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Background Most patients with atrial fibrillation ( AF ) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF . Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time‐dependent covariate in multivariable Cox models of all‐cause and cause‐specific mortality during a median follow‐up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA 2 DS 2 ‐ VAS c scores, renal function, or left ventricular function. There were significant differences in race ( P =0.001), sinus node dysfunction ( P =0.004), and treatment with calcium‐channel blockers ( P =0.006) and anticoagulation ( P =0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all‐cause mortality (adjusted hazard ratio [ HR ], 1.15 per 5‐bpm decrease; 95% CI , 1.01 to 1.32; P =0.04). Similarly, increasing heart rate >65 bpm was associated with higher all‐cause mortality (adjusted HR , 1.10 per 5‐bpm increase; 95% CI , 1.05 to 1.15; P <0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF , there is a J‐shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL : http://clinicaltrials.gov/ . Unique identifier: NCT01165710.

Background— Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. Methods and Results— We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c -statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c -statistic of 0.77. Conclusions— We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.

Background— Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. Methods and Results— We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51–0.97 and HR, 0.84; 95%, CI 0.67–1.04; interaction P =0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61–1.04 and HR, 0.65; 95% CI, 0.55–0.77; interaction P =0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84–1.22 and HR, 0.84; 95% CI, 0.73–0.96; interaction P =0.10). Conclusions— More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Background— Instruments to assess symptom burden and quality of life among patients with atrial fibrillation (AF) have not been well evaluated in community practice or associated with patient outcomes. Methods and Results— Using data from 10 087 AF patients in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), symptom severity was evaluated using the European Heart Rhythm Association (EHRA) classification system, and quality of life was assessed using the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire. The association between AF-related symptoms, quality of life, and outcomes was assessed using Cox regression. The majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3–4). EHRA symptom class was well correlated with the AFEQT score (Spearman correlation coefficient −0.39). Over 1.8 years of follow-up, AF symptoms were associated with a higher risk of hospitalization (adjusted hazard ratio for EHRA ≥2 versus EHRA 1 1.23, 95% confidence interval, 1.15–1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted hazard ratio for lowest quartile of AFEQT versus highest 1.49, 95% confidence interval, 1.2–1.84), but not other major adverse events, including death. Conclusions— In a community-based study, most patients with AF were symptomatic and had impaired quality of life. Quality of life measured by the AFEQT correlated closely with symptom severity measured by the EHRA class. AF symptoms and lower quality of life were associated with higher risk of hospitalization but not mortality during follow-up.

Background The characteristics of patients undergoing atrial fibrillation ( AF ) ablation and subsequent outcomes in community practice are not well described. Methods and Results Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT ‐ AF ), we investigated the prevalence and impact of catheter ablation of AF . Among 9935 patients enrolled, 5.3% had previous AF ablation. Patients with AF ablation were significantly younger, more frequently male, and had less anemia, chronic obstructive pulmonary disease, and previous myocardial infarction (P<0.05 for all analyses) than those without previous catheter ablation of AF . Ablated patients were more likely to have a family history of AF , obstructive sleep apnea, paroxysmal AF , and moderate‐to‐severe symptoms (P<0.0001 for all analyses). Patients with previous ablation were more often in sinus rhythm on entry into the registry (52% vs. 32%; P<0.0001). Despite previous ablation, 46% in the ablation group were still on antiarrhythmic therapy. Oral anticoagulation was prescribed in 75% of those with previous ablation versus 76% in those without previous ablation (P=0.5). The adjusted risk of death (hazard ratio [ HR ], 0.78; 95% confidence interval [ CI ], 0.52 to 1.18; P=0.2) and cardiovascular ( CV ) hospitalization ( HR , 1.06; 95% CI , 0.90 to 1.26; P=0.5) were similar in both groups. Patients with incident AF ablation had higher risk of subsequent CV hospitalization than matched patients without incident ablation ( HR , 1.67; 95% CI , 1.24 to 2.26; P=0.0008). Conclusions In U.S. clinical practice, a minority of patients with AF are managed with catheter ablation. Subsequent to ablation, there were no significant differences in oral anticoagulation use or outcomes, including stroke/non–central nervous system embolism/transient ischemic attack or death. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01165710.

