p.19 抽出テキスト

CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e19

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

ANS maintains AF Atrial sympathetic and parasympathetic hyperinnervation and spatial heterogeneity, coupled with electrical fractionation and altered atrial electrophysiology, contribute to substrate.7–10 Modifiable AF risk factors promote ANS dysfunction.3 AF produces autonomic afferent reflex deficiencies elicited by decreased cardiac volume11,12 and increases sympathetic activity.13 Afferent abnormalities disrupt blood volume and pressure homeostasis. Similar abnormalities to AF were identified in HF.14 Afferent ANS dysfunction could link autonomic with anatomic remodeling (atrial dilatation15), contributing to AF self-perpetuation.

2.4 Genetics

Both common forms and familial AF are heritable.1–3 Multiple recent genome-wide association studies have documented >100 loci specific for AF.4,5 Numerous AF loci appear consistent across multiethnic groups,5 with some population variation.6,7 With large genomewide genotyped cohorts such as the UK Biobank and the US National Heart, Lung, and Blood Institute’s (NHLBI’s) Trans Omics for Precision Medicine, the genetic architecture of AF is now emerging. A UK Biobank study identified TTN loss of function variants in 0.44% of participants, 14% of whom had AF.8 In a Trans Omics for Precision Medicine study of nearly 1300 participants <66 years of age with AF, 10.1% harbored a disease-associated genetic variant in genes associated with inherited cardiomyopathy or arrhythmia syndromes (most common were TTN, MYH7, MYH6, LMNA, and KCNQ1), and 62.8% had variants of undetermined significance. Disease-associated variants were more prevalent at younger age of AF onset, 16.8% in those <30 years.9 A smaller study of persons of Hispanic or African American descent reported 7% of persons with AF onset at ≤66 years of age harbored rare likely pathogenic or pathogenic sequence variants, mostly in myocardial structural proteins and ion channels.10

Figure 7. Mechanisms and Pathways Leading to AF. The pathways that contribute to the development of AF create a substrate for reentry and provide triggers that can initiate arrhythmic activity. AF indicates atrial fibrillation; PAC, premature atrial contraction; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; and RAAS, reninangiotensin-aldosterone system.

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