The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease-rationale and design of the GESS study.

BACKGROUND: Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide and is associated with multiple inherited and environmental risk factors. This study is designed to identify, design, and develop a panel of genetic markers that combined with clinical and angiographic information, will facilitate the creation of a personalized risk prediction algorithm (GEnetic Syntax Score-GESS). GESS score could be a reliable tool for predicting cardiovascular risk for future adverse events and for guiding therapeutic strategies. METHODS: GESS (ClinicalTrials.gov Identifier: NCT03150680) is a prospective, non-interventional clinical study designed to enroll 1080 consecutive patients with no prior history of coronary revascularization procedure, who undergo scheduled or emergency coronary angiography in AHEPA, University General Hospital of Thessaloniki. Next generation sequencing (NGS) technology will be used to genotype specific single-nucleotide polymorphisms (SNPs) across the genome of study participants, which were identified as clinically relevant to CAD after extensive bioinformatic analysis of literature-based SNPs. Enrichment analyses of Gene Ontology-Molecular Function, Reactome Pathways and Disease Ontology terms were also performed to identify the top 15 statistically significant terms and pathways. Furthermore, the SYNTAX score will be calculated for the assessment of CAD severity of all patients based on their angiographic findings. All patients will be followed-up for one-year, in order to record any major adverse cardiovascular events. DISCUSSION: A group of 228 SNPs was identified through bioinformatic and pharmacogenomic analysis to be involved in CAD through a wide range of pathways and was correlated with various laboratory and clinical parameters, along with the patients' response to clopidogrel and statin therapy. The annotation of these SNPs revealed 127 genes being affected by the presence of one or more SNPs. The first patient was enrolled in the study in February 2019 and enrollment is expected to be completed until June 2021. Hence, GESS is the first trial to date aspiring to develop a novel risk prediction algorithm, the GEnetic Syntax Score, able to identify patients at high risk for complex CAD based on their molecular signature profile and ultimately promote pharmacogenomics and precision medicine in routine clinical settings. Trial registration GESS trial registration: ClinicalTrials.gov Number: NCT03150680. Registered 12 May 2017- Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03150680 .

Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.

AIM: The most frequent conduction complications with transcatheter aortic valve implantation (TAVI) are complete atrioventricular (AV) block and new bundle branch block (BB). The purpose of this study was to assess clinical, electrocardiographic, and electrophysiological predictors of conduction abnormalities in patients (pts) undergoing TAVI with the CoreValve prosthesis. The secondary end points were the long-term rhythm follow-up and the recovery of conduction. METHODS AND RESULTS: Forty-five consecutive pts with severe aortic stenosis, New York Heart Association II/III, and normal or slightly impaired left ventricular function who underwent CoreValve transcatheter implantation were randomized 2:1 to electrocardiographic and electrocardiographic plus electrophysiological evaluations. Pacemakers were implanted in pts with complete AV block. Follow-up was performed at 1, 6, 12, and 24 months. Conduction was affected in the total group of pts undergoing TAVI. The PR lengthened compared with the baseline but did not exceed the normal cut-off of 200 ms, and the QRS widened, basically due to new left bundle branch blocks (LBBBs). Within 1 month of follow-up, 10 pts (22%) developed complete AV block (9 peri-procedurally-20%) and 15 pts (33%) developed a new bundle BB, with LBBBs being the most common (14-31%). In the 30 pts who underwent an electrophysiological study, analysis showed that prolonged HV intervals were prognostic for pacemaker implantation. Follow-up in the total study group revealed that only 4 of the 10 (9%) initial implantations remained completely pacemaker dependent. CONCLUSION: Conduction was affected in all pts undergoing TAVI, but serious complications that required permanent pacing generally occurred in pts with pre-existing conduction abnormalities.

Four-year clinical results of transcatheter self-expanding Medtronic CoreValve implantation in high-risk patients with severe aortic stenosis.

BACKGROUND: transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement for patients with severe aortic stenosis considered inoperable or at high operative risk, but the long-term outcome remains unknown. HYPOTHESIS: we assessed the 4-year clinical and echocardiographic outcomes of patients undergoing TAVI with the self-expanding Medtronic CoreValve prosthesis. METHODS: sixty-three patients (mean age 80 ± 6 years) with severe aortic stenosis (AS) at high risk for surgical aortic valve replacement (Logistic EuroSCORE 28.8 ± 10.9%) were included in this study. RESULTS: all-cause cumulative mortality at 1, 2, 3 and 4 years was 14.3, 25.4, 28.6 and 36.5%, respectively. The cumulative incidence of documented major stroke at 4 years was 6.3%. In survivors, there was a significant improvement in functional status at 4 years. Paravalvular leak (trivial/mild to moderate) was observed in the majority of patients post-TAVI with no case of progression to severe regurgitation at 4-year follow-up. In multivariate analysis, independent predictor for increased all-cause mortality was left ventricular ejection fraction <40% (HR: 5.347, 95% CI: 1.126-25.381, P = 0.035). CONCLUSION: our study demonstrated favourable long-term (4 years) outcomes after successful TAVI using the third-generation Medtronic CoreValve device.

Corrigendum: Nicotine absorption from electronic cigarette use: comparison between experienced consumers (vapers) and naïve users (smokers).

This Article contains a typographical error in the Methods section under the subheading "Materials and clinical procedure". "The results of the two tests after excluding the question on cigarette and EC consumption were also reported (as FTCD-modified and CDS-modified, Table 1)." should read: "The results of the two tests after excluding the question on cigarette and EC consumption were also reported (as FTCD-modified and CDS-modified, Table 2)."

Nicotine absorption from electronic cigarette use: comparison between experienced consumers (vapers) and naïve users (smokers).

Electronic cigarettes (ECs) are nicotine delivery devices that are proposed as tobacco harm reduction products to smokers. Nicotine delivery from ECs is potentially important in their efficacy as smoking substitutes. Herein, nicotine delivery from using a new-generation EC device (variable-wattage, set at 9 W) was evaluated, comparing experienced (vapers) with naïve users (smokers). Twenty-four vapers and 23 smokers participated to the study. They were asked to obtain 10 puffs in 5 minutes and then use the EC ad lib for 60 more minutes (total duration of use: 65 minutes). An 18 mg/mL nicotine-containing liquid was used. Blood samples were obtained at baseline, 5-minutes and every 15 minutes thereafter, while number of puffs and average puff duration were recorded. Although at baseline both groups had similar plasma nicotine levels, smokers consistently exhibited lower levels at all time-periods; at 5-minutes the levels were lower by 46%, while during the subsequent period they were lower by 43% (at 65-minutes) to 54% (at 20-minutes). Both groups took similar number of puffs, but smokers had average puff duration of 2.3 s compared to 3.5 s in vapers. Even in vapers, plasma nicotine levels at 5 minutes were lower than those observed after smoking 1 tobacco cigarette.

Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices.

A wide range of electronic cigarette (EC) devices, from small cigarette-like (first-generation) to new-generation high-capacity batteries with electronic circuits that provide high energy to a refillable atomizer, are available for smokers to substitute smoking. Nicotine delivery to the bloodstream is important in determining the addictiveness of ECs, but also their efficacy as smoking substitutes. In this study, plasma nicotine levels were measured in experienced users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml nicotine-containing liquid. Plasma nicotine levels were higher by 35-72% when using the new- compared to the first-generation device. Compared to smoking one tobacco cigarette, the EC devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after 5 minutes of use. New-generation EC devices were more efficient in nicotine delivery, but still delivered nicotine much slower compared to tobacco cigarettes. The use of 18 mg/ml nicotine-concentration liquid probably compromises ECs' effectiveness as smoking substitutes; this study supports the need for higher levels of nicotine-containing liquids (approximately 50 mg/ml) in order to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes.