Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

The Comparative Effectiveness and Safety of Different Anticoagulation Strategies for Treatment of Left Atrial Appendage Thrombus in the Setting of Chronic Anticoagulation for Atrial Fibrillation or Flutter.

PURPOSE: To compare effectiveness of different treatments for atrial fibrillation (AF) patients who were scheduled for cardioversion (CV) or ablation (CA) presenting with left atrium appendage (LAA) thrombus despite chronic oral anticoagulation therapy (OAC). METHODS: This was a retrospective cohort study. We analyzed 2014-2019 medical records of patients scheduled for CV or CA of AF who were diagnosed with LAA thrombus despite optimal OAC and had a follow-up transesophageal echocardiogram (TOE). Changes in treatment were divided into the following groups: switch to a drug with different mechanism of action, switch to a drug with similar mechanism of action, initiation of combination therapy, or deliberate no change in treatment. Patients with contraindications to non-vitamin K antagonists were excluded from the analysis. RESULTS: We analyzed data of 129 patients comprising 181 cycles of treatment. The overall effectiveness of LAA thrombus dissolution was 51.9% regardless of the number of cycles and 42.6% for the first cycle of treatment. Any change of treatment was more effective than deliberate no change-OR 2.97 [95% CI: 1.07-8.25], P = 0.031, but no particular strategy seemed to be more effective than the other. Left atrium area (OR 0.908 [95% CI: 0.842-0.979]) and number of treatment cycles (OR 0.457 [95% CI: 0.239-0.872]) were both adversely related to thrombus resolution. There was one ischemic and three bleeding adverse events during the treatment. CONCLUSION: LAA thrombus resolution in patients already on OAC may require a change of previous OAC treatment but the overall effectiveness of dissolution seems to be about 50%.

Acute Hemodynamic Effects of Simultaneous and Sequential Multi-Point Pacing in Heart Failure Patients With an Expected Higher Rate of Sub-response to Cardiac Resynchronization Therapy: Results of Multicenter SYNSEQ Study.

The aim of the SYNSEQ (Left Ventricular Synchronous vs. Sequential MultiSpot Pacing for CRT) study was to evaluate the acute hemodynamic response (AHR) of simultaneous (3P-MPP syn) or sequential (3P-MPP seq) multi-3-point-left-ventricular (LV) pacing vs. single point pacing (SPP) in a group of patients at risk of a suboptimal response to cardiac resynchronization therapy (CRT). Twenty five patients with myocardial scar or QRS ≤ 150 or the absence of LBBB (age: 66 ± 12 years, QRS: 159 ± 12 ms, NYHA class II/III, LVEF ≤ 35%) underwent acute hemodynamic assessment by LV + dP/dtmax with a variety of LV pacing configurations at an optimized AV delay. The change in LV + dP/dt max (%ΔLV + dP/dt max) with 3P-MPP syn (15.6%, 95% CI: 8.8%-22.5%) was neither statistically significantly different to 3P-MPP seq (11.8%, 95% CI: 7.6-16.0%) nor to SPP basal (11.5%, 95% CI:7.1-15.9%) or SPP mid (12.2%, 95% CI:7.9-16.5%), but higher than SPP apical (10.6%, 95% CI:5.3-15.9%, p = 0.03). AHR (defined as a %ΔLV + dP/dt max ≥ 10%) varied between pacing configurations: 36% (9/25) for SPP apical, 44% (11/25) for SPP basal, 54% (13/24) for SPP mid, 56% (14/25) for 3P-MPP syn and 48% (11/23) for 3P-MPP seq.Fifteen patients (15/25, 60%) had an AHR in at least one pacing configuration. AHR was observed in 10/13 (77%) patients with a LBBB but only in 5/12 (42%) patients with a non-LBBB (p = 0.11). To conclude, simultaneous or sequential multipoint pacing compared to single point pacing did not improve the acute hemodynamic effect in a suboptimal CRT response population. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02914457.

Pharmacological Cardioversion in Patients with Recent-Onset Atrial Fibrillation and Chronic Kidney Disease Subanalysis of the CANT II Study.

Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) in emergency departments (ED). This is a subanalysis of the CANT II study, evaluating the effectiveness and safety of antazoline in patients (n = 777) at three stages of chronic kidney disease (CKD): Group I > 60 mL/min (n = 531), Group II 45−59 mL/min (n = 149), and Group III < 45 mL/min (n = 97). Patients in Group III were older and with a higher prevalence of co-morbidities; however, we did not find statistically significant differences in the overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs. 35%; p < 0.001), and it increased almost significantly in patients receiving propafenone (69.9 vs. 100%; p = 0.067). In patients in Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone; however, in patients in Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p = 0.002 and p = 0.034, respectively). The rate of safety endpoint was the highest in patients in Group III (eGFR < 45 mL/min), and it was significantly higher than in patients in Groups I and II (p = 0.008 and p = 0.036, respectively). We did not observe antazoline-related adverse events in any of the studied groups of patients. This real-world registry analysis revealed a different influence of CKD on the effectiveness of individual drugs, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm.

Efficacy and safety of antazoline for cardioversion of atrial fibrillation: propensity score matching analysis of a multicenter registry (CANT II Study).

INTRODUCTION: Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of antazoline, a first­generation antihistamine, for cardioversion of recent­onset AF in the setting of an emergency department. PATIENTS AND METHODS: This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new­onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment. RESULTS: Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post­PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2). CONCLUSIONS: Antazoline appears to be an efficacious agent for termination of AF in real­world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.

A quality of life, clinical and biochemical improvements after catheter ablation of persistent arrhythmia in patients with structural heart disease and arrhythmia-mediated cardiomyopathy.

BACKGROUND: Arrhythmia-mediated cardiomyopathy (AMC) is an essential clinical situation that is commonly underdiagnosed. Successful arrhythmia control leads to improvement in health-related quality of life (HRQoL) and heart failure (HF) symptoms in patients with structural heart disease (SHD). AIMS: The study aimed to evaluate the impact of catheter ablation (CA) of persistent arrhythmia on HRQoL, biochemical and clinical parameters HF in patients with SHD and AMC. METHODS: Patients with SHD, on optimal medical treatment, with persistent arrhythmia and strong suspicion of AMC, scheduled for CA were prospectively enrolled. Study procedures included: HRQoL measurement (the Minnesota Living with Heart Failure Questionnaire [MLHFQ] and the EuroQol Research Foundation [EQ-5D-3L] questionnaire), biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], troponin T [TnT], matrix metalloproteinase-9 [MMP-9], soluble suppression of tumorigenesis-2 [sST2], tissue inhibitor of matrix metalloproteinase-1 [TIMP-1]), transthoracic echocardiography and clinical assessment. RESULTS: At 6 months, 30/35 (86%) patients were free of persistent arrhythmia. Patients who underwent successful CA had a significant improvement in HRQoL: MLHFQ (median [interquartile range, IQR], -22 [-28; -11]; P <0.001), EQ5D-3L score (mean [standard deviation], 21.8 (16.8); P <0.001); EQ5D-3L index (median [IQR], 0.09 (0.05; 0.18); P <0.001). A significant decrease in injury bio markers was observed: NT-proBNP (median [IQR], -414 [-1397; -318] pg/ml; P <0.001), TnT (median [IQR], -2.27 (-8.52; 0.55) ng/l; P <0.01) but not in fibrosis biomarkers: (median [IQR], sST2: 2.20 [-5.4; 4.3] ng/ml; P = 0.741, MMP-9: 34 [-376; 283] ng/ml; P = 0.881, TIMP-1: 11.1 [-17.1; 31.9] ng/ml; P = 0.215). There was a significant increase of left ventricular ejection fraction (LVEF) (mean [SD], 9.8 [5.9] %; P <0.01). CONCLUSIONS: Successful CA significantly improved clinical status, LVEF, and HRQoL of patients with SHD and AMC.

Rapid pharmacological cardioversion of recent-onset atrial fibrillation using antazoline in elderly patients.

INTRODUCTION: There is insufficient evidence on the efficacy and safety of pharmacological cardioversion of recent­onset atrial fibrillation (AF) in elderly patients. Antazoline has been shown to be effective and safe in various patient populations. OBJECTIVES: We aimed to compare the clinical efficacy and safety of intravenous antazoline for pharmacological cardioversion of recent­onset AF between patients aged 75 years or older and those younger than 75 years. PATIENTS AND METHODS: This retrospective analysis was conducted using data derived from emergency room medical records of patients referred for pharmacological cardioversion due to symptomatic AF lasting less than 48 hours. The threshold for old age was set at 75 years. Conversion to sinus rhythm was considered the primary efficacy outcome. The primary safety outcome was defined as any adverse event requiring hospitalization. RESULTS: The study included 334 participants, of whom 110 patients were aged 75 years or older (study group) and 224 patients were younger than 75 years (controls). Successful cardioversion was achieved using lower mean (SD) antazoline doses in the study group than in controls: 151 (59) mg vs 168 (58) mg (P = 0.039). Study and control groups showed a similar efficacy and safety of antazoline (78.2% and 68.3%, respectively; odds ratio [OR], 1.66; 95% CI, 0.98-1.31; P = 0.06) as well as hospitalization rates (0.9% and 4.0%, respectively; OR, 0.22; 95% CI, 0.03-1.75; P = 0.17). CONCLUSIONS: Intravenous antazoline seems to be effective and safe for pharmacological cardioversion of recent­onset AF in elderly patients in the emergency setting.

Quality and utility of [123I]I-metaiodobenzylguanidine cardiac SPECT imaging in nondiabetic postinfarction heart failure patients qualified for implantable cardioverter defibrillator.

OBJECTIVE: Impaired cardiac adrenergic activity has been demonstrated in heart failure (HF) and in diabetes mellitus (DM). [123I]I-metaiodobenzylguanidine (MIBG) enables assessment of the cardiac adrenergic nervous system. Tomographic imaging of the heart is expected to be superior to planar imaging. This study aimed to determine the quality and utility of MIBG SPECT in the assessment of cardiac innervation in postinfarction HF patients without DM, qualified for implantable cardioverter defibrillator (ICD) in primary prevention of sudden cardiac death. METHODS: Consecutive patients receiving an ICD on the basis of contemporary guidelines were prospectively included. Planar MIBG studies were followed by SPECT. The essential analysis was based on visual assessment of the quality of SPECT images ("high", "low" or "unacceptable"). The variables used in the further analysis were late summed defect score for SPECT images and heart-to-mediastinum rate for planar images. MIBG images were assessed independently by two experienced readers. RESULTS: Fifty postinfarction nondiabetic HF subjects were enrolled. In 13 patients (26%), the assessment of SPECT studies was impossible. In addition, in 13 of 37 patients who underwent semiquantitative SPECT evaluation, the assessment was equivocal. Altogether, in 26/50 patients (52%, 95% confidence interval 38-65%), the quality of SPECT images was unacceptable or low and was limited by low MIBG cardiac uptake and by comparatively high, interfering MIBG uptake in the neighboring structures (primarily, in the lungs). CONCLUSIONS: The utility of MIBG SPECT imaging, at least with conventional imaging protocols, in the qualification of postinfarction HF patients for ICD, is limited. In approximately half of the postinfarction HF patients, SPECT assessment of cardiac innervation can be impossible or equivocal, even without additional damage from diabetic cardiac neuropathy. The criteria predisposing the patient to good-quality MIBG SPECT are: high values of LVEF from the range characterizing the patients qualified to ICD (i.e., close to 35%) and left lung uptake intensity in planar images comparable to or lower than heart uptake.

Patient perspective and safety of remote monitoring of implantable cardioverter-defibrillators in the Polish Nationwide Multicenter Registry: the Medtronic CareLink network evaluation.

BACKGROUND: Remote monitoring of cardiovascular implantable electronic devices allows the assessment of system effectiveness, arrhythmia occurrence, and indirectly, clinical changes. Medical interventions can be performed earlier because of a faster transfer of information to the monitoring site, even in the case of asymptomatic arrhythmias or abnormalities in the operation of the system. AIMS: The aim of the study was to assess the effectiveness of remote monitoring of implantable cardioverter-defibrillators and evaluation in an outpatient setting during 12-month follow -up. METHODS: We analyzed 176 patients at 10 sites (men, 84.1%). The mean (SD) age of the patients was 60.7 (12.5) years (range, 20-86 years), and mean (SD) follow -up period was 405 (70) days (range, 131-723 days). RESULTS: A total of 354 outpatient and 514 remote follow -up visits were conducted. Episodes of arrhythmias and device malfunctions were detected with similar frequency in outpatient visits and in remote visits. During the study period, patient sense of safety increased. More patients preferred joined remote and outpatient visits as the optimal healthcare model. As the patient survey showed, the greatest benefit of the CareLink network was fast intervention and an increased sense of safety. CONCLUSIONS: The strategy of remote monitoring appeared to be feasible, safe, and patient friendly, demonstrating that the majority of patients do not require an additional in -person visit within 1 year from the device implantation just to confirm the proper functioning of the implantable cardioverter--defibrillators.

The long term risk of lead failure in patients with cardiovascular implantable electronic devices undergoing catheter ablation.

Objectives. The aim of the study was to assess the long-term influence of catheter ablation (CA) of different arrhythmias on cardiovascular implantable electronic devices (CIED) endocardial leads durability. Design. This was a retrospective case-control study. Ablation protocols and in- or outpatient medical records were reviewed to identify and extract data on adult patients with CIED undergoing a CA. A cohort of patients with hypertrophic cardiomyopathy and implantable cardioverter-defibrillators (ICD) served as a historical control group. The primary endpoint was the diagnosis of lead damage defined as permanent loss of proper function demanding replacement or removal. Results. Among 145 patients n = 177 catheter ablations were performed. Patients' mean age was 66.4 ± 10.5, 66.1% had an ICD or ICD with cardiac resynchronization function (CRT-D), 18.1% had >1 CA. During median 812 days [IQR 381-1588] of follow-up, there were 11 (6.2%) cases of lead damage in the examined and 13 cases (13%) in the control group, p = 0.054. None of the technical aspects of the CA (indication, type of catheter, transseptal sheath) influenced the primary outcome. Both the number of leads and observation time after CA were significantly related to the risk of endocardial lead damage. Conclusion. This study did not find any significant influence of CA on the long-term durability of CIED endocardial leads. Reported risk factors were consistent with general population of CIED patients.

Intravenous antazoline, a first-generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio-venous conduction and high clinical effectiveness (AntaEP Study).

AIMS: Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic properties resulting in a rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm (SR). The aim of the study was to assess the influence of antazoline on atrio-venous conduction and other electrophysiological parameters in patients undergoing AF ablation. METHODS: An experimental prospective study. Patients scheduled for the first-time AF ablation, in SR and not on amiodarone were enrolled. Atrio-venous conduction assessment and invasive electrophysiological study (EPS) were performed before and after intravenous administration of 250 mg of antazoline. In case of AF induction during EPS, antazoline was administered until conversion to SR or a cumulative dose of 300 mg. RESULTS: We enrolled 14 patients: 13 (93%) men, mean age 63.4 (59.9-66.8) years, mean CHA2 DS2 -VASc score 1.6 (1.0-2.2). Antazoline was administered in a mean dose 257.1 (246.7-267.6) mg. Pulmonary vein potentials and atrial capture during pulmonary vein stimulation were present before and after the administration of antazoline. Wenckebach point and atrial conduction times did not change significantly, but atrio-ventricular node effective refractory period improved-324.7 (275.9-373.5) ms vs 284.3 (256.2-312.4) ms, P = 0.02. Antazoline was effective in all 5 (100%) cases of AF induction during EPS. There were no serious adverse events. CONCLUSION: Due to the lack of influence on atrio-venous conduction and high clinical effectiveness, antazoline may be suitable for pharmacological cardioversion of AF occurring during AF ablation.