Dariusz Kozłowski

Lone Atrial Fibrillation - What Do We Know?

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Despite the common association of AF with cardiovascular disease, some patients can be classified as ‘lone AF’. The latter is essentially a diagnosis of exclusion, and should be preceded by careful evaluation, including thorough collection of medical history, physical examination, blood pressure measurement, laboratory tests, ECG, echocardiography and, possibly, chest x-ray and exercise testing. Lone AF patients were initially thought to have a good prognosis with respect to thromboembolism and mortality, compared with the general AF population, but more recent data suggest otherwise. This review focuses on the clinical epidemiology and management aspects of lone AF, as well as various associated novel risk factors, such as familial, genetic and socioeconomic factors, alcohol, sports activity and biochemical markers.

Mastocytosis in children and adults: clinical disease heterogeneity

Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition consists of a heterogeneous group of disorders characterized by a pathological accumulation of mast cells in tissues including the skin, bone marrow, liver, spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in children and adults. Childhood onset mastocytosis is usually cutaneous and transient while in adults the condition commonly progresses to a systemic form. The heterogeneity of clinical presentation of mastocytosis is typically related to the tissue mast cell burden, symptoms due to the release of mast cell mediators, the type of skin lesions, the patients age at the onset and associated haematological disorders. Therefore, a multidisciplinary approach is recommended. The present article provides an overview of clinical symptoms, diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and management of mastocytosis patients in clinical practice.

Prevention of sudden cardiac death in patients with chronic kidney disease.

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients’ prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.

Day-by-day variability of spontaneous baroreflex sensitivity measurements: implications for their reliability in clinical and research applications

Objective To assess day-by-day variability of spontaneous baroreflex sensitivity (BRS) measurements, providing implications for their reliability in clinical and research studies. Methods Forty-four healthy volunteers and 57 patients with previous myocardial infarction (MI) underwent an 8 + 8 min (spontaneous + paced breathing) recording of ECG and noninvasive arterial pressure on two consecutive days. BRS was computed according to the sequence method (BRS_seq), the original and modified transfer function method (BRS_TF and BRS_TFmod) and the alpha method (BRS_αLF and BRS_αHF). Absolute and relative reliability were assessed by the 95% limits of random variation (LoV) and by the intraclass correlation coefficient (ICC), respectively. The sample size needed to detect a clinically relevant change was also estimated. Results In healthy volunteers during spontaneous breathing, BRS_seq, BRS_TF, BRS_αLF and BRS_αHF could not be measured in 18, 3, 2 and 2% of recordings, respectively. By definition, BRS_TFmod could always be measured. The 95% LoV indicated that individual day-by-day changes may range from −50% to +101% for BRS_TFmod (best case) and from −58% to +135% for BRS_αHF (worst case). The ICC ranged from 0.70 (BRS_seq) to 0.76 (BRS_TFmod). The sample size varied from 56 (BRS_TFmod) to 80 (BRS_seq). In MI patients, measurability was lower whereas reliability indexes were similar. Results during paced breathing were similar. Conclusion Day-by-day variability should be taken into account when using spontaneous BRS measurements to detect treatment effects in individual patients. The observed substantial to good relative reliability, as assessed by the ICC, indicates that spontaneous BRS measurements are suitable to detect differences between individuals, which is a prerequisite for proper diagnosis and prognosis.

Vernakalant hydrochloride for the treatment of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Rhythm control strategy for AF is limited by drug toxicity and side effects, and recent trials have shown that this strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance rhythm control, with the possibility of sinus rhythm restoration and maintenance. A promising find in the search for new antiarrhythmic therapies is atrial-tissue specific ion channels. The findings that the ultrarapid delayed rectifier (IKur) and the inwardly rectifying, acetylcholine-regulated current (IK-Ach) exist in atrial but not ventricular tissue increase the probability that atrioselective drugs without ventricular proarrhythmic toxicity can be developed for treatment of patients with AF. There are also other potential targets for atrial-selective therapy: transient outward current (Ito), rapidly and slowly activating delayed rectifier currents (IKr and IKs), atrial sodium current (INa) and atrially expressed connexins. New drugs under development with promising atrial-selectivity include: tertiapin, NIP-142, NIP-141, JTV-519, AVE0118, AVE1231, DPO-1, AZD7009 and many others. Among such new agents, vernakalant hydrochloride is currently in an advanced phase of development and has already been evaluated in clinical trials. In this overview, we describe the history and current state of developmental process of the drug, as well as its mechanism of action and influence on electrophysiological parameters. Vernakalant seems to be effective in terminating recent-onset AF, but is not efficacious in long-lasting AF and atrial flutter. The drug may be relatively free of proarrhythmic effects, and exerts a protective effect on ventricular tissue and ventricular repolarization. It is expected that the intravenous formulation will soon be approved for the pharmacological termination of recent-onset AF.

Dronedarone: An overview

Abstract Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Until recently, a rhythm control strategy for AF has been limited by drug toxicity and side-effects, and landmark AF trials have shown that such a strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance the rhythm control strategy, with the possibility of sinus rhythm restoration and maintenance. One of the promising drugs recently approved for clinical use is dronedarone. This drug has amiodarone-like antiarrhythmic and electrophysiological properties, despite it having a modified structure and lacking an iodine moiety. Thus, dronedarone lacks amiodarones organ toxicity (including adverse thyroid and pulmonary effects). The efficacy of dronedarone has been investigated in several clinical trials, proving its effect in the prevention of AF recurrence, rate control in paroxysmal/persistent and permanent AF, reduction of cardiovascular hospitalization or death from any cause, and others. Indirect comparisons with amiodarone, as well as one head-to-head study of the two drugs, indicate that the relative safety of dronedarone may be at a cost of its lower antiarrhythmic efficacy compared with amiodarone.

Histological Examination of the Topography of the Atrioventricular Nodal Artery within the Triangle of Koch

The treatment of choice in patients with drug‐resistant atrioventricular nodal reentry tachycardia is radiofrequency fast or slow pathway ablation. Ablation of the reentrant circuit in the region of the His bundle, when approached from the anterior‐superior region (fast pathway), can result in complete AV block. This is less likely if the posterior‐inferior (in the region of coronary sinus ostium) approach is used (slow pathway ablation). The possibility that radiofrequency energy may damage the vascular sjdpply to the AV node must be considered. In order to confirm this hypothesis observation was conducted on the autopsy material of 50 human hearts (20F, 30M) from 18 to 81 years of age. Specimens were taken containing the triangle of Koch (the apex‐ right fibrous trigone, the base‐ coronary sinus ostium). These histological blocks were sectioned in the frontal plane and stained using Massons method. Kochs triangle was divided in the sagittal plane into 3 parts: inferior (between the base and the attachment of the tricuspid valve), central (between the base and the apex of the right fibrous trigone) and superior (between this trigone and the tendon of Todaro). It was observed that the AVN artery at the coronary sinus ostium level (the base of the triangle of Koch) was positioned in 68% in the central and in 32% in the inferior part of Kochs triangle. The AVN artery in the central part was removed from the endocardium 1mm (18%), 2mm (42%), 3mm (22%), 4mm (18%). In the inferior part imm (26%), 2mm (37%), 3mm (37%). No statistically significant relationship was observed between those groups. Conclusions: 1) in 20% of examined hearts the AVN artery lay just beneath the endocardium near the coronary sinus ostium 2) there is a risk of the AVN artery coagulation during radiofrequency ablation m the slow pathway region.

The knowledge of public access to defibrillation in selected cities in Poland

Introduction The Public Access to Defibrillation (PAD) program was designed to raise the awareness of sudden cardiac death (SCA) pre-hospital management among the community. The goal of the following research was to confirm the final impact of the Polish PAD program on various resident groups that differ by age, training and education level. Material and methods The trial total number of participants reached 404 people from three cities divided into two groups. In group one (n = 295) were randomly selected people inside the trial area and in group two (n = 109) we had individuals who were theoretically trained in basic life support (BLS) algorithms, including the use of an automatic external defibrillator (AED). The research method was based on two different questionnaires completed by participants from each group. Results The greatest knowledge of SCA, as well as the use of AED, and the best practical skills, were possessed by the residents of cities with a population over 100 000, aged between 18 and 30 years, who completed secondary or higher education (31.7%). The group with the smallest knowledge about SCA lived in the country (10.7%). The second group with little knowledge of the subject consisted mostly of individuals with primary education (4.19%) or professional abilities and over 50 years old (2.16%). Conclusions There must be some actions taken in order to increase the community awareness concerning automatic defibrillation. Training on AED and the possibility of practical exercise needs to be organized and should be conducted especially among residents of the countryside and people under 30 or over 50 years old.

Morphogenetic aspects of the septomarginal trabecula in the human heart

Introduction The septomarginal trabecula is a constant element of the anatomy of the human heart, which connects the interventricular septum and the anterior wall of the right ventricle. Considering the diversity of opinions about the structure and numerous studies suggesting its important role in haemodynamics and conduction of electrical impulses in the heart, we decided to study this element in detail. Material and methods The research was conducted on 220 human hearts. Attention was mainly paid to the structure and topography of the trabecula. Its relation to the anterior papillary muscle was also a part of the study. Results The presence of this morphologically diverse element was confirmed in each of the studied hearts. In most cases the trabecula originated from the upper part of the interventricular septum, separating at an angle increasing proportionally to the number of branches of the crista supraventricularis as well as the number of secondary trabeculae. The criteria established for the study, which included the course of the trabecula in the lumen of the right ventricle and its relation to the anterior papillary muscle, let us distinguish 4 types of septomarginal trabecula (I, II, III, IV). The most common was type III, the undivided trabecula, tightly connecting with the anterior papillary muscle. Conclusions Based on the results of the following study we propose a hypothesis on the genesis of respective parts of the septomarginal trabecula and a plausible sequence of changes they undergo during human ontogenesis and phylogenesis of the primates.

Entropy Measures in the Assessment of Heart Rate Variability in Patients with Cardiodepressive Vasovagal Syncope

Sample entropy (SampEn) was reported to be useful in the assessment of the complexity of heart rate dynamics. Permutation entropy (PermEn) is a new measure based on the concept of order and was previously shown to be accurate for short, non-stationary datasets. The aim of the present study is to assess if SampEn and PermEn obtained from baseline recordings might differentiate patients with various outcomes of the head-up tilt test (HUTT). Time-domain heart rate variability (HRV) indices and several nonlinear parameters were calculated using 500 RR interval-long ECG recordings done before tilting in patients with a history suggesting vasovagal syncope. Groups of patients with so-called cardiodepressive vasovagal syncope (VVS_2) during HUTT and patients who did not faint during the test were compared. Two types of HUT tests were analyzed: with spontaneous (SB) or controlled breathing (CB). In our study, SampEn was higher in VVS_2 patients during SB, and PermEn was higher in VVS_2 patients during CB. Irrespective of the type of breathing during the test, SampEn and PermEn were similar in patients with the same type of reaction during HUTT. The use of several entropy-based parameters seems to be useful in HRV assessment in patients with vasovagal fainting.