Oral amiodarone and propranolol in maintenance therapy of postimplantation tachycardia: An observational study.

Left ventricular assist devices (LVADs) are widely used as end-stage therapy in patients with advanced heart failure, whereas implantation increases the risks of development of sustained ventricular tachycardia at the later postimplantation stage. Therefore, this study aimed to evaluate the clinical efficacy of orally administered amiodarone and propranolol in 3 patients with ventricular tachycardia (VT) after LVAD implantation who were resistant to initial anti-antiarrhythmic drugs. This retrospective cohort study consisted of the initial evaluation of the clinical data of 14 adult patients who underwent implantation of LVAD between January 2019 and March 2021. A total of 3 patients with resistant VT were finally included. In all cases, the patients were initially administered amiodarone in the different doses intravenously to stabilize the critical condition, whereas its oral form along with that of propranolol was used as maintenance therapy in the first 2 cases. In the third case, amiodarone was withdrawn because of the risk of development of hyperthyroidism, while oral propranolol was used in the treatment. The assessment in the 16-month follow-up period after discharge did not show presence of non-sustained and sustained VT in all 3 cases. In the ventricular arrhythmia-free group, the total mortality rate within the follow-up period was 11.1 ±â€…7.78 months in the 3 patients. We suggest that maintenance oral therapy of propranolol and amiodarone can significantly decrease the risks of complications in patients with VT after implantation of ventricular assist device in the long term.

Designing Microneedle Patch for Prophylaxis of Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, which often occurs within 30 postoperative days, especially peaking at 2-3 days. Antiarrhythmic medications such as amiodarone are recommended in clinical practice for the prophylaxis and treatment of POAF. However, conventional oral administration is hindered due to delayed drug action and high risks of systemic toxicity, and emerging localized delivery strategies suffer from a limited release duration (less than 30 days). Herein, we develop a microneedle (MN) patch for localized delivery of amiodarone to the atria in a "First Rapid and Then Sustained" dual-release mode. Specifically, this patch is composed of a needle array integrated with an amiodarone-loaded reservoir for a sustained and steady release for over 30 days; and an amiodarone-containing coating film deposited on the needle surface via the Langmuir-Blodgett technique for a rapid release at the first day. Upon this design, only one MN patch enables a higher drug accumulation in the atrial tissue at the first day than oral administration and simultaneously remains therapeutical levels for over 30 days, despite at a significantly reduced drug dosage (5.08 mg in total versus ∼10 mg per day), thereby achieving ideal preventive effects and safety in a rat model. Our findings indicate that this MN device provides a robust and efficient delivery platform for long-term prophylaxis of POAF.

Acute hepatotoxicity of intravenous amiodarone in a Becker muscular dystrophy patient with decompensated heart failing and ABCB4 gene mutation: as assessed for causality using the updated RUCAM.

BACKGROUND: Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. CASE PRESENTATION: We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient's liver function and clinical status rehabilitated. CONCLUSIONS: ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.

Amiodarone chewable gels as a potential appproach for paediatric congenital cardiopathies treatment: Comparison between animal and vegetal gelling agents.

The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients with dysphagia. An interesting alternative to overcome these problems are non-conventional formulations like chewable gels, commonly known as 'gummies'. Therefore, this work addresses the design, development and characterization of gummies using gelatine and pectin, for the vehiculization of the antiarrhythmic amiodarone (AMIO). Applying a Design of Experiments (DoE) approach, four gelatine (GG1-GG4) and eight pectin formulations (PG1-PG8) were developed. Considering the obtained results for responses during DoE evaluation (i.e., volume, syneresis, hardness, and gumminess), GG3 and PG8 were selected for complete characterization. Water activity, pH, drug content, texture parameters (adhesiveness, springiness, cohesiveness, and fracturability), disintegration time, in vitro dissolution, and microbiological features were evaluated. The obtained results were within the expected values for this type of formulation. The dissolution profiles showed a 94 % - 99 % of the AMIO content released for GG3 and PG8, respectively, so they could be considered suitable as immediate release dosage forms. In conclusion, the chewable gels were successfully developed and characterised, suggesting a potential means to accomplish a final prototype for the improvement of congenital cardiopathies treatment.

Peripartum ventricular tachycardia and PVC-induced cardiomyopathy: delivering optimal care when it's time to deliver.

Ventricular tachycardia (VT) is a rare but potentially fatal complication in pregnancy. We present a case of a pregnant woman with cardiomyopathy due to frequent premature ventricular complexes (PVCs) and VT originating from the left ventricular outflow tract. After presenting late in the third trimester, the decision was made to deliver the fetus after 4 days of medication titration due to continued sustained episodes of VT. After delivery, the patient continued to have frequent PVCs and VT several months after discharge, and she ultimately underwent a PVC ablation with dramatic reduction in PVC burden and improvement in cardiomyopathy. Multidisciplinary planning with a pregnancy heart team led to appropriate contingency planning and a successful delivery. This case highlights how multidisciplinary management is best practice in pregnancy complicated by VT and the need for better diagnostic guidelines for PVC-induced cardiomyopathy in the setting of pregnancy.

Flecainide overdose-induced wide-complex tachyarrhythmia treated with sodium bicarbonate infusion.

Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval.

Intranasal etripamil for rapid treatment of paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia that, although usually benign, can occur unpredictably, cause disabling symptoms and significantly impair quality of life. If spontaneous resolution does not occur, the only current self-treatment is for the patient to attempt vagal maneuvers, however, these are frequently unsuccessful. Hospital attendance is then required for intravenous therapy. Etripamil, an intranasal calcium channel blocker similar to verapamil, may be able to fill this therapeutic gap, allowing rapid self-treatment of PSVT at home. This narrative review discusses the latest evidence for etripamil and its potential role in future clinical practice.

Paroxysmal supraventricular tachycardia (PSVT) is an abnormal heart rhythm, causing the heart to beat rapidly. There are several ways to treat PSVT. This article discusses a new therapy, etripamil. One treatment involves breathing techniques called 'vagal maneuvers'. These avoid medication and sometimes stop the abnormal rhythm, however, in many cases, this does not work. An alternative is a tablet taken when symptoms occur. Unfortunately, tablets take time to absorb, meaning symptoms may continue until the medication takes effect, and this approach does not work for everyone. If these approaches fail, patients suffering from PSVT may need to seek treatment at a hospital. This may involve intravenous therapy, with certain drugs causing unpleasant sensations of chest discomfort. Some patients may also be kept in the hospital for monitoring. Although PSVT can often be cured via a catheter ablation procedure, this is invasive (involving wires inserted via veins in the groin), so not everyone wishes to pursue this, and in some cases, it cannot be performed safely. There is a need for a rapid, safe, and effective treatment that patients can administer at home when PSVT occurs. Etripamil shows promise. Because it is a nasal spray, etripamil allows rapid absorption into the body ­ much faster than a tablet. Etripamil is not yet available on the market; however, several studies have demonstrated its effectiveness and safety, so it may be available in the near future. Promising evidence for etripamil in certain groups, such as elderly patients, is still lacking.

The efficacy and safety of intraoperative intravenous amiodarone in patients undergoing on-pump coronary artery bypass grafting surgery: a systemic review and PRISMA-compliant meta-analysis.

BACKGROUND: To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG) patients. METHODS: A meta-analysis of randomized controlled trials was conducted. Pubmed, Embase, Cochrane Library, Ovid, China National Knowledge Infrastructure, and the Wan Fang database until July 1th, 2023. The primary outcomes of interest included the incidences of intra- and post-operative atrial fibrillation (POAF), ventricular fibrillation, or any arrhythmia, including atrial fibrillation, ventricular fibrillation, ventricular tachycardia, premature ventricular contraction, and sinus bradycardia. For continuous and dichotomous variables, treatment effects were calculated as the weighted mean difference (WMD)/risk ratio (RR) and 95% confidence interval (CI). RESULTS: A database search yielded 7 randomized controlled trials including 608 patients, where three studies, including three treatments (amiodarone, lidocaine, and saline), contributed to the clinical outcome of atrial fibrillation, ventricular fibrillation, or any arrhythmia. Meta-analysis demonstrated that amiodarone can significantly reduce the incidence of POAF (RR, 0.39; 95%CI: 0.20, 0.77; P = 0.007, I2 = 0%) in patients undergoing on-pump CABG; there was no statistically significant influence on intra-operative atrial fibrillation, intra- and post-operative ventricular fibrillation, or any arrhythmia. CONCLUSIONS: The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on-pump CABG. More well-designed clinical trials are needed to validate this result.

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

BACKGROUND: INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. OBJECTIVES: This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. METHODS: Patients self-administered FlecIH over 8 minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. RESULTS: Mean age was 60.5 years, mean body mass index was 27.0 kg/m2, and 34.7% of the patients were women. All patients had ≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for ≤24 hours. The conversion rate was 42.6% (95% CI: 33.0%-52.6%) with a median time to conversion of 14.6 minutes. The conversion rate was 46.9% (95% CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. CONCLUSIONS: The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Efficacy of Shensong Yangxin capsule combined with dronedarone in paroxysmal atrial fibrillation after ablation.

OBJECTIVE: To investigate whether postoperative administration of Shensong Yangxin capsules (SSYX) and dronedarone for atrial fibrillation (AF) can reduce the recurrence of paroxysmal AF after radiofrequency ablation, thus providing a more optimal choice of antiarrhythmic medication during the blank period. METHODS: We included 120 patients with paroxysmal AF who underwent radiofrequency ablation at our hospital between July 2020 and July 2022. They underwent routine circumferential pulmonary vein ablation and, subsequently, left and right atrial pressure monitoring to assess sinoatrial node recovery time under burst 400/300 ms stimulation. Postoperatively, the patients were randomly divided into 2 groups (60 patients each). The control group was administered dronedarone orally for 3 months and the study group was treated with SSYX combined with dronedarone. This study aimed to compare differences in clinical efficacy of the treatment between the 2 groups. RESULTS: The left and right atrial pressures in both groups were higher than those in the preoperative period (P < .05), with no statistically significant differences between the 2 groups (P > .05). Sinoatrial node recovery time under burst 400/300 ms stimulation showed no statistical difference between the 2 groups (P > .05). At 3 months and 1 year postoperatively, the AFEQT scale scores for both groups were lower than those before treatment (P < .05), with the study group scoring lower than the control group at 3 months (P < .05). However, no statistically significant difference was observed between the 2 groups at 1 year postoperatively (P > .05). At 3 months postoperatively, the sinus rhythm maintenance rate and heart rate were higher in the intervention group than in the control group (P < .05); however, these differences between the 2 groups were not statistically significant at 1 year postoperatively (P > .05). CONCLUSION SUBSECTIONS: The combination of SSYX and dronedarone could effectively reduce the early recurrence of paroxysmal AF after radiofrequency ablation, increase heart rate, and improve the quality of life.

Diagnosis and Management of Paroxysmal Supraventricular Tachycardia.

Importance: Paroxysmal supraventricular tachycardia (PSVT), defined as tachyarrhythmias that originate from or conduct through the atria or atrioventricular node with abrupt onset, affects 168 to 332 per 100 000 individuals. Untreated PSVT is associated with adverse outcomes including high symptom burden and tachycardia-mediated cardiomyopathy. Observations: Approximately 50% of patients with PSVT are aged 45 to 64 years and 67.5% are female. Most common symptoms include palpitations (86%), chest discomfort (47%), and dyspnea (38%). Patients may rarely develop tachycardia-mediated cardiomyopathy (1%) due to PSVT. Diagnosis is made on electrocardiogram during an arrhythmic event or using ambulatory monitoring. First-line acute therapy for hemodynamically stable patients includes vagal maneuvers such as the modified Valsalva maneuver (43% effective) and intravenous adenosine (91% effective). Emergent cardioversion is recommended for patients who are hemodynamically unstable. Catheter ablation is safe, highly effective, and recommended as first-line therapy to prevent recurrence of PSVT. Meta-analysis of observational studies shows single catheter ablation procedure success rates of 94.3% to 98.5%. Evidence is limited for the effectiveness of long-term pharmacotherapy to prevent PSVT. Nonetheless, guidelines recommend therapies including calcium channel blockers, ß-blockers, and antiarrhythmic agents as management options. Conclusion and Relevance: Paroxysmal SVT affects both adult and pediatric populations and is generally a benign condition. Catheter ablation is the most effective therapy to prevent recurrent PSVT. Pharmacotherapy is an important component of acute and long-term management of PSVT.

Expedited loading with intravenous sotalol is safe and feasible-primary results of the Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) Registry.

BACKGROUND: Loading of oral sotalol for atrial fibrillation requires 3 days, frequently in the hospital, to achieve steady state. The Food and Drug Administration approved loading with intravenous (IV) sotalol through model-informed development, without patient data. OBJECTIVE: We present results of the first multicenter evaluation of this recent labeling for IV sotalol. METHODS: The Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) Registry was a multicenter observational registry of patients undergoing elective IV sotalol load for atrial arrhythmias. Outcomes, measured from hospital admission until first outpatient follow-up, included adverse arrhythmia events, efficacy, and length of stay. RESULTS: Of 167 consecutively enrolled patients, 23% were female; the median age was 68 (interquartile range, 61-74) years, and the median CHA2DS2-VASc score was 3 (interquartile range, 2-4). Overall, 99% were admitted for sotalol initiation (1% for dose escalation), with a target oral sotalol dose of either 80 mg twice daily (85 [51%]) or 120 mg twice daily (78 [47%]); 62 patients (37%) had an estimated creatinine clearance ≤90 mL/min. On presentation, 40% of patients were in sinus rhythm, whereas 26% underwent cardioversion before sotalol infusion. In 2 patients, sotalol infusion was stopped for bradycardia or hypotension. In 6 patients, sotalol was discontinued before discharge because of QTc prolongation (3), bradycardia (1), or recurrent atrial arrhythmia (2). The mean length of stay was 1.1 days, and 95% (n = 159) were discharged within 1 night. CONCLUSION: IV sotalol loading is safe and feasible for atrial arrhythmias, with low rates of adverse events, and yields shorter hospitalizations. More data are needed on the minimal duration required for monitoring in the hospital.

The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume.

AIMS: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA). METHODS AND RESULTS: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]. CONCLUSION: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m². TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.

Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study.

INTRODUCTION: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown. METHODS/DESIGN: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study. CONCLUSION: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure. CLINICAL TRIAL REGISTRATION: NCT05213104 (clinicaltrials.gov).

Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Comparing methods of adenosine administration in paroxysmal supraventricular tachycardia: a pilot randomized controlled trial.

BACKGROUND: Intravenous adenosine is the recommended treatment for paroxysmal supraventricular tachycardia (PSVT). There is no official recommended method of giving adenosine. We compared the success rates between a standard and alternative method of first dose intravenous adenosine in PSVT. METHODS: A pilot parallel randomized controlled study was conducted in the emergency department of a tertiary care hospital. Eligible patients were stable PSVT adult patients. We used block randomization and divided them into two groups, the standard method (double syringe technique of 6 mg of adenosine), and the alternative method (similar to the standard method, then immediately followed by elevating the arm to 90° perpendicular to a horizontal plane for 10 s). The primary outcome was the success rate of electrocardiogram (ECG) response which demonstrated termination of PSVT (at least two-fold of the RR-interval widening or sinus rhythm conversion). Secondary outcomes were complications within one minute after the injection. RESULTS: We allocated 15 patients in each group and analyzed them as intention-to-treat. The success rate was 86.7% in the alternative group and 80% in the standard group (risk difference 6.7%, 95% confidence interval - 19.9 to 33.2%, P 1.00). Complications within one minute after adenosine injection were also similar in both groups, 14 of 15 patients (93%) in each group had no complications, without significant difference. CONCLUSIONS: No evidence of the difference between alternative and standard methods occurred, in terms of the success rate of ECG response and complications within one minute after adenosine injection. The standard method of adenosine injection is a safe, easy-to-administer, and widely available treatment for PSVT. TRIAL REGISTRATION: TCTR20200609001.