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Importance: Patients with atrial fibrillation (AF) have impaired health-related quality of life primarily owing to symptoms related to AF episodes; however, quality of life can be influenced by AF therapies, AF complications, the frequency of follow-up visits and hospitalizations, illness perceptions, and patient factors, such as anxiety or depression., Objective: To determine the association between change in AF burden and quality of life in the year following ablation., Design, Setting, and Participants: The current study is a secondary analysis of a prospective, parallel-group, multicenter, single-masked randomized clinical trial (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation: Double Short vs Standard Exposure Duration [CIRCA-DOSE] study), which took place at 8 Canadian centers. Between September 2014 and July 2017, 346 patients older than 18 years with symptomatic, primarily low-burden AF refractory to antiarrhythmic therapy referred for first catheter ablation were enrolled. All patients received an implantable cardiac monitor at least 30 days before ablation and were followed up with up to December 2018. Data were analyzed from April 2020 to June 2021., Interventions: Patients were randomized 1:1:1 to contact force-guided radiofrequency ablation, 4-minute cryoballoon ablation, or 2-minute cryoballoon ablation. The exposure in the present analysis is the absolute difference in AF burden prior to ablation and 12 months following ablation, as evaluated by the Atrial Fibrillation Effect on Quality of Life (AFEQT) Score., Main Outcomes and Measures: Absolute difference in quality of life from baseline to 12 months postablation., Results: Of 346 included patients, 231 (66.7%) were male, and the median (interquartile range) age was 60 (52-66) years. A total of 328 patients (94.8%) had paroxysmal AF. The median (interquartile range) preablation AF burden was 2.0% (0.1-11.9), and the AF burden decreased to 0% at 12 months postablation. At 12 months, a 1-point improvement in AFEQT score was observed for every absolute reduction in daily AF burden of 15.8 minutes (95% CI, 7.2-24.4; P < .001), or every 0.63% (95% CI, 0.30-0.95; P < .001) reduction in relative AF burden from baseline., Conclusions and Relevance: In patients with primarily low-burden paroxysmal AF, the reduction in AF burden following ablation may be associated with a clinically meaningful improvement in quality of life., Trial Registration: ClinicalTrials.gov Identifier: NCT01913522.

