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BMJ Case Reports Nov 2023
Topics: Humans; Amiodarone; Anti-Arrhythmia Agents; Chemical and Drug Induced Liver Injury
PubMed: 37914162
DOI: 10.1136/bcr-2023-256679 -
Journal of the Academy of... Jun 2024
PubMed: 38852623
DOI: 10.1016/j.jaclp.2024.06.001 -
Cardiology Clinics May 2024The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify... (Review)
Review
The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of β-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.
Topics: Humans; Heart Arrest; Anti-Arrhythmia Agents; Amiodarone; Lidocaine; Epinephrine; Ventricular Fibrillation; Cardiopulmonary Resuscitation
PubMed: 38631795
DOI: 10.1016/j.ccl.2024.02.012 -
Primary Care Mar 2024Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD... (Review)
Review
Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD include promoting a healthy lifestyle, following United States Preventive Service Task Force recommendations related to cardiovascular disease, and controlling comorbid conditions. For a patient experiencing SCA, early cardiopulmonary resuscitation and defibrillation should be performed. Implantable cardioverter defibrillators are more effective at secondary prevention compared with drug therapy but medications such as amiodarone, beta-blockers, and sotalol may be helpful adjuncts to reduce the risk of SCD or improve a patient's symptoms (eg, palpitations and inappropriate defibrillator shocks).
Topics: Humans; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Heart Arrest; Defibrillators, Implantable; Sotalol
PubMed: 38278568
DOI: 10.1016/j.pop.2023.07.008 -
Critical Care Medicine Sep 2023To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.
OBJECTIVES
To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.
DESIGN
Multicenter, prospective, inception cohort study.
SETTING
Forty-four ICUs in 12 countries in four geographical regions.
SUBJECTS
Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99).
CONCLUSIONS
In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.
Topics: Adult; Humans; Atrial Fibrillation; Cohort Studies; Prospective Studies; Incidence; Risk Factors; Intensive Care Units
PubMed: 37078722
DOI: 10.1097/CCM.0000000000005883 -
European Heart Journal Feb 2024Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from...
BACKGROUND AND AIMS
Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used.
METHODS
A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC.
RESULTS
The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses.
CONCLUSION
In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.
Topics: Humans; Female; Aged; Male; Amiodarone; Atrial Fibrillation; Anti-Arrhythmia Agents; Israel; Lung Diseases, Interstitial; Lung Neoplasms
PubMed: 37939798
DOI: 10.1093/eurheartj/ehad726 -
JACC. Clinical Electrophysiology Aug 2023The overall survival in patients undergoing lung transplantation is poor. Although postsurgical atrial arrhythmias seem to play a major role in the morbidity and... (Review)
Review
The overall survival in patients undergoing lung transplantation is poor. Although postsurgical atrial arrhythmias seem to play a major role in the morbidity and mortality of this population, data regarding the clinical and interventional management of this complication are still controversial. Through a review of the literature in the field, we observed that not only the surgical technique is clearly arrhythmogenic, but the new administration of peri-procedure beta-blockers and amiodarone for arrhythmia prevention and treatment, respectively, seems harmful in these postsurgical patients. However, low-dose beta-blockers administered after surgery seem feasible in arrhythmia prevention in specific patient subgroups, and, aside from amiodarone, alternative antiarrhythmic agents can be safely and effectively used to treat symptomatic patients on top of adequate rate control. Finally, as to complex atrial arrhythmias occurring late after lung transplant surgery, radiofrequency catheter ablation seems a feasible treatment option. In light of this evidence and considering the absence of clear recommendations in the field, we suggest a practical approach that may help the clinician in the management of this postsurgical complication. However, as most of these considerations are drawn from small-sized and retrospective studies, more evidence is needed in the future to clarify which medical and interventional strategies may best treat these postsurgical arrhythmias and thus potentially improve the outcome of these frail patients.
Topics: Humans; Atrial Fibrillation; Retrospective Studies; Lung Transplantation; Amiodarone; Anti-Arrhythmia Agents
PubMed: 37648342
DOI: 10.1016/j.jacep.2023.01.021 -
Pharmaceutics Aug 2023Amiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to the lowering of the dose by...
BACKGROUND
Amiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to the lowering of the dose by utilizing a cardiomyocyte-targeting peptide (CTP), a cell-penetrating peptide identified by our prior phage display work.
METHODS
CTP was synthesized thiolated at the N-terminus, conjugated to amiodarone via Schiff base chemistry, HPLC purified, and confirmed with MALDI/TOF. The stability of the conjugate was assessed using serial HPLCs. Guinea pigs (GP) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80 mg/kg), CTP-amiodarone (5 days; 26.3 mg/kg), or CTP (5 days; 17.8 mg/kg), after which the GPs were euthanized, and the hearts were excised and perfused on a Langendorff apparatus with Tyrode's solution and blebbistatin (5 µM) to minimize the contractions. Voltage (RH237) and Ca-indicator dye (Rhod-2/AM) were injected, and fluorescence from the epicardium split and was captured by two cameras at 570-595 nm for the cytosolic Ca and 610-750 nm wavelengths for the voltage. Subsequently, the hearts were paced at 250 ms with programmed stimulation to measure the changes in the conduction velocities (CV), action potential duration (APD), and Ca transient durations at 90% recovery (CaTD). mRNA was extracted from all hearts, and RNA sequencing was performed with results compared to the control hearts.
RESULTS
The CTP-amiodarone remained stable for up to 21 days at 37 °C. At ~1/15th of the dose of amiodarone, the CTP-amiodarone decreased the CV in hearts significantly compared to the control GPs (0.92 ± 0.05 vs. 1.00 ± 0.03 ms, = 0.0007), equivalent to amiodarone alone (0.87 ± 0.08 ms, = 0.0003). Amiodarone increased the APD (192 ± 5 ms vs. 175 ± 8 ms for vehicle, = 0.0025), while CTP-amiodarone decreased it significantly (157 ± 16 ms, = 0.0136), similar to CTP alone (155 ± 13 ms, = 0.0039). Both amiodarone and CTP-amiodarone significantly decreased the calcium transients compared to the controls. CTP-amiodarone and CTP decreased the CaTD to an extent greater than amiodarone alone ( < 0.001). RNA-seq showed that CTP alone increased the expression of DHPR and SERCA2a, while it decreased the expression of the proinflammatory genes, NF-kappa B, TNF-α, IL-1β, and IL-6.
CONCLUSIONS
Our data suggest that CTP can deliver amiodarone to cardiomyocytes at ~1/15th the total molar dose of the amiodarone needed to produce a comparable slowing of CVs. The ability of CTP to decrease the AP durations and CaTD may be related to its increase in the expression of Ca-handling genes, which merits further study.
PubMed: 37631321
DOI: 10.3390/pharmaceutics15082107