Matthew G. Whitbeck

Increased mortality among patients taking digoxin—analysis from the AFFIRM study

AIMS Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. METHODS AND RESULTS The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. CONCLUSION Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Is there an association between external cardioversions and long-term mortality and morbidity? Insights from the Atrial Fibrillation Follow-up Investigation of Rhythm Management study.

Background— Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. Methods and Results— We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P<0.0001). Conclusions— In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.Background —Cardiac electrical therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardiac defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regards to cardiovascular mortality and morbidity. Methods and Results —We analyzed the data of the 4,060 patients from the AFFIRM trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality and hospitalizations post ECVe were studied. Over an average follow-up of 3.5 years, 660 patients (16.3%) died, 331(8.2%) from cardiovascular causes. A total of 207(5.1%) and 1697(41.8%) patients had low ejection fraction (EF) and non-paroxysmal atrial fibrillation (AF) respectively. 2460 patients received no ECVe; while 1600 experienced ≥1 ECVe. Death occurred in 412(16.7%), 196(16.5%), 39(13.5%), and 13(10.4%) of patients with 0, 1, 2, and ≥3 ECVe respectively. There was no significant association between ECVe and mortality within any of the four subgroups defined by EF and AF type, although myocardial infarction (MI), coronary artery bypass graft (CABG), and digoxin were significantly associated with death (Estimated hazard ratios: 1.65; 1.59 and 1.62 respectively, p<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% vs. 5.8%; Estimated odds ratio: 1.39, p<0.0001). Conclusions —In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, MI, and CABG were significantly associated with mortality.

QRS duration predicts death and hospitalization among patients with atrial fibrillation irrespective of heart failure: evidence from the AFFIRM study

AIMS The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF. METHODS AND RESULTS QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90-119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29-2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07-1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90-119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90-119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14). CONCLUSION Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF.

Double Atrial Septal Defect: Diagnosis and Closure Guidance with 3D Transesophageal Echocardiography

Atrial septal defect (ASD) is a common form of congenital heart disease that often persists well into adulthood before discovery or intervention. The authors report the case of a patient referred for routine percutaneous ASD closure that was found on three‐dimensional (3D) transesophageal echocardiography to have two large separate ostium secundum defects which were subsequently closed under 3D echocardiographic guidance. (Echocardiography 2011;28:E115‐E117)

Is there an Association Between External Cardioversions and Long Term Mortality and Morbidity - Insights from the AFFIRM Study

Background— Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. Methods and Results— We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P<0.0001). Conclusions— In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.Background —Cardiac electrical therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardiac defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regards to cardiovascular mortality and morbidity. Methods and Results —We analyzed the data of the 4,060 patients from the AFFIRM trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality and hospitalizations post ECVe were studied. Over an average follow-up of 3.5 years, 660 patients (16.3%) died, 331(8.2%) from cardiovascular causes. A total of 207(5.1%) and 1697(41.8%) patients had low ejection fraction (EF) and non-paroxysmal atrial fibrillation (AF) respectively. 2460 patients received no ECVe; while 1600 experienced ≥1 ECVe. Death occurred in 412(16.7%), 196(16.5%), 39(13.5%), and 13(10.4%) of patients with 0, 1, 2, and ≥3 ECVe respectively. There was no significant association between ECVe and mortality within any of the four subgroups defined by EF and AF type, although myocardial infarction (MI), coronary artery bypass graft (CABG), and digoxin were significantly associated with death (Estimated hazard ratios: 1.65; 1.59 and 1.62 respectively, p<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% vs. 5.8%; Estimated odds ratio: 1.39, p<0.0001). Conclusions —In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, MI, and CABG were significantly associated with mortality.

Balloon-Facilitated Delivery of a Left Ventricular Pacing Lead

While modern implant tools have contributed greatly to the success of cardiac resynchronization therapy, technical challenges remain. A common problem is the inability to advance left ventricular pacing leads into branch veins that are tortuous or arise at steep angles. In these cases, advancement of the lead causes it to buckle and prolapse into the coronary sinus or great cardiac vein. Lead prolapsed can be avoided by employing a balloon to temporarily obstruct the coronary sinus or great cardiac vein just upstream from the branch vein. The balloon redirects the force of advancement laterally into the branch vein, facilitating delivery. (PACE 2013; 36:e31–e34)

DIGOXIN AND MORTALITY: INSIGHTS FROM THE AFFIRM STUDY

Abstract Category: 26. Clinical Electrophysiology—Supraventricular ArrhythmiasPresentation Number: 906-6Authors: Matthew G. Whitbeck, Richard Charnigo, Milagros M. Zegarra, Jignesh Shah, Gustavo X. Morales, Charles Campbell, Alison Bailey, Tracy Macaulay, Claude S. Elayi, University of Kentucky, Lexington, KY Background: Digoxin remains a widely used medication worldwide for congestive heart failure (CHF) and rate control of atrial fibrillation (AF). There are, however, conflicting data about its safety, particularly in patients with AF. Since the Digitalis Investigation Group (DIG) study, several studies have identified digoxin as a predictor of increased mortality. Our objective was to determine whether digoxin increased mortality independently of CHF and ejection fraction (EF) in patients enrolled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.Methods: The AFFIRM database was analyzed using Cox proportional hazards regression modeling to determine the associations of overall and cardiovascular mortality with digoxin among patients without CHF or low EF and among patients with either CHF or low EF, controlling for cardioversions, AF type, and baseline characteristics.Results: Among patients without low EF or CHF, digoxin significantly elevated the hazard for overall mortality by an estimated 45.3% (Estimated Hazard Ratio [EHR] = 1.45, 95% CI = 1.17 to 1.8, p = 0.0006). There was also a trend toward an elevated risk of cardiovascular mortality (EHR = 1.36, 95% CI = 0.98 to 1.91, p = 0.068). Among patients with either low EF or CHF, digoxin significantly elevated the hazard for overall mortality by an estimated 41.9% (EHR = 1.42, 95% CI = 1.11 to 1.82, p = 0.0057) and for cardiovascular mortality by an estimated 49.5% (EHR = 1.49, 95% CI = 1.08 to 2.06, p = 0.0145).Conclusion: Digoxin was significantly associated with increased cardiovascular and total mortality irrespective of CHF or low EF in patients who participated in the AFFIRM study.

Is There an Association Between External Cardioversions and Long-Term Mortality and Morbidity?Clinical Perspective: Insights From the Atrial Fibrillation Follow-Up Investigation of Rhythm Management Study

Background— Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. Methods and Results— We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P<0.0001). Conclusions— In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.Background —Cardiac electrical therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardiac defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regards to cardiovascular mortality and morbidity. Methods and Results —We analyzed the data of the 4,060 patients from the AFFIRM trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality and hospitalizations post ECVe were studied. Over an average follow-up of 3.5 years, 660 patients (16.3%) died, 331(8.2%) from cardiovascular causes. A total of 207(5.1%) and 1697(41.8%) patients had low ejection fraction (EF) and non-paroxysmal atrial fibrillation (AF) respectively. 2460 patients received no ECVe; while 1600 experienced ≥1 ECVe. Death occurred in 412(16.7%), 196(16.5%), 39(13.5%), and 13(10.4%) of patients with 0, 1, 2, and ≥3 ECVe respectively. There was no significant association between ECVe and mortality within any of the four subgroups defined by EF and AF type, although myocardial infarction (MI), coronary artery bypass graft (CABG), and digoxin were significantly associated with death (Estimated hazard ratios: 1.65; 1.59 and 1.62 respectively, p<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% vs. 5.8%; Estimated odds ratio: 1.39, p<0.0001). Conclusions —In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, MI, and CABG were significantly associated with mortality.

Is There an Association Between External Cardioversions and Long-Term Mortality and Morbidity?Clinical Perspective

Background— Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. Methods and Results— We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P<0.0001). Conclusions— In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.Background —Cardiac electrical therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardiac defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regards to cardiovascular mortality and morbidity. Methods and Results —We analyzed the data of the 4,060 patients from the AFFIRM trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality and hospitalizations post ECVe were studied. Over an average follow-up of 3.5 years, 660 patients (16.3%) died, 331(8.2%) from cardiovascular causes. A total of 207(5.1%) and 1697(41.8%) patients had low ejection fraction (EF) and non-paroxysmal atrial fibrillation (AF) respectively. 2460 patients received no ECVe; while 1600 experienced ≥1 ECVe. Death occurred in 412(16.7%), 196(16.5%), 39(13.5%), and 13(10.4%) of patients with 0, 1, 2, and ≥3 ECVe respectively. There was no significant association between ECVe and mortality within any of the four subgroups defined by EF and AF type, although myocardial infarction (MI), coronary artery bypass graft (CABG), and digoxin were significantly associated with death (Estimated hazard ratios: 1.65; 1.59 and 1.62 respectively, p<0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% vs. 5.8%; Estimated odds ratio: 1.39, p<0.0001). Conclusions —In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, MI, and CABG were significantly associated with mortality.