Role of ideal cardiovascular health metrics in reducing risk of incident arrhythmias.

AIMS: Cardiovascular health (CVH) has been proven to reduce cardiovascular disease burden and mortality, but data are lacking regarding cardiac arrhythmias. The aim of this study was to assess the association between CVH metrics and atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias. METHODS AND RESULTS: This study analysed data from the Atherosclerosis Risk in Communities (ARIC) cohort, with participants recruited from four different communities across the United States. Cardiovascular health metrics were scored at baseline (1987-89) following the American Heart Association's recommendations and categorized as poor, intermediate, or ideal. Arrhythmia episodes were diagnosed by International Classification of Diseases (ICD)-9 code. Adjusted associations were estimated using Cox models and event rates and population attributable fractions were calculated by CVH metrics category. The study population consisted of 13 078 participants, with 2548 AF, 1363 ventricular arrhythmias, and 706 bradyarrhythmias occurred. The adjusted hazard ratios (HRs) for ideal (vs. poor) CVH metrics were 0.59 [95% confidence interval (CI): 0.50-0.69] for AF, 0.38 (95% CI: 0.28-0.51) for ventricular arrhythmias, and 0.70 (95% CI: 0.51-0.97) for bradyarrhythmia. The risk of incident arrhythmias decreased steadily as the CVH metrics improved from 0 to 14 scores. The adjusted population attributable fractions were calculated to be 29.9% for AF, 54.4% for ventricular arrhythmias, and 21.9% for bradyarrhythmia, respectively. The association between CVH metrics and incident arrhythmias was also seen in people who remained free of coronary heart disease over the follow-up. CONCLUSION: Achieving ideal CVH metrics recommendations by AHA in midlife was associated with a lower risk of incident arrhythmias later in life.

Intermediate and ideal levels of cardiovascular health (CVH) metrics are associated with a markedly reduced risk of developing incident arrhythmias, including atrial fibrillation/flutter, ventricular arrhythmias, and bradyarrhythmia, independent of coronary heart disease. A majority of incident arrhythmias could be prevented if the risk profile of the entire population was optimized. These findings emphasize the significance of public health policies that improve CVH to reduce the social and economic burden of arrhythmias.

Higher Cumulative Blood Pressure in Midlife Predicts an Increased Risk of Atrial Fibrillation: Evidence From the Atherosclerosis Risk in Communities Study.

BACKGROUND: Elevated blood pressure (BP) is reportedly associated with an increased risk of atrial fibrillation (AF). However, the association between cumulative BP exposure in midlife and incident AF in mid-to-late life remains unclear. METHODS AND RESULTS: Participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study with 4 consecutive BP measurements and no prevalent AF at baseline were included. Cumulative BP was calculated as the area under the curve from visit 1 to visit 4. Incident AF was identified by study visit ECGs, hospital discharge codes, or death certificates. A total of 9892 participants were included (44.6% men and mean age 62.9±5.7 years at visit 4) with 1550 (15.7%) individuals who developed new-onset AF during an average follow-up of 15.4 years. The incidence rates of AF per 1000 person-years across the 4 quartiles of cumulative systolic BP were 7.9, 9.2, 12.5, and 16.9, respectively. After multivariable adjustment, the hazard ratios for incident AF among participants in the highest quartile of cumulative systolic BP, pulse pressure, and mean arterial pressure were 1.48 (95% CI, 1.27-1.72), 1.81 (95% CI, 1.53-2.13), and 1.22 (95% CI, 1.05-1.41), respectively, compared with those in the lowest quartile. The addition of cumulative systolic BP or pulse pressure slightly improved the ability to predict new-onset AF. CONCLUSIONS: Higher exposure to cumulative systolic BP, pulse pressure, and mean arterial pressure was significantly associated with increased risk of incident AF.

Sacubitril/valsartan reduces susceptibility to atrial fibrillation by improving atrial remodeling in spontaneously hypertensive rats.

