AIMS: The cardiac conduction system (CCS) is progressively specified during development by interactions among a discrete number of transcription factors (TFs) that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain TFs with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity; however, the basis for these alterations has not been established. Here, we studied the role of Meis TFs in cardiomyocyte development and function during mouse development and adult life. METHODS AND RESULTS: We studied Meis1 and Meis2 conditional deletion mouse models that allowed cardiomyocyte-specific elimination of Meis function during development and inducible elimination of Meis function in cardiomyocytes of the adult CCS. We studied cardiac anatomy, contractility, and conduction. We report that Meis factors are global regulators of cardiac conduction, with a predominant role in the CCS. While constitutive Meis deletion in cardiomyocytes led to congenital malformations of the arterial pole and atria, as well as defects in ventricular conduction, Meis elimination in cardiomyocytes of the adult CCS produced sinus node dysfunction and delayed atrio-ventricular conduction. Molecular analyses unravelled Meis-controlled molecular pathways associated with these defects. Finally, we studied in transgenic mice the activity of a Meis1 human enhancer related to an single-nucleotide polymorphism (SNP) associated by Genome-wide association studies (GWAS) to PR (P and R waves of the electrocardiogram) elongation and found that the transgene drives expression in components of the atrio-ventricular conduction system. CONCLUSION: Our study identifies Meis TFs as essential regulators of the establishment of cardiac conduction function during development and its maintenance during adult life. In addition, we generated animal models and identified molecular alterations that will ease the study of Meis-associated conduction defects and congenital malformations in humans.

• MeSH
• Action Potentials MeSH
• Phenotype MeSH
• Homeodomain Proteins * genetics   metabolism   MeSH
• Myocytes, Cardiac * metabolism   pathology   MeSH
• Myocardial Contraction MeSH
• Mice, Knockout MeSH
• Sinoatrial Node metabolism   physiopathology   MeSH
• Heart Conduction System * metabolism   physiopathology   growth & development   MeSH
• Arrhythmias, Cardiac physiopathology   metabolism   genetics   MeSH
• Heart Rate * MeSH
• Myeloid Ecotropic Viral Integration Site 1 Protein * genetics   metabolism   deficiency   MeSH
• Age Factors MeSH
• Heart Defects, Congenital metabolism   genetics   physiopathology   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

Popáleniny predstavujú jedny z najčastejších úrazov, ktoré si vyžadujú odbornú starostlivosť a pozornosť, najmä v domácom prostredí. Ich výskyt je častý u detí aj dospelých a môže mať rôzne príčiny, ako sú popáleniny horúcou vodou, ohňom, elektrickým prúdom alebo chemickými látkami. Hoci sú popáleniny pomerne bežné, nesprávna prvá pomoc a následná starostlivosť môžu viesť k závažným komplikáciám, vrátane infekcií, oneskoreného hojenia alebo vzniku jaziev. Cieľom tohto článku je poskytnúť čitateľom komplexný prehľad o správnych metódach domácej starostlivosti pri popáleninách. Bude sa zaoberať odporúčanými postupmi, ako aj situáciami, ktorým je potrebné sa vyhnúť. Diskutovať sa budú bežne používané metódy ošetrenia, ako sú ochladzovanie popáleniny studenou vodou a aplikácia voľnopredajných krémov. Rovnako dôležité je zdôrazniť, kedy je potrebné vyhľadať odbornú lekársku pomoc a aký je význam správnej starostlivosti o rany pri podpore rýchleho hojenia a minimalizácii rizík. Tento článok si kladie za cieľ vybaviť čitatelov potrebnými znalosťami na správne ošetrenie drobných popálenín doma, čím prispeje k zvýšeniu kvality starostlivosti o pacientov a prevencii možných komplikácií.

