Search Results (45)

In this study, we have performed 3D numerical simulations of the excitation and contraction of thin slab-like samples of myocardium tissue. The samples included a narrow region of almost non-excitable tissue simulating impaired myocardium. In the numerical experiments, we considered the heterogeneity of myocardium excitation and the ${\mathrm{Ca}}^{2+}$ activation of its contraction, as well as the orientation of the muscle fibers. Those characteristics varied throughout the thin wall of the sample. The simulations were performed in our numerical framework for the problems of cardiac electromechanics developed recently. The framework was previously tested for the benchmark problems in which formulations took into account only myocardium electrophysiology and passive mechanics. The study could be considered as an approbation of the framework performance with the fully coupled mathematical model of myocardium electromechanics. Here we dealt with the problems requiring a multiscale approach, taking into account cell-level electrophysiology, cell-level mechano-chemical processes, macromechanics (strain and stress) of the 3D sample, and interconnections between the levels. It was shown how the tissue heterogeneity and its strain affected the propagation of excitation–contraction waves in the sample, including, in particular, the formation of spiral waves. Full article

Left atrial mechanical dysfunction is common in horses following the treatment of atrial fibrillation (AF). This study aimed to evaluate the use of an acoustic cardiography monitor (Audicor^®) in quantifying cardiac mechanical and hemodynamic function in horses with AF before and after treatment and to correlate these findings with echocardiographic measures. Twenty-eight horses with AF and successful transvenous electrical cardioversion were included. Audicor^® recordings with concomitant echocardiographic examinations were performed one day before, one day after, and two to seven days after cardioversion. Key variables measured by Audicor^® included electromechanical activating time (EMAT), heart rate-corrected EMATc, left ventricular systolic time (LVST), heart rate-corrected LVSTc, systolic dysfunction index (SDI), and intensity and persistence of the third and fourth heart sound (S3, S4). A repeated-measures ANOVA with Tukey’s test was used to compare these variables over time, and linear regression and Bland–Altman analyses were applied to assess associations with echocardiographic findings. Following conversion to sinus rhythm, there was a significant decrease in EMATc and LVSTc (p < 0.0001) and a significant increase in LVST (p = 0.0001), indicating improved ventricular systolic function, with strong agreement between Audicor^® snapshot and echocardiographic measures. However, S4 quantification did not show clinical value for assessing left atrial function after conversion. Full article

Background: Congenital long QT syndrome (LQTS) is a rare cardiac disorder caused by repolarization abnormalities in the myocardium that predisposes to ventricular arrhythmias and sudden cardiac death. Potassium channel-mediated LQT1 and LQT2 are the most common types of channelopathy. Recently, LQTS has been acknowledged as an electromechanical disease. Methods: A total of 87 genotyped LQT1/LQT2 patients underwent cardiac evaluation. A comparison between LQT1 and LQT2 electrical and mechanical parameters was performed. Results: LQT2 patients had worse electrical parameters at rest: a longer QTc interval (p = 0.007), a longer T_pe in lead V2 (p = 0.028) and in lead V5 (p < 0.001), and a higher T_pe/QT ratio in lead V2 (p = 0.011) and in lead V5 (p = 0.005). T_pe and T_pe/QT remained significantly higher in the LQT2 group after brisk standing. T_pe was longer in LQT2 patients compared with LQT1 patients during peak exercise (p = 0.007) and almost all recovery periods in lead V2 during EST. The mid-cavity myocardium mean radial contraction duration (CD) was longer in LQT2 patients (p = 0.02). LQT2 patients had a longer mean radial CD in mid-septal (p = 0.015), mid-inferior (p = 0.034), and mid-posterior (p = 0.044) segments. Conclusions: Potassium channel-mediated LQTS has different effects on cardiac electromechanics with a more pronounced impact on LQT2 patients. T_pe was more prominent in the LQT2 cohort, not only at rest and brisk standing but also during EST exercise and at recovery phases. The altered mean radial CD in the mid-cavity myocardium was also specific for LQT2 patients. Full article

