Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.

Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.

Molecular Mechanisms and Therapeutic Implications of Endothelial Dysfunction in Patients with Heart Failure.

Heart failure is a complex medical syndrome that is attributed to a number of risk factors; nevertheless, its clinical presentation is quite similar among the different etiologies. Heart failure displays a rapidly increasing prevalence due to the aging of the population and the success of medical treatment and devices. The pathophysiology of heart failure comprises several mechanisms, such as activation of neurohormonal systems, oxidative stress, dysfunctional calcium handling, impaired energy utilization, mitochondrial dysfunction, and inflammation, which are also implicated in the development of endothelial dysfunction. Heart failure with reduced ejection fraction is usually the result of myocardial loss, which progressively ends in myocardial remodeling. On the other hand, heart failure with preserved ejection fraction is common in patients with comorbidities such as diabetes mellitus, obesity, and hypertension, which trigger the creation of a micro-environment of chronic, ongoing inflammation. Interestingly, endothelial dysfunction of both peripheral vessels and coronary epicardial vessels and microcirculation is a common characteristic of both categories of heart failure and has been associated with worse cardiovascular outcomes. Indeed, exercise training and several heart failure drug categories display favorable effects against endothelial dysfunction apart from their established direct myocardial benefit.

Non-Alcoholic Fatty Liver Disease and Echocardiographic Parameters of Left Ventricular Diastolic Function: A Systematic Review and Meta-Analysis.

The cardiovascular implications of non-alcoholic fatty liver disease (NAFLD) have been associated with heart failure with preserved ejection fraction (HFpEF). The purpose of this review was to conduct a bibliographic search regarding the correlation between NAFLD and the echocardiographic parameters of left ventricular diastolic function. A systematic literature search was conducted in PubMed and Embase for original research data reporting on the association of NAFLD with diastolic function markers [E/e', left atrial volume index (LAVi), left ventricular mass index (LVMi)]. Meta-analysis was performed using the meta and dmetar packages in R studio v.1.4.1106, with p < 0.05 values being considered significant. Results are expressed as the standardized mean difference (SMD) for continuous variables and as the odds ratio (OR) for categorical variables, with respective 95% confidence intervals (CI). Heterogeneity between studies was expressed with index Ι2. From the preliminary search, 2619 articles were found from which 31 studies were included in the final statistical analysis. The meta-analysis of 8 studies which reported on the prevalence of diastolic dysfunction showed that it was increased in patients with NAFLD (OR: 2.07, 95% CI 1.24-3.44 with p = 0.01, I2: 80% with p < 0.01). The meta-analysis of 21 studies showed significantly higher E/e' in NAFLD patients (SMD 1.02, 95% CI 0.43-1.61 with p < 0.001, I2: 97% with p < 0.001). Individuals with NAFLD had increased LAVi (SMD: 0.87, 95% CI 0.38-1.37 with p < 0.001, I2: 96% with p < 0.001) and LVMi (SMD: 0.89, 95% CI 0.31-1.48 with p = 0.003, I2: 100% with p < 0.001). To conclude, in the meta-analysis of 31 observational studies, NAFLD patients were found to have affected left ventricular diastolic function, supporting the hypothesis of NAFLD being associated with HFpEF.

Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment.

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they are largely determined by variations in the Lp(a) gene (LPA) locus encoding apo(a). Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular (CV) events. Despite this crucial role of Lp(a), its measurement lacks a globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such as statins, fibrates and ezetimibe, have a mediocre effect on Lp(a) levels, although it is not yet clear whether such treatments can affect CV events and prognosis. This narrative review aims to summarize knowledge regarding the mechanisms mediating the effect of Lp(a) on inflammation, atherosclerosis and thrombosis and discuss current diagnostic and therapeutic potentials.

Arterial stiffness and microvascular disease in type 2 diabetes.

BACKGROUND: The clustering of arterial stiffness with microvascular disease (MD) and their effects on the clinical outcome of patients with type 2 diabetes (T2D) remains not fully clarified. METHODS: In a prospective study of 414 patients with T2D, we investigated the prognostic value of arterial stiffness and MD for clinical outcomes. Participants were assessed for the presence of MD (ie diabetic retinopathy, nephropathy and neuropathy) and arterial stiffness by pulse wave velocity (PWV) and followed-up for a median of 30 (range 1-60) months. The primary endpoint of the study was the composite endpoint of major adverse cardiovascular events, that is, cardiovascular and non-cardiovascular mortality and non-fatal myocardial infarction/stroke. RESULTS: A total of 146 (35.3%) patients had evidence of MD at baseline. In cox regression models, MD and PWV were independently associated with the composite clinical endpoint; for MD hazard ratio (HR), 3.24, 95%CI, 1.10-9.54, P=.032, and for PWV HR, 1.20, 95%CI, 1.06-1.36, P=.004) after adjustment for traditional risk factors, and enhanced risk discrimination and reclassification. The subgroup of patients with MD and high PWV was associated with increased incidence of the composite clinical endpoint (20.9% vs 1.8% in those with no MD & low PWV, P=.001). Importantly, absence of MD at baseline was associated with no mortality events during the follow-up period. PWV at baseline was not associated with MD progression during follow-up. CONCLUSIONS: These findings support that screening for arterial stiffness and MD in the routine clinical assessment of patients with T2D may enhance prognostication and cardiovascular risk reclassification.

One-year clinical and echocardiographic outcomes of direct implantation of a self-expanding valve.

OBJECTIVE: To present 1 year clinical and echocardiographic outcomes of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial. BACKGROUND: Intermediate-term data from randomized studies investigating the safety and efficacy of direct implantation are lacking. METHODS: DIRECT trial randomized 171 consecutive patients with severe aortic stenosis at four tertiary centers to undergo TAVI with the use of self-expanding prostheses with (pre-BAV) or without pre-dilatation (no-BAV). The primary endpoint was device success according to the VARC-2 criteria. All patients underwent a clinical and echocardiographic follow-up at 1 year. All-cause and cardiac mortality, stroke, heart failure hospitalization, and new pacemaker implantation were recorded. RESULTS: At 1 year, four deaths were recorded in pre-BAV group (4.7%) and three deaths in no-BAV group (3.5%). There was no difference in Kaplan-Meier plots between the two groups in all-cause mortality at 1 year (log-rank p = .72). Similarly, there was no difference in the incidence of permanent pacemaker implantation between the two groups at 1 year (27/67-40.3% in no-BAV group versus 20/69-29% in pre-BAV group, log-rank p = .24). There was no significant difference between pre-BAV and no BAV group in aortic valve area (1.84 ± 0.39 cm2 vs. 1.85 ± 0.44 cm2 , p = .90), mean aortic valve gradient (8.36 ± 5.04 vs. 8.00 ± 4.04 mmHg, p = .65) and moderate or severe paravalvular regurgitation (5-6.6 vs. 4-5.7%, respectively) at 1 year. The same applied independently from the performance of post-dilatation at baseline. CONCLUSIONS: Direct, without pre-dilatation, implantation of a self-expanding valve has no impact on one-year clinical and echocardiographic outcomes, independently also from the baseline performance of post-dilatation.

Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease.

BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). METHODS: Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels. RESULTS: After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 µg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 µg/L and in the 1st tertile (Lp-PLA2 values < 101 µg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 µg/L. A linear regression analysis showed that Lp-PLA2 values > 138 µg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with ß-blockers. CONCLUSIONS: Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

Prognostic role of diastolic dysfunction in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: Prior studies have shown that left ventricular diastolic dysfunction (DD) is associated with increased mortality after surgical aortic valve replacement but studies on transcatheter aortic valve replacement (TAVR) are limited and have not taken into account mitral annular calcification (MAC), which limits the use of mitral valve annular tissue Doppler imaging. We performed a single-center retrospective analysis to better evaluate the role of baseline DD on outcomes after TAVR. METHODS: After excluding patients with atrial fibrillation, mitral valve prostheses and significant mitral stenosis, 359 consecutive TAVR patients were included in the study. Moderate-to-severe MAC was present in 58% of the patients. We classified patients into severe versus nonsevere DD based on the evaluation of elevated left ventricular filling pressure. The outcome measure was all-cause mortality or heart failure hospitalization. RESULTS: Over a mean follow-up time of 13 months, severe DD was associated with an increased risk for the outcome measure (HR 2.02 [1.23-3.30], p = .005). However, this association was lost in a propensity-matched cohort. In multivariate analysis, STS score was the only independent predictor of all cause mortality of heart failure hospitalization (HR 1.1 [1.05-1.15], p < .001). CONCLUSIONS: We evaluated the role of baseline DD on outcomes after TAVR by taking into account the presence of MAC. Severe DD was associated with increased all-cause mortality or heart failure hospitalization but not independently of other structural parameters and known predictors of the outcome measure.

Comparison of warfarin versus DOACs in patients with concomitant indication for oral anticoagulation undergoing TAVI; results from the ATLAS registry.

The optimal antithrombotic therapy for patients undergoing TAVI with concomitant indication for oral anticoagulation remains unclear. In this high-risk population group, there is a paucity of data with regards to the use of DOACs. In the present study we compared long-term clinical outcomes of TAVI patients requiring anticoagulation, treated with warfarin versus DOACs. Consecutive patients, who underwent TAVI with indication for oral anticoagulation from the multicenter ATLAS registry were studied and divided in two groups depending on the chosen anticoagulation regimen, warfarin vs. DOACs. 30-day survival, as well as estimated 1 and 2-year all-cause mortality were compared between groups. The secondary endpoint included in-hospital major or life-threatening bleeding. The study group included 217 patients (102 treated with warfarin; 115 treated with DOACs). Kaplan-Meier estimated survival was found to be statistically similar in the warfarin and DOAC groups (90.6% vs. 93.7% for 1-year and 84.5% vs. 88.5%, for 2-year survival, respectively, Plog-rank = 0.984). Adjusted hazard ratio for all cause mortality was similar between the two groups (HRwarfarin vs. DOAC = 1.15; 95% CI 0.33 to 4.04, p = 0.829). Propensity matching revealed similar results. At 30-days, all-cause mortality was found to be comparable between the two groups. With regards to BARC defined bleeding complications, major and life-threatening complications did not differ between the two anticoagulation groups (6% vs. 8% for warfarin and DOACs respectively, p = 0.857). DOACs seem to demonstrate a similar safety and efficacy profile compared to warfarin in TAVI patients with a concomitant indication for oral anticoagulation.

Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure.

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.

Real-world comparison of the new 34 mm self-expandable transcatheter aortic prosthesis Evolut R to its 31 mm core valve predecessor.

OBJECTIVES: The aim of the present study was to compare the incidence of periprocedural complications and short-term outcomes between the second-generation recapturable 34 mm Evolut-R and its first-generation 31 mm predecessor. BACKGROUND: Although already in extensive clinical use in real world patients, the periprocedural complications and clinical outcomes of the new 34 mm device have not been investigated yet. METHODS: Consecutive patients who had undergone transcatheter aortic valve implantation in two centers with either a 31 mm CoreValve or a 34 mm Evolut-R device were retrospectively studied. Periprocedural complications of malpositioning, valve-in-valve implantation, conversion to full sternotomy or percutaneous coronary intervention and vascular complications were compared between the two groups. Short-term outcomes at discharge were compared using Valve Academic Research Consortium (VARC-2) criteria. RESULTS: The study group included 106 patients (35 Evolut-R 34 mm; 71 CoreValve 31 mm). Significantly lower rates of valve-in-valve implantation were demonstrated for the 34 mm group compared to the first-generation device (0% vs. 11.9%, respectively, P = 0.036). All other periprocedural complications were similar between groups. At discharge, the rates of new pacemaker implantation (5.7% vs. 26.8%, P = 0.037) and bleeding complications (2.9% vs. 19.6%, P = 0.025) were statistically significantly lower among the 34 mm group. With regards to VARC-2 defined combined endpoints, rates of early safety were significantly improved among the 34 mm group compared to 31 mm group (0% vs. 27.9%, respectively, P = 0.004). CONCLUSIONS: The recently introduced 34 mm Evolut-R seems to demonstrate an improved safety profile, as evidenced by the reduced bleeding rates, lower rates of valve-in-valve implantation and lower PPM rates compared to its 31 mm predecessor.

Intracardiac echocardiography for percutaneous patent foramen ovale and atrial septal defect occlusion.

BACKGROUND: Transesophageal echocardiography (TEE) plays a unique role in transcatheter closure of atrial septal defects (ASD) and patent foramen ovale (PFO). However, problems such as the need for general anesthesia, possible trauma from endotracheal intubation, presence of "blind spots," and occasional inadequate imaging of some cardiac structures have necessitated better imaging techniques. Our study aimed to compare the findings of TEE during the initial diagnostic examination with those from intracardiac echocardiography (ICE) acquired during the interventional procedure. METHODS: A total of 65 patients in whom TEE was used for the diagnosis of ASD or PFO were included. Of these, 40 patients (61.5%) had ASD with significant left to right shunt and 25 (38.5%) patients had PFO associated with transient ischemic attack or stroke. ICE imaging was performed under local anesthesia in all patients to guide interatrial communication closure. RESULTS: ICE provided adequate views of the defects and surrounding structures during the various stages of device deployment. In eight patients (12.3%) an additional anatomical variation was detected. All patients had successful device implantation and were discharged 1 day after the procedure. CONCLUSION: ICE is a safe and high-quality imaging technique for guiding transcatheter ASD and PFO occlusion. Additionally, ICE can both facilitate device implantation and detect cardiac abnormalities that are not identified with TEE during the initial diagnostic investigation.

3D Bioprinting Methods and Techniques: Applications on Artificial Blood Vessel Fabrication.

Three-dimensional (3D) printing has rapidly evolved, with major applications in the field of medicine. One of the greatest advances leading to 3D bioprinting was the development of biomaterials, cells and supporting components for the fabrication of functional living tissues. Several different methods and techniques of 3D bioprinting are briefly described in this review article, and applications of 3D printing for the fabrication of artificial blood vessels and grafts are presented. Advances in additive manufacturing techniques, medical imaging modalities, biomaterials and cellular engineering will lead to further developments in the fabrication of patient-specific vascular tissue constructs. Future multidisciplinary research and innovations are expected to further transform the fields of tissue engineering and regenerative medicine.

Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance.

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease.

BACKGROUND: Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. MATERIALS AND METHODS: We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. RESULTS: During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS: These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

Le "canceur des fumeurs" in 19th century: the contribution of the French surgeon Étienne-Frédéric Bouisson (1813-1884).

At the beginning of the 19th century, the alarming rise in tobacco consumption and its consequences in health preoccupied physicians. Several medical authors pointed out the harmful effects of smoking, enumerating related disorders. In 1821, the hygienist Alexandre Parent du Châtelet (1790-1835) and the chemist Félix d'Arcet (1814-1847), studied the effects of tobacco in health and concluded that it was a relatively healthy habit providing also a kind of immunity from contagious diseases. The tobacco controversy opened up and continued for almost 40 years. In 1861, the professor of surgery and politician Étienne-Frédéric Bouisson (1813-1884) in his work entitled: "Tribut à la chirurgie ou mémoires sur divers sujets de cette science" (Tribute to surgery or dissertations on various topics of this science) related for the first time tobacco consumption to oral cancer, applying medical statistics and analyzing meticulously all the available data.

Contemporary Antiplatelet Treatment in Acute Coronary Syndrome Patients with Impaired Renal Function Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: To assess the clinical impact of impaired renal function (IRF), in "real-world" acute coronary syndrome (ACS) patients, receiving clopidogrel, prasugrel, or ticagrelor. METHODS: This was a prospective, observational, multicenter, cohort study of ACS patients undergoing percutaneous coronary interventions (PCI) with IRF (creatinine clearance <60 mL/min by Cockroft-Gault equation), who were recruited into the Greek Antiplatelet Registry (GRAPE). Patients were followed-up until 1 year for major adverse cardiovascular events (MACE; a composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and BARC (Bleeding Academic Research Consortium) bleeding. RESULTS: Out of 2,047 registered patients, there were 344 (16.8%) with IRF. At the 1-year follow-up, MACE occurred in 18.6 and 6.2% of those patients with and without IRF, respectively: adjusted hazard ratio (HR) = 2.13 (95% confidence interval, CI 1.16-3.91), p = 0.02. IRF patients were also at higher risk of death and BARC type ≥2 and ≥3 bleeding: adjusted HR = 3.55 (95% CI 1.73-7.27), p = 0.001; HR = 2.75 (95% CI 1.13-6.68), p = 0.03; and HR = 6.02 (95% CI 2.30-15.77), p < 0.001, respectively. Combined MACE and BARC type ≥2 bleeding occurred in 34.0 and 14.0% of those with and without IRF, respectively: adjusted HR = 2.65 (95% CI 1.36-5.16), p = 0.004. At discharge, clopidogrel was more frequently prescribed in IRF patients (61.0 vs. 33.1%, p < 0.001). CONCLUSIONS: Real-world ACS patients with IRF subjected to PCI demonstrate higher thrombotic and bleeding risks than patients with normal renal function.

Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance.

OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. RESULTS: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. CONCLUSIONS: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.