Onset Of Fibrillation Research Articles

Changes in the Stoichiometry of Uniplex Decrease Mitochondrial Calcium Overload and Contribute to Tolerance of Cardiac Ischemia/Reperfusion Injury in Hypothyroidism.

Background: Thyroid hormone status in hypothyroidism (HT) downregulates key elements in Ca2+ handling within the heart, reducing contractility, impairing the basal energetic balance, and increasing the risk of cardiovascular disease. Mitochondrial Ca2+ transport is reduced in HT, and tolerance to reperfusion damage has been documented, but the precise mechanism is not well understood. Therefore, we aimed to determine the stoichiometry and activity of the mitochondrial Ca2+ uniporter or uniplex in an HT model and the relevance to the opening of the mitochondrial permeability transition pores (mPTP) during ischemia/reperfusion (I/R) injury.Methods: An HT model was established in Wistar rats by treatment with 6-propylthiouracil for 28 days. Uniplex composition and activity were determined in cardiac mitochondria. Hearts were perfused ex vivo to induce I/R injury, and functional parameters related to contractility and tissue viability were evaluated.Results: The cardiac stoichiometry between two subunits of the uniplex (MICU1/MCU) increased by 25% in animals with HT. The intramitochondrial Ca2+ content was reduced by 40% and was less prone to the mPTP opening. After I/R injury, ischemic contracture and the onset of ventricular fibrillation were delayed in animals with HT, concomitant with a reduction in oxidative damage and mitochondrial dysfunction.Conclusions: Our results suggest that HT is associated with an increase in the cardiac MICU1/MCU ratio, thereby changing the stoichiometry between these subunits to increase the threshold to cytosolic Ca2+ and reduce mitochondrial Ca2+ overload. Our results also demonstrate that this HT model can be used to explore the role of mitochondrial Ca2+ transport in cardiac diseases due to its induced tolerance to cardiac damage.

Usefulness of Visfatin as a Predictor of Atrial Fibrillation Recurrence After Ablation Procedure

Visfatin is an adipokine produced by visceral fat tissue and takes part in fibrosis and inflammatory response. In the heart muscle, it is connected with the progression of atherosclerosis. Currently, there is no data on how visfatin affects atrial fibrillation (AF) onset. The study aimed to establish if baseline visfatin levels are connected with the risk of arrhythmia recurrence after AF ablation. In this prospective, long-term, observational study, we enrolled 290 consecutive patients admitted for AF ablation. All patients were screened for cardiovascular risk factors and had blood serum taken to measure visfatin concentrations before the ablation procedure. The end point of the study was a recurrence of the AF, defined as at least one AF episode of at any moment during the follow-up period. The screening included AF of at least 30 second duration assessed with electrocardiogram (ECG) monitoring, including 24-hour ECG Holter monitoring, implantable pacemakers, implantable defibrillators, or subcutaneous ECG monitoring devices. After excluding patients disqualified from the procedure the study population consisted of 236 patients, mean age 57.8 years (64.8% male). Mean body mass index in the population was 29.6 ± 4.8 kg/m2 and arterial hypertension was highly prevalent (73.3% of patients). In 129 (54.7%) cases we observed recurrence of AF during the follow-up period. Patients with AF recurrence had higher visfatin levels (1.7 ± 2.4 vs 2.1 ± 1.9 ng/ml; p <0.0001) and multivariate logistic regression analysis containing age, sex, and other independent variables showed that patients with elevated visfatin levels were almost 3-time more likely to experience AF recurrence (odds ratio 2.92; 95% confidence interval 1.60 to 5.32). In conclusion, patients with higher visfatin levels are at elevated risk of arrhythmia recurrence after ablation for AF. Visfatin can be a useful marker for risk stratification in this group of patients.

Huge Hiatal Hernia Mimicking a Mass with Compressive Effects on the Left Atrium Causing Paroxysmal Atrial Fibrillation

An 82-year-old female patient presented with complaints of dyspnea and increasing palpitations caused by food reflux. There was no risk factor except hypertension. On physical examination, the heart rate was 120 beats/min and arrhythmic and blood pressure was 130/80 mmHg. Electrocardiography showed high-rate atrial fibrillation. Laboratory parameters were unremarkable. Echocardiography illustrated a hyperechogenic and well-circumscribed mass, 40×55 mm size, in the posterior left atrium (Figure 1, Video 1). The mass size increased with breathing and the Valsalva maneuver. There was no pathology on chest radiography. The atrial fibrillation returned to sinus rhythm spontaneously, but paroxysmal atrial fibrillation attacks were observed, which were related to food reflux at follow-up. Subsequently, cardiac computed tomography, performed to determine the etiology, failed to demonstrate any pathological findings involving the left atrium. However, there was a sliding hernia in the paraesophageal region compressing the left atrium from the inferior-posterior region (Figure 2). Hiatal hernia surgery was recommended on account of the intermittently repeating symptoms. The patient refused the operation, and she is under follow-up with medical treatment.

Rs4968309 in Myosin Light Chain 4 (MYL4) Associated With Atrial Fibrillation Onset and Predicts Clinical Outcomes After Catheter Ablation in Atrial Fibrillation Patients Without Structural Heart Disease.

Atrial fibrillation (AF) is the most common arrhythmia with serious complications and a high rate of recurrence after catheter ablation. Recently, mutation ofMYL4was reported as responsible for familial atrial cardiomyopathy and AF. This study aimed to determine the association between polymorphism inMYL4with the onset and recurrence of AF. A total of 7 single-nucleotide polymorphisms were selected by linkage disequilibrium and genotyped in 510 consecutive AF patients and 192 controls without structural heart disease. A total of 246 AF patients who underwent cryoballoon ablation had a 1-year scheduled follow-up study for AF recurrence. C allele and CC genotype of rs4968309 and A allele of rs1515751were associated with AF onset both before and after adjustment of covariation (age, sex, hypertension, and diabetes). AF type and left atrial size were different among the genotypes of rs4968309. Moreover, CC genotype of rs4968309 increased susceptibly of AF recurrence after cryoballoon ablation. The prevalence of hypertension was associated with rs1515752, and left atrial size was associated with the genotype of rs2071438. C allele and CC genotype of rs4968309 inMYL4were associated with AF onset and recurrence. Moreover, the A allele of rs1515751 had a significant association with AF onset. The polymorphisms ofMYL4can predict AF onset and prognosis after ablation in AF patients without structural heart disease.

Left Atrial Strain for Predicting Atrial Fibrillation Onset in Hypertensive Patients.

We aimed to find new predictive parameters for atrial fibrillation (AF) onset in hypertensive patients using two-dimensional (2D) conventional and speckle tracking echocardiography of the left atrium (LA). One hundred and eight patients with essential hypertension (HTN) were prospectively enrolled, from which 67 patients had no other important comorbidities (HTN group), while 41 patients had a recent AF episode, but were in sinus rhythm at the moment of enrollment (HTN and AF group). LA diameters and maximal volume, LV mass, LV ejection fraction and diastolic function were assessed through 2D conventional echocardiography. Moreover, peak longitudinal and contractile strain of LA walls (PALS and PACS, respectively) were analyzed by speckle tracking technique. Patients were followed up for 1year and recurrent 24-h rhythm monitoring was done, in order to identify atrial fibrillation. Age and time from diagnosis of HTN were higher in HTN and AF group than in HTN group (68.02 ± 19years versus 57.2 ± 1.52years, p = 0.001 and 62.2 ± 9.2months versus 40.4 ± 6.4months, p = 0.04). All LA diameters and LA maximal volume were significantly larger in HTN and AF group (for LA antero-posterior diameter p = 0.02, for all the rest p < 0.0001). LV ejection fraction was preserved in both groups, being significantly lower in HTN and AF patients (58.44 ± 0.79 versus 60.75 ± 0.57, p = 0.02). LV mass was higher in HTN and AF group and these patients had also a more severe diastolic dysfunction, (E/A ratio 1.8 ± 0.51 versus 0.9 ± 0.02, p = 0.04) and lower septal and lateral A' velocities (p < 0.0001 and p = 0.002). The peak LA longitudinal and contractile strain values were also significantly lower in HTN and AF group versus HTN group (for all p < 0.0001). Among the echocardiographic parameters, we identified PALS and PACS as predictors for AF, with a good discriminating capacity (AUC = 0.88 for PALS and AUC = 0.86 for PACS). Compared to patients with isolated hypertension, patients with hypertension and AF display several echocardiographic differences. Among them, LA strain parameters could be useful predictors of AF occurrence in hypertensive patients.

