Moon‐Hyoung Lee

Ventricular fibrillation is the leading cause of sudden cardiac death. In fibrillation, fragmented electrical waves meander erratically through the heart muscle, creating disordered and ineffective contraction. Theoretical and computer studies, as well as recent experimental evidence, have suggested that fibrillation is created and sustained by the property of restitution of the cardiac action potential duration (that is, its dependence on the previous diastolic interval). The restitution hypothesis states that steeply sloped restitution curves create unstable wave propagation that results in wave break, the event that is necessary for fibrillation. Here we present experimental evidence supporting this idea. In particular, we identify the action of the drug bretylium as a prototype for the future development of effective restitution-based antifibrillatory agents. We show that bretylium acts in accord with the restitution hypothesis: by flattening restitution curves, it prevents wave break and thus prevents fibrillation. It even converts existing fibrillation, either to a periodic state (ventricular tachycardia, which is much more easily controlled) or to quiescent healthy tissue.

The factors that contribute to the occurrence of sudden cardiac death (SCD) in patients with chronic myocardial infarction (MI) are not entirely clear. The present study tests the hypothesis that augmented sympathetic nerve regeneration (nerve sprouting) increases the probability of ventricular tachycardia (VT), ventricular fibrillation (VF), and SCD in chronic MI. In dogs with MI and complete atrioventricular (AV) block, we induced cardiac sympathetic nerve sprouting by infusing nerve growth factor (NGF) to the left stellate ganglion (experimental group, n=9). Another 6 dogs with MI and complete AV block but without NGF infusion served as controls (n=6). Immunocytochemical staining revealed a greater magnitude of sympathetic nerve sprouting in the experimental group than in the control group. After MI, all dogs showed spontaneous VT that persisted for 5.8+/-2.0 days (phase 1 VT). Spontaneous VT reappeared 13.1+/-6.0 days after surgery (phase 2 VT). The frequency of phase 2 VT was 10-fold higher in the experimental group (2.0+/-2.0/d) than in the control group (0.2+/-0.2/d, P<0.05). Four dogs in the experimental group but none in the control group died suddenly of spontaneous VF. We conclude that MI results in sympathetic nerve sprouting. NGF infusion to the left stellate ganglion in dogs with chronic MI and AV block augments sympathetic nerve sprouting and creates a high-yield model of spontaneous VT, VF, and SCD. The magnitude of sympathetic nerve sprouting may be an important determinant of SCD in chronic MI.

AIMS: Atrial fibrillation (AF) is generally regarded as a risk factor for dementia, though longitudinal studies assessing the association between AF and dementia have shown inconsistent results. This study aimed to determine the effect of AF on the risk of developing dementia using a longitudinal, community-based, and stroke-free elderly cohort. METHODS AND RESULTS: The association of incident AF with the development of incident dementia was assessed from 2005 to 2012 in 262 611 dementia- and stroke-free participants aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. Incident AF was observed in 10 435 participants over an observational period of 1 629 903 person-years (0.64%/year). During the observational period, the incidence of dementia was 4.1 and 2.7 per 100 person-years in the incident AF and propensity score-matched AF-free groups, respectively. After adjustment, the risk of dementia was significantly increased by incident AF with a hazard ratio (HR) of 1.52 [95% confidence interval (CI) 1.43-1.63], even after censoring for stroke (1.27, 95% CI 1.18-1.37). Incident AF increased the risk of both Alzheimer (HR 1.31, 95% CI 1.20-1.43) and vascular dementia (HR 2.11, 95% CI 1.85-2.41). Among patients with incident AF, oral anticoagulant use was associated with a preventive effect on dementia development (HR 0.61, 95% CI 0.54-0.68), and an increasing CHA2DS2-VASc score was associated with a higher risk of dementia. CONCLUSION: Incident AF was associated with an increased risk of dementia, independent of clinical stroke in an elderly population. Oral anticoagulant use was linked with a decreased incidence of dementia.

Background An integrated care approach might be of benefit for clinical outcomes of patients with atrial fibrillation (AF). This study evaluated whether compliance with the Atrial fibrillation Better Care (ABC) pathway for integrated care management (“A” Avoid stroke; “B” Better symptom management; “C” Cardiovascular risk and Comorbidity optimization) would improve population-based clinical outcomes in a nationwide AF cohort. Methods and Results From the Korea National Health Insurance Service database, a total of 204,842 nonvalvular AF patients were enrolled between January 1, 2005 and December 31, 2015. Patients that fulfilled all criteria of the ABC pathway were defined as the “ABC” group, and those who did not were the “Non-ABC” group. Over a mean follow-up of 6.2 ± 3.5 years, the ABC pathway compliant group had lower rates of all-cause death (0.80 vs. 2.72 per 100 person-years, p &lt; 0.001) and the composite outcome of “death, ischemic stroke, major bleeding, and myocardial infarction” (2.34 vs. 5.92 per 100 person-years, p &lt; 0.001) compared with the Non-ABC compliant group. Adjusted Cox multivariable regression showed that the ABC group had a significantly lower risk of all-cause death (adjusted hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.78–0.86) and the composite outcome (adjusted HR 0.86; 95% CI, 0.83–0.89). With the increasing numbers of ABC pathway criteria fulfilled, the risk of all-cause death and composite outcome were progressively lowered. Conclusion In the first study of a nationwide population cohort, we show that compliance with the simple ABC pathway is associated with improved clinically relevant outcomes of patients with AF. Given the high health care burden associated with AF, such a streamlined holistic approach to AF management should be implemented, to improve the care of such patients.

BACKGROUND: Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. METHOD AND RESULTS: We performed rapid right atrial pacing in 6 dogs for 111+/-76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470+/-406 and 231+/-126 per mm(2), respectively, which was significantly (P:<0.001) higher than the nerve density in control tissues (25+/-32 and 88+/-40 per mm(2), respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317+/-36 and 155+/-85 per mm(2), respectively, and was significantly (P:<0.001) higher than the nerve density in control tissues (9+/-13 and 30+/-7 per mm(2), respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119+/-61 and 91+/-40 per mm(2), respectively, which was significantly (P:<0.001) higher than the nerve density in control tissues (10+/-15 and 38+/-39 per mm(2), respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. CONCLUSIONS: Significant nerve sprouting and sympathetic hyperinnervation are present in a canine model of sustained AF produced by prolonged right atrial pacing. The magnitude of nerve sprouting and hyperinnervation was higher in the right atrium than in the left atrium.