Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Transcatheter closure of ruptured right-coronary aortic sinus fistula to right ventricle

A 22-year-old man was referred for evaluation of exertional fatigue. On examination, there were no overt signs of congestive heart failure. Transthoracic and transesophageal echocardiography revealed rupture of the right coronary aortic sinus of Valsalva into the right ventricle. It was successfully closed with a 12 X 10 Amplatzer duct occluder

Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation

Real-time cardiovascular magnetic resonance subxiphoid pericardial access and pericardiocentesis using off-the-shelf devices in swine

BACKGROUND: Needle access or drainage of pericardial effusion, especially when small, entails risk of bystander tissue injury or operator uncertainty about proposed trajectories. Cardiovascular magnetic resonance (CMR) might allow enhanced imaging guidance. METHODS AND RESULTS: We used real-time CMR to guide subxiphoid pericardial access in naïve swine using commercial 18G titanium puncture needles, which were exchanged for pericardial catheters. To test the value of CMR needle pericardiocentesis, we also created intentional pericardial effusions of a range of volumes, via a separate transvenous-transatrial catheter. We performed these procedures in 12 animals. Pericardiocentesis was performed in 2:47 ± 1:43 minutes; pericardial access was performed in 1:40 ± 4:34 minutes. The procedure was successful in all animals. Moderate and large effusions required only one needle pass. There were no complications, including pleural, hepatic or myocardial transit. CONCLUSIONS: CMR guided pericardiocentesis is attractive because the large field of view and soft tissue imaging depict global anatomic context in arbitrary planes, and allow the operator to plan trajectories that limit inadvertent bystander tissue injury. More important, CMR provides continuous visualization of the needle and target throughout the procedure. Using even passive needle devices, CMR enabled rapid pericardial needle access and drainage. We believe this experience supports clinical testing of real-time CMR guided needle access or drainage of the pericardial space. We suspect this would be especially helpful in “difficult” pericardial access, for example, in distorted thoracic anatomy or loculated effusion