Chemical cardioversion of recent-onset atrial fibrillation in the emergency department using vernakalant hydrochloride achieves safe and rapid restoration of sinus rhythm and facilitates same day discharge.

BACKGROUND: Vernakalant hydrochloride is a rapid-acting antiarrhythmic drug licensed in the EU since 2010 for the conversion of recent-onset atrial fibrillation with proven efficacy and safety when compared with placebo and amiodarone in randomized clinical trials. AIMS: The aim of our study was to determine the feasibility of same day discharge (following 2 h monitoring) from the emergency department after successful cardioversion using vernakalant hydrochloride. METHODS: Patients with recent-onset atrial fibrillation treated in the emergency department of a large Dublin academic teaching hospital. Patients received a maximum of two weight based 10 min infusions of vernakalant. Hypotensive events (>30% initial blood pressure), arrhythmias, conversion rates, and time to conversion were recorded. RESULTS: Sinus rhythm was restored in 35 out of 42 patients (83%) in an average of 8.8 min (median 8 min), average CHA2DS2-VASc of 0.92, HAS-BLED of 0.21 and average symptoms duration of 12 h. There were no hypotensive or arrhythmogenic events. 41 out of 42 patients were discharged after 2 h of monitoring. CONCLUSIONS: Vernakalant hydrochloride has provided a quick, safe, and practical means of achieving rapid restoration of sinus rhythm in our ED population with stable recent-onset AF who would otherwise not have undergone routine electrically cardioversion and same day discharge.

Evaluating cardioversion outcomes for atrial fibrillation on novel oral anticoagulants versus warfarin: experience at a tertiary referral centre.

BACKGROUND: Current guidelines recommend anticoagulation prior to cardioversion in patients with atrial fibrillation of >48 h or unknown duration to reduce thromboembolic risk. Therapeutic anticoagulation with warfarin, with INR between 2 and 3, is consistently achieved in approximately 60% of patients. AIMS: We evaluated outcomes and assessed differences in direct current cardioversion (DCCV) in patients treated with warfarin and novel oral anticoagulants (NOAC) at our institution. METHODS: A retrospective analysis of consecutive DCCV at a tertiary referral over 18 months was conducted. Analysis of cardioversion records allowed completion of a standardised dataset. Clinical variables recorded included (1) CHADSVASC score, (2) anticoagulant use, and (3) bleeding complications. RESULTS: During this period 187 DCCVs were scheduled; 119 on warfarin and 68 on NOAC. DCCV was deferred in 26% (n = 31) of the warfarin group and 4.4% (n = 3) of the NOAC group (p = 0.0002). The average time interval between referral and DCCV was 144.43 and 109.32 days for the warfarin and NOAC groups, respectively (p value = 0.023). 7.56% (n = 9) of the warfarin population had a bleeding event compared to a 2.94% total bleeding rate in NOAC group (p = 0.213). Deferral of elective DCCV and additional anticoagulant monitoring was estimated at €1160 per procedure. CONCLUSION: In elective cardioversions, the group anticoagulated with NOAC was less likely to have subtherapeutic anticoagulation and hence deferred procedures and had reduced health care consumption when compared to the group anticoagulated with warfarin.

Morphological patterns of death by myocytes in arrhythmogenic right ventricular dysplasia.

There are two forms of nuclear loss from eukaryotic cells: biochemical DNA degradation in apoptosis and nuclear extrusion from the cell body as seen in mammalian erythroblasts. In biopsies of right ventricular myocardium from 8 patients with arrhythmogenic right ventricular dysplasia (ARVD), we found not only a terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling (TUNEL)-positive nucleus in mononuclear myocytes, but also 1 or 2 TUNEL-positive nuclei in multinuclear myocytes. With electron microscopy, we found a nuclear dislocation to the cell periphery, followed by its extrusion into the extracellular space. Both the migration and extrusion of the nuclei of myocytes resemble the morphogenesis of human erythroblasts. Nuclear extrusion from myocytes may be another form of programmed cell death. In support of this possibility, we also found evidence of cytoplasmic degradation in right ventricular myocytes from our ARVD cases, a process similar to one often seen in developmental programmed cell death and differing from typical nuclear apoptosis. In our ARVD cases, we thus found several different patterns of cell death, all associated with initial preservation of the plasmalemma and avoidance of local inflammation. All these features may be different responses to common signals for selective non-necrotic (apoptotic) death of right ventricular myocytes.

Primary prevention of sudden cardiac death in heart failure: will the solution be shocking?

Sudden cardiac death (SCD) may occur in as many as 40% of all patients who suffer from heart failure. This review describes the scope of the problem, risk factors for SCD, the effect of medications used in heart failure on SCD and the potential effect of the implantable cardioverter-defibrillator in primary prevention.

Hypertrophic cardiomyopathy: presentation and pathophysiology.

HCM is a heterogeneous disease with various clinical presentations. Recent advances in understanding the genetic abnormalities responsible for ventricular hypertrophy promise to improve our ability to diagnose this condition and to identify subgroups who are at the highest risk of cardiovascular mortality. Numerous difficulties remain in treating patients with HCM, including obtaining relief of symptoms and preventing SCD, but several new treatment options are currently being evaluated. In the future, randomized trials comparing the major treatment options (eg, pharmacologic therapy, myotomy/myectomy, mitral valve replacement, pacemaker implantation, and nonsurgical septal reduction) will be needed to provide guidance concerning the optimal treatment of patients with HCM.

Serial measures of sinoatrial and atrioventricular nodal function in ambulatory patients.

We hypothesized that the outpatient assessment of SA and AV nodal (SAN, AVN) function could be a useful tool to determine the effectiveness of drugs and other treatments. We sought to examine the reproducibility, safety and ease of acquiring serial measurements of these parameters. Ten patients with permanent pacemakers underwent low current chest wall stimulation while their device was programmed to unipolar atrial triggered mode. Measurements at multiple conditioning drive train frequencies were obtained for: sinus nodal recovery time (SNRT); corrected sinus nodal recovery time (CSNRT); SA conduction time (SACT); AVN block cycle length (AVNBCL); and AVN effective refractory period (AVNERP). AVN function curves were also constructed. All studies were repeated after 2 weeks. Measures of sinus nodal and AVN function did not show significant differences between the two studies. The following co-efficients of correlation were obtained: SNRT800, r = 0.79; CSNRT800, r = 0.71; SNRT600, r = 0.71; CSNRT600, r = 0.44; SACT, r = 0.75; AVNBCL, r = 0.98; AVNERP800, r = 0.55; and AVNERP600, r = 0.99. AVN function curves did not significantly differ between week 1 versus week 2 at conditioning drive trains of either 800 ms or 600 ms. These data suggest that serial noninvasive electrophysiological measures of AVN and SAN function are reproducible over 2 weeks. Using data in this study, estimates of the sample size necessary for the evaluation of the effects of investigational drugs on the SAN and AVN in future studies are possible.

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

Dual device therapy in the setting of changing ICD technology: device-device interaction revisited.

This case report concerns an adverse device-device interaction between a replacement ICD and a dual chamber rate responsive pacemaker. It was observed that subtle changes in the design of sensing circuits between an older first-generation ICD and the newer third-generation ICD device led to unexpected and dramatic changes in the interactive behavior of a dual device system. The new ICD was connected to chronically implanted hardware. The sensing behavior of the newer ICD included a shorter time constant in the decay of the automatic gain control function, resulting in triple sensing of both the atrial and ventricular paced stimuli and the evoked QRS complex. Physicians should be aware of new design changes in the future so as to anticipate such interactions. In the setting of rapidly changing technology, extra caution must be exercised when choosing to implant two devices in the same patient.

Lateral and anterior reciprocal electrocardiographic changes: relationship to ST segment elevation and underlying coronary artery disease in inferior myocardial infarction.

The electrocardiogram in patients with acute inferior myocardial infarction frequently displays ST depression in non-infarct leads. The significance of this finding is uncertain. The relationship between ST depression, ST elevation and arteriographic severity of coronary artery disease was explored. 22 patients with acute inferior myocardial infarction, receiving thrombolysis and undergoing acute (within seven hours of the onset of chest pain) coronary angiography were studied prospectively. The electrocardiographic ST segment elevation in the inferior leads and ST segment depression in the lateral and in the anterior precordial leads were measured. In each group of leads, the maximum value of ST deviation in any lead as well as the sum of the values for ST deviation in the individual leads was determined. Gensini scores of total coronary artery disease and component scores for the major coronary arteries were determined from the coronary arteriogram. There was a strong correlation of maximum inferior ST elevation with both maximum lateral ST depression (r = 0.96, p < 0.001) and with maximum anterior precordial ST depression (r = 0.78, p < 0.001). The corresponding correlations for sum of ST deviations were r = 0.91, p < 0.001 and r = 0.79, p < 0.001 respectively. There was no relationship between Gensini scores of coronary artery disease and measures of electrocardiographic ST segment depression or elevation. Electrocardiographic ST depression in non-infarct leads in patients with inferior myocardial infarction, does not provide information regarding the degree of coronary artery disease. The ST depression in both lateral and anterior precordial leads correlates with and is a reflection of inferior ST elevation.

d-Sotalol decreases defibrillation energy requirements in humans: a novel indication for drug therapy.

INTRODUCTION: We assessed the effect of d-sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects. The d-isomer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d-sotalol would decrease defibrillation voltage and energy requirements in humans. METHODS AND RESULTS: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation "threshold" measurements), ventricular effective refractory period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d-sotalol. There was a significant decrease in defibrillation energy (E50 = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consistent with the Class III effect of d-sotalol, ventricular effective refractory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001), and action potential duration was prolonged from 296 +/- 28 to 340 +/- 22 msec (P < 0.001). Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects. CONCLUSIONS: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27% at concentrations producing a 16% +/- 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.

Atrioventricular node reentry with 'smooth' AV node function curves: a different arrhythmia substrate?

BACKGROUND: Some patients with otherwise typical AV node reentry do not manifest discontinuous AV node function curves. We examined the effects of an ablation in the slow-pathway region in patients with smooth AV node function curves. METHODS AND RESULTS: Fifteen patients with AV node reentrant tachycardia (AVNRT) and discontinuous AV node function curves were compared with 15 patients with AVNRT and smooth AV node function curves. In the group with discontinuous curve, the "net" anterograde effective refractory period (AERP) of the AV node increased (270 +/- 28 versus 304 +/- 37 ms, P = .03) and AERP of the remaining fast pathway decreased (367 +/- 100 versus 304 +/- 37 ms, P = .026) after the ablation. In the group with a smooth curve, the AERP of the AV node increased (266 +/- 42 versus 299 +/- 76 ms, P = .07) and the anterograde Wenckebach cycle length increased (336 +/- 66 versus 379 +/- 86 ms, P = .008) after the ablation. Retrograde conduction over the AV node was similar in both groups and was unchanged after ablation. The longest attainable AH interval (AHmax) measured during atrial extrastimulus testing was more prolonged in patients with a discontinuous curve than in patients with a smooth curve (326 +/- 48 versus 250 +/- 70 ms, P = .002). The AHmax shortened in both groups after ablation (326 +/- 48 versus 173 +/- 34 ms, P < .0001, and 250 +/- 70 versus 179 +/ 34 ms, P < .0003, respectively) and were similar. Successful ablation in the slow-pathway zone in patients with a smooth AV node function curve resulted in the loss of the "tail" of the curve representing the slow pathway. CONCLUSIONS: These data suggest that the smooth AV node function curve consists of two distinct components representing both fast and slow AV node pathways even when the typical discontinuity is absent.