Background: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE. After excluding patients with other (n = 14 [2.1%]) or unknown (n = 30 [4.4%]) ethnicity, 364 (53.7%) whites and 270 (39.8%) Asians comprised the study group., Results: There was no difference in AE age onset (41.3 ± 16.1 years in whites vs 43.3 ± 12.3 years in Asians; P = .285). Higher proportions of whites were observed in pediatric and elderly populations. Asians were predominantly men (98.1% vs 85.7% in whites; P < .001) and frequently presented with aborted cardiac arrest (71.1% vs 56%; P < .001). Asians tended to display more spontaneous type 1 BrS-ECG pattern (71.5% vs 64.3%; P = .068). A family history of sudden cardiac death was noted more in whites (29.1% vs 11.5%; P < .001), with a higher rate of SCN5A mutation carriers (40.1% vs 13.2% in Asians; P < .001), as well as more fever-related AEs (8.5% vs 2.9%; P = .011). No difference was observed between the 2 groups regarding history of syncope and ventricular arrhythmia inducibility., Conclusion: There are important differences between Asian and white patients with BrS. Asian patients present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG. However, they have less family history of sudden cardiac death and markedly lower SCN5A mutation rates. The striking difference in SCN5A mutation rates should be tested in future studies., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge., Background: A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome., Methods: Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included., Results: Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome., Conclusions: The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study explored early repolarization (ER) pattern inheritance between survivors of unexplained cardiac arrest (UCA) and their first-degree relatives., Background: ER is considered a factor that confers an increased risk of sudden death. A monogenic explanation for ER is seldom evident after cascade screening., Methods: UCA survivors and their first-degree relatives enrolled in the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry) were included in the study. ER was defined and characterized according to accepted criteria. Logistic regression was performed to explore the association between ER status in the UCA survivor and first-degree relative groups based on the presence of an ER pattern in their related family members after adjusting for age, sex, and ethnicity., Results: A total of 289 patients from 14 Canadian sites were studied (age: 43.0 ± 15.9 years; 148 women), and 945 electrocardiograms were analyzed. Seventy-five patients had the ER pattern. There was a significantly higher prevalence of the ER pattern in UCA survivors who had first-degree relatives with the ER pattern (adjusted odds ratio: 5.79; 95% confidence intervals [CIs]: 1.79 to 18.7). There was also a nonsignificant higher prevalence of the ER pattern in first-degree relatives of UCA survivors with the ER pattern (OR: 2.43; 95% CI: 0.70 to 8.43). The highest prevalence of the ER pattern was seen in first-degree relatives of UCA survivors with ER syndrome (29%)., Conclusions: The ER pattern appeared to be more common among UCA survivors and first-degree relatives whose related family members had similar changes on electrocardiography, which suggested that genetically complex factors contribute to electrocardiographic patterns that predispose to cardiac arrest., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: There is limited information on gender differences in patients with Brugada syndrome (BrS) who experienced arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between males and females in patients with BrS with their first AE., Methods: The multicenter Survey on Arrhythmic Events in BRUgada Syndrome collected data on the first AE in 678 patients with BrS including 619 males (91.3%) and 59 females (8.7%) aged 0.27-84 years (mean age 42.5 ± 14.1 years) at the time of AE occurrence., Results: After excluding pediatric patients, it was found that females were older than males (49.5 ± 14.4 years vs 43 ± 12.7 years, respectively; P = .001). Higher proportions of females were observed in the pediatric and elderly populations. In Asians, the male to female ratio for AEs was ≈9-fold higher than that in White. Spontaneous type 1 BrS ECG was associated with an earlier onset of AEs in pediatric females. A similar prevalence (≈65%) of spontaneous type 1 BrS ECG was present in males and females above the age of 60 years. Females less frequently showed spontaneous type 1 BrS ECG (41% vs 69%; P < .001) or arrhythmia inducibility at electrophysiology study (36% vs 66%; P < .001). An SCN5A mutation was more frequently found in females (48% vs 28% in males; P = .007)., Conclusion: This study confirms that female patients with BrS are much rarer, display less type 1 Brugada ECG, and exhibit lower inducibility rates than do males. It shows for the first time that female patients with BrS with AE have higher SCN5A mutation rates as well as the relationship between gender vs age at the onset of AEs and ethnicity., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The literature on fever-related arrhythmic events (AEs) in Brugada syndrome (BrS) is currently limited to few case reports and small series., Objective: The present study aimed to describe the characteristics of fever-related AE in a large cohort of patients with BrS., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or after prophylactic implantable cardioverter-defibrillator implantation (n = 252)., Results: In 35 of 588 patients (6%) with available information, the AE occurred during a febrile illness. Most of the 35 patients were male (80%), Caucasian (83%), and proband (70%). The mean age at the time of AE was 29 ± 24 years (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest and 6 (17%) with arrhythmic storm. Family history of sudden death, history of syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%, and 71% of patients, respectively. Ventricular fibrillation was induced at electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in 14 of 28 patients (50%). The highest proportion of fever-related AE was observed in the pediatric population (age <16 years), with a disproportionally higher event rate in the very young (age 0-5 years) (65%). Males were involved in all age groups and females only in the pediatric and elderly groups. Fever-related AE affected 17 Caucasians aged <24 years, but no Asians aged <24 years., Conclusion: The risk of fever-related AE in BrS markedly varies according to age group, sex, and ethnicity. Taking these factors into account could help the clinical management of patients with BrS with fever., (Copyright © 2018 Heart Rhythm Society. All rights reserved.)

