Long noncoding RNA GAS5 attenuates cardiac fibroblast proliferation in atrial fibrillation via repressing ALK5.

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have caught more attention for their role in the progression of many diseases. Among them, lncRNA GAS5 (Growth Inhibition Specificity 5) was studied in this research to identify how it affects the progression of atrial fibrillation (AF). PATIENTS AND METHODS: In 40 patients with AF and 30 patients with sinus rhythm (SR), the GAS5 expression of the right atrial appendage (RAA) tissues was detected by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the cell proliferation assay was conducted in AC16 cells transfected with GAS5 inhibitor and mimics, respectively. Furthermore, the qRT-PCR was performed to uncover the mechanism. RESULTS: In the research, the expression of GAS5 in RAA tissues was decreased significantly in AF patients than that in SR ones. Moreover, overexpression of GAS5 inhibited cell growth in AC16 cells, while knockdown of GAS5 promoted cell growth in AC16 cells. In addition, further experiments revealed that ALK5 was a target of GAS5 and its expression in AF tissues negatively correlated to GAS5 expression. CONCLUSIONS: These results indicate that GAS5 could inhibit cell proliferation of AF via suppressing ALK5, which may offer a new vision for interpreting the mechanism of AF development.

Heart rate and outcomes in patients with heart failure with preserved ejection fraction: A dose-response meta-analysis.

Although elevated resting heart rate is related to poor outcomes in heart failure (HF) with reduced ejection fraction, the association in HF with preserved ejection fraction (HFpEF) remains inconclusive. Therefore, we conducted a dose-response meta-analysis to examine the prognostic role of heart rate in patients with HFpEF.We searched PubMed and Embase databases until April 2017 and manually reviewed the reference lists of relevant literatures. Random effect models were used to pool the study-specific hazard ratio (HR) of outcomes, including all-cause death, cardiovascular death, and HF hospitalization.Six studies with 7 reports were finally included, totaling 14,054 patients with HFpEF. The summary HR (95% confidence interval [CI]) for every 10 beats/minute increment in heart rate was 1.04 (1.02-1.06) for all-cause death, 1.06 (1.02-1.10) for cardiovascular death, and 1.05 (1.01-1.08) for HF hospitalization. Subgroup analyses indicated that these positive relationships were significant in patients with sinus rhythm but not in those with atrial fibrillation. There was also evidence for nonlinear relationship of heart rate with each of the outcomes (All P for nonlinearity < .05).Higher heart rate in sinus rhythm is a risk factor for adverse outcomes in patients with HFpEF. Future trials are required to determine whether heart rate reduction may improve the prognosis of HFpEF.

Reduced dose apixaban resolving dual cardiac chamber thrombi in a patient with ischaemic cardiomyopathy in sinus rhythm.

Left atrial (LA) thrombus is a known sequela of atrial fibrillation (AF) but it is less frequently encountered in patients in sinus rhythm. Left ventricular (LV) dysfunction may predispose patients without evidence of atrial tachyarrhythmias to atrial thrombosis. Warfarin is the standard treatment for cardiac chamber thrombosis and prevention of the associated thromboembolic complications. Despite that apixaban was found to be superior to warfarin in prevention of stroke and systemic embolism in patients with AF, evidence for its use in treatment of cardiac chamber thrombi is scarce and is limited to case reports. We report a case of simultaneously occurring LV and LA thrombi successfully treated with reduced dose apixaban in a patient with ischaemic cardiomyopathy and in sinus rhythm. Although apixaban maybe a potential effective treatment for intracardiac thrombi, further studies are needed to demonstrate efficacy and safety of this agent in larger patient populations.

Impact of BNP level and peak VO2 on future heart failure events: comparison between sinus rhythm and atrial fibrillation.

This study aimed to examine the discrete impacts of peak oxygen consumption (VO2) and brain natriuretic peptide (BNP) levels on future heart failure (HF) events in sinus rhythm (SR) and atrial fibrillation (AF). A total of 1447 patients who underwent symptom-limited cardiopulmonary exercise testing and whose BNP values were determined simultaneously were analysed (SR, N = 1151 and AF, N = 296). HF events were defined as HF hospitalization or HF death. Over a mean follow-up period of 1472 days, 140 HF events were observed. A high BNP value (dichotomized by median value) was independently associated with HF events in SR (HR 8.08; 95 % CI 4.02-16.26; p < 0.0001), but not in AF patients (HR 1.97; 95 % CI 0.91-4.28; p = 0.087) with a significant interaction between the rhythms. By contrast, low-peak VO2 was independently associated with HF events in both rhythms (AF; HR 5.81; 95 % CI 1.75-19.30; p = 0.004, SR; HR 2.04; 95 % CI 1.19-3.49; p = 0.009), with a marginal interaction between them. In bivariate Cox models, low-peak VO2 had much stronger predictive power for HF events than high-BNP in AF, whereas high-BNP was more powerful than low-peak VO2 in SR. The prognostic value of BNP and peak VO2 for future HF events seemed to be different between SR and AF.

Intervenção em dispositivos cardíacos eletrônicos implantáveis sob uso de anticoagulante oral: experiência inicial / Intervention in cardiac implantable electronic devices in use of oral anticoagulant: initial experience

O manejo de dispositivos cardíacos eletrônicos implantáveis em portadores de arritmias atriais ou outras condições que demandem uso crônico de anticoagulante oral sempre gerou grande conflito nas cirurgias. Este trabalho traz a experiência da realização de intervenções com dispositivos cardíacos eletrônicos implantáveis em serviço especializado em arritmias cardíacas, apresentando resultados similares aos da literatura e que devem mudar paradigmas. Método: Realizamos intervenções desde implante de marcapassos monocamerais até upgrade para marcapassos/ cardiodesfibriladores multissítio em usuários de anticoagulantes orais, incluindo varfarina e os novos anticoagulantes orais ou de ação direta (dabigatrana, rivaroxabana e apixabana). As intervenções foram realizadas por médicos experientes e todos os pacientes foram reexaminados 15 dias após a cirurgia para retirada dos pontos e revisão clínica e do dispositivo. Resultados: Os procedimentos foramrealizados em 20 pacientes, em 5 dos quais foi mantido o uso de anticoagulantes de ação direta. A ocorrência de hematoma na loja se deu em 3 pacientes (INR de 3,4 e 2,63 e outro com apixabana) e todos tiveram boa evolução após conduta expectante sem retirada do anticoagulante oral, com reabsorção completa 30 dias depois.Naqueles em uso de varfarina, o INR médio foi de 2,85, sendo o menor de 2 e o maior, de 4,14. Em nossa série decasos conseguimos reproduzir dados do estudo BRUISE, que demonstrou diferença significativa na ocorrência dehematoma quando se adotou estratégia de intervenção realizando ponte com heparina. Em nossa série, 3 pacientesapresentaram hematoma, sem necessidade de intervenção (somente acompanhamento clínico) e sem aumentar o tempo de internação. Nossa série de casos incluiu os anticoagulantes de ação direta disponíveis no mercado.Conclusão: Este trabalho traz dados similares aos dos grandes estudos...

The management of implantable electronic cardiac devices in patients with atrial arrhythmias or other conditions that require the chronic use of oral anticoagulants has always generated great controversy in surgery. This study reports the experience of performing interventions with implantable electronic cardiac devices in specialized cardiac arrhythmia services with similar results to literature data, which must surely change paradigms. Method: We performed interventions ranging from single-chamber pacemaker implant to upgrade to multisite pacemakers/cardiodefibrillator in patients receiving oral anticoagulants including warfarin and the new oral or direct action anticoagulants (dabigatran, rivaroxaban and apixaban). Experienced surgeons performed the interventions. All of the patients were reexamined 15 days after the surgery to remove stiches,for clinical and device evaluation. Results: We performed procedures in 20 patients; in 5 of them direct oralanticoagulants were maintained. Significant hematomas were observed in 3 patients (INR of 3.4 and 2.63 andanother with apixaban), and all of them had good outcomes after a watchful waiting while maintaining the oralanticoagulant, with complete reabsorption after thirty days. In patients receiving warfarin, mean INR was 2.85, the lowest was 2.0 and the highest 4.14. In our series of cases we reproduced data from BRUISE study, which showed a significant difference in the occurrence of hematoma when the intervention strategy included a “bridge”with heparin. In our series, 3 patients had hematoma, but did not require an intervention (only clinical follow-up)and there was no increase in the length of stay. We used direct action anticoagulants available in the market.Conclusion: Our study provides similar data to major studies...

Mean platelet volume is related with ischemic stroke in patients with sinus rhythm.

Stroke is the leading cause of disability worldwide. It is known that atrial fibrillation and left atrial enlargement contribute ischemic stroke, and mean platelet volume (MPV) increases in patients with ischemic stroke and atrial fibrillation. We aimed to determine whether higher MPV is associated with ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched healthy individuals as control group (Group 2). After physical and echocardiographic examination, 24-48 h Holter monitoring and complete blood counts were studied. There were no statistically significant differences in age, sex rates, and comorbidities between groups. Left atrial diameter was higher in Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was significantly higher in Group 1 (P < 0.001) and was an independent determinant [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In conclusion, higher MPV is associated with acute ischemic stroke in patients with sinus rhythm and without heart failure or left atrial enlargement. MPV and left atrial diameter are independent predictors of ischemic stroke in this patient population.

[A case of symptomatic sinus dysfunction described in oculopharyngeal muscular dystrophy. Fortuitous association or syndrome?]. / Un cas de dysfonction sinusale symptomatique décrit dans la dystrophie musculaire oculopharyngée. Association fortuite ou syndromique ?

Oculopharyngeal muscular dystrophy is a rare genetic disease manifesting after 45years old, affecting the levator muscles of eyelids and muscles of swallowing. We report the first case of a patient of 73years old suffering from an oculopharyngeal muscular dystrophy hospitalized for syncope, a complication of severe sinus dysfunction, requiring the implantation of a pacemaker.

An adult case of polysplenia syndrome associated with sinus node dysfunction, dextrocardia, and systemic venous anomalies.

A 54-year-old woman was referred to our hospital for symptomatic sinus bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with dextrocardia during childhood and discovered to have heterotaxy syndrome when she had an appendectomy during her teenager years. Chest and abdominal examinations by computed tomography showed multiple spleens located on the right side and abnormal drainages of the superior and inferior vena cava. Left isomerism was diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior vena cava, pacemaker leads were implanted using the right cephalic vein approach. Her fainting symptoms disappeared after pacemaker implantation.

Cost of acute stroke care for patients with atrial fibrillation compared with those in sinus rhythm.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for stroke. Cost-effectiveness studies of anticoagulants for stroke prevention in AF rarely utilise AF-stroke-specific cost data in their analyses, as data are limited. Data that exist do not account for AF found on prolonged cardiac monitoring after stroke, further underestimating the clinical and economic burden of AF-stroke. OBJECTIVE: Our objective was to investigate differences in direct medical costs of acute stroke care among patients with and without AF. METHODS: Data were prospectively collected from 213 consecutive patients with confirmed stroke (196 ischaemic [IS], 17 intracranial haemorrhage [ICH]), admitted to a UK district general hospital between November 2011 and October 2012. Sociodemographic, clinical and cardiac monitoring characteristics were recorded, and resource use was calculated using a 'bottom-up' approach. Univariate and multivariate stepwise regressions were performed to identify predictors of direct cost. RESULTS: Among patients with IS, 73 had AF (37%). These patients were older, experienced greater stroke severity, lengths of hospitalisation, inpatient mortality and discharge to institutionalised care than those without AF. Mean acute care costs for the year 2012 were £6,978 (standard deviation [SD] 6,769, range 510-36,952). Mean (SD) costs were significantly higher for patients with AF than for those without (£9,083 [7,381] vs. £5,729 [6,071], p = <0.001). AF independently predicted acute care cost along with history of heart failure and stroke severity. The adjusted independent effect of having AF on costs was an additional £2,173 (95% confidence interval 91-4,254; p = 0.041). Costs for patients with an ICH did not differ according to cardiac rhythm. CONCLUSION: Direct medical costs of acute stroke care for patients with AF may be 50% greater than for patients without. Economic studies should take this into account to ensure the benefits of anticoagulants are not underestimated.

Cardiac vagal control and children's adaptive functioning: a meta-analysis.

Polyvagal theory has influenced research on the role of cardiac vagal control, indexed by respiratory sinus arrhythmia withdrawal (RSA-W) during challenging states, in children's self-regulation. However, it remains unclear how well RSA-W predicts adaptive functioning (AF) outcomes and whether certain caveats of measuring RSA (e.g., respiration) significantly impact these associations. A meta-analysis of 44 studies (n=4996 children) revealed small effect sizes such that greater levels of RSA-W were related to fewer externalizing, internalizing, and cognitive/academic problems. In contrast, RSA-W was differentially related to children's social problems according to sample type (community vs. clinical/at-risk). The relations between RSA-W and children's AF outcomes were stronger among studies that co-varied baseline RSA and in Caucasian children (no effect was found for respiration). Children from clinical/at-risk samples displayed lower levels of baseline RSA and RSA-W compared to children from community samples. Theoretical/practical implications for the study of cardiac vagal control are discussed.

Respiratory sinus arrhythmia during sleep in children with upper airway obstruction.

Upper airway obstruction during adulthood is associated with cardiovascular morbidity; cardiovascular consequences of childhood upper airway obstruction are less well established. This study aimed at investigating the effect of childhood upper airway obstruction on respiratory sinus arrhythmia as a measure of cardiac vagal modulation during night-time sleep. Overnight polysomnography was conducted in 40 healthy children (20 M; age: 7.5 ± 2.6 years; body mass index percentile: 60.7 ± 26.4%) and 40 children with upper airway obstruction (24 M; age: 7.5 ± 2.7 years; body mass index percentile: 65.8 ± 31.9%). We used the phase-averaging technique to compute respiratory sinus arrhythmia amplitude and phase delay. To study sleep stage effects and the effect of upper airway obstruction, respiratory sinus arrhythmia was measured during all artefact-free sleep episodes, and after exclusion of respiratory events. A significant increase in respiratory sinus arrhythmia amplitude and phase delay was observed during stage 4 sleep as compared with rapid eye movement sleep in both groups (amplitude: controls = 0.10 ± 0.03 versus 0.07 ± 0.02 s, P < 0.01, respectively, and upper airway obstruction = 0.07 ± 0.03 versus 0.05 ± 0.03 s, P < 0.05, respectively; phase delay: controls = 3.1 ± 0.1 versus 3.0 ± 0.1 rad, P < 0.05, respectively, and upper airway obstruction = 3.13 ± 0.04 versus 3.04 ± 0.08 rad, P < 0.01, respectively). A significant association between respiratory sinus arrhythmia and apnea/hypopnea index was observed during stage 2 sleep in children with upper airway obstruction. Compared with healthy controls, a significant decrease in respiratory sinus arrhythmia amplitude during stage 2 sleep was observed in children with upper airway obstruction (0.09 ± 0.03 versus 0.06 ± 0.03 s, P < 0.05). However, this difference was not apparent when respiratory events were excluded from analysis. Importantly, respiratory sinus arrhythmia showed a strong negative correlation with body mass index. In conclusion, night-time respiratory sinus arrhythmia in children is sleep stage dependent and normal during quiet sleep in children with relatively mild upper airway obstruction.

Preschoolers' daytime respiratory sinus arrhythmia and nighttime sleep.

We examined the association between preschoolers' (N=29; 20 boys; M age = 3.99 years, SD=.69) daytime parasympathetic nervous system (PNS) activity indexed by respiratory sinus arrhythmia (RSA) and their nighttime sleep. Children's baseline RSA was assessed in the laboratory. Sleep was monitored for seven consecutive nights at the child's home via actigraphy and the following sleep parameters were derived: sleep minutes, sleep activity index and sleep efficiency. Regression analyses showed that after controlling for potential confounds, higher RSA was a predictor of lower sleep activity and higher sleep efficiency. Results highlight the importance of physiological regulation for the sleep of healthy preschool children.

Inapparent atrial flutter due to atrial dissociation.

Percutaneous and surgical procedures intended to potentially cure atrial fibrillation require creating lines of conduction block in specific locations throughout the atrial chambers. In patients presenting with recurrent atrial fibrillation, repeat procedures are often performed, resulting in more extensive regions of conduction block and the potential for regions of dissociated atrial rhythms. The present case describes a patient post-multiple ablation procedures who presented with a symptomatic atrial arrhythmia, the mechanism of which was hidden by the presence of extensive atrial dissociation. Electrophysiologic study revealed the appropriate mechanism and a beneficial ablative procedure was then successfully accomplished.

Anticoagulation therapy in patients with heart failure due to systolic dysfunction and sinus rhythm: analysis of REDINSCOR registry.

INTRODUCTION AND OBJECTIVES: In patients with heart failure, left ventricular ejection fraction ≤35% and sinus rhythm without conditions such as atrial fibrillation, thrombus or history of thromboembolic events, the use of anticoagulation is controversial. Our objective was to evaluate the anticoagulation strategy in these patients, variables associated with its use, and its effects on various cardiovascular events. METHODS: Of the patients included in the REDINSCOR registry with left ventricular ejection fraction ≤35% and sinus rhythm without other anticoagulation indications (including patients with heart failure from 19 Spanish centres), we compared those who received this treatment with the remaining patients. RESULTS: Between 2007 and 2010, 2263 patients were included, of whom 902 had left ventricular ejection fraction ≤35% and sinus rhythm. Of these, 237 (26%) were receiving anticoagulation therapy. Variables associated with this treatment were a lower left ventricular ejection fraction, ischemic etiology, advanced functional class, wider QRS, larger left atrial diameter, and hospitalization. After 21(11-32) months of median follow-up, there were no significant differences in total mortality (14% versus 12.5%) or stroke (0.8% versus 0.9%). A propensity score adjusted multivariate analysis showed a reduction in a combined end-point including cardiac death, heart transplantation, coronary revascularization, and cardiovascular hospitalization (hazard ratio: 0.74; 95% confidence interval, 0.56-0.97; P=.03) in patients receiving anticoagulation therapy. No information regarding bleeding was collected in the follow-up. CONCLUSIONS: In a large and contemporary series of patients with heart failure, left ventricular ejection fraction ≤35% and sinus rhythm, 26% received anticoagulation therapy. This was not associated with lower mortality or stroke incidence, although there was a reduction in major cardiac events.

Comparative proteomic analysis of atrial appendages from rheumatic heart disease patients with sinus rhythm and atrial fibrillation.

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice, and contributes to cardiovascular morbidity and mortality. Despite significant advances in the understanding of the mechanisms associated with AF, the number of effective biomarkers and viable therapeutic targets remains relatively limited. In this study, 2-DE and MS/MS analysis was used to identify differentially expressed proteins in human atrial appendage tissues from patients with AF (n=4) compared to controls with sinus rhythm (SR; n=5). All subjects had rheumatic heart disease. Following 2-DE analysis, Coomassie Brilliant Blue staining and MS/MS identification, a total of 19 protein spots were found to be differentially expressed between the AF and SR groups. By cluster and metabolic/signaling pathway analysis, these proteins were divided into three major groups: proteins involved in the cytoskeleton and myofilament, energy metabolism associated proteins, and proteins associated with oxidative stress. The proteins identified in this study may enable a better understanding of the molecular mechanisms of AF, and may provide useful biomarkers and novel targets for drug development.

Enhanced detection of paroxysmal atrial fibrillation by early and prolonged continuous holter monitoring in patients with cerebral ischemia presenting in sinus rhythm.

BACKGROUND AND PURPOSE: Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission. Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the standard of care including a 24-hour Holter recording. METHODS: In the observational Find-AF trial (ISRCTN 46104198), consecutive patients presenting with symptoms of cerebral ischemia were included. Patients free from atrial fibrillation at presentation received 7-day Holter monitoring. RESULTS: Two hundred eighty-one patients were prospectively included. Forty-four (15.7%) had atrial fibrillation documented by routine electrocardiogram on admission. All remaining patients received Holter monitors at a median of 5.5 hours after presentation. In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation, the detection rate with early and prolonged (7 days) Holter monitoring (12.5%) was significantly higher than for any 24-hour (mean of 7 intervals: 4.8%, P = 0.015) or any 48-hour monitoring interval (mean of 6 intervals: 6.4%, P = 0.023). Of those 28 patients with new atrial fibrillation on Holter monitoring, 15 (6.7%) had been discharged without therapeutic anticoagulation after routine clinical care (ie, with data from 24-hour Holter monitoring only). Detection rates were 43.8% or 6.3% for short supraventricular runs of ≥ 10 beats or prolonged episodes (> 5 hours) of atrial fibrillation, respectively. Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event. CONCLUSIONS: Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7, leading to a relevant change in therapy in a substantial number of patients. Early initiation of monitoring does not appear to be crucial. Hence, prolonged Holter monitoring (≥ 7 days) should be considered for all patients with unexplained cerebral ischemia.

Transient sinus node dysfunction with acute hepatitis of unknown etiology.

We reported a case of a 72-year-old male, known diabetic on insulin, referred because of complete atrioventricular block. He was found to have acute hepatitis during which he developed transient atrial arrhythmia, and sinus node dysfunction. His cardiac symptoms disappeared completely after hepatitis improvement. All of his cardiac investigations were normal including electrocardiogram, echocardiography and thalium stress test. At 3 and 6 months follow up, his Holter monitoring did not show any further arrhythmia, and he denied any further episodes of palpitation or pre-syncope. We reviewed the literature regarding the relationship between hepatitis and atrial arrhythmia.