Lack of difference in T wave variability between patients at risk of sudden cardiac death and healthy subjects.

BACKGROUND: T wave variability (Tvar) is a proposed method to predict sudden cardiac death (SCD). The purpose of this trial was to evaluate the reproducibility of Tvar measurements over time and demonstrate a difference in Tvar between patient populations at risk for ventricular arrhythmias and healthy subjects. METHODS: Sixty subjects were enrolled in into 3 groups: healthy subjects (Population I), patients at high risk of SCD (Population II), and patients with a recent ventricular tachyarrhythmia event (Population III). Recording and analysis of T wave amplitude variance (TAV) as a measure of Tvar was performed at baseline and 3 months. RESULTS: TAV could not be interpreted in 12 of 43 patients in Populations II and III due to PVCs or noise. No subject had a TAV value suggestive of high risk of SCD as per a previously defined cutoff of >59 µV. Median (range) values of TAV in µV at baseline for Populations I, II and III were 26 (15-39), 21 (13-43), and 24 (18-41), respectively (p = 0.39). TAV was reproducible within population's from baseline to 3 months (p = 0.27, 0.53, 0.17 for Populations I, II and III, respectively). There was no significant difference between TAV values of high risk patients and healthy subjects. CONCLUSION: Tvar was reproducible primarily in patients with left ventricular dysfunction. However, the role of Tvar as a risk stratifying tool remains inconclusive.

Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator.

The most effective pharmacological management of frequent ventricular tachyarrhythmia events in patients with an implantable defibrillator who failed or did not tolerate amiodarone is unknown. The aim of this retrospective cohort study was to assess the efficacy and tolerability of mexiletine in such patients. The patients served as self-controls. The number of treated ventricular tachyarrhythmia episodes (primary outcome); mortality, shocks from the defibrillator, and electrical storm events (secondary outcomes) during mexiletine therapy was compared with a matched duration of observation just before initiating mexiletine in 29 patients who were treated with a median dose of 300 mg/d of mexiletine and were followed for a median of 12 months. None of the patients had to stop mexiletine due to side effect. There was a significant reduction in the incidence of ventricular tachycardia/fibrillation episodes (median 2 vs. 12 events, P = 0.001) and shocks (median 0 vs. 2 events, P = 0.003) in the first 3 months of treatment, but long-term efficacy was only observed among patients who continued amiodarone therapy. In conclusion, mexiletine, when added to amiodarone in case of amiodarone inefficacy, reduces ventricular tachycardia/fibrillation events and appropriate therapies in patients with an implantable cardioverter defibrillator. A randomized trial should validate the efficacy and safety of mexiletine as an adjunctive therapy to amiodarone.

Pre-hospital cardiac arrest in acute coronary syndromes: insights from the global registry of acute coronary events and the canadian registry of acute coronary events.

OBJECTIVES: Cardiac arrest in acute coronary syndromes (ACS) is associated with high morbidity and mortality. We examined the clinical characteristics, contemporary management patterns and outcomes of ACS patients with pre-hospital cardiac arrest. METHODS: The Global Registry of Acute Coronary Events and the Canadian Registry of Acute Coronary Events enrolled 14,010 ACS patients in 1999-2008. We compared the clinical characteristics, in-hospital treatment and outcomes between patients with and without pre-hospital cardiac arrest. RESULTS: Overall, 206 (1.4%) patients had cardiac arrest prior to hospital presentation. ACS patients with pre-hospital cardiac arrest were less frequently treated with aspirin, ß-blocker, angiotensin-converting enzyme inhibitors, and statins within the first 24 h of presentation, but the use of cardiac procedures was similar compared to the group without cardiac arrest. Patients with pre-hospital cardiac arrest had significantly higher rates of in-hospital adverse events. Factors independently associated with pre-hospital cardiac arrest included male gender, current smoker status, tachycardia, higher Killip class and ST-segment deviation. CONCLUSION: ACS patients with pre-hospital cardiac arrest continue to have more in-hospital complications and higher mortality. Their use of evidence-based medical therapies was lower but the use of cardiac procedures was similar compared to the group without cardiac arrest. Better utilization of evidence-based therapies in these patients may translate into improved outcomes.

