Ventricular Rate In Atrial Fibrillation Research Articles

CE-452779-1 IVABRADINE FOR CONTROLLING HEART RATE IN PERMANENT ATRIAL FIBRILLATION: RESULTS OF THE TRANSLATIONAL CLINICAL TRIAL BRAKE-AF

Ivabradine has been postulated to reduce the ventricular rate in atrial fibrillation. However, the mechanisms responsible for that reduction and its performance as rate-control drug are not known To evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety compared with digoxin in permanent atrial fibrillation The effects of ivabradine in atrioventricular nodal and ventricular cells were studied by in-vitro whole-cell patch-clamp experiments . Changes in If, INa, ICaL, ICaT, IKs, IKr, and IK1 conductances were integrated in mathematical simulations of nodal and ventricular action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine (5mg BID increased to 7.5mg BID after one month) versus digoxin (0.10-0.25mg QD adjusted by serum levels) for uncontrolled permanent atrial fibrillation despite beta-blockers or calcium channel blockers. Primary efficacy and safety endpoints were the reduction of the mean daytime heart rate at 3 months and a combination of syncope, clinically significant bradycardia or serious drug-related adverse events, respectively. The primary efficacy endpoint was evaluated by intention to treat using the O'Brien–Fleming method. Safety endpoints were evaluated with χ2 or Fisher’s exact tests Ivabradine 1 μM inhibited If and IKr by 28.9% and 22.8% (P<0.05) respectively. INa and ICaL were also reduced but only at 10 μM. Ivabradine slowed the firing frequency of a modelled human AV nodal action potential by 10.6% and induced a minimal prolongation of the ventricular action potential. The clinical trial randomized 35 patients to ivabradine and 33 to digoxin. Mean daytime heart rate decreased by 11.6 bpm (-11.5%) in the ivabradine arm (p=0.02) Vs 19.6 (-20.6%) in the digoxin arm (p<0.001) however, the non-inferiority margin of efficacy was not met (Z:-1.95; p=0.97). Primary safety endpoint occurred in 3 (8.6%) patients on ivabradine and in 8 (24.2%) on digoxin (p=0.10). Therapeutic adherence was lower in the digoxin arm (78.8% vs. 97.1%; p=0.02) Ivabradine produced a discrete heart rate reduction in patients with permanent atrial fibrillation. Compared with digoxin, ivabradine was less effective, better tolerated and had a similar rate of serious adverse events.The inhibition of If in the AV node seems the main mechanism responsible for the ivabradine-induced heart rate reduction in atrial fibrillation.

Ventricular rate in atrial fibrillation and the risk of heart failure and death.

While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [<60, 60-79, 80-99, and 100-110, > 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. Ventricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

Temporal Characteristics of Device-Based Individual and Integrated Risk Metrics in Patients With Chronic Heart Failure

BackgroundTemporal characteristics of a multimetric risk score and its individual parameters before, during, and after a heart failure (HF) event have not been defined. ObjectivesA large real-world patient cohort with implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) defibrillators was used to define these temporal characteristics. MethodsDeidentified health records were linked to manufacturer’s device database in 17,886 patients. Multimetric risk score combined daily measures of impedance, heart rate, activity, heart rate variability, and atrial fibrillation (AF) burden, AF ventricular rate, CRT pacing, and ventricular tachycardia episodes and shocks. HF event was defined as an inpatient, emergency department, or observation unit stay with primary diagnosis of HF and intravenous diuretic agents administration. Changes in risk parameters during 60 days before, during, and after an HF event were compared in patients with no HF readmissions vs patients with HF readmission. ResultsA total of 1,174 patients had HF events with no HF readmission, and 282 patients had HF events with HF readmission. Diagnostic risk score was higher on all 60 days before and after a HF event in patients with HF readmission compared with patients with no readmission (P < 0.001). Change in risk score from admission to discharge was similar in patients with and without HF readmission, but the risk score fell more significantly 7 after discharge and 30 days after admission in patients without HF readmission (P < 0.001). ConclusionsTemporal characteristics of risk metrics were significantly different in patients with no HF readmissions vs patients with HF readmission; patients without HF recurrence had larger recovery of risk metrics values toward normal.

