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Smartphone-based technology is increasingly used in veterinary medicine as a complementary tool for cardiac auscultation and ECG recording. This prospective observational study evaluates a digital stethoscope (DS) that consists of simultaneous phonocardiographic and one-lead ECG recording (dECG) in adult horses, comparing it with auscultation using a conventional stethoscope (CS) and reference base-apex ECG (rECG). A total of 104 horses underwent cardiac auscultation using CSs and DSs to detect arrhythmias and murmurs. Audio and dECG were acquired using the DS. The rECG tracings were also recorded. All ECG tracings were blindly evaluated for interpretability, measurements, and diagnosis. The Shapiro-Wilk test was used to assess the data distribution. Weighted Cohen's κ and Bland Altman plot analysis were applied to verify the agreement between reference vs. smartphone-based methods. Almost perfect agreement was found in detecting murmurs and/or arrhythmias between auscultation with the CS and DS, and between CS auscultation and re-listening to DS audio. Perfect agreement was observed between re-listening to DS audio and DS auscultation and in detecting murmur timing between CS and DS auscultation. Almost perfect agreement was found between rECG and dECG in detecting bradycardia, tachycardia, or normal heart rate (HR) and for P-wave polarity. The lack of variability with both methods for QRS polarity prevented statistical analyses from being performed. Fair agreement was found in the assessment of the presence of artifact. In conclusion, the DS reliably detected heart murmurs and arrhythmias through direct auscultation and re-listening to recordings, and accurately evaluated HR, wave and interval measurements, P-wave and QRS-complex polarities in adult horses., Competing Interests: Declarations. Ethics approval: The experiments were conducted following the Guide for the Care and Use of Animals in Research and Teaching, after the approval of the Ethic Committee of the University of Pisa (OPBA n. 53/2020). Consent to participate: All authors consent to participation in this publication. Consent to publish: All authors consent to publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background- Subclinical electrophysiological derangements occur at birth in foals. Smartphone-based ECG (spECG) is practical tools to assess heart rhythm and was recently validated in foals. Objectives-To assess the heart rate (HR) and rhythm at birth in clinically healthy foals born after spontaneous and induced parturition using a spECG. Animals- Newborn healthy foals born after at term spontaneous (SF) or induced foaling (IF). Methods- Cohort study. In SF and IF groups, a spECG was performed immediately at birth (T0) and after 5 min (T5). SpECG tracings were selected for quality. HR was manually calculated and was compared between groups and time-points. Tracings were manually interpreted for rhythm diagnosis. Results- Eighty-one spECG tracings owing to 42 healthy foals (36 SF, 6 IF) were of adequate quality. There were no significant differences in HR between SF and IF and between T0 and T5 (p > 0.05). Six foals were diagnosed with atrial fibrillation and 4 with sinus arrhythmia. Conclusions and clinical importance- The spECG was feasible and detected subclinical arrhythmias at birth. A potential relationship with induced foaling warrants confirmation. Provided good quality tracing is obtained, the device might assist in the clinical assessment at birth, especially in screening high-risk foals., Competing Interests: Declarations. Ethics approval: The experiments were conducted following the Guide for the Care and Use of Animals in Research and Teaching, after the approval of the Ethic Committee of the University of Pisa (OPBA #45865/2016). Consent of participation: Informed consent was obtained from all the owners of individual animals included in the study. Consent for publication: All authors consent to publish the manuscript. Conflict of interest: The authors declare that there is no conflict of interest. None of the authors had a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Electrocardiograms (ECG) are an important source of information on human heart health and are widely used to detect different types of arrhythmias., Objective: With the advancement of deep learning, end-to-end ECG classification models based on neural networks have been developed. However, deeper network layers lead to gradient vanishing. Moreover, different channels and periods of an ECG signal hold varying significance for identifying different types of ECG abnormalities., Methods: To solve these two problems, an ECG classification method based on a residual attention neural network is proposed in this paper. The residual network (ResNet) is used to solve the gradient vanishing problem. Moreover, it has fewer model parameters, and its structure is simpler. An attention mechanism is added to focus on key information, integrate channel features, and improve voting methods to alleviate the problem of data imbalance., Results: Experiments and verifications are conducted using the PhysioNet/CinC Challenge 2017 dataset. The average F1 value is 0.817, which is 0.064 higher than that for the ResNet model. Compared with the mainstream methods, the performance is excellent., Competing Interests: Declarations. Conflict of interest: The authors of this article declare no potential conflicts of interest. Informed Consent: The authors declare that informed consent was obtained from all patients involved in the study., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Brugada syndrome (BrS) is associated with abnormal electrophysiological properties at right ventricular epicardium, consisting of fragmented electrograms extending well beyond QRS termination. We aimed to evaluate the utility of signal-averaged electrocardiogram (SA-ECG) for the noninvasive assessment of late potentials (LP) and risk stratification of BrS patients., Methods: A prospective, observational, single-center study of BrS patients is submitted to SA-ECG with the determination of the total filtered QRS duration (fQRS), root mean square voltage of the 40 ms terminal portion of the QRS (RMS40), and duration of the low-amplitude electric potential component of the terminal portion of the QRS (LAS40). LP were considered positive when above standard cut-offs: fQRS > 114 ms, RMS40 < 20 µV, and LAS40 > 38 ms. The rates of malignant arrhythmic events (MAEs), defined as sudden death or appropriate shocks, were compared in relation to clinical characteristics and SA-ECG findings., Results: A total of 106 BrS patients (mean age, 48 ± 12 years, 67.9% male) were studied, 49% with type-1 spontaneous pattern and 81% asymptomatic. During a median follow up of 4.7 years, 10 patients (7.1%) suffered MAEs, including 4 sudden deaths. The presence of LP was significantly associated with the arrhythmic risk, which increased with the number of altered LP criteria. In comparison to the patients who had none or 1 altered LP criterium, MAE risk was 4.7 times higher in those with 2 altered criteria and 9.4 times higher in those with 3 altered LP criteria., Conclusions: SA-ECG may be a useful tool for risk stratification in BrS. The presence of 2 or 3 abnormal LP criteria could identify a subset of asymptomatic patients at high risk of arrhythmic events., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study introduces two models, ConvLSTM2D-liquid time-constant network (CLTC) and ConvLSTM2D-closed-form continuous-time neural network (CCfC), designed for abnormality identification using electrocardiogram (ECG) data. Trained on the Telehealth Network of Minas Gerais (TNMG) subset dataset, both models were evaluated for their performance, generalizability capacity, and resilience. They demonstrated comparable results in terms of F1 scores and AUROC values. The CCfC model achieved slightly higher accuracy, while the CLTC model showed better handling of empty channels. Remarkably, the models were successfully deployed on a resource-constrained microcontroller, proving their suitability for edge device applications. Generalization capabilities were confirmed through the evaluation on the China Physiological Signal Challenge 2018 (CPSC) dataset. The models' efficient resource utilization, occupying 70.6% of memory and 9.4% of flash memory, makes them promising candidates for real-world healthcare applications. Overall, this research advances abnormality identification in ECG data, contributing to the progress of AI in healthcare., (© 2024. The Author(s).)

Arrhythmia detection is essential when assessing the safety of novel drugs and therapies in preclinical studies. Many short-term arrhythmia monitoring methods exist, including non-invasive ECG and Holter. However, there are no reliable, long-term, non-invasive, or minimally invasive methods for cardiac arrhythmia follow-up in large animals that allows free movement with littermates. A long follow-up time is needed when estimating the impact of long-lasting drugs or therapies, such as gene therapy. We evaluated the feasibility and performance of insertable cardiac monitors (ICMs) in pigs for minimally invasive, long-term monitoring of cardiac arrhythmias that allows free movement and species-specific behavior. Multiple implantation sites were tested to assess signal quality. ICMs recognized reliably many different arrhythmias but failed to detect single extrasystoles. They also over-diagnosed T-waves, resulting in oversensing. Muscle activity and natural startles of the animals caused noise, leading to a heterogeneous signal requiring post-recording evaluation. In spite of these shortcomings, the ICMs showed to be very useful for minimally invasive long-term monitoring of cardiac rhythm in pigs., (© 2024. The Author(s).)

Purpose: This study introduces an algorithm specifically designed for processing unprocessed 12-lead electrocardiogram (ECG) data, with the primary aim of detecting cardiac abnormalities., Methods: The proposed model integrates Diagonal State Space Sequence (S4D) model into its architecture, leveraging its effectiveness in capturing dynamics within time-series data. The S4D model is designed with stacked S4D layers for processing raw input data and a simplified decoder using a dense layer for predicting abnormality types. Experimental optimization determines the optimal number of S4D layers, striking a balance between computational efficiency and predictive performance. This comprehensive approach ensures the model's suitability for real-time processing on hardware devices with limited capabilities, offering a streamlined yet effective solution for heart monitoring., Results: Among the notable features of this algorithm is its strong resilience to noise, enabling the algorithm to achieve an average F1-score of 81.2% and an AUROC of 95.5% in generalization. The model underwent testing specifically on the lead II ECG signal, exhibiting consistent performance with an F1-score of 79.5% and an AUROC of 95.7%., Conclusion: It is characterized by the elimination of pre-processing features and the availability of a low-complexity architecture that makes it suitable for implementation on numerous computing devices because it is easily implementable. Consequently, this algorithm exhibits considerable potential for practical applications in analyzing real-world ECG data. This model can be placed on the cloud for diagnosis. The model was also tested on lead II of the ECG alone and has demonstrated promising results, supporting its potential for on-device application., (© 2024. The Author(s).)

Introduction: During an acute migraine attack, changes in ventricular repolarisation parameters may occur due to an imbalance in the autonomic nervous system. Tpeak-tend (Tp-e) interval, Tp-e/QT ratio, and Tp-e/corrected QT (QTc) ratio are novel parameters of arrhythmogenesis and can be easily calculated in electrocardiography (ECG). The objective of this study is to demonstrate that novel ventricular repolarisation parameters can anticipate the risk of ventricular dysrhythmia in the migraine attack period., Methods: This research was a prospective case-control study, which recruited a total of 144 participants, including 74 migraine patients and 70 healthy volunteers in the control group (CG) who met the criteria for migraine with or without aura. All participants underwent 12-lead ECG recordings, and the study compared the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio with those of the CG., Results: The average age of patients experiencing migraine attacks was 38.14 ± 10.82, with 58 (76%) of these patients being female. The Tp-e interval mean was higher in the migraine attack group than the CG, with a statistically significant difference discovered (74.22 ± 20.20 ms [ms] compared to 65.39 ± 11.33 ms, p = 0.001). However, there were higher mean Tp-e/QT and Tp-e/QTc ratios in the migraine attack group compared to the CG, and this difference was found to be statistically significant (0.20 ± 0.05 vs. 0.17 ± 0.03, p = 0.001, 0.18 ± 0.52 vs 0.16 ± 0.29, p = 0.003, respectively)., Conclusion: Prolonged Tp-e interval and elevated Tp-e/QT and Tp-e/QTc ratios were observed in migraine patients who presented to the emergency department, indicating a potential risk of ventricular dysrhythmia., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 μg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac function was evaluated by echocardiography and electrocardiography (ECG). Action potentials (AP) and Ca 2+ transients were evaluated at whole heart level. Heart mitochondrial function was evaluated by high-resolution respirometry and H 2 O 2 release. NOD mice presented a reduction in hearth weight. Mitochondrial oxygen fluxes and H 2 O 2 release were similar between NOD and NOR mice. ECG revealed a QJ interval prolongation in NOD mice. Furthermore, AP duration at 30% of repolarization was increased, and it depicted slower Ca 2+ transient kinetics. NOD mice presented greater number/severity of ventricular arrhythmias both in vivo and in vitro. In conclusion, NOD mice evoked cardiac electrical and calcium handling disturbances similar to the observed in T1D. Graphical Abstract .

Apamin-sensitive small-conductance calcium-activated potassium (SK) current (I KAS ) plays an important role in cardiac repolarization under a variety of physiological and pathological conditions. The regulation of cardiac I KAS relies on SK channel expression, intracellular Ca 2+ , and interaction between SK channel and intracellular Ca 2+ . I KAS activation participates in multiple types of arrhythmias, including atrial fibrillation, ventricular tachyarrhythmias, and automaticity and conduction abnormality. Recently, sex dimorphisms in autonomic control have been noticed in I KAS activation, resulting in sex-differentiated action potential morphology and arrhythmogenesis. This review provides an update on the Ca 2+ -dependent regulation of cardiac I KAS and the role of I KAS on arrhythmias, with a special focus on sex differences in I KAS activation. We propose that sex dimorphism in autonomic control of I KAS may play a role in J wave syndrome.

Purpose: Myocardial healing following myocardial infarction (MI) is a complex process that is yet to be fully understood. Clinical attempts in regeneration of the injured myocardium using cardiac stem cells faced major challenges, calling for a better understanding of the processes involved at a more basic level in order to foster translation., Procedures: We examined the feasibility of volumetric optoacoustic tomography (VOT) in studying healing of the myocardium in different models of MI, including permanent occlusion (PO) of the left coronary artery, temporary occlusion (ischemia-reperfusion-I/R) and infarcted c-kit mutants, a genetic mouse model with impaired cardiac healing. Murine hearts were imaged at 100 Hz frame rate using 800 nm excitation wavelength, corresponding to the peak absorption of indocyanine green (ICG) in plasma and the isosbestic point of haemoglobin., Results: The non-invasive real-time volumetric imaging capabilities of VOT have allowed the detection of significant variations in the pulmonary transit time (PTT), a parameter affected by MI, across different murine models. Upon intravenous injection of ICG, we were able to track alterations in cardiac perfusion in I/R models, which were absent in wild-type (wt) PO or kit W /kit W-v PO mice. The wt-PO and I/R models further exhibited irregularities in their cardiac cycles., Conclusions: Clear differences in the PTT, ICG perfusion and cardiac cycle patterns were identified between the different models and days post MI. Overall, the results highlight the unique capacity of VOT for multi-parametric characterization of morphological and functional changes in murine models of MI.

To investigate the role of classical (CLM, CD14 ++ CD16 - ), intermediate (INTM, CD14 ++ CD16 + ), and non-classical (Non-CLM, CD14 + CD16 ++ ) monocytes in scar formation after ST-elevation myocardial infarction (STEMI), evaluated with cardiac magnetic resonance (CMR). One hundred two patients with a first STEMI had serial blood analyses after 1, 3, and 7 days. A CMR was performed at 7 days and 6 months, depicting scar core (CO), border zone (BZ), and the presence of BZ channels. CLM and INTM levels progressively decreased, correlated with the scar mass, CO, and BZ at 7 days and 6 months (p < 0.05), and inversely with left ventricular ejection fraction (LVEF, p < 0.01). Non-CLM levels gradually increased, correlated with BZ mass and the presence of BZ channels at 7 days and 6 months (p < 0.001).CLM and INTM are associated with infarct size and inversely with LVEF, whereas Non-CLM are associated with BZ mass and the presence of potentially arrhythmogenic substrate.

Detection of QRS-complex in the electrocardiogram (ECG) plays a decisive role in cardiac disorder detection. We face many challenges in terms of powerline interference, baseline drift, and abnormal varying peaks. In this work, we propose an exploratory data analysis (EDA) based efficient QRS-complex detection technique with minimal computational load. This paper includes median and moving average filter for pre-processing of the ECG. The peak of filtered ECG is enhanced to third power of the signal. The root mean square (rms) of the signal is estimated for the decision making rule. This technique adapted the new concept for isoelectric line identification and EDA based QRS-complex detection. In this paper, total 10,70,981 beats were used for validation from MIT BIH-Arrhythmia Database (MIT-BIH), Fantasia Database (FDB), European ST-T database (ESTD), a self recorded dataset (SDB), and fetal ECG database (FTDB). Overall sensitivity of 99.65 % and positive predictivity rate of 99.84 % have been achieved. The proposed technique doesn't require selection, setting, and training for QRS-complex detection. Thus, this paper presents a QRS-complex detection technique based on simple decision rules.

There is a paucity of data comparing irrigated to non-irrigated catheters in the ablation of accessory pathways (AP) in adult patients. Retrospective analysis of first-time AP ablations performed at our institution from May 2010 to June 2017. A total of 69 AP ablations were studied; irrigated catheters were used in 78.3% cases. Mean age was 40.9 ± 14.3 years and 56.7% were male. Among APs, 63.8% were left sided and 56.5% were concealed. The total procedure time was 232.0 ± 89.0 min, ablation time was 3.1 ± 5.1 min, and fluoroscopy time was 13.9 ± 15.4 min. The overall acute success rate of ablation was 62/69 (89%). Success rates trended higher with irrigated catheters in both groups and were significant for the population as a whole (94.4% vs. 73.3%, p = 0.04). Analyzing the entire cohort, success rates were significantly higher in ablations using irrigated catheters.

Myocarditis is as an important cause of sudden cardiac death (SCD) among athletes. The incidence of SCD ascribed to myocarditis did not change after the introduction of pre-participation screening in Italy, due to the transient nature of the disease and problems in the differential diagnosis with the athlete's heart. The arrhythmic burden and the underlying mechanisms differ between the acute and chronic setting, depending on the relative impact of acute inflammation versus post-inflammatory myocardial fibrosis. In the acute phase, ventricular arrhythmias vary from isolated ventricular ectopic beats to complex tachycardias that can lead to SCD. Atrioventricular blocks are typical of specific forms of myocarditis, and supraventricular arrhythmias may be observed in case of atrial inflammation. Athletes with acute myocarditis should be temporarily restricted from physical exercise, until complete recovery. However, ventricular tachycardia may also occur in the chronic phase in the context of post-inflammatory myocardial scar.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a wide spectrum of clinical manifestations. Patients can be asymptomatic or suffer major adverse events including sudden cardiac death, ventricular arrhythmias, and heart failure. Identification of individuals with HCM who are at risk for these complications remains challenging. While echocardiography remains the mainstay of diagnostic evaluation, cardiac magnetic resonance imaging (CMR) is an important adjunctive diagnostic modality with emerging applications for risk-stratification of adverse events in the HCM population. Although not included in current guidelines for HCM management, there is increasing evidence to support the use of CMR for routine prognostic assessment of HCM patients. In this review we discuss the use of CMR techniques, including late gadolinium enhancement, T1 mapping, and quantification of extracellular volume fraction, for the risk stratification of three major adverse events in HCM: sudden cardiac death, ventricular arrhythmias, and congestive heart failure.

With improved screening and the advent of many novel therapeutics, patients with cancer are living longer and often surviving their disease. Cardiovascular complications have significant impact on both short- and long-term morbidity and mortality in these patients. While a great deal of attention has been paid to cardiomyopathy and heart failure, many other cardiotoxicities can occur, often at higher rates. Arrhythmias are a particularly common cardiovascular complication of cancer therapeutics and can range from benign to life threatening. Moreover, management of these rhythm disturbances can be challenging in cancer patients for various reasons including drug interactions, as well as underlying hematologic and metabolic disturbances. In this review, we describe the most common therapeutics associated with arrhythmias in cancer patients and provide a discussion about the potential basic and translational mechanisms leading to the development of the various rhythm disturbances which may help to guide prevention and treatment decisions. Clinicaltrials.gov Identifier: NCT02928497.

The understanding of cardiac arrhythmia under genetic mutations has grown in interest among researchers. Previous studies focused on the effect of the D172N mutation on electrophysiological behavior. In this study, we analyzed not only the electrophysiological activity but also the mechanical responses during normal sinus rhythm and reentry conditions by using computational modeling. We simulated four different ventricular conditions including normal case of ten Tusscher model 2006 (TTM), wild-type (WT), heterozygous (WT/D172N), and homozygous D172N mutation. The 2D simulation result (in wire-shaped mesh) showed the WT/D172N and D172N mutation shortened the action potential duration by 14%, and by 23%, respectively. The 3D electrophysiological simulation results showed that the electrical wavelength between TTM and WT conditions were identical. Under sinus rhythm condition, the WT/D172N and D172N reduced the pumping efficacy with a lower left ventricle (LV) and aortic pressures, stroke volume, ejection fraction, and cardiac output. Under the reentry conditions, the WT condition has a small probability of reentry. However, in the event of reentry, WT has shown the most severe condition. Furthermore, we found that the position of the rotor or the scroll wave substantially influenced the ventricular pumping efficacy during arrhythmia. If the rotor stays in the LV, it will cause very poor pumping performance. Graphical Abstract A model of a ventricular electromechanical system. This whole model was established to observe the effect of D172N KCNJ2 mutation on ventricular pumping behavior during sinus rhythm and reentry conditions. The model consists of two components; electrical component and mechanical component. The electrophysiological model based on ten Tusscher et al. with the IK1 D172N KCNJ2 mutation, and the myofilament dynamic (cross-bridge) model based on Rice et al. study. The 3D electrical component is a ventricular geometry based on MRI which composed of nodes representing single-cell with electrophysiological activation. The 3D ventricular mechanic is a finite element mesh composed of single-cells myofilament dynamic model. Both components were coupled with Ca2+ concentration. We used Gaussian points for the calcium interpolation from the electrical mesh to the mechanical mesh.

Late gadolinium enhancement (LGE) has an established prognostic value in otherwise normal hearts, when detected with a subepicardial or intramyocardial pattern; nevertheless, the clinical relevance of isolated right ventricular insertion point (RVIP) LGE is yet to be defined. From a retrospectively identified cohort of 2000 consecutive patients undergoing CMR, we selected 420 patients according to study's inclusion and exclusion criteria (270 males, mean age 38 ± 17 years) with apparently normal hearts: besides 36 patients with non-ischemic pattern LGE (other-LGE group), we found isolated RVIP-LGE in 44 patients and absence of LGE (no-LGE group) in 340 patients. Clinical follow-up was performed for a median of approximately 6 years. Primary composite endpoint included cardiac death, resuscitated cardiac arrest, and appropriate implantable cardiac defibrillator shock. Prevalence of cardiac events was significantly lower in RVIP-LGE than in the other-LGE group (p = 0.006). Kaplan Meier curve analysis demonstrated no significant differences between patients with RVIP-LGE and no-LGE for the primary endpoint. On contrast, patients with other-LGE had worse prognosis than those with RVIP-LGE or no-LGE (p < 0.0001). RVIP-LGE in subjects without additional evidence of cardiac damage does not convey worse prognosis when compared to subjects without LGE and it should not be considered a marker of disease. Its diagnostic and prognostic significance is to be considered irrelevant.

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the genetics underlying PPGLs and the recommendation for genetic testing of all patients with PPGL are emphasized. Finally, the newer imaging methods for evaluating of PPGLs are discussed and highlighted.

Available evidence suggests a pathogenetic role of sleep breathing disorders in both atrial and ventricular arrhythmias with non-negligible clinical implications. Scientific literature has reported convincing findings on the link between sleep breathing disorders and arrhythmias. The coexistence of these conditions should be appropriately managed because OSA treatment may reduce arrhythmia recurrence. This paper provides an overview of the main physiopathologic mechanisms underlying the association between sleep apnea and arrhythmias and discusses the impact of sleep apnea on arrhythmia management in clinical practice.

Evaluation of a new Windkessel model based pulse contour method (WKflow) to calculate stroke volume in patients undergoing intra-aortic balloon pumping (IABP). Preload changes were induced by vena cava occlusions (VCO) in twelve patients undergoing cardiac surgery to vary stroke volume (SV), which was measured by left ventricular conductance volume method (SVlv) and WKflow (SVwf). Twelve VCO series were carried out during IABP assist at a 1:2 ratio and seven VCO series were performed with IABP switched off. Additionally, SVwf was evaluated during nine episodes of severe arrhythmia. VCO's produced marked changes in SV over 10-20 beats. 198 paired data sets of SVlv and SVwf were obtained. Bland-Altman analysis for the difference between SVlv and SVwf during IABP in 1:2 mode showed a bias (accuracy) of 1.04 ± 3.99 ml, precision 10.9% and limits of agreement (LOA) of - 6.94 to 9.02 ml. Without IABP bias was 0.48 ± 4.36 ml, precision 11.6% and LOA of - 8.24 to 9.20 ml. After one thermodilution calibration of SVwf per patient, during IABP the accuracy improved to 0.14 ± 3.07 ml, precision to 8.3% and LOA to - 6.00 to + 6.28 ml. Without IABP the accuracy improved to 0.01 ± 2.71 ml, precision to 7.5% and LOA to - 5.41 to + 5.43 ml. Changes in SVlv and SVwf were directionally concordant in response to VCO's and during severe arrhythmia. (R 2  = 0.868). The SVwf and SVlv methods are interchangeable with respect to measuring absolute stroke volume as well as tracking changes in stroke volume. The precision of the non-calibrated WKflow method is about 10% which improved to 7.5% after one calibration per patient.

In cardiomyocytes, electrical activity is coupled to cellular contraction, thus exposing all proteins expressed in the sarcolemma to mechanical stress. The voltage-gated sodium channel Nav1.5 is the main contributor to the rising phase of the action potential in the heart. There is growing evidence that gating and kinetics of Nav1.5 are modulated by mechanical forces and pathogenic variants that affect mechanosensitivity have been linked to arrhythmias. Recently, the sodium channel β1 subunit has been described to stabilise gating against mechanical stress of Nav1.7 expressed in neurons. Here, we tested the effect of β1 and β3 subunits on mechanosensitivity of the cardiac Nav1.5. β1 amplifies stress-induced shifts of V 1/2 of steady-state fast inactivation to hyperpolarised potentials (ΔV 1/2 : 6.2 mV without and 10.7 mV with β1 co-expression). β3, on the other hand, almost doubles stress-induced speeding of time to sodium current transient peak (Δtime to peak at - 30 mV: 0.19 ms without and 0.37 ms with β3 co-expression). Our findings may indicate that in cardiomyocytes, the interdependence of electrical activity and contraction is used as a means of fine tuning cardiac sodium channel function, allowing quicker but more strongly inactivating sodium currents under conditions of increased mechanical stress. This regulation may help to shorten action potential duration during tachycardia, to prevent re-entry phenomena and thus arrhythmias.

Transcatheter aortic valve implantation has become an established procedure to treat severe aortic stenosis. Correct device sizing/positioning is crucial for optimal outcome. Lotus valve sizing is based upon multiple aortic root dimensions. Hence, it often occurs that two valve sizes can be selected. In this study, patient-specific computer simulation is adopted to evaluate the influence of Lotus size/position on paravalvular aortic regurgitation (AR) and conduction abnormalities, in patients with equivocal aortic root dimensions. First, simulation was performed in 62 patients to validate the model in terms of predicted AR and conduction abnormalities using postoperative echocardiographic, angiographic and ECG-based data. Then, two Lotus sizes were simulated at two positions in patients with equivocal aortic root dimensions. Large valve size and deep position were associated with higher contact pressure, while only large size, not position, significantly reduced the predicted AR. Despite general trends, simulations revealed that optimal device size/position is patient-specific.

We have shown previously that during myocardial ischemia/reperfusion (MI/R), toll-like receptor 2 (TLR2) signaling regulates connexin 43 (Cx43) subcellular localization and function and dampens arrhythmia formation. We aimed to identify sites capable of TLR2-dependent redox modification within Cx43. Post-ischemic TLR2 -/- or wild-type (WT) mouse hearts were analyzed by OxICAT. Cx43 was mutated to exclude redox modification and transfected into HL-1 cardiomyocytes (CM) that were challenged with a TLR2 agonist. We identified Cys260 of Cx43 to be susceptible to reversible oxidation MI/R; TLR2 -/- leads to reduced H 2 O 2 production in post-ischemic isolated mitochondria and subsequently reduced oxidation of Cx43 at Cys260. Cx43 was dephosphorylated in WT, while phosphorylation was preserved in TLR2 -/- . Mutation of Cx43 (C260A) and lentiviral transfection in HL-1 CM accelerated pacemaker activity and reduced activity after TLR2 ligand stimulation. We here provide evidence for TLR2-dependent reversible oxidation of Cx43 at Cys260, which led to decreased Cx43 phosphorylation and affected CM pacemaker frequency and intercellular communication.

Hypertrophic cardiomyopathy (HCM), characterized by unexplained left ventricular hypertrophy, is one of the most common heritable cardiovascular diseases. The myosin regulatory light chain (MYL2) mutation R58Q has been associated with severe cardiac hypertrophy and sudden cardiac death (SCD). Herein, we provide the first patient-specific, induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of MYL2-R58Q. The MYL2-R58Q iPSC-CMs were nearly 30% larger than control iPSC-CMs at day 60. The percentage of myofibrillar disarray and cells with irregular beating in MYL2-R58Q iPSC-CMs was significantly higher than that in control cells. MYL2-R58Q iPSC-CMs had significantly decreased peak ΔF/F0 of calcium transients and delayed decay time than controls. Additionally, the L-type Ca 2+ channel (LTCC) (I Ca,L ) density at 0 mV was reduced significantly by 45.3%. Overall, the MYL2-R58Q iPSC-CMs recapitulated the HCM phenotype by exhibiting hypertrophy, myofibrillar disarray, increased irregular beating, decreased [Ca 2+ ] i transients, and unexpectedly a nearly 50% reduction in LTCC peak current.

Objectives: The study sought to assess retrospectively the prognostic impact of left ventricular ejection fraction (LVEF) in patients with electrical storm (ES)., Background: Data regarding the prognostic impact of impaired LVEF in ES patients is rare., Methods: Consecutive patients presenting with ES from 2002 to 2016 were included retrospectively. Patients with LVEF ≤ 35% were compared to patients with LVEF > 35%. The primary prognostic endpoint was long-term all-cause mortality, and secondary endpoints were rates of in-hospital mortality, rehospitalization, major adverse cardiac events (MACE), and ES recurrences (ES-R) at long-term follow-up., Results: A total of 80 patients with ES were included at 2.5 years of follow-up. 69% of patients suffered from LVEF ≤ 35%. ES patients with LVEF ≤ 35% were associated with higher rates of the primary endpoint of all-cause mortality (53% versus 8%, log-rank p = 0.0001; HR 8.524; 95% CI 2.030-35.793, p = 0.003), as well as the secondary endpoints of MACE (53% versus 20%; log rank p = 0.011; HR 3.213, 95% CI 1.241-8.316, p = 0.016) and ES-R (35% versus 8%; log rank p = 0.019; HR 4.821, 95% CI 1.122-20.706, p = 0.034). Furthermore, ES patients with LVEF ≤ 35% showed higher rates of rehospitalization due to acute heart failure (24% versus 8%, statistical trend p = 0.096). Notably, ES patients with LVEF > 35% were associated with increased rates of rehospitalization due to ventricular tachycardia (36% versus 18%, statistical trend p = 0.083)., Conclusions: ES patients with LVEF ≤ 35% were associated with increased rates of all-cause mortality, MACE, ES-R and heart failure-related rehospitalization at long-term follow-up. This study evaluated retrospectively the prognostic impact of LVEF in patients with ES. LVEF ≤ 35% was associated with increased long-term all-cause mortality (53% versus 8%; HR 8.524; 95% CI 2.030-35.793, p = 0.003), MACE (53% versus 20%; HR 3.213, 95% CI 1.241-8.316, p = 0.016), and ES recurrences (35% versus 8%; HR 4.821, 95% CI 1.122-20.706, p = 0.034), while trends were observed for higher rates of heart-failure related rehospitalization (24% versus 8%, p = 0.096) and MACE (49% versus 28%; p = 0.081).

Left atrium (LA) size has an important role in determining prognosis and risk stratification in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel technique for the quantification of LA function. Our aim was first to evaluate LA function by CMR-FT and volumetric analysis in patients with HCM; and secondly we sought to determine the association of LA-longitudinal strain (LA-LS) with major cardiovascular outcomes, particularly all cause mortality and heart failure. 75 patients with HCM and 75 control subjects underwent a conventional CMR study including assessment of LA function by CMR-FT (LA-LS) and volumetric analysis. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Compared to controls, LA-LS and all volumetric indices of LA function were significantly impaired in HCM even in patients with normal LA volume and normal LV filling pressures. LA-LS showed moderate-high correlation with LA-emptying fraction (total, active and passive LA-EF, r = 0.68, r = 0.67, r = 0.31, p < 0.001 for all) and with parameters of diastolic function (E/é, r = 0.4, p < 0.001). The age, minimum LA volume and % of LGE were independent predictors of LA-LS (p < 0.01 for all). During a mean follow-up of 3.3 ± 1.2 years LA-LS was associated with the primary (HR: 0.85 (0.73-0.98), p = 0.02) and the secondary end-point (HR: 0.88 (0.82-0.96), p = 0.003). LA-LS by CMR-FT provides accurate measurements of LA function in HCM patients. LA-LS may become a novel potential predictor of poor cardiac outcomes, particularly cardiovascular mortality and HF.

Objectives: We explored relationships between biochemical markers and cardiac responses of children with and without obstructive sleep apnoea (OSA) during exercise. We hypothesised that serum markers of sympathetic nervous system activity and low-grade inflammation would correlate with cardiac responses to exercise in children with or without OSA., Methodology: The study included 40 of 71 children with previously characterised responses to cardiopulmonary exercise testing. Measures included serum cytokine levels using a multiplex bead-based assay (interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and IFN-γ). Serum amyloid A (SAA) was quantified by nephelometry, and metanephrine/normetanephrine levels were measured by liquid chromatography, mass-spectroscopy. Comparisons were made between children with and without OSA, and with and without obesity. Relationships between biomarkers and various cardiac parameters were explored by linear regression., Results: Amongst the 40 children in this study, OSA was present in 23. Compared to the 17 children without OSA, those with OSA had higher resting serum IL-6 levels compared to those without (median 3.22 pg/ml vs. 2.31, p < 0.05). Regarding correlations with cardiac function after adjusting for OSA, IL-8 negatively correlated to heart rate (HR) response following exercise (p = 0.03) and IFN-γ negatively correlated with Stroke Volume Index (SVI) (p = 0.03). Both metanephrine and normetanephrine levels positively correlated with SVI (p = 0.04, p = 0.047; respectively) and QI (p = 0.04, p = 0.04; respectively) during exercise when adjusting for OSA., Conclusions: Children with OSA have raised morning levels of serum IL-6. Separately, higher levels of IFN-γ and IL-8 and lower levels of metanephrine and normetanephrine related to poorer cardiac function during exercise.

To investigate the effectiveness and safety of using the Ensite NavX three-dimensional (3D) mapping system during Radiofrequency catheter ablation (RFCA) of left accessory pathway (AP) disorders. A total of 227 patients having their left AP treated by RFCA, were classified into study group (n = 112) and the control group (n = 115). X-ray irradiation time and exposure doses during the course of the operations were recorded. Time taken to place the mapping catheter along with total duration of operations and procedural complications were compared. The X-ray irradiation time and exposure doses in the course of manipulating the ablation catheters were significantly lower in the study group compared to control (5.1 ± 2.3 min vs. 13.1 ± 3.1 min; P < 0.05 and 5.7 ± 2.6 mGy vs. 17.8 ± 4.3 mGy; P < 0.05, respectively). The total duration of operation was also significantly shorter in the study group compared to control (53.1 ± 18.8 min vs. 62.3 ± 20.6 min; P < 0.05). No procedural complications were reported in both groups. The irradiation time and exposure dose along with total operation duration was significantly reduced when the Ensite NavX mapping system was used during RFCA in comparison with traditional X-ray fluoroscopy method.

Differential high-resolution ECG (V1-V2) and pelvic electric potential measured between the coccyx and perineum were recorded simultaneously in resting supine position in men with autonomic nervous system disorders (N=37). In healthy volunteers (N=23), the effective (rms) value of PEP presented by median and interdecile range was 30 (20-80) μV within the frequency band of 0.03-80 Hz. In patients, the corresponding value was significantly higher: 140 (80-280) μV. In both groups, the amplitude harmonic spectrum of pelvic electric potential decreased monotonically with frequency according to 1/f1.6 law. In some patients (N=16), rare single or grouped high-amplitude impulses (up to 1 mV) of pelvic electric potential with total duration of about 1 sec were observed; of them, some persons (N=7) demonstrated practically one-to-one synchronous relations between these impulses and arrhythmia episodes indicating abnormal activity of the autonomic nervous system as their most probable common cause. The high-amplitude pelvic electric potential impulses were also observed in ECG records as interference signals with an amplitude attaining 50 μV. Thus, high-resolution ECG and pelvic electric potential can reveal the risk of abnormal neurogenic influences on the heart. The data obtained are discussed in relation to diagnostics of the autonomic nervous system disorders, neurogenic arrhythmias, and risk of sudden cardiac death.

The aim of the study is to understand in depth the meaning of "reentry", and to decipher if and how it can lead to malfunctions of the heart and possibly of the brain. A simple model is used to reveal the mechanism by which a single pulse of action potential rotating around a ring of excitable medium, the latter simulating a reentry circuit, can generate spirals (single and/or double) when the pulse can emerge from and develop outside the ring. Two mechanisms of spiral generation are demonstrated: (1) a mechanism in which a source of single spirals is created at the contact with the core soon after the pulse freeing action, their chirality being due to the sense of the preceding pulse rotation. Interestingly, these spirals, adhering to the core, become "double-spiral patterns" while leaving behind the seeds of the new single spirals. (2) A second possible mechanism, similar to the known "arms encountering methods", in which a double spiral (a figure of eight) is repeatedly created on the other side of the core. Similar procedures are assumed to occur in the heart, leading to tachycardia and fibrillation and possibly in the brain leading to epilepsy. The exact processes of the hitherto assumed spiral generations by reentry were established. The novel deep understanding of the mechanisms involved in these processes can lead to new methods of treating heart fibrillation (e.g., by judicial ablation).

A new semi-supervised approach based on deep learning and active learning for classification of electrocardiogram signals (ECG) is proposed. The objective of the proposed work is to model a scientific method for classification of cardiac irregularities using electrocardiogram beats. The model follows the Association for the Advancement of medical instrumentation (AAMI) standards and consists of three phases. In phase I, feature representation of ECG is learnt using Gaussian-Bernoulli deep belief network followed by a linear support vector machine (SVM) training in the consecutive phase. It yields three deep models which are based on AAMI-defined classes, namely N, V, S, and F. In the last phase, a query generator is introduced to interact with the expert to label few beats to improve accuracy and sensitivity. The proposed approach depicts significant improvement in accuracy with minimal queries posed to the expert and fast online training as tested on the MIT-BIH Arrhythmia Database and the MIT-BIH Supra-ventricular Arrhythmia Database (SVDB). With 100 queries labeled by the expert in phase III, the method achieves an accuracy of 99.5% in "S" versus all classifications (SVEB) and 99.4% accuracy in "V " versus all classifications (VEB) on MIT-BIH Arrhythmia Database. In a similar manner, it is attributed that an accuracy of 97.5% for SVEB and 98.6% for VEB on SVDB database is achieved respectively. Graphical Abstract Reply- Deep belief network augmented by active learning for efficient prediction of arrhythmia.

The expression of Epac proteins (exchange protein directly activated by cAMP) and calmodulin (CaM) was assessed by the content of the corresponding mRNA in biopsy specimens of cardiac atrium, left ventricle, and thoracic aorta of rats with alcoholic cardiomyopathy. In the myocardium, overexpression of Еpac1, Ерас2, and СаМ mRNA was found. The content of Epac2 mRNA in the left ventricle was elevated by 2.9 times (p=0.000001), in the left atrium by 3.2 times (p=0.00001), in the right atrium by 3 times (p=0.00001). In contrast to the myocardial tissue, the content of CaM mRNA in the thoracic aorta was not increased, but showed a tendency to decrease, when compared to the control values, while the level of Epac1 and Epac2 mRNA was increased. The assumption is made that regulatory proteins Epac and CaM can play a key role in arrhythmogenesis development under conditions of alcoholic cardiomyopathy.

We studied anti-ischemic activity of n-tyrozol under conditions of repeated transient myocardial ischemia in rats caused by repeated (5×3 min) occlusion of the left coronary artery. n-Tyrozol administered intraperitoneally in a dose of 20 mg/kg daily over 4 days before the ischemia modeling (the last injection 15 min prior to the start of the experiment) produced a clear-cut anti-ischemic effect: it reduced ST elevation and promoted more complete recovery of ECG during reperfusion. During reperfusion periods, n-tyrozol significantly decreased the risk of ventricular fibrillation and shortened the duration of tachyarrhythmia episodes (ventricular tachycardia and fibrillation).

Using a translation model of alcoholic cardiomyopathy in rats we showed the presence of an additional abnormal excitation focus in the area of the pulmonary vein lacunae in the left atrium and enhanced heterogeneity of the atrium depolarization pattern. These changes can determine electric instability of the myocardium and induce malignant heart rhythm disturbances including, sudden cardiac death.

The basis and reliability for timely diagnosis of cardiovascular diseases depend on the robust and accurate detection of QRS complexes along with the fiducial points in the electrocardiogram (ECG) signal. Despite, the several QRS detection algorithms reported in the literature, the development of an efficient QRS detector remains a challenge in the clinical environment. Therefore, this article summarizes the performance analysis of various QRS detection techniques depending upon three assessment factors which include robustness to noise, computational load, and sensitivity validated on the benchmark MIT-BIH arrhythmia database. Moreover, the limitations of these algorithms are discussed and compared with the standard signal processing algorithms, followed by the future suggestions to develop a reliable and efficient QRS methodology. Further, the suggested method can be implemented on suitable hardware platforms to develop smart health monitoring systems for continuous and long-term ECG assessment for real-time applications.

There has always been an appreciation of the role of Purkinje fibers in the fast conduction of the normal cardiac impulse. Here, we briefly update our knowledge of this important set of cardiac cells. We discuss the anatomy of a Purkinje fiber strand, the importance of longitudinal conduction within a strand, circus movement within a strand, conduction, and excitability properties of Purkinjes. At the cell level, we discuss the important components of the ion channel makeup in the nonremodeled Purkinjes of healthy hearts. Finally, we discuss the role of the Purkinjes in forming the heritable arrhythmogenic substrates such as long QT, heritable conduction slowing, CPVT, sQT, and Brugada syndromes.

Arrhythmia-induced beat-to-beat variability of blood pressure (BP) is deemed to hinder the reliability of non-invasive oscillometric measurements (NIBP) but few data support this belief. We assessed the impact of arrhythmia on a NIBP device never tested for this purpose. We compared, in intensive care unit patients with and without arrhythmia, the agreement between three pairs of NIBP (Infinity™ Delta monitor, Dräger medical systems) and invasive readings. For systolic, diastolic and mean BP, the mean bias between NIBP and invasive measurements was not higher, in 89 patients with arrhythmia, than that observed in 127 patients with regular rhythm (p = 0.93 for mean BP). Averaging three measurements overcame the higher within-subject variability of NIBP measurements during arrhythmia, and yielded similar agreement between the two techniques in patients with arrhythmia and with regular rhythm. The international organization for standardization criteria (mean bias < 5 and SD < 8 mmHg) were satisfied neither during arrhythmia nor during regular rhythm: for mean BP, mean bias of - 8.0 ± 6.5 and - 7.5 ± 6.1 mmHg, respectively. The detection of hypotension (systolic invasive BP < 90 mmHg or mean invasive BP < 65 mmHg) or hypertension (systolic invasive BP > 140 mmHg) by NIBP was similar during arrhythmia and regular rhythm [areas under the receiver operating characteristic curves (AUC ROC ) of 0.88-0.92, p > 0.13]. The detection of a 10% increase in mean invasive BP after cardiovascular intervention was also associated with similar AUC ROC s between the two groups. Provided that triplicates are averaged, the agreement between NIBP measured with the tested device and invasive measurements was not worse during arrhythmia than during regular rhythm.

The effects of therapeutic or preventive-therapeutic administration of water-soluble echinochrome analog U-441 on arrhythmia severity assessed by a set of myocardial spatio-temporal depolarization and repolarization parameters were examined on the model of acute myocardial ischemia in cats. Coronary occlusion increased activation time and decreased repolarization time in the ischemic zone; in addition, it increased both global and borderline (local) dispersions of repolarization. The linear regression model showed that only activation time values measured at the initial state and at termination of occlusion were associated with total arrhythmia score during ischemia (regression coefficient β=0.338, 95%CI=0.074-0.602, p=0.015 and β=0.720, 95%CI=0.323-1.117, p=0.001, respectively). The study revealed no association between administration of echinochrome analog U-441 and arrhythmia severity.

Ventricular arrhythmias (VA) are a recognized concern in dogs with degenerative mitral valve disease (DMVD). The coupling interval (CI) and the prematurity index (PI) have been shown to accurately differentiate between benign and malignant VA in people, where ventricular arrhythmias are known to be associated with an increased risk of development of signs of heart failure or sudden death. In this study, we characterized ventricular arrhythmias in dogs with symptomatic and asymptomatic DMVD. Seventy dogs with naturally-occurring DMVD and ventricular arrhythmias were retrospectively studied. A cross-sectional investigation including dogs with either symptomatic (stages C/D; n = 41) or asymptomatic (stages B1/B2; n = 29) DMVD was performed. Electrocardiographic tracings were reviewed to calculate both the CI and PI. In eight dogs these indices were compared with those obtained from both a Holter recording and a standard ECG tracing and no statistical differences were found (CI, p = 0.97; PI, p = 0.17). Even though CI and PI were determined in all animals enrolled in the study, VPC characteristics were only compared between symptomatic and asymptomatic dogs when a 24-h Holter recording was available (n = 49). The PI was different (p = 0.01) between symptomatic (0.65 ± 0.17) and asymptomatic (0.56 ± 0.18) dogs, but CI was considered similar (p = 0.91). Also, the symptomatic dogs had more polymorphic VPC (p = 0.002) and supraventricular arrhythmias (p = 0.0002) than the asymptomatic animals. Polymorphism, and repeating patterns of ventricular premature complexes, were characteristics frequently present in overtly symptomatic animals affected by mitral endocardiosis.

Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF, MIF, and GTFβ on the structure and metabolism of conduction cardiomyocytes was assessed in the control and under acute experimental aortic stenosis. After systemic administration of the cytokine complex in the control, structural abnormalities were revealed in a relatively low number of conduction cardiomyocytes; their relative number increased in the left ventricle and interventricular septum. When the complex was administered against the background of aortic stenosis, morphological changes in the conduction system were seen in a significant number of cells with their plasma imbibition, especially in the left ventricle and interventricular septum. Systemic administration of the natural cytokine complex inhibited the major metabolic processes in the conduction system, both in the control and under conditions of sharply increased hemodynamic load. In conduction cardiomyocytes, deceleration of glycolysis and citric acid cycle, inhibition of oxidation of free fatty acids and their metabolites, and suppression of shuttle mechanisms and biosynthetic reactions were observed. Increased blood levels of cytokines, primarily of the proinflammatory ones, can cause structural and metabolic disturbances in the cardiac conduction system and promote the development of arrhythmias, especially in case of sharply increased hemodynamic load.

Late sodium current (I NaL ) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak I Na . The endogenous I NaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced I Na,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure. It may there play important roles in arrhythmogenesis and mechanical dysfunction. Experimental and clinical research suggests that I NaL inhibition may prevent and treat cardiac arrhythmias and improve ventricular pump function. Selective I Na,L inhibitors, exemplified by ranolazine, GS-967 and GS-458967 have little or no effect on peak sodium current and/or I Kr , and carry no or minimal pro-arrhythmic risk compared to those associated with administration of classical class I or III antiarrhythmic drugs, particularly in patients with ischemic heart disease. This increased understanding of I NaL may be encouraging to clinicians in use of I NaL inhibitors to treat cardiac arrhythmias and mechanical dysfunction directly associated with enhanced I NaL such as LQTS type 3, and myocardial ischemia. This review discusses the roles of endogenous and enhanced I NaL in arrhythmogenesis and mechanical dysfunction, and the basic and clinical research of I NaL inhibitors.

We review the utilization of magnetic resonance imaging methods for classifying atrial tissue properties that act as a substrate for common cardiac arrhythmias, such as atrial fibrillation. We then review state-of-the-art methods for mapping this substrate as a predicate for treatment, as well as methods used to ablate the electrical pathways that cause arrhythmia and restore patients to sinus rhythm.

A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β -/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β -/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β -/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt) max and latency), recovery (action potential duration (APD 90 ) and resting membrane potential (RMP) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt) max and increased AP latency values in the Pgc-1β -/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt) max and longer AP latencies, but indistinguishable APD 90 and RMPs in arrhythmic compared to those in non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β -/- and WT hearts showed similar limiting gradients. However, Pgc-1β -/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β -/- hearts. Pgc-1β -/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.

Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy that leads to severe clinical complications. This study is to investigate whether or not prolonged QTc is a good indicator for evaluating the severity of fibrosis and predicting the prognosis of LVNC, and if native T1 can be used to quantify the fibrosis. 32 LVNC patients and 14 healthy controls with matched age and sex were examined by CMR and ECG to acquire native T1, QTc interval, and ECG abnormalities. 18 LVNC patients had normal QTc and 14 LVNC patients had prolonged QTc. The mean native T1 value of the normal controls, normal QTc and prolonged QTc patients was 1096.0 ± 41.5, 1141.98 ± 45.46, and 1182.67 ± 42.02 ms, respectively. One-way ANVOA showed significant differences in native T1 among three groups (F = 14.9, p < 0.001). In LVNC patients, the QTc interval significantly correlated with LVEF (p = 0.003, r = 0.51) and native T1 values (p = 0.015, R = -0.47). This suggests that prolonged QTc is associated with more severe compacted myocardial fibrosis, more cardiac dysfunction, and a poorer prognosis in LVNC patients. Follow-up data showed significant differences in adverse events between patients with normal QTc and patients with prolonged QTc (p = 0.036). Prolonged QTc interval leads to more severe compacted myocardial fibrosis, poorer cardiac dysfunction, and poorer prognosis in LVNC patients.

Amongst the complications of diabetes is arrhythmia, the risk of which depends on multiple factors. This study was designed to investigate several factors, including the effects of ATP-sensitive potassium current, lateralized connexins, and gap junction uncoupling. ATP-sensitive potassium channel (I KATP ) opening is caused by ischemia, which can occur in diabetic or non-diabetic hearts. I KATP opening was simulated in this work to determine if the risk of ischemia-induced arrhythmias is affected by diabetes. Simulations were performed using healthy and diabetic models of rat and rabbit ventricle. Results showed that the diabetic rat model is less vulnerable to reentrant arrhythmia than the healthy rat model. The diabetic rabbit model was more vulnerable to reentrant arrhythmia than the healthy rabbit model. In both rabbit models, the vulnerability increased as the gap junctional coupling decreased. Opening of I KATP resulted in larger window of vulnerability. Conduction reserve was simulated based on 1D simulations for both rat and rabbit models. There was no difference between rat and rabbit conduction reserve. Our results showed that the simulation results are model-dependent, i.e., results from the rabbit model are similar to human clinical data, while the results from the rat model contradict human clinical observations, suggesting a significant species-dependence in arrhythmia vulnerability in the diabetic heart.

Purpose: During cardiac mapping, it is critical to discriminate signals related to cardiac conduction versus those due to mechanical interaction with other cardiac structures such as valves. We sought to define characteristics that could facilitate discrimination of valve artifact from cardiac conduction signals., Methods: Patients with structurally normal heart undergoing mapping for ventricular arrhythmias arising from the vicinity of the aortic valve between January 2013 and May 2015 were included. Potentials felt to reflect aortic valve opening (occurring at the end of the QRS after the local ventricular signal) were termed A1, and those felt to reflect valve closure were termed A2., Results: A total of 24 patients had mapping in the sinuses of Valsalva, and 10 (average age 40 + 15, 60% male) were found to have additional signals (A1 and/or A2) notable during mapping. In all patients, intervals between A1 and A2 shortened after ectopic beats and lengthened after compensatory pauses. These variations in the interval matched the change in systolic duration on Doppler echocardiography. Overdrive atrial pacing was performed in four patients, which demonstrated progressive shortening of intervals between A1 and A2. Pacing always revealed local capture without affecting A1 or A2. In the one patient in whom ablation was performed in these areas, there was no effect on A1 or A2, suggesting these signals represented artifact., Conclusions: Valve-related signals in the aortic sinuses are commonly seen and can be distinguished. The interval between A1 and A2 correlated with mechanical systole and varied in a physiologically predictable manner with heart rate changes.