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.

Clinical Characteristics of Atrial Flutter and Its Response to Pharmacological Cardioversion with Amiodarone in Comparison to Atrial Fibrillation.

BACKGROUND: Unlike atrial fibrillation (AF), atrial flutter (AFl) is thought to be relatively refractory to pharmacological cardioversion (PC), but the evidence is scarce. The aim of this study was to evaluate the clinical characteristics and efficacy of the PC of AFl with amiodarone in comparison to AF. MATERIALS AND METHODS: This retrospective study covered 727 patients with urgent consult for AF/AFl in a high-volume emergency department between 2015 and 2018. AFl was diagnosed in 222 (30.5%; median age: 68 (62; 75) years; 65.3% men). In a nested case-control study, 59 control patients with AF, matched in terms of age and sex with 60 AFl patients, were subject to PC with amiodarone. The primary endpoint was return of sinus rhythm confirmed using a 12-lead ECG. RESULTS: The AFl population had a median CHA2DS2-VASc score of 3 (2; 4) and episode duration of 72 h (16; 120). In the AFl cohort, 36% of patients were initially subject to PC, 33.3% to electrical cardioversion (EC) and 40.5% to catheter ablation. In comparison to the AF group, the AFl patients required a longer hospitalization time, had a higher rate of EC (p < 0.001) and less frequent use of PC (p < 0.001) and, lower left ventricular ejection fraction (p < 0.001) and more pronounced cardiovascular risk factors. The efficacy of PC with amiodarone was significantly lower in AFl than AF group (39% vs. 65%, relative risk (RR) 0.60, p = 0.007). CONCLUSIONS: AFl patients shared a greater burden of comorbidities than AF patients, while the efficacy of PC in AFl was low. Patients should be initially managed with primary electrical cardioversion.

Electro- and echocardiographic features of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

BACKGROUND: Standard 12-lead electrocardiogram (ECG), next to medical history and physical examination, is a basic screening tool for hypertrophic cardiomyopathy in General practice. There are many electrocardiographic criteria of left ventricular hypertrophy, but their accuracy is usually weak in patients with systemic hypertension or aortic stenosis. Sensitivity of these criteria in patients with HCM has not been well described. AIM: To assess the prevalence of electrocardiographic criteria for LVH in patients with HCM and their relationship with echocardiographic parameters. MATERIAL AND METHODS: A total of 49 patients with HCM (mean age 53.2 ± 15.4 years; men/women: 31/18) were enrolled to study. Eight electrocardiographic criteria for LVH were evaluated and correlated with echocardiographic parameters. RESULTS: The ECG features of LVH were found in 36 (73.5%) subjects. These patients had increased thickness of intraventricular septum (20.5 ± 4.7 vs. 17.3 ± 3.2 mm, p = .03), LVM (340.5 ± 104.8 vs. 264.0 ± 61.5 g; p = .02), and LVMI (178.9 ± 48.8 vs. 125.9 ± 22.5; p = .002). All of ECG criteria for LVH had low sensitivity (14.3%-40.8%) for LVH diagnosis confirmed by echocardiography. The most common positive criterion was Cornell Voltage (20 patients; 40.8%). A total of 41 (83.4%) patients had T-wave inversion in limb and/or precordial leads. LVMI correlated positively with R-wave amplitude in aVL (R = 0.34; p = .03), Gubner-Ungerleider voltage (R = 0.4; p = .009), and Cornell Voltage (R = 0.31; p = .04). CONCLUSION: ECG criteria for LVH are characterized by poor sensitivity in patients with HCM. Cornell Voltage and criteria based on limb leads correlate positively with LVMI.

Recurrent cerebrovascular events in patients with a history of cryptogenic stroke or transient ischemic attack and patent foramen ovale in a long­term follow­up.

INTRODUCTION: Cryptogenic stroke may be associated with a patent foramen ovale (PFO). Both cardiovascular risk factors and transcatheter closure of PFO may have an impact on the risk of recurrent cerebrovascular events. OBJECTIVES: The aim of the study was to assess the occurrence and risk factors of recurrent cerebrovascular events (rCVE) in patients with a history of cryptogenic stroke or transient ischemic attack (TIA) and PFO. PATIENTS AND METHODS: Overall, 392 patients (median [interquartile range, IQR] age 39.5 [30-49] years, 64.3% women, 35.7% men) with a history of cryptogenic stroke / TIA and confirmed PFO underwent a long­term follow­up with a median (IQR) of 51.5 (35-65) months. The primary end point was defined as rCVE including stroke and TIA. RESULTS: During the follow­up, 17 patients with a history of cryptogenic stroke / TIA and confirmed PFO (4.3%, 11 women, 6 men) developed rCVE. In a multivariable analysis, the Risk of Paradoxical Embolism (RoPE) score was associated with a lower risk of rCVE (odds ratio [OR], 0.61 per 1 point; 95% CI, 0.45-0.84; P = 0.002). The transcatheter closure of PFO did not have a significant impact on rCVE in the study population (P = 0.19). CONCLUSIONS: The occurrence of rCVE in the patients with cryptogenic stroke / TIA and PFO reached 4.3% regardless of a high percentage of patients who underwent the PFO closure. RoPE score was associated with a lower risk of rCVE in the study population.

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.

Exhaled Air Metabolome Analysis for Pulmonary Arterial Hypertension Fingerprints Identification-The Preliminary Study.

Pulmonary arterial hypertension (PAH) is a rare disease with a serious prognosis. The aim of this study was to identify biomarkers for PAH in the breath phase and to prepare an automatic classification method to determine the changing metabolome trends and molecular mapping. A group of 37 patients (F/M: 8/29 women, mean age 60.4 ± 10.9 years, BMI 27.6 ± 6.0 kg/m2) with diagnosed PAH were enrolled in the study. The breath phase of all the patients was collected on a highly porous septic material using a special patented holder PL230578, OHIM 002890789-0001. The collected air was then examined with gas chromatography coupled with mass spectrometry (GC/MS). The algorithms of Spectral Clustering, KMeans, DBSCAN, and hierarchical clustering methods were used to perform the cluster analysis. The identification of the changes in the ratio of the whole spectra of biomarkers allowed us to obtain a multidimensional pathway for PAH characteristics and showed the metabolome differences in the four subgroups divided by the cluster analysis. The use of GC/MS, supported with novel porous polymeric materials, for the breath phase analysis seems to be a useful tool in selecting bio-fingerprints in patients with PAH. The four metabolome classes which were obtained constitute novel data in the PAH population.

Electrocardiographic criteria for left ventricular hypertrophy in aortic valve stenosis: Correlation with echocardiographic parameters.

BACKGROUND: Aortic valve stenosis (AS) generates a chronic pressure overload that induces left ventricular hypertrophy (LVH). The aim of this study was to assess the prevalence of the electrocardiographic criteria for LVH in patients with clinically significant AS and to evaluate the relationship between the ECG criteria for LVH and echocardiographic parameters. METHODS: The clinical data of 95 patients with moderate to severe AS were retrospectively analyzed. Eight ECG criteria for LVH were used and compared to the results of transthoracic echocardiography (TTE). RESULTS: In 59% of patients, at least one of the ECG criteria for LVH was found. These patients had a greater LVMI (142.1 ± 35.6 vs. 124.1 ± 22.5 g/m2 , p = 0.01) and peak aortic jet velocity (4.2 ± 0.8 vs. 3.8 ± 0.9 m/s, p = 0.01) along with smaller aortic valve area (0.72 ± 0.28 vs. 0.86 ± 0.22 cm2 , p = 0.02) compared to patients with a negative ECG for LVH. The ECG parameters had a low sensitivity (6%-36.9%) with a specificity of up to 100%. The Cornell Voltage criteria had the best sensitivity with a specificity of 63.6% and the highest correlation with the LVMI (r = 0.38, p < 0.001). All of the ECG parameters correlated positively with the peak aortic jet velocity as well as with the mean aortic gradient. CONCLUSION: The electrocardiographic criteria for LVH in patients with moderate or severe AS have a poor sensitivity in identifying LVH confirmed by TTE. The values of the selected ECG criteria for LVH correlate weakly with both the TTE indices of LVH and the markers of AS severity.

Pharmacological Cardioversion With Antazoline in Atrial Fibrillation: The Results of the CANT Study.

Background Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrillation with intravenous antazoline ( CANT [Cardioversion With Antazoline Mesylate] study) in the setting of the emergency department. Methods and Results After reviewing 1984 medical records, 450 eligible patients (22.7%) with short-duration atrial fibrillation subject to pharmacological cardioversion were enrolled in a retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of the attending physician. The primary end point was successful cardioversion in the emergency department. The safety end point comprised bradycardia <45 bpm, hypotension, syncope, or death. The study population (mean age, 65.5±11.9 years; 52.9% females) was characterized by a median atrial fibrillation episode duration of 10 hours. Antazoline, alone or in combination, was administered in 24.2% (n=109) and 40% (n=180), respectively; amiodarone was administered in 46.7% and propafenone in 9.3%, while ≥2 antiarrhythmic drugs were administered in 19.8% of patients. Antazoline had the highest success rate of pharmacological cardioversion among all drugs (85.3%), which was comparable with propafenone (78.6%; relative risk, 1.09, 95% confidence interval, 0.91-1.30; P=0.317) and higher than amiodarone treatment (66.7%; relative risk, 1.28, 95% confidence interval, 1.13-1.45; P<0.001; number needed to treat, 5.4). The rate of cardioversion with antazoline alone was higher than combined amiodarone and/or propafenone (68.1%; relative risk, 1.25; 95% confidence interval, 1.12-1.40, P=0.0001). No safety end points were reported in the antazoline group, while 5 incidents occurred in the non-antazoline cohort ( P=0.075). Conclusions Antazoline represents an efficacious and safe method of pharmacological cardioversion in a real-life setting.