Three-dimensional localization versus fluoroscopically only guided ablations: a meta-analysis.

OBJECTIVES: Data regarding efficacy and safety of three-dimensional localization systems (3D) are limited. We performed a meta-analysis of randomized trials comparing combined fluoroscopy- and 3D guided to fluoroscopically-only guided procedures. DESIGN: A systematic search was performed using multiple databases between 1990 and 2010. Outcomes were acute and long-term success, ablation, procedure and fluoroscopic times, radiation dose (RD), and complications. RESULTS: Thirteen studies involving 1292 patients were identified. 3D were tested against fluoroscopic guidance in 666 patients for supraventricular tachycardia (SVT), atrial flutter (AFL), atrial fibrillation (AF), and ventricular tachycardia (VT). Acute and long-term freedom from arrhythmia was not significantly different between 3D and control for AFL (acute success, 97% vs. 93%, p = 0.57; chronic success, 93% vs. 96%, p = 0.90) or for SVT (acute success, 94% vs. 100%, p = 0.36; chronic success, 88% vs. 88%, p = 0.80). A shorter fluoroscopic time was achieved with 3D in AFL (p < 0.001) and in SVT (p = 0.002). RD was significantly less for both AFL (p = 0.002) and SVT (p = 0.01). Ablation and procedure time and complications were not statistically different. CONCLUSIONS: Success, procedure time, and complications were similar between fluoroscopy- and 3D-guided ablations. Fluoroscopic time and RD were significantly reduced for ablation of AFL and SVT with 3D.

Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database.

BACKGROUND: Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied. OBJECTIVE: To examine potential sex differences in ICD implantation and device outcomes. DESIGN: Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. SETTING: 18 ICD implantation and follow-up centers in Ontario, Canada. PATIENTS: 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. MEASUREMENTS: Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. RESULTS: Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). LIMITATION: The differential effects of sex on prereferral events were not examined. CONCLUSION: Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.

Relationship Between Left Ventricular Strain Assessment by Cardiac Magnetic Resonance Imaging and Response to Cardiac Resynchronization Therapy.

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions.

Role of antiarrhythmic drugs in patients with implantable cardioverter defibrillators.

The transvenous implantable cardioverter defibrillator (ICD) has emerged as the primary therapy for patients at high risk of life-threatening ventricular arrhythmias. A high number of ICD recipients will require subsequent adjunctive treatment with antiarrhythmic drugs (AADs). This review provides an overview of potential reasons for AAD initiation, candidates for treatment, current medical options, and possible drug-device interactions.

Diagnostic value of body surface potential mapping in assessment of the coronary artery lesion after angina pectoris and without repolarization changes on the electrocardiogram.

BACKGROUND: The body surface potential mapping (BSPM) method is sensitive in detecting minor electrical potential abnormalities, but its diagnostic value is unclear in detection and localization of significant coronary artery lesion (CAL) in patients after angina pectoris and without ischemic electrocardiogram abnormalities at the time of the BSPM record. METHODS AND RESULTS: Characteristic features and quantitative parameters of the isopotential maps during the depolarization were evaluated and compared with the result of coronary angiography in 228 patients (164 males; age, 61.6 +/- 9.5 years). Twenty-three of them had their first angina, but the others had a history of earlier angina, unstable angina, non-ST-elevation infarction. Fifty-nine healthy subjects (32 males; age, 53.3 +/- 12.2 years) served as control. The diagnostic power was high in detection of CAL among patients with previous ischemic events, but it was low in first angina. The accuracy of the CAL localization by multiple regression was different: at 90% specificity level, the sensitivity was near 80% for right/posterior descending CAL and slightly more than 60% for left anterior descending CAL but only 19% for first marginal/first diagonal CAL. CONCLUSIONS: The BSPM changes during the depolarization could well indicate CAL only after previous ischemic events. Sensitivity and specificity of the CAL localization depended on the extension and location of the underlying myocardium damage.

