Spyridon Deftereos

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 m2 in the colchicine group versus 23.2 (18.5‐33.4) mL/1.73 m2 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.

Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis.

Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11–0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03–0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments.

Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis

Objective— Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. Approach and Results— We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (⩽24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09–0.92; P=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07–10.0; P=0.037). Conclusions— We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.

Adenosine-Guided Pulmonary Vein Antral Isolation for Paroxysmal Atrial Fibrillation: A Randomized Study

The prognostic significance of adenosine‐mediated pulmonary vein (PV) dormant conduction and whether such conduction should be eliminated still remain controversial. This randomized study aimed to investigate whether adenosine‐guided ablation of the reconnection gaps improves the long‐term outcomes of pulmonary vein antral isolation (PVAI) for paroxysmal atrial fibrillation (AF).

A meta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome

Aims The early repolarization (ER) pattern has been linked to an increased risk for arrhythmic death in various clinical settings. There are limited and conflicting data regarding the prognostic significance of ER pattern in Brugada syndrome (BS). The aim of this meta-analysis was to provide a detailed analysis of the currently available studies regarding the arrhythmic risk in patients with BS and ER pattern. Methods and results Current databases were searched until May 2015. A random-effect meta-analysis of the effect of ER pattern on the incidence of arrhythmic events in patients with BS was performed. Five studies were included comprising a total of 1375 patients with BS. An ER pattern was reported in 177 patients (12.8%). During follow-up (44.9-93 months), 143 patients (10.4%) suffered an arrhythmic event. Overall, BS patients with ER pattern displayed an increased risk of arrhythmic events compared to patients without ER (OR 3.29, 95% CI: 2.06 to 5.26, P < 0.00001; Heterogeneity: P = 0.11, I2 = 48%). Three studies provided data regarding ER pattern location. Inferior, lateral, or inferolateral ER pattern location was observed in 20.3%, 32.2%, and 48%, respectively. An inferolateral ER location conferred the higher arrhythmic risk (OR 4.87, 95% CI: 2.64 to 9.01, P< 0.00001; Heterogeneity: P = 0.85, I2 = 0%). Conclusion This meta-analysis suggests that the ER pattern is associated with a high risk of arrhythmic events in patients with BS. In particular, BS patients with inferolateral ER (global ER pattern) displayed the highest arrhythmic risk.

Amino-terminal B-natriuretic peptide levels and postablation recurrence in hypertensive patients with paroxysmal atrial fibrillation.

BACKGROUND Amino-terminal B-type natriuretic peptide (NT-proBNP) has been shown to predict postablation recurrences of atrial fibrillation (AF); however, given the associations of natriuretic peptides with various cardiovascular parameters potentially related to AF, whether the observed association with recurrence is truly an independent one is not clear. OBJECTIVE The purpose of this analysis was to assess the association of NT-proBNP levels with AF recurrence after radiofrequency ablation. METHODS This was a post hoc analysis of a prospective study of 296 hypertensive patients with symptomatic paroxysmal AF and no history of heart failure who were scheduled to undergo pulmonary vein isolation. NT-proBNP was measured at baseline, and patients were followed for a median of 13.7 months. RESULTS NT-proBNP levels at baseline were higher in patients with recurrence (269 pg/mL [199-361 pg/mL]) vs those who remained arrhythmia-free (188 pg/mL [146-320 pg/mL], P<.001). In a univariate Cox regression model, each higher quartile of NT-proBNP corresponded to a 47% (95% confidence interval 21.5%-77.9%) increase in the risk of recurrence. However, when baseline clinical AF burden, in terms of the number of clinical AF episodes in the previous year, was added to the model, the association of NT-proBNP lost its significance (adjusted hazard ratio 1.22, 95% confidence interval 0.94-1.57). CONCLUSION This is the largest series to date showing that NT-proBNP is a univariate predictor of postablation AF recurrence. However, it seems that adjustment for other covariates, including the number of AF episodes within the previous year, renders this association nonsignificant.

The Role of Colchicine in the Prevention of Cerebrovascular Ischemia

INTRODUCTION Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. METHODS In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia. We also highlight the potential role of colchicine in the suppression of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism prevention. RESULTS Accumulating evidence suggests that inflammation is of key importance in the pathophysiology of atherosclerotic plaque de-stabilization and thromboembolism, with inflammatory cells being involved in all stages of atherosclerosis development. Therefore, anti-inflammatory therapies targeting the atherosclerotic plaque inflammation may be important contributors in plaque stabilization and in the prevention of thromboembolic events. Colchicine is known to have multiple anti-inflammatory properties including inhibition of microtubule polymerization, leading to reduced secretion in monocyte-macrophages. Currently the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate the effect of a daily low-dose of colchicine in reducing the rate of recurrent stroke and major vascular events. CONCLUSION Inflammatory pathways seem to be key mediators in the development of atherosclerotic process, atheromatous plaque destabilization and thromboembolism. Colchicine as a novel therapeutic agent could be a safe and effective inhibitor of the inflammation cascade in patients with extra- or intracranial atherosclerosis or arteriolosclerosis, resulting in reduced vascular events.

Percutaneous patent foramen ovale closure for secondary stroke prevention: Network meta-analysis

Objective Current guidelines report no benefit for patent foramen ovale (PFO) closure compared to medical treatment in patients with cryptogenic ischemic stroke (IS) or TIA. Two recent randomized controlled clinical trials have challenged these recommendations. Methods We performed a systematic review and network meta-analysis of randomized controlled trials to estimate the safety and efficacy of closure compared to medical treatment, and to compare available devices. We conducted pairwise meta-analyses for closure vs medical therapy, irrespective of the device used, and for each device vs medical therapy. Results Our literature search highlighted 6 studies. PFO occlusion was associated with reduced risk of recurrent IS (risk ratio [RR] 0.42, 95% confidence interval [CI] 0.20–0.91) and IS/TIA (RR 0.65, 95% CI 0.48–0.88) but with increased risk of new-onset atrial fibrillation (AF) (RR 4.59, 95% CI 2.01–10.45) compared to medical treatment. In indirect analyses, both Amplatzer (AMP) and GORE devices were found to be associated with a lower risk of new-onset AF compared to STARFlex (SFX) (RR 0.25, 95% CI 0.10–0.65 and RR 0.28, 95% CI 0.08–0.95). Moreover, AMP was found to be associated with a lower risk of recurrent IS/TIA events compared to the SFX device (RR 0.35, 95% CI 0.14–0.91). In the clustered ranking plot on the risk of IS against new-onset AF, GORE was comparable to AMP; however, on the risk of IS/TIA against new-onset AF, AMP appeared to be superior to the GORE device. In both ranking plots, SFX was highlighted as the worst option. Conclusion PFO closure is associated with reduced risk of recurrent IS or IS/TIA and with increased risk of new-onset AF.

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.

Remote monitoring of the cardiac rhythm: where do we stand today?

Remote monitoring systems, in their current forms, are networked communication solutions allowing exchange of digitized data from implanted or wearable devices. These data usually include electrocardiographic recordings, but nowadays they may encompass much more than that, allowing a continuously updated knowledge of a multitude of device‐ or patient‐related parameters. Remote monitoring has been shown, as one would have expected, to reduce the need for office visits and allow earlier detection—and thus management—of arrhythmic events. However, although there are hints that they may also be associated with improved clinical outcomes, the absence of randomized trials dictates a cautious interpretation of existing evidence. Furthermore, there are still several questions regarding their cost‐effectiveness, the patient populations that could benefit from them, as well as how the transmitted data should be interpreted and acted upon by physicians. In this review, we present and critically examine the current state of affairs of remote cardiac rhythm monitoring systems.