Gustavo Morales

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.

Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation

BACKGROUND Ablation of long-standing persistent atrial fibrillation (AF) remains challenging, with a lower success rate than paroxysmal AF. A reliable ablation endpoint has not been demonstrated yet, although AF termination during ablation may be associated with higher long-term maintenance of sinus rhythm (SR). OBJECTIVE The purpose of this study was to determine whether the method of AF termination during ablation predicts mode of recurrence or long-term outcome. METHODS Three hundred six patients with long-standing persistent AF, free of antiarrhythmic drugs (AADs), undergoing a first radiofrequency ablation (pulmonary vein [PV] antrum isolation and complex fractionated atrial electrograms) were prospectively included. Organized atrial tachyarrhythmias (AT) that occurred during AF ablation were targeted. AF termination mode during ablation was studied in relation to other variables (characteristics of arrhythmia recurrence, redo procedures, the use of adenosine/isoproterenol for redo, and comparison of focal versus macroreentrant ATs). Long-term maintenance of SR was assessed during the follow-up. RESULTS During AF ablation, six of 306 patients converted directly to SR, 172 patients organized into AT (with 38 of them converting in SR with further ablation), and 128 did not organize or terminate and were cardioverted. Two hundred eleven of 306 patients (69%) maintained in long-term SR without AADs after a mean follow-up of 25 +/- 6.9 months, with no statistical difference between the various AF termination modes during ablation. Presence or absence of organization during ablation clearly predicted the predominant mode of recurrence, respectively, AT or AF (P = .022). Among the 74 redo ablation patients, 24 patients (32%) had extra PV triggers revealed by adenosine/isoproterenol. Termination of focal ATs was correlated with higher long-term success rate (24/29, 83%) than termination of macroreentrant ATs (20/35, 57%; P = .026). CONCLUSION AF termination during ablation (conversion to AT or SR) could predict the mode of arrhythmia recurrence (AT vs. AF) but did not impact the long-term SR maintenance after one or two procedures. AT termination with further ablation did not correlate with better long-term outcome, except with focal ATs, for which termination seems critical.

Catheter ablation of atrial fibrillation without the use of fluoroscopy

BACKGROUND In performing catheter ablation of paroxysmal atrial fibrillation (PAF), the advent of electroanatomical mapping (EAM) has significantly reduced fluoroscopy time. Recent advances in the ability of EAM systems to simultaneously visualize multiple catheters have allowed some operators to perform certain procedures, such as catheter ablation of supraventricular tachycardias, with zero fluoroscopy use. OBJECTIVE The purpose of this study was to evaluate the feasibility and safety of pulmonary vein (PV) isolation with zero fluoroscopy use, using a combination of three-dimensional EAM and intracardiac echocardiography (ICE). METHODS Using the NavX EAM system, the right atrial (RA) and coronary sinus (CS) geometries were created without fluoroscopy. Fluoroless transseptal puncture was performed under ICE guidance. Using a deflectable sheath and a multipolar catheter, the left atrial (LA) and PV anatomies were rendered and, in select cases, integrated with a three-dimensional computed tomography (CT) image. Irrigated radiofrequency ablation was performed to encircle each pair of ipsilateral PVs. RESULTS This series included 20 consecutive PAF patients. RA/CS mapping required 5.5 ± 2.6 minutes. In all patients, single (n = 18) or dual (n = 2) transseptal access was successfully achieved. The LA-PV anatomy was rendered using either a circular (14 patients) or penta-array (six patients) catheter in 22 ± 10 minutes; CT image integration was used in 11 patients. Using 49 ± 18 ablation lesions/patient, electrical isolation was achieved in 38/39 ipsilateral PV isolating lesion sets (97%). The procedure time was 244 ± 75 minutes. There were no complications. CONCLUSION Completely fluoroless catheter ablation of paroxysmal AF is safely feasible using a combination of ICE and EAM.

Inside-out access: A new method of lead placement for patients with central venous occlusions

BACKGROUND Physicians will increasingly encounter patients who require rhythm management devices but have venous obstructions that prevent conventional access. Alternate access options, such as thoracotomy or transiliac approaches, exist but are associated with greater cost and morbidity. OBJECTIVE The purpose of this study is to describe a novel method of vascular access that allows prepectoral placement of conventional pacing and defibrillation leads in patients with complex central venous occlusions. METHODS Eight patients with central venous occlusions were referred for device implantation. Inside-out central venous access (IOCVA) was obtained via a percutaneous femoral approach. A catheter-dilator system was advanced via the right atrium to the most central point of venous occlusion. The occluded vein segment was punctured with a directionally guided needle, which was advanced along intravascular or extravascular tissue planes to the subclavian region. A solid wire needle was oriented toward the skin surface and advanced through the soft tissues until it exists from the body. The wire was used to pull rigid dilators through the occluded segment. Standard transvenous leads were implanted though the newly created channel. RESULTS All patients with total central venous occlusions (4 superior vena cava, 4 brachiocephalic and bilateral subclavian) had successful, prepectoral device implants (4 left-sided, 1 single-chamber, 4 dual-chamber, 3 biventricular). No procedure-related complications occurred. All patients had normal device function at follow-up of 485 ± 542 days. CONCLUSION IOCVA is an effective method of pacemaker and defibrillator implantation for patients with central venous occlusions. Further clinical evaluation of this novel method is needed.

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.

Incidence, predictors, and outcomes associated with pneumothorax during cardiac electronic device implantation: A 16-year review in over 3.7 million patients

BACKGROUND Pneumothorax (PTX) is a potential complication of vascular access during cardiac implantable electronic device (CIED) procedures and is being scrutinized as a health care-acquired condition. OBJECTIVE The purpose of this study was to determine the trends in PTX incidence in the United Stated over a 16-year period and to determine whether PTX is associated with increased mortality after adjustment for other factors. METHODS Using weighted sampling in the largest inpatient health database in the United States (National Inpatient Sample), we evaluated data from patients with a primary procedure of CIED implantation from 1998 to 2013 who had at least 1 new vascular access (new or upgrade of prior CIED). The unadjusted and adjusted associations of PTX with mortality and other parameters were examined. RESULTS Among 3,764,703 CIED procedures, PTX occurred in 47,839 cases (1.3%). The apparent incidence of PTX peaked at 1.6% in 2012 and 2013, although this result may have been affected by a concomitant decrease of inpatient (vs outpatient) CIED. PTX was significantly associated with pulmonary complications, chest tube insertion, length of stay, and costs. Mortality was statistically higher in patients with PTX (1.2% vs 0.7%; P <.001), a relationship that remained significant in a multivariate logistic regression analysis (odds ratio 1.50, 95% confidence interval 1.36-1.65; P <.001). Age >80 years, female gender, Caucasian race, chronic obstructive pulmonary disease, and dual-chamber (vs single-chamber) device were all associated with higher odds for PTX occurrence. Placement of a chest tube was a major determinant of worse outcomes and higher costs. CONCLUSION PTX remains an important complication of CIED procedures and is associated with increased morbidity, mortality, and costs.

Giant J-wave (Osborn wave) unrelated to hypothermia

A 30-year-old male was admitted for gastroenteritis with abnormal serum calcium [ionized Ca2+ (ICa) of 4.1 mg/dL] which was corrected …

Digoxin and short term mortality after acute STEMI: Results from the MAGIC trial

BACKGROUND The safety of digoxin has been a subject of debate for decades, most recently among patients with atrial fibrillation (AF). Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure. Data about digoxin in this setting are scarce. HYPOTHESIS We hypothesize that digoxin maybe associated with increased mortality when used during the acute phase of ST segment myocardial infarction. METHODS We investigated the association between digoxin and mortality in patients enrolled in the MAGnesium In Coronaries (MAGIC) study, which evaluated the efficacy of early magnesium administration in STEMI. Multiple Cox proportional hazards models were examined to assess the aforementioned association after correction for clinical characteristics and comorbidities. RESULTS After excluding 639 (10.3%) patients for missing data, we analyzed the remaining 5574 patients. There were 852 (15.3%) deaths during the one month follow-up and 170 (3.0%) patients on digoxin concomitantly, among which 42 patients (24.7%) died. There was a statistically significant association between digoxin and increased mortality in the unadjusted statistical analysis; however, this association disappeared after correction for clinical characteristics and comorbidities in the primary multivariable analysis (estimated hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.62-1.19, p=0.372) and in three additional multivariable analyses. CONCLUSION Digoxin use as a new or preexisting medication during the acute phase of STEMI in the MAGIC trial was not associated with a significant increase in mortality after correcting for clinical characteristics and comorbidities.

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.

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.