Burns are one of the most common injuries requiring specialized care and attention, particularly in the home environment. Their occurrence is frequent among both children and adults, and they can have various causes, such as burns from hot water, fire, electrical current, or chemical substances. Although burns are relatively common, incorrect first aid and subsequent care can lead to serious complications, including infections, delayed healing, or the formation of scars. The aim of this article is to provide readers with a comprehensive overview of the proper methods of home care for burns. It will address recommended procedures as well as situations that should be avoided. Commonly used treatment methods, such as cooling the burn with cold water and applying over-the-counter creams, will be discussed. Equally important is the emphasis on when to seek professional medical help and the significance of proper wound care in promoting quick healing and minimizing risks. This article aims to equip individuals with the necessary knowledge for the appropriate treatment of minor burns at home, thereby contributing to the enhancement of patient care quality and the prevention of potential complications.

• MeSH
• Home Nursing * methods   MeSH
• Wound Healing MeSH
• Humans MeSH
• Aftercare methods   MeSH
• Burns * classification   nursing   MeSH
• First Aid methods   MeSH
• Check Tag
• Humans MeSH

Stimulací indukovaná kardiomyopatie (pacing-induced cardiomyopathy, PIcm) nemá mezinárodně akceptovanou definici, obecně se ale pod tímto pojmem rozumí srdeční selhání s ejekční frakcí levé komory < 50 % a současně její redukce ≥ 10 % po implantaci kardiostimulátoru bez jiné příčiny. Jedná se o komplikaci konvenční kardiostimulace, která je asociována s vyšší mortalitou z kardiovaskulárních příčin a ze všech příčin a častější nutností hospitalizací. Podíl komorové stimulace, který zvyšuje riziko vzniku PIcm, je > 20 %, nelze ale říct, že je nižší podíl bezpečný nebo že vyšší jednoznačně škodí. už při indikaci k trvalé kardiostimulaci je nutné identifikovat pacienty s vyšším rizikem vzniku PIcm a nabídnout jiné, (zatím) alternativní metody stimulace. u pacientů s konvenční kardiostimulací je nutné optimalizovat programaci k potlačení nežádoucí komorové stimulace s cílem co nejvíce snížit riziko vzniku PIcm. V případě již rozvinutého PIcm přichází v úvahu upgrade na srdeční resynchronizační léčbu (crT) nebo na stimulaci převodního systému (cSP), přičemž je vhodné výkon provést s co nejkratším časovým odstupem od rozpoznání PIcm.

Pacing-induced cardiomyopathy (PICM) does not have an internationally accepted definition. In general, the term refers to the heart failure with a left ventricular EF below 50% and its reduction ≥ 10% after implantation of a pacemaker without known cause. The pacing burden that increases the risk of PICM is > 20%. On the other hand, it cannot be said that a lower pacing burden is safe or that a higher pacing burden is clearly harmful. It is necessary to identify patients with a higher risk of developing PICM before the implantation of a pacemaker and offer other (for now) alternative methods of pacing. In the case of an already developed PICM, an upgrade to a CRT or a CSP should be considered. If indicated it is recommended to perform the upgrade without unnecessary delay after the recognition of the PICM.

• MeSH
• Electric Stimulation Therapy methods   MeSH
• Electrodes, Implanted adverse effects   MeSH
• Cardiomyopathies * epidemiology   etiology   prevention & control   therapy   MeSH
• Cardiac Pacing, Artificial * methods   adverse effects   MeSH
• Humans MeSH
• Heart Conduction System MeSH
• Heart Disease Risk Factors MeSH
• Cardiac Resynchronization Therapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND: The ventricular trabeculae play a role, among others, in the impulse spreading in ectothermic hearts. Despite the morphological similarity with the early developing hearts of endotherms, this trabecular function in mammalian and avian embryos was poorly addressed. RESULTS: We simulated impulse propagation inside the looping ventricle and revealed delayed apical activation in the heart with inhibited trabecular growth. This finding was corroborated by direct imaging of the endocardial surface showing early activation within the trabeculae implying preferential spreading of depolarization along with them. Targeting two crucial pathways of trabecular formation (Neuregulin/ErbB and Nkx2.5), we showed that trabecular development is also essential for proper conduction patterning. Persistence of the slow isotropic conduction likely contributed to the pumping failure in the trabeculae-deficient hearts. CONCLUSIONS: Our results showed the essential role of trabeculae in intraventricular impulse spreading and conduction patterning in the early endothermic heart. Lack of trabeculae leads to the failure of conduction parameters differentiation resulting in primitive ventricular activation with consequent impact on the cardiac pumping function.

• MeSH
• Neuregulins MeSH
• Mammals MeSH
• Heart * MeSH
• Heart Ventricles * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. METHODS: This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32 years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4 weeks; early groups underwent 2 weeks intervention immediately following the first study site visit (days 0-13) and late groups 2 weeks after the first study site visit (days 14-27). Active and sham taVNS included 2 weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. RESULTS: Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. CONCLUSION: Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.

• MeSH
• Adult MeSH
• Single-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Memory * physiology   MeSH
• Transcutaneous Electric Nerve Stimulation * methods   MeSH
• Vagus Nerve Stimulation * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions. In this study, we describe an approach for optical mapping of the retrogradely perfused chick heart in the last third of the incubation period. This system showed stability for electrophysiological measurement for several hours. This feature allowed analysis of the number and functionality of the APs separately in each clinically relevant position. Under physiological conditions, we also recorded the shortening of the AV delay with annulus fibrosus maturation and analyzed ventricular activation patterns after conduction through APs at specific locations. We observed a gradual regression of AP with an area-specific rate (left-sided APs disappeared first). The results also revealed a sudden drop in the number of active APs between embryonic days 16 and 18. Accessory myocardial AV connections were histologically documented in all positions around the annulus fibrosus even after hatching. The fact that no electrically active AP was present at this stage highlights the necessity of electrophysiological evaluation of accessory atrioventricular connections in studying AP formation.NEW & NOTEWORTHY We present the use of retrograde perfusion and optical mapping to investigate, for the first time, the regression of accessory pathways during annulus fibrosus maturation, separately examining each clinically relevant location. The system enables measurements under physiological conditions and demonstrates long-lasting stability compared with other approaches. This study offers applications of the model to investigate electrical and/or functional development in late embryonic development without concern about heart viability.

• MeSH
• Action Potentials * MeSH
• Chick Embryo MeSH
• Atrioventricular Node embryology   physiopathology   MeSH
• Perfusion MeSH
• Animals MeSH
• Check Tag
• Chick Embryo MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms. METHODS/DESIGN: In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, β=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites. DISCUSSION: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm. TRIAL REGISTRATION: NCT06025123.

• MeSH
• Time Factors MeSH
• Electric Countershock methods   MeSH
• Cardiopulmonary Resuscitation methods   MeSH
• Humans MeSH
• Recovery of Function * MeSH
• Return of Spontaneous Circulation MeSH
• Hypothermia, Induced * methods   MeSH
• Emergency Medical Services * methods   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Clinical Trial Protocol MeSH
• Randomized Controlled Trial MeSH

