Amiodarone-treated Patients Research Articles

Detailed analysis of electrogram peak frequency to guide ventricular tachycardia substrate mapping.

Differentiating near-field (NF) and far-field (FF) electrograms (EGMs) is crucial in identifying critical arrhythmogenic substrate during ventricular tachycardia (VT) ablation. A novel algorithm annotates NF-fractionated signals enabling EGM peak frequency (PF) determination using wavelet transformation. This study evaluated the algorithms' effectiveness in identifying critical components of the VT circuit during substrate mapping. A multicentre, international cohort undergoing VT ablation was investigated. VT activation maps were used to demarcate the isthmus zone (IZ). Offline analysis was performed to evaluate the diagnostic performance of low-voltage area (LVA) PF substrate mapping. A total of 30 patients encompassing 198 935 EGMs were included. The IZ PF was significantly higher in sinus rhythm (SR) compared to right ventricular paced (RVp) substrate maps (234 Hz (195-294) vs. 197 Hz (166-220); P = 0.010). Compared to LVA PF, the IZ PF was significantly higher in both SR and RVp substrate maps (area under curve, AUC: 0.74 and 0.70, respectively). The LVA PF threshold of ≥200 Hz was optimal in SR maps (sensitivity 69%; specificity 64%) and RVp maps (sensitivity 60%; specificity 64%) in identifying the VT isthmus. In amiodarone-treated patients (n = 20), the SR substrate map IZ PF was significantly lower (222 Hz (186-257) vs. 303 Hz (244-375), P = 0.009) compared to amiodarone-naïve patients (n = 10). The ≥200 Hz LVA PF threshold resulted in an 80% freedom from VT with a trend towards reduced ablation lesions and radiofrequency times. LVA PF substrate mapping identifies critical components of the VT circuit with an optimal threshold of ≥200 Hz. Isthmus PF is influenced by chronic amiodarone therapy with lower values observed during RV pacing.

Postoperative Atrial Fibrillation After Surgical Aortic Valve Replacement: Amiodarone and Warfarin Use

IntroductionThe association between amiodarone treatment for postoperative atrial fibrillation (POAF) after surgical aortic valve replacement (SAVR) and both the return to normal sinus rhythm (NSR) and anticoagulation use at discharge has not been extensively studied. MethodsWe retrospectively identified all patients who underwent biological SAVR with or without concomitant coronary artery bypass grafting (CABG) at a Veterans Affairs Medical Center (2005-2015). We reviewed new-onset POAF, amiodarone use, return to NSR, and anticoagulation use with warfarin. Discharge rhythm and warfarin administration were compared among patients with POAF who were treated with amiodarone and patients who did not receive amiodarone. ResultsOf the 395 patients (186 AVR/coronary artery bypass grafting; 209 AVR) studied, POAF developed in 191 patients (48.0%); 80.1% (153/191) of these patients received amiodarone. Among patients treated with amiodarone, 70.6% (108/153) were in SR at the time of discharge versus 65.8% (25/38) of POAF patients who were not treated with amiodarone (P = 0.57). Among amiodarone-treated patients, 30.7% (47/153) were discharged with warfarin; among patients not treated with amiodarone, 31.6% (12/38) were discharged with warfarin (P = 0.92). Among amiodarone-treated patients discharged in NSR, 89.9% (97/108 patients) were not discharged with warfarin; among patients not treated with amiodarone who were discharged in NSR, 92% (23/25) were not discharged with warfarin (P = 0.74). ConclusionsPOAF after SAVR appears common. Although amiodarone is often used for POAF patients, its use does not appear to be associated with surgeons' decision to anticoagulate patients. Surgeons’ preferences for using rhythm control and antithrombotic therapy for POAF after SAVR warrant further exploration.

Invasive Heart Rate Control as a Salvage Therapy in Amiodarone-induced Thyroid Storm.

Atrial fibrillation (AF) is the most common arrhythmia, and amiodarone is one of the most commonly used drugs for medical cardioversion of AF, which should be used carefully due to its toxic effects. Amiodaroneinduced thyrotoxicosis (AIT) may develop in amiodarone-treated patients. In contrast, the most common rhythm disturbance accompanying a thyroid storm is AF. This association may put both AF and thyrotoxicosis treatment into a vicious circle, leading to AI cardiomyopathy. Herein, we aimed to present atrioventricular node ablation as a salvage therapy in a patient with AIT who had AF-causing hemodynamic impairment, resistance to medical therapy, and cardioversion.

Effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset atrial fibrillation

New-onset of atrial fibrillation (NOAF) in critically ill patients is the most common acute cardiac dysrhythmia, but evidence-based data regarding treatment strategies are scarce. In this retrospective monocentric study, we compared effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset of atrial fibrillation. We identified a total of 209 patients for the main analysis. Amiodarone as compared to digitalis was associated with a clinically relevant faster time to heart rate control < 110 bpm (2 h (IQR: 1 h to 6 h) versus 4 h (2 h to 12 h); p = 0.003) and longer durations of sinus rhythm during the first 24 h of treatment (6 h (IQR: 6 h to 22 h) versus 0 h (IQR: 0 h to 16 h); p < 0.001). However, more bradycardic episodes occurred in association with amiodarone than with digitalis (7.7% versus 3.4%; p = 0.019). Use of amiodarone was associated with an increase of noradrenalin infusion rate compared to digitalis (23.9% versus 12.0%; p = 0.019). Within the tertile of patients with the highest CRP measurements, amiodarone treated patients presented with a higher decrease in heart rate than digoxin treated patients. Clinical trials comparing different NOAF treatment strategies are much needed and should report on concomitant sympathetic activity and inflammatory status.

Autophagy alleviates amiodarone-induced hepatotoxicity

Amiodarone is a widely used antiarrhythmic drug that can cause the development of steatohepatitis as well as liver fibrosis and cirrhosis. The molecular mechanisms of amiodarone-mediated liver injury remain largely unknown. We therefore analyzed amiodarone-mediated hepatocellular injury in patients with chronic heart failure, in primary hepatocytes and HepG2 cells. We found that amiodarone-treated patients with chronic heart failure revealed significantly higher serum levels of caspase-cleaved keratin-18, an apoptosis biomarker, compared to healthy individuals or patients not receiving amiodarone. Furthermore, amiodarone treatment of hepatocytes resulted in apoptosis associated with lipid accumulation and ER-stress induction. Liver cell steatosis was accompanied by enhanced de novo lipogenesis which, after reaching peak levels, declined together with decreased activation of ER stress. The decline of amiodarone-mediated lipotoxicity was associated with protective autophagy induction. In contrast, in hepatocytes treated with the autophagy inhibitor chloroquine as well as in autophagy gene (ATG5 or ATG7)-deficient hepatocytes, amiodarone-triggered toxicity was increased. In conclusion, we demonstrate that amiodarone induces lipid accumulation associated with ER stress and apoptosis in hepatocytes, which is mirrored by increased keratin-18 fragment serum levels in amiodarone-treated patients. Autophagy reduces amiodarone-mediated lipotoxicity and could provide a therapeutic strategy for protection from drug-induced liver injury.

Amiodarone disrupts cholesterol biosynthesis pathway and causes accumulation of circulating desmosterol by inhibiting 24-dehydrocholesterol reductase.

We have earlier reported that amiodarone, a potent and commonly used antiarrhythmic drug increases serum desmosterol, the last precursor of cholesterol, in 20 cardiac patients by an unknown mechanism. Here, we extended our study to a large number of cardiac patients of heterogeneous diagnoses, evaluated the effects of combining amiodarone and statins (inhibitors of cholesterol synthesis at the rate-limiting step of hydroxy-methyl-glutaryl CoA reductase) on desmosterol levels and investigated the mechanism(s) by which amiodarone interferes with the metabolism of desmosterol using in vitro studies. We report in a clinical case-control setting of 236 cardiac patients (126 with and 110 without amiodarone treatment) that amiodarone medication is accompanied by a robust increase in serum desmosterol levels independently of gender, age, body mass index, cardiac and other diseases, and the use of statins. Lipid analyses in patient samples taken before and after initiation of amiodarone therapy showed a systematic increase of desmosterol upon drug administration, strongly arguing for a direct causal link between amiodarone and desmosterol accumulation. Mechanistically, we found that amiodarone resulted in desmosterol accumulation in cultured human cells and that the compound directly inhibited the 24-dehydrocholesterol reductase (DHCR24) enzyme activity. These novel findings demonstrate that amiodarone blocks the cholesterol synthesis pathway by inhibiting DHCR24, causing a robust accumulation of cellular desmosterol in cells and in the sera of amiodarone-treated patients. It is conceivable that the antiarrhythmic potential and side effects of amiodarone may in part result from inhibition of the cholesterol synthesis pathway.

P1900Amiodarone treatment duration and reasons for permanent drug discontinuation in patients with atrial fibrillation

Abstract Background and purpose Amiodarone is commonly use in patients with atrial fibrillation (AF), but the organ toxicity side effects limit its long-term use. We investigated the rates of and reasons for permanent amiodarone discontinuation among patients with AF in contemporary clinical practice. Methods A single-centre, ongoing, registry-based observational longitudinal study included consecutive AF patients prescribed with amiodarone in our hospital from January 2015 to December 2017. All patients underwent a loading protocol of 400–600 mg of amiodarone daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter. Results Of 657 AF patients taking amiodarone (Mean age 62.2±11.0, female n=215 (32.6%), hypertension n=504 (76.7%), diabetes mellitus n=107 (16.3%), coronary arterial disease n=139 (19.8%), History of Myocardial infarction 86 (13.1%), Stroke/TIA 60 (9.1%), chronic kidney disease 157 (23.9%)), the drug was permanently discontinued in total of 248 patients (37.7%). The reasons for amiodarone discontinuation are shown in Figure. On multivariable Cox-regression analysis, physician's decision (HR 5.6; 95% CI 3.9–7.9, p&lt;0.001) and amiodarone side effects (HR 3.9; 95% CI 2.9–5.1, p&lt;0.001) were significantly associated with permanent amiodarone discontinuation. The overall time to discontinuation was 23.2±24.1 months. Compared with others, time to discontinuation was shorter in patients post AF ablation (17.3±21.3 vs 24.5±24.5, p=0.05), longer in those with AF progression (29.2±31.0 vs 20.9±20.3, p=0.014) and similar in patients with amiodarone side effects (23.7±17.7 vs 23.0±26.8, p=0.813). Pulmonary toxicity and proarrhythmia were not observed among study patients (Figure). Chart 1 Conclusion Our study showed that permanent discontinuation of amiodarone in contemporary clinical practice was due to the drug side effects in 12% of amiodarone-treated AF patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whereas the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), also was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in AF patients in daily practice.

6083Amiodarone in contemporary clinical practice: the rates of and reasons for permanent drug discontinuation

Abstract Background and purpose Amiodarone is the most effective antiarrhythmic drug, but its long-term use is limited by organ toxicity. We studied the rates of and factors associated with permanent amiodarone discontinuation in clinical practice. Methods An ongoing prospective single-centre registry-based observational study included consecutive amiodarone-naïve patients treated for cardiac arrhythmias in a university hospital between January 2015 and December 2017. Amiodarone was administered in loading doses of 400–800 mg daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter. Results Of 1032 patients (mean age 61.5±11.4 years), 30.0% were females, and amiodarone was used for atrial fibrillation (AF, n=657, 63.7%), atrial flutter (n=187, 18.1%), other supraventricular arrhythmias (n=118, 11.4%), premature ventricular beats (n=239, 23.2%) or ventricular tachycardias (n=236, 22.9%). The most prevalent comorbidities were hypertension (n=761, 73.7%), coronary artery disease (n=283, 27.4%), heart failure (n=197, 19.2%), chronic kidney disease (n=266, 25.8%) and diabetes mellitus (n=196, 19.0%). Amiodarone was permanently discontinued due to its side effects in 103 patients (10.0%), physician's fear of complications in 73 (7.1%), patient preference in 4 (0.4%) or for miscellaneous reasons in 6 (0.6%). In another 161 patients (15.6%), the discontinuation was due to catheter ablation of index arrhythmia (n=90) or progression to permanent AF (n=71). On multivariable Cox-regression analysis, physician decision was significantly associated with amiodarone discontinuation (HR 4.2; 95% CI 3.3–5.5, p&lt;0.001) along with the drug side effects (HR 3.0; 95% CI 2.4–3.8, p&lt;0.001). Overall, amiodarone was permanently discontinued 347 patients (33.6%), after mean 21.4±25.2 months of treatment (median 13.0, IQR 203). The mean time to discontinuation was significantly shorter in patients with drug discontinued due to physician's decision (16.5±15.9 vs 22.7±26.9, p=0.013) and slightly longer in those with amiodarone side effects (24.9±25.8 vs 19.9±24.8 months, p=0.093) than in others. Side effects resulting in permanent amiodarone discontinuation were: hyperthyreosis (66, 6.4%), hypothyreosis (19, 1.8%), liver injury (5, 0.5%), bradycardia/AV block (9, 0.9%), QT prolongation (2, 0.2%) and corneal deposits (4, 0.4%). Pulmonary toxicity was not observed among study patients. Conclusion Our study showed that permanent amiodarone discontinuation in contemporary practice was due to its side effects in 10% of amiodarone-treated patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whilst the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in daily practice.

Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study

IntroductionSupraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR)....

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality

Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT.

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and amiodarone-induced hypothyroidism.

Chronic metformin treatment was found to reduce elevated thyrotropin levels. Amiodarone treatment is associated with a range of effects in thyroid function from mild derangements to overt thyroid dysfunction. No previous study has investigated the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with amiodarone-induced hypothyroidism. The study included three age-, sex- and weight-matched groups of amiodarone-treated patients with type 2 diabetes: patients with treated overt hypothyroidism (group I, n=15), patients with untreated subclinical hypothyroidism (group II, n=15), and subjects without thyroid disorders (group III, n=18). The lipid profile, fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin, insulin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 6 months of metformin treatment (2.55-3g daily). In all groups of patients, metformin reduced plasma glucose and triglycerides, serum insulin, glycated hemoglobin as well as HOMA1-IR. The estimated glomerular filtration rate, thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. In patients with untreated amiodarone-induced hypothyroidism, but not in the other groups of patients, metformin reduced serum levels of thyrotropin and this effect correlated weakly with its action on insulin sensitivity. The obtained results indicate that the effect of metformin on hypothalamic-pituitary-thyroid axis activity is partially related to thyroid function. Metformin treatment may bring clinical benefits to patients with amiodarone-induced hypothyroidism and poor tolerance of exogenous L-thyroxine.

Amiodarone-Associated Optic Neuropathy: A Nationwide Study

To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. Retrospective population-based cohort study. Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. Hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

Vernakalant-facilitated electrical cardioversion: comparison of intravenous vernakalant and amiodarone for drug-enhanced electrical cardioversion of atrial fibrillation after failed electrical cardioversion.

AimsElectrical cardioversion is one cornerstone for the rhythm control strategy of atrial fibrillation (AF), which is, however, hampered by immediate AF recurrence (IRAF) or failed electrical cardioversion (FECV). We aimed to investigate the potential role of vernakalant for facilitated electrical cardioversion in cardioversion-resistant AF.Methods and resultsThe subjects of this study were 63 patients referred to the Heart Centre Leipzig between November 2011 and May 2014 for transthoracic electrical cardioversion of AF. All patients experienced after antiarrhythmic-naïve electrical cardioversion either IRAF (n = 44; 70%) or FECV (n = 19; 30%). After drug infusion, electrical cardioversion was successful in 66.7% of vernakalant-treated as opposed to 46.7% of amiodarone-treated patients (P = 0.109). Multivariate analysis revealed treatment with vernakalant (OR 0.057, 95% CI 0.006–0.540, P = 0.013), treatment with ACEI or ARB (OR 0.101, 95% CI 0.015–0.691 P = 0.019), and IRAF after initial CV (OR 0.047, 95% CI 0.004–0.498, P = 0.011) as predictors for successful, drug-facilitated electrical cardioversion. Subgroup analysis of 18 patients with previous AF ablation revealed a significantly higher success rate of electrical cardioversion after infusion of vernakalant than after infusion of amiodarone (66.7 vs. 11.1%, P = 0.016).ConclusionVernakalant may therefore be considered as a useful agent for facilitated electrical cardioversion in cardioversion-resistant AF.

EP News: Clinical

Flaker et al (J Am Coll Cardiol 2014;64:1541, PMID 25301455) examined the association of thrombotic events and bleeding with the use of amiodarone in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Overall, 2051 patients (11.4%) received amiodarone at randomization. Patients treated with warfarin and amiodarone had a lower time in the therapeutic range than did patients not treated with amiodarone (56.5% vs 63.0%; P < .0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/y vs 1.19%/y; hazard ratio [HR] 1.47; P = .0322). When apixaban and warfarin were compared, patients who received amiodarone were found to have a stroke or systemic embolism rate of 1.24%/y vs 1.85%/y (HR 0.68), a death rate of 4.15%/y vs 5.65%/y (HR 0.74), and a major bleeding rate of 1.86%/y vs 3.06%/y (HR 0.61). The authors conclude that amiodarone use was associated with a significantly increased stroke and systemic embolism and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding as compared with warfarin in amiodarone-treated patients and patients who were not treated with amiodarone.

Efficacy of amiodarone in patients with atrial fibrillation with and without left ventricular dysfunction: a pooled analysis of AFFIRM and AF-CHF trials.

Despite amiodarone's established safety profile in the setting of heart failure, it is unknown whether its impact on cardiovascular outcomes in patients with atrial fibrillation is modulated by left ventricular function. A pooled analysis of 3,307 patients (age 68.0 ± 0.2 years; 31.1% female) enrolled in AFFIRM and AF-CHF trials was conducted to assess the effect of rhythm control with amiodarone on cardiovascular outcomes, according to left ventricular systolic function. In amiodarone-treated patients (N = 1,107), freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences according to left ventricular function (P = 0.8754). Similarly, the adjusted proportion of time spent in atrial fibrillation (15.0 ± 1.8%) did not vary according to ventricular function (P = 0.6094). Over 40.0 ± 0.3 months of follow-up, 1,963 (59.4%) patients required at least one hospitalization, 1,401 (42.6%) of whom had cardiovascular-related hospitalizations. Adjusted all-cause and cardiovascular hospitalization rates were similar with amiodarone versus rate control in all patients and in subgroups with and without severe left ventricular dysfunction. A total of 729 (22.0%) patients died, 498 (15.1%) from cardiovascular causes. Adjusted all-cause and cardiovascular mortality rates were similar with amiodarone versus rate control overall and in subgroups with and without severe left ventricular dysfunction. Amiodarone's efficacy in maintaining sinus rhythm and reducing the burden of atrial fibrillation is similar in the presence or absence of severe left ventricular dysfunction. Rhythm control with amiodarone is associated with comparable hospitalization and mortality rates to rate control in patients with and without left ventricular dysfunction.

Amiodarone, Anticoagulation, and Clinical Events in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial

BackgroundAmiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. ObjectivesThis study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. MethodsBaseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. ResultsIn ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. ConclusionsAmiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone.

Use and outcomes of antiarrhythmic therapy in patients with atrial fibrillation receiving oral anticoagulation: results from the ROCKET AF trial.

Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. To study the use and outcomes of AAD therapy in anticoagulated patients with AF. Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin). Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33). Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.

In vivoprobe-based confocal laser endomicroscopy in amiodarone-related pneumonia

Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP). Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD. Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (>20 μm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p<0.001; HP-AMR-IP versus other groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively. In conclusion, pCLE appears to be a valuable tool for the in vivo diagnosis of AMR-IP in subacute ILD patients.

Amiodarone and the thyroid: a 2012 update.

Amiodarone-induced thyroid dysfunction occurs in 15-20% of amiodarone-treated patients. Amiodarone-induced hypothyroidism (AIH) does not pose relevant problems, is easily controlled by L-thyroxine replacement, and does not require amiodarone withdrawal. Most frequently AIH develops in patients with chronic autoimmune thyroiditis. Amiodarone- induced thyrotoxicosis (AIT) is most frequently due to destructive thyroiditis (type 2 AIT) causing discharge of thyroid hormones from the damaged, but otherwise substantially normal gland. Less frequently AIT is a form of hyperthyroidism (type 1 AIT) caused by the iodine load in a diseased gland (nodular goiter, Graves' disease). A clearcut differentiation between the two main forms is not always possible, despite recent diagnostic advances. As a matter of fact, mixed or indefinite forms do exist, contributed to by both thyroid damage and increased thyroid hormone synthesis. Treatment of type 1 (and mixed forms) AIT is based on the use of thionamides, a short course of potassium perchlorate and, if treatment is not rapidly effective, oral glucocorticoids. Glucocorticoids are the first-line treatment for type 2 AIT. Amiodarone should be discontinued, if feasible from a cardiac standpoint. Continuation of amiodarone has recently been associated with a delayed restoration of euthyroidism and a higher chance of recurrence after glucocorticoid withdrawal. Whether amiodarone treatment can be safely reinstituted after restoration of euthyroidism is still unknown. In rare cases of AIT resistance to standard treatments, or when a rapid restoration of euthyroidism is advisable, total thyroidectomy represents a valid alternative. Radioiodine treatment is usually not feasible due to the low thyroidal iodine uptake.