Risk of Atrial Fibrillation in Patients with Congenital Heart Disease: Results of a Propensity Score-Matched, Nationwide Cohort Study.

Aim: The objective was to compare the rate of atrial fibrillation (AF) onset in patients with congenital heart disease (CHD) compared to controls.Methods: Using a large number of samples extracted from nationwide cohort data in Taiwan, the authors used a propensity-matching procedure and multivariable Cox models to assess the risk of AF by CHD.Results: A cohort of 19,439 CHD patients and a propensity-matched cohort of 19,439 control patients were included in this study. The cumulative incidence of AF was significantly higher in the CHD cohort than in the non-CHD cohort (p<0.001). After controlling for confounding factors, the adjusted hazard ratio (aHR) of AF was 4.23 (95% confidence interval [CI] 3.31－5.41) in the CHD cohort, compared to the non-CHD cohort.Conclusion: A significant association between CHD and AF risk was found.

Parathormone, vitamin D and the risk of atrial fibrillation in older adults: A prospective study

Background & aimsVitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults. Methods and resultsData come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression.Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4–15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3–24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9–32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27–2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28–3.42). ConclusionThe risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.

QT prolongation and variability: new ECG signs of atrial potentials dispersion before atrial fibrillation onset.

QT interval may be considered an indirect marker of atrial repolarization. Aim of our study was to verify if QT interval variations precede the onset of atrial fibrillation (AF). We analyzed 21 AF onsets recorded at 24-h Holter ECG. Triggering supraventricular extrabeats (TSVEB) were identified and matched to nontriggering supraventricular extrabeats (NTSVEB) with the same prematurity index. QT and QTc intervals and their variability (max-min QT interval) were measured in the 10 beats preceding TSVEB and NTSVEB. QTc (470.1 ± 56.7 vs. 436.7 ± 25.6 ms; P = 0.006), QT (36.8 ± 13.1 vs. 21.1 ± 10.1 ms; P = 0.001) and QTc variability (41.5 ± 15.8 vs. 23.1 ± 11.9; P = 0.001) significantly varied between TSVEB and NTSVEB. By stratifying AF onsets in vagal (n = 10) and adrenergic (n = 11) according to Heart Rate Variability, significant differences emerged concerning QT (35.20 ± 16.48 vs. 22.70 ± 10.23 ms, P = 0.006) and QTc variability (39.30 ± 18.32 vs. 25.60 ± 12.91 ms, P = 0.029) for vagal onsets and QTc (477.73 ± 57.50 vs. 438.00 ± 28.55 ms, P = 0.045), QT (38.36 ± 9.79 vs. 19.73 ± 10.21 ms, P = 0.005) and QTc variability (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.004) for adrenergic onsets. By stratifying AF onsets in type I (n = 7) or II (n = 14) according to a cycle length variation in the 30 s before the onset greater or smaller than 10% respectively, significant differences were noted concerning QTc (477.73 ± 57.50 vs. 438 ± 28.55 ms, P = 0.045), QT (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.005) and QTc variability (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.004) in type I and QT (35.20 ± 16.48 vs. 22.70 ± 10.23 ms, P = 0.006) and QTc variability (39.30 ± 18.32 vs. 25.60 ± 12.91 ms, P = 0.029) in type II onsets. Prolongation and QT variability represent a relevant substrate marker in the genesis of AF, independently of the trigger type.

SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.

Kv1.5 (Potassium voltage-gated channel subfamily A member 5) has been regarded as a promising target of interventions for atrial fibrillation (AF). SNX17 (sorting nexin 17), a member of the SNXs (sorting nexin family), regulates the intracellular trafficking of membrane proteins through its FERM (four-point-one, ezrin, radixin, moesin) domain. However, whether SNX17 regulates the trafficking process of Kv1.5 remains unknown. A SNX17 knockout rat line was generated to test the role of SNX17 in atrial electrophysiology. The protein expression of SNX17 and membrane ion channels was detected by Western blotting. Electrophysiology changes in the atrial tissue and myocytes were analyzed by optical mapping and patch clamp, respectively. Acetylcholine and electrical stimulation were used to induce AF, and ECG recording was adopted to assess the influence of SNX17 deficiency on AF susceptibility. The spatial relationship between Kv1.5 and SNX17 was evaluated by immunostaining and confocal scanning, and the functional region of SNX17 regulating Kv1.5 trafficking was identified using plasmids with truncated SNX17 domains. Embryonic death occurred in homozygous SNX17 knockout rats. SNX17 heterozygous rats survived, and the level of the SNX17 protein in the atrium was decreased by ≈50%. SNX17 deficiency increased the membrane expression of Kv1.5 and atria-specific ultrarapid delayed rectifier outward potassium current ( IKur) density, resulting in a shortened action potential duration, and eventually contributing to AF susceptibility. Mechanistically, SNX17 facilitated the endocytic sorting of Kv1.5 from the plasma membrane to early endosomes via the FERM domain. SNX17 mediates susceptibility to AF by regulating endocytic sorting of the Kv1.5 channel through the FERM domain. SNX17 could be a potential target for the development of new drugs for AF.

Impact of Beta adrenergic receptors polymorphism on the onset of ventricular fibrillation during the acute phase of myocardial infarction

Ventricular fibrillation complicating acute myocardial ischemia is the main cause of sudden cardiac death. We investigated whether two known ADBR2 and ADRB1 polymorphisms are associated with ventricular fibrillation (VF) in the context of myocardial infarction (MI). A total of 831 patients were recruited during the MAP-IDM study: 392 patients who experienced VF during the acute phase of primary MI and 439 controls with MI without VF. Patients were genotyped for the ADRB2 Gln27Glu, the ADRB1 Arg389Gly polymorphisms by RT-PCR. Unconditional logistic regression models were fitted, after adjustment on center, age and sex. Age was included as a 5 age-group variable (27–44, 45–54, 55–64, 65–74, 75–88) using dummy variables, including interaction terms between sex and age-groups. Cases and controls did not differ significantly in age, in sex-ratio, BMI, in smoker ratio and in troponin peak value. VF patients have a lower left ventricular ejection fraction (LVEF) (46.1% vs. 51.9%, P < 0.001). We observe a protective effect of polymorphism homozygous ADRB1-Gly49Gly (OR = 0.15, P = 0.03) and a slight tendency to risk sudden death for ADRB1-Arg389Arg (non significative). Analysis revealed a risk effect for polymorphism heterozygous ADRB2 Gln27Glu regarding a faster delay in the occurrence of FV ( P < 0,05). The ADRB2 Gln27Glu variant seems to predispose patients to fast onset VF in the setting of cardiac ischemia whereas the homozygous ADRB1Gly49Gly variant seems to protect patient to VF in the context of myocardial infarction.

Silent atrial fibrillation is associated with P-wave duration index in patients with cardiac resynchronisation therapy.

IntroductionAtrial fibrillation (AF) attacks can be silent, symptomatic, or emerge with its complications in pacemaker-implanted patient groups. P-wave duration index (PWDI), a novel parameter, is calculated by dividing the P-wave duration (PWD) by the PR interval. This study aimed to investigate the relation between PWDI and silent AF development in cardiac resynchronisation therapy defibrillator (CRT-D)-applied patients.Material and methodsThe study population consisted of 181 CRT-D device-implanted patients. Atrial fibrillation attacks that last at least 30 s with no symptoms were accepted as silent AF.ResultsPatients were separated into two groups: ”with silent AF” and ”without silent AF“. The without silent AF group comprised 121 patients (mean age: 62.9 ±8.7 years, 62% male). The with silent AF group included 60 patients (mean age: 67.9 ±9.7 years, 60% male). The silent AF group had significantly higher mean age (p = 0.001). PR duration was significantly higher in the without silent AF group (p = 0.001). Patients with first-degree IAB and PWDI values were significantly higher in the with silent AF group (p-values were 0.001 and < 0.001, respectively). Age (OR = 1.073, 95% CI: 1.028–1.119, p = 0.001) and PWDI (OR = 1.053, 95% CI: 1.028–1.078, p < 0.001) were detected as independent predictors for silent AF in the binomial logistic regression analysis. In the ROC analysis, a PWDI cut-off value of 0.67 determined silent AF with 81.7% sensitivity and 51.4% specificity (AUC = 0.701, p < 0.001).ConclusionsP-wave duration index was significantly associated with silent AF in patients with CRT-D.

Food-Related Atrial Fibrillation? The Potential Role of Biogenic Amines in “Nutri-Arrhythmias” Genesis

Atrial fibrillation (AF) is the most common type of arrhythmia: a disorganized electrical atrial activity leading to irregular ventricular beats. Its most common risk factors include high blood pressure, congenital and valvular heart diseases, aging, heart failure and coronary heart diseases. Other risk factors include excessive alcohol intake, tobacco smoking, diabetes mellitus and thyrotoxicosis. However, many cases are not associated with any of these risk factors: probably, in these patients, immunological, functional and even dietary mechanisms may be responsible to induce cardiac arrhythmias. Several studies have focused on immunological and neurohumoral mechanisms; however, little information is available about the potential relationship between dietary patterns and atrial fibrillation episodes. This case report describes a potential correlation between biogenic amines in ingested food and recurrent atrial fibrillation onset in a 61-years old man in absence of a remarkable clinical history and of the most common risk factors. The nutritional team instituted a food protocol: a low calories diet and eliminating biogenic amines-rich foods. During the follow-up (16 months), there was a noticeable weight loss and no arrhythmic episodes happened again. This clinical case provides evidence for a possible new relationship between some kinds of food and heart conduction (defining the very novel field of arrhythmogenic foods and of “nutri-arrhythmias”), recognizing biogenic amines-rich foods abuse as the potential trigger and substrate for atrial fibrillation. Therefore, we suggested that clinical history in patients with new onset AF should also include questions concerning the ingestion of histamine-rich foodstuffs (or other amines-rich food) and alcohol consumption: their effects may result to be synergistic in the alteration of cardiac rhythm and may explain the recurrence of an unexplained atrial fibrillation.

Relationship between hemodynamic parameters and severity of ischemia-induced left ventricular wall thickening during cardiopulmonary resuscitation of consistent quality.

Ischemia-induced left ventricular (LV) wall thickening compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR). However, accurate assessment of the severity of ischemia-induced LV wall thickening during CPR is challenging. We investigated, in a swine model, whether hemodynamic parameters, including end-tidal carbon dioxide (ETCO2) level, are linearly associated with the severity of ischemia-induced LV wall thickening during CPR of consistent quality. We retrospectively analyzed 96 datasets for ETCO2 level, arterial pressure, LV wall thickness, and the percent of measured end-diastolic volume (%EDV) relative to EDV at the onset of ventricular fibrillation from eight pigs. Animals underwent advanced cardiovascular life support based on resuscitation guidelines. During CPR, LV wall thickness progressively increased while %EDV progressively decreased. Systolic and diastolic arterial pressure and ETCO2 level were significantly correlated with LV wall thickness and %EDV. Linear mixed effect models revealed that, after adjustment for significant covariates, systolic and diastolic arterial pressure were not associated with LV wall thickness or %EDV. ETCO2 level had a significant linear relationship with %EDV (P = 0.004). However, it could explain only 28.2% of the total variance of %EDV in our model. In conclusion, none of the hemodynamic parameters examined in this study appeared to provide sufficient information on the severity of ischemia-induced LV wall thickening.

Methacycline displays a strong efficacy in reducing toxicity in a SCA3 Caenorhabditis elegans model

BackgroundWe have previously demonstrated the neuroprotective activity of tetracycline on a Spinocerebellar Ataxia 3 nematode model. Here, we present the screening of a small library of tetracycline congeners in order to identify the most effective compound in preventing ataxin-3 aggregation. MethodsWe performed the assays on the Josephin Domain as it is directly involved in the onset of fibrillation. We used thioflavin T and solubility assays to spot out the most effective tetracycline congeners; Fourier transform infrared and NMR spectroscopies to characterize their mode of action. We employed an ataxic Caenorhabditis elegans model to evaluate the pharmacological efficacy of tetracycline congeners. ResultsMethacycline was identified as the most effective compound. Like tetracycline, methacycline neither significantly affected the aggregation kinetics nor did it change the secondary structures of the final aggregates but increased the solubility of the aggregated species. Saturation transfer NMR experiments demonstrated methacycline capability to only bind the oligomeric species of Josephin Domain. Competition assays also showed that methacycline binds to the Josephin Domain more tightly than tetracycline. The treatment with methacycline induced a significant improvement in motility and locomotion of the transgenic C. elegans without changing its lifespan. The efficacy was distinctly stronger than that of tetracycline. Noteworthy, unlike tetracycline, methacycline was able to retard aging-related decline in motility of even the healthy worms used. ConclusionsThe apparent absence of toxic effects displayed by methacycline, along with its stronger efficacy in contrasting expanded ataxin-3 toxicity, makes it a possible candidate for a chronic treatment of the disease.

21Concurrent increase of sympathetic tone and atrial ectopic activity precede the onset of post-operative atrial fibrillation

21Concurrent increase of sympathetic tone and atrial ectopic activity precede the onset of post-operative atrial fibrillation

Myocardial fibrosis and atrial fibrillation

Atrial fibrillation is the most prevalent arrhythmia, and tends to progress. Any structural changes in the heart may lead to its progressive remodelling with increased deposition of connective tissue and fibrosis. Predominance of collagen types I and III synthesis over its degradation leads to accumulation of fibers and to fibrosis. Increase of atrial fibrosis is usually found on autopsy and biopsy. There is relation revealed, of atrial fibrosis grade and postsurgery atrial fibrillation. The mechanisms participating in the structural remodelling and progression of atrial fibrosis are not studied well enough, but there is known role of renin-angiotensinaldosterone system, transforming growth factor, inflammation and matrix metalloproteases. As an alternative, one should consider non-invasive diagnostic methods: magnetic resonance imaging of the heart and biomarkers level measurement. Hyperactivation of the renin-angiotensin-aldosterone system facilitates structural remodelling of the heart and progression of atrial fibrosis. Hyperexpression of the transforming growth factor leads to selective atrial fibrosis, heterogeneity of excitation conduction and fibrillation onset. Matrix metalloproteases are the marker of extracellular degradation. Study of fibrosis biomarkers makes it to increase significantly the efficacy of atrial fibrillation course prediction.

Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro.

BackgroundVentricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution‐based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant‐alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions.Methods and ResultsOptical mapping voltage signals from canine right‐ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1‐dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign‐change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic‐regression approach showed that model‐prediction effects were significant for both conduction block (P<1×10−15, coefficient 44.36) and sustained ventricular fibrillation (P=0.0046, coefficient, 1.63) events.ConclusionsThe observed sign‐change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant‐alternans‐based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.

Development of Heart Failure From Transient Atrial Fibrillation Attacks inResponders to Cardiac Resynchronization Therapy.

This study aimed to clarify the clinical impact of transient atrial fibrillation (AF) attacks themselves and the efficacy of cardiac resynchronization therapy (CRT) in patients with intermittent AF. The benefit of CRT in patients with intermittent AF, especially the effect of the AF attacks themselves, remains unclear. Among our cohort of 269 consecutive CRT patients, we compared the percent of biventricular pacing (BIVP%) and other clinical characteristics between patients with intermittent AF and those with sinus rhythm (SR). During a median follow-up of 942 days (interquartile range: 379 to 1,464 days) a total of 22 patients, including 59% of CRT responders, developed heart failure (HF) due to a transient AF attack itself, and that accounted for 21% of all HF events. The BIVP% during the AF attacks was significantly lower than that during SR (p< 0.05). When compared to the SR groups, patients with intermittent AF had a significantly higher risk of developing HF or death (hazard ratio: 2.2; 95% confidence interval: 1.3 to 3.8). However, the patients who received a BIVP% of≥90% during AF attacks were comparable to those with SR (hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.0). A substantial number of patients developed HF due to transient AF attacks themselves even in the CRT responders, and the reason was mainly due to the loss of the BIVP%.

The Impact of Telemedicine on Teamwork and Workload in Pediatric Resuscitation: A Simulation-Based, Randomized Controlled Study.

Telemedicine provides access to specialty care to critically ill patients from a geographic distance. The effects of using telemedicine on (1) teamwork and communication (TC), (2) task workload during resuscitation, and (3) the processes of critical care have not been well described. To evaluate the impact of telemedicine on (1) TC, (2) task workload during a resuscitation, and (3) the processes of critical care during a simulated pediatric resuscitation. Prospective single-center randomized trial. Teams of two physicians (senior and junior resident) and two standardized confederate nurses were randomized to either telemedicine (telepresent senior physician team leader) or usual care (both physicians in the room) during a simulated infant resuscitation. Simulations were video recorded and assessed for teamwork, workload, and processes of care using the Simulated Team Assessment Tool (STAT), the NASA Task Load Index (NASA-TLX) tool, and time between onset of ventricular fibrillation and defibrillation, respectively. Twenty teams participated. There was no difference in teamwork between the groups (mean STAT score 72% vs. 69%; p = 0.383); however, there was a significantly greater workload in the telemedicine group (mean TLX score 56% vs. 48%, p = 0.020). Using linear regression, no difference was found in time-to-defibrillation between groups (p = 0.671), but higher teamwork scores predicted faster time to defibrillation (p = 0.020). In this simulation-based study, a telepresent team leader was associated with increased team workload compared to usual care. However, no differences were noted in teamwork and processes of care metrics.

Unravelling the inhibitory activity of Chlamydomonas reinhardtii sulfated polysaccharides against \u03b1-Synuclein fibrillation

α-Synuclein (α-Syn) is an intrinsically disordered presynaptic protein, whose aggregation is critically involved in Parkinson’s disease (PD). Many of the currently available drugs for the treatment of PD are not sufficiently effective in preventing progress of the disease and have multiple side-effects. With this background, efficient drug candidates, sulfated polysaccharides from Chlamydomonas reinhardtii (Cr-SPs) were isolated and investigated for their effect on inhibition of α-Syn fibrillation and dissolution of preformed α-Syn fibrillar structures through a combination of spectroscopic and microscopic techniques. The kinetics of α-Syn fibrillation demonstrates that Cr-SPs are very effective in inhibiting α-Syn fibrillation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis gel-image shows presence of soluble protein in the presence of Cr-SPs after completion of the fibrillation process. The morphological changes associated with fibrillation monitored by transmission electron microscopy showed that Cr-SPs efficiently bind with α-Syn and delay the conversion of α-helical intermediate into β-sheet rich structures. Cr-SPs are also effective even if onset of α-Syn fibrillation has already started and they also have the ability to dissolve pre-formed fibrils. Thus, the current work has substantial therapeutic implications towards unlocking the immense potential of algal products to function as alternative therapeutic agents against PD and other protein aggregation related disorders.