The yield of a comprehensive investigation protocol for the diagnosis of true idiopathic ventricular fibrillation in a real-life clinical setting.

Traditionally, aborted cardiac arrest (ACA) due to documented ventricular fibrillation (VF) in the absence of structural heart disease has been termed idiopathic VF. By careful evaluation, a specific etiology can be found in a substantial proportion of patients. The aim of this survey was to assess the yield of an advanced diagnostic work-up to reveal a causative etiology in a real-life clinical setting. Patients from the University Hospital Brno's ACA database were analyzed (514 patients in total). Forty-six patients (31 males) fulfilled the inclusion criteria, which were: (1) absence of structural pathology on echocardiography; (2) absence of coronary artery disease; and (3) absence of reversible cause of ACA. The diagnostic work-up consisted in cardiac magnetic resonance imaging, stress testing, sodium channel blocker challenge, and genetic testing according to the availability of the method and patient compliance. A specific disease was found in 17 individuals (37.0%), although at least one diagnostic step was refused by 13 patients (28.3%). True idiopathic VF was confirmed in 7 patients (15.2%), for whom the entire diagnostic work-up did not reveal any specific pathology. Our real-life survey shows that, even with an incomplete diagnostic work-up (due to the unavailability of a particular method or variable patient compliance), a specific diagnosis can be identified in more than one third of the cases of "idiopathic" VF, which can thus enable targeted treatment and family screening.

Adverse Effects of Meditation: Autonomic Nervous System Activation and Individual Nauseous Responses During Samadhi Meditation in the Czech Republic.

Buddhist meditation practices, including Samadhi meditation, which forms the basis for mindfulness practice, are broadly promoted as pathways to wellbeing, but evidence of their adverse effects is emerging. In a single-group observational study with assessments of autonomic system before, during, and after Samadhi meditation, we explore the relationship between post-meditation nausea symptoms and the degree of change in autonomic system activity during meditation as compared to before and after in 57 university students (42 women; mean age = 22.6) without any previous experience in meditation or yoga practices. We hypothesize that nauseous feelings in meditation are connected to a rapid increase of activity in the sympathetic nervous system, as indicated by decreased heart-rate variability (HRV). We additionally explore links between meditation-induced nausea and two markers of parasympathetic activity: increased HRV and vasovagal syncope. Engaging in meditation and increased nausea during meditation were both associated with increased markers of HRV parasympathetic activity, but 12 individuals with markedly higher nausea demonstrated increased HRV markers of sympathetic activity during meditation. Vasovagal syncope was observed but found to be unrelated to nausea levels. Drivers of adverse effects of meditation in some individuals require further investigation.

Appropriate and inappropriate therapies of implantable cardioverterdefibrillators.

Implantable cardioverter-defibrillators (ICD) reduce mortality of patients with risk of sudden cardiac death in primary and secondary prevention. Patients with implanted ICD can receive appropriate and inappropriate therapies with different incidence in both indication groups. There are some factors which can predict the incidence of ICD therapies. In some cases higher incidence of ICD therapies could negatively impact quality of patients lives. As predictive factors for higher incidence of appropriate therapies are discussed: reduced left venctricular ejection fraction, body mass index, chronic renal failure and frequent hospitalization for acute decompensation of chronic heart failure. As predictive factors for higher incidence of inappropriate therapies are discussed supraventricular tachycardia in patients history and single-chamber implantable kardioverter- defibrillator. The article summarizes indication criteria, incidence, predictive factors and treatment of appropriate and inappropriate therapies.

Differences in right-to-left vs left-to-right interventricular conduction times in patients indicated to cardiac resynchronization therapy.

INTRODUCTION: Differences in conduction times from right ventricle to left ventricle and from left ventricle to right ventricle respectively were observed during biventricular devices implantation when changing pacing vector direction. In this article the phenomenon of interventricular conduction time differences is described and assessed in relationship to various clinical and electrophysiological parameters. METHODS: In 62 consecutive patients (9 females) interventricular conduction times between right and left ventricle in both directions were measured during cardiac resynchronization therapy device implantation procedure. Complex pacing protocol was performed. RESULTS: Investigated individuals was divided into 3 subgroups according to type of interventricular conduction pattern and statistically tested with various clinical data. Substantial differences in right-to-left vs left-to-right conduction times (> 5 ms, range 7-72 ms) were observed in 24 (39%) of all patients. They were more common in patients with dilated cardiomyopathy (20 of 38, 53%) compared to 4 (17%) of 24 patients with coronary artery disease (p = 0.011). The phenomenon occurred more often in hypertensive patients (p = 0.012). Other tested factors were nonsignificant. CONCLUSIONS: There are almost no data on this topic. The occurrence of conduction difference phenomenon is quite common in dilated cardiomyopathy while it is rare in coronary artery disease. We assume the diffuse nature of the disease and the way of remodeling of myocardium play the main role. Knowledge of this phenomenon could be useful in personalized cardiac resynchronization therapy optimization.