Microvolt QRS Alternans Without Microvolt T-Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P<0.01) and proportion of TWA+ studies (16% versus 46%, P<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA-negative patients (138±23 versus 113±26 ms, P<0.01). At 3.5 years follow-up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA-negative patients (30% versus 8%, P=0.02) but similar in TWA+ and TWA-negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5-14; P=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4-fold, which merits further study as a risk stratifier.

Influence of ventriculoatrial timing on hemodynamics and symptoms during supraventricular tachycardia.

AIMS: Patients with reentrant supraventricular tachycardia (SVT) are often highly symptomatic and the mechanism of symptoms is not well understood. We hypothesized that variation in ventriculoatrial interval (QRS to P) modulates the left atrial pressure and symptoms during tachycardia. METHODS AND RESULTS: Three hundred twenty-six patients awaiting electrophysiological study completed a questionnaire regarding "neck pounding" or "shirt flapping" during tachycardia. Mean left atrial pressure was measured during simulated atrioventricular reentry tachycardia (AVRT) and atrioventricular nodal reentry tachycardia (AVNRT) in 18 patients. Pulmonary venous flow reversal was assessed using transesophageal echocardiography in 12 dogs when pacing at 220 bpm with different VA delays (0 to 250 ms). "Shirt flapping" is present more often during AVNRT than during AVRT (58.6% vs 43.8%, respectively, P < 0.05). Simulated AVNRT is associated with higher left atrial pressure compared with AVRT (19.4 +/- 4.8 mmHg vs 13.7 +/- 3.9 mmHg, respectively, P < 0.05). In dogs, pulmonary venous flow reversal during atrial systole was observed with significantly decreasing amplitude as VA delays increased: 668 +/- 167% at 0 ms; 492 +/- 138% at 100 ms; 278 +/- 148% at 180/ms; and 134 +/- 91% at 220 ms. CONCLUSION: "Shirt flapping" and "neck pounding" frequently occur during AVNRT. LA contractions during AV valve closure increase left atrial pressure and may explain differences in certain symptoms between AVNRT and AVRT.

Assessment of resynchronization therapy on functional status and quality of life in patients requiring an implantable defibrillator.

BACKGROUND: The effect of cardiac resynchronization therapy (CRT) on physical function and Quality of Life (QoL) in patients who require an implantable defibrillator but do not meet guideline criteria for CRT has not been studied in detail. METHODS AND RESULTS: This was a randomized study of 72 patients with high risk of sudden cardiac death, ejection fraction (EF) < or =35%, mild-to-moderate heart failure symptoms, and QRS > 120 ms. Patients received a CRT defibrillator and were randomized to CRT turned ON or OFF. Objective and subjective measures were performed at baseline and after 6 months. There was no difference in change in left ventricular end-systolic volume (ESV) by radionuclid angiogram scan, the primary endpoint, between the CRT ON group (DeltaESV =-7 +/- 52 mL), and CRT OFF group (DeltaESV =-30 +/- 47 mL). Similarly, echocardiogram measures of ESV and EF showed no difference between the two groups. In the CRT ON group, selected measures of QoL and subjective exercise tolerance but not heart failure symptoms improved significantly. Six-minute walk distance prolonged in the CRT ON group (baseline 313.6 +/- 114.4 m, 6-month 365.0 +/- 122.5 m, P = 0.01), but the difference in change in walk distance between the two groups was not significant. CONCLUSION: Further studies with larger sample size and longer follow-up will be required to allow definite conclusions regarding the potential benefit of CRT in this patient population.

Impact of AV conduction disorders on SafeR mode performance.

