Number Of Ventricular Premature Beats Research Articles

Sex- and age-dependent susceptibility to ventricular arrhythmias in the rat heart ex vivo

The incidence of life-threatening ventricular arrhythmias, the most common cause of sudden cardiac death (SCD), depends largely on the arrhythmic substrate that develops in the myocardium during the aging process. There is a large deficit of comparative studies on the development of this substrate in both sexes, with a particular paucity of studies in females. To identify the substrates of arrhythmia, fibrosis, cardiomyocyte hypertrophy, mitochondrial density, oxidative stress, antioxidant defense and intracellular Ca2+ signaling in isolated cardiomyocytes were measured in the hearts of 3- and 24-month-old female and male rats. Arrhythmia susceptibility was assessed in ex vivo perfused hearts after exposure to isoproterenol (ISO) and hydrogen peroxide (H2O2). The number of ventricular premature beats (PVBs), ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes, as well as intrinsic heart rate, QRS and QT duration, were measured in ECG signals recorded from the surfaces of the beating hearts. After ISO administration, VT/VFs were formed only in the hearts of males, mainly older ones. In contrast, H2O2 led to VT/VF formation in the hearts of rats of both sexes but much more frequently in older males. We identified several components of the arrhythmia substrate that develop in the myocardium during the aging process, including high spontaneous ryanodine receptor activity in cardiomyocytes, fibrosis of varying severity in different layers of the myocardium (nonheterogenic fibrosis), and high levels of oxidative stress as measured by nitrated tyrosine levels. All of these elements appeared at a much greater intensity in male individuals during the aging process. On the other hand, in aging females, antioxidant defense at the level of H2O2 detoxification, measured as glutathione peroxidase expression, was weaker than that in males of the same age. We showed that sex has a significant effect on the development of an arrhythmic substrate during aging. This substrate determines the incidence of life-threatening ventricular arrhythmias in the presence of additional stimuli with proarrhythmic potential, such as catecholamine stimulation or oxidative stress, which are constant elements in the pathomechanism of most cardiovascular diseases.

Number of ventricular premature beats and other causes of cardiomyopathy associated with arrhythmia: case reports

We report a case of two patients with frequent idiopathic premature ventricular contractions. One of them had more than 25% of ventricular contractions per day leading to fast development of cardiomyopathy and its complete regression upon ventricular arrhythmia elimination. The second one had from 40% to 73% of ventricular contractions per day including non-sustained and sustained ventricular tachycardia without any structural changes of the heart during 28 years of follow-up.

PO-02-152 EFFECTS OF SYMPATHETIC STIMULATION ON REPOLARIZATION AND ARRHYTHMOGENESIS DURING LEFT LATERAL MYOCARDIAL ISCHEMIA

Left stellate ganglion stimulation (LSGS) is arrhythmogenic during acute myocardial ischemia of the anterior wall of the left ventricle. We hypothesized, as a counterpart, that right stellate ganglion stimulation (RSGS) is proarrhythmic when ischemia is produced by occlusion of the circumflex coronary artery. In 7 anesthetized female open-chested pigs, ventricular repolarization was measured in unipolar electrograms from 128 epicardial sites on the left lateral ventricular wall in an electrode grid of 14x30 mm (interelectrode distance 2 mm). Seven subsequent episodes of 5 minutes of acute ischemia (5 minutes occlusion of the circumflex coronary artery with 20 minutes reperfusion). Right atrial pacing was performed throughout the experiment at cycle length of 450 ms. The second occlusion served as a control. During the third and fourth occlusion, left or right stellate ganglion stimulation (LSGS or RSGS), respectively, was initiated after 3 minutes of ischemia for 30 seconds. The protocol was repeated after decentralization of both stellate ganglia and bilateral cervical vagotomy. Between 3 and 5 minutes of ischemia, RSGS caused a median of 9 (interquartile range 3-12), ventricular premature beats and in 2 instances ventricular tachycardia and fibrillation. The number of ventricular premature beats was significantly less during LSGS and control conditions (Figure, panel A), during which no ventricular tachycardia or fibrillation occurred. Following decentralization, RSGS was no longer significantly more arrhythmogenic than LSGS or control conditions (Figure, panel A). Additionally, we found that LSGS-induced changes in repolarization are evident in non-ischemic tissue, but not in ischemic tissue, during coronary occlusion (Figure, panel B, note the overlapping T-waves in the ischemic region). LSGS no longer has an effect on myocardium that has been ischemic for 3 minutes by occlusion of the circumflex coronary artery. RSGS was arrhythmogenic in this setting, while LSGS was not. This supports the clinical findings that bilateral sympathectomy is superior to left sympathectomy alone.