NISHIMURA, R.A. et al.: Hemodynamic and symptomatic consequences of ventricular pacing. After implantation of a ventricular demand pacemaker (VVI), occasional patients continue to have dizziness, syncope, or near syncope (“pacemaker syndrome”). To identify patients in whom VVI pacing may have deleterious effects, we compared cuff blood pressure responses to VVI pacing with blood pressure responses to atrioventricsler sequential pacing (DVI) or sinus rhythm in 50 consecutive patients. Patients with intact ventriculoatrial conduction had a much greater decrease in systolic blood pressure with VVI pacing (24 ± 11 mm Hg) than those with ventriculoatrial dissociation (−4 ± 15 mm Hg) (P<0.005). Patients who were in heart failure had a lesser decrease in blood pressure with VVI pacing than did those without failure (P<0.05); 13 of the 14 heart failure patients lacked ventriculoatrial conduction. Ten patients had symptomatic dizziness after VVI pacing; the incidence of symptoms was higher in patients with ventriculoatrial conduction (9 of 23) than in those without ventriculoatrial conduction (1 of 27) (P<0.003). We conclude that the presence of intact ventriculoatrial conduction appears to be a crucial determinent of the hemodynamic response to VVI pacing, and its presence may identify patients who are at risk for “pacemaker syndrome.”

Objective Atrial fibrillation (AF) often progresses from paroxysmal or persistent to more sustained forms, but the rate and predictors of AF progression in clinical practice are not well described. Methods Using the Outcomes Registry for Better Informed Treatment of AF, we analysed the incidence and predictors of progression and tested the discrimination and calibration of the HATCH (hypertension, age, TIA/stroke, chronic obstructive pulmonary disease, heart failure) and CHA2DS2VASc scores for identifying AF progression. Results Among 6235 patients with paroxysmal or persistent AF at baseline, 1479 progressed, during follow-up (median 18 (IQR 12–24) months). These patients were older and had more comorbidities than patients who did not progress (CHADS2 2.3±1.3 vs 2.1±1.3, p<0.0001). At baseline, patients with AF progression were more often on a rate control as opposed to a rhythm control strategy (66 vs 56%, p<0.0001) and had higher heart rate (72(64–80) vs 68(60–76) bpm, p<0.0001). The strongest predictors of AF progression were AF on the baseline ECG (OR 2.30, 95% CI 1.95 to 2.73, p<0.0001) and increasing age (OR 1.16, 95% CI1.09 to 1.24, p<0.0001, per 10 increase), while patients with lower heart rate (OR 0.84, 95% CI 0.79 to 0.89, p<0.0001, per 10 decrease ≤80) were less likely to progress. There was no significant interaction between rhythm on baseline ECG and heart rate (p=0.71). The HATCH and CHA2DS2VASc scores had modest discriminatory power for AF progression (C-indices 0.55 (95% CI 0.53 to 0.58) and 0.55 (95% CI 0.52 to 0.57)). Conclusions Within 1.5 years, almost a quarter of the patients with paroxysmal or persistent AF progress to a more sustained form. Progression is strongly associated with heart rate, and age.

Background Survivors of ventricular fibrillation out of hospital cardiac arrest ( VF ‐ OHCA ) due to a potentially reversible cause such as acute myocardial infarction (MI) or ischemia are considered to be at low risk of recurrent arrhythmia. Implantable cardioverter defibrillators ( ICD ) are not routinely recommended in such patients. However, the outcome of these patients in the era of rapid coronary revascularization and ICD therapy is not known. Methods and Results We examined the outcome of 114 consecutive survivors of VF OHCA due to acute MI or ischemia in Olmsted County, MN from 1990 to 2011. An ICD was implanted in 45/114 patients. ICD recipients had lower EF [median ( IQR ) 38 (26 to 54) versus 48 (35 to 58) %, P =0.04]. During a median ( IQR ) follow‐up of 9.9 (4.4 to 14.6) years, ICD implantation was associated with reduced cardiac mortality ( HR 0.24 [0.07 to 0.88], P =0.031) and a trend towards reduced all‐cause mortality ( HR 0.56 [0.30 to 1.02], P =0.059) after adjusting for the first principal component. One or more appropriate ICD therapies were delivered in 19/45, with half of the patients receiving therapy within 1 year. Patients with EF ≤35% at discharge continued to be at long‐term risk for ICD therapy compared with those with EF >35% who were at increased risk predominantly in the first 8 months. EF and revascularization were not significantly associated with ICD therapy in the multivariable analysis. Conclusions Patients with VF ‐ OHCA in the setting of acute MI or myocardial ischemia remain at high risk of recurrent ventricular arrhythmias, particularly if EF ≤35%. This suggests that ICD implantation may be reasonable if EF ≤35%.