Fonarow, Gregg C.

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.

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— Racial and ethnic minorities are under-represented in clinical trials of primary prevention implantable cardioverter-defibrillators (ICDs). This analysis investigates the association between primary prevention ICDs and mortality among Medicare, racial/ethnic minority patients. Methods and Results— Data from Get With The Guidelines-Heart Failure Registry and National Cardiovascular Data Registry’s ICD Registry were used to perform an adjusted comparative effectiveness analysis of primary prevention ICDs in Medicare, racial/ethnic minority patients (nonwhite race or Hispanic ethnicity). Mortality data were obtained from the Medicare denominator file. The relationship of ICD with survival was compared between minority and white non-Hispanic patients. Our analysis included 852 minority patients, 426 ICD and 426 matched non-ICD patients, and 2070 white non-Hispanic patients (1035 ICD and 1035 matched non-ICD patients). Median follow-up was 3.1 years. Median age was 73 years, and median ejection fraction was 23%. Adjusted 3-year mortality rates for minority ICD and non-ICD patients were 44.9% (95% confidence interval [CI], 44.2%–45.7%) and 54.3% (95% CI, 53.4%–55.1%), respectively (adjusted hazard ratio, 0.79; 95% CI, 0.63–0.98; P =0.034). White non-Hispanic patients receiving an ICD had lower adjusted 3-year mortality rates of 47.8% (95% CI, 47.3%–48.3%) compared with 57.3% (95% CI, 56.8%–57.9%) for those with no ICD (adjusted hazard ratio, 0.75; 95% CI, 0.67%–0.83%; P <0.0001). There was no significant interaction between race/ethnicity and lower mortality risk with ICD ( P =0.70). Conclusions— Primary prevention ICDs are associated with lower mortality in nonwhite and Hispanic patients, similar to that seen in white, non-Hispanic patients. These data support a similar approach to ICD patient selection, regardless of race or ethnicity.

Background— Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. Methods and Results— The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P =0.0003) and mechanical valve replacements (9.6% versus 2.4%; P <0.0001); however, there was no difference in CHA 2 DS 2 -VASc scores (scores ≥2 in 94% versus 95%; P =0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P <0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P =0.0001). Conclusions— Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Background— Cardiac resynchronization therapy with defibrillator (CRT-D) reduces morbidity and mortality among selected patients with heart failure in clinical trials. The effectiveness of this therapy in clinical practice has not been well studied. Methods and Results— We compared a cohort of 4471 patients from the National Cardiovascular Data Registry’s Implantable Cardioverter-Defibrillator (ICD) Registry hospitalized primarily for heart failure and who received CRT-D between April 1, 2006, and December 31, 2009, to a historical control cohort of 4888 patients with heart failure without CRT-D from the Acute Decompensated Heart Failure National Registry (ADHERE) hospitalized between January 1, 2002, and March 31, 2006. Both registries were linked with Medicare claims to evaluate longitudinal outcomes. We included patients from the ICD Registry with left ventricular ejection fraction ≤35% and QRS duration ≥120 ms who were admitted for heart failure. We used Cox proportional hazards models to compare outcomes with and without CRT-D after adjustment for important covariates. After multivariable adjustment, CRT-D was associated with lower 3-year risks of death (hazard ratio, 0.52; 95% confidence interval, 0.48–0.56; P <0.001), all-cause readmission (hazard ratio, 0.69; 95% confidence interval, 0.65–0.73; P <0.001), and cardiovascular readmission (hazard ratio, 0.60; 95% confidence interval, 0.56–0.64; P <0.001). The association of CRT-D with mortality did not vary significantly among subgroups defined by age, sex, race, QRS duration, and optimal medical therapy. Conclusions— CRT-D was associated with lower risks of mortality, all-cause readmission, and cardiovascular readmission than medical therapy alone among patients with heart failure in community practice.

Background— Patients with heart failure and atrial fibrillation are at higher risk of thromboembolic events than patients with heart failure alone. Yet, the use of anticoagulation therapy varies in clinical practice, especially among older patients, for whom its effectiveness is poorly understood. Methods and Results— Using clinical registry data linked to Medicare claims from 2005 to 2011, we examined outcomes of older patients hospitalized with heart failure and atrial fibrillation who newly initiated anticoagulation therapy at discharge. We used Cox proportional hazards models and inverse probability-weighted treatment estimates to adjust for selection bias. Main outcomes were mortality and readmission at 1 and 3 years. Among 5105 patients in 195 hospitals, 1623 (31.8%) started anticoagulation therapy at discharge. Treated patients had lower unadjusted rates of all-cause mortality (26.4% versus 42.8%; P <0.001) and all-cause readmission (58.4% versus 63.7%; P <0.001) at 1 year. After inverse weighting for the probability of treatment and adjustment for other discharge medications, anticoagulation therapy was associated with significantly lower 1-year mortality (hazard ratio, 0.70; 99% confidence interval, 0.59–0.82), but there was no statistically significant difference in the risk of all-cause readmission (hazard ratio, 0.89; 99% confidence interval, 0.78–1.01) or other readmission outcomes. Results were similar at 3 years. Conclusions— Initiation of anticoagulation therapy at hospital discharge was associated with improved mortality at 1 and 3 years but was not associated with improved cardiovascular readmission among older patients with heart failure and atrial fibrillation.

Background Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P <0.0001), more likely to be white (92% versus 89%, P =0.005), more likely to have private insurance (33% versus 25%, P <0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P <0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P <0.0001), lower CHADS 2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P <0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P <0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P =0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P <0.0001). Conclusions Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL : Clinicaltrials.gov. Unique identifier: NCT 01165710.

Background— Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC. Methods and Results— We analyzed OAC use among 10 098 patients with AF from 174 community-based outpatient practices enrolled in 2010–2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS 2 ), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS 2 scores, from 53% for CHADS 2 =0 to 80% for CHADS 2 ≥2 ( P <0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 ( P <0.001). A significant interaction existed between ATRIA and CHADS 2 scores ( P =0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS 2 stroke risk had a smaller impact on use of OAC. Conclusions— In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.