Angiopoietin-2 predicts morbidity in adults with Fontan physiology.

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM

Pacemaker Prevention Therapy in Drug–refractory Paroxysmal Atrial Fibrillation: Reliability of Diagnostics and Effectiveness of Prevention Pacing Therapy in Vitatron™ Selection® device

Introduction. Atrial fibrillation (AF), the most common and rising disorder of cardiac rhythm, is quite difficult to control and/or to treat. Non pharmacological therapies for AF may involve the use of dedicated pacing algorithms to detect and prevent atrial arrhythmia that could be a trigger for AF onset. Selection 900E/AF2.0 Vitatron DDDRP pacemaker (1) keeps an atrial arrhythmia diary thus providing detailed onset reports of arrhythmias of interest, (2) provides us data about the number of premature atrial contractions (PACs) and (3) plots heart rate in the 5 minutes preceding the detection of an atrial arrhythmia. Moreover, this device applies four dedicated pacing therapies to reduce the incidence of atrial arrhythmia and AF events. Aim of the Study. To analyze the reliability to record atrial arrhythmias and evaluate effectiveness of its AF preventive pacing therapies. Material and Methods. We enrolled 15 patients (9 males and 6 females, mean age of 71±5 years, NYHA class I–II), with a DDDRP pacemaker implanted for a “bradycardia–tachycardia” syndrome, with advanced atrioventricular conduction disturbances. We compared the number and duration of AF episodes’ stored in the device with a contemporaneous 24h Holter monitoring. After that, we switched on the atrial arrhythmias detecting algorithms, starting from an atrial rate over 180 beats per minute for at least 6 ventricular cycles, and ending with at least 10 ventricular cycles in sinus rhythm. Thereafter, in order to evaluate the possible reduction in PACs number and in number and duration of AF episodes, we tailored all the four pacing preventive algorithms. Patients were followed for 24±8 months (from 20 to 32 months). Results. All 59 atrial arrhythmia episodes occurred in the first part of this trial, were correctly recorded by both systems, with a correlation coefficient (r) of 0.96. During the follow–up, we observed a significant reduction not only in PACs number (from 83±12/day to 2.3±0.8/day) but also in AF episodes (from 46±7/day to 0.12±0.03/day) and AF burden (from 93%±6% to 0.3%±0.06%). An increase in atrial pacing percentages (from 3%±0.5% to 97%±3%) was also contemporaneously observed. Conclusion. In this pacemaker, detection of atrial arrhythmia episodes is highly reliable, thus making available an appropriate monitoring of heart rhythm, mainly suitable in AF asymptomatic patients. Moreover, the significant reduction of atrial arrhythmia episodes indicates that this might represent a suitable therapeutic option for an effective preventive therapy of AF in paced brady–tachy patients

Arrhythmia induction using isoproterenol or epinephrine during electrophysiology study for supraventricular tachycardia

Background Electrophysiology study (EPS) is an important part of the diagnosis and workup for supraventricular tachycardia (SVT). Provocative medications are used to induce arrhythmias, when they are not inducible at baseline. The most common medication is the β1‐specific agonist, isoproterenol, but recent price increases have resulted in a shift toward the nonspecific agonist, epinephrine. Objective We hypothesize that isoproterenol is a better induction agent for SVT during EPS than epinephrine. Methods We created a retrospective cohort of 131 patients, who underwent EPS and required medication infusion with either isoproterenol or epinephrine for SVT induction. The primary outcome was arrhythmia induction. Results Successful induction was achieved in 71% of isoproterenol cases and 53% of epinephrine cases (P = 0.020). Isoproterenol was significantly better than epinephrine for SVT induction during EPS (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.14‐4.85; P = 0.021). There was no difference in baseline variables or complications between the two groups. Other variables associated with successful arrhythmia induction included a longer procedure duration and atrioventricular nodal re‐entry tachycardia as the clinical arrhythmia. In a multivariable model, isoproterenol remained significantly associated with successful induction (OR, 2.57; 95% CI, 1.002‐6.59; P = 0.05). Conclusions Isoproterenol was significantly better than epinephrine for SVT arrhythmia induction. However, epinephrine was safe and successfully induced arrhythmias in the majority of patients who received it. Furthermore, when atropine was added in epinephrine‐refractory cases, in a post hoc analysis there was no difference in arrhythmia induction between medications. Cost savings could thus be significant without compromising safety

Rate-dependent and antiarrhythmic reentrant tachycardia (AVNRT) effects of simvastatin in isolated rabbit atrioventricular nodal model

Background and purpose: Several previous studies have shown the direct and indirect effects of statins on supraventricular and ventricular arrhythmia. The purpose of the present study is to determine (1) whether Simvastatin modifies the rate-dependent properties of the AV node, (2) to what extent such changes are related to effect of Simvastatin on the basic properties of AV nodal conduction and refractoriness. Materials and methods: AV nodal refractoriness (AVERP & AVFRP) and rate dependency protocols Fatigue and Facilitation were used to assesse the electrophysiological properties of AV node. We used an isolated perfussed rabbit with AV nodal preparation in one group (N=8). The stimulation protocols were carried out during control phase and in the presence of various concentrations of Simvastatin (0.5 , 0.8 , 1, 3 ,10 μm). Results: Simvastatin in concentration-dependent manner successfully prolonged effective and functional nodal refractory period (AVERP & AVFRP). Also an increase in Wenckebach cycle length was observed. Simvastatin in high concentration (3,10 μm) increases the arrhythmia threshold. Various concentrations of simvastatin increased fatigue, but it reached to significant level only at 30 μM. Conclusion: Simvastatin has potential anti-AVNRT effects by elevating arrhythmia threshold and prolongation of nodal refractoriness

Cardiac Arrhythmia and Geomagnetic Activity

Background: The purpose of this paper is a review of a number of studies considering links between life threatening cardiac arrhythmias, sudden cardiac death (SCD) and the level of environmental physical activity factors like geomagnetic activity (GMA) and opposite them cosmic ray and high energy proton flux. This is a part of studies in the field named Clinical Cosmobiology. Methods: Temporal distribution of cardiac arrhythmias and SCD daily and monthly were compared to the level of GMA, space proton flux, cosmic ray activity according to neutron activity (impulse/min) on the earth's surface. The cosmophysical data was obtained from the cosmic science institutions in the USA, Russia and Finland (cosmic ray data, partially). Results: As it follows from the results of the quoted studies there is an inverse relationship between the frequency of cardiac arrhythmic events and SCD and the level of daily GMA. Conclusions: Now studies are in progress considering the role of neutron (cosmic ray) activity in the natural history of the mentioned events. According to the various studies, we can presume that the GMA has some protective effect on cardiac arrhythmias and SCD

Short runs of atrial arrhythmia and stroke risk: a European-wide online survey among stroke physicians and cardiologists

Methods: An online survey of cardiologists and stroke physicians was carried out to assess current management of patients with short runs of atrial arrhythmia within Europe. Results: Respondents included 311 clinicians from 32 countries. To diagnose atrial fibrillation, 80% accepted a single 12-lead ECG and 36% accepted a single run of < 30 seconds on ambulatory monitoring. Stroke physicians were twice as likely to accept < 30 seconds of arrhythmia as being diagnostic of atrial fibrillation (OR 2.43, 95% CI 1.19–4.98). They were also more likely to advocate anticoagulation for hypothetical patients with lower risk; OR 1.9 (95% CI 1.0–3.5) for a patient with CHA2DS2-VASc = 2. Conclusion: Short runs of atrial fibrillation create a dilemma for physicians across Europe. Stroke physicians and cardiologists differ in their diagnosis and management of these patients

Potassium channel subunits encoded by the KCNE gene family: physiology and pathophysiology of the MinK-related peptides (MiRPs).

Voltage-gated potassium channels provide tightly Controlled, ion-specific pathways across membranes and are key to the normal function of nerves muscles. They arise from the assembly of four pore-forming proteins called alpha-subunits. To attain the properties of native currents, alpha-subunits interact with additional molecules such as the mink-related peptides (MiRPs), single-transmembrane subunits encoded by the KCNE genes. Significantly, mutations in KCNE 1, 2 and 3 have been linked either to life-threatening cardiac arrhythmia or a disorder of skeletal muscle, familial periodic paralysis. The capacity of MiRPs to partner with multiple alpha-subunits in experimental cells appears to reflect still undiscovered roles for the KCNE-encoded peptides in vivo. Here, we consider these unique peptides in health disease and discuss future research directions

Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

IntroductionAndersen-Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis.MethodsWe report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations.ResultsAll patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter-defibrillator was utilized in 40% of cases.ConclusionsKCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death