Citations

AbstractBackgroundConventional cardiac resynchronization therapy (CRT) involves implantation of a coronary sinus pacing lead through a delivery sheath, which typically requires a large venous access through a safe sheath of 9 French or greater in size. In patients who have very limited access due to scar tissue from previous implants or critical venous stenosis/closure, such large caliber access may not be available.Methods and ResultsWe report a case of CRT procedure in an 84‐year‐old male with a previous history of ischemic dilated cardiomyopathy (ejection fraction 40%) who was dependent on right ventricular pacing with worsening heart failure symptoms. The patient was incidentally discovered to have chronic total closure (CTO) of the left subclavian vein during the procedure. Although the CTO was crossed by a wire and dilated, the venous access was limited to a 7 French sheath which rendered conventional CRT through coronary sinus lead implant impossible. However, using the left bundle branch area pacing (LBBAP) technique which requires a smaller venous access, we were able to successfully achieve CRT. Postprocedure, the patient's paced QRS duration narrowed from 198 to 130 ms. His heart failure symptoms improved, and ejection fraction increased to 45% one‐month after the procedure.ConclusionsIn patients with vascular access limited to a small caliber sheath not suitable for conventional CRT, LBBAP may help achieve procedural success and improve clinical outcome.

ABSTRACT G0S2 and HIG2 are two selective inhibitors of ATGL (also known as PNPLA2), the key enzyme for intracellular lipolysis. Whereas G0S2 regulates triglyceride (TG) mobilization in adipocytes and hepatocytes, HIG2 functions to enhance intracellular TG accumulation under hypoxic conditions. A homologous hydrophobic domain (HD) is shared by G0S2 and HIG2 (also known as HILPDA) for binding to ATGL. However, the determinants of their lipid droplet (LD) localization are unknown. Here, we study how G0S2 and HIG2 are targeted to LDs, and identify both ATGL-independent and -dependent mechanisms. Structural prediction and studies in cells reveal that ATGL-independent localization of G0S2 to both the endoplasmic reticulum (ER) and LDs is mediated by a hairpin structure consisting of two hydrophobic sequences. Positively charged residues in the hinge region play a crucial role in sorting G0S2, which initially localizes to ER, to LDs. Interestingly, the role of these positive charges becomes dispensable when ATGL is co-expressed. In comparison, HIG2, which lacks a similar hairpin structure, is dependent on ATGL for its full LD targeting. Thus, our studies identify specific structural features and mechanisms for mediating accumulation of these two ATGL inhibitors on LDs.