Lieferengpass Digitoxin

Digitalis glycosides are used control ventricular rate in atrial fibrillation or in advanced heart failure with reduced ejection fraction. There is a bottleneck for digitoxin supply until 2023. Thus, the indications for treatment with Digitalis glycosides should be (re-)evaluated in each case. If there is an indication for treatment with Digitalis, digoxin can be used. As digoxin elimination relies much more on kidney function than digitoxin, overdosing can occur more frequently, especially when renal function worsens. Thus, circulating digoxin levels should be determined more frequently, and lower digoxin dosages should be used in patients with renal insufficiency.

Digoxin Holiday

Digoxin is used in clinical practice for two major purposes: To improve ventricular performance in heart failure with reduced ejection fraction and to control the ventricular rate in atrial fibrillation. It is a cardiac glycoside with a positive inotropic effect and causes atrioventricular nodal inhibition through vagomimetic effect. It also decreases the sympathetic drive generated by the failing circulation, which provides a rational in using the drug in congestive heart failure (CHF) with sinus rhythm. The use of this drug is a standard therapy in the treatment of CHF with atrial fibrillation. However, the dose adjustment of this drug is difficult because of the variation in its pharmacokinetic characteristics, the variability in its clearance, and the lack of a good relationship between the dose and the desired effect and its narrow therapeutic range. This creates difficulty for clinicians to choose the appropriate dosage of the drug to get the desired benefit without the risk of toxicity. In many countries, serum concentration monitoring is not always possible, so it is common in clinical practice to drop the medication for 1 or 2 days a week, giving the drug a ‘holiday,’ to avoid the risk of toxicity. This is contrary to the use of this drug without interruption in countries where routine serum concentration monitoring is possible. This review provides a summary of the evidence relating to the rationale behind using digoxin holiday and the therapeutic implications of digoxin holiday. Much of the information is available from prospective crossover clinical trials. There are no randomised control trials of digoxin holiday in patients with heart failure and/or atrial fibrillation.

Interference of enzalutamide on digoxin immunoassay: A case report

Androgen sensitive prostate cancer is a malignancy that may be treated with hormonal therapy. Enzalutamide, an androgen receptor antagonist, is indicated in patients with metastatic castration-resistant prostate cancer. The drug inhibits translocation of activated androgen receptors into the cell nucleus and prevents DNA binding, thereby inducing cell death and tumour regression. Digoxin is a widely used cardiac glycoside to treat heart failure and reduce ventricular rate in atrial fibrillation. Therapeutic drug monitoring is essential due to its narrow therapeutic index. However, digoxin assays can be affected by many substances including digoxin-like immunoreactive substances (DLIS), medications such as spironolactone, canrenoate, various Chinese medicines and anti-digoxin antibody. We present a case of falsely elevated digoxin levels due to enzalutamide interaction with the chemiluminescent microparticle immunoassay.

A Compelling Case for Less Aggressive Arrhythmia Management in Patients With Chronic Heart Failure and Long-Standing Atrial Fibrillation