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Even though electrical injuries are common in the emergency room, guidelines, consensus, and general recommendations for the management of these patients do not exist in Europe. Documented cases of delayed arrhythmias are rare and their connection with electrical injury has not been fully confirmed. We also use cardio-specific markers for the risk stratification of myocardial injury, but there is no significant study referring to their utility in this clinical situation. These reasons led us to retrospectively analyze all cases of electrical injuries over 23 years to determine the prevalence of cardiac arrhythmias (mainly malignant arrhythmias and delayed arrhythmias). METHODS: We retrospectively searched all patients admitted to the University Hospital in Pilsen, CZ, with a diagnosis of electric injury (ICD diagnostic code T754) from 1997 to 2020. The hospital ́s information system was used to research the injury; data were drawn from patient medical records. RESULTS: We identified 333 cases of electrical injury in our hospital. Men accounted for about two-thirds, and women one-third. Children accounted for about one-third of cases. Most were low-voltage injuries (< 1000 V, 91.6%). All participants had an initial ECG, and 77.5% of patients had continuous ECG monitoring, usually lasting 24 h. Cardiac arrhythmias were noticed in 39 patients (11.7%). The most frequent arrhythmias were: ventricular fibrillation, sinus tachycardia, bradycardia and arrhythmia, atrial fibrillation, and supraventricular tachycardia. The ECG showed cardiac conduction abnormalities in 28 patients (8.1%), and ten patients (3%) had supraventricular or ventricular extrasystoles. In ten cases (3%), we found changes in ST segments and T waves on the initial ECG. Thirty-one patients (9.3%) suffered a loss of consciousness and 50 patients (15.02%) reported paresthesia. The most frequent ion disbalances were hypokalemia (18%) and hypocalcemia (3.3%). Patients with an ion disbalance had significantly more arrhythmias and newly diagnosed cardiac conduction abnormalities. Troponin levels (cTnI or hs-cTnT) were measured in 258 cases (77.48%) and found to be elevated above the 99th percentile in 19 cases (5.7%). Almost one-third of patients had burns of various degrees of seriousness, and 41 patients (12.3%) had concomitant traumatic injuries. Eleven patients underwent pre-hospital resuscitation, three died in the hospital, and another died as result of intracranial hemorrhage. CONCLUSION: All malignant arrhythmias occurred immediately after the electrical injury, delayed life-threatening arrhythmias were not observed, and no predictive factors of malignant arrhythmias were found. While elevations of cardiac troponins were observed sporadically, they did not appear helpful for risk stratification. In patients with arrhythmias, ion disbalance may be more critical. We concluded that asymptomatic, uninjured adult and pediatric patients with normal initial ECG findings do not need continuous ECG monitoring and may be discharged home. Recommendations for high-risk patients and patients with mild ECG abnormalities at admission are less obvious.

• MeSH
• Child MeSH
• Adult MeSH
• Electrocardiography MeSH
• Atrial Fibrillation * complications   MeSH
• Humans MeSH
• Cardiac Conduction System Disease complications   MeSH
• Electric Injuries * complications   diagnosis   epidemiology   MeSH
• Retrospective Studies MeSH
• Tachycardia, Sinus MeSH
• Accidents MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

This study aimed to identify time parameters predicting favourable CRT response. A total of 38 patients with ischemic cardiomyopathy, qualified for CRT implantation, were enrolled in the study. A 15% reduction in indexed end-systolic volume after 6 months was a criterion for a positive response to CRT. We evaluated QRS duration, measured from a standard ECG before and after CRT implantation and obtained from mapping with NOGA XP system (AEMM); and the delay, measured with the implanted device algorithm (DCD) and its change after 6 months (ΔDCD); and selected delay parameters between the left and right ventricles based on AEMM data. A total of 24 patients presented with a positive response to CRT versus 9 non-responders. After CRT implantation, we observed differences between responders and non-responders group in the reduction of QRS duration (31 ms vs. 16 ms), duration of paced QRS (123 ms vs. 142 ms), and the change of ΔDCDMaximum (4.9 ms vs. 0.44 ms) and ΔDCDMean (7.7 ms vs. 0.9 ms). The difference in selected parameters obtained during AEMM in both groups was related to interventricular delay (40.3 ms vs. 18.6 ms). Concerning local activation time and left ventricular activation time, we analysed the delays in individual left ventricular segments. Predominant activation delay of the posterior wall middle segment was associated with a better response to CRT. Some AEMM parameters, paced QRS time of less than 120 ms and reduction of QRS duration greater than 20 ms predict the response to CRT. ΔDCD is associated with favourable electrical and structural remodelling.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

• MeSH
• Time Factors MeSH
• Electrocardiography MeSH
• Humans MeSH
• Cardiac Resynchronization Therapy * MeSH
• Heart Failure * therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH