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Abstract A collective tribute to a colleague, friend, and mentor from those that have known him through his journey of the meanderings of the arterial pulse in health and disease; a journey that extended beyond borders and confines, with far-reaching personal and global impact. The Editorial Board of the Artery Research Journal and the Executive Committee of the Artery Society extend their due respects to Prof. Michael O’Rourke.

Background: Despite recent guidelines appropriate lipid-lowering treatment (LLT) remains suboptimal in everyday clinical practice. Aims: We aimed to describe clinical practice of use of LLT for at least high CV risk populations in a Hellenic real-world setting and assess how this relates to the European Society of Cardiology treatment guidelines. Methods: We analyzed data from a retrospective cohort study of the National Registry of patients with dyslipidemia between 1/7/2017 and 30/6/2019 who were at least of high CV risk and filled a dual or triple lipid-lowering treatment (dLLT, tLLT) prescription. The primary outcomes of interest of this analysis were to report on the patterns of LLT use in at least high CV risk patients. Results: A total of 994,255 (45.4% of Greeks on LLT) were of at least high CV risk and 120,490 (5.5%) were on dLLT or tLLT. The percentage of patients with reported statin intolerance ranged from 2 to 10%. While persistence was reported to be satisfactory (>85% for both dLLT or tLLT), adherence was low (ranging between 14 and 34% for dLLT). In 6-month intervals, the percentage of patients achieving a low-density lipoprotein cholesterol (LDL-C) target below 100 md/dL ranged from 20% to 23% for dLLT and 34%–37% for tLLT. Conclusions: The prevalence of at least high CV risk patients among patients receiving LLT in Greece is substantial. Despite the high persistence and probably due to the low adherence to treatment, LDL-C remains above targets in more than two thirds of patients.

Background: The widespread use of fluoroquinolones has been associated with the formation, dissection, and rupture of aortic aneurysms. Arterial biomarkers are established predictors of cardiovascular events. The present study was designed to investigate the effect of quinolones on arterial stiffness and aortic size for the first time. Methods: We studied 28 subjects receiving short-term (Results: Subjects had similar values of arterial biomarkers, blood pressure measurements, and aortic diameters at baseline. At follow-up, no significant change was observed between the two groups regarding the hemodynamic parameters and arterial biomarkers (p > 0.05 for all), i.e., cfPWV (7.9 ± 2.6 m/s for the control group vs. 8.1 ± 2.4 m/s for the fluoroquinolones group; p = 0.79), AIx@75 (22.6 ± 9.0% for the control group vs. 26.6 ± 8.1% for the fluoroquinolones group; p = 0.09), and aortic diameters. Conclusions: To our knowledge, FRAGILES is the first study to provide insights into the possible effects of fluoroquinolones on arterial biomarkers, showing that, at least in the short term, treatment with fluoroquinolones does not affect aortic function and diameter.

Pericardial effusions, especially large ones, have traditionally been regarded with concern by clinicians due to the sometimes unpredictable development of life-threatening cardiac tamponade. In the European Society of Cardiology Guidelines on pericardial diseases, the simplified algorithm for pericardial effusion triage and management recommends pericardial drainage in cases of cardiac tamponade and/or suspicion of bacterial or neoplastic etiology. In the presence of acute pericarditis, empiric anti-inflammatory treatment should be given, while when a specific indication known to be associated with pericardial effusion is found, then treatment of the underlying cause is indicated. Notably, the most challenging subgroup of patients includes those with large, asymptomatic, C-reactive-protein-negative, idiopathic effusions. In the latter subjects, pericardial drainage is proposed in cases of chronic effusions (lasting more than three months). However, this recommendation is based on scant data stemming from small-sized non-randomized studies. Nevertheless, recent evidence in a larger cohort of patients pointed out that a watchful waiting strategy is a safe option in terms of complication-free survival. This review summarizes the contemporary evidence on this challenging topic and provides recommendations for tailoring individual patient treatments.

Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I 2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I 2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I 2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I 2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I 2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I 2 = 0%) were similar between the groups. Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. Trial registration: PROSPERO registration ID: CRD42023448707.

