Automatic Activity Arising in Cardiac Muscle Sleeves of the Pulmonary Vein

Ectopic activity in the pulmonary vein cardiac muscle sleeves can both induce and maintain human atrial fibrillation. A central issue in any study of the pulmonary veins is their difference from the left atrial cardiac muscle. Here, we attempt to summarize the physiological phenomena underlying the occurrence of ectopic electrical activity in animal pulmonary veins. We emphasize that the activation of multiple signaling pathways influencing not only myocyte electrophysiology but also the means of excitation–contraction coupling may be required for the initiation of triggered or automatic activity. We also gather information regarding not only the large-scale structure of cardiac muscle sleeves but also recent studies suggesting that cellular heterogeneity may contribute to the generation of arrythmogenic phenomena and to the distinction between pulmonary vein and left atrial heart muscle.

Slow pseudo sinus rhythm and atrial tachycardia of right superior venous pulmonary origin

ABSTRACT Paroxysmal atrial tachycardia usually presents as a sudden acceleration of the atrial rate combined with modifications of the P wave morphology. A 22-year-old patient presented with very fast and very slow atrial ectopic activity. He complained of repetitive episodes of fast tachycardia, some accompanied with dizziness. When the ectopic discharge was slow, no clear-cut difference between the sinus rate and the ectopic rate was seen and thus the atrial rhythm appeared quite regular. The ectopic focus was situated deep inside the right upper pulmonary vein (RSPV). After RSPV isolation a persistent sinus rhythm was established and since then the patient has been asymptomatic for 3 years. Thus, subtle changes in the P wave morphology without a significant change in the heart rate in patients presenting with palpitations can give a clue to the diagnosis of the tachycardia and the localization of the ectopic focus.

Impact of excessive supraventricular ectopic activity detected in the acute phase of stroke or TIA on AF detection and death within 24 months – results of the prospective MonDAFIS study

Background/Introduction Detection of atrial fibrillation (AF) and subsequent initiation of oral anticoagulation remain key goals in the care of stroke patients. The European Society of Cardiology guideline recommend continuous ECG monitoring for at least 72 hours in stroke patients without previously known AF. Excessive supraventricular ectopic activity (ESVEA) has been identified as a marker for patients at risk for AF in the general population. Robust data on the clinical relevance of ESVEA detected in the acute phase of ischemic stroke or transient ischemic attack (TIA) are lacking. Purpose To assess the impact of ESVEA (defined as presence of supraventricular beats ≥480/day or at least one atrial run of ≥10 and <30 seconds during continuous ECG monitoring for 72 hours) in patients with acute ischemic stroke/TIA without (previously) known AF on recurrent stroke, all-cause death and detection of a first episode of AF within 24 months. Methods The investigator-initiated, prospective, open, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke study randomized 3,465 acute stroke patients without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter-ECG recording for up to seven days in-hospital (NCT02869386). ECG core-lab analysis included the number of atrial ectopic beats per day, the number of atrial runs as well as the duration of the longest atrial run per 24 hours. Patients were followed-up for two years. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding and all-cause death in ESVEA patients, patients with newly diagnosed AF vs. non-ESVEA patients with sinus rhythm at baseline. Data were analyzed using Fisher's exact test. Results In 1,714 patients randomized to the intervention group, 1,693 (98.8%) had analyzable ECG recordings of a median duration of 121 hours (IQR 73–166). 1,435 (84.8%) patients had continuous ECG monitoring for the first 72 hours. At this time, ESVEA was detected in 363 (25.3%) of 1,435 patients, while a first episode of AF was detected in 48 (3.3%). At 24 months, AF was newly detected in 57 (15.7%) ESVEA patients vs. 53 (6.2%) non-ESVEA patients (p<0.001) with available follow-up. At 24 months, 68 (24.5%) ESVEA patients vs. 77 (9.0%) non-ESVEA patients were on oral anticoagulation (p<0.001). The composite of recurrent stroke, myocardial infarction, major bleeding and death at 24 months did not differ significantly between ESVEA patients vs. non-ESVEA patients (14.3% vs. 11.6%; p=0.389). However, all-cause death was higher in ESVEA patients (6.6% vs. 3.1% in non-ESVEA patients; p=0.01). Conclusions ESVEA detected after acute ischemic stroke/TIA identifies patients at high-risk for AF and may be used to guide prolonged ECG monitoring. The higher risk of death in ESVEA patients vs. non-ESVEA patients within 24 months after stroke/TIA deserves further investigation. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Vital GmbH, Bayer HealthCare Pharmaceuticals, Germany.

High Density Intramural Mapping of Post-Infarct Premature Ventricular Contractions.

Background: Spontaneous ventricular premature contractions (PVCs) in the post infarct milieu is assumed to be due to automaticity. However, the mechanism has not been studied with appropriate mapping tools. Objective: To study the mechanism of spontaneous PVCs with high density intramural mapping in a canine model, to test the hypothesis that post-infarct PVCs are due to re-entry rather than automaticity. Methods: In 15 anesthetized dogs, using 768 intramural unipolar electrograms, simultaneous recordings were made. After 30 mins of stabilization, recordings were made during the first 10 minutes of ischemia, and activation maps were constructed of individual beats. Acute ischemia was produced by clamping the left anterior descending coronary artery proximal to the first diagonal branch. The analysis was limited to the activation pattern of spontaneous ventricular beats. Results: In all experiments ST-T alternans occurred. In 8 of 15 dogs spontaneous ventricular beats occurred. In all 8 of these experiment earliest, ectopic activity occurred in the endocardium, well within the ischemic zone. From there, activity spread rapidly along the subendocardium, with endo-to epicardial spread along the non ischemic myocardium. Epicardial breakthrough always occurred at the border of the ischemic myocardium. In 3 dogs, delayed potentials were observed, which were earliest at the ischemic epicardium and extended transmurally with increasing delay towards the endocardium, where they culminated in a premature beat. Conclusion: Graded responses that occur with each sinus beat intramurally, when able to propagate from epicardium to endocardium is the mechanism by which PVCs are generated in post-infarct myocardium.

Characterisation of the R2R3 Myb subgroup 9 family of transcription factors in tomato

Tomato (Solanum lycopersicum) has many epidermal cell outgrowths including conical cells and multiple types of trichomes. These include the anther-specific trichome mesh which holds the anthers connate. The R2R3 Myb Subgroup 9 family of transcription factors is involved in development of epidermal cell outgrowths throughout the angiosperms. No previous study has examined all members of this transcription factor family in a single species. All 7 R2R3 Myb Subgroup 9 genes were isolated from tomato. They were ectopically expressed in tobacco to assess their ability to induce epidermal cell outgrowth. Endogenous expression patterns were examined by semi-quantitative RT-PCR at different stages of floral development relative to the development of anther trichomes. We report variation in the degree of epidermal cell outgrowth produced in transgenic tobacco for each ectopically expressed gene. Based on expression profile and ectopic activity, SlMIXTA-2 is likely involved in the production of leaf trichomes while SlMYB17-2 is the best candidate for the regulation of the anther trichome mesh. Analysis of the phenotypes of transgenic plants ectopically expressing all 7 genes has revealed the different extent to which members of the same transcription factor subfamily can induce cellular outgrowth.HighlightCharacterisation of all members of an important family of transcription factors within tomato showing that all are able to induce epidermal cell outgrowths to varying degrees.

Coronary heart disease and atrial fibrillation: a vicious cycle

The population suffering from coronary heart disease (CHD) complicated by atrial fibrillation (AF) is rising rapidly. A strong correlation between the two diseases has been reported, and the many common risk factors they share may play prominent roles in their development. In addition, CHD can directly promote the progression of AF by affecting reentry formation, focal ectopic activity, and neural remodeling. At the same time, AF also affects CHD through three aspects: 1) atherosclerosis, 2) the mismatch of blood supply and oxygen consumption, and 3) thrombosis. In conclusion, CHD and AF can aggravate each other and seem to form a vicious cycle. For patients with CHD complicated by AF, principal studies and guidelines have focused on antithrombotic treatment and rhythm control, which are paramount for these patients. Of note, our review sheds light on the strategies to break the cycle of the two diseases, which may be fundamental to treat these patients and optimize the benefit.

Supraventricular ectopic activity as a predictor of atrial fibrillation – what we didn't see 10 years ago

Background Cardioembolism induced by atrial fibrillation (AF) is responsible for up to 33% of all ischemic strokes. 24-hour Holter monitoring in stroke and transient ischemic attack (TIA) patients is used as a routine investigation to search for occult paroxysmal atrial fibrillation (PAF), which may have crucial prognostic impact. Excessive supraventricular ectopic activity (ESVEA) is also a stroke risk factor, probably related to the risk of developing AF. Purpose To observe the incidence of AF at a long-term follow-up and to evaluate the clinical, electrocardiographic and echocardiographic predictors of new onset AF in stroke patients. Methods Patients in sinus rhythm who performed Holter between October 2009 and October 2011 in the setting of post stroke or TIA were included; patients with previous AF were excluded. These patients were followed for 8 to 10 years. Clinical, electrocardiographic and echocardiographic data were collected. ESVEA was defined by ≥500 premature atrial contractions per 24 hours or any sustained supraventricular tachycardia episode. Results 104 patients were included, 54% were male, with a mean age of 63.8±14.7 years at the time of the event. In relation to cardiovascular risk factors, 59% had hypertension, 47% dyslipidemia, 14% diabetes, 44% were smokers or previous smokers; 67% of patients were high consumers of alcohol. 79.8% had a stroke and 21.2% a TIA. 24-hour Holter monitoring revealed ESVEA in 13.5% of patients and PAF in 1.9%. All patients with PAF had a previous stroke and were older than 55. At a follow-up of 8–10 years, new onset AF was detected in 11.5%; these patients had similar mortality comparing to those in sustained sinus rhythm (21.2% vs 16.7%, p=0.724). Alcohol intake, an established risk factor for development of AF, was associated with a non-significant increase of AF (17.3% vs 11.5%) while the presence of cardiovascular risk factors was not associated with AF development. We found a statistically significant difference between patients with and without ESVEA concerning to new onset of AF (35.7% vs 8.0%, p=0.010). ESVEA seems to be related with a higher mortality at a long follow-up, although this difference wasn't statistically significant (35.7% vs 18.2%, p=0.132). Concerning to echocardiographic parameters, patients whit left atrium enlargement showed a higher incidence of AF at follow-up (14.7% vs 7.9%), and the presence of mitral regurgitation were not related with new onset of AF. Patients' age was also not related with new onset of AF during follow-up. Conclusion Atrial fibrillation is considered the main cause of stroke. Our study showed that ESVEA is a strong predictor of new onset AF and highlights that Holter monitoring could be an important tool not only to diagnose AF but also to identify patients in risk of develop AF. Diagnostic of new AF during long-term follow up didn't correlate with higher mortality. Funding Acknowledgement Type of funding source: None