Atrial Fibrillation Induction and Determination of Atrial Vulnerable Period Using Very Low Energy Synchronized Biatrial Shock in Normal Subjects and in Patients with Atrial Fibrillation

The atrial vulnerable periods (A VP)for shock induction of atrial fibrillation (AF) in humans have not been clearly defined. Furthermore, the safety and efficacy of using low energy biatrial shock delivered transvenously for AF induction are unknown. We tested the safety and efficacy of using very low energy biatrial shocks, delivered between the right atrium and the coronary sinus for AF induction and used this technique to characterize the A VP in nine controls and nine patients with AF. Thirty-volt and 60-V 3/3-ms biphasic shocks were delivered, starting from 50 ms before the atrial effective refractory period with 20-ms increments until the end of the QRS interval to determine the AVP front, AVP end, and the AVP duration. Successful AF induction could be achieved in eight (89%) of the nine controls and in nine (100%) of the nine patients with AF without any complication. In patients with AF, the AVP front started significantly earlier within the QRS complex, and the AVP duration and the AVP duration/QRS percent ratios were also significantly greater as compared to controls. Furthermore, a higher induction shock energy in patients with AF was associated with an increase in AF inducibility and significantly increased the AVP duration and A VP duration/QRS percent ratio as compared to the controls. This study demonstrated the safe and efficacy of delivering a very low energy biatrial shock during the AVP within the R wave for AF induction. The characteristics of A VP in patients with AF were significantly different from normal subjects.     

Sleep disorders and their clinical significance in children with Down syndrome

Aim Our aim was to review basic aspects of sleep disorders in children with Down syndrome in the light of present‐day findings of such disorders in children in general, including other groups of children with developmental disabilities. Methods A literature search of adverse developmental effects of sleep disturbance, types of sleep disturbance in children with Down syndrome, their aetiology, including possible contributions of physical and psychiatric comorbidities and medication effects, principles of assessment and diagnosis, and treatment issues, was carried out. Results Sleep disturbance is particularly common in children with developmental disorders including Down syndrome. Although there are just three basic sleep problems (sleeplessness or insomnia, excessive daytime sleepiness, and parasomnias) there are many possible underlying causes (sleep disorders), the nature of which dictates the particular treatment required. In children with Down syndrome, in addition to the same influences in other children, various comorbid physical and psychiatric conditions are capable of disturbing sleep. Possible adverse medication effects also need to be considered. Interpretation Screening for sleep disorders and their causes should be routine; positive findings call for detailed diagnosis. Management should acknowledge the likely multifactorial aetiology of the sleep disorders in Down syndrome. Successful treatment can be expected to alleviate significantly the difficulties of both child and family.     

The Acute Toxicity of Inhaled Beryllium Metal in Rats

The Acute Toxicity of Inhaled Beryllium Metal in Rats. HALEY,P. J., FINCH, G. L., HOOVER, M. D., AND CUDDIHY, R. G. (1990).Fundam. Appl. Toxicol. 15, 767–778. We exposed rats onceby nose only for 50 min to a mean concentration of 800 µg/m³of beryllium metal (initial lung burden, 625 µg) to characterizethe acute toxic effects within the lung. Histological changeswithin the lung and enzyme changes within bronchoalveolar lavage(BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and171 days postexposure (dpe). Beryllium metal-exposed rats developedacute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolarfibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesionswere replaced by minimal interstitial and intraalveolar fibrosis.Necrotizing inflammation was observed again at 59 dpe whichprogressed to chronic-active inflammation by 115 dpe. This inflammationworsened progressively, as did alveolar macrophage and epithelialhyperplasia, becoming severe at 171 dpe. Low numbers of diffuselydistributed lymphocytes were also present but they were notassociated with granulomas as is observed in beryllium-induceddisease in man. Throughout the experiment, total numbers ofcells were elevated within the BAL samples due primarily toincreased numbers of neutrophils. Lymphocytes were not elevatedin BAL samples collected from beryllium-exposed rats at anytime after exposure. Lactate dehydrogenase (LDH), ß-glucuronidase,and protein levels were elevated in BAL fluid from 3 through14 dpe but returned to near normal levels by 31 dpe. LDH increasedonce again at 59 dpe and remained elevated at 171 dpe. ß-Glucuronidaseand protein levels were slightly, but not significantly, elevatedfrom 31 through 171 dpe. Results indicate that inhalation ofberyllium metal by rats results in severe, acute chemical pneumonitisthat is followed by a quiescent period of minimal inflammationand mild fibrosis. Progressive, chronic-active, fibrosing pneumonitisis observed later. Chronic beryllium lung disease of man isan immunologically mediated granulomatous lung disease, whereasberyllium-induced lung lesions in rats appear to be due to directchemical toxicity and foreign-body-type reactions.     

Relationship Between Serum Potassium Concentration and Risk of Recurrent Ventricular Tachycardia or Ventricular Fibrillation

INTRODUCTION: Electrolyte abnormalities are considered a correctable cause of a life-threatening ventricular arrhythmia according to American Heart Association/American College of Cardiology Practice Guidelines, and ventricular tachycardia or ventricular fibrillation in the setting of an electrolyte abnormality is considered a class III indication for defibrillator implantation. However, there are little data to support this recommendation. The purpose of this study was to determine the risk of a recurrent sustained ventricular arrhythmia in patients with a low serum potassium concentration at the time of an initial episode of a sustained ventricular arrhythmia. METHODS AND RESULTS: One hundred sixty-nine consecutive patients who presented with a sustained ventricular arrhythmia and a serum potassium concentration determined on the day of the arrhythmia underwent defibrillator implantation. All patients had structural heart disease and left ventricular ejection fraction of 0.32+/-0.15. On the day of the index arrhythmia, 30% of the patients had a serum potassium concentration <3.5 or >5.0 mEq/L, including 7% who had a serum potassium concentration <3.0 or >6.0 mEq/L. For the entire cohort of patients, freedom from a recurrent sustained ventricular arrhythmia was 18% at 5 years and was not significantly different among patients with a serum potassium concentration <3.5 mEq/L (23%), between 3.5 and 5.0 mEq/L (16%), and >5.0 mEq/L (5%; P = 0.1). CONCLUSION: The results of the present study suggest that patients with structural heart disease and an abnormal serum potassium concentration at the time of an initial episode of sustained ventricular tachycardia or ventricular fibrillation are at high risk for a recurrent ventricular arrhythmia; therefore, implantable defibrillator therapy may be reasonable.     

Radiofrequency Catheter Ablation of the Atrioventricular Junction by a Supravalvular Noncoronary Aortic Cusp Approach

Radiofrequency catheter ablation of the atrioventricular janction is usually achieved from either the right or left atrioventricular junction. We describe a new approach in which the atrioventricular junction was successfully ablated from the supravalvular region of the noncoronary cusp of the aortic valve in an unusual patient in whom conventional approaches were unsuccessful.     

The Origin of Epicardial Ventricular Tachycardia Revealed by Entrainment From a Permanent Epicardial Left Ventricular Pacing Lead

Entrainment From Left Ventricular Pacing Lead. Recognizing ventricular tachycardias (VTs) that require epicardial ablation is desirable, but challenging when prior surgery prevents percutaneous epicardial mapping. This patient had cardiomyopathy, prior cardiac surgery, and VT that failed endocardial ablation. Observing that the Bi‐V implantable cardioverter defibrillator (ICD), left ventricular (LV) lead was epicardial to the area of infarct scar, it was used to pace during VT. Entrainment with concealed fusion with long stimulus to QRS interval, consistent with an epicardial VT circuit, was observed. Surgical cryoablation targeting the area around the LV lead eliminated VT. Thus pacing maneuvers from permanent epicardial leads can occasionally help identify an epicardial VT origin. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1293‐1295, November 2010)     

Stroke Risk Stratification in a “Real‐World” Elderly Anticoagulated Atrial Fibrillation Population

Stroke Risk Stratification . Introduction: Appropriate stroke risk stratification is essential to ensure suitable tailoring of antithrombotic therapy. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation (AF) who are at substantial risk of stroke despite optimal anticoagulant therapy, in a “real world” consecutive elderly AF cohort. Methods: Six hundred and sixty‐two consecutive AF patients (mean [SD] age 74 [7.7] years; 36.1% female) referred to the Anticoagulation Clinic of the Azienda Ospedaliera Careggi of Florence, Italy, were included and followed‐up for a mean 3.6 ± 2.7 years for the incidence of thromboembolic (TE) events. The ability of the new CHA₂DS₂‐VASc schema to predict TE was compared with other contemporary stroke risk schema (including CHADS₂, NICE 2006, ACC/AHA/ESC 2006, and ACCP 2008), by determining the c‐statistic. Results: Univariate predictors of TE events were female gender (odds ratio 1.9; 95%CI [confidence intervals] 1.01–3.70) and previous stroke/transient ischemic attack (TIA)/TE (OR 5.6; 95%CI 2.70–11.45), although after adjustment only previous stroke/TIA/TE was an independent predictor of TE (OR 5.5; 95%CI 2.68–11.31; P = 0.0001). All stroke risk schema had modest discriminating ability, with c‐statistics ranging from 0.54 (atrial fibrillation investigators [AFI]) to 0.72 (CHA₂DS₂‐VASc). The CHADS₂ and CHA₂DS₂‐VASc schemes having the best c‐statistics (0.717 and 0.724, respectively) with significant discriminating value between risk strata (both P < 0.001). The proportion of patients assigned to individual risk categories varied widely across the schema, with those categorized as “moderate‐risk” ranging from 5.3% (CHA₂DS₂‐VASc) to 49.2% (CHADS₂‐classical). Conclusion: In this “real world” cohort, current published risk schemas have modest predictive ability, with the CHADS₂ and CHA₂DS₂‐VASc schemes having the best predictive value for thromboembolism. Future trials could assess the value of alternative strategies for thromboprophylaxis in high‐risk anticoagulated patients identified by these schemes. (J Cardiovasc Electrophysiol, Vol. 22, pp. 25‐30, January 2011)     

Effects of Optical Enantiomers CK-4000(S) and CK 4001(R) on Defibrillation and Enhancement of Shock- Induced Extension of Action Potential Duration

Antiarrhythmic Drugs and DFT. Introduction: Class III antiarrhythmics have been reported to lower defibrillation threshold (DFT); however, the mechanism(s) of this effect is unknown. Recent evidence suggests that DFT strength DC shocks may terminate reentrant arrhythmias through prolongation of action potential duration and refractory periods. Since Class III antiarrhythmic drugs prolong repolarization, we examined the hypothesis that these drugs enhance shock-induced action potential duration extension (APDE), which might contribute to lowering of DFT. Methods and Results: In order to investigate the specificity of drug effects on action potential repolarization following a shock, an optical enantiomer with mixed β-blocking and Class III effects (CK-4000) and its enantiomer with “pure” Class III antiarrhythmic effects (CK-4001) were compared against placebo in a canine defibrillation model (n = 8 per group). At the 3 mg/kg dose, the enantiomers nonstereoselectively lowered DFT voltage by 19 ± 15% (CK-4000, P < 0.05 compared to placebo) and 25 ± 12% (CK-4001, P < 0.05 compared to placebo), indicating that Class III antiarrhythmic actions alone were sufficient for this effect. Similarly, CK-4000 and CK-4001 at 3 mg/kg enhanced APDE (P < 0.01 compared to placebo) by 20 ± 11% and 24 ± 17%, respectively. APDF prolongation significantly correlated with reduction in DFT voltage for both CK-4000 (r = -0.55, P < 0.03) and CK4001 (r = -0.63, P < 0.01). At 3 mg/kg, the enantiomers stereoselectively prolonged action potential duration (APD₇₅) by an average of 37 ± 14% (CK-4000, P < 0.001) and 23 ± 14% (CK-4001, P < 0.001), and ventricular effective refractory period (VERP) by 38 ± 15% (CK-4000, P < 0.01) and 27 ± 13% (CK-4001, P < 0.05). Prolongations of APD₇₅ and VERP did not correlate with reductions of DFT in individual dogs. Conclusions: These results show that Class III antiarrhythmics and DFT strength shocks additively delay repolarization, which suggests that drug enhancement of APDE may contribute to their effects on DFT.