Colchicine After Pulmonary Vein Isolation: Is Inflammation the New Anti-Arrhythmic Target

Filgueiras-Rama, David; Montoro, Nieves; Gómez-Gallanti, Alfonso; Garófalo, Daniel; Peinado, Rafaél

doi:10.1016/j.jacc.2012.12.042

Cited by 4 publications

(3 citation statements)

References 8 publications

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“…Yet, there is also broader potential clinical applicability of this approach, as thermal ablative techniques have been incorporated into the treatment of a large number of diseases, including therapies such as pulmonary vein ablation for cardiac arrhythmias, esophageal ablation of Barrett’s esophagus, and in newer endovascular treatments for renovascular hypertension, mitral regurgitation, vascular stenosis, and venous reflux disease [ 45 – 48 ]. For several of these, secondary systemic inflammatory reactions (mediated by cytokines such as IL-6, C-reactive protein, and tumor necrosis factor) have been linked to treatment failure [ 49 , 50 ], and have been the basis for the incorporation of adjuvant peri-procedural anti-inflammatory drug therapies [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy

et al. 2015

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PurposeRadiofrequency thermal ablation (RFA) of hepatic and renal tumors can be accompanied by non-desired tumorigenesis in residual, untreated tumor. Here, we studied the use of micelle-encapsulated siRNA to suppress IL-6-mediated local and systemic secondary effects of RFA.MethodsWe compared standardized hepatic or renal RFA (laparotomy, 1 cm active tip at 70±2°C for 5 min) and sham procedures without and with administration of 150nm micelle-like nanoparticle (MNP) anti-IL6 siRNA (DOPE-PEI conjugates, single IP dose 15 min post-RFA, C57Bl mouse:3.5 ug/100ml, Fisher 344 rat: 20ug/200ul), RFA/scrambled siRNA, and RFA/empty MNPs. Outcome measures included: local periablational cellular infiltration (α-SMA+ stellate cells), regional hepatocyte proliferation, serum/tissue IL-6 and VEGF levels at 6-72hr, and distant tumor growth, tumor proliferation (Ki-67) and microvascular density (MVD, CD34) in subcutaneous R3230 and MATBIII breast adenocarcinoma models at 7 days.ResultsFor liver RFA, adjuvant MNP anti-IL6 siRNA reduced RFA-induced increases in tissue IL-6 levels, α-SMA+ stellate cell infiltration, and regional hepatocyte proliferation to baseline (p<0.04, all comparisons). Moreover, adjuvant MNP anti-IL6- siRNA suppressed increased distant tumor growth and Ki-67 observed in R3230 and MATBIII tumors post hepatic RFA (p<0.01). Anti-IL6 siRNA also reduced RFA-induced elevation in VEGF and tumor MVD (p<0.01). Likewise, renal RFA-induced increases in serum IL-6 levels and distant R3230 tumor growth was suppressed with anti-IL6 siRNA (p<0.01).ConclusionsAdjuvant nanoparticle-encapsulated siRNA against IL-6 can be used to modulate local and regional effects of hepatic RFA to block potential unwanted pro-oncogenic effects of hepatic or renal RFA on distant tumor.

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Section: Discussionmentioning

confidence: 99%

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy

et al. 2015

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“…Based on these observations, it has been speculated that inflammation based therapies could even offer novel therapeutic options to patients suffering from AF [14, 15]. However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce.…”

Section: Introductionmentioning

confidence: 99%

Routine 18F-FDG PET/CT does not detect inflammation in the left atrium in patients with atrial fibrillation

Lange

Avramović

Frommeyer

et al. 2017

Int J Cardiovasc Imaging

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Increasing evidence supports a role of inflammation in the development of atrial fibrillation (AF). However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce. In this study, we used 18-Fluor-Deoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) to determine atrial inflammation in patients with and without AF. Retrospectively, 18F-FDG PET/CT scans were analyzed. 37 patients with a history of AF were compared to an age and sex matched control group with no history of AF. Standardized uptake values were obtained in the atrial walls, in the left ventricular wall, and in the right ventricular blood pool, respectively. Target to background ratios (TBR) were determined in the atrial and left ventricular walls and compared between the two groups. TBR values of the left atrial wall were slightly but not significantly higher in patients with AF (1.21 ± 0.27) compared to those without AF (1.14 ± 0.29; p = 0.85). Likewise, a weak but not significant difference was observed in signal intensities in the right atrial wall between patients in the AF (1.14 ± 0.45) and the control group (0.96 ± 0.2; p = 0.41). TBR values of the left ventricular myocardium did not differ between the groups; no significant correlation was found between the TBR in the left and right atrial wall and blood glucose levels. 18F-FDG PET/CT performed under routine conditions did not detect a significant difference in inflammatory activity in the left or right atrium between patients with and without AF. Contrary to previous reports, these results therefore do not clearly support a role for ongoing atrial inflammation in patients with AF. Prospective clinical studies using myocardial glucose uptake suppression strategies may be helpful to clarify these issues.

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“…The traditional gout medication colchicine is established for treatment of pericarditis and has recently been introduced for anti‐inflammatory therapy after pulmonary vein isolation for treatment of atrial fibrillation (AF) . In a randomized, controlled study, the recurrence rate of AF in patients after pulmonary vein isolation was significantly lower in patients treated with colchicine (0.5 mg twice daily) as compared with placebo during a follow‐up period of 3 months .…”

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confidence: 99%

Colchicine Increases Ventricular Vulnerability in an Experimental Whole‐Heart Model

Frommeyer

Krawczyk

Dechering

et al. 2017

Basic Clin Pharma Tox

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The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in two concentrations (1 and 3 μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion. Furthermore, there was no significant increase in dispersion of repolarization. However, colchicine induced a dose-dependent significant decrease of effective refractory period (ERP; 1 μM: -19 ms, 3 μM: -22 ms; p < 0.05). In the present study, acute infusion of colchicine in isolated rabbit hearts resulted in a reduction of ERP in the presence of a stable myocardial repolarization. This led to a significantly elevated inducibility of ventricular fibrillation. In 4 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a pro-arrhythmic or toxic effect of colchicine and underline that further clinical studies on potential adverse effects should be conducted before the drug can be recommended for routine use after atrial fibrillation ablation.

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Colchicine After Pulmonary Vein Isolation: Is Inflammation the New Anti-Arrhythmic Target

Cited by 4 publications

References 8 publications

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy

Routine 18F-FDG PET/CT does not detect inflammation in the left atrium in patients with atrial fibrillation

Colchicine Increases Ventricular Vulnerability in an Experimental Whole‐Heart Model

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