PURPOSE: CAN-SAVE R is a Canadian multicenter study that compares the effects of a new pacing mode algorithm designed to minimize right ventricular (V) pacing versus DDD mode with a long atrioventricular (AV) delay in a general population of pacemaker (PM) recipients. STUDY PARTICIPANTS: Patients with permanent atrial fibrillation (AF) or high-degree AV block (AVB) were excluded. We present preliminary data collected in 208 patients (mean age=71 +/- 11 years, 68% men), for the 2-month baseline period during which all PM were programmed in the new pacing mode. The pacing indications were sinus node disease (SND) without AVB in 39%, AVB without SND in 30%, SND and AVB in 16%, and miscellaneous in 15% of patients. RESULTS: The mean percent V pacing in the overall population was 9.5 +/- 23.8% (range=0-100%, median <1%), ranging between 0.5 +/- 1.5% (median=0) in patients without AVB and 18.7 +/- 31.2% in patients (median = 1) with AVB. Adverse events potentially related to the new pacing mode were observed in two patients with AVB. CONCLUSIONS: A new pacing mode was effective and safe in a general population of PM recipients without permanent AVB and was associated with an overall <1% median V pacing. CAN-SAVE R will compare the long-term effects of the new pacing mode with DDD with a long AV delay on clinical outcomes and cardiac function.

Unexpected High Prevalence of Cardiovascular Disease Risk Factors and Psychiatric Disease Among Young People With Sudden Cardiac Arrest.

Background It is believed that most sudden cardiac arrests ( SCA s) in young people occur in previously healthy people with rare risk factors for sudden death. Few studies have investigated large populations with complete ascertainment. Our objective was to use multisource records to identify and classify all out-of-hospital cardiac arrests in the Greater Toronto Area (population 6.6 million) in people aged 2 to 45 years from 2009 to 2012. Methods and Results Expert reviewers employed a systematic process, with emergency medical services, in-hospital and coroner records, to adjudicate the cause of death as SCA from cardiac or noncardiac causes. We report the adjudicated etiologies, circumstances, triggers, and characteristics of the SCA cohort. Of 2937 eligible out-of-hospital cardiac arrest cases, 608 (20.7%) SCA s had an adjudicated etiology of cardiac cause (120 survivors and 488 nonsurvivors). Two thirds of these SCA patients had a history of cardiovascular disease, and over 50% had been diagnosed with ≥1 cardiovascular disease risk factor. Moreover, 20.1% of SCA s were diagnosed with psychiatric disease and 30% had central nervous system drugs prescribed. Over 30% of SCA patients had central nervous system active drugs, including drugs of abuse detected postmortem, with opioids and ethanol being detected most frequently. Potentially heritable structural cardiac diseases accounted for only 6.9% of SCA events, with acquired cardiac diseases comprising the rest. Conclusions The underlying causes of SCA , in people aged 2 to 45 years, often occur in those with previously diagnosed cardiovascular diseases, and are associated with contributory factors including prescribed medications, recreational drugs, and a concomitant psychiatric history.

Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.

BACKGROUND: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.

"Presumed cardiac" arrest in children and young adults: A misnomer?

AIM: To use a novel methodology to assess the incidence and specific causes of Out-of-Hospital Cardiac Arrest (OHCA) within a young urban cohort. METHODS: All EMS attended OHCA patients in a large urban area, between 2009 and 2012, aged 2-45 years, treated or untreated, who died or survived, and that were designated as "no obvious cause" etiology by trained data abstractors were included. Using multisource (medical and coroner) records, an expert panel adjudicated the causes of the OHCAs as: confirmed cardiac causes, confirmed non- cardiac causes, and other causes. RESULTS: Of a total of 1993 cases EMS designated as "no obvious cause", only 29.9% (595/1993) were due to confirmed cardiac causes; the rest were due to other causes (non-cardiac etiologies): confirmed drug overdose (n=624), trauma (n=108), cancer (n=69), complex chronic care (n=65) and non-cardiac acute illness - mostly vascular, infectious, and metabolic (n=376). The annual incidence rate of "no obvious cause" OHCAs after initial field classification was 12.97/100,000 pt. years (95% CI 12.40, 13.50), compared to 3.87/100,000 pt. years (95% CI 3.56, 4.18) for the confirmed cardiac OHCAs after adjudication. The predominant underlying etiologies of confirmed cardiac OHCAs were coronary heart disease and structural heart disease. CONCLUSIONS: In young adults with OHCA, confirmed cardiac causes were responsible in a minority of cases, and they differed in presentation from those with confirmed non- cardiac causes. Establishing rigorous case ascertainment strategies with linkage to multiple data sources will facilitate a more reliable evaluation of the causes of these events.