Background: Despite the increasing use of transcatheter aortic valve procedures, many patients still require surgical aortic valve replacement (SAVR). Assessing arterial properties in patients undergoing SAVR for aortic valve stenosis can be challenging, and the existing evidence is inconclusive. Our study aimed to investigate the impact of SAVR on vascular stiffness and the quality of life, as well as the different effects of valve type on arterial properties. Methods: We included 60 patients (mean age 70.25 ± 8.76 years, 65% men) with severe symptomatic aortic stenosis who underwent SAVR. Arterial stiffness (cfPWV, baPWV) and vascular parameters (AIx@75, central pressures, SEVR) were measured at baseline, pre-discharge, and 1-year post-operation. The QOL was assessed using the generic questionnaire—short-form health survey 36 (SF-36) pre-operatively and at 1 year. Results: Post-SAVR, cfPWV increased immediately (7.67 ± 1.70 m/s vs. 8.27 ± 1.92 m/s, p = 0.009) and persisted at 1 year (8.27 ± 1.92 m/s vs. 9.29 ± 2.59 m/s, p ≤ 0.001). Similarly, baPWV (n = 55) increased acutely (1633 ± 429 cm/s vs. 2014 ± 606 cm/s, p < 0.001) and remained elevated at 1 year (1633 ± 429 cm/s vs. 1867 ± 408 cm/s, p < 0.001). Acute decrease in Alx@75 (31.16 ± 10% vs. 22.48 ± 13%, p < 0.001) reversed at 1 year (31.16 ± 10% vs. 30.98 ± 9%, p = 0.71). SEVR improved (136.1 ± 30.4% vs. 149.2 ± 32.7%, p = 0.01) and persisted at 1 year (136.1 ± 30.4% vs. 147.5 ± 30.4%, p = 0.01). SV had a greater cfPWV increase at 1 year (p = 0.049). The QOL improved irrespective of arterial stiffness changes. Conclusions: After SAVR, arterial stiffness demonstrates a persistent increase at 1-year, with valve type having a slight influence on the outcomes. These findings remain consistent despite the perceived QOL.

Background The aim of this study was to develop a structured 2‐step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. Methods and Results Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2‐step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study–based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter‐defibrillator. The primary end point was the time until the event of recurrent syncope (syncope‐free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow‐up of ≈4 years. After the structured 2‐step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter‐defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow‐up of ≈2.5 years (29.29±12.58 months, P=0.03). Conclusions The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2‐step electrophysiology‐inclusive algorithm as a potentially low‐cost, 1‐day, structured tool for these patients.

Background: Greece was recently reclassified from low- to medium-risk country in terms of cardiovascular disease, with 27% of cardiovascular deaths attributed to hypercholesterolemia. EMENO nationwide survey (2013-2016) assessed the epidemiology of dyslipidemia in the general population in Greece. Methods: A random sample of adults was drawn by multistage stratified random sampling based on 2011 census. Standardized questionnaires and blood tests for total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and triglycerides were used. Hypercholesterolemia was defined as TC ≥ 240/200 mg/dL and/or the use of lipid-lowering drugs, hyper-LDL-cholesterolemia as LDL-C ≥160/130/100 mg/dL and/or the use of drugs, hypo-HDL-cholesterolemia as HDL-C

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

Abstract The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified “risky clusters” of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed.

Resumo Fundamento O SAGE foi desenvolvido para identificar hipertensos com chance de velocidade de onda de pulso (VOP) aumentada. Até o momento, as publicações do escore foram em hipertensos. Objetivo Verificar a capacidade do SAGE de identificar os normotensos ou pré-hipertensos com chance de aumento da VOP. Métodos Transversal retrospectivo, incluiu exames de normotensos e pré-hipertensos que realizaram a medida central da pressão arterial e apresentavam os parâmetros para o cálculo do escore. Para cada pontuação do escore, foi analisada a sensibilidade, especificidade, valor preditivo positivo e negativo utilizando como ponto de corte para o diagnóstico positivo VOP ≥ 10m/s, ≥9,08 m/s (percentil 75) e ≥7,30 m/s (percentil 50). Um valor de p

Objective: Syncope, whose cause is unknown after an initial assessment, has an uncertain prognosis. It is critical to identify patients at the highest risk who may require a pacemaker and to identify the cause of recurrent syncope to prescribe proper therapy. The aim of this study was to evaluate the effect of permanent pacing on the incidence of syncope in patients with unexplained syncope and electrophysiology study (EPS)-proven atrioventricular (AV) node disease. Methods: This was an observational study based on a prospective registry of 236 consecutive patients (60.20 ± 18.66 years, 63.1% male, 60.04 ± 9.50 bpm) presenting with recurrent unexplained syncope attacks admitted to our hospital for invasive EPS. The decision to implant a permanent pacemaker was made in all cases by the attending physicians according to the results of the EPS. A total of 135 patients received the antibradycardia pacemaker (ABP), while 101 patients were declined. Results: The mean of reported syncope episodes was 1.97 ± 1.10 (or presyncope 2.17 ± 1.50) before they were referred for a combined EP-guided diagnostic and therapeutic approach. Over a mean follow-up of approximately 4 years (49.19 ± 29.58 months), the primary outcome event (syncope) occurred in 31 of 236 patients (13.1%), and 6 of 135 (4.4%) patients in the ABP group as compared to 25 of 101 (24.8%) in the no pacemaker group (p

