A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt

Background: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. Objective: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. Methods: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. Results: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire-guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002). Conclusions: AHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling

The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy

Aims The ageing heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favourable gene-environment interaction. We have previously shown that carriers of a longevity-associated variant (LAV) of the BPIFB4 gene enjoy prolonged health spans and lesser cardiovascular complications. Moreover, supplementation of LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in limb ischaemia, atherosclerosis, and diabetes models. Here, we asked whether the LAV-BPIFB4 gene could address the unmet therapeutic need to delay the heart's spontaneous ageing. Methods and results Immunohistological studies showed a remarkable reduction in vessel coverage by pericytes in failing hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygous LAV-BPIFB4 genotype. Moreover, pericytes isolated from older hearts showed low levels of BPIFB4, depressed pro-angiogenic activity, and loss of ribosome biogenesis. LAV-BPIFB4 supplementation restored pericyte function and pericyte-endothelial cell interactions through a mechanism involving the nucleolar protein nucleolin. Conversely, BPIFB4 silencing in normal pericytes mimed the heart failure pericytes. Finally, gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and pericyte coverage. Conclusions We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the heart's ageing. These findings open to using LAV-BPIFB4 to reverse the decline of heart performance in older people

The progression from obesity to type 2 diabetes in Alström syndrome.

Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri.Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri

Systematic and detailed analysis of behavioural tests in the rat Middle Cerebral Artery Occlusion (MCAO) model of stroke: tests for long-term assessment

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits; especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to 2 months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington’s and Parkinson’s disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of MCAO (30min) and were imaged 24hrs later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24hrs, 7 days, and 1 and 2 months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine induced rotations were the most reliable for assessing long-term deficits in the 30 min transient MCAO model of stroke

Atrial fibrillation cryoablation is an effective day case treatment: the UK PolarX vs. Arctic Front Advance experience.

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation (AF). There are limited data on the PolarX Cryoballoon. The study aimed to establish the safety, efficacy, and feasibility of same day discharge for Cryoballoon PVI. METHODS AND RESULTS: Multi-centre study across 12 centres. Procedural metrics, safety profile, and procedural efficacy of the PolarX Cryoballoon with the Arctic Front Advance (AFA) Cryoballoon were compared in a cohort large enough to provide definitive comparative data. A total of 1688 patients underwent PVI with cryoablation (50% PolarX and 50% AFA). Successful PVI was achieved with 1677 (99.3%) patients with 97.2% (n = 1641) performed as day case procedures with a complication rate of <1%. Safety, procedural metrics, and efficacy of the PolarX Cryoballoon were comparable with the AFA cohort. The PolarX Cryoballoon demonstrated a nadir temperature of -54.6 ± 7.6°C, temperature at 30 s of -38.6 ± 7.2°C, time to -40°C of 34.1 ± 13.7 s, and time to isolation of 49.8 ± 33.2 s. Independent predictors for achieving PVI included time to reach -40°C [odds ratio (OR) 1.34; P < 0.001] and nadir temperature (OR 1.24; P < 0.001) with an optimal cut-off of ≤34 s [area under the curve (AUC) 0.73; P < 0.001] and nadir temperature of ≤-54.0°C (AUC 0.71; P < 0.001), respectively. CONCLUSIONS: This large-scale UK multi-centre study has shown that Cryoballoon PVI is a safe, effective day case procedure. PVI using the PolarX Cryoballoon was similarly safe and effective as the AFA Cryoballoon. The cryoablation metrics achieved with the PolarX Cryoballoon were different to that reported with the AFA Cryoballoon. Modified cryoablation targets are required when utilizing the PolarX Cryoballoon

Atrial fibrillation cryoablation is an effective day case treatment: the UK PolarX vs. Arctic Front Advance experience

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation (AF). There are limited data on the PolarX Cryoballoon. The study aimed to establish the safety, efficacy, and feasibility of same day discharge for Cryoballoon PVI. METHODS AND RESULTS: Multi-centre study across 12 centres. Procedural metrics, safety profile, and procedural efficacy of the PolarX Cryoballoon with the Arctic Front Advance (AFA) Cryoballoon were compared in a cohort large enough to provide definitive comparative data. A total of 1688 patients underwent PVI with cryoablation (50% PolarX and 50% AFA). Successful PVI was achieved with 1677 (99.3%) patients with 97.2% (n = 1641) performed as day case procedures with a complication rate of &lt;1%. Safety, procedural metrics, and efficacy of the PolarX Cryoballoon were comparable with the AFA cohort. The PolarX Cryoballoon demonstrated a nadir temperature of -54.6 \ub1 7.6\ub0C, temperature at 30 s of -38.6 \ub1 7.2\ub0C, time to -40\ub0C of 34.1 \ub1 13.7 s, and time to isolation of 49.8 \ub1 33.2 s. Independent predictors for achieving PVI included time to reach -40\ub0C [odds ratio (OR) 1.34; P &lt; 0.001] and nadir temperature (OR 1.24; P &lt; 0.001) with an optimal cut-off of ≤34 s [area under the curve (AUC) 0.73; P &lt; 0.001] and nadir temperature of ≤-54.0\ub0C (AUC 0.71; P &lt; 0.001), respectively. CONCLUSIONS: This large-scale UK multi-centre study has shown that Cryoballoon PVI is a safe, effective day case procedure. PVI using the PolarX Cryoballoon was similarly safe and effective as the AFA Cryoballoon. The cryoablation metrics achieved with the PolarX Cryoballoon were different to that reported with the AFA Cryoballoon. Modified cryoablation targets are required when utilizing the PolarX Cryoballoon

Biodistribution PET/CT study of hemoglobin-DFO-89Zr complex in healthy and lung tumor-bearing mice

Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time89 Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine β93 is the sole attachment moiety to the αβ-protomer of Hb. The Hb-DFO complex shows quantitative uptake of89 Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89 Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells