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Minimally invasive approaches to address coronary artery disease, such as robotic coronary bypass grafting, are emerging in surgery and have been shown to be beneficial with a reduction in morbidity. The perioperative management of this subset of patients is crucial to the success of the operation as there are several preoperative and postoperative issues and considerations that need to be addressed. A meticulous preoperative workup with an extensive history, physical exam, and appropriate imaging are instrumental to ensure a successful operation. Protocolized postoperative care is also essential to garnish the most benefit from this minimally invasive approach. All of these factors, in conjunction with a heart team approach and surgeon experience, are imperative for the successful outcome of robotic coronary artery revascularization.

During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting a role for the circadian clock in temporal control of histone turnover and coordinated cardiomyocyte gene expression. We sought to elucidate roles for the master circadian transcription factor, Bmal1, in histone turnover, chromatin organization, and myocyte-specific gene expression and cell growth in the neonatal period. Bmal1 knockdown in neonatal rat ventricular myocytes decreased myocyte size, total cellular protein synthesis, and transcription of the fetal hypertrophic gene Nppb after treatment with serum or the α-adrenergic agonist phenylephrine. Depletion of Bmal1 decreased the expression of clock-controlled genes Per2 and Tcap, as well as Sik1, a Bmal1 target upregulated in adult versus embryonic hearts. Bmal1 knockdown impaired Per2 and Sik1 promoter accessibility as measured by micrococcal nuclease-quantitative PCR and impaired histone turnover as measured by metabolic labeling of acid-soluble chromatin fractions. Sik1 knockdown in turn decreased myocyte size, while simultaneously inhibiting natriuretic peptide B transcription and activating Per2 transcription. Linking these changes to chromatin remodeling, depletion of the replication-independent histone variant H3.3a inhibited myocyte hypertrophy and prevented phenylephrine-induced changes in clock-controlled gene transcription. Bmal1 is required for neonatal myocyte growth, replication-independent histone turnover, and chromatin organization at the Sik1 promoter. Sik1 represents a novel clock-controlled gene that coordinates myocyte growth with hypertrophic and clock-controlled gene transcription. Replication-independent histone turnover is required for transcriptional remodeling of clock-controlled genes in cardiac myocytes in response to growth stimuli.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/- drug treatment; +/- cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.

BackgroundChronic sympathetic stimulation drives desensitization and downregulation of β1 adrenergic receptor (β1AR) in heart failure. We aim to explore the differential downregulation subcellular pools of β1AR signaling in the heart.Methods and resultsWe applied chronic infusion of isoproterenol to induced cardiomyopathy in male C57BL/6J mice. We applied confocal and proximity ligation assay to examine β1AR association with L-type calcium channel, ryanodine receptor 2, and SERCA2a ((Sarco)endoplasmic reticulum calcium ATPase 2a) and Förster resonance energy transfer-based biosensors to probe subcellular β1AR-PKA (protein kinase A) signaling in ventricular myocytes. Chronic infusion of isoproterenol led to reduced β1AR protein levels, receptor association with L-type calcium channel and ryanodine receptor 2 measured by proximity ligation (puncta/cell, 29.65 saline versus 14.17 isoproterenol, P

The heart beats approximately 100,000 times per day in humans, imposing substantial energetic demands on cardiac muscle. Adenosine triphosphate (ATP) is an essential energy source for normal function of cardiac muscle during each beat, as it powers ion transport, intracellular Ca2+ handling, and actin-myosin cross-bridge cycling. Despite this, the impact of excitation-contraction coupling on the intracellular ATP concentration ([ATP]i) in myocytes is poorly understood. Here, we conducted real-time measurements of [ATP]i in ventricular myocytes using a genetically encoded ATP fluorescent reporter. Our data reveal rapid beat-to-beat variations in [ATP]i. Notably, diastolic [ATP]i was

BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM. RESULTS: In our study, Nexn global knockout mice and mice carrying human equivalent G645del mutation are studied using functional gene rescue assays. AAV-mediated gene delivery is conducted through systemic intravenous injections at the neonatal stage. Heart tissues are analyzed by immunoblots, and functions are assessed by echocardiography. Here, we identify functional components of Nexilin and demonstrate that exogenous introduction could rescue the cardiac function and extend the lifespan of Nexn knockout mouse models. Similar therapeutic effects are also obtained in G645del mice, providing a promising intervention for future clinical therapeutics. CONCLUSIONS: In summary, we demonstrated that a single injection of AAV-Nexn was capable to restore the functions of cardiomyocytes and extended the lifespan of Nexn knockout and G645del mice. Our study represented a long-term gene replacement therapy for DCM that potentially covers all forms of loss-of-function mutations in NEXN.