AIM: Sacubitril/valsartan (Sac/Val, LCZ696), the world's first angiotensin receptor-neprilysin inhibitor (ARNi), has been widely used in the treatment of heart failure. However, the use of Sac/Val in the treatment of atrial fibrillation (AF), especially AF with hypertension, has been less reported. We investigated the effect of Sac/Val on atrial remodeling and hypertension-related AF. METHODS: The AF induction rate and electrophysiological characteristics of spontaneously hypertensive rats (SHRs) treated with Sac/Val or Val were detected by rapid atrial pacing and electrical mapping/optical mapping. The whole-cell patch-clamp and Western blot were used to observe electrical/structural remodeling of atrial myocytes/tissue of rats and atrium-derived HL-1 cells cultured under 40 mmHg in vitro. RESULTS: Sac/Val was superior to Val in reducing blood pressure, myocardial hypertrophy and susceptibility of AF in SHRs. The shorten action potentials duration (APD), decreased L type calcium channel current (ICa,L) and Cav1.2, increased ultrarapid delayed rectified potassium current (Ikur) and Kv1.5 in atrial myocytes/tissue of SHRs could be better improved by Sac/Val, as well as the levels of atrial fibrosis. While the protein expression of angiotensin-converting enzyme-1 (ACE-1), angiotensin, angiotensin II type I AT1 receptor (AT1R) and neprilysin (NEP) were increased, which could be more effective ameliorated by Sac/Val than Val. Furthermore, Val + Sacubitrilat (LBQ657) (an active NEP inhibitor) was also superior to LBQ657 or Val in improving the electrical and structural remodeling of HL-1 cells through inhibiting NEP. CONCLUSION: Sac/Val can improve atrial structural and electrical remodeling induced by hypertension and reduce the AF susceptibility by inhibiting RAS and NEP. The above effects of Sac/Val were superior to Val alone.

Prevalence and incidence of heart failure among community in China during a three-year follow-up.

BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS: Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Acetyltransferase p300 regulates atrial fibroblast senescence and age-related atrial fibrosis through p53/Smad3 axis.

Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis. And then, biochemical assays and in vivo electrophysiological examination were performed on older AF patients, aging mice, and senescent atrial fibroblasts. The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac-p53)/p21, Smad3/p-Smads, and fibrosis-related factors. (2) p300 inhibitor curcumin and p300 knockdown treated aging mouse and senescence human atrial fibroblasts reduced the senescence ratio of atrial fibroblasts, ameliorated the atrial fibrosis, and decreased the AF inducibility. In contrast, over-expression of p300 can lead to the senescence of atrial fibroblasts and atrial fibrosis. (3) p53 knockdown decreased the expression of aging and fibrosis-related proteins. (4) Co-immunoprecipitation and immunofluorescence showed that p53 forms a complex with smad3 and directly regulates the expression of smad3 in atrial fibroblasts. Our findings suggest that the mechanism of atrial fibrosis induced by aging is, at least, partially dependent on the regulation of p300, which provides new sights into the AF treatment, especially for the elderly.

Atrial fibrillation mechanisms before and after pulmonary vein isolation characterized by noncontact charge density mapping.

BACKGROUND: The interaction of the pulmonary vein (PV) and putative nonpulmonary triggers of atrial fibrillation (AF) remains unclear and has yet to translate into patient-tailored ablation strategies. OBJECTIVE: The purpose of this study was to use noncontact mapping to detail the global conduction patterns in paroxysmal and persistent AF and how they are modified during PV ablation. METHODS: Forty patients during AF ablation underwent mapping using a noncontact catheter (AcQMap, Acutus Medical, Inc., Carlsbad, CA) before and after PV isolation (PVI). Propagation history maps were analyzed postprocedure for each patient to categorize conduction patterns into focal, organized reentrant, and disorganized patterns (F-Patterns, O-Patterns, and D-Patterns, respectively). RESULTS: Activation patterns identified by using a noncontact mapping system can be subclassified from 3 main patterns into subtypes (macroreentrant and localized reentrant [MR and LR] subtypes and disorganized 1 and disorganized 2 [D1 and D2] subtypes). Persistent AF demonstrated more D-Patterns and less O-Patterns and F-Patterns than did paroxysmal AF. In addition, patients with PAF inducible after PVI demonstrated a higher region number and higher prevalence of MR subtypes than did those noninducible. PVs remained the critical region and included almost one-third of all patterns across any AF types. PVI was effective to eliminate PV-related functional phenotypes and affected recurrence with other patterns. CONCLUSION: Activation patterns identified using AcQMap can be classified into 3 main patterns (F-Patterns, O-Patterns, and D-Patterns) as well as subtypes (MR and LR subtypes and D1 and D2 subtypes). PerAF was different from PAF in demonstrating a higher region number and higher prevalence of D-Patterns but a lower region number and lower prevalence of O-Patterns and F-Patterns.

