Risultati per: Antiaritmici (Amiodarone)

Circulation, Volume 150, Issue Suppl_1, Page A4135425-A4135425, November 12, 2024. Background:Aberrant diastolic Ca2+leak through the cardiac ryanodine receptor (RyR2) is an important cause of heart failure (HF) and lethal arrhythmia. Dantrolene (DAN) specifically binds to the Leu601-Cys620of N terminal domain in RyR2 and stabilizes the tetrameric structure of RyR2, preventing the Ca2+leak through RyR2. Our previous study as a proof-of-concept showed that intravenous injection (i.v.) of DAN was effective in termination and prevention of refractory ventricular tachycardia (VT) storm in HF.Research Question:How much is loading dose of DAN i.v. to terminate VT storm in HF? We hypothesized that the optimal dose was within 3mg/kg from our previous study.Aim:This study aimed to verify that 3mg/kg DAN i.v. was optimal for the termination of amiodarone-resistant VT storm in HF.Methods:This was an open-label, uncontrolled, single-center study. The detail in the study design and methods is shown inFig.1. We studied patients with episodes of VT storm regardless of medications, such as amiodarone and beta-blockers, recommended by HF guidelines. DAN(3mg/kg) was intravenously added on the above guideline treatment. The acute anti-arrhythmic efficacy of DAN was assessed as follows: 1) proportion of patients whose VT storm was terminated by 3mg/kg DAN i.v., 2) incidence rate of VT storm within 24 hours before and after DAN i.v..Results:The consecutive 7 patients with refractory VT storm were enrolled in this study (median age:72 years old, male/female: 4/3, median LVEF29%). Underlying heart disease included 3 ischemic cardiomyopathy, 3 acute myocardial infarction after successful percutaneous coronary intervention and 1 tachycardia-induced cardiomyopathy. 2 of 7 patients underwent mechanical circulatory support before DAN i.v. because of pulseless VT. All patients were classified as NYHA class III/IV. 3 mg/kg of DAN i.v. ceased VT storm within 60 min in 7/7 (100%)(Fig.2, left).The number of sustained VT within 24 h after DAN i.v. were significantly lower than those within 24 h prior to DAN administration(Fig 2, right). A representative case is shown inFig.3The VT storms refractory to amiodarone and landiolol (beta-blocker) as well as sedation showed complete response to 3mg/kg DAN i.v..Conclusions:DAN, a RyR2 stabilizer, was effective in the termination of VT storm in HF resistant to guideline directed medical treatment. This is the first study to evaluate the optimal dose of DAN i.v. against the refractory VT storm in HF.

Circulation, Volume 148, Issue Suppl_1, Page A13366-A13366, November 6, 2023. Introduction:Atrial fibrillation (AF) is the most common arrythmia with significant health system burden and emergency room/hospital admissions. We conducted this study to understand the efficacy of managing AF with first line short term outpatient amiodarone followed by catheter ablation (pulmonary vein isolation). Amiodarone was continued for 6 months post catheter ablation (CA). We looked at a primary end point of recurrence of AF and the drug side effects during the year post CA.Hypothesis:If this strategy of short-term amiodarone with early ablation of AF is effective, then we could incorporate this in an AF management care plan.Methods:In this retrospective cohort study, we used TriNetX database to collect data on patients with amiodarone initiation with CA and those who were given Dofetilide or Sotalol, followed by CA. We collected data between March 1, 2020, and June 1, 2021. We created a propensity score matching of a 1:1 to match on the covariates: Age, Male, Female, CAD, Heart Failure, Diabetes, COPD, BMI. The endpoint is occurrence of AF within 365 days of medication initiation.Results:A total of 40,640 patients were included in the analysis. Of those patients, Cohort 1 comprised amiodarone initiation with catheter ablation (n=176) compared to Dofetilide or Sotalol which had (n=40,474). After the propensity match, we included 176 individual patients in each cohort. The amiodarone group had more men (79.5% vs 58.8, P

Circulation, Volume 148, Issue Suppl_1, Page A396-A396, November 6, 2023. Introduction:Although there is a possibility that the effectiveness of amiodarone may differ among a particular subgroup, there are few studies on the differential effects of amiodarone for the out-of-hospital cardiac arrest (OHCA) patients with a shockable rhythm.Objective:To identify subgroups with differential responses to amiodarone in OHCA with shockable rhythm by a novel machine learning approach.Methods:We used data from the Japanese nationwide OHCA registry of the Japanese Association for Acute Medicine. The OHCA patients who had initial shockable rhythm upon hospital arrival were included. The primary outcome was a good neurological outcome at 30 days, defined as a Cerebral Performance Categories score ≤2. We developed a linear score by outcome weighting learning (OWL) method with logistic loss to identify subgroups with differential effects of amiodarone. The difference in the effect of amiodarone between subgroups based on the developed score was evaluated by repeated cross-validation (RCV), and hypothesis testing was performed by the permutation method.Results:Among 68,111 OHCA patients in the registry, data of 2333 patients with initial shockable rhythm upon hospital arrival were analyzed. Our developed score showed that the longer duration from call to EMS to hospital arrival, hypothermia at hospital arrival, and no defibrillation until hospital arrival were important variables that had a trend of increasing the beneficial effect of amiodarone (Table). The effect of amiodarone on neurological outcomes varied significantly among the subgroups identified by the developed scores (OR: 1.05 (95%CI: 0.99-1.13), P[RCV]= 0.038).Conclusions:We successfully developed a model that discriminates between the patients for whom amiodarone had a harmful effect on their neurological outcome from those for whom amiodarone had a beneficial effect. In the patients for whom amiodarone had a harmful effect, the other treatment approaches may be needed.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 146, Issue Suppl_1, Page A9368-A9368, November 8, 2022. Introduction:Amiodarone is a commonly used pharmacotherapy in patients with atrial fibrillation (AF) with potential for drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs). We aimed to assess the bleeding risk after co-prescription of amiodarone and DOACs among adults with AF.Methods:We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF > 66 years on a DOAC between April 1, 2011-March 31, 2018. Cases were patients admitted with major bleeding (index date). Controls were matched in a 2:1 ratio to cases. We categorized exposure to amiodarone before the index date as: a) current users (amiodarone within 60 days); b) past users (amiodarone within 61 to 140 days); and c) unexposed (no amiodarone prescription or amiodarone prescription >140 days before index date). Conditional logistic regression models were used to examine the association between bleeding and amiodarone co-prescription.Results:Among 86,679 AF patients on a DOAC, we identified 2,766 cases (3.2%) admitted with major bleeding. The median age of AF patients was 80 years (interquartile range 75-85); 48.3% were women. After multivariable adjustment, there was a significant association between major bleeding and current use of amiodarone (adjusted odds ratio (aOR) 1.53; 95% confidence interval (CI) 1.24-1.89, p

Circulation, Volume 146, Issue Suppl_1, Page A10926-A10926, November 8, 2022. Introduction:Many prediction algorithms for warfarin maintenance dose (WD) were constructed based on the clinical and genetic information of the patients without extracorporeal circulation devices (ECDs). However, it is unclear whether might be useful for the patients with ECD, such as left ventricular assist devices (LVAD), who still require warfarin.Hypothesis:The WD algorithms constructed using non-ECD patients could be useful for LVAD patients.Methods:An observational study, the Human Genome Research Ethics Committee of OU approved (#756), was conducted at the Osaka University (OU) Hospital on 108 LVAD patients receiving warfarin therapy. Genetic polymorphisms of CYP2C9*1, *3, and VKORC1-1639G >A were tested using TaqMan genotyping assay kits. WD was defined as the administered dose during the periods when the PT-INR value was within its target range. We investigated the difference between the actual warfarin dose (AWD) and the calculated warfarin dose (CWD) using an algorithm proposed by the International Warfarin Pharmacogenetics Consortium (IWPC), which we verified with 125 Japanese non-ECD patients previously (Eur J Clin Pharmacol, 75:901).Results:The percentage of patients whose difference between CWD and AWD was within 20% of AWD showed no significant difference between the LVAD and the non-ECD (%; I, LVAD, 41.7, non-ECD, 49.6, p=0.23). The root mean squared percentage error (RMSPE) to the AWD was similar between the groups (%; LVAD, 42, non-ECD, 37). As the algorithm requires if amiodarone is concomitant with warfarin, we probed the effect of the amiodarone dose on the CWD. Interestingly, RMSPE of the LVAD with ≥ 200 mg/day of amiodarone (≥ 200A) was higher compared to those with < 200 mg/day (

Circulation, Volume 146, Issue Suppl_1, Page A10988-A10988, November 8, 2022. Case description:A 61 year-old male with a hx of CAD s/p CABG and HFrEF s/p AICD presents with a 4-day history of dizziness and shortness of breath; he was found to be in ventricular tachycardia (VT) storm. ICD interrogation was found to have 13 shocks in 24 hours. His thyroid function tests (TFT) were abnormal: TSH undetectable, elevated FT4 7.7 (0.93-1.7) and T3 246.6 (84-202) ng/dL, respectively. He was diagnosed with severe thyrotoxicosis, likely due to amiodarone-induced thyrotoxicosis (AIT) type 2 and a Burch-Wartofsky score of 50, highly suggestive of thyroid storm (TS). He was started on hydrocortisone, prednisone, propylthiouracil, and metoprolol for the TS. Procainamide drip had been initiated for VT and titrated until VT was controlled. Repeat TFTs in 48 hours showed no changes in TSH or FT4, but T3 had normalized. Procainamide and hydrocortisone were discontinued after VT frequency had decreased.Discussion:An electrical storm (ES) is a state of electrical instability characterized by multiple episodes of VT in 24 hours. In patients with ICD, it is defined as >3 anti-tachycardic pacing therapies or shock. Most patient with ES have severe underlying structural heart disease with various inciting events such as thyrotoxicosis. Amiodarone is the drug of choice in VT; however, complications such as AIT should be recognized. Thyroid hormone has a direct arrhythmogenic effect on the heart through various cellular mechanisms. In our patient, amiodarone was discontinued after the diagnosis of AIT. Procainamide and antithyroid therapy were started, which subsequently controlled the VT. Resistance to therapy can occur, and more elaborate interventions such as plasmapheresis are an option to remove amiodarone, its metabolites, and free thyroid hormones.Conclusion:Amiodarone is the most efficacious medication for VT. However, it is important to recognize possible life-threatening complications of this medication, such as AIT, which itself can exacerbate VT.

Circulation, Volume 146, Issue Suppl_1, Page A9457-A9457, November 8, 2022. Background:Primary graft dysfunction (PGD) is devastating. Amiodarone therapy prior to cardiac transplantation (TxP) is common but has recently been reported as potential cause of PGD.Case:66-year-old male with non-ischemic cardiomyopathy, severely reduced LVEF with LVAD, recurrent VT on amiodarone for 6 months presented with ICD shocks. Amiodarone was increased due to VT storm in the setting of Rhinovirus infection. Infusions with amiodarone and lidocaine were started but repeat IV boli of lidocaine and amiodarone were needed. VT-ablation was not feasible due to multiple morphologies. He underwent TxP with an ideal organ from a 28 yo donor. Paragonix SherpaPak was used for transport. Pre-explanation EF was 70% with serologies positive for EBV (+/+), Strongyloides (+/-), negative for Toxoplasmosis (-/-), CMV (-/-). Donor heart was arrested with appropriate cardioplegia and no distention occurred. Total ischemic time was 3 hours 10 minutes, warm ischemic time 40 minutes, crossclamp time in recipient 2 hours 2 minutes with total cardiopulmonary bypass time 2 hours 58 minutes. Coming off bypass both ventricles appeared markedly dilated with severely reduced function and due to high doses of inotropic and vasopressor support veno-arterial ECMO was placed. The chest was left open and during postoperative course in the intensive care unit pressor and inotropes could slowly weaned. Induction therapy was administered with ATG, Solumedrol and mycophenolate mofetil. Strongyloides infection was treated with four doses of Ivermectin. On postoperative day LVEF recovered to 40-45% with moderately reduced RV function and patient was successfully decannulated from VA ECMO with chest closure. Endomyocardial biopsies showed no signs of rejection throughout. After prolonged ICU and rehab stay patient has now recovered to independent life.Conclusion:Amiodarone associated PGD may be underreported and increasing awareness of this etiology may warrant early empiric discontinuation of the medication if transplantation remains a therapeutic option in the future.

Circulation, Volume 146, Issue Suppl_1, Page A15919-A15919, November 8, 2022. Background:Early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients who had recently (within 1 year) been diagnosed with atrial fibrillation (AF). In real-world data, the most commonly selected initial rhythm control strategy was the Class III anti-arrhythmic drug (AAD) amiodarone, but adverse outcomes related amiodarone toxicity was not well reported in this population. This study sought to investigate the fatal and non-fatal adverse outcomes related amiodarone toxicity in early rhythm control of patients with AF.Methods:Using the database of Korean National Health Insurance Service, we analyzed the adverse outcomes related amiodarone toxicity in 140,908 (rhythm control: 57,148, rate control: 83,760) patients with AF undergoing rhythm control or rate control therapy, initiated within 1 year of AF diagnosis, between 2005 and 2015.Results:The most commonly used rhythm control strategy was the class III drug amiodarone (22,877 (40.0%) of 57,148 patients in early rhythm control), followed by class Ic drugs. Patients with amiodarone for initial rhythm control strategy showed higher rate of interstitial lung disease (1.43% vs. 0.75%, p

Circulation, Volume 146, Issue Suppl_1, Page A10726-A10726, November 8, 2022. Introduction:Amiodarone remains underutilized as an anti-arrhythmic due to significant off-target toxicities with long-term use. We hypothesized that the required dose could be minimized by targeting amiodarone to cardiomyocytes by utilizing a cardiomyocyte targeting peptide (CTP).Methods:CTP (APWHLSSQYSRT) was conjugated to amiodarone via a disulfide bond, HPLC purified, characterized by MALDI/TOF, and stability at 37°C assessed using serial HPLCs over 21 days. Adult, male guinea pigs (GP; n=4/group) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80mg/Kg), 1/10ththe molar dose of CTP-amiodarone (5 days), or CTP (5 days), followed by euthanasia, hearts excised, perfused on a Langendorff apparatus with Tyrode’s solution, and placed in a custom-designed chamber blebbistatin (5 μM) to minimize contractions. Bolus injections of voltage (RH237) and Ca2+-indicator dye (Rhod-2/AM) were injected to simultaneously map cardiac action potentials (APs) and Ca2+transients (CaT), at 610-750nm and 570-595nm, respectively with 2 CMOS cameras, followed by pacing at 250ms to measure conduction velocity (CV), AP and CaT durations (at 90% recovery).Results:CTP-amiodarone produced a single HPLC peak at 16mins that remained stable for 21 days. CTP-amiodarone and amiodarone decreased conduction velocities in myocytes significantly compared to control GPs (0.92±0.05, 0.87±0.08ms, vs. 1.00±0.03m/s respectively, p

Circulation, Volume 146, Issue Suppl_1, Page A12278-A12278, November 8, 2022. Introduction:Catheter ablation for atrial fibrillation is a common therapeutic strategy for paroxysmal and persistent AF patients, but long-term success rates are imperfect. Maintenance of sinus rhythm prior to ablation with antiarrhythmic drug therapy has improved outcomes in patients undergoing ablation compared to ablation procedure alone. Amiodarone has superior efficacy relative to other AADs. Whether the failure of amiodarone to maintain sinus rhythm prior to ablation is a predictor of poor outcomes is unknown.Methods:Total 307 patients received amiodarone in a span of 1y before undergoing catheter ablation for AF from January 2014 to March 2019. Patients were divided into amiodarone success (n=183) and amiodarone failure (n=124) groups based on the response to pre-ablation amiodarone treatment. Follow-up was done for 12 months post-ablation to assess outcomes (arrhythmia recurrence and adverse events). Procedural success was defined by the absence of documented arrhythmia ( >30s) without any antiarrhythmic agents beyond a 90d blanking period.Results:Ablation procedure success rate at 1y was 57.7% overall. 1y success rate in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs. 60.5%; p=0.54). Success rates following ablation did not vary by the response to amiodarone when analyzed for paroxysmal or persistent AF subgroups.Conclusion:Failure to restore and maintain sinus rhythm on amiodarone therapy is not a predictor of adverse ablation procedure outcomes and should not be used as a patient selection criteria for consideration of ablation.