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Review

Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review

by
Ewen Le Quilliec
1,2,†,
Alexia Fundere
2,†,
Doa’a G. F. Al-U’datt
3 and
Roddy Hiram
1,2,*
1
Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
2
Research Center, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada
3
Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2023, 11(9), 2427; https://doi.org/10.3390/biomedicines11092427
Submission received: 2 August 2023 / Revised: 28 August 2023 / Accepted: 29 August 2023 / Published: 30 August 2023
(This article belongs to the Special Issue Early Diagnosis, Pathogenesis and Treatment Strategies of Atrial Fibrillation)
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Abstract

:

Highlights

What are the main findings?
  • Abnormally increased concentrations of ingested or inhaled pollutants can lead to cardiac oxidative stress and inflammation.
  • Untreated cardiac inflammation promotes myocardial fibrosis and cardiac arrhythmias.
What is the implication of the main findings?
  • Patients hospitalized for acute pesticide poisoning often suffer from episodes of atrial or ventricular fibrillation.
  • Management of pollutant poisoning associated with AF includes detoxification (i.e., gastric lavage) and prompt rhythm control.

Abstract

Atrial fibrillation (AF) is the most common type of cardiac rhythm disorder. Recent clinical and experimental studies reveal that environmental pollutants, including organophosphorus–organochloride pesticides and air pollution, may contribute to the development of cardiac arrhythmias including AF. Here, we discussed the unifying cascade of events that may explain the role of pollutant exposure in the development of AF. Following ingestion and inhalation of pollution-promoting toxic compounds, damage-associated molecular pattern (DAMP) stimuli activate the inflammatory response and oxidative stress that may negatively affect the respiratory, cognitive, digestive, and cardiac systems. Although the detailed mechanisms underlying the association between pollutant exposure and the incidence of AF are not completely elucidated, some clinical reports and fundamental research data support the idea that pollutant poisoning can provoke perturbed ion channel function, myocardial electrical abnormalities, decreased action potential duration, slowed conduction, contractile dysfunction, cardiac fibrosis, and arrhythmias including AF.

1. Introduction

Atrial fibrillation (AF) is the most common and important type of cardiac arrhythmia [1]. Aging and conditions like diabetes, obesity, hypertension, lung disorders, myocardial infarction, or unhealthy lifestyle habits such as abuse of alcohol or smoking, have been designated among major AF risk factors [2,3,4,5,6,7,8]. AF is associated with severe complications such as stroke, heart failure, and sudden death [1]. AF patients are subjected to increased morbidity and mortality causing serious degradation of their quality of life [1,9].
Mounting evidence suggests that environmental factors, including exposure to air pollution, pesticides, herbicides, or passive smoking, are responsible for serious cardiotoxicity contributing to enhancing the risk of AF [10,11,12]. The mechanisms underlying the development of AF substrate following exposure to pollutants remain poorly described. It is suspected that air pollutants, pesticides, or herbicides could provoke myocardial remodeling leading to inflammation, cardiac fibrosis, and electrical changes that may participate in increasing the risk of cardiac arrhythmias and AF [13,14,15].
During the last two decades, significant advancements have helped to ameliorate the management of cardiac arrhythmias which contributed to improving AF patients’ quality of life [9]. However, more efforts need to be accomplished to efficiently prevent and cure cardiac arrhythmias and AF. Hence, a better understanding of the impact of environmental pollution on the incidence of AF may lead to the discovery of new preventive and curative therapeutic approaches.
This paper aims to report the recent knowledge about the mechanisms relating to environmental pollution and AF. In this review, we discussed the role of acute and chronic exposure to pollutants on the occurrence of AF. We explored clinical and experimental studies suggesting involvement of inflammation and cardiac fibrosis in the association between AF and pollutant exposure. We finally reported the current knowledge and potential future perspectives in the management of patients with AF caused by pollutant exposure.

2. Methods

We provide a comprehensive narrative synthesis of evidence extracted from the existing literature. This evidence comes from clinical and research reports purposefully identified as related to pollutant poisoning and cardiovascular disease, including cardiac rhythm disorder and AF. Papers references in this narrative review of literature were peer-reviewed and critically evaluated based on the methodological quality and consistency of results and conclusions. Eligible articles reviewed in the current article were all published previously and indexed in scientific databases until July 2023.
This narrative review comprises an introductory and contextualizing paragraph, followed by a discussion on the association between environmental pollutants and the incidence of cardiac disorders including atrial fibrillation. The following search formula: (“pollutant” OR “pesticide” OR “herbicide”) [title/abstract] + (“heart”, “cardiac”) [title/abstract] + (“atrial fibrillation”) was used to search in electronic databases such as Medline, PubMed, ScienceDirect, and Scopus. Articles with English full texts only were reviewed. Primarily, abstracts obtained from previously cited databases were analyzed to scrutinize studies relevant to environmental pollution, including air pollution, occupational toxic compounds, pesticides, or insecticides, in the context of cardiac diseases. We considered relevant articles in which pollutants (according to the definition of the World Health Organization [WHO]) were studied or applicable to heart and cardiac diseases. To describe, contextualize, and propose perspectives of research and practice, about important concepts or essential mechanisms relevant to the current theme of environmental pollution in cardiac arrhythmias, additional references have been included to strengthen the discussion and characterize potential biochemical cascades that may underly the pathophysiological mechanisms.

3. Evidence of the Association between Air Pollution and Cardiac Arrhythmias

3.1. Definition, Nomenclature, and Sources of Air Pollutants

Air pollution is defined as the acute or persistent presence of inhalable dangerous and potentially health-threatening substances in the atmosphere [16]. Air pollutants mainly originate from natural sources, anthropogenic emissions, or a mix of both [17]. Natural sources of air pollutants include volcanic activity, sea salt spray, windblown dust, or plants’ volatile organic compounds (VOC) [18,19,20]. Anthropogenic emissions are, by definition, provoked by human activity and include fossil-fuel burning, industrial processes, agriculture, or waste management [21,22,23] (Figure 1).
Air pollutants can be categorized into two groups: primary pollutants (emitted directly in the atmosphere) and secondary pollutants (produced via gas chemical reactions or physical processes) [17,24,25]. Gasses defined as primary air pollutants are potential precursors for secondary air pollutants [24,25]. Primary air pollutants include particulate matter (PM), ammonia (NH3), black carbon (BC), carbon monoxide (CO), methane (CH4), non-methane VOC (NMVOC), nitrogen oxides (NOx), or sulfur dioxide (SO2) [26]. Secondary air pollutants include PM, ozone (O3), nitrogen dioxide (NO2), and oxidized VOC [27] (Figure 2).
Air pollution can cause various disorders, including acute respiratory infection, chronic obstructive pulmonary disease, stroke, lung cancer, or ischemic heart disease [17,28].

3.2. Clinical Evidence of Air Pollution Associated with Cardiac Arrhythmias

Recent evidence shows that exposition to air pollutants is associated with the development of cardiovascular diseases [29]. In a recent article published in The Lancet, it has been reported that air pollution is responsible for about 19% of total deaths related to cardiovascular disease (CVD) [30]. CVD is described as one of the major AF risk factors [1,31]. In 2019, Kwon et al., demonstrated, that in a nationwide cohort from the Korean general population, short-term exposure to 10-µg/m3 increase in ambient air pollutant PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) was associated with a significant 4.5% increase of emergency visits for AF [32]. These conclusions were consistent with the observations made by Hsiu Hao Lee et al., in 2019, reporting that, in a cohort of 670 patients from Taiwan, short-term exposure to air pollutant PM2.5 was associated with about 20% increase in hospitalization for AF in the 2-first days following exposure [10]. More recently, in an article published in 2020, Adjani A. Peralta and collaborators reported that exposure to PM2.5 was associated with a 39% increase in hospitalization for ventricular arrhythmias (VA) in a cohort of 176 VA patients from Boston, in the United States of America [33]. In 2021, in a meta-analysis evaluating 18 studies, Chao Yue and colleagues discovered that air pollutant exposure is associated with an increased prevalence of AF in the general population [34]. In Canada, a retrospective study by Saeha Shin and collaborators revealed that air pollution was associated with an increased incidence of stroke and AF [35] (Table 1).
Globally, air pollution is a major concern associated with serious CVD events, including cardiac arrhythmias and AF, leading to decreased quality of life. Hence, novel socio-cultural strategies, new lifestyle habits, and innovative therapeutic approaches are required to decrease and prevent air pollution and the associated respiratory and cardiovascular disorders.

3.3. Specific Situation of Firefighters

When addressing the impact of air pollution on the incidence of cardiovascular disease and cardiac arrhythmia, a firefighter is one of the specific professions that come to mind, because the protagonists are frequently exposed to important concentrations of inhalable hazardous components, including aldehydes, benzene, CO, dichlorofluoromethane, hydrogen chloride, hydrogen cyanide, SO2, and PM [41,42]. It has been shown that during fire suppression activities, firefighters are more likely to develop CVD abnormalities, including thrombus formation, associated with acute myocardial infarction [41]. Firefighters constitute a unique population affected by air pollutants, as they are subjected to both personal and occupational exposure, which represents an enhanced risk to their cardiovascular health [43]. It has been reported that coronary heart disease is responsible for 39% of on-duty deaths among firefighters in the USA [44]. In 2021, Steven M. Moffatt and collaborators reported that sudden cardiac events are the major risk factor for duty-associated death (~50%) in the firefighter population [45,46]. In a cohort of 10860 active firefighters from the USA, the prevalence of AF was significantly increased with the number of fires fought per year, from 2% (<5 fires per year) to 4.5% (>31 fires per year) [43].
Although firefighters are a professional group significantly affected by air pollution, it is important to study and recognize the potential impact of occupational exposure on CVD and cardiac health in other activities, including people working in agriculture, gas refineries, or ores [17,47]. In this context, various studies suggest an important deleterious role of other environmental pollutants, including pesticides and herbicides on human health [48]. The following sections will discuss evidence of the association between pesticide exposure and the development of CVD and cardiac arrhythmias.

4. Relation between Pesticide Exposure and Cardiac Rhythm Disorders

The negative impact of toxic substances, including pesticides, on the environment and human and mammalian health is a major concern worldwide [48,49,50]. Mounting evidence suggests a significant implication of pesticides in the development of human disorders, including CVD [48,50]. Pesticides include various categories: insecticides, fungicides, herbicides, plant growth regulators, algicides, miticides, nematicides, and rodenticides [51,52] that can be divided into natural (mineral oils and plant-derived) and synthetic (organic and inorganic) compounds [53,54]. In terms of chemical structure, the most commonly used classes of organic pesticides include organochlorides, organophosphorus, pyrethroids, triazines, carbamates, or neonicotinoids [53,55] (Figure 3).
In this section, we will focus on the reported impact of organochlorides and organophosphorus in the development of cardiac arrhythmias and AF.

4.1. Organophosphorus Exposure and Cardiac Rhythm Alterations

4.1.1. Clinical Reports of Organophosphorus Exposure Associated with Cardiac Arrhythmias

Organophosphates, also called organophosphorus, are esters of phosphoric acid [56]. Organophosphorus poisoning is a major clinical and public health problem worldwide, concerning developed, developing, and underdeveloped countries [57]. Various clinical reports support that acute and prolonged exposure to organophosphorus is associated with the occurrence of cardiac arrhythmias, including AF [58,59,60,61,62]. In addition to cardiac rhythm abnormalities, the manifestations of organophosphorus intoxication can also include central nervous system perturbation, acute myocardial injury, heart failure, acute renal damage, hepatic dysfunction, and respiratory disorder [63,64]. In a case report published in 2017, Dr M. Maheswari and Dr S. Chaudhary described that a patient accidentally poisoned with organophosphorus was admitted to the emergency room with acute-onset AF. It has been shown that detoxification of organophosphorus compound was accompanied by sinus rhythm recovery [58]. In a retrospective study analyzing clinical data from 98 patients admitted from 2013 to 2017 for acute exposure to organophosphorus pesticide, poisoning was associated with a significantly higher incidence of cardiac arrhythmia and heart failure compared to the control group [63]. Detoxification included gastrolavage (30 °C; 10–30 L), intravenous pralidoxime, and atropine administration (0.5 to 3 mg every 0.5 to 2 h), depending on the severity of intoxication [63].
Organophosphorus compounds are diverse and according to their chemical structure, they can be sub-classified as organophosphates, organophosphonates, phosphine oxides, phosphonium salts, organophosphines, phosphaalkenes, phosphaalkynes, or diphosphenes [65]. A particular organophosphonate called glyphosate is a very popular and commercially available herbicide reported to have serious carcinogenic effects [66,67,68,69] (Figure 4). In the following section, we discuss the association between glyphosate exposure and the incidence of cardiac rhythm disorders.

4.1.2. Organophosphonate Exposure: Particular Case of Glyphosate Poisoning and Cardiac Rhythm Disorders

Glyphosate is a phosphonate glycine. Its molecular weight is 169.073 g/mol. The chemical structure of glyphosate includes monobasic (carboxylic) and dibasic (phosphonic) acidic sites and an amino acid glycine [69] (Figure 4). The primary target of glyphosate is the shikimate pathway, which produces the aromatic amino acids phenylalanine, tyrosine, and tryptophan in plants and microorganisms [70]. When glyphosate started to be commercialized, due to its specific effects on vegetables, its toxicity on mammals, including animals and humans was minimized or unsuspected [66]. However, numerous case studies demonstrating adverse consequences of glyphosate exposure in patients started to emerge [66,71]. Studies have shown that excessive exposure and high plasma concentrations of glyphosate can lead to severe cardiac, liver, and kidney injuries [11,72,73]. In the heart, studies have shown that exposure to glyphosate is a contributing factor in a variety of electrophysiological depolarization and repolarization conduction problems, such as a prolonged QTc, intraventricular block, and atrioventricular (AV) conduction delay [11,74]. These alterations contribute to the development of life-threatening arrhythmias, including tachyarrhythmia, atrial fibrillation, or ventricular fibrillation [75,76].
Roundup is a widely commercialized glyphosate-based herbicide [68]. Roundup residues are often detected in tap water, food, or groundwater [77]. Hence, the impact of this compound on human health is a major concern in countries where it is or has been extensively used [67]. In a case report published in 2020 by Dr Brunetti and collaborators, a patient who used 50% concentrate Roundup without gloves for weeks was hospitalized and ECG showed significantly prolonged QTc, prolonged PR interval, and first-degree AV block [11]. Although extensive data are available about the association between Roundup exposure and the development of cancer, reproductive system, respiratory system, and cardiac function, more investigations are required to characterize its impact on AF incidence.

4.2. Organochlorus Exposure and Cardiac Arrhythmias

4.2.1. Association between Organochlorus Exposure and Cardiac Arrhythmias

Organochlorine pesticides are synthetic compounds used worldwide, in agricultural and industrial applications [78]. It was reported that 40% of all pesticides commonly used, belong to the organochlorine group [78]. The most frequently used organochlorine pesticides include molecules such as dichlorodiphenyltrichloroethane (DDT), dichloro diphenyl dichloroethane (DDE), chlordane, lindane, aldrin, benzene hexachloride (BHC), chlordecone, dioxin, endosulphane, pentachlorophenol, polychlorinated biphenyls (PCBs), taxophene (Campheclor) [78,79] (Figure 4). They are classified by the World Health Organization (WHO), as hazardous, with potential toxic effects on human health [80]. Organochlorine pesticide toxicity is characterized by their high persistence, due to low solubility in aqueous environments and high solubility in lipid areas [78]. Persistent organochlorine pollutants (POPs) are a major concern because the general population is quasi-constantly exposed to low, moderate, or high doses via alimentation, through water consumption, vegetables, animal meat, fish fats, or milk products [81,82,83].
In a mice model of atherosclerosis, PCB administration was associated with increased angiotensin II-induced aortic aneurysm and atherosclerotic lesions [84]. Also in mice, dioxin administration was associated with increased systemic hypertension and left ventricular hypertrophy [85]. In mice, PCB administration was associated with cardiac hypertrophy and abnormal blood pressure [86]. A Clinical report suggested that lindane ingestion (accidental or intentional) was associated with the occurrence of atrial fibrillation and flutter [87]. A study of the frog atrium suggests that lindane-associated rhythm disorder may reside in the fact that lindane increases rapid delayed outward K+ currents which provokes action potential repolarization in the atria [88].
More basic research and fundamental investigations are required to better characterize and understand the association between organochlorine exposure and the incidence of cardiac arrhythmias. In the next section, we discuss the evidence of the role of chlordecone, a yet forbidden organochlorine, on the occurrence of cardiac arrhythmias. This compound offers an interesting perspective of analysis, because it has been intensively used, and then abolished. Hence, we can retrospectively and prospectively evaluate the impact of its exposure and the consequences of its effects on human health even years after its utilization.

4.2.2. Focus on the Chlordecone Cardiotoxicity

Chlordecone (CLD), also known as Kepone, is an organochlorine pesticide that was intensively used in various industrialized countries from 1972 to 1993, particularly in the United States, South America, and the Caribbean, to repel an insect known as the black banana weevil [89,90,91]. CLD is classified as a persistent organic pollutant (POP) identified as carcinogenic in the Stockholm Convention of 2009 [92,93,94]. The utilization and commercialization of CLD—except for research purposes—is currently forbidden worldwide [94]. Although this molecule is no longer used for two decades, significant concentrations persist in the soils and groundwaters of countries where CLD has been spread, making it one of the main pollutants found in table water and frequently found in rivers [95,96]. The latent presence of CLD represents a permanent danger for the exposed populations [95,96,97]. CLD exposure has been described to be associated with an increased incidence of various disorders, including breast cancer, prostate cancer, neurodegenerative and endocrine diseases, or fertility/fetal abnormalities [91,95,96,97,98,99,100,101].
Little is known about the role of CLD in the development and/or aggravation of cardiac diseases. The lack of information does not reflect a lack of effect, but a poorly studied spectrum of the poison’s effect on human health.
Recent data suggest that CLD can perturbate the activity of the Na+/K+ ATPase pump in the myocardium [101,102], disturb the interaction of catecholamines with cardiac cells [99], annihilate Mg2+/ATPase at the cardiomyocyte mitochondrial level [101,102,103], and inhibit calcium (Ca2+) machinery via attenuation of Ca2+/ATPase and decreased sarcoplasmic reticulum calcium uptake [104]. These enzymes play a crucial role in normal myocardial physiology and homeostasis of cardiac activity [105]. Moreover, it has been shown that the deregulation of Na+, K+, Ca2+, or/and Mg2+ is responsible for the development and aggravation of cardiac diseases including AF [106,107,108] (Figure 5).

5. Proposed Mechanisms Underlying the Association between Pesticide Poisoning and the Occurrence of Cardiac Arrhythmias and AF

5.1. Generalities

The mechanisms involved in the pathophysiology of AF have been described at the molecular, cellular, and tissular levels. Conditions affecting the atria can lead to arrhythmia and AF when cardiac remodeling involves malfunction of ion channels implicated in the elaboration of the action potential, conduction anomalies, occurrence of electrical re-entry, or development of atrial fibrosis [109]. Pesticides and pollutants are suspected to provoke systemic or/and cardiac inflammation, oxidative stress, or cardiac structural remodeling [15,110]. Studies recently assessed the effects of air pollution on the induction of AF [110,111]. Reports suggest that air pollutants including PM, CO, H2S, SO2, O3, or NO2 may provoke cardiac arrhythmias or AF by (i) perturbating electrical conduction via attenuation of connexin-43 function, (ii) reduction of IKur currents, (iii) increase of INa currents, (v) promotion of Ca2+ cytosolic overload, (vi) enhancement of RyR activity, (vii) reduction of SERCA function, (viii) increase of action potential duration and (vii) by prolongation of QT intervals [110,111] (Figure 6).

5.2. Proposed Concept of Pollutant-Induced Cardiac Inflammation and AF

Investigations focusing on the impact of pollutants on the development of cardiac arrhythmias and AF are needed. Fundamental data and experimental models of air pollution, organochloride, and organophosphate exposure will help to better understand the impact of such poisoning on cardiac health. Although speculative but supported by the current knowledge available, we propose here a possible cascade of molecular and cellular events that may occur following exposure to environmental poisons, which may lead to cardiac arrhythmias and AF.
When an individual is exposed to inhaled or consumed environmental pollutants, pathogen-associated molecular patterns (PAMPs), or damage-associated molecular patterns (DAMPs) production increases in the organism [109]. PAMPs and DAMPs are recognized by pattern-recognition receptors, which are expressed on the surface membrane of cardiac cells, including macrophages, neutrophils, endothelial cells, cardiomyocytes, or fibroblasts [112]. The activity of pattern-recognition receptors promotes the activation of various pro-inflammatory signals involving a variety of intracellular inflammasome complexes, including the NACHT, LRR, and PYD domains-containing protein-3 (NLRP3) [113]. The NLRP3 inflammasome is implicated in the development and progression of multiple cardiovascular maladies such as systemic hypertension, myocardial infarction, or cardiac arrhythmias [114]. The assembled and activated NLRP3 inflammasome promotes the maturation of the inactive isoforms pro-interleukin-(IL)-1β and pro-IL-18 into active IL-1β and IL-18 [109,113,114,115]. Moreover, NLRP3-induced gasdermin-D (GSDMD) cleavage into N-terminus GSDMD (GSDMD-Nt) generates the formation of pores through the cellular membrane allowing the products of the inflammasome activity, including IL-1β and IL-18 to be excreted and play further autocrine, paracrine, and endocrine pro-inflammatory signaling [116]. Furthermore, studies have shown that the blood level of circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) is significantly increased in patients following short-term and long-term air pollution exposure [117,118]. An abnormally elevated level of NT-proBNP is well-accepted as a predictor of cardiovascular events and cardiac arrhythmias, including AF [119,120]. Although few data are available, studies support that a trifactorial relation may exist between air pollution, increased NT-proBNP levels, and the incidence of AF [117].
If untreated and unresolved, the inflammatory status may lead to cardiomyocytes-, fibroblasts- and pro-inflammatory-(M1)-macrophage-induced production of inflammation-related compounds such as IL-6, TNFα, or NF-kB [121,122,123,124]. In the heart, such inflammatory signaling coupled with evident poisoning-induced oxidative stress has been demonstrated to promote abnormal calcium-Ca2+-handling, RyR2 dysfunction, delayed or shortened repolarization, triggered action potential, shortened effective refractory periods, and atrial fibrosis [15,109,125,126]. The chronicity of this deleterious cascade can provoke the formation of cardiac fibrosis, myocardial hypertrophy, and gap-junction lateralization provoking atrial electrical abnormalities such as ectopic activity and re-entry, leading to increased susceptibility to AF [15,109,125,127] (Figure 7).

6. Perspectives and Management

Studies have evaluated acute versus long-term pesticide exposure to pesticides and the incidence of cardiovascular events and the incidence of AF [38,128]. However, very few data are available about the acute and long-term cardiac remodeling induced by pesticides leading to AF [128]. In other words, although we have a comprehensive idea of acute exposure associated with acutely induced AF, the currently available knowledge is limited about whether acute exposure can lead to long-term damages that may increase the risk of AF.
Our current review article reports and discusses studies that have reported the incidence of AF following pollutant exposure, but an interesting perspective would be to perform an additional systematic review of acute and long-term pollutant damages related to AF. In such type of review article, it would be important to consider pollutant concentration (acute and long-term) and their consequences in inducing acute and long-term damages responsible for AF episodes.
Here we propose an algorithm that may help to diagnose and manage AF following acute or long-term pollution exposure (Figure 8). When a patient arrives at the hospitalization room with cardiac arrhythmia, including AF, the care provider must identify whether the patient was recently exposed to abnormally elevated levels of pollutants [38,127,128]. The history of pollution exposure should also be questioned when interrogating the patient about his/her potential long-term exposure to pollutants (occupational [agriculture, firefighter, garbage collector]; habitat [polluted cities, near gas emission factories, near highways]) [22,43,47]. Immediate decontamination of the patient should be performed, often via gastric lavage, to evacuate pollutants from the system [129]. Prompt rhythm control strategies should be applied to promote sinus rhythm recovery. Medications should be used with caution to avoid non-recommended chemical interactions. If not counter-indicated, anticoagulation can be used to avoid clot formation and prevent stroke [130].

7. Conclusions

The impact of pollution on cardiac health is a major concern worldwide, due to the important and irreversible environmental and behavioral changes faced by humans and all living beings. Clinical and fundamental research have demonstrated that the toxicity of commonly used pesticides, or herbicides is related to the development of cardiac arrhythmias including AF. Although the mechanisms of pesticide-induced AF remain unclear, more investigation will help to better understand how to prevent and cure pollution-associated arrhythmogenicity.

8. Future Directions and Call for Action

Mounting evidence suggests that air pollutants and some pesticides/herbicides/insecticides including compounds of the organophosphorus and organochloride categories may lead to acute or chronic cardiac rhythm disorder following ingestion or inhalation of elevated concentrations. Populations concerned by primary services activities, or occupational intoxication due to frequent utilization and close contact with pesticides (home gardening, agriculture) must be considered and observed thoroughly to prevent the risk of cardiac disorder and AF [125,126]. Although few data are available, this narrative review article is a “call for action” to assess the urgent need for more fundamental and clinical research evaluating the association between environmental pollutants and the risk of cardiac toxicity, arrhythmias, and AF. Such studies will help to improve the diagnosis and management of AF while contributing to ameliorating the guidelines, policies, and recommendations in terms of pesticide utilization.

Author Contributions

R.H. conceptualized the study. E.L.Q., A.F., D.G.F.A.-U. and R.H. reviewed the literature and wrote the manuscript. E.L.Q. and R.H. created the figures and tables. All authors have read and agreed to the published version of the manuscript.

Funding

This work is supported by an Excellence Scholarship Grant from the Faculty of Medicine of the Université de Montréal to E.L.Q.; the Canada Foundation for Innovation John R. Evans Leaders Fund (grant number 42228) to R.H.; and a Research Grant from the Montreal Heart Institute’s Foundation (grant number 4800) to R.H.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors are thankful to Lucie Lefebvre and Carlos Lobos-Yevenes for secretarial assistance with the manuscript. The authors thank Servier Medical Art and UXWing icons galleries that were used to create the current figures and illustraitons.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Andrade, J.; Khairy, P.; Dobrev, D.; Nattel, S. The Clinical Profile and Pathophysiology of Atrial Fibrillation: Relationships Among Clinical Features, Epidemiology, and Mechanisms. Circ. Res. 2014, 114, 1453–1468. [Google Scholar] [CrossRef] [PubMed]
  2. Wang, A.; Green, J.B.; Halperin, J.L.; Piccini, J.P., Sr. Atrial Fibrillation and Diabetes Mellitus: JACC Review Topic of the Week. J. Am. Coll. Cardiol. 2019, 74, 1107–1115. [Google Scholar] [CrossRef] [PubMed]
  3. Nalliah, C.J.; Sanders, P.; Kottkamp, H.; Kalman, J.M. The role of obesity in atrial fibrillation. Eur. Heart J. 2016, 37, 1565–1572. [Google Scholar] [CrossRef] [PubMed]
  4. Wilke, T.; Groth, A.; Mueller, S.; Pfannkuche, M.; Verheyen, F.; Linder, R.; Maywald, U.; Bauersachs, R.; Breithardt, G. Incidence and Prevalence of Atrial Fibrillation: An Analysis Based on 8.3 Million Patients. Europace 2013, 15, 486–493. [Google Scholar] [CrossRef]
  5. Hiram, R.; Provencher, S. Pulmonary Disease, Pulmonary Hypertension and Atrial Fibrillation. Card. Electrophysiol. Clin. 2021, 13, 141–153. [Google Scholar] [CrossRef]
  6. Heijman, J.; Muna, A.P.; Veleva, T.; Molina, C.E.; Sutanto, H.; Tekook, M.; Wang, Q.; Abu-Taha, I.H.; Gorka, M.; Künzel, S.; et al. Atrial Myocyte NLRP3/CaMKII Nexus Forms a Substrate for Postoperative Atrial Fibrillation. Circ. Res. 2020, 127, 1036–1055. [Google Scholar] [CrossRef]
  7. Zhang, H.Z.; Shao, B.; Wang, Q.Y.; Wang, Y.H.; Cao, Z.Z.; Sun, J.Y.; Gu, M.F. Alcohol Consumption and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis of Prospective Studies. Front. Cardiovasc. Med. 2022, 9, 802163. [Google Scholar] [CrossRef]
  8. Chamberlain, A.M.; Agarwal, S.K.; Folsom, A.R.; Duval, A.R.; Soliman, E.Z.; Ambrose, M.; Eberly, L.E.; Alonso, A. Smoking and incidence of atrial fibrillation: Results from the Atherosclerosis Risk in Communities (ARIC) study. Heart Rhythm. 2011, 8, 1160–1166. [Google Scholar] [CrossRef]
  9. Andrade, J.G.; Aguilar, M.; Atzema, C.; Bell, A.; Cairns, J.A.; Cheung, C.C.; Cox, J.L.; Dorian, P.; Galdstone, D.J.; Healey, J.S.; et al. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Com-prehensive Guidelines for the Management of Atrial Fibrillation. Can. J. Cardiol. 2020, 36, 1847–1948. [Google Scholar] [CrossRef]
  10. Lee, H.H.; Pan, S.C.; Chen, B.Y.; Lo, S.H.; Guo, Y.L. Atrial fibrillation hospitalization is associated with exposure to fine particulate air pollutants. Environ. Health 2019, 18, 117. [Google Scholar] [CrossRef]
  11. Brunetti, R.; Maradey, J.A.; Dearmin, R.S.; Belford, P.M.; Bhave, P.D. Electrocardiographic abnormalities associated with acute glyphosate toxicity. Heart Rhythm Case Rep. 2019, 6, 63–66. [Google Scholar] [CrossRef]
  12. Gress, S.; Lemoine, S.; Puddu, P.E.; Séralini, G.E.; Rouet, R. Cardiotoxic Electrophysiological Effects of the Herbicide Roundup(®) in Rat and Rabbit Ventricular Myocardium In Vitro. Cardiovasc. Toxicol. 2015, 15, 324–335. [Google Scholar] [CrossRef] [PubMed]
  13. Dayton, S.B.; Sandler, D.P.; Blair, A.; Alavanja, M.; Beane Freeman, L.E.; Hoppin, J.A. Pesticide use and myocardial infarction incidence among farm women in the agricultural health study. J. Occup. Environ. Med. 2010, 52, 693–697. [Google Scholar] [CrossRef] [PubMed]
  14. Peritore, A.F.; Franco, G.A.; Molinari, F.; Arangia, A.; Interdonato, L.; Marino, Y.; Cuzzocrea, S.; Gugliandolo, E.; Britti, D.; Crupi, R. Effect of Pesticide Vinclozolin Toxicity Exposure on Cardiac Oxidative Stress and Myocardial Damage. Toxics 2023, 11, 473. [Google Scholar] [CrossRef] [PubMed]
  15. Topacoglu, H.; Unverir, P.; Erbil, B.; Sarikaya, S. An unusual cause of atrial fibrillation: Exposure to insecticides. Am. J. Ind. Med. 2007, 50, 48–49. [Google Scholar] [CrossRef]
  16. Brunekreef, B.; Holgate, S.T. Air pollution and health. Lancet 2002, 360, 1233–1242. [Google Scholar] [CrossRef] [PubMed]
  17. Manisalidis, I.; Stavropoulou, E.; Stavropoulos, A.; Bezirtzoglou, E. Environmental and Health Impacts of Air Pollution: A Review. Front. Public Health 2020, 8, 14. [Google Scholar] [CrossRef]
  18. Mueller, W.; Cowie, H.; Horwell, C.J.; Hurley, F.; Baxter, P.J. Health Impact Assessment of Volcanic Ash Inhalation: A Comparison With Outdoor Air Pollution Methods. Geohealth 2020, 4, e2020GH000256. [Google Scholar] [CrossRef]
  19. Angle, K.J.; Crocker, D.R.; Simpson, R.M.C.; Mayer, K.J.; Garofalo, L.A.; Moore, A.N.; Mora Garcia, S.L.; Or, V.W.; Srinivasan, S.; Farhan, M.; et al. Acidity across the interface from the ocean surface to sea spray aerosol. Proc. Natl. Acad. Sci. USA 2021, 118, e2018397118. [Google Scholar] [CrossRef]
  20. Middleton, N.; Yiallouros, P.; Kleanthous, S.; Kolokotroni, O.; Schwartz, J.; Dockery, D.W.; Demokritou, P.; Koutrakis, P. A 10-year time-series analysis of respiratory and cardiovascular morbidity in Nicosia, Cyprus: The effect of short-term changes in air pollution and dust storms. Environ. Health 2008, 7, 39. [Google Scholar] [CrossRef] [PubMed]
  21. Xu, J.; Niehoff, N.M.; White, A.J.; Werder, E.J.; Sandler, D.P. Fossil-fuel and combustion-related air pollution and hypertension in the Sister Study. Environ. Pollut. 2022, 315, 120401. [Google Scholar] [CrossRef] [PubMed]
  22. Massarelli, C.; Losacco, D.; Tumolo, M.; Campanale, C.; Uricchio, V.F. Protection of Water Resources from Agriculture Pollution: An Integrated Methodological Approach for the Nitrates Directive 91-676-EEC Implementation. Int. J. Environ. Res. Public Health 2021, 18, 13323. [Google Scholar] [CrossRef] [PubMed]
  23. Siddiqua, A.; Hahladakis, J.N.; Al-Attiya, W.A.K.A. An overview of the environmental pollution and health effects associated with waste landfilling and open dumping. Environ. Sci. Pollut. Res. Int. 2022, 29, 58514–58536. [Google Scholar] [CrossRef]
  24. Mustafic, H.; Jabre, P.; Caussin, C.; Murad, M.H.; Escolano, S.; Tafflet, M.; Périer, M.C.; Marijon, E.; Vernerey, D.; Empana, J.P.; et al. Main air pollutants and myocardial infarction: A systematic review and meta-analysis. JAMA 2012, 307, 713–721. [Google Scholar] [CrossRef] [PubMed]
  25. Xiang, W.; Wang, W.; Du, L.; Zhao, B.; Liu, X.; Zhang, X.; Yao, L.; Ge, M. Toxicological Effects of Secondary Air Pollutants. Chem. Res. Chin. Univ. 2023, 39, 326–341. [Google Scholar] [CrossRef]
  26. Bălă, G.P.; Râjnoveanu, R.M.; Tudorache, E.; Motișan, R.; Oancea, C. Air pollution exposure-the (in)visible risk factor for respiratory diseases. Environ. Sci. Pollut. Res. Int. 2021, 28, 19615–19628. [Google Scholar] [CrossRef]
  27. Pye, H.O.T.; Appel, K.W.; Seltzer, K.M.; Ward-Caviness, C.K.; Murphy, B.N. Human-health impacts of controlling secondary air pollution precursors. Environ. Sci. Technol. Lett. 2022, 9, 96–101. [Google Scholar] [CrossRef]
  28. Tran, V.V.; Park, D.; Lee, Y.C. Indoor Air Pollution, Related Human Diseases, and Recent Trends in the Control and Improvement of Indoor Air Quality. Int. J. Environ. Res. Public Health 2020, 17, 2927. [Google Scholar] [CrossRef]
  29. Fiordelisi, A.; Piscitelli, P.; Trimarco, B.; Coscioni, E.; Iaccarino, G.; Sorriento, D. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail. Rev. 2017, 22, 337–347. [Google Scholar] [CrossRef]
  30. GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017, 390, 1736. [Google Scholar]
  31. Hadley, M.B.; Vedanthan, R.; Fuster, V. Air pollution and cardiovascular disease: A window of opportunity. Nat. Rev. Cardiol. 2018, 15, 193–194. [Google Scholar] [CrossRef]
  32. Kwon, O.K.; Kim, S.H.; Kang, S.H.; Cho, Y.; Oh, I.Y.; Yoon, C.H.; Kim, S.Y.; Kim, O.J.; Choi, E.K.; Youn, T.J.; et al. Association of short- and long-term exposure to air pollution with atrial fibrillation. Eur. J. Prev. Cardiol. 2019, 26, 1208–1216. [Google Scholar] [CrossRef] [PubMed]
  33. Peralta, A.A.; Link, M.S.; Schwartz, J.; Luttmann-Gibson, H.; Dockery, D.W.; Blomberg, A.; Wei, Y.; Mittleman, M.A.; Gold, D.R.; Laden, F.; et al. Exposure to Air Pollution and Particle Radioactivity with the Risk of Ventricular Arrhythmias. Circulation 2020, 142, 858–867. [Google Scholar] [CrossRef]
  34. Yue, C.; Yang, F.; Li, F.; Chen, Y. Association between air pollutants and atrial fibrillation in general population: A systematic re-view and meta-analysis. Ecotoxicol. Environ. Saf. 2021, 208, 111508. [Google Scholar] [CrossRef]
  35. Shin, S.; Burnett, R.T.; Kwong, J.C.; Hystad, P.; Van Donkelaar, A.; Brook, J.R.; Goldberg, M.S.; Tu, K.; Copes, R.; Martin, R.V.; et al. Ambient Air Pollution and the Risk of Atrial Fibrillation and Stroke: A Population-Based Cohort Study. Environ. Health Perspect. 2019, 127, 87009. [Google Scholar] [CrossRef] [PubMed]
  36. Link, M.S.; Luttmann-Gibson, H.; Schwartz, J.; Mittleman, M.A.; Wessler, B.; Gold, D.R.; Dockery, D.W.; Laden, F. Acute exposure to air pollution triggers atrial fibrillation. J. Am. Coll. Cardiol. 2013, 62, 816–825. [Google Scholar] [CrossRef]
  37. Chen, M.; Zhao, J.; Zhuo, C.; Zheng, L. The Association Between Ambient Air Pollution and Atrial Fibrillation. Int. Heart J. 2021, 62, 290–297. [Google Scholar] [CrossRef]
  38. Dahlquist, M.; Frykman, V.; Stafoggia, M.; Qvarnström, E.; Wellenius, G.A.; Ljungman, P.L.S. Short-term ambient air pollution exposure and risk of atrial fibrillation in patients with intracardiac devices. Environ. Epidemiol. 2022, 6, e215. [Google Scholar] [CrossRef] [PubMed]
  39. Saifipour, A.; Azhari, A.; Pourmoghaddas, A.; Hosseini, S.M.; Jafari-Koshki, T.; Rahimi, M.; Nasri, A.; Shishehforoush, M.; Lahijanza-deh, A.; Sadeghian, B.; et al. Association between ambient air pollution and hospitalization caused by atrial fibrillation. ARYA Atheroscler. 2019, 15, 106–112. [Google Scholar]
  40. Gallo, E.; Folino, F.; Buja, G.; Zanotto, G.; Bottigliengo, D.; Comoretto, R.; Marras, E.; Allocca, G.; Vaccari, D.; Gasparini, G.; et al. Daily Exposure to Air Pollution Particulate Matter Is Associated with Atrial Fibrillation in High-Risk Patients. Int. J. Environ. Res. Public Health 2020, 17, 6017. [Google Scholar] [CrossRef]
  41. Hunter, A.L.; Shah, A.S.V.; Langrish, J.P.; Raftis, J.B.; Lucking, A.J.; Brittan, M.; Venkatasubramanian, S.; Stables, C.L.; Stelzle, D.; Marshall, J.; et al. Fire Simulation and Cardiovascular Health in Firefighters. Circulation 2017, 135, 1284–1295. [Google Scholar] [CrossRef] [PubMed]
  42. Brandt-Rauf, P.W.; Fallon, L.F., Jr.; Tarantini, T.; Idema, C.; Andrews, L. Health hazards of fire fighters: Exposure assessment. Br. J. Ind. Med. 1988, 45, 606–612. [Google Scholar] [CrossRef] [PubMed]
  43. Vanchiere, C.; Thirumal, R.; Hendrani, A.; Dherange, P.; Bennett, A.; Shi, R.; Gopinathannair, R.; Olshansky, B.; Smith, D.L.; Dominic, P. Association Between Atrial Fibrillation and Occupational Exposure in Firefighters Based on Self-Reported Survey Data. J. Am. Heart Assoc. 2022, 11, e022543. [Google Scholar] [CrossRef] [PubMed]
  44. Geibe, J.R.; Holder, J.; Peeples, L.; Kinney, A.M.; Burress, J.W.; Kales, S.N. Predictors of on-duty coronary events in male firefighters in the United States. Am. J. Cardiol. 2008, 101, 585–589. [Google Scholar] [CrossRef] [PubMed]
  45. Moffatt, S.M.; Stewart, D.F.; Jack, K.; Dudar, M.D.; Bode, E.D.; Mathias, K.C.; Smith, D.L. Cardiometabolic health among United States firefighters by age. Prev. Med. Rep. 2021, 23, 101492. [Google Scholar] [CrossRef]
  46. Khaja, S.U.; Mathias, K.C.; Bode, E.D.; Stewart, D.F.; Jack, K.; Moffatt, S.M.; Smith, D.L. Hypertension in the United States Fire Service. Int. J. Environ. Res. Public Health 2021, 18, 10. [Google Scholar] [CrossRef]
  47. Hsu, C.Y.; Chang, Y.T.; Lin, C.J. How a winding-down oil refinery park impacts air quality nearby? Environ. Int. 2022, 169, 107533. [Google Scholar] [CrossRef]
  48. Zago, A.M.; Faria, N.M.X.; Fávero, J.L.; Meucci, R.D.; Woskie, S.; Fassa, A.G. Pesticide exposure and risk of cardiovascular disease: A systematic review. Glob. Public Health 2022, 17, 3944–3966. [Google Scholar] [CrossRef]
  49. Mesnage, R.; Bernay, B.; Séralini, G.E. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology 2013, 313, 122–128. [Google Scholar] [CrossRef]
  50. Adeyemi, J.A.; Ukwenya, V.O.; Arowolo, O.K.; Olise, C.C. Pesticides-induced Cardiovascular Dysfunctions: Prevalence and Associated Mechanisms. Curr. Hypertens. Rev. 2021, 17, 27–34. [Google Scholar] [CrossRef]
  51. Kim, Y.H.; Lee, J.H.; Hong, C.K.; Cho, K.W.; Park, Y.H.; Kim, Y.W.; Hwang, S.Y. Heart rate-corrected QT interval predicts mortality in glyphosate-surfactant herbicide-poisoned patients. Am. J. Emerg. Med. 2014, 32, 203–207. [Google Scholar] [CrossRef] [PubMed]
  52. Hassaan, M.A.; El Nemr, A. Pesticides pollution: Classifications, human health impact, extraction and treatment techniques. Egypt. J. Aquat. Res. 2020, 46, 207–220. [Google Scholar] [CrossRef]
  53. Pathak, V.M.; Verma, V.K.; Rawat, B.S.; Kaur, B.; Babu, N.; Sharma, A.; Dewali, S.; Yadav, M.; Kumari, R.; Singh, S.; et al. Current status of pesticide effects on environment, human health and it’s eco-friendly management as bioremediation: A comprehensive review. Front. Microbiol. 2022, 13, 962619. [Google Scholar] [CrossRef] [PubMed]
  54. Souto, A.L.; Sylvestre, M.; Tölke, E.D.; Tavares, J.F.; Barbosa-Filho, J.M.; Cebrián-Torrejón, G. Plant-derived pesticides as an alternative to pest management and sustainable agricultural production: Prospects, applications and challenges. Molecules 2021, 26, 4835. [Google Scholar] [CrossRef]
  55. Parra-Arroyo, L.; González-González, R.B.; Castillo-Zacarías, C.; Martínez, E.M.M.; Sosa-Hernández, J.E.; Bilal, M.; Iqbal, H.M.N.; Barcelò, D.; Parra-Saldìvar, R. Highly hazardous pesticides and related pollutants: Toxicological, regulatory, and analytical aspects. Sci. Total Environ. 2022, 807, 151879. [Google Scholar] [CrossRef] [PubMed]
  56. Adeyinka, A.; Muco, E.; Pierre, L. Organophosphates. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. [Google Scholar]
  57. Vale, A. Organophosphorus insecticide poisoning. BMJ Clin. Evid. 2015, 2015, 2102. [Google Scholar]
  58. Maheshwari, M.; Chaudhary, S. Acute Atrial Fibrillation Complicating Organophosphorus Poisoning. Heart Views 2017, 18, 96–99. [Google Scholar] [CrossRef]
  59. Pannu, A.K.; Bhalla, A.; Vishnu, R.I.; Garg, S.; Prasad Dhibar, D.; Sahrma, N.; Vijayvergiya, R. Cardiac injury in organophosphate poisoning after acute ingestion. Toxicol. Res. 2021, 10, 446–452. [Google Scholar] [CrossRef]
  60. Siegal, D.; Kotowycz, M.A.; Methot, M.; Baranchuk, A. Complete heart block following intentional carbamate ingestion. Can. J. Cardiol. 2009, 25, e288–e290. [Google Scholar] [CrossRef]
  61. Paul, U.K.; Bhattacharyya, A.K. ECG manifestations in acute organophosphorus poisoning. J. Indian Med. Assoc. 2012, 110, 98–108. [Google Scholar]
  62. Tisdale, J.E.; Wroblewski, H.A.; Overholser, B.R.; Kingery, J.R.; Trujillo, T.N.; Kovacs, R.J. Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: A prospective, observational study in a large urban academic medical center in the US. Drug Saf. 2012, 35, 459–470. [Google Scholar] [CrossRef] [PubMed]
  63. Chen, K.X.; Zhou, X.H.; Sun, C.A.; Yan, P.X. Manifestations of and risk factors for acute myocardial injury after acute organophos-phorus pesticide poisoning. Medicine 2019, 98, e14371. [Google Scholar] [CrossRef] [PubMed]
  64. Ramadori, G.P. Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients. Int. J. Mol. Sci. 2023, 24, 6658. [Google Scholar] [CrossRef] [PubMed]
  65. Worek, F.; Thiermann, H.; Wille, T. Organophosphorus compounds and oximes: A critical review. Arch. Toxicol. 2020, 94, 2275–2292. [Google Scholar] [CrossRef]
  66. Tarazona, J.V.; Court-Marques, D.; Tiramani, M.; Reich, H.; Pfeil, R.; Istace, F.; Crivellente, F. Glyphosate toxicity and carcinogenicity: A review of the scientific basis of the European Union assessment and its differences with IARC. Arch. Toxicol. 2017, 91, 2723–2743. [Google Scholar] [CrossRef]
  67. Soares, D.; Silva, L.; Duarte, S.; Pena, A.; Pereira, A. Glyphosate Use, Toxicity and Occurrence in Food. Foods 2021, 10, 2785. [Google Scholar] [CrossRef]
  68. Novotny, E. Glyphosate, Roundup and the Failures of Regulatory Assessment. Toxics 2022, 10, 321. [Google Scholar] [CrossRef]
  69. National Center for Biotechnology Information. PubChem Compound Summary for CID 3496, Glyphosate. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Glyphosate (accessed on 7 July 2023).
  70. Zulet-Gonzalez, A.; Gorzolka, K.; Döll, S.; Gil-Monreal, M.; Royuela, M.; Zabalza, A. Unravelling the Phytotoxic Effects of Glypho-sate on Sensitive and Resistant Amaranthus palmeri Populations by GC-MS and LC-MS Metabolic Profiling. Plants 2023, 12, 1345. [Google Scholar] [CrossRef]
  71. Gillezeau, C.; Van Gerwen, M.; Shaffer, R.M.; Rana, I.; Zhang, L.; Sheppard, L.; Taioli, E. The evidence of human exposure to glyphosate: A review. Environ. Health 2019, 18, 2. [Google Scholar] [CrossRef]
  72. Mills, P.J.; Caussy, C.; Loomba, R. Glyphosate Excretion is Associated with Steatohepatitis and Advanced Liver Fibrosis in Pa-tients With Fatty Liver Disease. Clin. Gastroenterol. Hepatol. 2020, 18, 741–743. [Google Scholar] [CrossRef]
  73. Gunatilake, S.; Seneff, S.; Orlando, L. Glyphosate’s Synergistic Toxicity in Combination with Other Factors as a Cause of Chronic Kidney Disease of Unknown Origin. Int. J. Environ. Res. Public Health 2019, 16, 2734. [Google Scholar] [CrossRef]
  74. Ghosh, S.; Tale, S.; Kolli, M.; Kaur, S.; Garbhapu, A.; Bhalla, A. Cardiogenic shock with first-degree heart block in a patient with glyphosate-surfactant poisoning. Trop. Doct. 2021, 51, 244–246. [Google Scholar] [CrossRef] [PubMed]
  75. Chang, C.B.; Chang, C.C. Refractory cardiopulmonary failure after glyphosate surfactant intoxication: A case report. J. Occup. Med. Toxicol. 2009, 4, 2. [Google Scholar] [CrossRef] [PubMed]
  76. Gress, S.; Lemoine, S.; Séralini, G.E.; Puddu, P.E. Glyphosate-based herbicides potently affect cardiovascular system in mammals: Review of the literature. Cardiovasc. Toxicol. 2015, 15, 117–126. [Google Scholar] [CrossRef] [PubMed]
  77. Noori, J.S.; Dimaki, M.; Mortensen, J.; Svendsen, W.E. Detection of Glyphosate in Drinking Water: A Fast and Direct Detection Method without Sample Pretreatment. Sensors 2018, 18, 2961. [Google Scholar] [CrossRef]
  78. Jayaraj, R.; Megha, P.; Sreedev, P. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environ-ment. Interdiscip. Toxicol. 2016, 9, 90–100. [Google Scholar] [CrossRef]
  79. Saoudi, A.; Fréry, N.; Zeghnoun, A.; Bidondo, M.L.; Deschamps, V.; Göen, T.; Garnier, R.; Guldner, L. Serum levels of organochlorine pesticides in the French adult population: The French National Nutrition and Health Study (ENNS), 2006–2007. Sci. Total. Environ. 2014, 472, 1089–1099. [Google Scholar] [CrossRef]
  80. Seo, S.H.; Choi, S.D.; Batterman, S.; Chang, Y.S. Health risk assessment of exposure to organochlorine pesticides in the general popu-lation in Seoul, Korea over 12 years: A cross-sectional epidemiological study. J. Hazard. Mater. 2022, 424, 127381. [Google Scholar] [CrossRef]
  81. Naso, B.; Perrone, D.; Ferrante, M.C.; Bilancione, M.; Lucisano, A. Persistent organic pollutants in edible marine species from the Gulf of Naples, Southern Italy. Sci. Total Environ. 2005, 343, 83–95. [Google Scholar] [CrossRef]
  82. Witczak, A.; Pohoryło, A.; Abdel-Gawad, H. Endocrine-Disrupting Organochlorine Pesticides in Human Breast Milk: Changes during Lactation. Nutrients 2021, 13, 229. [Google Scholar] [CrossRef]
  83. Mitiku, B.A.; Mitiku, M.A. Organochlorine pesticides residue affinity in fish muscle and their public health risks in North West Ethiopia. Food Sci. Nutr. 2022, 10, 4331–4338. [Google Scholar] [CrossRef] [PubMed]
  84. Arsenescu, V.; Arsenescu, R.; Parulkar, M.; Karounos, M.; Zhang, X.; Baker, N.; Cassis, L.A. Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice. Toxicol. Appl. Pharmacol. 2011, 257, 148–154. [Google Scholar] [CrossRef] [PubMed]
  85. Kopf, P.G.; Huwe, J.K.; Walker, M.K. Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. Cardiovasc. Toxicol. 2008, 8, 181–193. [Google Scholar] [CrossRef] [PubMed]
  86. La Merrill, M.A.; Sethi, S.; Benard, L.; Moshier, E.; Haraldsson, B.; Buettner, C. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice. Environ. Health Perspect. 2016, 124, 1722–1727. [Google Scholar] [CrossRef] [PubMed]
  87. Wiles, D.A.; Russell, J.L.; Olson, K.R.; Walson, P.D.; Kelley, M. Massive lindane overdose with toxicokinetics analysis. J. Med. Toxicol. 2015, 11, 106–109. [Google Scholar] [CrossRef]
  88. Sauviat, M.P.; Colas, A.; Pages, N. Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (IKr) in frog atrial myocytes? BMC Pharmacol. 2002, 2, 15. [Google Scholar] [CrossRef]
  89. National Center for Biotechnology Information. PubChem Compound Summary for CID 299, Chlordecone. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Chlordecone (accessed on 7 July 2023).
  90. Devault, D.A.; Amalric, L.; Bristeau, S. Chlordecone consumption estimated by sewage epidemiology approach for health policy assessment. Environ. Sci. Pollut. Res. Int. 2018, 25, 29633–29642. [Google Scholar] [CrossRef]
  91. Parrales-Macias, V.; Michel, P.P.; Tourville, A.; Raisman-Vozari, R.; Haïk, S.; Hunot, S.; Bizat, N.; Lannuzel, A. The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans. Worms Cells 2023, 12, 1336. [Google Scholar] [CrossRef]
  92. Cannon, S.B.; Veazey, J.M., Jr.; Jackson, R.S.; Burse, V.W.; Hayes, C.; Straub, W.E.; Landrigan, P.J.; Liddle, J.A. Epidemic kepone poisoning in chemical workers. Am. J. Epidemiol. 1978, 107, 529–537. [Google Scholar] [CrossRef]
  93. Cabidoche, Y.M.; Achard, R.; Cattan, P.; Clermont-Dauphin, C.; Massat, F.; Sansoulet, J. Long-term pollution by chlordecone of tropi-cal volcanic soils in the French West Indies: A simple leaching model accounts for current residue. Environ. Pollut. 2009, 157, 1697–1705. [Google Scholar] [CrossRef]
  94. Jennings, A.A.; Li, Z. Residential surface soil guidance applied worldwide to the pesticides added to the Stockholm Convention in 2009 and 2011. J. Environ. Manag. 2015, 160, 226–240. [Google Scholar] [CrossRef]
  95. Wecker, P.; Lecellier, G.; Guibert, I.; Zhou, Y.; Bonnard, I.; Berteaux-Lecellier, V. Exposure to the environmentally-persistent insecti-cide chlordecone induces detoxification genes and causes polyp bail-out in the coral P. damicornis. Chemosphere 2018, 195, 190–200. [Google Scholar] [CrossRef]
  96. Benoit, P.; Mamy, L.; Servien, R.; Li, Z.; Latrille, E.; Rossard, V.; Bessac, F.; Patureau, D.; Martin-Laurent, F. Categorizing chlordecone potential degradation products to explore their environmental fate. Sci. Total Environ. 2017, 574, 781–795. [Google Scholar] [CrossRef] [PubMed]
  97. Nedellec, V.; Rabl, A.; Dab, W. Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: Hazards, expo-sure-response functions, and exposures. Environ. Health 2016, 15, 75. [Google Scholar] [CrossRef]
  98. Multigner, L.; Ndong, J.R.; Giusti, A.; Romana, M.; Delacroix-Maillard, H.; Cordier, S.; Jégou, B.; Thome, J.P.; Blanchet, P. Chlordecone exposure and risk of prostate cancer. J. Clin. Oncol. 2010, 28, 3457–3462. [Google Scholar] [CrossRef] [PubMed]
  99. Multigner, L.; Kadhel, P.; Rouget, F.; Blanchet, P.; Cordier, S. Chlordecone exposure and adverse effects in French West Indies popu-lations. Environ. Sci. Pollut. Res. Int. 2016, 23, 3–8. [Google Scholar] [CrossRef]
  100. Rouget, F.; Kadhel, P.; Monfort, C.; Viel, J.F.; Thome, J.P.; Cordier, S.; Multigner, L. Chlordecone exposure and risk of congenital anomalies: The Timoun Mother-Child Cohort Study in Guadeloupe (French West Indies). Environ. Sci. Pollut. Res. Int. 2020, 27, 40992–40998. [Google Scholar] [CrossRef] [PubMed]
  101. Desaiah, D. Comparative effects of chlordecone and mirex on rat cardiac ATPases and binding of 3H-catecholamines. J. Environ. Pathol. Toxicol. 1980, 4, 237–248. [Google Scholar] [PubMed]
  102. Vasić, V.; Momić, T.; Petković, M.; Krstić, D. Na⁺,K⁺-ATPase as the Target Enzyme for Organic and Inorganic Compounds. Sensors 2008, 8, 8321–8360. [Google Scholar] [CrossRef]
  103. Desaiah, D. Interaction of chlordecone with biological membranes. J. Toxicol. Environ. Health 1981, 8, 719–730. [Google Scholar] [CrossRef] [PubMed]
  104. Kodavanti, P.R.; Cameron, J.A.; Yallapragada, P.R.; Desaiah, D. Effect of chlordecone (Kepone) on calcium transport mechanisms in rat heart sarcoplasmic reticulum. Pharmacol. Toxicol. 1990, 67, 227–234. [Google Scholar] [CrossRef] [PubMed]
  105. Priest, B.T.; McDermott, J.S. Cardiac ion channels. Channels 2015, 9, 352–359. [Google Scholar] [CrossRef] [PubMed]
  106. Alonso, A.; Rooney, M.R.; Chen, L.Y.; Norby, F.L.; Saenger, A.K.; Soliman, E.Z.; O’Neal, W.T.; Hootman, K.C.; Selvin, E.; Lutsey, P. Circulating electrolytes and the prevalence of atrial fibrillation and supraventricular ectopy: The Atherosclerosis Risk in Communities (ARIC) study. Nutr. Metab. Cardiovasc. Dis. 2020, 30, 1121–1129. [Google Scholar] [CrossRef] [PubMed]
  107. Kaplan, A.D.; Joca, H.C.; Boyman, L.; Greiser, M. Calcium Signaling Silencing in Atrial Fibrillation: Implications for Atrial So-dium Homeostasis. Int. J. Mol. Sci. 2021, 22, 10513. [Google Scholar] [CrossRef]
  108. Bhatti, H.; Mohmand, B.; Ojha, N.; Carvounis, C.P.; Carhart, R.L. The Role of Magnesium in the Management of Atrial Fibrillation with Rapid Ventricular Rate. J. Atr. Fibrill. 2020, 13, 2389. [Google Scholar]
  109. Dobrev, D.; Heijman, J.; Hiram, R.; Li, N.; Nattel, S. Inflammatory signalling in atrial cardiomyocytes: A novel unifying principle in atrial fibrillation pathophysiology. Nat. Rev. Cardiol. 2023, 20, 145–167. [Google Scholar] [CrossRef]
  110. Yang, Y.; Wei, S.; Zhang, B.; Li, W. Recent Progress in Environmental Toxins-Induced Cardiotoxicity and Protective Potential of Natural Products. Front. Pharmacol. 2021, 12, 699193. [Google Scholar] [CrossRef]
  111. Zhang, S.; Lu, W.; Wei, Z.; Zhang, H. Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms. Front. Cardiovasc. Med. 2021, 8, 736151. [Google Scholar] [CrossRef]
  112. Lin, L.; Knowlton, A.A. Innate immunity and cardiomyocytes in ischemic heart disease. Life Sci. 2014, 100, 1–8. [Google Scholar] [CrossRef]
  113. Yao, C.; Veleva, T.; Scott, L., Jr.; Cao, S.; Chen, G.; Jeyabal, P.; Pan, X.; Alsina, K.M.; Abu-Tahe, I.; Ghezelbash, S.; et al. Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation. Circulation 2019, 138, 2227–2242, Correction in Circulation 2019, 139, e889. [Google Scholar] [CrossRef]
  114. Younes, R.; LeBlanc, C.A.; Hiram, R. Evidence of Failed Resolution Mechanisms in Arrhythmogenic Inflammation, Fibrosis and Right Heart Disease. Biomolecules 2022, 12, 720. [Google Scholar] [CrossRef] [PubMed]
  115. Hiram, R. Cardiac cytokine therapy? Relevance of targeting inflammatory mediators to combat cardiac arrhythmogenic remodeling. Int. J. Cardiol. Heart Vasc. 2021, 37, 100918. [Google Scholar] [CrossRef] [PubMed]
  116. Wang, C.; Yang, T.; Xiao, J.; Xu, C.; Alippe, Y.; Sun, K.; Kanneganti, T.D.; Monahan, J.B.; Abu-Amer, Y.; Lieberman, J.; et al. NLRP3 inflammasome activation triggers gasdermin D-independent inflammation. Sci. Immunol. 2021, 6, eabj3859. [Google Scholar] [CrossRef] [PubMed]
  117. Dahlquist, M.; Frykman, V.; Kemp-Gudmunsdottir, K.; Svennberg, E.; Wellenius, G.A.; Ljungman, P.L. Short-term associations between ambient air pollution and acute atrial fibrillation episodes. Environ. Int. 2020, 141, 105765. [Google Scholar] [CrossRef]
  118. Hart, J.E.; Hohensee, C.; Laden, F.; Holland, I.; Whitsel, E.A.; Wellenius, G.A.; Winkelmayer, W.C.; Sarto, G.E.; Warsinger Martin, L.; Manson, J.E.; et al. Long-Term Exposures to Air Pollution and the Risk of Atrial Fibrillation in the Women’s Health Initiative Cohort. Environ. Health Perspect. 2021, 129, 97007. [Google Scholar] [CrossRef] [PubMed]
  119. Rudolf, H.; Mügge, A.; Trampisch, H.J.; Scharnagl, H.; März, W.; Kara, K. NT-proBNP for risk prediction of cardiovascular events and all-cause mortality: The getABI-study. Int. J. Cardiol. Heart Vasc. 2020, 29, 100553. [Google Scholar] [CrossRef]
  120. Brady, P.F.; Chua, W.; Nehaj, F.; Connolly, D.L.; Khashaba, A.; Purmah, Y.J.; Ul-Qamar, M.J.; Thomas, M.R.; Varma, C.; Schnabel, R.B.; et al. Interactions Between Atrial Fibrillation and Natriuretic Peptide in Predicting Heart Failure Hospitalization or Cardiovascular Death. J. Am. Heart Assoc. 2022, 11, e022833. [Google Scholar] [CrossRef]
  121. Xia, R.; Tomsits, P.; Loy, S.; Zhang, Z.; Pauly, V.; Schüttler, D.; Clauss, S. Cardiac Macrophages and Their Effects on Arrhythmogenesis. Front. Physiol. 2022, 13, 900094. [Google Scholar] [CrossRef]
  122. Hiram, R. Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases. Mol. Biol. Rep. 2022, 49, 5179–5197. [Google Scholar] [CrossRef]
  123. He, G.; Tan, W.; Wang, B.; Chen, J.; Li, G.; Zhu, S.; Xie, J.; Xu, B. Increased M1 Macrophages Infiltration Is Associated with Thrombogenesis in Rheumatic Mitral Stenosis Patients with Atrial Fibrillation. PLoS ONE 2016, 11, e0149910. [Google Scholar] [CrossRef]
  124. Nasser, M.I.; Zhu, S.; Huang, H.; Zhao, M.; Wang, B.; Ping, H.; Geng, Q.; Zhu, P. Macrophages: First guards in the prevention of cardiovascular diseases. Life Sci. 2020, 250, 117559. [Google Scholar] [CrossRef]
  125. Berg, Z.K.; Rodriguez, B.; Davis, J.; Katz, A.R.; Cooney, R.V.; Masaki, K. Association Between Occupational Exposure to Pesticides and Cardiovascular Disease Incidence: The Kuakini Honolulu Heart Program. J. Am. Heart Assoc. 2019, 8, e012569. [Google Scholar] [CrossRef]
  126. Bulka, C.M.; Daviglus, M.L.; Persky, V.W.; Durazo-Arvizu, R.A.; Lash, J.P.; Elfassy, T.; Lee, D.J.; Ramos, A.R.; Tarraf, W.; Argos, M. Association of occupational exposures with cardiovascular disease among US Hispanics/Latinos. Heart 2019, 105, 439–448. [Google Scholar] [CrossRef]
  127. Bennett, M.; Nault, I.; Koehle, M.; Wilton, S. Air Pollution and Arrhythmias. Can. J. Cardiol. 2023. ahead of print. [Google Scholar] [CrossRef]
  128. Błaszczyk, R.T.; Gorlo, A.; Dukacz, M.; Konopka, A.; Głowniak, A. Association between exposure to air pollution and incidence of atrial fibrillation. Ann. Agric. Environ. Med. 2023, 30, 15–21. [Google Scholar] [CrossRef] [PubMed]
  129. Li, Y.; Yu, X.; Wang, Z.; Wang, H.; Zhao, X.; Cao, Y.; Wang, W.; Eddleston, M. Gastric lavage in acute organophosphorus pesticide poisoning (GLAOP)—A randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning. BMC Emerg. Med. 2006, 6, 10. [Google Scholar] [CrossRef]
  130. Grande, G.; Ljungman, P.L.S.; Eneroth, K.; Bellander, T.; Rizzuto, D. Association between Cardiovascular Disease and Long-term Exposure to Air Pollution with the Risk of Dementia. JAMA Neurol. 2020, 77, 801–809. [Google Scholar] [CrossRef]
Biomedicines 11 02427 g001
Figure 1. Main sources of air pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both.
Figure 1. Main sources of air pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both.
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Figure 2. A list of primary and secondary pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both. CH4: Methane; CO: Carbon Monoxide; NH3: Ammoniac; NO2: NMVOC: Non-Methane Volatile Organic Compounds; Nitrogen Dioxide; NOx: Nitrogen Oxides; O3: Ozone; SO2: Sulfur Dioxide; VOC: Volatile Organic Compounds.
Figure 2. A list of primary and secondary pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both. CH4: Methane; CO: Carbon Monoxide; NH3: Ammoniac; NO2: NMVOC: Non-Methane Volatile Organic Compounds; Nitrogen Dioxide; NOx: Nitrogen Oxides; O3: Ozone; SO2: Sulfur Dioxide; VOC: Volatile Organic Compounds.
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Figure 3. Categories of Pesticides. Pesticides, including insecticides and herbicides, can be classified as natural and synthetic. Natural pesticides can be sub-categorized according to their origin as mineral oils or plant-based pesticides. Synthetic pesticides include organic and inorganic pesticides.
Figure 3. Categories of Pesticides. Pesticides, including insecticides and herbicides, can be classified as natural and synthetic. Natural pesticides can be sub-categorized according to their origin as mineral oils or plant-based pesticides. Synthetic pesticides include organic and inorganic pesticides.
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Figure 4. A list of the most popular Organochlorides and Organophosphorus. Organochlorides, including DDT, DDE, PCBs, and organophosphorus, including organophosphonates such as glyphosate, are among the most commonly used and commercialized pesticides worldwide. BHC: benzene hexachloride; DDT: dichlorodiphenyltrichloroethane; DDE: dichloro diphenyl dichloroethane; PCB: polychlorinated biphenyls.
Figure 4. A list of the most popular Organochlorides and Organophosphorus. Organochlorides, including DDT, DDE, PCBs, and organophosphorus, including organophosphonates such as glyphosate, are among the most commonly used and commercialized pesticides worldwide. BHC: benzene hexachloride; DDT: dichlorodiphenyltrichloroethane; DDE: dichloro diphenyl dichloroethane; PCB: polychlorinated biphenyls.
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Figure 5. Reported effects of chlordecone on the heart. Chlordecone poisoning has been associated with dysfunction of the myocardium, cardiomyocyte mitochondrial, and calcium-dependent contractility. ATPase: Adenosine Triphosphatase; Ca2+: Calcium; Cl: Chlordecone; Mg2+: Magnesium; Na+: Sodium; O: oxygen.
Figure 5. Reported effects of chlordecone on the heart. Chlordecone poisoning has been associated with dysfunction of the myocardium, cardiomyocyte mitochondrial, and calcium-dependent contractility. ATPase: Adenosine Triphosphatase; Ca2+: Calcium; Cl: Chlordecone; Mg2+: Magnesium; Na+: Sodium; O: oxygen.
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Figure 6. Possible mechanisms associating pesticide exposure to the development of atrial fibrillation. Ca2+: calcium; Cx43: connexin 43; IKur: ultra-rapid delayed rectifier outward potassium current; INa: inward sodium current; RyR2: ryanodine receptor; SERCA: sarco/endoplasmic reticulum Ca2+-ATPase.
Figure 6. Possible mechanisms associating pesticide exposure to the development of atrial fibrillation. Ca2+: calcium; Cx43: connexin 43; IKur: ultra-rapid delayed rectifier outward potassium current; INa: inward sodium current; RyR2: ryanodine receptor; SERCA: sarco/endoplasmic reticulum Ca2+-ATPase.
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Figure 7. A potential implication of the inflammatory response to pesticide poisoning, leading to atrial fibrillation. Pesticide poisoning provokes tissular injury following primary contact with skin, eyes, or digestive system. The toxic interaction leads to local injury and reaction provoking tissular damage signals impaired by DAMPs and PAMPs, which lead to the activation and the excretion of inflammatory signals that can affect other systems, via the blood circulation. Reported affected systems include, among others, the brain, the liver, the kidney, and the heart. Circulating pesticide metabolites and inflammatory signals may promote the amplification of cardiac inflammatory status, which, if unresolved can lead to chronic inflammation and cardiac fibrosis. Fibrosis is associated with abnormal conduction and atrial refractoriness, which contributes to increasing the risk of cardiac arrhythmias and atrial fibrillation. DAMPs: damage-associated molecular patterns; GSDMD: gasdermin-D; IL: interleukin; NFkB: nuclear factor kappa B; NLRP3: NACHT, LRR, and PYD domains-containing protein-3; Nt: N-terminal; P38 MAPK: p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinase; PAMPs: pathogen-associated molecular patterns; PMN: polymorphonuclear neutrophils; TGF-b: transforming growth factor beta; TNF-a: tumor necrosis factor-alpha.
Figure 7. A potential implication of the inflammatory response to pesticide poisoning, leading to atrial fibrillation. Pesticide poisoning provokes tissular injury following primary contact with skin, eyes, or digestive system. The toxic interaction leads to local injury and reaction provoking tissular damage signals impaired by DAMPs and PAMPs, which lead to the activation and the excretion of inflammatory signals that can affect other systems, via the blood circulation. Reported affected systems include, among others, the brain, the liver, the kidney, and the heart. Circulating pesticide metabolites and inflammatory signals may promote the amplification of cardiac inflammatory status, which, if unresolved can lead to chronic inflammation and cardiac fibrosis. Fibrosis is associated with abnormal conduction and atrial refractoriness, which contributes to increasing the risk of cardiac arrhythmias and atrial fibrillation. DAMPs: damage-associated molecular patterns; GSDMD: gasdermin-D; IL: interleukin; NFkB: nuclear factor kappa B; NLRP3: NACHT, LRR, and PYD domains-containing protein-3; Nt: N-terminal; P38 MAPK: p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinase; PAMPs: pathogen-associated molecular patterns; PMN: polymorphonuclear neutrophils; TGF-b: transforming growth factor beta; TNF-a: tumor necrosis factor-alpha.
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Figure 8. A proposed algorithm for AF-patient management following pollutant poisoning. AF: atrial fibrillation; NT-proBNP: N-terminal pro-brain natriuretic peptide; IL: interleukin; WHO: World Health Organization.
Figure 8. A proposed algorithm for AF-patient management following pollutant poisoning. AF: atrial fibrillation; NT-proBNP: N-terminal pro-brain natriuretic peptide; IL: interleukin; WHO: World Health Organization.
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Table 1. Clinical studies highlighting the association between air pollution and cardiac arrhythmias. AF: atrial fibrillation; CO: carbon monoxide; NO2: nitrogen dioxide; O3: ozone; PM: particulate matter; SO2: Sulfur dioxide; VA: ventricular arrhythmias.
Table 1. Clinical studies highlighting the association between air pollution and cardiac arrhythmias. AF: atrial fibrillation; CO: carbon monoxide; NO2: nitrogen dioxide; O3: ozone; PM: particulate matter; SO2: Sulfur dioxide; VA: ventricular arrhythmias.
PollutantPatient PopulationInduced
Arrhythmia
(Incidence/Prevalence)		Reference
TotalAge (Years)SexCountry
PM2.5124,010
patients		48.5 ± 12.5Male: 48.8% Female: 51.2%South KoreaAF
95% CI = 1.02–1.09		Kwon OK et al., 2019
[32]
PM2.5670
patients		70.5 ± 14Male: 51%
Female: 49%		TaiwanAF
95% CI = 1.03–1.44		Lee HH et al., 2019
[10]
PM2.5176
patients		60 ± 20Male: 77%
Female: 23%		USAVA
95% CI = 1.15–1.90		Peralta A et al., 2020
[33]
PM2.5Meta-analysis (18 studies)USA
Canada
Europe
Asia		AF
95% CI = 1.01–1.10		Yue C et al., 2021
[34]
PM2.5; NO2 O3; Ox5,071,956
patients		53.2 ± 12.9Male: 48%
Female: 52%		CanadaAF
95% CI = 1.01–1.04		Shin S et al., 2019
[35]
PM2.5; PM10
SO2; NO2 O3; CO		176
patients		58 ± 32Male: 70%
Female: 30%		USAAF
95% CI = 1.08–1.47		Link MS et al., 2013
[36]
PM2.5; SO2; NO2 O3Meta-analysis (18 studies)USA
Europe
Asia		AF
95% CI = 1.02–1.06		Chen M et al., 2021
[37]
PM2.5125
patients		77.6 ± 7.8Male: 61.5% Female: 38.5%SwedenAF
95% CI = 1.01–1.10		Dahlquist M et al., 2022
[38]
NO2369
patients		66.3 ± 15.9Male: 46.9%
Female: 53.1%		IranAF
95% CI = 1.02–1.55		Saifipour A et al., 2019
[39]
PM2.5; PM10145
patients		70.5 ± 6.5Male: 75.2%
Female: 24.8%		ItaliaAF
95% CI = 1.34–4.28		Gallo E et al., 2020
[40]
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Le Quilliec, E.; Fundere, A.; Al-U’datt, D.G.F.; Hiram, R. Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review. Biomedicines 2023, 11, 2427. https://doi.org/10.3390/biomedicines11092427

AMA Style

Le Quilliec E, Fundere A, Al-U’datt DGF, Hiram R. Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review. Biomedicines. 2023; 11(9):2427. https://doi.org/10.3390/biomedicines11092427

Chicago/Turabian Style

Le Quilliec, Ewen, Alexia Fundere, Doa’a G. F. Al-U’datt, and Roddy Hiram. 2023. "Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review" Biomedicines 11, no. 9: 2427. https://doi.org/10.3390/biomedicines11092427

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