Automated Quantification of Low-Amplitude Abnormal QRS Peaks From High-Resolution ECG Recordings Predicts Arrhythmic Events in Patients With Cardiomyopathy.

BACKGROUND: Cardiomyopathy patients are at risk of sudden death, typically from scar-related abnormalities of electrical activation that promote ventricular tachyarrhythmias. Abnormal intra-QRS peaks may provide a measure of altered activation. We hypothesized that quantification of such QRS peaks (QRSp) in high-resolution ECGs would predict arrhythmic events in implantable cardioverter-defibrillator (ICD)-eligible cardiomyopathy patients. METHODS AND RESULTS: Ninety-nine patients with ischemic or non-ischemic dilated cardiomyopathy undergoing prophylactic ICD implantation were prospectively enrolled (age 62±11 years, left ventricular ejection fraction 27±7%). High-resolution (1024 Hz) digital 12-lead ECGs were recorded during intrinsic rhythm. QRSp was quantified for each precordial lead as the total number of low-amplitude deflections that deviated from their respective naive QRS template. The primary end point of arrhythmic events was defined as appropriate ICD therapy or sustained ventricular tachyarrhythmias. After a median follow-up of 24 (15-43) months, 20 (20%) patients had arrhythmic events. Both QRSp and QRS duration were greater in those with arrhythmic events (both P<0.001) and this was consistent for QRSp for both cardiomyopathy types. In a multivariable Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRSp, only QRSp was an independent predictor of arrhythmic events (hazard ratio, 2.1; P<0.001). Receiver operating characteristic analysis revealed that a QRSp ≥2.25 identified arrhythmic events with greater sensitivity (100% versus 70%, P<0.05) and negative predictive value (100% versus 89%, P<0.05) than QRS duration ≥120 ms. CONCLUSIONS: QRSp measured from high-resolution digital 12-lead ECGs independently predicts ventricular tachyarrhythmias in ICD-eligible cardiomyopathy patients. This novel QRS morphology index has the potential to improve sudden death risk stratification and patient selection for prophylactic ICD therapy.

The burden of atrial fibrillation: should we abandon antiarrhythmic drug therapy?

Atrial fibrillation (AF) is the most common sustained arrhythmia, exacting a substantial toll in cardiovascular morbidity and mortality. Until recently, the prevailing philosophy has been that restoration and maintenance of normal sinus rhythm, as opposed to control of ventricular response rate, was the optimal approach to treatment of AF. A series of landmark trials (AFFIRM, RACE, STAF, and PIAF) have called this strategy into question, suggesting outcomes are equivalent with both approaches. These data do not mean that rhythm control is not beneficial, but highlight the limitations of current therapies to achieve and maintain sinus rhythm. Limitations of the rhythm-control strategy may be related to our difficulty in accurately documenting symptomatic benefit from this approach, the lack of efficacy and excessive adverse-effect burden associated with currently available antiarrhythmic agents, and selection biases in the enrollment of patients in clinical trials of rhythm control versus rate control, making the trials incompletely representative of the population eligible for therapy. New pharmacologic agents under development feature increased atrial selectivity or multi-channel-blocking properties (or both). As a result, these compounds may be more effective in prolonging atrial refractoriness and may also have reduced proarrhythmic potential. It is premature to abandon the concept of rhythm control in AF until we have trials designed to include younger and highly symptomatic patients, more sensitive tools to measure symptomatic improvement, and safer, more effective antiarrhythmic agents.