Concentration of apelin inversely correlates with atrial fibrillation burden.

AIM: Asymptomatic atrial fibrillation (AF) detection and pulmonary veins isolation (PVI) outcome prediction remain challenging. Our aim was to study the association between apelin and paroxysmal AF in patients undergoing radiofrequency catheter PVI. METHODS: Sixty-three consecutive patients (55 ± 8years, 12 females) with paroxysmal AF without a structural heart disease and implanted ECG loop recorders undergoing PVI and healthy control group of 34 persons (41 ± 9.5years, 21 females) were included. Apelin plasmatic concentrations were measured before and three months after PVI. AF burden was continually assessed for three years. RESULTS: Apelin was significantly decreased in AF patients compared to the healthy controls (0.79 ± 0.09 vs 0.98 ± 0.06 ng/ml; p < 0.00001). Apelin plasmatic concentration of 0.89 ng/ml had 94 % specificity and 89 % sensitivity for AF prediction with the area under the curve (AUC) of 0.96. After propensity matching to sex, age and comorbidities, apelin concentration was significantly lower in AF group (0.78 ± 0.1 vs 0.99 ±0.06  ng/ml; p < 0.0001; AUC: 0.97). There was a significant inverse correlation between apelin concentration and AF burden both before and after PVI (Rho = ‒0.22; p = 0.05) and (Rho = ‒0.51; p = 0.006), respectively. There was no significant association between pre-PVI apelin and PVI long-term outcome. CONCLUSION: In patients without a structural heart disease apelin showed a significant specificity and sensitivity for AF prediction and inversely correlated with AF burden (Tab. 3, Fig. 3, Ref. 34).

Association of apelin and AF in patients with implanted loop recorders undergoing catheter ablation.

BACKGROUND: Previous studies showed an association between apelin and atrial fibrillation (AF). The aim of this study was to analyse the effect of pulmonary vein isolation (PVI) in patients with paroxysmal AF on plasmatic apelin concentrations. METHODS: Nine consecutive patients (aged from 43 to 69 years, 3 females and 6 males) with documented paroxysmal atrial fibrillation and implanted loop recorders (ILR) for continuous ECG monitoring were included in this study. All the patients underwent a radiofrequency catheter ablation with PVI. RESULTS: The plasmatic concentration of apelin increased after PVI. The average plasmatic concentration of apelin before PVI was 0.299 ng/ml (±0.16), 3 months after PVI 0.462 ng/ml (±0.10) and 9 months after PVI 0.565 ng/ml (±0.146). There was an increase in the concentration of apelin 3 months and 9 months after the PVI by 0.163 ng/ml (p=0.07) and by 0.266 ng/ml (p=0.01), respectively. The concentration of apelin inversely correlated with the AF burden (r=-0.44, p=0.03). CONCLUSIONS: Our study showed a significant increase in apelin levels after the reduction of AF burden via PVI and an inverse correlation with AF burden. Apelin might be a promising marker of AF (Tab. 2, Fig. 2, Ref. 28).

Use of Bioresorbable Vascular Scaffold technology in treating coronary bifurcation lesions: A report about long-term clinical results and review of available literature.

INTRODUCTION: BVS proved safe in humans. ABSORB trials showed them performing similar to Drug Eluting Stents in simple coronary interventions. We assessed a registry of 63 patients with bifurcation lesions, treated by BVS and followed their outcomes up-to 5 years. METHODS: Patients who satisfied the inclusion criteria were included. Data about contact information, baseline characteristics, findings of coronary angiogram, details of their interventional treatment; short and long-term outcomes up till 5 years was collected. RESULTS: Acute feasibility of implantation in bifurcation was high (98 %). Rate of stent thrombosis, acute or sub-acute, was 3.1 %. Rate of re-intervention was 38 %. The average time for an event to occur was 1.6±0.8 years. Over 5 years, 56 % had developed MACE. Patients with MACE were more likely females, hypertensive, smokers, with acute presentations (p=NS), and diabetic (72 % vs 33 % non-diabetic; p=0.002). Patients treated with hybrid strategy of BVS and DES were more likely to develop MACE (64 % vs 49 % for others; P=ns). Patients treated by simple provisional stenting were less likely to develop MACE (45 % vs 60.5 %; p=ns). The average SYNTAX score of MACE patients was 27 vs 20; p=0.06). Diabetes was independently associated with MACE. Hypertension was of borderline statistical significance (2-sided Log rank for Hypertension p=0.06, for Diabetes p=0.01). DISCUSSION: The use of multiple stenting strategies to treat true bifurcation lesions using BVS is feasible with low rate of serious adverse events, albeit on the long run, the rate of re-intervention is high and stringent follow up is required (Tab. 7, Fig. 3, Ref. 37).

Eisenmenger syndrome - an electrocardiographic and echocardiographic assessment of the right ventricle.

BACKGROUND: Eisenmenger syndrome represents severe, irreversible, and end-stage pulmonary arterial hypertension (PAH) associated with congenital heart defects. For long-term outcome optimal right ventricular (RV) adaptation is crucial with precise assessment of its hypertrophy, dilatation and function. OBJECTIVES: Associations of electrocardiographic (ECG) and echocardiographic (ECHO) RV characteristics were analyzed. METHODS: Included were 52 patients (39F/13M), median age 45 years (24-78). Following ECG parameters were analyzed: Butler-Leggett formula (B-L), Sokolow-Lyon criterion (S-L), QRS duration (QRS), maximum spatial QRS vector magnitude (QRS max); and ECHO parameters: RV diameter (RVd), RV wall thickness (RVAW), RV/LV function. RESULTS: Following significant ECG-ECHO associations were demonstrated: S-L criterion and B-L formula with RVAW (p 120 ms only with severely dilated RV (RVd > 45 mm), while QRS max 33 mm); A new combined scoring system was introduced. CONCLUSIONS: In Eisenmenger syndrome RV hypertrophy is compensatory; diagnosis of prognostically unfavorable RV dilatation is therefore important. Combined ECG-ECHO analysis enables more accurate risk stratification. QRS duration > 120 ms seems to be a late marker; QRS max together with ECHO parameters may help to distinguish patients at higher risk for clinical deterioration (Tab. 3, Fig. 8, Ref. 53).

Structural assessment of myocardial infarction scars and left ventricular function with cardiac magnetic resonance imaging in patients at high risk of sudden cardiac death.

OBJECTIVES: Results of qualitative and quantitative analyses of scars and LV (left ventricle) function acquired by means of cardiac magnetic resonance (CMR) were correlated with a subsequent occurrence of malignant ventricular arrhythmias in patients at high risk of sudden cardiac death (SCD). METHODS: We have prospectively followed 47 patients (mean age 60 ± 11 years) who were hospitalized for an implantable cardioverter-defibrillator (ICD) implantation to prevent SCD. All post-MI patients had severe residual LV dysfunction (LVEF 33±14%). Patients were examined with CMR. Based on CMR analysis, we evaluated the basic functional parameters of LV as well as mass, volume, transmurality and heterogeneity of the post-MI scar. RESULTS: The patients with malignant arrhythmias were characterized by smaller LV end-diastolic diameters (LVED 192 ± 79 vs 254 ± 47 mm, p = 0.003) and end-systolic diameters (LVES 131 ± 80 vs 181 ± 45 mm, p = 0.01). As for the other observed functional and morphological CMR parameters, no significant differences between the two groups were detected. CONCLUSION: These results indicate that post-MI patients with severe residual left ventricular dysfunction and dilatation are in the long term characterized by a lower incidence of malignant arrhythmias compared to the patients with less dilated LV with a comparably severe LV dysfunction (Tab. 2, Fig. 3, Ref. 26). Text in PDF www.elis.sk.

The relation between oxidative stress biomarkers and atrial fibrillation after pulmonary veins isolation.

INTRODUCTION: The current paradigm claims a link between oxidative stress and atrial fibrillation. The aim of our research was to study a relation between the percentage of time spent in atrial fibrillation (AF burden) and concentrations of oxidative stress biomarkers, before and after pulmonary veins isolation (PVI). METHODOLOGY: We included 19 patients (mean age 55±10years, 4 females and 15 males) with implanted loop recorders undergoing PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products and thiobarbituric-acid reacting substances (TBARS) were measured and AF burden was recorded immediately before and 3months after the PVI. AF burden was also recorded 9months after the PVI. RESULTS: Post procedural AGEs concentration significantly negatively correlated with AF burden after 3months (ρ=-0.63; p<0.01) and 9months (ρ=-0.5; p=0.04), respectively as well as TBARS concentration significantly negatively correlated with AF burden after 9months (ρ=-0.61; p=0.01). CONCLUSION: Our study showed AGEs and TBARS to be potential predictors for AF burden after the PVI. We suppose that the more oxidative stress after the PVI is provoked, the more fibrotic tissue is produced. That means a better electrical isolation of pulmonary veins and consequently a lower AF burden.

Occurrence of symptoms after catheter ablation of atrial fibrillation.

OBJECTIVES: The aim of our study was to verify the efficiency of catheter ablation of atrial fibrillation (CA AF) according to the "atrial fibrillation (AF) burden"(time spent in AF) and symptoms related to AF. METHODS: We retrospectively analysed a selected set of 133 patients with atrial fibrillation (81% men, 19% women) who underwent an invasive therapy in the form of CA AF and at the same time had an implanted long-term ECG loop recorder (Reveal XT) in a period of eight years. We investigated AF burden and objective symptoms of AF by data obtained from a long-term implantable ECG loop recorder. Subjective symptoms related to AF were identified during outpatient controls. RESULTS: Firstly, our results demonstrate for the first time a clinically relevant increase in the occurrence of asymptomatic episodes of AF after CA AF. Secondly, when analysing AF symptoms and AF burden at the same time, CA AF in terms of reduction of symptoms and shortening the time in AF had a better effect in patients undergoing 1 procedure (CA AF) compared to patients undergoing repeated procedures (re CA AF). CONCLUSION: The increase in the occurrence of asymptomatic episodes of AF is of considerable importance both for the clinical evaluation of ablation efficacy and for individualized clinical management of patients, especially with respect to antithrombotic therapy (Fig. 10, Ref. 19).

Variations of heart rate variability parameters prior to the onset of ventricular tachyarrhythmia and sinus tachycardia in ICD patients. Results from the heart rate variability analysis with automated ICDs (HAWAI) registry.

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

Cardiac channelopathies in pediatric patients - 7-years single center experience.

INTRODUCTION: Channelopathies are associated with mutations of genes encoding proteins creating or interacting with the specialized ion channels in myocardial cell membranes, thus forming arrhythmogenic substrate predisposing the patient to sudden cardiac death. The study focuses the clinical and ECG presentation and management of children with channelopathies in Slovakia. SUBJECT AND METHODS: Twenty-two children with suspected channelopathy were admitted to Children's Cardiac Center Bratislava in the years 2007-2014. Genetic testing was made in 19 patients. RESULTS: Fourteen patients were symptomatic. Long QT syndrome was genetically proven in eight and catecholaminergic polymorphic ventricular tachycardia in five patients. Twenty children are treated with beta-blockers, five in combination with mexiletine or flecainide. Nine patients received implantable cardiac defibrillator and one underwent left cardiac sympathetic denervation. CONCLUSION: Both clinical presentation and genetic testing must be considered in the diagnostic and therapeutic process of channelopathies. Early diagnosis allows for adequate treatment and lifestyle modification.

Clinical implementation of cardiac resynchronization therapy-regional disparities across selected ESC member countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

Body surface integral maps in patients with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The aim of this study was to evaluate changes in QRST integral maps in patients with ARVC. BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disorder of predominantly right ventricle characterized with arrhythmic events possibly leading to sudden cardiac death. QRST integral maps reflect local disparities of ventricular repolarization and resulting vulnerability to arrhythmias. METHODS: A group of 8 patients with ARVC and a control group of 8 patients with a concealed accessory pathway were studied. Body surface mapping was performed using a 63-lead Savard's system. RESULTS: Mean QRST integral map of patients with ARVC showed abnormal characteristics. The area of negativity was larger than normal and extended to lower border of thorax. Departure map of the mean QRST integral map of patients with ARVC showed areas with departure index < 2 and > 2 in lower part of chest and upper part of back. When statistically analyzed, areas with p < 0.05 covered nearly lower half of chest and upper half of back. CONCLUSIONS: We consider body surface QRST integral mapping to be an adequate method for evaluation of dispersion of ventricular repolarization in ARVC patients (Tab. 1, Fig. 5, Ref. 17).

Arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a progressive disease of predominantly right ventricle, characterized by ventricular arrhythmias possible leading to sudden cardiac death. Genetic predisposition was confirmed more than 15 years ago. Autosomal dominant are forms ARVD1-9, Naxos disease (with subtype Carvajal syndrome) is recessive. In ARVC/D forms associated with desmosomal disorders are ventricular arrhythmias caused by the presence of myocardial damage and in forms associated with ryanodine receptor mutation is electrical instability and subsequent myocardial damage caused by calcium cell overload. Main clinical signs are ventricular arrhythmias originated from areas with slow conduction. Progression of ARVC/D is manifested by RV dilatation and LV echocardiographic abnormalities both considered as main risk factors of fatal ventricular arrhythmias and sudden cardiac death. Therapeutic possibilities include antiarrhythmic drugs, catheter ablation and implantation of cardioverter-defibrillator, in severe right or both ventricle involvement even heart failure treatment (Tab. 1, Ref. 56).

Effect of head-down bed rest on the neuroendocrine response to orthostatic stress in physically fit men.

The role of neuroendocrine responsiveness in the development of orthostatic intolerance after bed rest was studied in physically fit subjects. Head-down bed-rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic training. The standing test was performed before, after training and on day 4 of the HDBR. Orthostatic intolerance was observed in one subject before and after training. The blood pressure response after training was enhanced (mean BP increments 18+/-2 vs. 13+/- 2 mm Hg, p<0.05, means +/- S.E.M.), although noradrenaline response was diminished (1.38+/-0.18 vs. 2.76+/-0.25 mol.l(-1), p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP response was blunted, and noradrenaline as well as plasma renin activity (PRA) responses were augmented (NA 3.10+/-0.33 mol.l(-1), p<0.001; PRA 2.98+/-1.12 vs. 0.85+/-0.15 ng.ml(-1), p<0.05). Plasma noradrenaline, adrenaline and aldosterone responses in orthostatic intolerant subjects were similar to the tolerant group. We conclude that six weeks of training attenuated the sympathetic response to standing and had no effect on the orthostatic tolerance. In orthostatic intolerance the BP response induced by subsequent HDBR was absent despite an enhanced sympathetic response.

Endocrine activation in tachycardias.

This article reviews the complex character of neuroendocrine response to paroxysmal tachycardia. While the endocrine influences in arrhythmogenesis are well perceived by the cardiologists, less attention has been paid to influence of tachycardia on neuroendocrine activation. However, this may significantly alter the clinical course of tachycardias and its responses to pharmacotherapeutic interventions. Main characteristics of hormones with direct relationship to cardiovascular system (ANP, AVP, catecholamines, angiotensin and others) are listed with description of regulation of their secretion and main biological effects, especially with regard to regulation of circulation. Changes in hemodynamics during tachycardia with accompanying changes in ANP, AVP renin-angiotensin-aldosterone system, sympatho-neural and sympatho-adrenal activation are reviewed. Further research and understanding require more complex approach and concentration on interrelationship of different regulatory hormones in tachycardia. (Fig. 2, Ref. 96.)

The defibrillator in acute myocardial infarction trial (DINAMIT): study protocol.

BACKGROUND: The implantable cardioverter/defibrillator (ICD) has been shown to be superior to antiarrhythmic drug therapy for the secondary prevention of sudden cardiac death. Its role in the primary prevention of sudden death after myocardial infarction is unknown. Methods and Results The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) is a randomized, open-label, parallel-group comparison of ICD therapy versus no ICD therapy in selected survivors of acute myocardial infarction. It will test the hypothesis that reduction of sudden arrhythmogenic death by means of the ICD will result in reduction of overall mortality rates in patients at high risk after acute myocardial infarction. Accordingly, this international multicenter study aims to enroll patients shortly after their infarction (day 6 to day 40) who have reduced left ventricular function (left ventricular ejection fraction

Examining the influence of gender on medical students' decision making.

Gender bias, described among practicing physicians, has rarely been examined in medical students. The current study examined the influence of gender bias on medical students' clinical decision making. We experimentally manipulated patient gender in 27 written clinical vignettes embedded in the United States Medical Licensing Examination (USMLE) Step 2 examination (a multiple-choice test of clinical decision making). Female and male patient versions of selected test cases were created within three categories: (1) diseases with previously established evidence of gender bias in the diagnosis or management of the disease, (2) diseases with a higher prevalence in a specific gender, and (3) diseases with similar prevalence in both genders and without evidence of gender bias in the literature. Among the 3059 students who wrote the USMLE Step 2 examination in August 1998, there were small but significant differences in performance on the 12 gender bias cases. Students performed worse for the female patient version of the cases compared with the male patient version of the cases (mean of 55.8% correct for female cases compared with 57.7% correct for male cases) (p < 0. 01). Our data suggest that students were variably influenced by gender bias in their investigation and management of patients in a written test of clinical decision making.