INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.
- MeSH
- Action Potentials MeSH
- Bundle-Branch Block * physiopathology therapy diagnosis MeSH
- Time Factors MeSH
- Cardiomyopathy, Dilated physiopathology therapy diagnosis MeSH
- Electrocardiography * MeSH
- Ventricular Function, Left * MeSH
- Hemodynamics * MeSH
- Middle Aged MeSH
- Humans MeSH
- Predictive Value of Tests * MeSH
- Cardiac Resynchronization Therapy Devices MeSH
- Aged MeSH
- Heart Rate MeSH
- Cardiac Resynchronization Therapy * MeSH
- Heart Failure physiopathology therapy diagnosis MeSH
- Stroke Volume MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The immunosuppressive roles of galectin-3 (Gal-3) in carcinogenesis make this lectin an attractive target for pharmacological inhibition in immunotherapy. Although current clinical immunotherapies appear promising in the treatment of solid tumors, their efficacy is significantly weakened by the hostile immunosuppressive tumor microenvironment (TME). Gal-3, a prominent TME modulator, efficiently subverts the elimination of cancer, either directly by inducing apoptosis of immune cells or indirectly by binding essential effector molecules, such as interferon-gamma (IFNγ). METHODS: N-(2-Hydroxypropyl)methacrylamide (HPMA)-based glycopolymers bearing poly-N-acetyllactosamine-derived tetrasaccharide ligands of Gal-3 were designed, synthesized, and characterized using high-performance liquid chromatography, dynamic light scattering, UV-Vis spectrophotometry, gel permeation chromatography, nuclear magnetic resonance, high-resolution mass spectrometry and CCK-8 assay for evaluation of glycopolymer non-toxicity. Pro-immunogenic effects of purified glycopolymers were tested by apoptotic assay using flow cytometry, competitive ELISA, and in vitro cell-free INFγ-based assay. RESULTS: All tested glycopolymers completely inhibited Gal-3-induced apoptosis of monocytes/macrophages, of which the M1 subtype is responsible for eliminating cancer cells during immunotherapy. Moreover, the glycopolymers suppressed Gal-3-induced capture of glycosylated IFNγ by competitive inhibition to Gal-3 carbohydrate recognition domain (CRD), which enables further inherent biological activities of this effector, such as differentiation of monocytes into M1 macrophages and repolarization of M2-macrophages to the M1 state. CONCLUSION: The prepared glycopolymers are promising inhibitors of Gal-3 and may serve as important supportive anti-cancer nanosystems enabling the infiltration of proinflammatory macrophages and the reprogramming of unwanted M2 macrophages into the M1 subtype.
- MeSH
- Acrylamides chemistry pharmacology MeSH
- Apoptosis drug effects MeSH
- Galectin 3 * antagonists & inhibitors MeSH
- Galectins MeSH
- Interferon-gamma * metabolism MeSH
- Blood Proteins MeSH
- Humans MeSH
- Macrophages drug effects MeSH
- Monocytes * drug effects MeSH
- Tumor Microenvironment drug effects MeSH
- Polymers * chemistry pharmacology MeSH
- Antineoplastic Agents * pharmacology chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Long QT syndrome (LQTS) presents a group of inheritable channelopathies with prolonged ventricular repolarization, leading to syncope, ventricular tachycardia, and sudden death. Differentiating LQTS genotypes is crucial for targeted management and treatment, yet conventional genetic testing remains costly and time-consuming. This study aims to improve the distinction between LQTS genotypes, particularly LQT3, through a novel electrocardiogram (ECG)-based approach. Patients with LQT3 are at elevated risk due to arrhythmia triggers associated with rest and sleep. Employing a database of genotyped long QT syndrome E-HOL-03-0480-013 ECG signals, we introduced two innovative parameterization techniques-area under the ECG curve and wave transformation into the unit circle-to classify LQT3 against LQT1 and LQT2 genotypes. Our methodology utilized single-lead ECG data with a 200 Hz sampling frequency. The support vector machine (SVM) model demonstrated the ability to discriminate LQT3 with a recall of 90% and a precision of 81%, achieving an F1-score of 0.85. This parameterization offers a potential substitute for genetic testing and is practical for low frequencies. These single-lead ECG data could enhance smartwatches' functionality and similar cardiovascular monitoring applications. The results underscore the viability of ECG morphology-based genotype classification, promising a significant step towards streamlined diagnosis and improved patient care in LQTS.
- MeSH
- Adult MeSH
- Electrocardiography * methods MeSH
- Genotype MeSH
- Humans MeSH
- Machine Learning * MeSH
- Support Vector Machine MeSH
- Long QT Syndrome * genetics diagnosis physiopathology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
BACKGROUND: Diabetes mellitus (DM) causes myocardial electrical remodeling and promotes ventricular tachycardia and/or fibrillation (VT/VF). However, experimental studies have been frequently unsuccessful in developing a DM model with the expected high level of arrhythmic outcomes. The present study aims at evaluating cardiac electrophysiological properties in the rats with different Type 1 DM (T1DM) durations and identifying an electrophysiological phenotype associated with the high incidence of VT/VF. METHODS: The experiments were performed in 109 male Wistar rats (6-10 weeks old), subdivided into the groups of control, 4-weeks and 8-weeks T1DM (streptozotocin model). The animals were studied with epicardial electrophysiological mapping, whole-cell patch-clamp and histological examination. The VT/VF susceptibility was tested in ischemia/reperfusion induced in the anesthetized animals. RESULTS: In the 4-weeks T1DM group, we observed the increase in the incidence of reperfusion VT/VF, collagen deposition and dispersion of repolarization, slowed longitudinal and transverse conduction velocity, prolonged action potential duration, increased INa and ICaL currents, nonchanged Ito and IK1 currents. In the 8-weeks T1DM group, the VT/VF incidence, dispersion of repolarization, INa and Ito currents decreased. Other parameters persisted unchanged as compared to the 4-weeks T1DM group. CONCLUSIONS: Relatively early (4 weeks) diabetic electrical remodeling was proarrhythmic and included augmentation of sodium and calcium currents in the presence of fibrosis and slowed conduction and increased dispersion of repolarization. An unexpected finding was that diabetic arrhythmogenesis was associated with the increase in depolarizing transmembrane currents. Further research is warranted to elucidate molecular mechanisms and test the potential for the control of observed changes.
- MeSH
- Diabetes Mellitus, Type 1 * complications physiopathology MeSH
- Diabetes Mellitus, Experimental physiopathology complications MeSH
- Ventricular Fibrillation physiopathology MeSH
- Tachycardia, Ventricular physiopathology etiology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Rats, Wistar * MeSH
- Ventricular Remodeling MeSH
- Arrhythmias, Cardiac physiopathology etiology MeSH
- Heart Ventricles physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.
- MeSH
- Action Potentials * physiology MeSH
- Potassium * blood metabolism MeSH
- Myocardial Ischemia * physiopathology blood metabolism MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Myocardial Reperfusion Injury blood physiopathology metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Continuous deep septal pacing and signal recording during implantation of left bundle branch pacing (LBBP) lead enables to monitor beat-to-beat changes of electrocardiogram (ECG) and myocardial current of injury (COI) as the lead crosses the septum. OBJECTIVES: This study aimed to characterize patterns of continuous QRS, ST-T, and COI change for monitoring of the lead depth and instantaneous determination of the obtained capture type (LBBP vs left ventricular septal pacing [LVSP]). METHODS: The ECG and COI during lead implantation were scrutinized for sudden changes of V6 R-wave peak time, V1 initial and terminal R-wave amplitude, V3-V6 R-wave amplitude, repolarization pattern and S-wave amplitude in I, V5-V6, and COI drop. The sudden and gradual transition patterns were diagnosed depending on the presence or absence of the above beat-to-beat ECG phenomena, respectively. RESULTS: A total of 212 pacemaker recipients were analyzed; LBBP and LVSP were obtained in 77.4% and 22.6%, respectively. There were 4.7 ± 2.1 and 0.2 ± 0.6 beat-to-beat phenomena in LBBP and LVSP patients, respectively. The sudden transition pattern, recognized in 80.7%, had sensitivity and specificity for LBBP diagnosis of 98.8% and 81.2%, respectively. A sudden drop of COI (29.4 ± 8.5 mV to 12.8 ± 4.9 mV) was observed in 53.9% patients (LBBP was simultaneously obtained in 92.7%). CONCLUSIONS: Capture of left bundle branch during lead penetration is a beat-to-beat phenomenon. Two transseptal transition patterns were identified: 1) sudden, which is typical for obtaining LBBP; and 2) gradual, which is typical for obtaining LVSP. A sudden COI drop, a very observable phenomenon, also identified reaching the left subendocardial area.
- MeSH
- Bundle-Branch Block physiopathology therapy MeSH
- Electrocardiography * MeSH
- Bundle of His physiopathology MeSH
- Cardiac Pacing, Artificial methods MeSH
- Pacemaker, Artificial MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Septum physiopathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
V současné době nejsou známa rozmezí normálních hodnot QT intervalu pro konkrétní věkové skupiny v dětství a pubertě. V rámci tohoto projektu budou u dětí a adolescentů provedeny kontinuální 12-svodové elektrokardiografické záznamy v průběhu standardizovaných posturálních autonomních provokačních testů. V těchto záznamech bude provedena analýza již dříve ověřeného souboru ukazatelů a charakteristik morfologie a heterogenity repolarizace. Tak budou stanoveny věkově a pohlavně specifické normy pro QT/RR závislost a související korekční matematické vzorce s cílem zpřesnění časné diagnózy abnormalit QT intervalu a dalších souvisejících repolarizačních patologií.; Presently, sex-specific normality limits of QT interval are not known for different age-groups of children and adolescents. In this project continuous, 12-lead electrocardiographic monitoring will be performed in children and adolescents during standardised postural autonomic provocations. A previously verified battery of repolarization morphology indices and of repolarization heterogeneity characteristics will be investigated. The project will establish age- and sex-related normative QT/RR patterns and corresponding heart rate correction formulae to serve more accurate early diagnosis of QT interval abnormalities and of repolarization-related pathologies.
- Keywords
- děti, children, adolescenti, adolescents, repolarizace, pohlavně závislé rozdíly, QT interval, repolarization, sex-related differences, QT interval,
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
Celosvětově se vyskytující zoonotická onemocnění jako brucelóza zvyšují mortalitu na onemocnění srdce i výskyt maligních arytmií. Variabilita srdeční frekvence (heart rate variability, HRV) se měří neinvazivně se spolehlivým výsledkem. Nižší hodnoty HRV ukazují na autonomní dysfunkci. K detekci komorových arytmií se používají poměry intervalu Tp-e/QT (QT) a korigovaného QT (QTc). Cíl: U pacientů s brucelózou jsme zkoumali vztah mezi autonomní dysfunkcí a repolarizací komor (ventricular repolarization, VR). Hodnocení se provádělo neinvazivně měřením parametrů HRV a VR. Metody: Do studie bylo zařazeno 100 pacientů s brucelózou; jejich průměrný věk byl 39,2 ± 1,1 roku. Kontrolní skupinu srovnatelného věku a poměru obou pohlaví tvořilo 100 zdravých dobrovolníků průměrného věku 44,3 roku. Vypočítávali a zaznamenávali jsme hodnoty Tp-e, QT a QTc i poměr Tp-e/QTc stejně jako hodnoty HRV. Výsledky: Pacienti s brucelózou měli značně vyšší hodnoty QTmax , QTcmax , QTmin a QTcmin než kontroly. Poměry rozptylu hodnot Tp-e, cTp-e, Tp-e/QTc a Tp-e byly statisticky významně vyšší u pacientů s brucelózou než u kontrolních jedinců (80,2 ± 4,4 a 73,8 ± 5,4; p < 0,001, resp. 87,5 ± 6,2 a 82,6 ± 7,8; p = 0,001, 0,20 ± 0,01 a 0,21 ± 0,01; p = 0,004 a 29,4 ± 11,9 a 21,7 ± 10,2). U pacientů s brucelózou byly nalezeny vyšší poměry LF/ HF během dne a během noci (p < 0,001). Poměry LF/HF během dne a během noci příznivě korelovaly s hodnotami Tpe_cQT (r = 0,700; p < 0,001, resp. r = 0,746; p < 0,001). Závěry: Při elektrokardiografickém vyšetření měli pacienti s brucelózou delší intervaly Tp-e a vyšší poměry QT i QTc. U pacientů s brucelózou byly zjištěny jisté známky zvýšené HRV včetně poměru LF/HF. Byla prokázána příznivá korelace hodnot LF/HF a Tp-e/QTc. Brucelóza může působit subklinické postižení srdce a autonomní dysfunkci. Tito pacienti vyžadují důslednější screening komorových arytmií.
Background: Global zoonotic diseases like brucellosis increase cardiac mortality and malignant arrhythmias. Heart rate variability (HRV) measures heart rate non-invasively and reliably. Lower HRV suggests autonomic dysfunction. The Tp-e/QT interval (QT) and corrected QT (QTc) ratios are used to detect ventricular arrhyth- mogenesis. Objective: In brucellosis, we examined the relationship between autonomic dysfunction and ventricular repolarization (VR). This was done noninvasively by assessing HRV and VR parameters. Methods: One hundred patients with brucellosis had a mean age of 39.2±1.1 years. One hundred healthy volunteers with a mean age of 44.3 years made up the control group, which was age and sex matched. We calculated and recorded Tp-e, QT, QTc, and Tp-e/QTc, as well as HRV values. Results: Brucellosis patients had considerably greater QTmax, QTcmax, QTmin, and QTcmin than controls. Tp-e, cTp-e, Tp-e/QTc, and Tp-e dispersion ratios were significantly greater in brucellosis patients compared to the control group (80.2±4.4 and 73.8±5.4, p <0.001; 87.5±6.2 and 82.6±7.8, p = 0.001; 0.20±0.01 and 0.21±0.01, p = 0.004; 29.4±11.9 and 21.7±10.2. Patients with brucellosis had greater LF/HF ratios during daylight and overnight (p <0.001). Daytime and nighttime LF/HF ratios were favourably linked with Tpe_cQT (r = 0.700, p <0.001, and r = 0.746, p <0.001, respectively). Conclusions: On electrocardiography, brucellosis patients had longer Tp-e intervals, QT ratios, and QTc ratios. Brucellosis patients had increased HRV traits, including the LF/HF ratio. LF/HF and Tp-e/QTc correlated favourably. Brucellosis may cause subclinical cardiac engagement and autonomic dysfunction. These pa- tients need more ventricular arrhythmia screening.
- MeSH
- Brucellosis * complications MeSH
- Adult MeSH
- Electrocardiography methods MeSH
- Cardiovascular Diseases etiology MeSH
- Humans MeSH
- Autonomic Nervous System Diseases * etiology complications MeSH
- Arrhythmias, Cardiac etiology complications MeSH
- Heart Rate * MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
Kontext: Zátěžové vyšetření (exercise stress testing, EST) může u jedinců s Wolffovým–Parkinsonovým–Whiteovým (WPW) syndromem vést ke stanovení falešně pozitivní diagnózy infarktu myokardu (IM). Kazuistika: Třicetiletý pacient měl v anamnéze dva měsíce před vyšetřením palpitace a presynkopální stav. Skóre pravděpodobnosti před vyšetřením (pre-test probability, PTP) bylo 1 % a vstupní EKG záznam vykazoval typické znaky WPW syndromu. Dodatečně byla provedena stratifikace rizika formou EST s použitím Bruceova protokolu. V prekordiálních svodech byla při 4. stupni zátěže zaznamenána perzistentní komorová preexcitace (ventricular preexcitation, VPE) s ascendentní 3mm depresí úseku ST, přičemž svod aVR vykazoval 3mm elevaci úseku ST. Závěr: Pro odlišení IM od abnormální repolarizace u jedinců s WPW syndromem je naprosto zásadní znalost primárních abnormalit ST-T. Pro zjištění příčiny změn vlny ST-T je nezbytná nejdříve „identifikace“ pacienta na základě klinických charakteristik a skórování rizika podle PTP. U pacientů s nízkým rizikem a se zátěží vyvolanými změnami úseku ST v kontextu WPW syndromu je nutno uvažovat o falešně pozitivním výsledku vyšetření. Pro odlišení změn během EST v přítomnosti preexcitace je zapotřebí použít holistický přístup, při němž se berou v úvahu výsledky klinického vyšetření, skórování rizika PTP a znalost EKG charakteristik pacienta.
Background: Exercise stress testing (EST) can cause false-positive diagnoses of myocardial infarction (MI) in individuals with Wolff-Parkinson-White (WPW) syndrome. Case: A 30-year-old male had a history of palpitation and near syncope 2 months before examination. The pre-test probability (PTP) score was 1% and baseline ECG showed typical features of WPW syndrome. Additionally, risk stratification was performed with EST using the Bruce protocol. Persistent ventricular preexcitation (VPE) with upsloping 3.0 mm ST-segment depression was found in precordial leads at the fourth stage, while the aVR lead showed a 3.0 mm ST-segment elevation. Conclusion: Understanding the primary ST-T abnormalities was essential to differentiate MI from abnormal repolarization in individuals with WPW syndrome. Initial identification based on clinical characteristics and PTP risk scoring is crucial for distinguishing the cause of ST-T wave changes. Low-risk patients with exercise- -induced ST changes in the context of WPW syndrome should be considered to have received a false-positive exercise test result. A holistic method by clinical investigation, PTP risk scoring, and the identification of ECG characteristics are needed to distinguish the changes during EST in the presence of preexcitation.
- MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Electrocardiography methods MeSH
- Myocardial Infarction diagnostic imaging MeSH
- Cardiovascular Abnormalities physiopathology prevention & control MeSH
- Humans MeSH
- Pre-Excitation Syndromes diagnostic imaging diagnosis MeSH
- Wolff-Parkinson-White Syndrome * diagnostic imaging diagnosis MeSH
- Exercise Test * methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
Rozdíl os komplexu QRS a vlny T (frontal QRS-T angle, fQRSTa) je elektrokardiografický parametr odrážející prostorový vztah mezi vektory depolarizace a repolarizace v srdci; určují jej úhly mezi vektory QRS a vlnou T ve frontální rovině. Širší fQRSTa je obecně spojován se zvýšenou komorovou ektopickou aktivitou, poruchou funkce levé komory a zvýšeným rizikem kardiovaskulárních onemocnění (KVO); podle několika studií je širší QRSTa spojen se zvýšeným rizikem rozvoje KVO včetně infarktu myokardu, srdečního selhání a náhlé srdeční smrti. Celkově lze z dostupných důkazů usuzovat, že fQRSTa je užitečný marker kardiovaskulárního rizika a může mít značný význam pro prevenci a léčbu KVO. Poznání vztahu mezi QRSTa a KVO si nicméně vyžádá další výzkum, který zároveň pomůže stanovit optimální využití tohoto ukazatele v klinické praxi.
The frontal QRS-T angle is an electrocardiographic measurement that reflects the spatial relationship between the depolarization and repolarization vectors in the heart. It is determined by the angles between the QRS and T wave vectors in the frontal plane. A wider QRS-T angle is associated with increased ventricular ectopic activity, impaired left ventricular function, and increased risk of cardiovascular diseases (CVDs). Several studies have suggested that a wider frontal QRS-T angle is associated with an increased risk of developing CVDs, including myocardial infarction, heart failure, and sudden cardiac death. Overall, the evidence suggests that the frontal QRS-T angle is a useful marker of CV risk and may have important clinical implications for the prevention and management of CVDs. However, further research is needed to fully understand the relationship between the QRS-T angle and CVD, and to determine the optimal use of this marker in clinical practice.
- Keywords
- Úhel QRS-T,
- MeSH
- Diagnostic Techniques, Cardiovascular MeSH
- Electrocardiography * methods MeSH
- Cardiovascular Diseases diagnostic imaging etiology MeSH
- Humans MeSH
- Death, Sudden, Cardiac etiology prevention & control MeSH
- Heart physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH