Pulse check in pharmacies I Author: Michaela Frnková Supervisor: PharmDr. Kateřina Malá, Ph.D. Consultant: PharmDr. Anna Rejmanová, Ph.D. De artment o ocial an linical Pharmac , Fac lt o Pharmac in ra ec Králov , harle University Introduction: Atrial fibrillation is one of the most common supraventricular disorders of the heart rhythm. Unless properly treated, it leads to higher mortality and morbidity rates. Early detection of such fibrillation, which is often asymptomatic, may prevent further associated complications, especially ischemic stroke, and a sudden cardiac death. Aim: The thesis focused on the feasibility of involving pharmacists in the screening of the patients with heart rhythm disorders. Further increase awareness of the possibilities and meaning of monitoring heart rhythm disorders in pharmacies and ensure that patients can verify their own heart rate at home. Methods: The heart rhythm measurements were carried within four weeks (11/2017; 11/2018; 6/2019; 12/2019), during the global health initiative "Know o r l e". Mea ring took place at the pharmacy in Pardubice; the pharmacy offers individual consultations to patients. Participation in the screening for the atrial fibrillation was offered to all incoming pharmacy persons who were older than 40 years and without chronic...

Objectives: To determine the association between genetic variants on chromosome 4q25 and atrial fibrillation (AF) in a Taiwanese population. Methods: We enrolled 200 patients with AF (mean age: 67 ± 13 years) and 158 controls (mean age: 63 ± 10 years). The genotypes of five SNPs, RS2634073, RS2200733, RS13143308, RS2220427 and RS10033464, were determined using multiplex single base extension methods. Results: The distribution of the RS2200733 and RS10033464 genotypes did not significantly deviate from the Hardy-Weinberg equilibrium in the control group. The distribution of the RS2200733 genotypes differed significantly between the AF group and the controls (p = 0.03), whereas the distribution of the RS10033464 genotypes did not (p = 0.49). At RS2200733, patients with the CC genotype exhibited a 0.45 times higher risk of developing AF than those with the TT genotype (p = 0.02) and a recessive model was suggested (p = 0.01). After adjusting for various covariates, patients with the CC genotype remained recessively associated with a lower risk of developing AF than those with the TT genotype (odds ratio: 0.27, 95% confidence interval: 0.11-0.65; p < 0.01). Conclusions: In the Taiwanese, there is an association between SNP RS2200733 - but not RS10033464 - and the development of AF. Based on a recessive model of inheritance, individuals with SNP RS2200733 genotype CC are at a lesser risk of developing AF.

The autonomic nervous system plays an integral role in the modulation of normal cardiac electrophysiology. This is achieved via a complex network of pre- and postganglionic sympathetic and parasympathetic fibers that synapse on extrinsic and intrinsic cardiac ganglia and ultimately directly innervate cardiac myocytes. Alterations in autonomic tone may induce changes in local cellular electrophysiology that may manifest clinically in a number of ways, ranging from changes in heart rate to changes in heart rhythm. These relationships between autonomic tone and the evolution of cardiac dysrhythmias are areas of evolving research, with increasing evidence for a key role for autonomic ganglia in the pathogenesis of atrial fibrillation and sympathetic nerves in the predilection toward ventricular tachycardia in areas of myocardial scar. In this review, we highlight what is known about the anatomy and physiology of the cardiac autonomic nervous system, the evidence supporting the relationship of autonomic tone to clinically significant arrhythmias, and a variety of mechanisms (eg, direct ion channel effects) and diagnostic tools that exist to help define this relationship. Further emphasized are potential future avenues of research needed to elucidate the relationship between changes in normal autonomic tone and the pathogenesis of cardiac arrhythmias.

X-Linked Sinus Node Dysfunction and Atrial Fibrillation. Introduction: Atrial fibrillation (AF) is a heritable disorder with male predilection, suggesting a sex chromosome defect in certain patients. Loss-of-function truncation mutations in EMD, encoding the nuclear membrane protein emerin, cause X-linked Emery-Dreifuss muscular dystrophy (EDMD) characterized by localized contractures and skeletal myopathy in adolescence, sinus node dysfunction (SND) in early adulthood, and atrial fibrillation as a variably associated trait. This study sought to identify the genetic basis for male-restricted, nonsyndromic sinus node dysfunction and AF in a multigenerational family. Methods and Results: Genealogical and medical records, and DNA samples, were obtained. Progressive SND and AF occurred in four males related through maternal lineages, consistent with X-linked inheritance. Skeletal myopathy was absent, even at advanced ages. Targeted X chromosome genotyping mapped the disease locus to Xq28, implicating EMD as a positional candidate gene. DNA sequencing revealed hemizygosity for an in-frame 3-bp deletion in EMD (Lys37del) in affected males, disrupting a residue within the LEM binding domain critical for nuclear assembly but leaving the remainder of the protein intact. Buccal epithelial cell staining with emerin antibody demonstrated near-total functional loss of emerin. Female relatives underwent prospective electrocardiographic and genetic testing. Those heterozygous for Lys37del had ∼50-70% emerin-positive nuclei and variable degrees of paroxysmal supraventricular arrhythmia. Conclusions: Mutation of EMD can underlie X-linked familial AF. Lys37del is associated with epithelial cell emerin deficiency, as in EDMD, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease. Targeted genetic testing of EMD should be considered in patients with SND-associated AF and/or family history suggesting X-linked inheritance.

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Atrial fibrillation (AF) is associated with high risk of systemic thromboembolism leading to significant morbidity and mortality. Warfarin, previously the mainstay for stroke prevention in AF, requires close monitoring because of multiple food and drug interactions. In recent years, food and drug administration has approved several direct oral anticoagulants (DOACs) for use in patients with nonvalvular AF. These agents have not been studied in patients with valvular AF who are at an even higher risk of systemic thromboembolism. DOACs do not require frequent blood testing or changes in dosage except when renal function deteriorates, however, the lack of established antidotes for many of these agents remains a challenge. Also, currently there is no head-to-head comparison between these agents to guide clinical choice. This article discusses the advantages and disadvantages of currently approved oral antithrombotics in nonvalvular AF, with a special emphasis on the DOACs and their individual characteristics.

There is epidemiological and experimental evidence suggesting that exercise training may reduce the mortality rate from coronary heart disease, in particular the sudden death rate, and that it may improve the peak functional capacity of the heart. This thesis includes experimental work that is relevant to both these questions.

Patients with atrial fibrillation (AF) are at increased risk of stroke. Warfarin anticoagulation therapy reduces the incidence of stroke and increases the incidence of hemorrhagic events. This dissertation further informs the decision to use anticoagulation therapy in AF patients by examining outcomes in patients with major hemorrhages, further examination of stroke risk in diabetic patients with AF, and by evaluating the association between warfarin and stroke while accounting for competing risk events. These studies utilized data from the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) and ATRIA-CVRN (Cardiovascular Research Network) (Study 1 only) studies which consist of patients from Kaiser Permanente Northern and Southern California. Study 1 examined short and long-term mortality in patients who experienced major gastrointestinal (GI) hemorrhages. In the ATRIA cohort, patients using and not using warfarin at the time of GI hemorrhage were equally likely to die within 30-days, while in ATRIA-CVRN, patients using warfarin were much less likely to die within 30-days (adjusted mortality rate ratio (aMRR): 0.33, 95% CI: 0.16-0.70). For longer-term mortality, both cohorts were consistent with a reduced mortality rate among patients whose GI hemorrhage occurred while using warfarin. Study 2 assessed the association between diabetes characteristics (duration of diabetes and glycemic control) and incidence of ischemic stroke among patients with AF and diabetes. Duration ≥ 3 years was associated with a large increase in rate of stroke (adjusted hazard ratio (aHR): 2.04, 95% CI: 1.27-3.26) compared to patients with duration < 3 years. Patients with the poorest glycemic control (hemoglobin A1c (HbA1c) values ≥ 9.0%) did not have an increased rate of ischemic stroke compared to patients with HbA1c < 7.0%. Study 3 evaluated the association between warfarin and thromboembolism in analyses that did and did not account for competing death events. In analyses not accounting for competing events, the adjusted HR was 0.61 (95% CI: 0.54-0.69), and after accounting for competing death events this association was attenuated (aHR: 0.87, 95% CI: 0.77-0.99). In summary, these studies add to the literature about the benefits of warfarin therapy and risk of stroke in patients with AF, findings that can improve decisions about use of anticoagulants in patients with AF.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18868号 / 医博第3979号 / 新制||医||1008(附属図書館) / 31819 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 坂田 隆造, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20626号 / 社医博第84号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 佐藤 俊哉, 教授 木村 剛, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM