASGR1 loss-of-function is surprisingly larger than predicted by its effect on the levels of non-HDL-C, which suggests that the atheroprotective effects of del12 mutation go beyond the lowering of serum cholesterol levels. This has shed some light on a new path - the sialylation pathway - possibly leading to a novel therapy that neutralize ASGR1 for heart disease prevention and treatment.

Takotsubo cardiomyopathy: A potentially serious trap (Data from the International Takotsubo Cardiomyopathy Registry).

Takotsubo cardiomyopathy (TTC) is an acute cardiac condition characterized by transient left ventricular dysfunction with wall motion abnormalities, most commonly in the form of apical ballooning. Despite being considered as a generally benign condition, many studies have emphasized potentially sinister outcomes associated with TTC. In this article, we review the most recent results of the International Takotsubo Registry, which investigated the clinical features, prognostic predictors, and outcomes of 1750 patients.