Piezo1 Participated in Decreased L-Type Calcium Current Induced by High Hydrostatic Pressure via. CaM/Src/Pitx2 Activation in Atrial Myocytes.

Hypertension is a major cardiovascular risk factor for atrial fibrillation (AF) worldwide. However, the role of mechanical stress caused by hypertension on downregulating the L-type calcium current (ICa,L), which is vital for AF occurrence, remains unclear. Therefore, the aim of the present study was to investigate the role of Piezo1, a mechanically activated ion channel, in the decrease of ICa,L in response to high hydrostatic pressure (HHP, one of the principal mechanical stresses) at 40 mmHg, and to elucidate the underlying pathways. Experiments were conducted using left atrial appendages from patients with AF, spontaneously hypertensive rats (SHRs) treated with valsartan (Val) at 30 mg/kg/day and atrium-derived HL-1 cells exposed to HHP. The protein expression levels of Piezo1, Calmodulin (CaM), and Src increased, while that of the L-type calcium channel a1c subunit protein (Cav1.2) decreased in the left atrial tissue of AF patients and SHRs. SHRs were more vulnerable to AF, with decreased ICa,L and shortened action potential duration, which were ameliorated by Val treatment. Validation of these results in HL-1 cells in the context of HHP also demonstrated that Piezo1 is required for the decrease of ICa,L by regulating Ca2+ transient and activating CaM/Src pathway to increase the expression of paired like homeodomain-2 (Pitx2) in atrial myocytes. Together, these data demonstrate that HHP stimulation increases AF susceptibility through Piezo1 activation, which is required for the decrease of ICa,L via. the CaM/Src/Pitx2 pathway in atrial myocytes.

Connexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the current density of ICa,L and ICa,T . Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Prevalence and modifiable risk factors of degenerative valvular heart disease among elderly population in southern China.

OBJECTIVE: To investigate the prevalence and modifiable risk factors of degenerative valvular heart disease (DVHD) among elderly population in southern China. METHODS: A stratified multistage sampling method was used to recruit subjects. The contents of the survey included the questionnaire, laboratory examination, echocardiography, and other auxiliary examinations. The possible risk factors of DVHD were analyzed by logistic regression analysis. RESULTS: A total of 3538 subjects ≥ 65 years of age were enrolled. One thousand three hundred and seven subjects (36.9%) were diagnosed with DVHD. Degenerative was the most common etiology of VHD. Prevalence of DVHD increased with advancing age. The prevalence of DVHD differed by living region (χ 2 = 45.594, P < 0.001), educational level ( χ 2 = 50.557, P < 0.001), and occupation ( χ 2 = 36.961, P < 0.001). Risk factors associated with DVHD included age (two-fold increased risk for each 10-year increase in age), elevated level C-reactive protein (OR = 1.346, 95% CI: 1.100-1.646), elevated level low density lipoprotein (OR = 1.243, 95% CI: 1.064-1.451), coronary artery disease (OR = 1.651, 95% CI: 1.085-2.513), smoking (OR = 1.341, 95% CI: 1.132-1.589), and hypertension (OR = 1.414, 95% CI: 1.221-1.638). Other significant risk factors included reduced or elevated level red blood cell (OR = 1.347, 95% CI: 1.031-1.761; OR = 1.599, 95% CI: 1.097-2.331; respectively), elevated level platelets (OR = 1.891, 95% CI: 1.118-3.198), elevated level uric acid (OR = 1.282, 95% CI: 1.112-1.479), and stroke (OR: 1.738, 95% CI = 1.085-2.513). CONCLUSIONS: The survey characterized the baseline conditions of DVHD cohort of elderly population in Guangzhou city. The established and emerging risk factors for DVHD may represent challenges and opportunities for therapy.

High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy.

Mitochondrial dysfunction and impaired Ca2+ handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its level of phosphorylation, and the Orai1 (Ca2+ release-activated calcium channel protein 1) calcium channel is important for the increase in Ca2+ entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca2+ influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca2+ entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1-Drp1 axis is a novel target for treating DCM.

Activation of PKCα participates in the reduction of Ikur in atrial myocytes induced by tumour necrosis factor-α.

The atrial-specific ultra-rapid delayed rectifier K+ current (Ikur) plays an important role in the progression of atrial fibrillation (AF). Because inflammation is known to lead to the onset of AF, we aimed to investigate whether tumour necrosis factor-α (TNF-α) played a role in regulating Ikur and the potential signalling pathways involved. Whole-cell patch-clamp and biochemical assays were used to study the regulation and expression of Ikur in myocytes and in tissues from left atrial appendages (LAAs) obtained from patients with sinus rhythm (SR) or AF, as well as in rat cardiomyocytes (H9c2 cells) and mouse atrial myocytes (HL-1 cells). Ikur current density was markedly reduced in atrial myocytes from AF patients compared with SR controls. Reduction of Kv1.5 protein levels was accompanied by increased expression of TNF-α and protein kinase C (PKC)α activation in AF patients. Treatment with TNF-α dose-dependently reduced Ikur and protein expression of Kv1.5 but not Kv3.1b in H9c2 cells and HL-1 cells. TNF-α also increased activity of PKCα. Specific PKCα inhibitor Gö6976 alleviated the reduction in Ikur induced by TNF-α, but not the reduction in Kv1.5 protein. TNF-α was involved in the electrical remodelling associated with AF, probably by depressing Ikur in atrial myocytes via activation of PKCα.

Left atrial enlargement and non-paroxysmal atrial fibrillation as risk factors for left atrial thrombus/spontaneous Echo contrast in patients with atrial fibrillation and low CHA2DS2-VASc score.

OBJECTIVE: To determine the risk factors for thromboembolism in lower risk patients with non-valvular atrial fibrillation (AF) and low CHA2DS2-VASc scores, which remain undefined. METHODS: We retrospectively analyzed the baseline clinical characteristics, routine laboratory parameters, and echocardiographic measurements of 705 patients (71.1% male; mean age: 52.10 ± 9.64 years) with low CHA2DS2-VASc score (0 or 1; 1 point for female sex) out of 1346 consecutive patients with non-valvular AF who underwent transesophageal echocardiography (TEE) at Guangdong Cardiovascular Institute between January 2013 and December 2015. RESULTS: Patients with left atrial thrombus (LAT) or spontaneous echo contrast (SEC) on TEE (24/705, 4%) showed a higher incidence rate of vascular disease (54.2% vs. 32.9%, P = 0.045) and non-paroxysmal AF (79.2% vs. 29.4%, P < 0.001), larger left atrial diameter (43.08 ± 4.59 vs. 36.02 ± 5.53 mm, P < 0.001), and lower left ventricular ejection fraction (58.23 ± 8.82% vs. 64.15 ± 7.14%, P < 0.001) than those without. Multivariate logistic regression analysis identified left atrial diameter [odds ratio (OR) = 1.171, 95% confidence interval (CI): 1.084-1.265, P < 0.001] and non-paroxysmal AF (OR = 3.766, 95% CI: 1.282-11.061, P = 0.016) as independent risk factors for LAT/SEC. In ROC curve analysis, a left atrial dimeter cutoff of 37.5 mm yielded 95.0% sensitivity and 62.7% specificity (AUC: 0.847, P < 0.0001, 95% CI: 0.793-0.914). CONCLUSION: In patients with non-valvular AF with low CHA2DS2-VASc score, the presence of LAT or SEC was associated with left atrial enlargement, which had moderate predictive value, and non-paroxysmal AF.

Abnormal Ca2+ handling contributes to the impairment of aortic smooth muscle contractility in Zucker diabetic fatty rats.

Vascular dysfunction is a common pathological basis for complications in individuals affected by diabetes. Previous studies have established that endothelial dysfunction is the primary contributor to vascular complications in type 2 diabetes (T2DM). However, the role of vascular smooth muscle cells (VSMCs) in vascular complications associated with T2DM is still not completely understood. The aim of this study is to explore the potential mechanisms associated with Ca2+ handling dysfunction and how this dysfunction contributes to diabetic vascular smooth muscle impairment. The results indicated that endothelium-dependent vasodilation was impaired in diabetic aortae, but endothelium-independent vasodilation was not altered. Various vasoconstrictors such as phenylephrine, U46619 and 5-HT could induce vasoconstriction in a concentration-dependent manner, such that the dose-response curve was parallel shifted to the right in diabetic aortae, compared to the control. Vasoconstrictions mediated by L-type calcium (Cav1.2) channels were attenuated in diabetic aortae, but effects mediated by store-operated calcium (SOC) channels were enhanced. Intracellular Ca2+ concentration ([Ca2+]i) in VSMCs was detected by Fluo-4 calcium fluorescent probes, and demonstrated that SOC-mediated Ca2+ entry was increased in diabetic VSMCs. VSMC-specific knockout of STIM1 genes decreased SOC-mediated and phenylephrine-induced vasoconstrictive response in mice aortae. Additionally, Orai1 expression was up-regulated, Cav1.2 expression was downregulated, and the phenotypic transformation of diabetic VSMCs was determined in diabetic aortae. The overexpression of Orai1 markedly promoted the OPN expression of VSMCs, whereas SKF96365 (SOC channel blocker) reversed the phenotypic transformation of diabetic VSMCs. Our results demonstrated that the vasoconstriction response of aortic smooth muscle was weakened in type 2 diabetic rats, which was related to the downregulation of the Cav1.2 channel and the up-regulation of the SOC channel signaling pathway.

Inability to capture with increasing current strength: Is this near-field or far-field?

We present a case of wide-complex tachycardia in which the clinical electrophysiological diagnosis was considered to be bundle branch re-entry ventricular tachycardia. A series of ventricular entrainment attempts were performed from the left and right ventricular septum to confirm the diagnosis. Entrainment pacing with a general current output (10 mA) was performed from the right ventricular septum with manifest fusion and a post-pacing interval similar to tachycardia cycle length. Thereafter, another entrainment attempt with a greater current output (20 mA) was performed from the same site. Paradoxically, concealed fusion was demonstrated by selective RB capture only, though there was no clear "RB" potential seen. In this case, we attempt to explain and illustrate the mechanism of paradoxical near-field inability to capture with increasing current strength.

High hydrostatic pressure induces atrial electrical remodeling through angiotensin upregulation mediating FAK/Src pathway activation.

Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes.

High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines.

AIMS: Hypertension is an independent risk factor for atrial fibrillation (AF). However, the direct effect of hydrostatic pressure on atrial electrical remodeling is unclear. The present study investigated whether hydrostatic pressure is responsible for atrial electrical remodeling and addressed a potential role of inflammation in this pathology. MAIN METHODS: Whole-cell patch-clamp recordings and biochemical assays were used to study the regulation and expression of ion channels in left atrial appendages in patients with AF, spontaneously hypertensive rats (SHRs), and atrium-derived cells (HL-1 cells) exposed to standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. KEY FINDINGS: Both TNF-α and MIF were highly expressed in patients with AF and SHRs. AF inducibility in SHRs was higher after atrial burst pacing, accompanied by a decrease in the L-type calcium current (ICa,L), an increase in the transient outward K+ current (Ito) and ultra-rapid delayed rectifier K+ current (IKur), and a shortened action potential duration (APD), which could be inhibited by atorvastatin. Furthermore, exposure to elevated pressure was associated with electrical remodeling of the HL-1 cells. The peak current density of ICa,L was reduced, while Ito and IKur were increased. Moreover, the expression levels of Kv4.3, Kv1.5, TNF-α, and MIF were upregulated, while the expression of Cav1.2 was downregulated in HL-1 cells after treatment with high hydrostatic pressure (40 mmHg). Atorvastatin alleviated the electrical remodeling and increased inflammatory markers in HL-1 cells induced by high hydrostatic pressure. SIGNIFICANCE: Elevated hydrostatic pressure led to atrial electrical remodeling and increased AF susceptibility by upregulating inflammation.

Association between elevated blood glucose level and non-valvular atrial fibrillation: a report from the Guangzhou heart study.

BACKGROUND: To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China. METHODS: The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence. RESULTS: The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40-2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14-2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12-2.91, P = 0.016). CONCLUSIONS: In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.

High prevalence of hyperuricaemia and its impact on non-valvular atrial fibrillation: the cross-sectional Guangzhou (China) Heart Study.

OBJECTIVES: There are country and regional variations in the prevalence of hyperuricaemia (HUA). The prevalence of HUA and non-valvular atrial fibrillation (NVAF) in southern China is unknown. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 11 488 permanent residents aged 35 or older from urban and rural areas of Guangzhou, China were enrolled. A questionnaire was used to compile each participant's demographic information and relevant epidemiological factors for HUA and NVAF. All participants were assessed using a panel of blood tests and single-lead 24-hour ECG. MAIN OUTCOME MEASURES: HUA was defined as serum uric acid level >420 µmol/L in men and >360 µmol/L in women. NVAF was diagnosed as per guidelines. RESULTS: The prevalence of HUA was 39.6% (44.8% in men and 36.7% in women), and 144 residents (1.25%) had NVAF. Prevalence of HUA increased with age in women but remained stably high in men. After adjusting for potential confounders, age, living in urban areas, alcohol consumption, central obesity, elevated fasting plasma glucose level, elevated blood pressure, lower high-density lipoprotein cholesterol level and elevated triglycerides level were associated with increased risk of HUA. Residents with HUA were at higher risk for NVAF. Serum uric acid level had a modest predictive value for NVAF in women but not men. CONCLUSIONS: HUA was highly prevalent among citizens of southern China and was a predictor of NVAF among women.

Unique electrocardiographic pattern "w" wave in lead I of idiopathic ventricular arrhythmias arising from the distal great cardiac vein.

BACKGROUND: The ECG characteristics of the distal coronary venous system ventricular arrhythmias (VAs) share common features with VAs arising from the aortic cusps or the endocardial left ventricular outflow tract (LVOT) beneath the cusps. The purpose of this study was to identify specific electrocardiographic and electrophysiological characteristics of VAs originating from the distal great cardiac vein (GCV). METHODS: Based on the successful ablation site, patients with idiopathic VAs from the distal GCV, left coronary cusp (LCC) or the subvalvular left ventricular outflow tract (LVOT) area were included in the present study. RESULTS: The final population consisted of 39 patients (35 males, mean age 51 ± 23 years). All VAs displayed a right bundle branch block (RBBB) morphology with inferior axis. Among these patients, 15 were successfully ablated at the GCV, 15 at the LCC and 9 at the subvalvular region. A "w" pattern in lead I was present in 12 out of 15 (80%) VAs originating from the distal GCV compared to none of VAs arising from the other two sites (p < 0.01). VAs with a GCV origin exhibited more commonly increased intrinsicoid deflection time, higher maximum deflection index and wider QRS duration compared to LCC and subvalvular sites (p < 0.05). Acceptable pace mapping at the successful ablation site was achieved in 10 patients. After an average of 36 ± 24 months follow up, 14 (93.3%) patients were free from VAs recurrence. CONCLUSION: A "w" pattern in lead I may distinguish distal GCV VAs from VAs arising from the LCC or the subvalvular region.