(1) Background: Patients with diabetes mellitus (DM) are at increased risk for heart failure (HF). Accurate data regarding the prevalence of HF stages among diabetics in Greece are scarce. (2) Aim: The present study will examine the prevalence and evolution of HF stages among patients with type II DM (T2DM) diagnosed in the past 10 years, with no previous history of HF and at high CV risk, in Greece, as well as will explore the potential determinants of the development of symptomatic HF in these patients. (3) Methods: Through a non-interventional, epidemiological, single-country, multi-center, prospective cohort study design, a sample of 300 consecutive patients will be enrolled in 11 cardiology departments that are HF centers of excellence. Patients will be either self-referred or referred by primary or secondary care physicians and will be followed for up to 24 months. Demographic, clinical, echocardiography, electrocardiography, cardiac biomarkers (troponin, NT-proBNP) and health-related quality of life questionnaire data will be recorded as well as clinical events, including mortality, HF hospitalizations and HF-related healthcare resource utilization. The primary outcomes are the proportion of patients diagnosed with symptomatic HF (ACC/AHA Stage C) at enrolment in the overall study population and the proportions of patients with HF stages A, B and C, as well as by NYHA functional classification in the overall study population. (4) Conclusions: The HF-LanDMark study is the first epidemiological study that will assess the prevalence of HF among T2DM patients in Greece that could potentially enhance prompt therapeutic interventions shown to delay the development of HF in the T2DM patient population (HF-LanDMark, Clinical Trials.gov number, NCT04482283).

The post-percutaneous coronary intervention (post-PCI) fractional flow reserve (FFR) can detect suboptimal PCI or residual ischemia and potentially lead to fewer adverse clinical outcomes. We sought to investigate the predictive value of the angiography-derived FFR for adverse cardiovascular events in patients after PCI. We conducted a comprehensive search of electronic databases, MEDLINE, EMBASE, and the Cochrane Library, for studies published until March 2023 that investigated the prognostic role of angiography-derived fractional flow reserve values after PCI. We investigated the best predictive ability of the post-PCI angiography-derived FFR and relative risk (RR) estimates with 95% confidence intervals (CIs) between post-PCI angiography-derived FFR values and adverse events. Thirteen cohort studies involving 6961 patients (9719 vascular lesions; mean follow-up: 2.2 years) were included in this meta-analysis. The pooled HR of the studies using specific cut-off points for post-PCI angiography-derived FFR was 4.13 (95% CI, 2.92–5.82) for total cardiovascular events, while the pooled HRs for target vessel revascularization, cardiac death, target vessel myocardial infarction, and target lesion revascularization were 6.87 (95% CI, 4.93–9.56), 6.17 (95% CI, 3.52–10.80), 3.98 (95% CI, 2.37–6.66) and 6.27 (95% CI, 3.08–12.79), respectively. In a sensitivity analysis of three studies with 1789 patients assessing the predictive role of the post-PCI angiography-derived FFR as a continuous variable, we found a 58% risk reduction for future adverse events per 0.1 increase in the post-PCI angiography-derived FFR value. In conclusion, post-PCI angiography-derived FFR is an effective tool for predicting adverse cardiovascular events and could be potentially used in decision making, both during PCI and in the long-term follow-up.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. The hallmark of HCM is myocardial fibrosis which contributes to heart failure, arrhythmias, and sudden cardiac death (SCD). Objective: To identify the factors implicated in heart failure symptoms and functional capacity of patients with HCM. Methods: In this cohort study, 43 patients with HCM were recruited. According to functional capacity and symptoms presentation, patients were categorized according to New York Heart Association (NYHA) classification, and echocardiographic measurements of left ventricle systolic and diastolic function were conducted. The echocardiographic assessment of right ventriculo–arterial coupling (RVAC) was made by calculating the tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP) ratio. Results: Almost half (51%) of our study population present symptoms of heart failure and were categorized as the symptomatic group—NYHA 2 or higher. Maximum LVOT gradient, RVSP, and the ratio of E/e’ were higher in the symptomatic group compared with the asymptomatic group. TASV was lower in the symptomatic group compared with the asymptomatic group (11 ± 1 cm/s vs. 13 ± 2 cm/s, p = 0.04). However, there was no difference in other potentially influential factors, such as heart rate or systemic blood pressure. The SCD risk score does not differ between the two studied groups. The RVAC (estimated with the TASV/RVSP ratio) was lower in the symptomatic group compared with the asymptomatic group (0.32 ± 0.09 vs. 0.46 ± 0.11, p < 0.001). Conclusion: A low RVAC (as estimated with TASV/RVSP ratio) value could represent an echocardiographic marker of right ventricular–arterial uncoupling in patients with HCM and impaired functional status.