Heart failure is a complex syndrome and our understanding and therapeutic approach relies mostly on its phenotypic presentation. Notably, the heart is characterized as the most energy-consuming organ, being both a producer and consumer, in order to satisfy multiple cardiac functions: ion exchange, electromechanical coordination, excitation–contraction coupling, etc. By obtaining further knowledge of the cardiac energy field, we can probably better characterize the basic pathophysiological events occurring in heart disease patients and understand the metabolic substance changes, the relationship between the alteration of energy production/consumption, and hence energetic deficiency not only in the heart as a whole but in every single cardiac territory, which will hopefully provide us with the opportunity to uncover the beginning of the heart failure process. In this respect, using (a) newer imaging techniques, (b) biomedicine, (c) nanotechnology, and (d) artificial intelligence, we can gain a deeper understanding of this complex syndrome. This, in turn, can lead to earlier and more effective therapeutic approaches, ultimately improving human health. To date, the scientific community has not given sufficient attention to the energetic starvation model. In our view, this review aims to encourage scientists and the medical community to conduct studies for a better understanding and treatment of this syndrome. Full article

Cardiac pacemakers are used for handling bradycardia, which is a cardiac rhythm of usually less than 60 beats per minute. Therapeutic dual-sensor pacemakers aim to preserve or restore the normal electromechanical activity of the cardiac muscle. In this article, a novel intelligent controller has been developed for implanted dual-sensor cardiac pacemakers. The developed controller is mainly based on intuitionistic fuzzy logic (IFL). The main advantage of the developed IFL controller is its ability to merge the qualitative expert knowledge of cardiologists in the proposed design of controlled pacemakers. Additionally, the implication of non-membership functions with the uncertainty term plays a key role in the developed fuzzy controller for improving the performance of a cardiac pacemaker over other fuzzy control schemes in previous studies. Moreover, the proposed pacemaker control system is efficient for managing all health-status conditions and constraints during the different daily activities of cardiac patients. Consequently, the healthcare of patients with implanted dual-sensor pacemakers can be efficiently improved intuitively. Full article

Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. The rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of the rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted, irrespective of CHA₂DS₂-VASc score in patients with a favorable bleeding profile; data on left appendage closure devices are still insufficient. Ventricular arrhythmias are also not uncommon, and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit. Full article

Mitral and aortic valve insufficiencies have been commonly reported in horses. The objective of this study was to establish the use of acoustic cardiography (Audicor^®) in horses with aortic (AI) or mitral valve insufficiency (MI). A total of 17 healthy horses, 18 horses with AI, and 28 horses with MI were prospectively included. None of the horses was in heart failure. Echocardiography and Audicor^® analyses were conducted. Electromechanical activating time (EMAT), rate-corrected EMATc, left ventricular systolic time (LVST), rate-corrected LVSTc, and intensity and persistence of the third and fourth heart sound (S3, S4) were reported by Audicor^®. Graphical analysis of the three-dimensional (3D) phonocardiogram served to visually detect murmurs. Audicor^® snapshot variables were compared between groups using one-way ANOVA followed by Tukey’s multiple-comparisons test. The association between Audicor^® snapshot variables and the corresponding echocardiographic variables was investigated by linear regression and Bland–Altman analyses. Heart murmurs were not displayed on Audicor^® phonocardiograms. No significant differences were found between Audicor^® variables obtained in clinically healthy horses and horses with valvular insufficiency. The Audicor^® device is unable to detect heart murmurs in horses. Audicor^® variables representing cardiac function are not markedly altered, and their association with corresponding echocardiographic variables is poor in horses with valvular insufficiency that are not in heart failure. Full article

The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has shown promise in preclinical models of myocardial infarction, but graft myocardium exhibits incomplete host–graft electromechanical integration and a propensity for pro-arrhythmic behavior. Perhaps contributing to this situation, hPSC-CM grafts show low expression of connexin 43 (Cx43), the major gap junction (GJ) protein, in ventricular myocardia. We hypothesized that Cx43 expression and function could be rescued by engineering Cx43 in hPSC-CMs with a series of phosphatase-resistant mutations at three casein kinase 1 phosphorylation sites (Cx43-S3E) that have been previously reported to stabilize Cx43 GJs and reduce arrhythmias in transgenic mice. However, contrary to our predictions, transgenic Cx43-S3E hPSC-CMs exhibited reduced Cx43 expression relative to wild-type cells, both at baseline and following ischemic challenge. Cx43-S3E hPSC-CMs showed correspondingly slower conduction velocities, increased automaticity, and differential expression of other connexin isoforms and various genes involved in cardiac excitation–contraction coupling. Cx43-S3E hPSC-CMs also had phosphorylation marks associated with Cx43 GJ internalization, a finding that may account for their impaired GJ localization. Taken collectively, our data indicate that the Cx43-S3E mutation behaves differently in hPSC-CMs than in adult mouse ventricular myocytes and that multiple biological factors likely need to be addressed synchronously to ensure proper Cx43 expression, localization, and function. Full article

Optimal heart function depends on perfect synchronization between electrical and mechanical activity. In this pilot study, we aimed to investigate the electromechanical activity of the heart in healthy cats and cats with cardiomyopathy with phonocardiography (PCG) synchronized to an electrocardiography (ECG) pilot device. We included 29 cats (12 healthy cats and 17 cats diagnosed with cardiomyopathy) and performed a clinical examination, PCG synchronized with ECG and echocardiography. We measured the following durations with the pilot PCG device synchronized with ECG: QRS (ventricular depolarization), QT interval (electrical systole), QS1 interval (electromechanical activation time (EMAT)), S1S2 (mechanical systole), QS2 interval (electrical and mechanical systole) and electromechanical window (end of T wave to the beginning of S2). The measured parameters did not differ between healthy cats and cats with cardiomyopathy; however, in cats with cardiomyopathy, EMAT/RR, QS2/RR and S1S2/RR were significantly longer than in healthy cats. This suggests that the hypertrophied myocardium takes longer to generate sufficient pressure to close the mitral valve and that electrical systole, i.e., depolarization and repolarization, and mechanical systoles are longer in cats with cardiomyopathy. The PCG synchronized with the ECG pilot device proved to be a valuable tool for evaluating the electromechanical activity of the feline heart. Full article

As the mechanism for worse prognosis after cardiac resynchronization therapy (CRT) upgrades in heart failure patients with RVP dependence (RVP-HF) has clinical implications for patient selection and CRT implementation approaches, this study’s objective was to evaluate prognostic implications of cardiac magnetic resonance (CMR) findings and clinical factors in 102 HF patients (23.5% female, median age 66.5 years old, median follow-up 4.8 years) with and without RVP dependence undergoing upgrade and de novo CRT implants. Compared with other CRT groups, RVP-HF patients had decreased survival (p = 0.02), more anterior late-activated LV pacing sites (p = 0.002) by CMR, more atrial fibrillation (p = 0.0006), and higher creatinine (0.002). CMR activation timing at the LV pacing site predicted post-CRT LV functional improvement (p < 0.05), and mechanical activation onset < 34 ms by CMR at the LVP site was associated with decreased post-CRT survival in a model with higher pre-CRT creatinine and B-type natriuretic peptide (AUC 0.89; p < 0.0001); however, only the higher pre-CRT creatinine partially mediated (37%) the decreased survival in RVP-HF patients. In conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF. Full article

Despite significant advancements in medical therapy, heart failure with reduced ejection fraction (HFrEF) continues to be a significant cause of death and disability. Reversible ischaemic left ventricular dysfunction due to viable myocardium is one such contributing factor. In these cases, coronary revascularization has shown promise in improving left ventricular function and prognosis. For patients with HFrEF and wide QRS, cardiac resynchronization therapy (CRT) is an effective option to address electromechanical dyssynchrony. However, approximately 30% of patients do not respond positively to CRT, highlighting the need to refine candidate selection for this treatment. In some patients with reduced HFrEF, there is a condition known as classical low-flow, low-gradient aortic stenosis (AS) that may be observed. This condition is characterized by a low transaortic flow, which leads to reductions in both the transaortic mean gradient and aortic valve area. Decision-making regarding revascularization, CRT, and pharmacological treatment play a crucial role in managing HFrEF. Cardiac imaging can be valuable in guiding decision-making processes and assessing the prognosis of patients with HFrEF. Among the imaging modalities, dobutamine stress echocardiography has come a long way in establishing itself as a feasible, safe, effective, relatively cheap non-invasive technique. The aim of this review is to explore the current literature on the utility of low-dose stress echocardiography in diagnosing and prognosticating patients with HFrEF. Full article

Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy. Full article

Background and objectives: Local anesthetic systemic toxicity (LAST) in children is extremely rare, occurring at an estimated rate of 0.76 cases per 10,000 procedures. However, among reported cases of LAST in the pediatric population, infants and neonates represent approximately 54% of reported LAST cases. We aim to present and discuss the clinical case of LAST with full clinical recovery due to accidental levobupivacaine intravenous infusion in a healthy 1.5-month-old patient, resulting in cardiac arrest necessitating resuscitation. Case presentation: A 4-kilogram, 1.5-month-old female infant, ASA I, presented to the hospital for elective herniorrhaphy surgery. Combined anesthesia was planned, involving general endotracheal and caudal anesthesia. After anesthesia induction, cardiovascular collapse was noticed, resulting in bradycardia and later cardiac arrest with EMD (Electromechanical Dissociation). It was noticed that during induction, levobupivacaine was accidentally infused intravenously. A local anesthetic was prepared for caudal anesthesia. LET (lipid emulsion therapy) was started immediately. Cardiopulmonary resuscitation was carried out according to the EMD algorithm, which lasted 12 min until spontaneous circulation was confirmed and the patient was transferred to the ICU. In ICU, the girl was extubated the second day, and the third day she was transferred to the regular pediatric unit. Finally, the patient was discharged home after a total of five days of hospitalization with full clinical recovery. A four-week follow-up has revealed that the patient recovered without any neurological or cardiac sequelae. Conclusions: The clinical presentation of LAST in children usually begins with cardiovascular symptoms because pediatric patients are already under general anesthesia when anesthetics are being used, as was the case in our case. Treatment and management of LAST involve cessation of local anesthetic infusion, stabilization of the airway, breathing, and hemodynamics, as well as lipid emulsion therapy. Early recognition of LAST as well as immediate CPR if needed and targeted treatment for LAST can lead to good outcomes. Full article

In cardiomyocytes, regular activity of the Na,K-ATPase (NKA) and its Na/K pump activity is essential for maintaining ion gradients, excitability, propagation of action potentials, electro-mechanical coupling, trans-membrane Na⁺ and Ca²⁺ gradients and, thus, contractility. The activity of NKA is impaired in ischemic heart disease and heart failure, which has been attributed to decreased expression of the NKA subunits. Decreased NKA activity leads to intracellular Na⁺ and Ca²⁺ overload, diastolic dysfunction and arrhythmias. One signal likely related to these events is hypoxia, where hypoxia-inducible factors (HIF) play a critical role in the adaptation of cells to low oxygen tension. HIF activity increases in ischemic heart, hypertension, heart failure and cardiac fibrosis; thus, it might contribute to the impaired function of NKA. This review will mainly focus on the regulation of NKA in ischemic heart disease in the context of stressed myocardium and the hypoxia–HIF axis and argue on possible consequences of treatment. Full article

Patients with chronic heart failure (HF) have a poor prognosis due to irreversible impairment of left ventricular function, with 5-year survival rates <60%. Despite advances in conventional medicines for HF, prognosis remains poor, and there is a need to improve treatment further. Cell-based therapies to restore the myocardium offer a pragmatic approach that provides hope for the treatment of HF. Although first-generation cell-based therapies using multipotent cells (bone marrow-derived mononuclear cells, mesenchymal stem cells, adipose-derived regenerative cells, and c-kit-positive cardiac cells) demonstrated safety in preclinical models of HF, poor engraftment rates, and a limited ability to form mature cardiomyocytes (CMs) and to couple electrically with existing CMs, meant that improvements in cardiac function in double-blind clinical trials were limited and largely attributable to paracrine effects. The next generation of stem cell therapies uses CMs derived from human embryonic stem cells or, increasingly, from human-induced pluripotent stem cells (hiPSCs). These cell therapies have shown the ability to engraft more successfully and improve electromechanical function of the heart in preclinical studies, including in non-human primates. Advances in cell culture and delivery techniques promise to further improve the engraftment and integration of hiPSC-derived CMs (hiPSC-CMs), while the use of metabolic selection to eliminate undifferentiated cells will help minimize the risk of teratomas. Clinical trials of allogeneic hiPSC-CMs in HF are now ongoing, providing hope for vast numbers of patients with few other options available. Full article