Atrial fibrillation (AF) is common in chronic heart failure, and some have advocated intensive rate and/or rhythm control strategies for these patients. However, the loss of atrial systole and irregularity of the ventricular response has not been shown to contribute to the progression of heart failure, and the presence or rate of long-standing AF in patients with chronic heart failure does not have prognostic significance. In randomized clinical trials, pharmacological rhythm control has not been shown to be superior to rate-control in influencing long-term outcomes, but the use of membrane-active antiarrhythmic drugs can increase the risk of both pump failure and arrhythmic deaths in patients with heart failure. Additionally, intensive efforts to slow the ventricular rate in AF can potentially cause clinically inapparent bradyarrhythmias, which can trigger rate-dependent lethal rhythm disturbances or hemodynamic abnormalities. In patients with AF, a more stringent approach to rate control (target rate <80/min) is not superior to a more lenient strategy (target rate <110/min) on the risk of major events. Little is known about the effects of catheter ablation of long-standing AF in established heart failure, particularly in patients with a preserved or a meaningfully reduced ejection fraction, but ablation can add to the fibrotic burden of the left atrium and impair its capacitance functions. For all of these reasons, the management of heart failure and long-standing AF should be primarily directed to slowing of the progression of their underlying cardiomyopathic process rather than the treatment of the arrhythmia. In addition, patients should receive long-term oral anticoagulation with non-vitamin K-antagonist oral anticoagulants to reduce the risk of thromboembolic events. The utility of intensive rate and rhythm control interventions for long-standing AF in patients with established heart failure requires further study.

Bag-Valve-Mask Ventilation After Induction for Intubation: PreVenting Hypoxemia?: July 2019 Annals of Emergency Medicine Journal Club

Bag-Valve-Mask Ventilation After Induction for Intubation: PreVenting Hypoxemia?: July 2019 Annals of Emergency Medicine Journal Club

Stanley Nattel.

Stanley Nattel.

MORTALITY AND MORBIDITY IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION EXPOSED TO DIGOXIN: COMPREHENSIVE DATA ACCORDING TO ATRIAL FIBRILLATION IN 23,708 PATIENTS FROM THE SWEDISH HEART FAILURE REGISTRY

Background: Digoxin is approved for the reduction of ventricular rate in atrial fibrillation (AF) and the management of heart failure with reduced ejection fraction (HFREF). However, data from randomized trials in HFREF with and without AF are limited and a long-term assessment of outcomes is

Digoxin Is Associated With Increased All-cause Mortality in Patients With Atrial Fibrillation Regardless of Concomitant Heart Failure

For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201-1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074- 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148-1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.

Autologous dermal fibroblast injections slow atrioventricular conduction and ventricular rate in atrial fibrillation in swine.

Nonpharmacological ventricular rate control in atrial fibrillation (AF) without producing atrioventricular (AV) block remains a clinical challenge. We investigated the hypothesis that autologous dermal fibroblast (ADF) injection into the AV nodal area would reduce ventricular response during AF without causing AV block. Fourteen pigs underwent electrophysiology study before, immediately, and 28 days after ≈ 200 million cultured ADFs (n = 8) or saline (n = 6) were injected under electroanatomical guidance in the AV nodal area, with continuous 28-day ECG recording. In the ADF group at 28 days postinjection, there were prolongations of PR interval (after versus before: 130 ± 13 versus 113 ± 14 ms, P = 0.04), of AH interval during both sinus rhythm (92 ± 13 versus 76.8 ± 8 ms, P < 0.01) and atrial pacing at 400 ms (102 ± 13 versus 91 ± 9 ms, P < 0.01), and of AV node Wenckebach cycle length (230 ± 19 versus 213 ± 24 ms, P < 0.01), with no changes in the control group. The RR interval during induced AF 28 days after injections was 24% longer in ADF-treated group compared with controls (488 ± 120 versus 386 ± 116 ms, P < 0.001). Histological analysis revealed presence of ADF-labeled cells in the AV nodal area at 28 days. Transient accelerated junctional rhythm during injections, and transient nocturnal Mobitz I AV conduction occurred early postinjection in both groups. Cells survived for 4 weeks and significantly slowed AV conduction and ventricular rate in acutely induced AF. Critically, despite a large number of injections in the AV nodal area and marked effects on AV conduction, AV block did not occur. Further studies are necessary to determine the clinical feasibility and safety of this strategy for ventricular rate control in AF.

Digoxin Use to Control Ventricular Rate in Patients with Atrial Fibrillation and Heart Failure Is Not Associated with Increased Mortality.

Introduction. Digoxin is used to control ventricular rate in atrial fibrillation (AF). There is conflicting evidence regarding safety of digoxin. We aimed to evaluate the risk of mortality with digoxin use in patients with AF using meta-analyses. Methods. PubMed was searched for studies comparing outcomes of patients with AF taking digoxin versus no digoxin, with or without heart failure (HF). Studies were excluded if they reported only a point estimate of mortality, duplicated patient populations, and/or did not report adjusted hazard ratios (HR). The primary endpoint was all-cause mortality. Adjusted HRs were combined using generic inverse variance and log hazard ratios. A multivariate metaregression model was used to explore heterogeneity in studies. Results. Twelve studies with 321,944 patients were included in the meta-analysis. In all AF patients, irrespective of heart failure status, digoxin is associated with increased all-cause mortality (HR [1.23], 95% confidence interval [CI] 1.16–1.31). However, digoxin is not associated with increased mortality in patients with AF and HF (HR [1.08], 95% CI 0.99–1.18). In AF patients without HF digoxin is associated with increased all-cause mortality (HR [1.38], 95% CI 1.12–1.71). Conclusion. In patients with AF and HF, digoxin use is not associated with an increased risk of all-cause mortality when used for rate control.

Therapeutic Effects of Selective Atrioventricular Node Vagal Stimulation in Atrial Fibrillation and Heart Failure

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF.

Minimizing Inappropriate or “Unnecessary” Implantable Cardioverter-Defibrillator Shocks

Life-saving shocks are the raisons d'etre of implantable cardioverter-defibrillators (ICDs). Paradoxically, shocks also cause much of the morbidity associated with ICDs. Consistently, shocks reduce quality of life,1,2 and rarely, they may cause proarrhythmia.3,4 Additionally, shocks have been reported to be associated with excess mortality.5 Experts disagree about whether shocks are responsible for this excess mortality,6 but they do agree that ICDs should deliver the fewest shocks necessary to protect patients from ventricular tachycardia (VT) or ventricular fibrillation (VF). Minimizing ICD shocks requires a comprehensive approach, beginning with patient selection,7 general medical care (eg, preventing electrolyte abnormalities), and general cardiac care (preventing ischemia and treating heart failure). It includes the use of antiarrhythmic drugs and catheter ablation both to prevent VT or supraventricular tachycardia (SVT) and to control the ventricular rate in atrial fibrillation (AF) as well as the appropriate choice of hardware and device programming. This review focuses on ICD features and programming to minimize shocks. Figure 1 summarizes the sequential processes required for an ICD to deliver a shock. The sense amplifiers convert the continuous electrogram (EGM) from the tip of the right ventricular (RV) lead into a series of instantaneously sensed events representing ventricular depolarization. This series of sensed events is processed by ICD algorithms, including those for initial detection; SVT-VT discrimination; and in some models of ICDs, enhancements to minimize oversensing. If the rhythm is classified as a VT, antitachycardia pacing (ATP) can be delivered. The ICD then performs a redetection process, which results in determination that the device-defined VT either has terminated or persists. If VT is redetected, the process iterates until all programmed ATPs are delivered. The ICD then charges the high-voltage capacitors, during which time a final round of ATP may be delivered. After capacitor …

Contemporary Indications and Therapeutic Implications for Digoxin Use

Heart failure (HF) is a leading cause of morbidity and mortality. Appropriate medical therapy using angiotensin converting enzyme inhibitors and beta-blockers improves outcomes in HF, whereas the role of digoxin is still not clearly defined. Digoxin is currently recommended for patients with HF who are symptomatic despite standard therapy and for controlling the ventricular rate in atrial fibrillation. Digoxin is a time-tested drug that accounts for 20 million drug prescriptions annually in the United States. It has favorable hemodynamic effects for patients with HF and atrial tachyarrhythmias. We conducted a systematic literature search for the current indications for digoxin. Despite extensive research and safety data, the literature suggests that digoxin is underused in clinical settings. Citing the literature where available, our review highlights the various clinical settings where digoxin is indicated. Despite difficulties with designing prospective studies in acute HF settings and lack of outcomes data, we believe that digoxin will continue to serve an important role in optimizing care in certain acute and chronic cardiac conditions.

Effect of prophylactic amiodarone in patients with rheumatic valve disease undergoing valve replacement surgery

The study was carried out to evaluate the effect of prophylactic single-dose intravenous amiodarone in patients undergoing valve replacement surgery. Maintenance of sinus rhythm is better than maintenance of fixed ventricular rate in atrial fibrillation (AF) especially in the presence of irritable left or right atrium because of enlargement. Fifty-six patients with valvular heart disease with or without AF were randomly divided into two groups. Group I or the amiodarone group (n=28) received amiodarone (3 mg/kg in 100 ml normal saline) and group II or the control group received same volume of normal saline. The standardized protocol for cardiopulmonary bypass was maintained for all the patients. AF occurred in 7.14% patients in group I, and in group II, 28.57% (P=0.035); ventricular tachycardia/fibrillation was observed in 21.43% patients in group I and 46.43% patients in group II (P=0.089) after release of aortic clamp. Most of the patients in group I (92.86%) maintained sinus rhythm without cardioversion or defibrillation after release of aortic cross clamp (P=0.002). Defibrillation or cardio version was needed in 7.14% patients in group I and 28.57% patients in group II (P=0.078). A single prophylactic intraoperative dose of intravenous amiodarone decreased post bypass arrhythmia in this study in comparison to the control group. Single dose of intraoperative amiodarone may be used to decrease postoperative arrhythmia in open heart surgery.

Vagal tone augmentation to the atrioventricular node in humans: Efficacy and safety of burst endocardial stimulation

Control of atrioventricular (AV) nodal conduction by endocardial stimulation of efferent AV nodal vagal fibers [atrioventricular nodal vagal stimulation (AVNS)] is a promising approach for long-term device-based modulation of ventricular rate during atrial fibrillation (AF). However, few data on the efficacy of AVNS delivered as high-frequency stimulus packages (burst AVNS) in humans are available. The purpose of this study was to determine whether burst AVNS can to modulate AV nodal conduction during AF and whether burst AVNS delivered during sinus rhythm (SR) in the effective atrial refractory period allows safe implantation of a permanent lead in a position suitable for AVNS. Twenty patients (10 in SR and 10 in AF) who were candidates for dual-chamber pacemaker implantation for sick sinus syndrome were enrolled in the study. The posteroseptal right atrium was mapped to identify a location at which burst AVNS would achieve AV nodal conduction modulation (lengthening of PR interval in SR and reduction of ventricular rate in AF). Subsequently, a lead was screwed in at that site and burst stimulation (pulse rate 50 Hz, burst duration 180 ms) was delivered at different burst rates, pulse durations, and amplitudes. In all SR patients, PR-interval prolongation was evoked at 90 and 120 bursts/minute with pulse durations < or =1 ms. Specifically, the mean voltages required to obtain PR-interval prolongation and advanced AV block were 4.3 +/- 2.2 V and 5.4 +/- 1.8 V (at 90 bursts/minute and 1 ms), respectively. Similarly, ventricular rate reduction was obtained in all AF patients, starting from 90 bursts/minute and 0.5-ms pulse duration (at 5.4 +/- 1.8 V). Ventricular arrhythmias were never induced during AVNS. Endocardial right atrial burst AVNS reduces ventricular rate during AF. Burst AVNS delivered during SR in the effective atrial refractory period allows optimization of lead positioning for AVNS.

Is verapamil a double-edged sword in rate control of paroxysmal atrial fibrillation?

Over the last decade, remarkable progress has been made in the field of atrial fibrillation (AF) pathophysiology and management. There is no doubt that radiofrequency catheter ablation therapy improves the quality of life and left ventricular function in patients with symptomatic AF by improving the maintenance of sinus rhythm. 1 A new antiarrhythmic agent, dronedarone, was recently shown to reduce the composite outcome of cardiovascular hospitalization and death in patients with AF. 2 Moreover, novel approaches such as the dominant frequency (DF) analysis of atrial electrograms have offered clinicians a better insight into the pathogenesis of AF. 3 Despite these advancements, longterm maintenance of sinus rhythm is challenging, and persistent or permanent AF still develops in many patients. In these cases, control of the ventricular rate has an essential role in alleviating the symptoms and preventing the development of tachycardia-induced cardiomyopathy. Spectral analysis of atrial recordings increasingly has been used to detect areas with high atrial activation rate during AF. The main benefit of frequency domain analysis is that it can be applied to the complex electrograms of AF more easily than time domain measurements. 3 Experimental and clinical studies indicate that the DF sites within the pulmonary veins (PV) have an important role in the initiation and maintenance of paroxysmal AF. 4,5 Furthermore, it has been postulated that DF mapping can be used to guide rapid identification of extrapulmonary sites that drive AF. 6 In this issue, Kushiyama et al 7 report the results of a study that evaluated the effects of verapamil on regional distribution of DFs in the PVs and atria in 43 patients undergoing catheter ablation of paroxysmal AF. They found that the highest DF was localized in the PVs and showed that there was a substantial PV-to-atria DF gradient at baseline. These findings are in agreement with previous studies indicating that the PVs are the main drivers of paroxysmal AF. 4,5 It is well established that beta-blockers, calcium channel antagonists, and digitalis slow ventricular rate, but much fewer data are available on their effect on atrial arrhythmogenesis. Verapamil is a nondihydropyridine calcium channel antagonist with potent negative chronodropic and dromodropic effects. Due to its use-dependent dromodropic action, verapamil is highly effective in controlling rapid ventricular rate in AF, but has less effect on atrioventricular (AV) nodal conduction at a normal rate. Kushiyama et al 7 showed that verapamil caused variable changes in the PV excitation. The maximum PV DF increased in 65% of the patients and decreased in the remaining 35%. In contrast, verapamil consistently increased the DFs in all of the atrial recording sites. As a result of these tissue-specific effects, verapamil eliminated the PV-to-atria DF gradient. According to the investigators, this is attributable to regional heterogeneities of action potential morphology and ionic currents responsible for the repolarization (e.g., I CaL ) in the PV myocardial muscle sleeves and atria rather than to a reflex increase in sympathetic tone in response to a reduction in blood pressure. Prior studies indicate that the extrapulmonary DF areas and the absence of the PV-to-atria frequency gradient can be used to identify additional ablation targets. For example, Lin et al 6 have shown that the DF shifts to the right atrium when AF is initiated in the superior vena cava. Sanders et al 5 reported that termination of permanent AF requires ablation of extrapulmonary high-frequency sites in addition to PV isolation. Hence, it is tempting to speculate that ablation of the verapamil-induced atrial high-frequency areas may improve the long-term efficacy of catheter ablation of paroxysmal AF. The results of Kushiyama et al 7 are also important with regard to rate control of AF because they raise the possibility that verapamil may provoke paroxysmal AF by creating new high-frequency sources in the atria. In keeping with this, verapamil facilitated the induction of sustained AF. That is, in all of the 6 patients with no inducible AF at baseline, sustained AF was easily induced after verapamil by burst pacing from the coronary sinus. These findings are consistent with experimental data indicating that verapamil promotes maintenance of AF by shortening the atrial refractory period and AF cycle length and enhancing reentrant activity in the atria. 8 In lieu of these data, the usefulness of verapamil for ventricular rate control in patients with paroxysmal AF may be limited by its profibrillatory effect in

Atrial Fibrillation: The New Epidemic of the Ageing World.

The prevalence of atrial fibrillation (AF) increases with age. As the population ages, the burden of AF increases. AF is associated with an increased incidence of mortality, stroke, and coronary events compared to sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may be administered to reduce immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Digoxin should not be used to treat patients with paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds which are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in elderly patients , ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should be treated with aspirin 325 mg daily.