Intracardiac and extracardiac markers of inflammation during atrial fibrillation

Marcus, Gregory M.; Smith, Lisa M.; Ordovás, Karen; Scheinman, Melvin M.; Kim, Albert M.; Badhwar, Nitish; Lee, Randall J.; Tseng, Zian H.; Lee, Byron K.; Olgin, Jeffrey E.

doi:10.1016/j.hrthm.2009.10.004

Cited by 146 publications

(95 citation statements)

References 27 publications

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“…It is noteworthy that one of these studies (negative for an association) had enrolled a cohort, 45% of which had diabetes, cardiac failure, and/or myocardial infarction as comorbidities, all known to be associated with inflammation (Kimmel et al, 2013), while the other two (one negative and one weakly positive for the association) included no information on comorbidities. Furthermore, and perhaps more crucially significant, there is a well-documented relationship between atrial fibrillation, the major indication for use of warfarin and other vitamin K antagonists in these studies, and raised inflammatory biomarkers, especially IL-6 (Henningsen et al, 2009;Marcus et al, 2010;Celebi et al, 2011;Smit et al, 2012;Wu et al, 2013). Inevitably, a question arises concerning the extent to which the CYP2C9 genotype of the cohorts of these three studies was predictive of their CYP2C9 phenotype.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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Phenoconversion transiently converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, potentially with corresponding changes in clinical response. This phenomenon, typically resulting from coadministration of medications that inhibit certain drug metabolizing enzymes (DMEs), is especially well documented for enzymes of the cytochrome P450 family. Nonclinical evidence gathered over the last two decades also strongly implicates elevated levels of some proinflammatory cytokines, released during inflammation, in down-regulation of drug metabolism, especially by certain DMEs of the P450 family, thereby potentially causing transient phenoconversion. Clinically, phenoconversion of NAT2, CYP2C19, and CYP2D6 has been documented in inflammatory conditions associated with elevated cytokines, such as human immunodeficiency virus infection, cancer, and liver disease. The potential of other inflammatory conditions to cause phenoconversion has not been studied but experimental and anecdotal clinical evidence supports infectioninduced down-regulation of CYP1A2, CYP3A4, and CYP2C9 as well. Collectively, the evidence supports a hypothesis that certain inflammatory conditions associated with elevated proinflammatory cytokines may cause phenoconversion of certain DMEs. Since inflammatory conditions associated with elevated levels of proinflammatory cytokines are highly prevalent, phenoconversion of genotypic EM patients into transient phenotypic PMs may be more frequent than appreciated. Since drug pharmacokinetics, and therefore the clinical response, is influenced by DME phenotype rather than genotype per se, phenoconversion (whatever its cause) can have a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies. There is a risk that focusing on genotype alone may miss important associations between clinical outcomes and DME phenotypes, thus compromising future prospects of personalized medicine.

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Section: Discussionmentioning

confidence: 99%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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“…Pericardial fat has been linked with increased expression of local inflammatory markers, particularly in the LA, which may play a role in AF genesis (41,42). A recent study showed lower success rates after non-hybrid AF ablation in obese patients.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of simultaneous hybrid thoracoscopic endocardial catheter ablation of atrial fibrillation in obese and non-obese patients

Phan¹,

Pison

Wang

et al. 2017

J. Thorac. Dis.

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Background: We evaluated the safety and effectiveness of the hybrid thoracoscopic endocardial epicardial ablation technique for the treatment of atrial fibrillation (AF) in obese versus non-obese patients.Methods: Between January 2010 and January 2015, a cohort of 61 patients were retrospectively identified to undergo ablation of AF as a stand-alone procedure using a thoracoscopic, hybrid epicardial-endocardial technique. All patients underwent continuous 7-day Holter monitoring at 3, 6 months, 1 year and yearly thereafter.Results: A total of 40% of the obese cohort had persistent or long-standing AF, compared to 54.9% of the non-obese cohort. There were no deaths or conversion to cardiopulmonary bypass required. At 3-year follow-up, 60% of the obese group were in sinus rhythm (SR) with no episode of AF, atrial flutter or atrial tachycardia lasting 30 s off anti-arrhythmic drugs. This was compared to 70.6% in the non-obese group, with no significant difference between the groups (P=0.468). For success rates on anti-arrhythmic drugs, this was 80% in the obese group compared to 86% in the non-obese group at 3-year follow-up (P=0.637). No patient died and no thromboembolic/bleeding events or procedure-related complications occurred during the follow-up. Conclusions:In a retrospective cohort with approximately half with persistent or long-standing AF, thoracoscopic hybrid epicardial endocardial ablation proved to be equally effective and safe in obese versus non-obese patients. Current preliminary findings require further validation in multi-institutional prospective studies with larger sample sizes.

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“…146,487-489 Baseline CRP levels have been associated with the risk of recurrent AF after catheter ablation. 278 Recently, colchicine has been used to prevent atrial fibrillation recurrence after PV isolation. 490 It is also possible that AF in itself can result in inflammation and the development of an 'atrial myocarditis'.…”

Section: Role Of Myocarditismentioning

confidence: 99%

EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication

et al. 2016

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Intracardiac and extracardiac markers of inflammation during atrial fibrillation

Abstract: BACKGROUND-A decrease in inflammation after cure of atrial arrhythmias suggests that such arrhythmias are pro-inflammatory, and lower inflammatory marker levels in the coronary sinus suggest that atrial arrhythmias result in the intracardiac appropriation of inflammatory cytokines.

Cited by 146 publications

References 27 publications

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Effectiveness and safety of simultaneous hybrid thoracoscopic endocardial catheter ablation of atrial fibrillation in obese and non-obese patients

EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication

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