Anti-Arrhythmic Mechanisms of Epidural Blockade After Myocardial Infarction.

BACKGROUND: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachycardia and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction. METHODS: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (Smax) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation. RESULTS: TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity. CONCLUSIONS: TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in Smax, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.

Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Surgically Metabolic Resection of Pericardial Fat to Ameliorate Myocardial Mitochondrial Dysfunction in Acute Myocardial Infarction Obese Rats.

BACKGROUND: Pericardial fat (PF) is highly associated with cardiovascular disease but the effectiveness of surgical resection of PF is still unknown for myocardial mitochondrial structure and function in acute myocardial infarction (AMI) with obesity. The aim of this study was to demonstrate the difference in myocardial mitochondrial structure and function between obese AMI with additionally resected PF and those without resected PF. METHODS: Obese rats with 12-week high fat diet (45 kcal% fat, n = 21) were randomly assigned into 3 groups: obese control, obese AMI and obese AMI with additionally resected PF. One week after developing AMI and additional resection of PF, echocardiogram, myocardial mitochondrial histomorphology, oxidative phosphorylation system (OXPHOS), anti-oxidative enzyme and sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) in the non-infarcted area were assessed between these groups. RESULTS: There was significant improvement of systolic function in AMI with PF resection compared with the AMI group in the echocardiogram. Even though the electron microscopic morphology for the mitochondria seems to be similar between the AMI with PF resection and AMI groups, there was an improved expression of PGC-1α and responsive OXPHOS including NDUFB3, NDUFB5 and SDHB are associated with the ATP levels in the AMI with PF resection compared with those in the AMI group. In addition, the expression levels of antioxidant enzymes (MnSOD) and SERCA2 were improved in the AMI with PF resection compared with those in the AMI group. CONCLUSION: Surgical resection of PF might ameliorate myocardial mitochondria dysfunction in obese AMI.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Risk of New-Onset Acute Coronary Syndrome and Atrial Fibrillation in Patients With Rheumatoid Arthritis Compared With a Risk-Set and Propensity Score-Matched Cohort　- A Nationwide Cohort Study.

BACKGROUND: Rheumatoid arthritis (RA) has extra-articular manifestations of cardiovascular diseases and is associated with a high mortality rate in Western populations. This study aimed to investigate the risk of acute coronary syndrome (ACS) and atrial fibrillation (AF) associated with RA in a Korean population.Methods and Results:Patients were selected from a senior cohort from the Korean National Health Insurance Service in 2002, and followed until 31 December 2015. Patients with newly developed ACS and AF were identified and compared with controls for a 10-year period using time-dependent propensity and risk-set matching. A total of 4,217 incident RA patients and their 8,432 controls comprised the incident RA and matched cohorts, respectively. ACS was identified during 24,642 person-years [incidence rate (IR) 402 per 10,000 person-years, 95% confidence interval (CI) 330-489] among the RA cohort. In the matched cohort, 141 ACS patients were identified during 50,011 person-years (IR 282 per 100,000 person-years, 95% CI 239-333). RA patients were 1.43-fold more likely to develop ACS than the matched controls [hazard ratio (HR) 1.43, 95% CI 1.10-1.84], but showed similar occurrence risk of AF (HR 1.06, 95% CI 0.83-1.35). CONCLUSIONS: A higher risk for ACS and a similar risk for AF were found by risk-set matched analysis in a senior RA cohort compared with the control, using Korean nationwide long-term data.

Pre-implant global longitudinal strain as an early sign of pacing-induced cardiomyopathy in patients with complete atrioventricular block.

INTRODUCTION: Long-term right ventricular pacing is the only treatment for patients with a complete atrioventricular block (CAVB); however, it frequently triggers ventricular dys-synchrony with left ventricular (LV) dysfunction. Previous studies showed that an early decline of LV global longitudinal strain (GLS) predicts pacing-induced LV dysfunction. We aimed to investigate the potential ability of the initial LV strain to predict pacing-induced cardiomyopathy (PICM) through long-term follow-ups. METHODS: We retrospectively enrolled 80 patients with CAVB with normal LV function who were implanted with dual-chamber pacemakers between 2008 and 2018. Echocardiographic data and parameters (including longitudinal, radial, and circumferential strain based on speckle-tracking) were analyzed for the pre-implant (≤6 months) and post-implant periods. PICM was defined as a ≥10% reduction in the left ventricular ejection fraction (LVEF) resulting in an LVEF of <50% during the post-implant period. Predictors of PICM were identified using Cox proportional hazard models. RESULTS: Patients who developed PICM were more likely to exhibit lower baseline LV GLS, as well as wider native and pacing QRS durations, than those who did not develop PICM (P = .016, P = .011, and P = .026, respectively). In the multivariate analysis, pre-implant LV GLS (hazard ratio: 1.27; 95% confidence interval 1.009-1.492; P = .004) was independently associated with the development of PICM. CONCLUSION: A lower baseline LV GLS predicts an increased risk of PICM. Patients with CAVB exhibiting low GLS are at increased risk of PICM. More frequent follow-up visits are warranted in these patients, who may also require de novo His-bundle pacing or an upgrade to biventricular pacing.

Usefulness of an Implantable Loop Recorder in Diagnosing Unexplained Syncope and Predictors for Pacemaker Implantation.

BACKGROUND: An implantable loop recorder (ILR) is an effective tool for diagnosing unexplained syncope (US). We examined the diagnostic utility of an ILR in detecting arrhythmic causes of US and determining which clinical factors are associated with pacemaker (PM) implantation. METHODS: This retrospective, multicenter, observational study was conducted from February 2006 to April 2018 at 11 hospitals in Korea. Eligible patients with recurrent US received an ILR to diagnose recurrent syncope and document arrhythmia. RESULTS: A total of 173 US patients (mean age, 67.6 ± 16.5 years; 107 men [61.8%]) who received an ILR after a negative conventional workup were enrolled. During a mean follow-up of 9.4 ± 11.1 months, 52 patients (30.1%) had recurrent syncope, and syncope-correlated arrhythmia was confirmed in 34 patients (19.7%). The ILR analysis showed sinus node dysfunction in 24 patients (70.6%), supraventricular tachyarrhythmia in 4 (11.8%), ventricular arrhythmia in 4 (11.8%), and sudden atrioventricular block in 2 (5.9%). Overall, ILR detected significant arrhythmia in 99 patients (57.2%) irrespective of syncope. Among patients with clinically relevant arrhythmia detected by ILR, PM implantation was performed in 60 (34.7%), an intra-cardiac defibrillator in 5 (2.9%), and catheter ablation in 4 (2.3%). In a Cox regression analysis, history of paroxysmal atrial fibrillation (PAF) (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.33-4.12; P < 0.01) and any bundle branch block (BBB) (HR, 2.52; 95% CI, 1.09-5.85; P = 0.03) were significantly associated with PM implantation. CONCLUSION: ILR is useful for detecting syncope-correlated arrhythmia in patients with US. The risk of PM is high in US patients with a history of PAF and any BBB.

Implantable Cardioverter Defibrillator Shocks and Psychological Distress: Examining the Mediating Roles of Implantable Cardioverter Defibrillator-Related Concerns and Perceived Control.

BACKGROUND: Although the implantable cardioverter defibrillator (ICD) has a survival benefit for the prevention of sudden cardiac death, ICD recipients commonly experience emotional distress as a consequence of ICD shocks. OBJECTIVE: The aim of this study was to examine whether the association between ICD shocks and psychological distress (anxiety and depressive symptoms) is mediated by ICD-related concerns and perceived control among ICD recipients. METHODS: This was a multinational cross-sectional observational study of 334 ICD recipients. Patients reported the number of shocks received since ICD implantation and completed questionnaires to assess anxiety, depressive symptoms, ICD-related concerns, and perceived control. A path analysis was conducted to explore the relationship of receiving ICD shocks with anxiety and depressive symptoms and the mediating effects of ICD-related concerns and perceived control. RESULTS: Of the 334 ICD recipients, 39.2% experienced ICD shocks at least once since implantation. There was no direct effect of ICD shocks on anxiety and depressive symptoms. Experiencing ICD shocks was indirectly associated with an increased likelihood of anxiety and depressive symptoms via the pathways of ICD-related concerns and perceived control (indirect effects on anxiety = 0.060, 0.043; indirect effect on depressive symptoms = 0.025, 0.073). CONCLUSION: Experiencing defibrillator shocks was associated with psychological distress in ICD recipients; the relationship was fully mediated by ICD-related concerns and perceived control. These results suggest that clinicians should routinely assess ICD-related concerns and perceived control in patients with ICD. Research is needed to develop and test interventions to decrease emotional distress related to the ICD shock experience.

Long-term changes in heart rate variability after radiofrequency catheter ablation for atrial fibrillation: 1-year follow-up study with irrigation tip catheter.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) changes cardiac autonomic nerve activity. However, the long-term effect of RFCA has not yet been evaluated when an open irrigation tip catheter (OITC) was used. Therefore, we hypothesized that AF ablation changes heart rate variability (HRV) that would be maintained over 1 year after OITC ablation and be associated with clinical recurrence of AF. METHODS AND RESULTS: We analyzed pre-RFCA HRV (HRVpre ), HRV at 3 months (HRV3mo ) and 1 year (HRV1yr ) after RFCA using 24-hour Holter monitoring after excluding arrhythmic events in 144 patients (70% male, 57 ± 10 years old, 83% paroxysmal AF) who underwent RFCA with OITC. After RFCA with OITC, the increase in mean heart rate and the reduction in HF or LF/HF were significant at HRV3mo (P < 0.001) and were maintained at HRV1yr (P < 0.001). During 20 ± 8 months of follow-up, 33 of 144 patients (23%) showed clinical recurrence of AF. Patients in the nonrecurrence group showed significant reductions of rMSSD and HF at HRV3mo and HRV1yr , but patients with clinical recurrence did not. In Cox regression analysis, a reduction in LF/HF (ΔLF/HF) ≥0.26 at HRV3mo was significantly associated with clinical recurrence of AF (hazard ratio 2.52, 95% CI 1.19-5.32, P = 0.015). CONCLUSION: In contrast to previous reports about long-term HRV recovery after AF ablation with a conventional catheter, change in cardiac autonomic nervous activity was maintained for 1 year after RFCA when an OITC was used. A reduction in ΔLF/HF ≥0.26 at HRV3mo was independently associated with clinical recurrence of AF after RFCA.

Additional linear ablation from the superior vena cava to right atrial septum after pulmonary vein isolation improves the clinical outcome in patients with paroxysmal atrial fibrillation: prospective randomized study.

AIMS: Although circumferential pulmonary vein isolation (CPVI) has been considered as the cornerstone for paroxysmal atrial fibrillation (PAF) ablation, there has been a substantial recurrence rate. We conducted a prospectively randomized study to evaluate whether additional linear ablation from the superior vena cava (SVC) to the right atrial (RA) septum (SVC-L) improves the clinical outcome. METHODS AND RESULTS: This study enroled 200 patients with PAF (male 74.5%, 56.8 ± 11.7 years old) randomly assigned to either the CPVI (n = 100) or CPVI + SVC-L (n = 100) groups. An RA isthmus ablation was performed in all patients. The CPVI + SVC-L group required a longer ablation procedure time (82.7 ± 17.9 min) than the CPVI group (63.6 ± 16.8 min, P < 0.001). The complication rates were 5% in CPVI + SVC-L group and 2% in CPVI group, respectively (P = 0.445). Two CPVI + SVC-L group patients had post-procedural sinus node dysfunction, which recovered within 24 h. During 12.2 ± 5.3 months of follow-up, the recurrence rate was significantly lower in the CPVI + SVC-L group (6%) than the CPVI group (27%, P < 0.001). The post-procedural 3-month follow-up heart rate variability in the CPVI + SVC-L group showed a significantly greater reduction in the rMSSD (25.2 ± 13.7 vs. 13.7 ± 8.5 ms, P < 0.001), HF (10.2 ± 7.1 vs. 5.5 ± 5.8 ms(2), P < 0.001), and LF/HF (1.6 ± 0.5 vs. 0.9 ± 0.3, P < 0.001) than in the CPVI group. CONCLUSION: In spite of a longer procedure time and risk of transient sinus node dysfunction, an SVC-L in addition to CPVI improved the clinical outcome of catheter ablation, and was associated with post-procedural autonomic neural remodelling in patients with PAF.

The feasibility of the initial postsystolic to systolic strain rate ratio as a predictor of the viability of ischemic myocardium with acute myocardial infarction.

BACKGROUND: Investigations of a strain index for the viability of ischemic myocardium with acute myocardial infarction (AMI) have been challenging. Therefore, the aim of this study was to evaluate patients with AMI to determine an optimal strain index for predicting the viability of ischemic myocardium. METHODS AND RESULTS: A total of 57 patients with AMI were assessed according to two-dimensional (2D) speckle tracking imaging strain and strain rate (SR), measured during the acute phase before urgent revascularization and at a 1-year follow-up postrevascularization. During the acute phase, all the myocardial segments were classified according to the acute end-systolic strain (Ses) values as normal (Ses ≤ -13%), hypocontractile (-13% < Ses ≤ -7%), or having a severe contractile abnormality (Ses > -7%). At the 1-year follow-up, we reassessed the recovery of the segments with a severe contractile abnormality. The viability of these segments was defined as an improved Ses (≤ -7%) at follow-up postrevascularization. The Ses values, postsystolic strain index (PSI), and SR values were significantly better in the viable segments than in the nonviable segments at both the acute phase and at follow-up (P < 0.001). The initial postsystolic to systolic SR ratio (SRps/SRs) had the best area under the curve (AUC = 0.897). In addition, a cutoff value of 0.6 predicted recovery from a severe contractile abnormality with a sensitivity of 75% and a specificity of 88%. CONCLUSIONS: The initial SRps/SRs ratio identified the viability of ischemic myocardium with AMI; therefore, this novel index may be clinically useful in the treatment of patients with AMI.

Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation.

Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction. Methods: MI was created in Yorkshire pigs ( N =22) by LAD occlusion. Six weeks post-MI, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. RV and LV hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation-recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity (BRS) and intrinsic cardiac neural activity, and ventricular effective refractory periods (ERP) and slope of restitution (S max ) were assessed before and after TEA. VT/VF inducibility was assessed by programmed electrical stimulation. Results: TEA reduced inducibility of VT/VF by 70%. TEA did not affect RV-systolic pressure or contractility, although LV-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular ERPs prolonged significantly at critical sites of arrhythmogenesis, and S max was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both BRS and intrinsic cardiac neural activity. Conclusion: TEA does not compromise RV function in infarcted hearts. Its anti-arrhythmic mechanisms are mediated by increases in ventricular ERP and ARIs, decreases in S max , and reductions in border zone heterogeneity. TEA improves parasympathetic function, which may independently underlie some of its observed anti-arrhythmic mechanisms. This study provides novel insights into the anti-arrhythmic mechanisms of TEA, while highlighting its applicability to the clinical setting. Abstract Illustration: Myocardial infarction is known to cause cardiac autonomic dysfunction characterized by sympathoexcitation coupled with reduced vagal tone. This pathological remodeling collectively predisposes to ventricular arrhythmia. Thoracic epidural anesthesia not only blocks central efferent sympathetic outflow, but by also blocking ascending projections of sympathetic afferents, relieving central inhibition of vagal function. These complementary autonomic effects of thoracic epidural anesthesia may thus restore autonomic balance, thereby improving ventricular electrical stability and suppressing arrhythmogenesis. DRG=dorsal root ganglion, SG=stellate ganglion.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

An Overview of the Mechanism behind Excessive Volume of Pericardial Fat in Heart Failure.

Heart failure (HF) is a clinical syndrome characterized by myocardial dysfunction leading to inefficient blood filling or ejection. Regardless of the etiology, various mechanisms, including adipokine hypersecretion, proinflammatory cytokines, stem cell proliferation, oxidative stress, hyperglycemic toxicity, and autonomic nervous system dysregulation in the pericardial fat (PCF), contribute to the development of HF. PCF has been directly associated with cardiovascular disease, and an increased PCF volume is associated with HF. The PCF acts as neuroendocrine tissue that is closely linked to myocardial function and acts as an energy reservoir. This review aims to summarize each mechanism associated with PCF in HF.

Identification of novel variants for complicating cardiac disease in the scrub typhus infection using whole genome sequencing.

BACKGROUND/AIMS: Scrub typhus infection has been known to complicate cardiovascular diseases mainly attributing to high mortality. Genetic susceptibility loci for complicating cardiac diseases such as atrial fibrillation, heart failure, and ischemic heart disease identified by genomic study have been limited in scrub typhus infection. Therefore, we investigated the genetic novel variants predicting complicating cardiac diseases in patients with confirmed scrub typhus infection using whole genome sequencing. METHODS: We performed a prospective study for eight consecutive patients with scrub typhus infection. During follow-up, six cases were clinically diagnosed with complicating cardiac diseases and two controls without complicating cardiac diseases. The whole genomes of the all patients were sequenced, and the individual sequence variants were compared between accordcase and control patients. Variant genotypes were compared and identified as a single nucleotide polymorphism (SNP) of the different genotype distributions between six cases and two controls. RESULTS: The GG genotype in SNP (rs4977397) of solute carrier 24 family member 2 (SLC24A2) gene and non-TT genotype in SNP (rs2676750) of adenosine deaminase, RNA specific, B2 (ADARB2) gene were distinctively found in the case patients with complicated cardiac disease, compared with control patents in the scrub typhus infection. CONCLUSION: We suggest that the SNPs of SLC24A2 and ADARB2 might be genetic surrogate markers for complicating cardiac diseases in the scrub typhus infection. Our study show that early detection based on individual sequence variants might be feasible to predict complicating cardiac diseases in patients with scrub typhus infection, if further studies with more participants confirm these findings.

γ-Oryzanol ameliorates fine dust-induced premature endothelial senescence and dysfunction via attenuating oxidative stress.

Various cardiovascular diseases are associated with endothelial senescence, and a recent study showed that fine dust (FD)-induced premature endothelial senescence and dysfunction is associated with increased oxidative stress. The aim of the present study was to investigate protective effect of rice bran extract (RBE) and its major component of γ-Oryzanol (γ-Ory) against FD-induced premature endothelial senescence. Porcine coronary artery endothelial cells (PCAECs) were treated with FD alone or with RBE or γ-Ory. Senescence-associated ß-galactosidase (SA-ß-gal) activity, expression of cell cycle regulatory proteins, and oxidative stress levels were evaluated. The results indicated that SA-ß-gal activity in the FD-treated PCAECs was attenuated by RBE and γ-Ory. Additionally, γ-Ory inhibited FD-induced cell cycle arrest, restored cell proliferation, and reduced the expression of cell cycle regulatory proteins. γ-Ory also inhibited oxidative stress and prevented senescence-associated NADPH oxidase and LAS activity in FD-exposed ECs suggesting that γ-Ory could protect against FD-induced ECs senescence and dysfunction.

Rhythm Control and Cardiovascular or Cerebrovascular Outcomes in Patients with Atrial Fibrillation: A Study of the CODE-AF Registry.

BACKGROUND: It is not clear whether the data regarding rhythm control during atrial fibrillation (AF) contained in AF registries is prognostically significant. Thus, this study investigated the relationship between rhythm control and cardiovascular outcomes in patients in contemporary AF registries. METHODS: This study was conducted using data from 6670 patients with AF receiving oral anticoagulation in the CODE-AF registry. We used propensity overlap weighting to account for differences in baseline characteristics between the rhythm control and rate control groups. The primary outcome was a composite of the rate of death due to cardiovascular causes, stroke, acute coronary syndrome, and heart failure. The secondary outcomes were individual components of the primary outcome. RESULTS: In the CODE-AF registry, 5407 (81.1%) patients were enrolled three months after AF diagnosis. During a median follow-up period of 973 days (interquartile range: 755-1089 days), a primary outcome event occurred in 72 patients in the rhythm control group (1.4 events per 100 person-years) and in 211 patients in the rate control group (1.8 events per 100 person-years). However, after overlap weighting, the incidence rates were 1.4 and 1.5 events per 100 person-years, respectively. No significant difference was found in either the primary outcome (weighted HR: 0.87; 95% CI: 0.66-1.17; p = 0.363) or secondary outcomes between the rhythm control and rate control groups. CONCLUSION: In a prospective AF registry in which most of the population was enrolled at least three months after AF diagnosis, no difference in the risk of cardiovascular or cerebrovascular outcomes was found between the rhythm control and rate control groups, suggesting the early rhythm control should be considered to improve the outcome of patients.

Oral Anticoagulation Therapy in Atrial Fibrillation Patients with Advanced Chronic Kidney Disease: CODE-AF Registry.

PURPOSE: Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. MATERIALS AND METHODS: Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m²) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. RESULTS: During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). CONCLUSION: Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC. ClinicalTrials.gov (NCT02786095).