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 .

Epidemiology and management of chronic thromboembolic pulmonary hypertension: experience from two expert centers.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece. METHODS: We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability. RESULTS: Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug. CONCLUSION: This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece.

The use of intra-coronary optical coherence tomography for the assessment of sirolimus-eluting stent fracture.

Drug-eluting stents (DES) have made a tremendous impact on the practice of percutaneous coronary intervention. Recently however, long-term DES failures have become a focal point, particularly with restenosis and thrombosis. An uncommon, yet important cause of DES failure is stent fracture. Of the two established first generation DES, the sirolimus-eluting stent (SES) has been particularly linked to cases of stent fracture, likely as a result of its closed cell design compared with other DES employing an open cell system. We present 2 cases of SES fracture confirmed using high-resolution intravascular optical coherence tomography giving unique insights into the in-vivo appearance of this complication.

Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS).

OBJECTIVES: Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and to examine novel invasive modalities to describe prevalence and temporal changes in putative characteristics of "high-risk" plaques. BACKGROUND: Conventional coronary imaging cannot identify "high-risk" lesions. METHODS: Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline and 6 months later in 67 patients with diverse clinical presentations. Different imaging techniques were compared within a common segment defined by multislice computed tomography (MSCT). RESULTS: Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In coronary arteries with <50% stenosis, there were no temporal changes in luminal and plaque dimensions measured by quantitative coronary angiography or IVUS; however, a significant reduction in abnormal strain pattern was detected on palpography (density high strain spots/cm: 1.6 +/- 1.5 vs. 1.2 +/- 1.4, p = 0.0123. These changes were mainly related to significant changes in patients who presented with ST-segment elevation myocardial infarction. The assessment of plaque echogenicity showed no temporal changes. There were no correlations between circulating biomarkers and quantifiable imaging parameters. CONCLUSIONS: Mild angiographic disease is associated with large atherosclerotic plaques on MSCT. Conventional invasive coronary imaging reveals static luminal and plaque dimensions on standard medical therapy with plaque hypoechogenicity remaining unchanged over the 6-month period. By contrast, palpography measurements of strain correlate with clinical presentation and significantly decrease on standard medical therapy. Novel imaging modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.