Detection of new atrial fibrillation in patients with cardiac implanted electronic devices and factors associated with transition to higher device-detected atrial fibrillation burden.

BACKGROUND: In patients with cardiac implanted electronic devices, detection of new atrial fibrillation (AF) is associated with an increased risk of stroke. OBJECTIVE: To characterize daily AF burden at first detection and the rate of temporal transition to higher device-detected AF burden. METHODS: A pooled analysis of data from 3 prospective projects was analyzed, and 6580 patients (mean age 68 ± 12 years, 72% male) with no history of AF and no use of anticoagulants at baseline were identified. Various thresholds of daily AF burden (5 minutes and 1, 6, 12, and 23 hours) were analyzed. RESULTS: Among the study population of 6580 patients, a new AF, with an AF burden of ≥5 minutes, was detected in 2244 patients (34%) during a follow-up period of 2.4 ± 1.7 years. Among these patients, 1091 (49.8%) transitioned to a higher AF-burden threshold during follow-up. A higher duration of daily AF burden manifest at first detection and CHADS2 score ≥2 were associated with faster transition to a subsequent higher burden. Approximately 24% of patients transitioned from a lower threshold to a daily AF burden of ≥23 hours during follow-up. CONCLUSION: More than one-third of patients with no history of AF developed device-detected AF, with attainment of different thresholds of daily AF burden over time. Continuous long-term monitoring, especially when the initial detection corresponds to a higher daily AF burden and the CHADS2 score is ≥2, could support timely clinical decisions on anticoagulation by capturing transitions to higher AF-burden thresholds.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices.

Aims: To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results: The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion: Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

Alamandine reverses hyperhomocysteinemia-induced vascular dysfunction via PKA-dependent mechanisms.

INTRODUCTION: Hyperhomocysteinemia (HHcy) impairs nitric oxide endothelium-dependent vasodilation, consequently leading to atherosclerosis, a risk factor for cardiovascular disease. Novel treatments for HHcy are necessary. AIM: We tested the hypothesis that alamandine, a vasoactive peptide of the renin-angiotensin system (RAS), could reverse HHcy-induced vascular dysfunction through the MrgD receptor and that this is mediated by the protein kinase A (PKA) pathway. Furthermore, we sought to determine a putative binding model of alamandine to the MrgD receptor through docking and molecular dynamics simulations. METHOD: The abdominal aorta was excised from New Zealand white rabbits (n = 15) and incubated with 3 mmol/L Hcy (to mimic HHcy) to induce vascular dysfunction in vitro. Vascular function was assessed by vasodilatory responses to cumulative doses of acetylcholine. RESULT: Vasodilation was significantly impaired in HHcy-incubated aortic rings while alamandine reversed this effect (control, 74.2 ± 5.0%; Hcy, 30.3 ± 9.8%; alamandine + Hcy, 59.7 ± 4.8%, P < .0001). KT5720 (PKA inhibitor) significantly inhibited the ability of alamandine to attenuate the impaired vasodilation caused by HHcy (KT5720 + Hcy + alamandine, 27.1 ± 24.1, P < .01). Following immunohistochemistry analysis, the MrgD receptor was highly expressed within the media and endothelial layer of aortic rings in HHcy compared to control (media: 0.23 ± 0.003 vs control 0.16 ± 0.01, P < .05 and endothelium: 0.68 ± 0.07 vs control 0.13 ± 0.02, P < .01, in PA/I (A.U) units). Computational studies also propose certain interactions of alamandine within the MrgD transmembrane domain. CONCLUSION: This study shows that alamandine is effective in reversing HHcy-induced vascular dysfunction, possibly through the PKA signaling pathway via MrgD. Our results indicate a therapeutic potential of alamandine in reversing the detrimental effects of HHcy.

Changes in Hematologic and Coagulation Profiles in Rabbits with Right-ventricle Pacing.

OBJECTIVES: The aim of this study was to evaluate changes in hematology and coagulation in rabbits with right-ventricle pacing without medication. ANIMALS AND METHODS: Blood was collected from ten non-anesthetized male rabbits from the jugular vein before and one month after pacemaker placement. Total erythrocyte, leukocyte and platelet count, hemoglobin, hematocrit and differential leukocyte count were done on automatic veterinary flow cytometry hematologic analyzer. Prothrombin time, activated partial thromboplastin time, fibrinogen level, D-dimers and kaolin-activated thromboelastography was measured from citrated blood. RESULTS: We found an increase in red blood cell mass and decrease in platelet count, while coagulation tests did not diff er between samplings. CONCLUSION: Right-ventricle pacing seems to have no influence on hemostasis in rabbits.

Corrigendum to "Regional variations in baseline characteristics of cardiac rhythm device recipients: The PANORAMA observational cohort study" [Int. J. Cardiol. Heart Vessels (2014) 90-96].

[This corrects the article DOI: 10.1016/j.ijchv.2014.06.008.].

Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices).

OBJECTIVE: The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. BACKGROUND: Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. DESIGN, SETTING, AND PATIENTS: A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. RESULTS: During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3-14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22-3.64, P = 0.008). CONCLUSIONS: Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.

Regional variations in baseline characteristics of cardiac rhythm device recipients: The PANORAMA observational cohort study.

BACKGROUND: The PANORAMA study was designed to collect concurrent data on subjects from different worldwide regions implanted with CRM devices. METHODS: In this prospective, multi-center study, we analyzed baseline data on 8586 subjects implanted with CRM devices with no additional selection criteria (66% pacemaker (IPG), 16% implantable cardiac defibrillators (ICD), 17% cardiac resynchronization therapy (CRT) and < 1% Internal Loop Recorder) from 156 hospitals across 6 geographical regions between 2005 and 2011. RESULTS: Regardless of the device implanted, subjects from the Middle East and India often had more diabetes than other regions. Eastern and Western Europe had higher rates of atrial fibrillation reported, and men were more likely to smoke than women (46% vs 11%, p < 0.001). Within the CRT cohort there was significant variation in the proportion of males receiving a device, ranging from 55% in India to 83% in Eastern Europe. CONCLUSIONS: We provide comprehensive descriptive data on patients receiving CRM devices from a range of geographies that are not typically reported in literature. We found significant variations in clinical characteristics and implant practices. Long term follow-up data will help evaluate if these variations require adjustments to outcome expectations.

Mutation analysis ion channel genes ventricular fibrillation survivors with coronary artery disease.

BACKGROUND: Observations from population-based studies demonstrated a strong genetic component of sudden cardiac death. The aim of this study was to test the hypothesis that ion channel genes mutations are more common in ventricular fibrillation (VF) survivors with coronary artery disease (CAD) compared to controls. METHODS: The entire coding sequence of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was analyzed in 45 (five females) CAD individuals-survivors of documented VF and in 90 matched healthy controls. In another control group of 141 matched patients with CAD without malignant arrhythmias, the exons containing rare coding variants found in the VF survivors were sequenced. RESULTS: The carrier frequency of all the rare sequence variants was significantly higher in the VF survivors (8/45, 17.8%) than in CAD controls (3/141, 2.2%, P = 0.001). In VF survivors, four coding variants in eight individuals were found. Three in KCNH2 gene: R148W and GAG186del are novel; P347S was previously related to long QT syndrome. In SCN5A gene, P2006A variant was found in five unrelated males. This variant has been demonstrated previously to have small effect on sodium channel kinetics. No rare coding variants were found in the healthy controls. The P2006A variant was found in three CAD controls. CONCLUSION: The prevalence of selected, rare coding variants in five long QT genes was significantly higher in cases versus controls, confirming a mechanistic role for these genes among a subgroup of patients with coronary disease and VF.

[Alternative methods of microvolt T wave alternans measurements in patients with left ventricular cardiac dysfunction]. / Alternativní metody merení mikrovolt alternans T-vlny u pacientu s dysfunkcí levé srdecní komory.

BACKGROUND: The presence of a microvolt T wave alternans (MTWA) is linked with increased risk of malignant arrhythmias and overall mortality. The most common method used for MTWA detection is a bicycle exercise test (BET). Method has still several limitations. AIM: To confirm that comparable MTWA results may be obtained by atrial and ventricular pacing during electrophysiology. To identify an anticipated relation between MTWA and malignant arrhythmia occurrence, or a death. METHODS: We obtained MTWA during BET and consequently during atrial and ventricular pacing. All patients underwent a routine electrophysiology testing prior to prophylactic ICD implantation. The results were compared. The occurrence of malignant arrhythmias and death were registered during follow-up. RESULTS: The group consisted of 39 patients. The results of MTWA obtained by BET, atrial and ventricular pacing did not show a significant difference. No difference was found among the three methods in the number of positive leads, and onset heart rate. Ventricular pacing increases the magnitude of MTWA comparing to the remaining two methods. No relation between MTWA results and occurrence of malignant arrhythmias or death was found. CONCLUSIONS: Atrial and ventricular pacing lead to comparable MTWA results as BET and may be used as alternative methods in patients where BET is not feasible.

Right ventricular perforation with an ICD defibrillation lead managed by surgical revision and epicardial leads--case reports.

The authors present two cases of patients with perforation of the right ventricular wall by the implantable cardioverter defibrillator (ICD) lead. The complication was resolved by cardiosurgical revision and epicardial leads stitched onto the diaphragmatic wall of the heart. The perforation was identified by electrical parameter changes of the leads, echocardiography, and computed tomography. Both patients had satisfactory values of electrical parameters and ICD function with epicardial leads. The importance of regular follow-up and a check of the lead parameters are emphasized.

Treatment of arrhythmic storm in implantable defibrillator patients.

BACKGROUND: A common ICD therapy-related complication is arrhythmic storm (AS). The objective of our study was to define the impact of AS on patients' prognoses in order to compare the total mortality of AS patients with the rest of the group. MATERIAL/METHODS: We studied 138 patients who received ICDs between 1994 and 2001. Patients who experienced one or more arrhythmic storms were statistically compared with patients who had no accumulation of malignant arrhythmia or no episodes. RESULTS: One thousand four hundred ninety episodes of arrhythmia were analyzed. Arrhythmia recurrence was present in 71% of the patients. The majority of episodes (78%) were ventricular tachycardias and only 3% of episodes were ventricular fibrillation. Seventy percent of all arrhythmic episodes were asymptomatic. The ICD therapy sensitivity was 99.7%. Thirty-eight arrhythmic storms in 19 patients (14%) were observed during follow-up. The occurrence of AS was twice as high among patients with LVEF <35% than the rest of the group (18% vs. 8%). The total survival of patients with AS was significantly lower than that of the ICD patients who did not experience an AS (36.8% vs. 16.8%, p=0.042). All episodes of arrhythmic clusters during the AS were ventricular tachycardias. CONCLUSIONS: Arrhythmic storm is a serious risk marker for cardiac death. Ventricular tachycardia is a basic rhythm disorder of AS episodes and occurs significantly more often than ventricular fibrillation. Arrhythmic storm is responsible for a 4.6 times more frequent re-admission to hospital.

Endothelin-1 gene polymorphism in patients with malignant arrhythmias.

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive patients with malignant ventricular arrhythmias and implantable cardioverterdefibrillators with a mean age of 62.7 +/- 12.2 years and a mean left ventricular ejection fraction of 0.37 +/- 11.0. Taq polymorphism of ET-1 was detected using our original polymerase chain reaction method. The polymerase chain reaction product with a length of 358 basepairs (bp) (primers 5'-CAA ACC GAT GTC CTC TGT A-3' and 5'-ACC AAA CAC ATT TCC CTA TT-3') in its non-mutated form contains a target sequence for TaqI restrictive enzyme, while a mutated product loses this cleavage site. Of 26 patients, nine (34%) had recurrent palpitations and eight (30.8%) had syncopes during their malignant arrhythmias. Nineteen patients were given amiodarone after implantable cardioverter-defibrillator insertion and seven were not treated with amiodarone. Fifteen patients had (++), 11 (+-) and 0 (- -) ET-1 genotype. The risk for syncopes was associated with the (++) genotype of the ET-1 gene (P = 0.01). Patients receiving amiodarone had significantly higher frequency of the (++) genotype (P = 0.011). All our results indicate that the presence of the ET-1 genotype (++) in patients with structural heart disease, severe left ventricular dysfunction and malignant ventricular arrhythmias increases the risk for these patients of hemodynamic collapse during these arrhythmias.

Endothelin-1 gene polymorphism in the identification of patients at risk for malignant ventricular arrhythmia.

BACKGROUND: The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known for its direct positive inotropic and chronotropic effects on isolated heart, and for growth effects. The aim of this pilot study was to investigate the frequency distribution of a common polymorphism of the endothelin (ET-1) gene and its possible relation to the hemodynamic consequences of malignant ventricular arrhythmia in patients with structural heart disease. MATERIAL/METHODS: We studied 26 consecutive patients with malignant ventricular arrhythmia and implantable cardioverter defibrillators (ICD), mean age 62.7 +/- 12.2 years, mean LVEF 0.37 +/- 11. The Taq polymorphism of ET-1 was detected using our original PCR method. The PCR product with a length of 358 bp in its non-mutated form contains a target sequence for the TaqI restrictive enzyme, while the mutated product loses this cleavage site. RESULTS: Out of the 26 patients, 9 (34%) had recurrent palpitations and 8 (30.8%) had syncopes during their malignant arrhythmic episodes. 19 of the patients were receiving amiodarone after ICD implantation, 7 were not. 15 patients had the (++) and 11 had the (+ -) ET-1 genotype; none had the (- -) genotype. The risk of syncopes was associated with the (++) genotype (p=0.01). Patients with amiodarone had a significantly higher frequency of the (++) genotype (p=0.011). CONCLUSIONS: All our results suggested that the presence of the (++)ET-1 genotype in patients with structural heart disease, severe left ventricular dysfunction, and malignant ventricular arrhythmia put these patients at a higher risk of hemodynamic collapse during arrhythmic episodes.