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Current perceptions of the epidemiology of atrial fibrillation.

ABSTRACT: Atrial fibrillation (AF), an escalating dysrhythmia, is accountable for extensive population morbidity and mortality. In the United States, approximately 2.3 million people are presently diagnosed with AF and it is estimated that this prevalence may increase to 5.6 million by 2050. Foremost predisposing risk factors for this dysrhythmia include advanced age and cardiovascular disease and its risk factors. The chief hazard of AF is embolic stroke, which is increased four- to fivefold, and in advanced age, it becomes a dominant stroke risk factor. AF also carries a doubled mortality rate.

SUBMITTER: Kannel WB

PROVIDER: S-EPMC2917063 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Current perceptions of the epidemiology of atrial fibrillation.

Kannel William B WB Benjamin Emelia J EJ

Cardiology clinics 20090201 1

Atrial fibrillation (AF), an escalating dysrhythmia, is accountable for extensive population morbidity and mortality. In the United States, approximately 2.3 million people are presently diagnosed with AF and it is estimated that this prevalence may increase to 5.6 million by 2050. Foremost predisposing risk factors for this dysrhythmia include advanced age and cardiovascular disease and its risk factors. The chief hazard of AF is embolic stroke, which is increased four- to fivefold, and in adva ...[more]

PMID: 19111760

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Project description:Slowly inactivating Na+ channels conducting "late" Na+ current (INa,late) contribute to ventricular arrhythmogenesis under pathological conditions. INa,late was also reported to play a role in chronic atrial fibrillation (AF). The objective of this study was to investigate INa,late in human right atrial cardiomyocytes as a putative drug target for treatment of AF. To activate Na+ channels, cardiomyocytes from transgenic mice which exhibit INa,late (?KPQ), and right atrial cardiomyocytes from patients in sinus rhythm (SR) and AF were voltage clamped at room temperature by 250-ms long test pulses to -30 mV from a holding potential of -80 mV with a 100-ms pre-pulse to -110 mV (protocol I). INa,late at -30 mV was not discernible as deviation from the extrapolated straight line IV-curve between -110 mV and -80 mV in human atrial cells. Therefore, tetrodotoxin (TTX, 10 ?M) was used to define persistent inward current after 250 ms at -30 mV as INa,late. TTX-sensitive current was 0.27±0.06 pA/pF in ventricular cardiomyocytes from ?KPQ mice, and amounted to 0.04±0.01 pA/pF and 0.09±0.02 pA/pF in SR and AF human atrial cardiomyocytes, respectively. With protocol II (holding potential -120 mV, pre-pulse to -80 mV) TTX-sensitive INa,late was always larger than with protocol I. Ranolazine (30 ?M) reduced INa,late by 0.02±0.02 pA/pF in SR and 0.09±0.02 pA/pF in AF cells. At physiological temperature (37°C), however, INa,late became insignificant. Plateau phase and upstroke velocity of action potentials (APs) recorded with sharp microelectrodes in intact human trabeculae were more sensitive to ranolazine in AF than in SR preparations. Sodium channel subunits expression measured with qPCR was high for SCN5A with no difference between SR and AF. Expression of SCN8A and SCN10A was low in general, and lower in AF than in SR. In conclusion, We confirm for the first time a TTX-sensitive current (INa,late) in right atrial cardiomyocytes from SR and AF patients at room temperature, but not at physiological temperature. While our study provides evidence for the presence of INa,late in human atria, the potential of such current as a target for the treatment of AF remains to be demonstrated.

Dataset Information

Current perceptions of the epidemiology of atrial fibrillation.

Publications

Current perceptions of the epidemiology of atrial fibrillation.

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