Background: Detailed information on the profile of patients with Brugada syndrome (BrS) presenting their first arrhythmic event (AE) after prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is limited., Objectives: The objectives of this study were (1) to compare clinical, electrocardiographic, electrophysiologic, and genetic profiles of patients who exhibited their first documented AE as aborted cardiac arrest (group A) with profiles of those in whom the AE was documented after prophylactic ICD implantation (group B) and (2) to characterize group B patients' profile using the class II indications for ICD implantation established by HRS/EHRA/APHRS expert consensus statement in 2013., Methods: A survey of 23 centers from 10 Western and 4 Asian countries enabled data collection of 678 patients with BrS who exhibited their AE (group A, n = 426; group B, n = 252)., Results: The first AE occurred in group B patients 6.7 years later than in group A (mean age 46.1 ± 13.3 years vs 39.4 ± 15.1 years; P < .001). Group B patients had a higher incidence of family history of sudden cardiac death and SCN5A mutations. Of the 252 group B patients, 189 (75%) complied with the HRS/EHRA/APHRS indications whereas the remaining 63 (25%) did not., Conclusion: Patients with BrS with the first AE documented after prophylactic ICD implantation exhibited their AE at a later age with a higher incidence of positive family history of sudden cardiac death and SCN5A mutations as compared with those presenting with aborted cardiac arrest. Only 75% of patients who exhibited an AE after receiving a prophylactic ICD complied with the 2013 class II indications, suggesting that efforts are still required for improving risk stratification., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Brugada syndrome (BrS) are at risk for ventricular arrhythmias (VAs) and sudden death. Identification of high-risk individuals beyond those with syncope or resuscitated sudden death remains a major challenge., Methods: We assessed the value of clinical, electrophysiological, and electrocardiographic (ECG) features, including depolarization and repolarization metrics, in predicting arrhythmic events and sudden death in consecutive patients with BrS diagnosed between 2002 and 2013 in Quebec, Canada. Qualifying electrocardiograms with the highest type 1 ST-segment elevations were reviewed and analyzed by 2 electrophysiologists who were blinded to clinical history. Survival analyses were adjusted for Firth bias correction and left truncation., Results: A total of 105 patients, 79.8% of whom were men, were diagnosed with BrS at a mean age of 46.2 ± 13.3 years and were followed for 59.6 ± 16.4 months. Ten (9.5%) had a history of cardiac arrest, 37 (35.2%) had syncope, and 7 (6.7%) experienced 20 arrhythmic events during follow-up, all consisting of appropriate ICD therapy (7 antitachycardia pacing; 13 shocks). In multivariate Cox regression analyses, a spontaneous type 1 electrocardiographic (ECG) pattern (hazard ratio [HR], 10.80; 95% confidence interval [CI], 1.03-113.87; P = 0.0476), maximal T peak-end (T p-e ) duration ≥ 100 ms (HR, 29.73; 95% CI, 1.33-666.37; P = 0.0325), and QRS duration in lead V 6 > 110 ms (HR, 15.27; 95% CI, 1.07-217.42; P = 0.0443) were independently associated with VAs or aborted sudden cardiac death., Conclusions: In a multicentre cohort with BrS from Quebec, Canada, VAs and sudden death were independently associated with standard 12-lead ECG features, including a spontaneous type 1 pattern, depolarization (QRS in lead V 6 ), and repolarization (maximal T p-e duration) criteria., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent., Methods and Results: The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis., Conclusions: Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032., (© 2016 American Heart Association, Inc.)

Poor R-wave progression (PRWP) in the precordial leads on random ECG is relatively frequent in the general population and includes a broad differential diagnosis. Here, we present for the first time a case of complete absence of precordial R waves associated with a prominent R wave in aVR due to the absence of the left-sided pericardium in a 44-year-old woman who experienced sudden cardiac death., (© 2012, Wiley Periodicals, Inc.)

Objectives: We evaluated the prevalence and characteristics of early repolarization in patients in CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry)., Background: Early repolarization has been implicated in a syndrome of polymorphic ventricular tachycardia and fibrillation in patients without organic heart disease., Methods: One hundred patients with apparently unexplained cardiac arrest and preserved ejection fraction underwent extensive clinical and genetic testing to unmask subclinical electrical or structural disease. A blinded independent analysis of the 12-lead electrocardiogram (ECG) was performed. Early repolarization was defined as ≥0.1 mV QRS-ST junction (J-point) elevation with terminal QRS slurring or notching in at least 2 contiguous inferior and/or lateral leads., Results: One hundred cardiac arrest patients were enrolled (40 females, age 43 ± 14 years). Forty-four were diagnosed with an established cause for cardiac arrest. Significant early repolarization was found in 19 patients, including 6 with a primary diagnosis that explained their cardiac arrest (14%), compared with 23% of the 56 patients with idiopathic ventricular fibrillation (IVF) (p = 0.23). J-point elevation in IVF patients had higher amplitude (0.25 ± 0.11 mV vs. 0.13 ± 0.05 mV, p = 0.02) and wider distribution (4.3 ± 1.3 leads vs. 2.8 ± 0.8 leads; p = 0.01) than those with an established cause of cardiac arrest. J-wave amplitude was fluctuant on serial ECGs; at least 1 ECG failed to demonstrate early repolarization in 58% of patients., Conclusions: Early repolarization is present in a significant proportion of causally diagnosed and idiopathic VF. It is often intermittent and more pronounced in IVF patients. (Registry of Unexplained Cardiac Arrest; NCT00292032)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary vein isolations (PVI) are being performed using a high‐power, short‐duration (HPSD) strategy. The purpose of this study was to compare the clinical efficacy and safety outcomes of an HPSD versus low‐power, long‐duration (LPLD) approach to PVI in patients with paroxysmal atrial fibrillation (AF). Methods: Patients were grouped according to a HPSD (≥40 W) or LPLD (≤35 W) strategy. The primary endpoint was the 1‐year recurrence of any atrial arrhythmia lasting ≥30 s, detected using three 14‐day ambulatory continuous ECG monitoring. Procedural and safety endpoints were also evaluated. The primary analysis were regression models incorporating propensity scores yielding adjusted relative risk (RRa) and mean difference (MDa) estimates. Results: Of the 398 patients included in the AWARE Trial, 173 (43%) underwent HPSD and 225 (57%) LPLD ablation. The distribution of power was 50 W in 75%, 45 W in 20%, and 40 W in 5% in the HPSD group, and 35 W with 25 W on the posterior wall in the LPLD group. The primary outcome was not statistically significant at 30.1% versus 22.2% in HPSD and LPLD groups with RRa 0.77 (95% confidence interval [CI]) 0.55–1.10; p =.165). The secondary outcome of repeat catheter ablation was not statistically significant at 6.9% and 9.8% (RRa 1.59 [95% CI 0.77–3.30]; p =.208) respectively, nor was the incidence of any ECG documented AF during the blanking period: 1.7% versus 8.0% (RRa 3.95 [95% CI 1.00–15.61; p =.049) in the HPSD versus LPLD group respectively. The total procedure time was significantly shorter in the HPSD group (MDa 97.5 min [95% CI 84.8–110.4)]; p <.0001) with no difference in adjudicated serious adverse events. Conclusions: An HPSD strategy was associated with significantly shorter procedural times with similar efficacy in terms of clinical arrhythmia recurrence. Importantly, there was no signal for increased harm with a HPSD strategy. [ABSTRACT FROM AUTHOR]

Background—Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear. Methods and Results—The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6–9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1–9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; P=0.04) but was associated with more variants of unknown significance (55% versus 5%; P<0.01). Conclusions—Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients. [ABSTRACT FROM AUTHOR]

Background: Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities.Methods and Results: Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims' relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%).Conclusions: Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032. [ABSTRACT FROM AUTHOR]

Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine to chronically inhibit CYP2D6. Patients (n = 102) with atrial fibrillation received propafenone 150 mg 3 times daily with either quinidine 100 mg twice daily or placebo. Throughout the study (follow-up, 199 ± 155 days), quinidine successfully inhibited CYP2D6: propafenone concentrations were 3 times higher in patients receiving quinidine (1033 ± 611 ng/mL vs 328 ± 229 ng/mL; P < .001). Moreover, 80% (n = 10) of patients with propafenone levels greater than 1500 ng/mL were in sinus rhythm at 1 year. In contrast, recurrence of atrial fibrillation occurred in 22 of 23 patients with propafenone levels less than 1000 ng/mL (P < .0001). Thus, chronic inhibition of CYP2D6 is achievable with low-dose quinidine in humans. Increased plasma levels of propafenone may be highly beneficial to prevent recurrence of atrial fibrillation. [ABSTRACT FROM PUBLISHER]

Sentinel Symptoms in Unexplained Cardiac Arrest. Background: Warning symptoms may provide an opportunity to diagnose genetic disorders leading to preventative therapy. We explored the symptom history of patients with apparently unexplained cardiac arrest to determine the frequency of sentinel symptoms. Methods: Patients with apparently unexplained cardiac arrest and no evident cardiac disease underwent systematic clinical evaluation. Patients and first-degree relatives were interviewed to determine the presence of cardiac symptoms, and those with syncope underwent 2 structured Calgary Syncope Score questionnaires to determine the probable mechanism of syncope. Results: One hundred consecutive cardiac arrest patients (age 43.0 ± 13.4 years, 60% male) and 63 first-degree relatives (age 37.6 ± 16.3 years, 54% female) were enrolled. Previous cardiac symptoms were present in 69% of cardiac arrest patients compared to 43% of family members (P = 0.001). Prior syncope was present in 26% of cardiac arrest patients, compared to 22% of family members (P = 0.59). Twenty-four of 25 cardiac arrest patients who completed the syncope questionnaires had a syncope versus seizure score <1 favoring syncope. The area under the receiver operator curve (ROC) for the syncope mechanism score was 0.79 for identifying patients with subsequent cardiac arrest (95% CI, 0.6328-0.9395, P = 0.004). A score of ≤-2 had a sensitivity of 68% and specificity of 85%. Thirty percent of patients with a proven genetic cause had preceding syncope versus 19% in patients with noninherited or idiopathic causes (P = 0.032). Conclusions: Syncope that may represent a sentinel event is present in a modest proportion of patients and family members, and is often suggestive of an arrhythmia. (J Cardiovasc Electrophysiol, Vol. 23, pp. 60-66, January 2012) [ABSTRACT FROM AUTHOR]