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.

Effect of pulmonary vein isolation on left atrial appendage flow in paroxysmal atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) functional modification in the context of pulmonary vein isolation has been a focus point of research and LAA emptying flow velocity (LAAEFV) is considered to reflect LAA contractility, stunning, and fibrosis. OBJECTIVE: In the present study, we sought to prospectively evaluate short-term LAAEFV changes after radiofrequency (RF) or cryoballoon ablation in paroxysmal AF. METHODS: This was a prospective substudy of the Effect of Cryoballoon and RF Ablation on Left Atrial Function (CryoLAEF) study (ClinicalTrials.gov Identifier: NCT02611869). Thirty patients, randomly assigned to RF or cryoablation, were prospectively followed. Transesophageal echocardiograms were performed at baseline and at 3 months postablation to measure LAAEFV. RESULTS: All measurements were performed in sinus rhythm. Overall, LAAEFV was 44.2 [38.5-62.8] cm/s at baseline and was increased to 70.8 [64.8-77.6] cm/s at 3 months' postablation (P < 0.001). Baseline LAAEFV was 52.5 [37.7-68.0] cm/s in the RF group and 42.8 [38.7-52.9] cm/s in the CryoBalloon group (P  =  0.653). At 3 months, the corresponding values were 68.5 [61.9-76.6] cm/s and 73.9 [69.2-79.9] cm/s, respectively (P  =  0.081 for the difference between the two groups at 3 months). The median change in LAAEFV was 11.0 [4.7-26.2] cm/s in the RF group versus 29.6 [15.8-37.0] cm/s in the CryoBalloon group (P  =  0.033). CONCLUSION: LAA function is improved after catheter ablation with RF or balloon cryoablation in patients with paroxysmal AF, evaluated while in sinus rhythm both at baseline and on follow-up.

Lazaroid U-74389G for cardioplegia-related ischemia-reperfusion injury: an experimental study.

BACKGROUND: The adverse effects of myocardial ischemia and reperfusion during cardiopulmonary bypass (CPB) have been thoroughly described. Lazaroid U-74389G, a 21 aminosteroid, has been shown to attenuate ischemia and reperfusion injury and improve recovery in a variety of experimental models. METHODS: Sixteen male swine were randomly divided in two groups. All animals underwent 45 min of ischemic cardioplegic arrest, with U-74389G addition to the standard cardioplegic solution, whereas controls underwent the same procedure without U-74389G. Creatine kinase-MB isoenzyme (CK-MB) and cardiac troponin T levels were measured immediately before CPB (time point 0), during the ischemic period (time point 1) and 30 (time point 2), 60 (time point 3), and 120 (time point 4) min after reperfusion. Myocardial biopsies were obtained at time points 0 and 4. RESULTS: CK-MB levels (in U/L) at time points 0-4 were 205 (186-235) versus 219 (196-269; P = 0.72), 215 (167-248) versus 253 (193-339; P = 0.23), 234 (198-255) versus 338 (249-441; P = 0.02), 244 (217-272) versus 354 (269-496; P = 0.01), and 285 (230-321) versus 439 (432-530; P < 0.01) in lazaroid-treated animals versus controls, respectively. Cardiac troponin T levels (in ng/L) at time points 0-4 were 58 (26-287) versus 237 (26-395; P = 0.72), 129 (61-405) versus 265 (145-525; P = 0.23), 261 (123-467) versus 474 (427-1604; P = 0.04), 417 (204-750) versus 841 (584-1818; P = 0.11), and 643 (353-1259) versus 1600 (1378-2313; P < 0.01), respectively. Necrosis grades at time point 4 were 0.0 (0.0-1.0) versus 1.5 (1.0-2.0; P < 0.01) in lazaroid-treated animals versus controls, respectively. CONCLUSIONS: The present study, in addition to reconfirming the well-described adverse effects of CPB, demonstrates the efficacy of the newer generation lazaroid U-74389G in alleviating these effects.

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction.

