The aim – to determine antiarrhythmic efficiency of eplerenone in the complex therapy of patients with arterial hypertension (AH) and frequent recurrences of atrial fibrillation (AF).
Material and methods. 146 patients with AH II stage and frequent recurrences of AF were examined. The age of the patients was from 37 till 86 years. Among them 68 (46.6 %) were males. Permanent antiarrhythmic therapy was prescribed in all patients. The antiarrhythmic efficiency was evaluated by patient-reported frequency of AF attacks and their course. Fixed combinations of perindopril with indapamide and losartan with hydrochlorothiazide were used as a starting antihypertensive therapy. Eplerenone 25 mg daily was added in a number of the patients. All patients were examined by determining serum aldosterone levels and daily ECG monitoring.
Results. Usage of eplerenone during 6 months decreased frequency of recurrences of AF and increased the duration of the period between recurrences (4.8 vs. 3.2 times, P=0.04). Antiarrhythmic effect of eplerenone was accompanied by significant increase of cases with complete elimination of supraventricular premature contractions (SPC) (P<0.001) and AF episodes (p=0.05), significant decrease of daily SPC frequency (P=0.007) and supraventricular paroxysmal tachycardias / atrial flutter episodes (P<0.04), decrease of QT interval dispersion (P<0.04). The probability of complete antiarrhythmic efficacy with additional use of eplerenone was significantly more in case of the adrenal AF (P<0.03). Factors increasing the probability of complete antiarrhythmic efficacy of eplerenone were: daily heart rate > 78 per minute, the ratio of left atrium /right atrium < 1.45, using of losartan in a dose of 100 mg/day, the dynamics of systolic blood pressure (BP) at the 4th week of treatment according to data of office measurement of BP > 32 mm Hg, and plasma level of aldosterone > 150 pg/ml.
Conclusions. Eplerenone provided additional antiarrhythmic effect in patients with AH and paroxysmal AF. Positive antiarrhythmic effect of eplerenone accompanied by a significant increase in cases with a complete elimination of SPC and AF episodes, significant decrease in the frequency of SPC for the day and SVPT/AF episodes, decrease in the dispersion of QT interval. The probability of complete antiarrhythmic efficacy with additional use of eplerenone significantly increases in the case of adrenal variant and decreases in the case of vagal varian of AF. As factors that increase the probability of complete antiarrhythmic efficacy of eplerenone are: daily HR > 78, the ratio LA/RA < 1.45, using of losartan in a dose of 100 mg/day, the dynamic of systolic BP at the 4th week of treatment according to data of office measurement of BP > 32 mm hg and plasma level of aldosterone > 150 pg/ml.
The aim – to evaluate the rate of resolution of left atrial appendage (LAA) thrombus and sludge after the use of anticoagulation therapy and evaluate the safety of cardioversion in patients with residual LAA thrombus and/or sludge on repeated transoesophageal echocardiography (TOE).
Material and methods. 39 patients with LAA thrombus and/or sludge on baseline TOE were included into the prospective observational study. The mean age was 61.7±9.5 years, mean CHA2DS2-VASc score 2.85±1.3, 11 (28.2 %) were females.
Results. There were 27 patients with LAA thrombus, 22 with LAA sludge, in 10 (45.45 %) cases thrombus was accompanied with sludge. After detection of thrombus and/or sludge, anticoagulation therapy was prescribed for 51.8±10.7 days before next TOE. Warfarin was prescribed in 19 (48.72 %) cases and treatment with novel oral anticoagulants (NOAC) – in 20 (51.28 %) patients. Complete thrombus resolution was noted in 18 (66.7 %) out of 27 cases, similar in both groups: in warfarin group it was found in 4/12 (33.3 %) and in NOAC group in 5/15 (33.3 %) of cases. In all cases residual thrombi had reduced size and were immobile. Sludge resolution rate was noted in 9 (40.9 %) out of 22: in warfarin group it was found in 7/11 (63.64 %) and in NOAC group – in 6/11 (54.55 %) cases. Cardioversion was registered in 14 (56 %) of patients with residual thrombus and/or sludge, among them 7 were with residual LAA thrombus: 3 patients had spontaneous cardioversion during first 30 days of follow-up, and DCC was performed in 4 highly symptomatic patients. There were no stroke or thromboembolic events during 30 days of follow-up. All patients were highly adherent to anticoagulation therapy.
Conclusions. Residual thrombi are frequent founding at repeated TOE. It seems that cardioversion might be considered in patients with reduced and immobile thrombi, being adherent to anticoagulation therapy.
The aim – to determine antiarrhythmic efficacy and safety of 1C class antiarrhythmic agents ethacizin and propafenone in patients with arterial hypertension (AH) and frequent recurrences of atrial fibrillation (AF).
Material and methods. 146 patients (age 37–86 years, 68 (46.6 %) males) with AH II stage and frequent recurrences of AF were examined. Antiarrhythmic therapy was used in all patients. The patient self-assessed the frequency of AF attacks and their course. The observation period from the time of the selection of effective antiarrhythmic therapy was 6 months. The actual average observation period for patients was 8.2±0.4 months.
Results. In general, 134 (91.8 %) of the treated patients had a positive antiarrhythmic effect within 6 months of the treatment. Thus, in 48 (35.8 %) cases it was total and in 86 (64.2 %) – partial antiarrhythmic effect (Р<0.0001). Propafenone was effective in 72 (62.6 %) cases, ethacizin – in 46 (62.2 %) patients (in vagal AF – 90.3 %). An additional use of bisoprolol increased the efficacy of ethacizin to 76.2 %. The study drugs decreased the frequency of arrhythmias attacks, increasing the time between the registered symptomatic episodes of AF by 5.7 times – from 12 to 80 days (Р<0.0001). In addition, the median duration of symptomatic episodes was significantly decreased by 5.0 times – from 12 to 2 hours (Р<0.0001).
Conclusions. The study proved antiarrhythmic efficacy and safety of ethacizin and propafenone in patients with arterial hypertension and paroxysmal atrial fibrillation.
The aim – to evaluate the risk of cardiovascular mortality in clinical practice with adherence to rhythm control strategy and anticoagulation therapy in patients with non-valvular atrial fibrillation and flutter (AF–AFl).
Material and methods. In a prospective observational study with a median follow-up of 36.8 (LQ 24.9–UQ 64.6) months we examined 293 patients with non-valvular AF–AFl, mean age 60.5±10.4 years, among them 81 (27.65 %) females. The mean CHA2DS2-VASc score was 2.25±1.46. All patients underwent clinical examination and transthoracic echocardiography. Transesophageal echocardiography was performed in 263 (89.76 %) patients.
Results. Cardiovascular death occurred in 20 (6.83 %) of cases during follow-up. 140 (52.83 %) patients were referred to the rhythm control group, and 125 (47.17 %) to the rate control group. Cardiac death occurred in only 1 (0.71 %) patient in the rhythm control group, versus 15 (12 %) patients of the rate control group (P<0,001). According to survey results, 138 (47.1 %) patients were adherent to the anticoagulation therapy (ACT), and 155 (52.9 %) were not adherent to. In the adherent to ACT group, cardiovascular death occurred in 4 (2.9 %) patients, versus 16 (10.32 %) in non-adherent group (P=0.004). In the multivariant regression model, history of stroke (relative risk (RR) 11.45, 95 % CІ 2.44–53.7, P=0.002) and myocardial infarction (RR 6.6, 95 % CІ 1.7–25.4, P=0,006), adherence to ACT (RR 0.07, 95 % CІ 0.014–0.34, P=0.001) and the rhythm control strategy (RR 0.06, 95 % CІ 0.01–0.48, P=0.008), independently reduced the risk of cardiovascular death.
Conclusions. Rhythm control strategy independently of adherence to ACT recommendations reduces the risk of cardiovascular death in patients with non-valvular AF–AFl.
The aim – to estimate changes of the myocardial structural and functional state and intracardiac hemodynamics in patients with non-valvular permanent atrial fibrillation (PAF) under treatment with β-blockers (BB), to determine the critical value of the heart rate being a negative predictor of the echocardiographic parameters during 6 month monitoring, to identify the preference for one of the HR control strategies.
Material and methods. 30 patients were included in this study. The duration of observation was 238.3±17.0 days, it consisted in 3 visits. Titration of the BB dose lasted 67.7±10.3 days (the interval between the first and second visits). Treatment with maximal or maximal tolerable dose of BB lasted 170.6±17.7 days (the interval between the second and final visits). During the follow-up period, echocardiography was performed twice – at 2 and 3 visits.
Results. During follow-up period significant changes were revealed, i.e. increase of LV end-diastolic dimension and its index in the general group and in women; of LV end-diastolic volume in women; the increase of LV mass index in the general group and in women; basal and transverse diameters of the RV and its area in diastole; pressure in the LA; early diastolic mitral in flow velocity and its relation to early diastolic mitral annular velocity; diameters of the PA and aorta root, mitral regurgitation. Correlation analysis revealed relationship between rate of mitral annular systolic velocity and the degree of severity of mitral regurgitation with the mean daily HR value according to 24 h Holter ECG. Along with lenient heart rate control after 6 months significant increase of the the interventricular septum thickness, basal RV diameter and PA diameter was observed; fractional change of the RV area decreased. At achievement of strict heart rate control fractional change of the RV area significantly increased compared to lenient one.
Conclusions. During follow-up period in patients with PAF we observed progression of LV diastolic dysfunction, heart valve dysfunction and increase of heart chambers, more significant in women, due to pressure overload. The median daily heart rate > 91 beats/min recorded during Holter ECG is a predictor of systolic function deterioration according to the tissue Doppler. Strict heart rate control has an advantage over the lenient one to improve the myocardial structural and functional state, the size and contractility of the right heart.
The aim – to evaluate the effectiveness and safety of warfarin therapy in patients with atrial fibrillation (AF) in the anticoagulation practice, the rate of CYP2C9, CYP4F2, VKORC1 genes polymorphism and their interrelation with hemorrhagic complications among Zaporizhzhia region residents.
Material and methods. We studied 41 patients with AF (mean age – 68.2±1.2 years, men – 19, women – 22) enrolled in a 1-year out-patient observation in the anticoagulation practice of Zaporizhzhia State Medical University clinics. All patients were treated with warfarin. CYP2C9, CYP4F2, VKORC1 genes polymorphism was determined using polymerase chain reaction method.
Results. During one year hemorrhagic complications (small bleedings) arose in 22 (53.66 %) patients with AF, receiving warfarin therapy. Bleedings were significantly more frequent in the group of patients with VKORC1 gene mutation: 69.5 % vs. 37.5 %, respectively (χ2=5.331; Р<0.05). It was found that the relative risk of bleeding under warfarin treatment in patients with VKORC1 gene mutation is 1.97 (95 % CI 1.039; 3.751; Р<0.05).
Conclusions. VKORC1 polymorphism is associated with increased frequency of hemorrhagic complications in patients with AF taking warfarin, indicating the relevance of a personalized approach to the warfarin dose titration using pharmacogenetic testing.
The aim – to evaluate clinical and echocardiographic predictors of ischemic stroke in patients with non-valvular atrial fibrillation and flutter (AF-AFl).
Material and methods. In a prospective observational study with a median follow-up of 36.8 months we examined 293 patients with non-valvular AF-AFl with a mean age 60.5±10.4 years, 81 (27.65 %) patients were females. Mean CHA2DS2-VASc score was 2.25±1.46. All patients underwent clinical examination and transthoracic echocardiography. Transesophageal echocardiography was performed in 263 (89.8 %) patients.
Results. Ischemic stroke (IS) occurred in 32 (10.92 %) cases: non-fatal IS – in 26 (8.87 %) cases, fatal IS – in 6 (2.05 %) cases. Onset of IS was associated with left atrial (LA) volume index ≥ 49 ml/m2 (Р=0,011), left atrial appendage spontaneous echo contrast (SEC) 3–4+ (Р<0.001), interventricular septum thickness (IVS) ≥ 1.7 cm (Р=0.02) and class EHRAm III–IV (Р<0,001). SEIL scale (SEC 3–4 + – 1 point, EHRAm III–IV – 1 point, IVS thickness ≥ 1.7 cm – 1 point, LA index ≥ 49 ml/m2 – 1 point) was an independent predictor of occurrence of IS, relative risk (RR) 2.38 (95 % CI 1.68–3.37), Р<0.001, independent of CHA2DS2-VASc, RR 1.28 (95 % CI 1.0–1.62), Р=0.045.
Conclusions. SEIL scale may be used for assessment the risk of ischemic stroke In patients with AF-AFl independent of CHA2DS2-VASc scale.
The aim – to determine the clinical, anamnestic characteristics and indicators of the structural and functional state of the myocardium, which may predict arrhythmia recurrence in patients with reverse episode of the first-diagnosed atrial fibrillation (AF) during 6-months follow-up.
Material and methods. Among 124 patients with first diagnosed AF in 88 patients AF episode terminated with sinus rhythm restoration. In order to compare the baseline clinical, anamnestic and instrumental characteristics, groups of patients with (n=44) and without (n=44) documented recurrence of AF were formed retrospectively. In these groups, the frequency of detection of risk factors, concomitant diseases, laboratory parameters, the course of the first episode of AF, data on echocardiography, and daily ECG monitoring after recovery of sinus rhythm were compared. Multifactor analysis was performed to determine the independent predictors of AF relapse.
Results.The relapsing course of AF is associated with older age, higher incidence of certain concomitant diseases, in particular, heart failure, hypertension and diabetes, and more severe left ventricular hypertrophy. The most significant predictors of the occurrence of arrhythmia recurrence after the first episode of AF after the restoration of sinus rhythm were CHA2DS2-VASc score (≥ 2 versus 0: odds ratio (OR) 3.135 (95 % confidence intervals (CI) 1.341–7.333); Р=0.008) and C-reactive protein level (≥ 6 mg/L versus < 6 mg/L: OR 3.041 (95 % CI 1.656–5.584) P<0.001).
Conclusions. During 6-months follow-up arrhythmia recurrence was registered in 50 % patients with first episode of AF. Independent predictors of the AF recurrence were CHA2DS2-VASc score two or more, as well as the CRP ≥ 6 mg/L. These aspects should be taken into account at individualized assessment of the need for antiarrhythmic and antithrombotic therapy in patients with first detected AF after restoration of sinus rhythm.
The aim – to determine the predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation (AF) after the sinus rhythm (SR) restoring, and to establish the role of the rs10465885 polymorphism in connexin-40 (Cx40) gene.
Material and methods. We enrolled 104 patients (pts) with non-sustained non-valvular AF (average age (53±10) years, 80 (76.9 %) men). The distribution of rs10465885 polymorphic variants in Cx40 gene (n=73) was as follows: TT – 17 (23.3 %) pts, CT – 33 (45.2 %), СС – 23 (31.5 %). We analyzed 122 cases of SR restoring: 32 (26.2 %) – pharmacological cardioversion (29 pts); 63 (51.6 %) – electrical cardioversion (ECV) (53 pts); 27 (22.2 %) – radiofrequency catheter ablation (RFA) (22 pts). The follow-up median was 23 months. According to the phenotypic parameters, associated with rs10465885, the sample of 104 pts (122 SR restoring cases) was stratified into 4 phenotypic clusters (PC): PC1 – 43 pts (57 SR restoring cases), PC2 – 24 (26); PC3 – 18 (20); and PC4 – 19 (19). According to PC and rs10465885 status (carriage or relatively high probability of non-CC or CC variant), the sample of 104 pts (122 SR restoring cases) was stratified into 4 integral clusters (IC): IC1 (PC1 + non-СС) – 26 pts (32 SR restoring cases); IC2 (PC1 + СС) – 17 (25); IC3 (combined group [РC234] + non-СС) – 49 (50); IC4 (РC234 + СС) – 12 (15).
Results. The risk of AF recurrence after ECV was 1,429 times higher than that of RFA. In addition, the risk of AF recurrence after restoration of SR in patients with the CHA2DS2-VASc scale score 1 was 1,550 times lower than in patients with 0 and ≥ 2 score. PC1, in comparison with PC234, was associated with a higher frequency of rs10465885 СС variant (taking into account the pts with a relatively high probability of СС carriage). PC1 was presented mainly by men under 40 years of age, with no pronounced structural and functional changes of the left ventricle. Additionally, PC1 was characterized by an earlier AF onset, the higher prevalence of subclinical AF, and a lower risk of stroke by the CHA2DS2-VASc scale. IC2 (vs IC4) was most significantly associated factor with the AF recurrence at 90 and 180 days after SR restoring.
Conclusions. The variant of SR restoring and the CHA2DS2-VASc score were the predictors of AF-free survival. The carriage (or relatively high probability of carriage) of the polymorphic variant rs10465885 СС in Cx40 gene additionally increases the risk of arrhythmia recurrence at the 3- and 6-month follow-up after SR restoration in patients with non-valvular AF and the PC1 features (as compared to PC234).
The aim – to study the level of the nerve growth factor (NGF) and serum norepinephrine level in elderly patients with ischemic heart disease (ІHD) and ventricular extrasystoles.
Material and methods. 90 people were examined, including: 60 patients with IHD at the age of 60–74 years, including: 30 people with IHD: stable angina, I–III, СHF, ventricular extrasystoles III–IVb class by Lown; 30 people with IHD diagnosis: stable angina, I, СHF, without ventricular extrasystoles, control – 15 relatively healthy elderly subjects (mean age 68.2±2.7 years) and 15 healthy young subjects (mean age 23.5±2.5 years). All patients underwent echocardiography (EchoCG), Holter ECG monitoring, heart rate variability, high resolution ECG (ECG BP) with study of the late ventricular potentials; the levels of NGF and norepinephrine in serum were studied as well.
Results. In elderly patients with IHD, increase of the serum levels of norepinephrine and NGF were revealed in comparison to the group of practically healthy elderly. In IHD patients with ventricular extrasystoles, multidirectional indices of the level of NGF are noted: in 20 patients there was a significant increase in the level of NGF, in 10 – slightly increased in comparison with the IHD group without rhythm disturbances.
Conclusion. The patients with normal level of NGF showed significant increase of heart cavities, more pronounced myocardial hypertrophy and reduced left ventricular contractility compared to the group in which the level of NGF was significantly elevated. Results of heart rate variability assessment in comparison groups showed that in patients with ventricular extrasystoles and high level of NGF there was a significant increase in sympathetic activity with minor changes in the morphofunctional state of the myocardium.