Abstract We explored whether radiomic features from T1 maps by cardiac magnetic resonance (CMR) could enhance the diagnostic value of T1 mapping in distinguishing health from disease and classifying cardiac disease phenotypes. A total of 149 patients (n = 30 with no heart disease, n = 30 with LVH, n = 61 with hypertrophic cardiomyopathy (HCM) and n = 28 with cardiac amyloidosis) undergoing a CMR scan were included in this study. We extracted a total of 850 radiomic features and explored their value in disease classification. We applied principal component analysis and unsupervised clustering in exploratory analysis, and then machine learning for feature selection of the best radiomic features that maximized the diagnostic value for cardiac disease classification. The first three principal components of the T1 radiomics were distinctively correlated with cardiac disease type. Unsupervised hierarchical clustering of the population by myocardial T1 radiomics was significantly associated with myocardial disease type (chi2 = 55.98, p

Background: Patients with diabetes mellitus (DM) and coronary artery disease (CAD) represent a high-risk population, where comorbidities are common and the progression of coronary heart disease is relatively rapid and extensive. The present survey, conducted nationwide in a Eurozone country, Greece, with a properly organized national health system, aimed to record specific data from a significant number of patients with diabetes and documented stable CAD (SCAD). Methods and results: We conducted our survey across the country, in private and public primary, secondary, and tertiary care centers. A total of 1900 patients aged 71 ± 10 years old who suffered from both DM and chronic coronary syndromes were registered. Of the patients registered, 574 (30.24%) were women. It was found that 506 (26.6%) of the 1900 surveyed patients showed typical angina symptoms, while another 560 (29.5%) patients had developed angina-equivalent symptoms according to their history. Additionally, 324 (17%) patients had atypical symptoms that could not easily be attributed to existing CAD and the remaining 510 (26.8%) of the 1900 patients did not exhibit any angina symptoms during their daily activities. Functional testing for myocardial ischemia was not performed in 833 patients (43.8%). Myocardial scintigraphy was the most commonly used noninvasive technique (644 patients, 34%), while 492 patients (25.9%) had an exercise test and 159 (8.4%) underwent stress echocardiography. Conclusion: Real-world data in this specific high-risk population of diabetic patients with SCAD offer the opportunity to identify and improve diagnostic and therapeutic practice in the healthcare system of a European Union country.

Abstract Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P

Although transcatheter aortic valve implantation has emerged as a very attractive treatment option for severe aortic valve disease, surgical aortic valve replacement (SAVR) is still considered the standard-of-care, particularly in younger patients. However, selecting the appropriate type of valve prosthesis for this patient population can pose challenges. The aim of this systematic review was to investigate morbidity and mortality in patients aged 50–70 years who have undergone a first-time SAVR, and to define and compare the outcomes of mechanical valve (MV) and biological valve (BV) prosthesis. A systematic search was conducted to investigate the clinical outcomes of MVs and BVs in patients aged 50–70 years following the PRISMA guidelines. A total of 16,111 patients were included in the studies with an average follow-up of 10 years. A total of 16 studies were selected, 12 of which included propensity-score-matching (PMS) analysis and 4 of which obtained results via multivariate analysis. The vast majority (13 studies) showed no greater survival benefit in either MVs and BVs, while three studies showed an advantage of MVs over BVs. Regarding complications, bleeding was the most common adverse event in patients undergoing MV replacement, while for patients receiving BV prosthesis, it was structural valve deterioration and reoperation. Although the data suggest that the BV option could be a safe option in patients younger than 70 years, more studies with contemporary data are needed to draw firm conclusions on the risks and benefits of BV or MV in SAVR. Physicians should individualize the surgical plan based on patient characteristics.

Abstract Background Significant sinus bradycardia (SB) in the context of sinus node dysfunction (SND) has been associated with neurological symptoms. The objective was to evaluate the effect of permanent pacing on the incidence of syncope in patients with rather mild degrees of SB, unexplained syncope, and “positive” invasive electrophysiologic testing. Methods This was an observational study based on a prospective registry of 122 consecutive mild SB patients (61.90 ± 18.28 years, 61.5% male, 57.88 ± 7.73 bpm) presenting with recurrent unexplained pre and syncope attacks admitted to our hospital for invasive electrophysiology study (EPS). Τhe implantation of a permanent antibradycardia pacemaker (ABP) was offered to all patients according to the results of the EPS. Eighty patients received the ABP, while 42 denied. Results The mean of reported syncope episodes was 2.23 ± 1.29 (or presyncope 2.36 ± 1.20) in the last 12 months before they were referred for a combined EP guided diagnostic and therapeutic approach. Over a mean follow‐up of approximately 4 years (50.39 ± 32.40 months), the primary outcome event (syncope) occurred in 18 of 122 patients (14.8%), 6 of 80 (7.5%) in the ABP group as compared to 12 of 42 (28.6%) in the no pacemaker group (P = .002). Conclusions Among patients with mild degree of SB and a history of unexplained syncope, a set of positivity criteria for the presence of EPS defined SND after differentiating reflex syncope, identifies a subset of patients who will benefit from permanent pacing.

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.

Background: In randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i. Methods: The cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year. Results: Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. “Totally” intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias). Conclusions: Our real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients.

Background: Aspirin and nonsteroidal anti-inflammatory drugs (A/NSAIDs) are the mainstay treatments for acute pericarditis. We sought to identify factors predicting failure of A/NSAIDs and switch to corticosteroid treatment (STCT) as well as the impact of STCT on pericarditis recurrence. Methods: We enrolled 148 patients with acute pericarditis receiving A/NSAIDs (n=110) or corticosteroids (n=38) as first-line treatment according to clinical indications. In case of poor response to A/NSAIDs (n=37), STCT was performed and factors contributing to such failure were explored. All patients were followed-up prospectively for 18 months for pericarditis recurrence. Results: In multivariate analysis, female sex (odds ratio [OR] =3.57, 95% confidence interval [CI]: 1.00-12.5), age (per decade, OR=0.75, 95% CI: 0.57-0.99), PR-segment depression (OR=4.43, 95% CI: 1.02-19.34), and a secondary cause of pericarditis (OR=13.52, 95% CI: 1.51-117.8) were independent predictors of poor response to A/NSAIDs and STCT. In cox regression analysis, the risk of recurrence was higher in patients requiring STCT (hazards ratio [HR] =3.22, 95% CI: 1.70-6.13) and in those initially treated with corticosteroids (H=2.06, 95% CI: 1.01-4.21) than in patients receiving A/NSAIDs only. Conclusions: Treatment failure with A/NSAIDs in acute pericarditis can be anticipated by certain patient characteristics. STCT identifies patients who are at the highest risk for recurrences, a risk that is approximately threefold higher than that of A/NSAIDs and 1.5-fold higher than that of corticosteroids as first-line treatment. Keywords: Acute pericarditis, Prognosis, Nonsteroidal anti-inflammatory drugs, Corticosteroids, Treatment failure

Background: Cardiac magnetic resonance (CMR) combined with late gadolinium enhancement (LGE) has revealed a non-negligible increased incidence of myocardial fibrosis (MF) in athletes compared to healthy sedentary controls.Objective: The aim of this systematic research and meta-analysis is to investigate and present our perspective regarding CMR indices in athletes compared to sedentary controls, including T1 values, myocardial extracellular volume (ECV) and positive LGE indicative of non-specific fibrosis, also to discuss the differences between young and veteran athletes.Methods: The protocol included searching, up to October 2021, of MEDLINE, EMBASE, SPORTDiscus, Web of Science and Cochrane databases for original studies assessing fibrosis via CMR in athletes. A mean age of 40 years differentiated studies' athletic populations to veteran and young.Results: The research yielded 14 studies including in total 1,312 individuals. There was a statistically significant difference in LGE fibrosis between the 118/759 athletes and 16/553 controls (Z = 5.2, P < 0.001, I2 = 0%, PI = 0.45). Notably, LGE fibrosis differed significantly between 546 (14.6%) veteran and 140 (25.7%) young athletes (P = 0.002). At 1.5T, T1 values differed between 117 athletes and 48 controls (P < 0.0001). A statistically significant difference was also shown at 3T (110 athletes vs. 41 controls, P = 0.0004), as well as when pooling both 1.5T and 3T populations (P < 0.00001). Mean ECV showed no statistically significant difference between these groups.Conclusions: Based on currently available data, we reported that overall LGE based non-specific fibrosis and T1 values differ between athletes and sedentary controls, in contrast to ECV values. Age of athletes seems to have impact on the incidence of MF. Future prospective studies should focus on the investigation of the underlying pathophysiological mechanisms.

Arrhythmias in pericardial syndromes have been poorly investigated and available data are mainly obtained from relevant studies however having different endpoints from arrhythmias. Thus, the incidence and prevalence of any type of arrhythmias may be actually higher than generally considered. Atrial arrhythmias, mainly atrial fibrillation and flutter have been reported as the most common rhythm disturbances in the setting of acute pericarditis. Concerning pathophysiology of atrial arrhythmias, in contrast to earlier hypothesis that they occur exclusively in the presence of an underlying structural heart disease, recent data support an arrhythmogenic potential of acute pericardial inflammation regardless of the presence of heart disease. In cases of myopericarditis, namely primarily pericarditis with evidence of myocardial involvement (i.e., troponin elevation without however overt left ventricular dysfunction and/or segmental wall motion abnormalities), ventricular arrhythmias appear to prevail. With reference to the rest of pericardial syndromes data on arrhythmias development are even more sparce. In particular, in constrictive pericarditis atrial tachyarrhythmias are the most commonly detected and seem to be related to disease severity and possibly to the underlying etiology. In this review we have summarized the available information on the incidence and prevalence of arrhythmias in pericardial syndromes. We wish to emphasize that the clinical significance of arrhythmias in this setting in terms of prognosis and optimal medical treatment (including need and safety of anticoagulation in atrial fibrillation/flutter complicating acute pericarditis), should be further investigated.

Objective: Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels predict cardiovascular risk. We aimed to determine the correlation of PCSK9 levels with predictors of cardiovascular risk, such as central hemodynamics and carotid intima-media thickness (cIMT), in subjects with familial dyslipidemias. Methods: Thirty-three asymptomatic subjects (age: 45.4 ± 12.3 years, 21 men) with either familial combined hyperlipidemia or heterozygous familial hypercholesterolemia, free from hypolipidemic therapy, underwent evaluation for central hemodynamics (aortic augmentation index [AIx@75] and augmented pressure [AP]) and cIMT. PCSK9 levels were measured by ELISA. Results: In the univariate model, circulating PCSK9 levels were related to age (r = 0.351, P = 0.045), AP (r = 0.442, P = 0.011), AIx@75 (r = 0.463, P = 0.007), and cIMT (r = 0.559, P = 0.011). In multivariate analysis, significant positive associations of AP, AIx@75, and cIMT with PCSK9 levels were observed after adjusting for relevant confounders (P = 0.018, P = 0.002, and P = 0.011, respectively). Patients with both high cIMT (>0.81 mm) and high AIx@75 (>20%) had significantly increased PCSK9 levels compared with subjects with both low cIMT and low AIx@75 (316 ng/ml vs. 155 ng/ml, P = 0.037). Conclusions: In familial dyslipidemias, PCSK9 levels are positively associated with predictors of cardiovascular risk, such as central hemodynamics and cIMT. These relationships may aid in the stratification of cardiovascular risk by identifying a high-risk subgroup within these entities. Keywords: Biomarkers, Central hemodynamics, Carotid Intima-Media Thickness (cIMT), Hyperlipidemias

Smoking during pregnancy is a risk factor associated with adverse pregnancy outcomes. Despite the fact that these outcomes are well known, a considerable proportion of pregnant women continue to smoke during this critical period. This paper evaluates critically smoking cessation interventions targeting pregnant women. We describe the findings of key published studies, review papers and expert statements to report the efficacy and safety of strategies for smoking cessation in pregnancy, including counselling and pharmacotherapy. Counselling appears to improve quit rates but mainly when used in combination with pharmacological therapy. Pharmacotherapy is recommended for women who are heavy smokers and are unable to quit smoking on their own. Nicotine replacement therapy is a reasonable first-line drug option. It is recommended that women who are pregnant, or planning to become pregnant, should be informed of potential risks for the foetus before considering smoking cessation therapy with bupropion or varenicline. Pregnant women view electronic nicotine delivery systems as being safer than combustible cigarettes, and this indeed may be the case; however, further evidence is required to assess their effectiveness as a smoking cessation aid and their safety for the mother and the child. Postpartum relapse is a significant problem, with approximately one out of two quitters relapsing in the first 2 months after delivery. These women should be considered ‘at risk’ and provided with ongoing support. Keywords: Pregnancy, Smoking, Smoking cessation, Counselling, Pharmacotherapy

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.

Despite the remarkable development of the medical industry in the current era, herbal products with therapeutic potentials arise as attractive alternative treatments. Consequently, Chios mastiha, a natural, aromatic resin obtained from the trunk and brunches of the mastic tree, has recently gained increasing scientific interest due to its multiple beneficial actions. Chios mastiha is being exclusively produced on the southern part of Chios, a Greek island situated in the northern Aegean Sea, and its therapeutic properties have been known since Greek antiquity. There is now substantial evidence to suggest that mastiha demonstrates a plethora of favorable effects, mainly attributed to the anti-inflammatory and anti-oxidative properties of its components. The main use of mastiha nowadays, however, is for the production of natural chewing gum, although an approval by the European Medicines Agency for mild dyspeptic disorders and for inflammations of the skin has been given. The aim of this article is to summarize the most important data about the therapeutic actions of Chios mastiha and discuss future fields for its medical application.

Introduction: Malignancies are the second leading cause of death worldwide. Treatment Monoclonal Antibody (MAbs)-based treatment of cancer has been established as one of the most successful therapeutic strategies in the last 20 years; however, there is a growing concern about the effects of these agents on patients’ cardiovascular profile. Areas Covered: In this manuscript we summarize current evidence regarding MAb effects on arterial stiffness, which is an recognised biomarker of cardiovascular risk. For this purpose, we explored two bibliographic databases [PubMed, Scopus] and one full-text database (Google-Scholar) for all publications published on MAbs’ effects on arterial stiffness until December 2019. Only few of the monoclonal antibody agents used in oncology have been investigated as per their effects on arterial properties and this limited evidence suggests that cancer therapy with monoclonal antibodies demonstrates either a temporary or long-term increase in arterial stiffness. Discussion: It seems that by targeting ‘checkpoints’ in cancer genesis, anticancer MAbs also affects vascular properties causing endothelial dysfunction and arterial stiffness. Furthermore, several MAbs cause hypertension and may as a result increase pulse wave velocity. On the other hand, MAbs that target inflammatory cytokines seem to improve cardiovascular survival however, their effect on arterial stiffness is yet to be investigated. Further research is warranted in order to elucidate the biochemical pathways, clinical implications and potential reversibility of monoclonal antibody chemotherapy-induced vascular dysfunction.

Abstract Purpose/Background/Objectives Acute kidney injury (AKI) is a serious postoperative complication. Increased arterial stiffness has been shown to be an independent risk factor for cardiovascular events. Our aim was to investigate whether arterial stiffness is a predictor of AKI in patients following surgical aortic valve replacement (SAVR). Methods Eighty-four patients (mean age 72 ± 8 years, 34 females) with moderate to severe aortic stenosis undergoing SAVR were included. As indicators of arterial stiffness aortic hemodynamics, carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) were assessed prior to surgery. Renal dysfunction was defined when eGFR was below 60 ml/min (n = 28, 33%). AKI was defined using KDIQO criteria. Results Twelve patients (14%) developed AKI. There was no significant difference in aortic hemodynamics and cfPWV between the two groups. baPWV significantly correlated with AKI (r = 0.313, p = 0.004). In logistic regression analysis, increase of baPWV per 1 Standard Deviation (Odds Ratio [OR] = 2.76, 95% Confidence intervals [CI]: 1.25–6.11, p = 0.012) and presence of renal dysfunction (OR = 14.93, 95% CI: 2.55–87.32, p = 0.003) were associated with higher risk for AKI even after adjustment for age, gender, systolic blood pressure and diabetes. baPWV was a stronger predictor of AKI than baseline creatinine (Area under the curve [AUC] 0.68, 95% CI: 0.52–0.84, p = 0.05 vs AUC 0.61, 95% CI: 0.46–0.77, p = 0.21; p < 0.05). Conclusion baPWV could be considered as a useful predictive biomarker for AKI after SAVR, especially in patients with renal dysfunction prior to surgery.

Purpose /Background /Objectives: Vitamin K antagonists (VKA) aggravate vascular calcifications burden, especially in haemodialysis patients potentially compounding their cardiovascular risk. We sought to investigate the relationship between VKA intake and aortic arch calcification (AAC) in patients with acute coronary syndrome (ACS). Methods: Two hundred patients admitted with ACS were included in the study (mean age 66 ± 15 years). The extent of aortic arch calcification (AAC) on a postero-anterior plain chest X-ray was divided into four grades (0 to 3). Grades 0 to 1 and grades 2 to 3 were categorized as lower and higher AAC grade respectively. Anticoagulants were categorized to VKA and to non-VKA anticoagulants including new oral anticoagulants and low-molecular weight heparin. Results: Twenty-eight (14%) patients at admission were on anticoagulants. Seventeen patients (8.5%) were treated with VKA and 12 patients (6%) with non-VKA anticoagulants. Higher ACC grade was observed in patients treated with VKA after adjustment for age, gender and chronic kidney disease. (Odds ratio [OR] = 3.64, 95% Confidence intervals [CI]: 1.08 to 12.20, p = 0.037). Interestingly, there was a non-statistically significant trend for reduced risk of higher AAC grade in patients treated with non-VKA anticoagulants (OR = 0.24, 95% CI: 0.04 to 1.47, p = 0.12). Age and history of chronic kidney disease were the most potent predictors of higher AAC grade (OR = 1.07, 95% CI: 1.03 to 1.10, p < 0.001 and OR = 6.07, 95% CI: 2.35 to 15.67, p < 0.001, respectively). Conclusion: Our study shows intake of VKA is associated with higher risk of AAC in ACS patients, while non-VKA anticoagulants might be associated lower AAC grade.

Purpose/Background/Objectives: Aortic stiffness and hemodynamics are independent predictors of adverse cardiovascular events. Transcatheter aortic valve implantation (TAVI) is growingly used in high surgical risk patients with aortic valve stenosis. We sought to investigate the effect of TAVI on aortic stiffness. Methods: Fifty-five high-risk patients (mean age 79.5 ± 8.8 years, 46% males) with severe symptomatic aortic stenosis undergoing TAVI were included. Arterial stiffness was estimated through carotid-femoral pulse wave velocity (cfPWV). Measurements were conducted prior to the implantation, at discharge and 1 year post-TAVI. Results: Prior to the implantation, cfPWV was 7.5 ± 1.4 m/s for the overall population. There was a statistically significant increase in measurements of aortic stiffness at discharge (7.5 ± 1.4 vs 8.3 ± 1.9 m/s for cfPWV with p = 0.043) without a statistically significant change in SBP (p = NS) (Figure 1). There was also a significant increase in cfPWV (8.7 ± 1.8 m/s) after 1 year compared to the pre-procedural assessment (p = 0.001). We also observed a non-significant increase in peripheral SBP at 1 year compared to SBP measurements at baseline and at discharge (153 ± 24 m/s vs 147 ± 21and 148 ± 22 m/s, respectively; p = 0.319) and these changes were independent of age and gender (Figure 1). Conclusion: Our study shows that both shortly as well as in the long-term after TAVI subjects experience an increase in aortic stiffness that is independent of changes in SBP. These findings further elucidate the hemodynamic consequences and provide evidence of a possible long-standing repercussion of TAVI. Figure 1

Purpose/Background/Objectives: Cardiac autonomic dysfunction is associated with increased cardiovascular mortality and arrhythmias. The aim of the study was to investigate the effect of heart rate variability (HRV) in the prognosis of future arrhythmic events. Methods: We studied 292 untreated at baseline hypertensives (mean age 53 ± 13, 153 males). Cardiac autonomic function was evaluated by analysis of short-term HRV using 24-h ambulatory blood pressure monitoring and the standard deviation of measurements. Left ventricular mass index (LVMI) was estimated echocardiographically. Aortic stiffness was assessed with carotid-femoral pulse wave velocity (cfPWV) and aortic augmentation index corrected for heart rate (AIx@75). Patients were followed up for 13 years. The primary endpoint was a composite of atrial/ventricular tachycardias, symptomatic multiple premature ventricular contractions, second and third-degree heart blocks and pacemaker/defibrillator placement. Results: Patients with the primary endpoint (n = 37.13%) had lower 24-h daytime HRV (9.6 beats per minute vs 11.1 beats per minute, p = 0.005), higher systolic blood pressure (168 mmHg vs 163 mmHg, p = 0.003), higher cfPWV (8.4 m/s vs 7.7 m/s, p = 0.005), higher LVMI (133 g/m2 vs 122 g/m2, p = 0.002) and higher AIx@75 (29.0% vs 26.3%, p = 0.043) compared to patients with no events. In Cox regression analysis, only higher HRV was associated with lower risk of arrhythmic events (Hazard ratio per 1 mmHg = 0.87, 95% Confidence intervals 0.76 to 0.995, p = 0.043) when adjusted for age, gender, cfPWV, LVMI and AIx@75. Conclusion: Lower heart rate variability is associated with increased risk of future arrhythmic events suggesting an early sympathovagal imbalance that could lead to future events.

Purpose/Background/Objectives: Hypertension is associated with increased cardiovascular risk, inflammation and arterial stiffness. We sought to investigate the role of inflammation and arterial stiffness in the prognosis of cardiovascular hospitalization in hypertensives patients over an extensive follow-up. Methods: One hundred and seventy-three patients (mean age 52.5 ± 13.2 years, 57% males) untreated hypertensives at baseline without cardiovascular disease, were included in the study. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). High-sensitivity C-reactive protein (hsCRP) was measured in venous blood samples. Results: During 13.6 ± 0.4 years of follow-up, forty-four patients (25.4%) patients were admitted in hospital due to cardiovascular causes. In multivariable logistic regression analysis, only higher hsCRP (Odds Ratio [OR] = 3.34, 95% Confidence intervals [CI]: 1.22–9.51, p = 0.020) and increased PWV (OR = 1.48, 95% Confidence intervals [CI]: 1.03–2.12, p = 0.036) were associated with higher risk of cardiovascular hospitalizations, which was independent of age, gender, systolic blood pressure, left ventricular mass index and presence of diabetes. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of hsCRP and PWV to discriminate subjects with cardiovascular hospitalization. The area under the curve (AUC) and 95% CIs of the ROC curves were AUC = 0.69 (95% CI: 0.59–0.78, p < 0.001) for hsCRP and AUC = 0.74 (95% CI: 0.65–0.83, p < 0.001) for PWV (Figure 1). Figure 1Diagonal segments are produced by ties. Conclusion: Our study shows the independent complimentary prognostic role of inflammation and arterial stiffness in the prognosis of hypertensives even in studies with extensive follow-up.

In recent years great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. The present article is an abridged version of an expert consensus document reporting the proceedings of several meetings of the European Network for Non Invasive Investigation of Large Arteries, and providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area. It provides recommendations for the determination of regional, local and systemic of arterial stiffness, and for the noninvasive determination of wave reflections. Clinical applications of arterial stiffness are also discussed.