OBJECTIVES: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. METHODS: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. RESULTS: RBCm count was correlated with CK-MB AUC (Spearman's ρ = 0.83, p < 0.001). The CK-MB AUC values per RBCm quartile (lower to upper) were: 3,351 (2,452-3,608), 5,005 (4,450-5,424), 5,903 (4,862-10,594), and 8,406 (6,848-12,782) ng × h/ml, respectively. From lower to upper quartiles, the maximal troponin I values were: 42.2 (23.3-49.3), 49.6 (28.8-54.1), 59.2 (41.4-77.3), and 69.1 (48.0-77.5) ng/ml (p = 0.005). In multivariable analysis, RBCm remained a significant predictor of CK-MB AUC (standardized ß = 0.63, adjusted p = 0.001). CONCLUSIONS: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury.

Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study.

BACKGROUND: Inflammatory processes have been identified as key mediators of the deleterious effects of ischemia/reperfusion in ST-segment-elevation myocardial infarction. Colchicine is a substance with potent anti-inflammatory properties, suitable for safe use in patients with cardiovascular disease. The purpose of this study was to test the hypothesis that a short course of colchicine treatment could lead to reduced infarct size. METHODS AND RESULTS: Patients presenting with ST-segment-elevation myocardial infarction ≤12 hours from pain onset (treated with primary percutaneous coronary intervention) were randomly assigned to colchicine or placebo for 5 days. The primary outcome parameter was the area under the curve of creatine kinase-myocardial brain fraction concentration. A subset of patients underwent cardiac MRI with late gadolinium enhancement 6 to 9 days after the index ST-segment-elevation myocardial infarction. One hundred fifty-one patients were included (60 in the MRI substudy). The area under the creatine kinase-myocardial brain fraction curve was 3144 (interquartile range [IQR], 1754-6940) ng·h(-1)·mL(-1) in the colchicine group in comparison with 6184 (IQR, 4456-6980) ng·h(-1)·mL(-1) in controls (P<0.001). Indexed MRI-late gadolinium enhancement-defined infarct size was 18.3 (IQR, 7.6-29.9) mL/1.73 m(2) in the colchicine group versus 23.2 (18.5-33.4) mL/1.73 m(2) in controls (P=0.019). The relative infarct size (as a proportion to left ventricular myocardial volume) was 13.0 (IQR, 8.0-25.3) % and 19.8 (IQR, 13.7-29.8) %, respectively (P=0.034). CONCLUSIONS: These results suggest a potential benefit of colchicine in ST-segment-elevation myocardial infarction, but further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936285.

In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome.

BACKGROUND: P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS: Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS: In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.

Effect of Angiotensin converting enzyme inhibitors on soluble tumor-necrosis-factor-related apoptosis-inducing ligand levels - association with neointimal hyperplasia in drug eluting stents.

OBJECTIVE: To test the hypothesis that angiotensin converting enzyme inhibitors (ACEi) affect soluble tumor-necrosis-factor-related apoptosis-inducing ligand (sTRAIL) and this interaction is associated with less in-drug-eluting-stent (DES) neointimal hyperplasia following percutaneous coronary intervention (PCI). METHODS: From our database of patients with elective PCI and baseline intravascular ultrasound (IVUS) evaluation of the implanted DES, we randomly selected 60 patients who were prescribed an ACEi and 60 matched controls, who did not receive an ACEi following PCI. All patients underwent coronary angiography and IVUS. sTRAIL was measured in samples from the stented coronary artery and a peripheral vein. RESULTS: sTRAIL concentration was higher in the ACEi group, both in coronary and peripheral samples: 104 [78-139] pg/ml versus 63 [45-100] pg/ml (P < 0.001) and 99 [73-135] pg/ml versus 69 [49-103] pg/ml (P = 0.002), respectively. There was an inverse association (standardized beta -0.760; P < 0.001) between sTRAIL and lumen area loss in both treatment groups. In the multivariable analysis, log(sTRAIL) was an independent negative predictor of lumen area loss (standardized beta -0.660, adjusted 95% confidence interval -0.722 to -0.466). CONCLUSIONS: Treatment with ACEi was associated with higher sTRAIL levels and lower lumen area loss in the IVUS evaluation of implanted DES. sTRAIL levels were negatively associated with in-stent neointima hyperplasia in these post-PCI patients.

