Aims This multicentre observational study aimed to prospectively assess the efficacy of left bundle branch area pacing (LBBAP) in heart failure patients with left bundle branch block (LBBB) and compare the 6-month outcomes between LBBAP and biventricular pacing (BVP). Methods and results Consecutive patients with LBBB and left ventricular ejection fraction (LVEF) ≤ 35% were prospectively recruited if they had undergone LBBAP as a primary or rescue strategy from three separate centres from March to December 2018. Patients who received BVP in 2018 were retrospectively selected by using 2 to 1 propensity score matching to minimize bias. Implant characteristics and echocardiographic parameters were assessed during the 6-month follow-up. LBBAP procedure succeeded in 81.1% (30/37) of patients, with selective LBBAP in 10 patients, and 3 of 20 patients combined non-selective LBBAP and LV lead pacing for further QRS narrowing. LBBAP resulted in significant QRS narrowing (from 178.2 ± 18.8 to 121.8 ± 10.8 ms, P < 0.001, paced QRS duration ≤ 130 ms in 27 patients) and improved LVEF (from 28.8 ± 4.5% to 44.3 ± 8.7%, P < 0.001) during the 6-month follow-up. The comparison between 27 patients with LBBAP alone and 54 of 130 matching patients with BVP showed that LBBAP delivered a greater reduction in the QRSd (58.0 vs. 12.5 ms, P < 0.001), a greater increase in LVEF (15.6% vs. 7.0%, P < 0.001), and greater echocardiographic (88.9% vs. 66.7%, P = 0.035) and super response (44.4% vs. 16.7%, P = 0.007) to cardiac resynchronization therapy. Conclusions LBBAP could deliver cardiac resynchronization therapy in most patients with heart failure and LBBB, and might be a promising alternative resynchronization approach to BVP.

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This first-in-human study demonstrated that Lu-EB-PSMA-617 had higher accumulation in mCRPC and that low imaging dose appears to be effective in treating tumors with highGa-PSMA-617 uptakes. Elevated uptakes of Lu-EB-PSMA-617 in kidneys and red bone marrow were well tolerated at the administered low dose. Further investigations with increased dose and frequency of administration are warranted.

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Radiolabeled somatostatin analog therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogs in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-humans study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analog, Lu-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate (Lu-DOTA-EB-TATE). Eight patients (6 men and 2 women; age range, 27-61 y) with advanced metastatic NETs were recruited. Five patients received a single dose, 0.35-0.70 GBq (9.5-18.9 mCi), ofLu-DOTA-EB-TATE and underwent serial whole-body planar and SPECT/CT scans at 2, 24, 72, 120, and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24, and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Administration of Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared withLu-DOTATATE, Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved a 7.9-fold increase of tumor dose delivery. The total-body effective doses were 0.205 ± 0.161 mSv/MBq forLu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receivingLu-DOTA-EB-TATE compared with those receiving Lu-DOTATATE (3.2 and 18.2-fold, respectively). By introducing an albumin-binding moiety, Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NETs as well as significantly increased accumulation in the kidneys and red marrow. It has great potential to be used in peptide receptor radionuclide therapy for NETs with lower dose and less frequency of administration.

Low vitamin D levels are associated with AF. It may be involved in its development.

The pathogenesis of septic myocardial depression is complicated. Mitochondrial dysfunction has been suggested to be one of the main reasons for the reduced cardiac function. As melatonin is an antioxidant with the potential to scavenge radicals in mitochondria, we therefore employed a sepsis model, that is, cecal ligation and double puncture (CLP) in rats, to study the melatonin effects on: (i), myocardial mitochondrial function; (ii), heart systolic function; and (iii), prognosis of septic rats. We demonstrate that melatonin treatment (30 mg/kg, 3, 6, 12, 18, 24 hr after CLP) (i) improved myocardial cytochrome c oxidase (CcOX) activity and blood lactate level, (ii) attenuated heart dysfunction with a higher left ventricular ejection fraction (EF), and (iii) promoted 48-h survival of the rats compared to CLP animals with no melatonin treatment. In conclusion, our results show that rat myocardial mitochondrial CcOX activity was depressed during severe sepsis accompanied by myocardial depression characterized by the decline of EF. In septic rats, melatonin increased the CcOX activity, improved heart systolic function, and lowered mortality rate. The clinical use of melatonin in septic myocardial depression should be tested in the future.

The purpose of this study was to investigate whether an artificial matrix can help neonatal cardiomyocytes restore an injured heart in a rat model of myocardial infarction (MI). The left coronary arteries of female Sprague Dawley (SD) rats were ligated to create MI models. Ventricular cardiomyocytes from 1- to 3-day-old SD rats (both sexes) were isolated, cultured, and labeled. Three weeks after MI, the animals were randomized into four groups: (i) group cell plus matrix (n = 12); (ii) group cell (n = 12); (iii) group matrix (n = 12); and (iv) group control (n = 11). Four weeks after transplantation, echocardiography and the Langerdoff model were used to assess heart function. Immunohistochemical staining and polymerase chain reaction (PCR) were performed to track the implanted cardiomyocytes and detect the sex-determining region Y gene on the Y chromosome. Histology study and PCR showed that transplanted cardiomyocytes survived, formed condensed tissue, and produced connected protein in group cell plus matrix. Heart function assessment indicated transplantation of cardiomyocytes plus matrix preserved left ventricle wall thickness, fraction shortening, and end-systolic internal diameter most effectively.