European Heart Journal - Cardiovascular Pharmacotherapy, Jun 28, 2021
Validity of subgroup data Credibility of subgroup data Geographic considerations Examples from li... more Validity of subgroup data Credibility of subgroup data Geographic considerations Examples from lipid and diabetes trials Examples from antithrombotic and anticoagulation trials Examples from recent studies Conclusions
and this arrhythmia has been associated to alterations in intracellular calcium handling. The pur... more and this arrhythmia has been associated to alterations in intracellular calcium handling. The purpose of this study was to test the hypothesis that ageing per se alters calcium handling in human atrial myocytes. Methods: Whole membrane currents were measured in the perforated patch configuration in human atrial myocytes from 74 patients free of atrial fibrillation and with normal left atrial size. Patients were categorized as young (<55 years, n=21), middle aged (between 55 and 75 years, n=42), and old (>75 years, n=11). Protein expression was determined with Western blot technique in right atrial samples from 7 young and 7 old patients. Results: The expression of the alpha-subunit of the L-type calcium channel was lower in old patients, and statistical analysis showed that aging progressively and significantly (p<0.01) reduced the L-type calcium current (ICa) amplitude, even when the effects of age, sex, ACE inhibitors, beta-blockers, angiotensin receptor blockers, calcium antagonists, and left ventricular ejection fraction were taken into account. ICa decreased from 2.4±0.3 pA/pF in the young to 1.2±0.3 pA/pF in the old patient group (p<0.01). The current-voltage relationship was not affected by age but fast ICa inactivation was significantly slower in old patients. The tau for ICa inactivation was 20.9±1.9 ms in old vs. 14.5±0.9 ms in young patients (p<0.01). Similarly the tau for slow ICa inactivation was 120±12 ms in old vs. 73±3 ms in young patients (p<0.001). The caffeine releasable sarcoplasmic reticulum (SR) calcium content also decreased with age (from 10.1±0.8 amol/pF in young to 7.3±0.7 amol/pF in old patients, p<0.05). This was accompanied by a significant decrease in the expression of both SERCA2 and calsequestrin-2 protein levels. By contrast, age did not affect the frequency of spontaneous SR calcium release induced transient inward currents (1.4±0.3 in young vs. 1.1±0.8 events/min in old patients, p=0.5). Moreover, age did not affect the ability of myocytes to maintain a uniform beat-to-beat response when the stimulation frequency was increased. Conclusions: Ageing is associated with depression of L-type calcium channel expression and current amplitude as well as a reduction of the SR calcium content linked to lower SERCA2 and calsequestrin-2 expression in human atrial myocytes. These alterations may blunt atrial contraction and relaxation. P5019 | BENCH Human cardiac Kir2.1, but not Kir2.3, channel expression is regulated by Nav1.
Cancer represents the second cause of death in the European Union after cardiovascular diseases, ... more Cancer represents the second cause of death in the European Union after cardiovascular diseases, accounting for 27% of all deaths. Anticancer drugs (ACDs) have poor cell selectivity and a narrow therapeutic margin, in such a way that small increases in their plasma levels lead to the appearance of adverse reactions in multiple tissues. The FACs can produce a wide range of adverse cardiovascular reactions (named cardiotoxicity) that increase morbidity and can even lead to death in some patients whose cancer has been cured by the ACD. The risk of cardiotoxicity increases with age, and since up to two-thirds of cancer patients are older than 65 years of age, cancer, cardiovascular diseases whose incidence increases with age and CAD-induced cardiotoxicity will coexist in this population. The diagnosis, prognosis, follow-up, and treatment of cardiotoxicity induced by CAFs represent a challenge in daily clinical practice that makes teamwork among cardiologists, oncologists, and hematologi...
Editorial on the Research Topic Medical Devices made of substances for human health: a challenge ... more Editorial on the Research Topic Medical Devices made of substances for human health: a challenge in terms of efficacy, safety and sustainability Alessandro Mugelli and Juan Tamargo Treatments without scientific proof of efficacy and safety are offered to and often used by individuals for their medical needs. Substance-based medical devices (SBMDs) are medical devices composed of substances or by combinations of substances as defined in Annex VIII, Rule 21 of the European Medical Device Regulation (MDR) (https://eur-lex.europa.eu/legal-content/ EN/TXT/?uri=CELEX%3A32017R0745). While SBMDs are similar to medicinal products (MPs) in their presentation and pharmaceutical form, they should achieve their therapeutic effect via a "non-pharmacological, immunological, or metabolic mechanism of action." Independently of the mechanism of action to reach their therapeutic effect, what is of utmost importance is that the therapeutic claim must be demonstrated by well-designed clinical trials and that the benefit/risk ratio reported when SBMDs are marketed should be corroborated by active postmarketing surveillance. Manufacturers must verify the quality and safety of the substances that are in the SBMD according to the EU legislation for patient safety, but this field also represents an opportunity for innovation and research. The new MDR has been in force since May 2021. As clearly reported in the perspective articles by Giovagnoni, "the MDR's inclusion of different types of product has created a significant opportunity for innovation." In fact, "the Regulation allowed to repurpose the therapeutic properties of natural complex substances, which were unused, or even considered complementary and alternative medicine, within an evidence-based framework and as part of the healthcare sector." The aim of this Research Topic is to give the clear message that the healthcare system, the scientific research community, and the industry should be prepared to accept the challenges of this profound regulatory change, transforming this change into opportunities for innovation and health improvement. Interestingly, in the EU, the regulatory changes on clinical research of MPs as well as the more general regulatory framework of medical devices, and in particular of SBMDs, have
European Heart Journal - Cardiovascular Pharmacotherapy
Cardiovascular diseases (CVD) remain the leading cause of death worldwide, and pharmacotherapy of... more Cardiovascular diseases (CVD) remain the leading cause of death worldwide, and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022, including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of ‘old’ drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensi...
Introduction: The factors that control the expression of Kir2.1 and NaV1.5 channels and the mecha... more Introduction: The factors that control the expression of Kir2.1 and NaV1.5 channels and the mechanisms that target such channels to subcellular and membrane macrodomains are incompletely understood...
European Heart Journal - Cardiovascular Pharmacotherapy, 2021
Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers ... more Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers to implementation. These are particularly important to explore within Europe, as there are differences in the populations, availability of resources, and expertise, as well as in ethico-legal frameworks. Differences in healthcare delivery across Europe present a challenge, but also opportunities to collaborate on pharmacogenomics implementation. Clinical workforce upskilling is already in progress but will require substantial input. Digital infrastructure and clinical support tools are likely to prove crucial. It is important that widespread implementation serves to narrow rather than widen any existing gaps in health equality between populations. This viewpoint supplements the working group position paper on cardiovascular pharmacogenomics to address these important themes.
Revista Española de Cardiología (English Edition), 2020
Please cite this article in press as: Gonzá lez-Juanatey JR, et al. Pharmacodynamic study of the ... more Please cite this article in press as: Gonzá lez-Juanatey JR, et al. Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents? Rev Esp Cardiol. 2020.
European Heart Journal - Cardiovascular Pharmacotherapy, 2019
Aims The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower e... more Aims The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of antithrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. Methods and results Study inclusion criteria were: enrolment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single-antiplatelet therapy (SAPT); dual-antiplatelet therapy vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30 447 patients were included. Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization [relative risk (RR) 0....
European Heart Journal - Cardiovascular Pharmacotherapy, 2019
Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiov... more Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.
Resumen La insuficiencia cardiaca (IC) presenta aspectos diferenciales entre generos en la epidem... more Resumen La insuficiencia cardiaca (IC) presenta aspectos diferenciales entre generos en la epidemiologia, fisiopatologia, formas clinicas de presentacion y tratamiento que han sido previamente estudiados. En primer lugar, la IC es una causa frecuente de muerte en la mujer (5,8 frente a 3,2% en los varones, segun datos del Instituto Nacional de Estadistica 2017), asi como de hospitalizacion y baja calidad de vida, a pesar de que inicialmente, una mayor prevalencia de fraccion eyeccion conservada en las mujeres, sugiera un mejor pronostico. Por otra parte, los farmacos basados en la evidencia cientifica y las terapias mas avanzadas se utilizan menos en las mujeres con IC. Los factores que pueden influir en estos aspectos diferenciales son objeto de esta revision.
Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulatio... more Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulation of cellular membrane structure and function. They are essential for mammalian cells as they are not able to synthesize their precursor α-linolenic acid (18:3n-3), which can then be converted to more biologically active n-3 PUFA, EPA, and DHA, by a series of desaturation and elongation reactions. In recent years, it has been found that increased intake of n-3 PUFA is associated with a reduced risk of cardiovascular morbidity and mortality. Fish is the main dietary source of n-3 PUFA, although the concentration of n-3 PUFA is below the large amounts required to achieve the therapeutic benefits derived from EPA and DHA. This led to the development of formulations of n-3 PUFA containing high concentrations of purified EPA and DHA in a fixed, predefined ratio, with higher but different oral bioavailability and reasonable patient compliance to be used for dietary supplementation. This article reviews the pharmacokinetic profile of n-3 PUFA, including the digestion and bioavailability, tissular distribution (incorporation in plasma lipids, blood cells, and cell membranes), metabolism (β-oxidation, enzymatic biotransformation, synthesis of eicosanoids and other lipid mediators such as resolvins and protectins), and excretion. Factors that modulate oral bioavailability of n-3 PUFA (chemical and galenic formulations, food intake) are also analyzed. Additionally, the safety profile of n-3 PUFA, with particular attention to an increased bleeding risk, drug interactions, and contraindications, is reviewed.
Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for i... more Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.
European Heart Journal - Cardiovascular Pharmacotherapy, Jun 28, 2021
Validity of subgroup data Credibility of subgroup data Geographic considerations Examples from li... more Validity of subgroup data Credibility of subgroup data Geographic considerations Examples from lipid and diabetes trials Examples from antithrombotic and anticoagulation trials Examples from recent studies Conclusions
and this arrhythmia has been associated to alterations in intracellular calcium handling. The pur... more and this arrhythmia has been associated to alterations in intracellular calcium handling. The purpose of this study was to test the hypothesis that ageing per se alters calcium handling in human atrial myocytes. Methods: Whole membrane currents were measured in the perforated patch configuration in human atrial myocytes from 74 patients free of atrial fibrillation and with normal left atrial size. Patients were categorized as young (<55 years, n=21), middle aged (between 55 and 75 years, n=42), and old (>75 years, n=11). Protein expression was determined with Western blot technique in right atrial samples from 7 young and 7 old patients. Results: The expression of the alpha-subunit of the L-type calcium channel was lower in old patients, and statistical analysis showed that aging progressively and significantly (p<0.01) reduced the L-type calcium current (ICa) amplitude, even when the effects of age, sex, ACE inhibitors, beta-blockers, angiotensin receptor blockers, calcium antagonists, and left ventricular ejection fraction were taken into account. ICa decreased from 2.4±0.3 pA/pF in the young to 1.2±0.3 pA/pF in the old patient group (p<0.01). The current-voltage relationship was not affected by age but fast ICa inactivation was significantly slower in old patients. The tau for ICa inactivation was 20.9±1.9 ms in old vs. 14.5±0.9 ms in young patients (p<0.01). Similarly the tau for slow ICa inactivation was 120±12 ms in old vs. 73±3 ms in young patients (p<0.001). The caffeine releasable sarcoplasmic reticulum (SR) calcium content also decreased with age (from 10.1±0.8 amol/pF in young to 7.3±0.7 amol/pF in old patients, p<0.05). This was accompanied by a significant decrease in the expression of both SERCA2 and calsequestrin-2 protein levels. By contrast, age did not affect the frequency of spontaneous SR calcium release induced transient inward currents (1.4±0.3 in young vs. 1.1±0.8 events/min in old patients, p=0.5). Moreover, age did not affect the ability of myocytes to maintain a uniform beat-to-beat response when the stimulation frequency was increased. Conclusions: Ageing is associated with depression of L-type calcium channel expression and current amplitude as well as a reduction of the SR calcium content linked to lower SERCA2 and calsequestrin-2 expression in human atrial myocytes. These alterations may blunt atrial contraction and relaxation. P5019 | BENCH Human cardiac Kir2.1, but not Kir2.3, channel expression is regulated by Nav1.
Cancer represents the second cause of death in the European Union after cardiovascular diseases, ... more Cancer represents the second cause of death in the European Union after cardiovascular diseases, accounting for 27% of all deaths. Anticancer drugs (ACDs) have poor cell selectivity and a narrow therapeutic margin, in such a way that small increases in their plasma levels lead to the appearance of adverse reactions in multiple tissues. The FACs can produce a wide range of adverse cardiovascular reactions (named cardiotoxicity) that increase morbidity and can even lead to death in some patients whose cancer has been cured by the ACD. The risk of cardiotoxicity increases with age, and since up to two-thirds of cancer patients are older than 65 years of age, cancer, cardiovascular diseases whose incidence increases with age and CAD-induced cardiotoxicity will coexist in this population. The diagnosis, prognosis, follow-up, and treatment of cardiotoxicity induced by CAFs represent a challenge in daily clinical practice that makes teamwork among cardiologists, oncologists, and hematologi...
Editorial on the Research Topic Medical Devices made of substances for human health: a challenge ... more Editorial on the Research Topic Medical Devices made of substances for human health: a challenge in terms of efficacy, safety and sustainability Alessandro Mugelli and Juan Tamargo Treatments without scientific proof of efficacy and safety are offered to and often used by individuals for their medical needs. Substance-based medical devices (SBMDs) are medical devices composed of substances or by combinations of substances as defined in Annex VIII, Rule 21 of the European Medical Device Regulation (MDR) (https://eur-lex.europa.eu/legal-content/ EN/TXT/?uri=CELEX%3A32017R0745). While SBMDs are similar to medicinal products (MPs) in their presentation and pharmaceutical form, they should achieve their therapeutic effect via a "non-pharmacological, immunological, or metabolic mechanism of action." Independently of the mechanism of action to reach their therapeutic effect, what is of utmost importance is that the therapeutic claim must be demonstrated by well-designed clinical trials and that the benefit/risk ratio reported when SBMDs are marketed should be corroborated by active postmarketing surveillance. Manufacturers must verify the quality and safety of the substances that are in the SBMD according to the EU legislation for patient safety, but this field also represents an opportunity for innovation and research. The new MDR has been in force since May 2021. As clearly reported in the perspective articles by Giovagnoni, "the MDR's inclusion of different types of product has created a significant opportunity for innovation." In fact, "the Regulation allowed to repurpose the therapeutic properties of natural complex substances, which were unused, or even considered complementary and alternative medicine, within an evidence-based framework and as part of the healthcare sector." The aim of this Research Topic is to give the clear message that the healthcare system, the scientific research community, and the industry should be prepared to accept the challenges of this profound regulatory change, transforming this change into opportunities for innovation and health improvement. Interestingly, in the EU, the regulatory changes on clinical research of MPs as well as the more general regulatory framework of medical devices, and in particular of SBMDs, have
European Heart Journal - Cardiovascular Pharmacotherapy
Cardiovascular diseases (CVD) remain the leading cause of death worldwide, and pharmacotherapy of... more Cardiovascular diseases (CVD) remain the leading cause of death worldwide, and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022, including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of ‘old’ drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensi...
Introduction: The factors that control the expression of Kir2.1 and NaV1.5 channels and the mecha... more Introduction: The factors that control the expression of Kir2.1 and NaV1.5 channels and the mechanisms that target such channels to subcellular and membrane macrodomains are incompletely understood...
European Heart Journal - Cardiovascular Pharmacotherapy, 2021
Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers ... more Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers to implementation. These are particularly important to explore within Europe, as there are differences in the populations, availability of resources, and expertise, as well as in ethico-legal frameworks. Differences in healthcare delivery across Europe present a challenge, but also opportunities to collaborate on pharmacogenomics implementation. Clinical workforce upskilling is already in progress but will require substantial input. Digital infrastructure and clinical support tools are likely to prove crucial. It is important that widespread implementation serves to narrow rather than widen any existing gaps in health equality between populations. This viewpoint supplements the working group position paper on cardiovascular pharmacogenomics to address these important themes.
Revista Española de Cardiología (English Edition), 2020
Please cite this article in press as: Gonzá lez-Juanatey JR, et al. Pharmacodynamic study of the ... more Please cite this article in press as: Gonzá lez-Juanatey JR, et al. Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents? Rev Esp Cardiol. 2020.
European Heart Journal - Cardiovascular Pharmacotherapy, 2019
Aims The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower e... more Aims The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of antithrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. Methods and results Study inclusion criteria were: enrolment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single-antiplatelet therapy (SAPT); dual-antiplatelet therapy vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30 447 patients were included. Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization [relative risk (RR) 0....
European Heart Journal - Cardiovascular Pharmacotherapy, 2019
Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiov... more Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.
Resumen La insuficiencia cardiaca (IC) presenta aspectos diferenciales entre generos en la epidem... more Resumen La insuficiencia cardiaca (IC) presenta aspectos diferenciales entre generos en la epidemiologia, fisiopatologia, formas clinicas de presentacion y tratamiento que han sido previamente estudiados. En primer lugar, la IC es una causa frecuente de muerte en la mujer (5,8 frente a 3,2% en los varones, segun datos del Instituto Nacional de Estadistica 2017), asi como de hospitalizacion y baja calidad de vida, a pesar de que inicialmente, una mayor prevalencia de fraccion eyeccion conservada en las mujeres, sugiera un mejor pronostico. Por otra parte, los farmacos basados en la evidencia cientifica y las terapias mas avanzadas se utilizan menos en las mujeres con IC. Los factores que pueden influir en estos aspectos diferenciales son objeto de esta revision.
Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulatio... more Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulation of cellular membrane structure and function. They are essential for mammalian cells as they are not able to synthesize their precursor α-linolenic acid (18:3n-3), which can then be converted to more biologically active n-3 PUFA, EPA, and DHA, by a series of desaturation and elongation reactions. In recent years, it has been found that increased intake of n-3 PUFA is associated with a reduced risk of cardiovascular morbidity and mortality. Fish is the main dietary source of n-3 PUFA, although the concentration of n-3 PUFA is below the large amounts required to achieve the therapeutic benefits derived from EPA and DHA. This led to the development of formulations of n-3 PUFA containing high concentrations of purified EPA and DHA in a fixed, predefined ratio, with higher but different oral bioavailability and reasonable patient compliance to be used for dietary supplementation. This article reviews the pharmacokinetic profile of n-3 PUFA, including the digestion and bioavailability, tissular distribution (incorporation in plasma lipids, blood cells, and cell membranes), metabolism (β-oxidation, enzymatic biotransformation, synthesis of eicosanoids and other lipid mediators such as resolvins and protectins), and excretion. Factors that modulate oral bioavailability of n-3 PUFA (chemical and galenic formulations, food intake) are also analyzed. Additionally, the safety profile of n-3 PUFA, with particular attention to an increased bleeding risk, drug interactions, and contraindications, is reviewed.
Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for i... more Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.
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