Contraindications/special warnings and precautions for use of contemporary oral antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The prevalence of contraindications/special warnings and precautions (CON/SWP) for clopidogrel, prasugrel and ticagrelor use is not adequately studied and might affect P2Y12 inhibitor choice in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the context of the GReek AntiPlatelet rEgistry (GRAPE) a detailed recording of CON/SWP for use of clopidogrel, prasugrel and ticagrelor was done for 1,280 consecutive, moderate-high-risk ACS patients undergoing PCI. At least 1 CON for use of clopidogrel, prasugrel and ticagrelor was present in 5 (0.4%), 49 (3.8%) and 12 patients (0.9%), respectively. Prevalence of at least 1 CON/SWP to clopidogrel (45.8%) was less frequent compared to prasugrel (49.1%) or ticagrelor (49.1%; P=0.02 and P=0.04, respectively), while 34% of patients had at least 1 CON/SWP to all the 3 P2Y12 inhibitors. At discharge, 482 (38.6%), 301 (24.1%) and 464 patients (37.2%) received clopidogrel, prasugrel and ticagrelor, respectively. Age ≥75 years, co-medication related to increased bleeding risk, and history of asthma/chronic obstructive pulmonary disease favored clopidogrel vs. prasugrel or ticagrelor use as discharge medication, while geographic region also affected this choice (C-statistic, 0.81; 95% CI: 0.78-0.83). CONCLUSIONS: In patients with ACS undergoing PCI the prevalence of CON to antiplatelet agents is low, whereas that of SWP is high. Certain SWP, along with regional trends may affect the choice of newer P2Y12 inhibitors vs. clopidogrel.

The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design.

OBJECTIVE: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. METHODS: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. RESULTS: Trial results will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.

Gout and arrhythmias: In search for causation beyond association.

Gout is a systemic disease, characterized by the formation and deposition of crystals in tissues (mainly in and around the joints) of individuals with elevated serum uric acid levels. Lately, a considerable number of reports relating elevated uric acid and/or gout with rhythm disorders, such as atrial fibrillation, have been published. This review summarizes evidence linking common arrhythmias and hyperuricemia/gout and discusses questions or controversies that surround it. Overall, existing evidence may not be overwhelming, but strongly suggests a positive correlation between uric acid levels and common rhythm disorders. Needless to say that such a link - as a univariate association between the two - is to be expected, given the extensive overlap of risk factors and comorbidities of hyperuricemia/gout and arrhythmias. However, the observed associations seem to persist - in most studies - after extensive adjustment for potential confounders. Still, multivariable analyses of epidemiologically collected data cannot substitute for proof coming from basic and clinical studies. There is obviously a need for further basic research to establish a causal relationship between uric acid effects and arrhythmias, as well as translational studies and clinical trials to investigate the therapeutic implications of such a relationship. Simply put, we are fairly certain that there is association, but proof of causation is what we are still in want of.

The Role of Colchicine in Treating Postoperative and Post-catheter Ablation Atrial Fibrillation.

PURPOSE: The goal of this review was to summarize, analyze, and compare trials studying the efficacy of colchicine in the prevention of atrial fibrillation (AF) post-operatively (POAF) and post-catheter ablation. Ongoing studies and current guidelines are also presented and reviewed. METHODS: Published studies on the field were identified through a literature search of the PubMed and clinicaltrials.gov databases. FINDINGS: Four original studies regarding POAF, two original studies regarding post-catheter ablation AF, and six meta-analyses were identified. In addition, the 3 most recent guidelines/expert consensus documents were scrutinized. IMPLICATIONS: AF occurs frequently after cardiac surgery (POAF) and catheter pulmonary vein isolation (postablation AF) and is associated with increased cardiovascular morbidity. A number of trials over the last few years have investigated the role of colchicine in the prevention of POAF and postablation AF targeting the local and systemic inflammatory process that leads to initiation and maintenance of AF. Available data imply that colchicine may have a preventive role in POAF and/or postablation AF. However, certain limitations of these studies underline the need for further investigation.

Antioxidant treatment in peripheral artery disease: the rationale is there, but what about clinical results?

Peripheral arterial disease is a major cause of morbidity and disability and has been consistently associated with an adverse overall prognosis. Oxidative stress has been linked to vascular disease, with several suggested pathogenetic mechanisms, leading to various insults of the arterial wall and, ultimately, to atherothrombotic disease. Considering that the pathophysiological background is quite compelling, attenuation of oxidative processes by means of various substances with antioxidant properties has been conceived as a promising therapeutic target. However, clinical results have been mostly disappointing and 'antioxidant' therapies are still far from being integrated into treatment algorithms for vascular disease.

The Role of Calcium Handling Mechanisms in Reperfusion Injury.

Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of death and disability worldwide. However, the mortality of MI has declined dramatically over the past several decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin converting enzyme inhibitors) and approaches to restore tissue perfusion (percutaneous coronary intervention and cardiopulmonary bypass). Animal studies have been shown that these treatments have been effective in reducing acute myocardial ischemic injury and limiting MI size. The paradox is that the process of reperfusion can itself amplify cell injury and death, known as myocardial ischemia-reperfusion injury (I/R). Intensive research has uncovered several complex mechanisms of cardiomyocyte damage after reperfusion,and potential therapeutic targets for preventing I/R. Importantly, it is now recognized that excessive elevation of intracellular and mitochondrial Ca2+during reperfusion predisposes the cells to hypercontracture, proteolysis and mitochondrial failure and eventually to necrotic or apoptotic death. These enormous alterations in cytosolic Ca2+ levels are induced by the Ca2+ channels of the sarcolemma(L-Type Ca2+channels, sodium/calcium exchanger), the endoplasmic/ sarcoplasmic reticulum (SERCA ATPase) and ryanodine receptors, SOCE(store-operated calcium entry), lysosomes and others, which are modified by I/R injury. The overall goal of this review is to describe the different pathways that lead to I/R injury via Ca2+ overload, focus on recent discoveries and highlight prospects for therapeutic strategies for clinical benefit.

Colchicine Pharmacokinetics and Mechanism of Action.

Colchicine is a tricyclic, lipid-soluble alkaloid derived from the plant of the Lily family Colchicum autumnale, sometimes called the "autumn crocus". It is predominantly metabolized in the gastrointestinal tract. Two proteins, P-glycoprotein (P-gp) and CYP3A4 seem to play a pivotal role, governing its pharmacokinetic. The commonest side effects are gastrointestinal (nausea, vomiting and particularly dose-related-diarrhea) occurring in 5-10% of patients. Colchicine exerts its unique action mainly through inhibition of microtubule polymerization. Microtubule polymerization affects a variety of cellular processes including maintenance of shape, signaling, division, migration, and cellular transport. Colchicine interferes with several inflammatory pathways including adhesion and recruitment of neutrophils, superoxide production, inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway attenuating the inflammatory response. This concise paper attempts to give a brief review of its pharmacokinetic properties and its main mechanisms of action.

Colchicine in Post-operative Atrial Fibrillation: A Review.

Post-operative atrial fibrillation (POAF) is a frequent entity increasing hospitalization duration, stroke and mortality. In the recent years, a few studies have sought to investigate the potential effect of colchicine in POAF prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In the present review article, we intend to provide a synopsis of clinical practice guidelines, summarize and critically approach current evidence for or against colchicine as a means of POAF prevention.

Calcium Handling and Arrhythmogenesis.

Intracellular calcium homeostasis plays a fundamental role in the electric and mechanical function of the heart by modulating action potential pattern and duration, by linking cell membrane depolarization to myocardial contraction and by regulating cardiac automaticity. Abnormalities of intracellular calcium regulation disrupt the electrophysiological properties of the heart and create an arrhythmogenic milieu, which promotes atrial and ventricular arrhythmogenesis and impairs cardiac automaticity and atrioventricular conduction. In this brief review, we summarize the basic genetic, molecular and electrophysiological mechanisms linking inherited or acquired intracellular Ca(2+) dysregulation to arrhythmogenesis.

Intra--and Intercellular Calcium Handling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.

Calcium Ions in Inherited Cardiomyopathies.

Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis.