The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

Secondary chordal resection with septal myectomy for treatment of symptomatic obstructive hypertrophic cardiomyopathy.

OBJECTIVES: Left ventricular outflow tract obstruction causes symptoms of heart failure in most patients with hypertrophic cardiomyopathy. Resection of the secondary mitral valve (MV) chordae has recently been shown to move the MV apparatus posteriorly, thereby eradicating the outflow gradient. The aim of this study was to evaluate whether secondary chordal resection concomitant to septal myectomy improves outcomes. METHODS: Between 2005 and 2020, a total of 165 patients underwent septal myectomy without MV repair or replacement in our Medical Center. Secondary MV chordal resection was performed in 60 patients, and their outcomes were compared with those of the remaining 105 patients who did not undergo chordal resection (controls). Mean age was 61 ± 13 and 58 ± 16 years, respectively (P = 0.205). RESULTS: There were no in-hospital deaths throughout the entire cohort. Of those patients who underwent secondary chordal resection, New York Heart Association functional class decreased from 3 (interquartile range 2-3) preoperatively to 1 (interquartile range 1-2) postoperatively (P < 0.001), and resting outflow gradient decreased from 91 ± 39 mmHg to 13 ± 8 mmHg (86% change, P < 0.001). Compared with controls, patients who underwent secondary chordal resection had a significant lower resting outflow gradient at follow-up (14 ± 7 mmHg vs 21 ± 15 mmHg, P = 0.002). The rate of moderate or more than moderate mitral regurgitation at 5 years was 2% in the secondary chordal resection group and 5% in the controls (hazard ratio 1.05, confidence interval 0.11-10.32; P = 0.965). CONCLUSIONS: In this observational study, we report that secondary chordal resection concomitant to septal myectomy for left ventricular outflow tract obstruction is safe, relieves heart failure symptoms and reduces left ventricular outflow tract gradient in appropriately selected patients.

Non-Valvular Findings before Trans-Catheter Aortic Valve Implantation and their Impact on the Procedure.

UNLABELLED: Background: Trans-cathetervalve implantation (TAVI) is a non- surgical alternative for patients with severe aortic stenosis (AS). Pre-procedural computed tomography angiography (CTA) allows accurate "road mapping," aortic annulus sizing and the detection of incidental findings. OBJECTIVES: To document the prevalence of non-valvular extracardiac findings on CTA prior to TAVI and the impact of these findings on the procedure. METHODS: Ninety AS patients underwent CTA as part of pre-TAVI planning. Scans extended from the clavicles to the groin. Non-vascular non-valvular findings were documented and graded as follows: (A) significant findings causing TAVI cancellation or postponement, (B) significant findings leading to a change in the TAVI procedure approach, (C) non-significant findings not affecting the TAVI procedure. RESULTS: TAVI was planned for 90 patients; their average age was 80.2 ± 7.5 years, 53% were females. Overall, non-valvular cardiac, extracardiac and extravascular significant and non-significant incidental findings were documented in 97% of scans (87/90). Significant pathologies causing TAVI cancellation or postponement (category A) were documented in 8%. Significant findings affecting the TAVI procedure (category B) were found in 16% of patients. CONCLUSIONS: Pre-TAVI CTA detected non-valvular extravascular pathologies leading to procedure cancellation/postponement or procedure modification in 8% and 16%, respectively. Comprehensive CTA evaluation that acknowledges the importance of such findings is of major importance since it might alter the TAVI procedure or even render it inappropriate.

RNA binding activity of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit from Chlamydomonas reinhardtii.

Transfer of the green algae Chlamydomonas reinhardtii from low light to high light generated an oxidative stress that led to a dramatic arrest in the synthesis of the large subunit (LSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The translational arrest correlated with transient changes in the intracellular levels of reactive oxygen species and with shifting the glutathione pool toward its oxidized form (Irihimovitch, V., and Shapira, M. (2000) J. Biol. Chem. 275, 16289-16295). Here we examined how the redox potential of glutathione affected the RNA-protein interactions with the 5'-untranslated region of rbcL. This RNA region specifically binds a group of proteins with molecular masses of 81, 62, 51, and 47 kDa in UV-cross-linking experiments under reducing conditions. Binding of these proteins was interrupted by exposure to oxidizing conditions (GSSG), and a new protein of 55 kDa was shown to interact with the RNA. The 55-kDa protein comigrated with Rubisco LSU in one- and two-dimensional gels, and its RNA binding activity was further verified by using the purified protein in UV-cross-linking experiments under oxidizing conditions. However, the LSU of purified and oxidized Rubisco bound to RNA in a sequence-independent manner. A remarkable structural similarity was found between the amino-terminal domain of Rubisco LSU in C. reinhardtii and the RNA binding domain, a highly prevailing motif among RNA-binding proteins. It appears from the crystal structure of Rubisco that the amino terminus of LSU is buried within the holoenzyme. We propose that under oxidizing conditions it is exposed to the surface and can, therefore, bind RNA. Accordingly, a recombinant form of the polypeptide domain that corresponds to the amino terminus of LSU was found to bind RNA in vitro with or without GSSG.