Already low drug dose antagonism of the renin-angiotensin aldosterone system decreases 1-year mortality and rehospitalization in old heart failure patients

Hospitalization for heart failure treatment (HHF) is an incisive event in the course of HF. Today, the large majority of HHF patients is ≥ 65 years and discharge HF drugs are most often not applied at dose levels acknowledged to provide prognostic benefit. This study therefore aims to investigate the treatment effect size of discharge HF drugs in old HHF patients. Drugs are analyzed according to pharmacological class. Individual discharge HF drug dose is reported as percentage of guidelines-recommended target dose. Primary endpoint was 1-year all-cause mortality (ACM) after discharge; the secondary endpoint combined 1-year ACM and first cardiovascular hospitalization within 1 year after discharge. Comparison between 65-80 years and > 80 years old study participants tested the relative treatment effect size as a function of respective age group. The 875 consecutive HHF patients had a median age of 82 years [76-87 years]; 48.6 % were females. Betablocker and diuretic treatment did not change the incidence of endpoints. Inhibition of the renin-angiotensin system (RASi), when compared to no treatment, decreased the incidence of endpoints both at the 1-25 % and the > 25 % target dose level. Antagonists of the mineralocorticoid receptor (MRA), when compared to no treatment, decreased the secondary endpoint at the 1-25 % target dose level but not at the > 25 % target dose level. The relative treatment effect size of RASi or MRA corresponded between the age strata for both endpoints. Low-dose RASi and MRA had beneficial effects in these old HHF patients

Non-severe aortic regurgitation increases short-term mortality in acute heart failure with preserved ejection fraction.

Mild or moderate aortic regurgitation (AR) has only little effect on cardiovascular outcome in people with normal left ventricular ejection fraction (EF); therefore, it is not perceived as a major clinical problem. This study investigates whether mild or moderate AR is associated with increased short-term mortality in patients hospitalized for treatment of acute heart failure (AHF) and whether mild or moderate AR impacts differently on short-term mortality in AHF patients with reduced EF (AHFrEF), mid-range EF (AHFmrEF), or preserved EF (AHFpEF). This mono-centric study included 505 consecutive adult patients hospitalized for de novo or worsening chronic HF not related to acute ischaemia or severe valvular pathology in the echocardiogram at index hospitalization. Cox regression analysis studied the impact of AR on all-cause mortality (ACM) over the 150 days' study period. Mild or moderate AR was associated with increased ACM (HR 1.75 [95% CI: 1.1-2.7]; P = 0.009). The prevalence of mild or moderate AR in the study population was 42% and not significantly different between AHFpEF (n = 227), AHFmrEF (n = 86), and AHFrEF (n = 192) study participants (37.9% vs. 50.0% vs. 42.7%; P = 0.144). In AHFpEF patients, the age-adjusted hazard for ACM was increased in patients with AR compared with patients without AR (HR 2.17 [95% CI: 1.1-4.2]; P = 0.002). The age-adjusted hazard for ACM was increased by a trend in AHFmrEF with AR (HR 7.11, [95% CI: 0.9-57.8]; P = 0.067) and not different between the AHFrEF groups (HR 0.95 [95% CI: 0.5-1.8]; P = 0.875). Mild or moderate AR increased ACM only in AHFpEF patients, highlighting a distinct clinical relevance

Developments in FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide. Each database record includes the population, ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related databases and the genetic variation together with its frequency in that population. Here, we report, in addition to the regular data content updates, significant developments in FINDbase, related to data visualization and querying, data submission, interrelation with other resources and a new module for genetic disease summaries. In particular, (i) we have developed new data visualization tools that facilitate data querying and comparison among different populations, (ii) we have generated a new FINDbase module, built around Microsoft’s PivotViewer (http://www.getpivot.com) software, based on Microsoft Silverlight technology (http://www.silverlight.net), that includes 259 genetic disease summaries from five populations, systematically collected from the literature representing the documented genetic makeup of these populations and (iii) the implementation of a generic data submission tool for every module currently available in FINDbase

Transcaval versus Supra-Aortic Vascular Accesses for Transcatheter Aortic Valve Replacement: A Systematic Review with Meta-Analysis.

A growing body of evidence suggests that extrathoracic vascular accesses for transcatheter aortic valve replacement (TAVR) yield favorable outcomes and can be considered as primary alternatives when the gold-standard transfemoral access is contraindicated. Data comparing the transcaval (TCv) to supra-aortic (SAo) approaches (transcarotid, transsubclavian, and transaxillary) for TAVR are lacking. We aimed to compare the outcomes and safety of TCv and SAo accesses for TAVR as alternatives to transfemoral TAVR. A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all articles comparing TCv-TAVR against SAo-TAVR published until September 2023. Outcomes included in-hospital or 30-day all-cause mortality (ACM) and postoperative complications. A total of three studies with 318 TCv-TAVR and 179 SAo-TAVR patients were included. No statistically significant difference was found regarding in-hospital or 30-day ACM (relative risk [RR] 1.04, 95% confidence interval [CI] 0.47-2.34, p = 0.91), major bleeding, the need for blood transfusions, major vascular complications, and acute kidney injury. TCv-TAVR was associated with a non-statistically significant lower rate of neurovascular complications (RR 0.39, 95%CI 0.14-1.09, p = 0.07). These results suggest that both approaches may be considered as first-line alternatives to transfemoral TAVR, depending on local expertise and patients' anatomy. Additional data from long-term cohort studies are needed

A Protocol for Space Charge Measurements in Full-size HVDC Extruded Cables

This position paper, prepared by the IEEE DEIS HVDC Cable Systems Technical Committee, illustrates a protocol recommended for the measurement of space charges in full-size HVDC extruded cables during load cycle qualification tests (either prequalification load cycles or type test load cycles). The protocol accounts for the experimental practices of space charge measurements in the thick insulation of coaxial cables in terms of poling time, depolarization time, heating and cooling of specimens, as well as for the experience gained very recently from such kind of measurements performed in the framework of qualification tests relevant to ongoing HVDC cable system projects. The goal of the protocol is not checking the compliance with any maximum acceptable limit of either space charge or electric field. Rather, this protocol aims at assessing the variation of the electric field profile in the cable insulation wall during poling time at the beginning and at the end of load cycle qualification tests for full-size HVDC extruded cables. Indeed, in the design stage the electric field distributions are determined by the cable geometry and by temperature gradient in the insulation. Thus, the design is based on macroscopic parameters conductivity and permittivity and how they depend upon temperature. Any disturbance of the electric field due to space charge accumulation will only be revealed during space charge measurements either in as-manufactured state or in the aged state after load cycle qualification tests

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft’s PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The above mentioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications

Graft calcifications and dysfunction following liver transplantation

BACKGROUND: The molecular events, following ischemia and reperfusion (I/R) of the liver during transplantation are largely unknown. There is evidence that apoptotic and necrotic events may take place, and occasionally result in primary graft dysfunction. We herein report two cases, where significant I/R injury correlated with the development of liver calcification and primary liver dysfunction. CASE PRESENTATION: Both patients with clinical and biochemical evidence of primary graft dysfunction demonstrated calcification at light and electron microscopy levels. In addition, one patient had macroscopic evidence of calcification on cross-sectional imaging. Both patients died secondary to the sequelae of the graft dysfunction. CONCLUSIONS: Severe I/R-induced injury to the liver, clinically leads to graft dysfunction. This is due to advanced apoptotic and/or necrotic events at the hepatocyte level that may, on the most severe form, lead to calcification. The study of microcalcification at the early posttransplant period could provide insight in the events taking place following significant ischemia/reperfusion-induced injury to the graft

Age- and Sex-Specific Nomographic CT Quantitative Plaque Data From a Large International Cohort.

With growing adoption of coronary computed tomographic angiography (CTA), there is increasing evidence for and interest in the prognostic importance of atherosclerotic plaque volume. Manual tools for plaque segmentation are cumbersome, and their routine implementation in clinical practice is limited. The aim of this study was to develop nomographic quantitative plaque values from a large consecutive multicenter cohort using coronary CTA. Quantitative assessment of total atherosclerotic plaque and plaque subtype volumes was performed in patients undergoing clinically indicated coronary CTA, using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool. A total of 11,808 patients were included in the analysis; their mean age was 62.7 ± 12.2 years, and 5,423 (45.9%) were women. The median total plaque volume was 223 mm <sup>3</sup> (IQR: 29-614 mm <sup>3</sup> ) and was significantly higher in male participants (360 mm <sup>3</sup> ; IQR: 78-805 mm <sup>3</sup> ) compared with female participants (108 mm <sup>3</sup> ; IQR: 10-388 mm <sup>3</sup> ) (P < 0.0001). Total plaque increased with age in both male and female patients. Younger patients exhibited a higher prevalence of noncalcified plaque. The distribution of total plaque volume and its components was reported in every decile by age group and sex. The authors developed pragmatic age- and sex-stratified percentile nomograms for atherosclerotic plaque measures using findings from coronary CTA. The impact of age and sex on total plaque and its components should be considered in the risk-benefit analysis when treating patients. Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis work flows could provide context to better interpret coronary computed tomographic angiographic measures and could be integrated into clinical decision making