CE-452779-3 RANDOMIZED PLACEBO-CONTROLLED TRIAL OF FLECAINIDE IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited arrhythmia disorder with a high risk of ventricular tachycardia (VT) or ventricular fibrillation (VF), and implantable cardioverter defibrillators (ICD) remain the palliative therapy of choice. We conducted an NIH-funded pilot clinical trial hypothesizing flecainide administration is more effective than placebo in reducing the burden of ventricular premature beats (VPBs) in ARVC patients. The study was designed as a randomized double-blinded placebo-controlled crossover trial in ARVC patients with administration of 100 mg bid of flecainide or matching placebo for 4 weeks each with a washout period. The primary specific aim was to determine whether flecainide administration is associated with a significant reduction of number of VPBs in comparison to placebo, measured on 7-day Zio-Patch ECG monitoring. Inclusion criteria required ARVC diagnosis with the 2010 ARVC Task Force Criteria at the age of at least 18 years, implanted ICD, and over 500 VPBs on a diagnostic 24-hour Holter recording. Patients were required to be treated with beta-blockers. Patients on other antiarrhythmic treatment required washout with reconfirmation of over 500 VPBs per 24 hour off antiarrhythmic medication. The effect of flecainide on log2(VPB rate) was analyzed using a weighted linear mixed effects analysis of variance model with fixed effects for treatment and period and a random effect for subject, with wights proportional to teh Zio-Patch monitoring time. There were 22 patients with ARVC and an ICD enrolled with a mean age 45+/-13 years, including 12 females. There were 19 patients with at least one Zio-Patch recording and 17 with both recordings. The Table includes details of arrhythmias on placebo and on flecainide. The mean and median number of VPBs/day was significantly lower on flecainide than placebo. At least 50% reduction in VPBs/day was observed in 79% and at least 75% reduction in 53% of patients. The primary analysis showed that flecainide reduced the VPB rate by 72% (p < 0.0001, 95% CI: 56-82%), adjusted for the period effect. There were 2 subjects with pro-arrhythmic response, but flecainide was safe for most of study patients. This is the first randomized clinical trial testing antiarrhythmic management in ARVC patients. Flecainide signficantly reduced the VPB rate and NSVT/VT/VF rate supporting clinical use of this medication in ARVC patients.

Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/PPARγ pathway in arrhythmic rats

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.

Left Atrium Involvement in Lymphoma Patients: Single Center Observational Study

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p&lt;0.05). Lymphoma patients had a higher number of premature ventricular beats at baseline than after treatment or in control [183 (14;841) vs 38 (14;94) and 9 (4;38) respectively]. There were no associations found between the parameters of LA structure and function and SVA. Moderate positive correlation between ESR and supraventricular premature complexes was found (rS=0.44; p&lt;0.05). A positive correlation between LA contractile function and inflammatory biomarkers were revealed: LA active ejection fraction (LA EFact) and ESR (rS=0.42, p&lt;0.05); LA volume index and β-globulin (rS=0.43, p&lt;0.05); LA EFact and neuregulin-1β (rS=0.42, p&lt;0.05); LA expansion index and neuregulin-1β (rS=0.55, p&lt;0.05).Conclusions. In lymphoma patients, LA phasic strain parameters were impaired regardless of anticancer treatment. The associations between inflammatory biomarkers with SVA and parameters of LA performance were found.

Feasibility of electroanatomic mapping and radiofrequency catheter ablation in Boxer dogs with symptomatic ventricular tachycardia.

BackgroundTreatment for Boxers with ventricular tachycardia (VT) is limited. Electroanatomic mapping (EAM) facilitates identification of arrhythmogenic substrate for radiofrequency catheter ablation (RFCA).ObjectiveDescribe the use of EAM to guide RFCA in Boxers with VT.AnimalsFive client‐owned Boxers with symptomatic VT or persistent VT despite antiarrhythmic medications.MethodsCase series evaluating clinical, EAM, and before and after RFCA Holter data.ResultsSustained VT was inducible in 3 dogs, but required aggressive stimulation protocols. Low‐voltage areas consistent with electroanatomic scar were found in 2 dogs, located at the right ventricular (RV) outflow tract and cranial RV. Two dogs had a focal activation pattern of VT and 1 dog had a reentrant mechanism. After RFCA, all dogs no longer collapsed and had fewer runs of VT, 3 of which had 0 runs of VT. Number of ventricular premature beats increased in 3 dogs and decreased in 2 dogs, 1 of which had nearly complete resolution of all arrhythmias. Procedural complications included ventricular fibrillation (n = 2) with successful defibrillation, bruising or hemorrhage at the vascular access site (n = 4), retroperitoneal hemorrhage (n = 1), aortic and mitral regurgitation (n = 1), onset of frequent supraventricular tachycardia (n = 1), and persistent right pelvic limb lameness (n = 1).Conclusions and Clinical ImportanceElectroanatomic mapping and RFCA are feasible in Boxers with VT. Based on this small cohort, RFCA may help decrease runs of VT and improve clinical signs. The anatomic substrate and electrophysiologic mechanisms are variable and require further study.

Melissa officinalis tea favourably affects the frequency of premature ventricular beats and cardiometabolic profile among patients with premature ventricular contraction: A randomised open-label controlled trial.

Premature ventricular contraction (PVC) as one of the most common arrhythmias could worsen the morbidity of cardiovascular events, particularly concurrent with other risk factors. Considering the probable side effects of antiarrhythmic drugs chronic use, prescribing herbal medicines for such conditions is on the rise. Melissa officinalis (MO) is widely identified as an antiarrhythmic and cardioprotective agent but there is limited evidence for its clinical use. This research, thus, aimed to investigate the effects of MO tea among patients with PVCs. The present 12-week randomised controlled trial enrolled 60 patients with confirmed diagnosis of moderate to low-grade PVCs. The patients in intervention group received MO teabags (containing 2-g dried leaves/250mL in hot water) two times/day in addition to lifestyle modification recommendations, while control group only received lifestyle modification recommendations. After collecting the data, blood samples were gathered to explore serum concentrations of glucose and lipid markers. The number of premature ventricular beats and heart rates was determined by 24-hour rhythm Holter monitoring. On average, the patients aged 47years and approximately 67.8% (n=40) were women. The ANCOVA adjusted for baseline values and confounders revealed that patients in the MO tea group had significantly lower concentrations of triglyceride (adjusted mean (AM)=144.75mg/dL), total cholesterol (AM=155.35mg/dL), and fasting blood sugar (AM=90.85mg/dL), compared with the controls (AM=174.27, 171.99, 99.84mg/dL, respectively (P-value ≤.042). However, the intervention failed to affect LDL-C and HDL-C levels significantly. Significantly reduced frequency of 24-hour premature ventricular beats in the MO tea group (AM=2142.39) was also noted compared with the controls (AM=3126.05); (P-value=.017). The 24-hour heartbeats showed only a significant decrease within the intervention group (P-value<.01). Together, these results seem to support the higher cardioprotective effects of MO as a medicinal plant than lifestyle modifications alone. Nevertheless, further exploration of this hypothesis is warranted using large-scaled clinical trials.

Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart.

AimsAlthough voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation.Methods and ResultsStudy involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3–4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis.ConclusionOur results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.

Melatonin pretreatment does not modify extrasystolic burden in the rat ischemia-reperfusion model.

The mechanism of reentrant ventricular tachyarrhythmias complicating acute myocardial ischemia is largely based on the interaction between an arrhythmogenic substrate and triggers. Melatonin was proposed as an antiarrhythmic medication and was shown to ameliorate the arrhythmogenic substrate. Also, melatonin provides a sympatholytic effect in different settings and might attenuate ectopic activity, which provides reentry triggers. In the present study, we aimed at evaluating the melatonin effects on cardiac sympathetic activity and the incidence of premature ventricular beats during the episode of ischemia-reperfusion. Experiments were done in a total of 26 control and 28 melatonin-treated (10 mg/kg, daily, for 7 days) male rats. Sympathetic fibers density was assessed by glyoxylic acid-induced fluorescence. Continuous electrocardiograms recording was performed during ischemia-reperfusion episodes (5 min/5 min, respectively) induced by reversible coronary occlusion. Myocardial expression of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis was assessed by Western blotting. No differences in the state of sympathetic innervation were observed in histochemical analysis. However, Western blotting analysis demonstrated that melatonin treatment suppressed tyrosine hydroxylase expression in the non-ischemic (p < 0.05 versus control) but not ischemic regions of myocardium. The melatonin-treated animals had longer RR-intervals in the baseline state than the control animals (264 ± 48 ms versus 237 ± 33 ms, p = 0.044, respectively), but this difference decayed during the period of ischemia due to the increase of heart rate in the treated group. The number of premature ventricular beats did not differ between the control and treated groups during the ischemic and reperfusion periods. One-week melatonin pretreatment caused a slight peripheral sympatholytic effect that attenuated during ischemia and completely disappeared by the onset of reperfusion. The slight expression of sympathetic downregulation was associated with the lack of any effect of melatonin on extrasystolic burden. Collectively, the data suggest that melatonin cannot target the triggers of reentrant arrhythmias.

Mechanism of ventricular premature beats elicited by left stellate ganglion stimulation during acute ischaemia of the anterior left ventricle.

AimsEnhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This ‘injury’ current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the ‘injury’ current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion.Methods and resultsIn nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization.ConclusionLSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts.

Olanzapine is an antipsychotic drug routinely used for the treatment of schizophrenia. Although the olanzapine treatment is associated with disturbed electrical heart activity, the exact mechanism underlying this severe adverse effect remains unclear. Recently, olanzapine administration was demonstrated to be associated with elevation of blood glucose and lower levels of free fatty acids. Therefore, we investigated the effect of acute olanzapine administration on pathways regulating the cardiac energy metabolism in an isolated heart. Electrical activity and contractile parameters were recorded in isolated, spontaneously beating, adult male rat hearts, perfused with either olanzapine (100 nmol/l) or the vehicle for 10 min. Regulation of key signalling molecules was evaluated by immunoblotting and ATP levels were measured spectrophotometrically. Olanzapine prolonged the QTc intervals and induced a higher number of premature ventricular beats. Furthermore, olanzapine significantly decreased the coronary flow, the rate-pressure product and the contractility (+dP/dt and -dP/dt). These changes were associated with an increased acetyl-CoA carboxylase phosphorylation and tissue ATP levels. We also found a trend for lower phosphorylation levels of Akt and its downstream products AS160, a key regulator of GLUT4 trafficking and glycogen synthase kinase‑3ß in olanzapine‑treated hearts when compared to vehicle-treated controls. These data should contribute to the elucidation of mechanisms that underlie the adverse cardiac effects of olanzapine.

Effect of ventricular premature catheter ablation on diastolic function in elderly patients

Objective To observe whether catheter ablation for ventricular premature complexes (PVC) has an effect on ventricular diastolic function in elderly patients. Methods Elderly patients older than 65 years of age who underwent catheter ablation from March 2012 to May 2015 for idiopathic ventricular premature complexes were enrolled.Preoperative echocardiography was performed using E/e′ for left ventricular diastolic function and venous brain natriuretic peptide (BNP) levels were measured.All patients underwent catheter ablation under the guidance of a three-dimensional mapping system.Cardiac ultrasound and BNP levels were repeated 6 months after ablation, and 24-hour electrocardiogram was performed to confirm ventricular premature complexes. Results There were a total of 89 patients with idiopathic ventricular premature complexes (PVC) who underwent catheter ablation.81 cases were successed at 6 months, with a success rate of 91.0%.At 6 months after ablation, the E/e′ values were significantly lower ((15.3±5.2) vs (10.2±3.2), (P 0.05). Conclusion The number of premature ventricular beats is associated with left ventricular diastolic function, and ventricular premature catheter ablation can improve left ventricular diastolic function in elderly PVC patients. Key words: Ventricular premature complexes; Catheter ablation; Diastolic function; Brain natriuretic peptide; The aged

Beneficial Effect of Mitochondrial Calcium Uniporter Overexpression in a Guinea Pig Heart Failure and Sudden Cardiac Death Model

Introduction: In the heart, excessive mitochondrial Ca2+ (mCa2+) can cause permeability transition pore opening and cell death. On the other hand, insufficient mCa2+ can also compromise energy supply/demand matching and mitochondrial reactive oxygen species scavenging capacity, especially at high workloads. The effect of increasing mCa2+ uniporter (MCU) expression in the context of heart failure (HF) has not been tested. Methods and Results: HF guinea pigs (ACi) were intramuscularly injected with adenoviral vectors expressing MCU with 3xFlag tag, leading to an increase of MCU-Flag levels by ∼30% above endogenous MCU expression. MCU overexpression restored mCa2+ handling in failing myocytes (1-F/F0 of MityCam at 1hz stimulation in the presence of isoproterenol (ISO): 0.27±0.02 in Sham, 0.21±0.01 in ACi, and 0.29±0.02 in ACi+MCU). Sarcomere shortening showed that the contractility of failing myocytes was significantly improved by MCU overexpression during high work load. MCU overexpression also potentiated cardiac output during β-adrenergic stimulation in perfused ACi hearts (the product of LV developed pressure and HR was increased by 36±22% in ACi vs 152±47% in ACi with MCU by ISO compared to baseline). To examined the effects of MCU overexpression in vivo, ACi heart was injected with vectors at 2w after aortic constriction, when cardiac decompensation usually accelerates. Cardiac function worsened in the untreated ACi in the following 2w (FS: 39±1% at 2w and 32±1% at 4w), whereas MCU overexpression significantly improved cardiac function (36±1% at 2w and 42±2 at 4w). ECG telemetry recordings also showed a substantial decrease in the number of premature ventricular beats. Conclusions: The results indicate that MCU overexpression in ACi hearts enhances contractility and responses to β-adrenergic stimulation in isolated myocytes and whole hearts while mitigating HF and inhibiting arrhythmias in vivo.

Treatment for ventricular arrhythmias in the absence of structural heart disease: from guidelines to clinical practice

To determine criteria for choosing management tactics in patients with ventricular arrhythmias (VA) in the absence of structural heart disease from the point of view of physicians and patients in clinical practice and to compare the immediate results of antiarrhythmic drug therapy (ADT) and radiofrequency ablation (RFA) with the trends in arrhythmic syndrome in the non-treatment group. Examinations were made in 90 patients (23 men and 67 women) (mean age, 44 (31; 57) years) with VA in the absence of structural heart disease. Preference was given to RFA (n = 32 (36%)), ADT (n = 37 (41%)), and follow-up tactics (n = 21 (23%)). At baseline and 1 month, Holter ECG monitoring was done; quality of life (QOL) was assessed; and anxiety and depression levels were detected using the SF-36 and HADS questionnaires. In addition, 71 physicians were surveyed about their preferences to the treatment of VA in individuals without structural heart disease. In the total group of patients, VA was unambiguously accompanied by the symptoms only in 47%. The signs of anxiety and depression were identified in 41 and 14% of cases, respectively. The efficiency of RFA was comparable to that of ADT (p > 0.1): a positive antiarrhythmic effect was observed in 71.9% of the patients in the RFA group and in 67.6% in the ADT group. During one month, 38.1% of the patients in the follow-up group showed a spontaneous substantial reduction in the number of ventricular premature beats (VPBs) or disappearance of unstable ventricular tachycardia (UVT), which met the criteria for a positive effect. At baseline, the QOL indicators on a social functioning scale in the RFA group were worse than those in the ADT group. At the same time, most QOL indicators in the patients who have chosen a wait-and-see tactic were significantly higher than those in the RFA and ADT subgroups. The patients treated with ethacyzin in the ADT group more frequently achieved a positive effect. In the interviewed physicians' opinion, the choice of a tactic depended on the impact of arrhythmia on health status (68%), the number of VPBs per day (61%), and the presence of UVT (56%). RFA or ADT was most often recommended when there were 10,000-15,000 or more VPBs per day ((49 and 35% of the respondents, respectively). 46.5% of the respondents stated that β-blockers were the drug of choice for idiopathic frequent VPBs. Only 30% of the respondents considered it appropriate to restrict to a follow-up in the presence of asymptomatic VPBs. Patient management in clinical practice generally complies with the current guidelines; however, much importance is attached to the severity of arrhythmia (the number of VPBs per day, the presence of UVT) in addition to the presence of symptoms. In the opinion of most physicians, the initiation of treatment is justified when there are 10,000-15,000 and more per day. QOL assessment may be promising in choosing the optimal management tactics for these patients. Treatment should not be initiated immediately in patients with a high level of QOL, especially in those with arrhythmia lasting less than 12 months, by taking into account that there can be a spontaneous improvement in 38% of cases within the next month. The immediate results of ADT and RFA are comparable in patients with VA in the absence of structural heart disease. The Class IC antiarrhythmic drug ethacyzin is the most effective agent that ensures positive changes in arrhythmic syndrome in 66.7% of cases with the rate of side effects being in 17.8%.

Young athletes with ventricular premature beats: Continuing or not intense training and competition?

Isolated ventricular premature beats (VPBs) are commonly found during pre-participation screening in athletes. Currently, the debate about the role of detraining in reducing the number of VPBs is still open. This study evaluated the arrhythmic risk in a population of young competitive athletes who showed VPBs during eligibility evaluation and that did not undergo detraining but continued practicing competitive sports. 3746 consecutive subjects underwent pre-participation screening. Athletes who showed VPBs were selected and underwent second level evaluation (Echocardiogram, 24hour Holter ECG and Exercise test). Athletes were re-evaluated after a follow-up period (6-48months) while they continued practicing competitive sports. 5.3% of the whole population showed ventricular arrhythmias. 73% of the subjects showed isolated VPBs. 88% of the subjects showed monomorphic VPBs, and 12% of athletes showed polymorphic VPBs. At echocardiogram, there was not any pathology which contraindicated competitive sport activity. At 24hour Holter ECG recording, mean number of daily VPBs was 1592±3217 (range 0-16678). At holter ECG follow-up (16±12months), the median number of VPBs decreased from 93 (IQR 20-3065) to a new value of 72 (IQR 2-1299). Continuing competitive sport in subjects with ventricular arrhythmias even though frequent but with a low grade of complexity and without structural cardiomyopathy does not increase sudden death risk.

The dependence of the ectopic electrical activity of the heart on the excess body weight in patients with essential hypertension in combination with ischemic heart disease (according to the daily ECG monitoring)

Вackground. Obesity, hypertension and myocardial ischemia due to coronary atherosclerosis are the most common combination of pathological conditions. Arrhythmias (except for atrial fibrillation) in patients with obesity and hypertension in combination with ischemic heart disease are neglected.The aim of our study was to ascertain the impact of excess body weight on thr ectopic electrical activity of the heart in hypertensive patients with concomitant coronary heart disease (according to the daily monitoring of heart rhythm).Material and methods. The study involved 91 patients with essential hypertension stage II, degree II with concomitant coronary heart disease aged 41-60 years, mean age 51,23 ± 5,30 years (men 69%). Depending on body mass index we divided patients into 2 groups. The first group included 70 patients aged 53 (48; 57) years (38% men) who had the body mass index over 25 kg / m2 (40 (44%) patients with excess body weight, and 30 (33%) patients with obesity). The second group included 21 (23%) patients aged 50 (47, 54) years with the body mass index from 18.5 kg / m2 to 24.9 kg / m2. The groups were comparable in age and sex.Results. Groups of patients had probable differences in terms of body weight (90 (80, 100) to 69 kg (61; 73) kg, p = 0.001), BMI (29.2 (26.6; 32.70 kg / m2 vs. 23.4 (22.4; 24.2) kg / m2, p = 0.001). However, the groups of patients did not differ in terms of height (173,86 ± 8,73 cm to 8,81 cm ± 170,95, p = 0.19). Patients with hypertension combined with coronary artery disease and overweight / obesity had significantly greater number of minutes of ST-segment elevation per day than patients with normal weight (12 (2, 180) min. vs. 7 (2, 169) min., p = 0.05). Inverse correlation was found between the number of premature ventricular beats per day and average daily heart rate (r = -0,5148; p = 0,002), the average heart rate per day (r = -0,4839 ; p = 0,004), the average heart rate per night (r = -0,4063; p = 0,019); and direct correlation between the number of premature ventricular beats per day and age (r = 0,2880; p = 0,047); the number of premature supraventricular beats per day and height (r = 0,3073; p = 0,034); the number of premature supraventricular beats per day and weight (r = 0,3271; p = 0,023); the total number of premature beats (supraventricular and ventricular) per day and age (r = 0,3415; p = 0,018); the total number of premature beats (supraventricular and ventricular) per night and height (r = 0,3620; p = 0,011).Conclusions. In patients with excessive body weight / obesity and hypertension with concomitant coronary artery disease increased number of premature ventricular beats per day is associated with bradycardia and depends on the age and the number of premature supraventricular beats per day depending on the height and weight. Ectopic electrical activity in patients with excessive body weight / obesity and hypertension with concomitant coronary heart disease is associated with myocardial ischemic changes, but independent of body mass index.

The effects of mebudipine on myocardial arrhythmia induced by ischemia-reperfusion injury in isolated rat heart

Reperfusion of the heart after an ischemic insult may lead to potentially lethal arrhythmias and cardimyocyte cell death via apoptosis and necrosis. In addition, previous studies showed that calcium channel blockers may have a protective role in the myocardium against arrhythmia and irreversible tissue injury. Therefore, this study was aimed to investigate the effects of mebudipine on myocardial arrhythmias and tissue injury induced by ischemia/reperfusion injury in isolated rat hearts. Male Wistar rats (250‑300g) were randomly divided to Sham group (without ischemia), control group (ischemia without drug), drug group (ischemia with mebudipine 0.1nM) and vehicle group (ischemia with ethanol 0.01%). The hearts of anaesthetized rats were removed and mounted on Langendorff apparatus and perfused by Krebs‑Henseleit solution under constant pressure of 75 mmHg at 37°C. Impulsive heart rate was monitored with bipolar golden electrodes. The electrocardiographs were recorded throughout the experiment and interpreted using the Lambeth convention. LDH and CPK activities in coronary effluent were analyzed spectrophotometrically. Hematoxilin &amp; Eosin staining was performed for evaluation of microscopic architecture of the myocardium and tissue injury. Pretreatment with mebudipine significantly decreased the number of ventricular premature beats (VPB) as compared with control group. The similar findings were seen in the number of ventricular tachycardia (VT) and fibrillation (VF) among groups. In addition, mebudipine significantly reduced the severity of arrhythmias in comparison with control hearts. Moreover, the drug group demonstrated marked improvement in edema and infiltration of inflammatory cells especially with regard to the degree of myonecrosis and cell lysis.Mebudipine diminished the number and the incidence of myocardial arrhythmias induced by reperfusion injury and the severity of tissue injury.

The Effects of Female Sex Hormones on Ventricular Premature Beats and Repolarization Parameters in Physiological Menstrual Cycle.

The effects of gender difference on cardiac electrophysiology have been well studied. In this study, we aimed to evaluate the effects of estradiol and progesteron changes occuring in physiological menstrual cycle on ventricular premature beats (VPBs) and cardiac repolarization parameters. Women of reproductive age with VPBs were included into the study group and healthy women were recruited as the control group. During the menstruation period, a 12-lead electrocardiography, blood samples, and 24-hour rhythm Holter were applied to the study group. Similarly, all tests were repeated in the estimated ovulation period (12-14 days before menstruation) by all cases. The study group consisted of 20 women patients with VPB, and the control group of 18 healthy women. While the number of VPB in the menstruation period was 210 beats/day (interquartile range [IQR]: 1,144), it decreased to 86 beats/day (IQR: 251) in the ovulation period with statistical significance (P < 0.05). Average heart rate in the menstruation period was 81.4 ± 10 beats/min and it significantly increased to 84.6 ± 8 beats/min in the ovulation period (P < 0.05). There were no differences in cardiac repolarization parameters in both menstruation and ovulation periods between the study and control groups. Comparing the menstruation and the ovulation periods, J-Tpeak interval, which reflects early repolarization, was shorter in the ovulation period (193 ± 27.7 ms and 201.1 ± 28.6 ms, respectively; P < 0.05). Other repolarization parameters did not show any significant difference. VPB frequency decreases with estradiol peak in the ovulation period. This suggests that estrogen may have protective effects against ventricular arrhythmias.

Interrelation of the heart rate turbulence with the clinical, functional and morphometric parameters among the patients with arterial hypertension

There have been explored 225 males in the age from 50 to 74 with an arterial hypertension (AH). For all the patients there have been carried out the recording of electrocardiogram (ECG) in the state of rest, ECG monitoring with a Holter identify indicators heart rate turbulence (HRT) and dynamic load testing (test with a 6 minute walk test, treadmill and bicycle ergometry). There was founded, that among the patients with an arterial hypertension after 50 years the number of ventricular premature beats grows up. With increasing of the age the normal values decrease and the pathological values increase heart rate turbulence (HRT), average slope of turbulence slope (TS). Dynamic load testing of patients after 70 years shows an increase in common, stress-induced ventricular arrhythmia, which is associated with ischemic-segment ST. Among the patients with arterial hypertension and frequent load-induced ventricular premature beats, in comparison with a rare, indicators of the HRT have a higher value. HRT among the patients with an arterial hypertension has a relationship with clinical and functional morfomerical indicators. The values turbulence onset (TO) of these were linked to the index left ventricular mass, pulse pressure, the number of ventricular premature beats, the average hemodynamic blood pressure, age and the values of circadian index (CI). The indicators TS are associated with index left ventricular mass, pulse pressure, the number of ventricular premature beats, with an average hemodynamic blood pressure, c values of the age and circadian index (CI).