The Na+-Ca2+ exchanger (NCX1) is the dominant Ca2+ extrusion mechanism in cardiac myocytes. NCX1 activity is inhibited by intracellular Na+ via a process known as Na+-dependent inactivation. A central question is whether this inactivation plays a physiological role in heart function. Using CRISPR/Cas9, we inserted the K229Q mutation in the gene (Slc8a1) encoding for NCX1. This mutation removes the Na+-dependent inactivation while preserving transport properties and other allosteric regulations. NCX1 mRNA levels, protein expression, and protein localization are unchanged in K229Q male mice. However, they exhibit reduced left ventricular ejection fraction and fractional shortening, while displaying a prolonged QT interval. K229Q ventricular myocytes show enhanced NCX1 activity, resulting in action potential prolongation, higher incidence of aberrant action potentials, a faster decline of Ca2+ transients, and depressed cell shortening. The results demonstrate that NCX1 Na+-dependent inactivation plays an essential role in heart function by affecting both cardiac excitability and contractility.

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

BackgroundRecently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress.MethodsWe performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling.ResultsWe first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction.ConclusionsCollectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.

The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell-cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.

Cardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenates cardiac function and substantially reverses the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress. In vivo echocardiography reveals reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restores the nanoscale distribution and clustering plasticity of ryanodine receptors and recovers Ca2+ transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlates with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.

Cells interpret a variety of signals through G-protein-coupled receptors (GPCRs) and stimulate the generation of second messengers such as cyclic adenosine monophosphate (cAMP). A long-standing puzzle is deciphering how GPCRs elicit different physiological responses despite generating similar levels of cAMP. We previously showed that some GPCRs generate cAMP from both the plasma membrane and the Golgi apparatus. Here we demonstrate that cardiomyocytes distinguish between subcellular cAMP inputs to elicit different physiological outputs. We show that generating cAMP from the Golgi leads to the regulation of a specific protein kinase A (PKA) target that increases the rate of cardiomyocyte relaxation. In contrast, cAMP generation from the plasma membrane activates a different PKA target that increases contractile force. We further validated the physiological consequences of these observations in intact zebrafish and mice. Thus, we demonstrate that the same GPCR acting through the same second messenger regulates cardiac contraction and relaxation dependent on its subcellular location.

Background and Purpose Experimental Approach Key results Conclusion and Implications Adenosine receptor activation induces delayed, sustained cardioprotection against ischaemia–reperfusion (IR) injury (24–72 h), but the mechanisms underlying extended cardioprotection duration remain unresolved. We hypothesized that a positive feedback loop involving adenosine receptor‐induced proteasomal degradation of adenosine kinase (ADK) and decreased myocardial adenosine metabolism extends the duration of cardioprotection.Mice were administered an ADK inhibitor, ABT‐702, to induce endogenous adenosine signalling. Cardiac ADK protein and mRNA levels were analysed 24–120 h later. Theophylline or bortezomib was administered 24 h after ABT‐702 to examine the late roles of adenosine receptors or proteasomal activity, respectively, in ADK expression and cardioprotection at 72 h. Coronary flow and IR tolerance were analysed by Langendorff technique. The potential for continuous adenosinergic cardioprotection was examined using heterozygous, cardiac‐specific ADK KO (cADK+/−) mice. Cardiac ADK expression was also examined after A1 or A3 receptor agonist, phenylephrine, lipopolysaccharide or sildenafil administration.ABT‐702 treatment decreased ADK protein content and provided cardioprotection from 24 to 72 h. ADK mRNA upregulation restored ADK protein after 96–120 h. Adenosine receptor or proteasome inhibition at 24 h reversed ABT‐702‐induced ADK protein deficit and cardioprotection at 72 h. cADK+/− hearts exhibited continuous cardioprotection. Diverse preconditioning agents also diminished cardiac ADK protein expression.A positive feedback loop driven by adenosine receptor‐induced ADK degradation and renewed adenosine signalling extends the duration of cardioprotection by ABT‐702 and possibly other preconditioning agents. The therapeutic potential of continuous adenosinergic cardioprotection is demonstrated in cADK+/− hearts. [ABSTRACT FROM AUTHOR]

Background Aims Conclusions Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure.Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients.This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management. [ABSTRACT FROM AUTHOR]

Ischemic preconditioning (IPC) appears to improve exercise performance although there is uncertainty about the intensity dependence of this effect. The present study sought to clarify effects of IPC on physiological responses at and below peak oxygen uptake, including the gas exchange threshold (GET). Ten male and female participants completed five cycling ramp tests (10 W/min) to failure, with the final two tests preceded by either IPC (4 × 5 min 220 mmHg bilateral leg occlusions) or SHAM (20 mmHg), in a randomised crossover design. The rates of O2 uptake ( V ˙ O2), carbon dioxide output ( V ˙ CO2), and expired ventilation ( V ˙ E) were measured at rest and throughout exercise. Exercise data were fitted using several functions to identify GET, two ventilatory thresholds and peak V ˙ O2. IPC increased V ˙ O2 at GET by ~ 9% (IPC: 1.89 ± 0.51 L/min, SHAM: 1.73 ± 0.56 L/min; p = 0.055) and power output at GET by ~ 11% (IPC: 133 ± 36 W, SHAM: 120 ± 39 W; p = 0.022). In addition, peak power output increased by 2.4% following IPC (IPC: 217 ± 50 W, SHAM: 212 ± 51 W; p = 0.052), but there was no significant effect of IPC on peak V ˙ O2 (IPC: 2.87 ± 0.68 L/min, SHAM: 2.84 ± 0.73 L/min; p = 0.60) or the ventilatory thresholds. The present results suggest that IPC improves GET and peak power output but not peak V ˙ O2 during a maximal graded test. [ABSTRACT FROM AUTHOR]

To evaluate the effect of body position on transesophageal atrial pacing (TEAP) in dogs. Prospective, experimental trial. A total of eight mixed-breed dogs, median body mass 25 kg (range 11–31 kg). TEAP was performed using a 6 Fr (2 mm) pacing catheter introduced transorally and positioned in the lower esophagus in left lateral recumbency. The catheter was withdrawn in 5 mm increments until successful TEAP. The minimum pacing threshold (MPT) was determined at each 5 mm increment until atrial capture could not be achieved at a maximal pulse amplitude of 40 mA. The zone of capture (ZOC) was the total distance over which TEAP was achieved. The same process was repeated in right lateral, ventral and dorsal recumbency. A linear mixed model was used to assess the impact of body position on TEAP and ZOC. TEAP was achieved in all body positions. There was significant random effect of individual dogs on ZOC (p = 0.048) but not on MPT (p = 0.109). MPT was 11.56 ± 8.65 mA (mean ± SD), 8.43 ± 2.29 mA, 10.63 ± 6.91 mA and 10 ± 7.44 mA for dorsal, left and right lateral, and ventral recumbency, respectively. ZOC was 5.12 ± 2.08 cm, 6.35 ± 2.41 cm, 5.94 ± 3.23 cm and 5.31 ± 2.2 cm for dorsal, left lateral and right lateral, and ventral recumbency, respectively. Neither ZOC (p = 0.363) nor MPT (p = 0.716) varied significantly between body positions. TEAP can be performed successfully in all body positions in dogs. Body position did not significantly influence MPT or ZOC values for TEAP. Further studies are needed to compare the efficacy of TEAP with the efficacy of standard pharmacological therapy for management of bradycardia during general anesthesia in dogs. [ABSTRACT FROM AUTHOR]

Background: First‐pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first‐pass perfusion MRI in light‐chain (AL) amyloidosis requires further evaluation. Purpose: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. Study Type: Prospective observational study. Population: 226 biopsy‐proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). Field Strength/Sequence: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first‐pass myocardial perfusion imaging with a saturation recovery turbo fast low‐angle shot (SR‐TurboFLASH) pulse sequence at 3.0T. Assessment: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first‐pass perfusion MR images. Statistical Tests: Independent‐sample t test, Mann–Whitney U test, Chi‐square test, Fisher's exact test, analysis of variance, or Kruskal–Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan–Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. Results: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow‐up of 35 months, 160 patients (70.8%) demonstrated all‐cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021–1.102), biochemical (HR 1.055, CI: 1.014–1.097), cardiac MRI‐derived (HR 1.077, CI: 1.034–1.123), and therapeutic (HR 1.063, CI: 1.024–1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. Data Conclusion: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. Level of Evidence: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: The increasing incidence of heart failure (HF) in the elderly leads to increased mortality, hospitalization, length of hospital stay, and health care costs. Older adults often face multiple drug treatments, comorbidities, frailty, and cognitive problems, which require early palliative care. However, these patients do not receive adequate palliative care. Objective: This concept analysis aimed to develop an in-depth understanding of palliative care for elderly patients with cardiac diseases in tertiary care. Design: The analysis was guided by Walker and Avant's method, and databases were searched using keywords, such as palliative care, tertiary care, elderly, and heart. Covidence was used to review the results using the inclusion and exclusion criteria. Results: The World Health Organisation's definition of palliative care is widely accepted. Palliative care for older adults with heart disease in tertiary care is preceded by chronic illness, polypharmacy, symptom burden, physical and cognitive decline, comorbidities, and psychosocial/spiritual issues. The main attributes of palliative care for this population include health care professionals and patient education, holistic patient/family-centered care, symptom management, shared decision-making, early integration, advanced care planning, and a multidisciplinary approach. Palliative care improves elderly cardiac patients' and their family satisfaction while reducing readmission, hospital stays, and unnecessary invasive procedures. Conclusion: Collaboration between hospitals, community organizations, transitional palliative care services, and research has the potential to improve early palliative care and the well-being of the elderly cardiac population. Advanced Practice Nurses (APNs) competencies play a crucial role in promoting palliative care in the elderly HF population. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) can have profound and potentially life‐threatening consequences on horses' health and performance capability. While CHDs are rare in the general horse population, the Arabian breed is disproportionately overrepresented and thus is widely suspected to be genetically predisposed. This review discusses the most common CHDs in Arabian horses, including ventricular septal defect (VSD), tetralogy of Fallot (TOF), patent duct arteriosus (PDA), tricuspid valve atresia (TVA) and atrial septal defect (ASD). This review also explores how future research into the genetic factors that likely underpin many CHDs can revolutionise the way these disorders are managed in Arabian horses. [ABSTRACT FROM AUTHOR]

Explainable artificial intelligence (XAI) elucidates the decision-making process of complex AI models and is important in building trust in model predictions. XAI explanations themselves require evaluation as to accuracy and reasonableness and in the context of use of the underlying AI model. This review details the evaluation of XAI in cardiac AI applications and has found that, of the studies examined, 37% evaluated XAI quality using literature results, 11% used clinicians as domain-experts, 11% used proxies or statistical analysis, with the remaining 43% not assessing the XAI used at all. We aim to inspire additional studies within healthcare, urging researchers not only to apply XAI methods but to systematically assess the resulting explanations, as a step towards developing trustworthy and safe models. [ABSTRACT FROM AUTHOR]

AbstractBackgroundCase reportConclusionsCardiac myxoma is a rare, benign tumour that commonly originates in the left atrium and may lead to embolic events. Parenchymal brain metastases represent a rare neurological manifestation. While surgical intervention is commonly used, there is limited information on long-term outcomes after radiotherapy treatment. This report describes a case of successful treatment of haemorrhagic brain metastases with radiotherapy and offers a literature review of long-term results after radiotherapy treatment.A 49-year-old woman presented with multiple haemorrhagic brain lesions and a cardiac mass. Surgical removal of the cardiac mass and the symptomatic brain lesion confirmed metastatic cardiac myxoma. Post-surgery, she experienced fatigued and neurocognitive impairment and was closely monitored. However, the metastases progressed. She subsequently received whole-brain radiotherapy, resulting in complete response. Seven years later, she remains in remission, although with enduring neurocognitive impairment.Whole-brain radiotherapy can provide long-term control of haemorrhagic brain metastases arising from cardiac myxoma. Radiotherapy dose and treatment volume need careful consideration to reduce toxicity. [ABSTRACT FROM AUTHOR]

Background: Echocardiography can be used to screen, confirm, and assist in the management of some cardiovascular diseases in people living with human immunodeficiency virus (HIV) (PLWH). Thus, complications from subclinical cardiovascular conditions or more apparent conditions, such as massive pericardial effusion with tamponade, can be promptly identified and managed to minimize cardiovascular morbidity and mortality associated with HIV infection. Since the introduction of antiretroviral therapy (ART) in Ghana approximately two decades ago, studies on the prevalence and patterns of echocardiographic abnormalities among PLWH on ART have been limited. This study was designed to assess the prevalence and patterns of echocardiographic abnormalities among PLWH on ART. Methods: This was a cross-sectional study. PLWH on ART (cases) attending the HIV clinic at Komfo Anokye Teaching Hospital (KATH) and HIV-negative blood donors (controls) were consecutively recruited and enrolled in this study. The interviews were performed via a standardized questionnaire. After a clinical examination was performed, all patients underwent two-dimensional (2D) and Doppler transthoracic echocardiograms. The prevalence and patterns of echocardiographic abnormalities were characterized. Results: There were 117 patients in each arm of the study. There were more females than males among both the cases (92 (78.6%) and controls (80 (68.4%)); however, the sex distribution was similar between the two groups (p = 0.075). For clinical characteristics such as age, weight, height and blood pressure, there were no statistically significant differences between the cases and controls. Echocardiographic abnormalities were more frequently observed and demonstrated a statistically significant difference between cases and controls, with an overall prevalence of 35.0% among cases and 19.7% among controls (p = 0.008). The echocardiographic abnormalities that demonstrated significant differences between the cases and controls were left ventricular (LV) diastolic dysfunction (28.2% versus 8.6%; p = 0.000) and LV hypertrophy (7% versus 0.9%; p = 0.017). Conclusion: Nearly 1 in 3 PLWH on ART had an echocardiographic abnormality in this Ghanaian study. Echocardiograms are recommended as helpful screening modalities for diagnosing cardiac abnormalities among PLWH on ART. [ABSTRACT FROM AUTHOR]

Homeostatic regulation plays a fundamental role in maintenance of multicellular life. At different scales and in different biological systems, this principle allows a better understanding of biological organization. Consequently, a growing interest in studying cause-effect relations between physiological systems has emerged, such as in the fields of cardiovascular and cardiorespiratory regulations. For this, mathematical approaches such as Granger causality (GC) were applied to the field of cardiovascular physiology in the last 20 years, overcoming the limitations of previous approaches and offering new perspectives in understanding cardiac, vascular and respiratory homeostatic interactions. In clinical practice, continuous recording of clinical data of hospitalized patients or by telemetry has opened new applicability for these approaches with potential early diagnostic and prognostic information. In this review, we describe a theoretical background of approaches based on linear GC in time and frequency domains applied to detect couplings between time series of RR intervals, blood pressure and respiration. Interestingly, these tools help in understanding the contribution of homeostatic negative feedback and the anticipatory feedforward mechanisms in homeostatic cardiovascular and cardiorespiratory controls. We also describe experimental and clinical results based on these mathematical tools, consolidating previous experimental and clinical evidence on the coupling in cardiovascular and cardiorespiratory studies. Finally, we propose perspectives allowing to complete the understanding of these interactions between cardiovascular and cardiorespiratory systems, as well as the interplay between brain and cardiac, and vascular and respiratory systems, offering a high integrative view of cardiovascular and cardiorespiratory homeostatic regulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (IKr) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We aimed to investigate the dynamics of hERG channels in response to sotalol and to identify regulators of the susceptibility to developing diLQT. METHODS: We measured electrophysiological activity and cellular distribution of hERG channels after hERG blocker treatment in iPS-CMs derived from patients with highest sensitivity (HS) or lowest sensitivity (LS) to sotalol administration in vivo (ie, on the basis of the measure of the maximal change in QT interval 3 hours after administration). Specific small interfering RNAs and CAVIN1-T2A-GFP adenovirus were used to manipulate CAVIN1 expression. RESULTS: Whereas HS and LS iPS-CMs showed similar electrophysiological characteristics at baseline, the late repolarization phase was prolonged and IKr significantly decreased after exposure of HS iPS-CMs to low sotalol concentrations. IKr reduction was caused by a rapid translocation of hERG channel from the membrane to the cytoskeleton-associated fractions upon sotalol application. CAVIN1, essential for caveolae biogenesis, was 2× more highly expressed in HS iPS-CMs, and its knockdown by small interfering RNA reduced their sensitivity to sotalol. CAVIN1 overexpression in LS iPS-CMs using adenovirus showed reciprocal effects. We found that treatment with sotalol promoted translocation of the hERG channel from the plasma membrane to the cytoskeleton fractions in a process dependent on CAVIN1 (caveolae associated protein 1) expression. CAVIN1 silencing reduced the number of caveolae at the membrane and abrogated the translocation of hERG channel in sotalol-treated HS iPS-CMs. CAVIN1 also controlled cardiomyocyte responses to other hERG blockers, such as E4031, vandetanib, and clarithromycin. CONCLUSIONS: Our study identifies unbridled turnover of the potassium channel hERG as a mechanism supporting the interindividual susceptibility underlying diLQT development and demonstrates how this phenomenon is finely tuned by CAVIN1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as =6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel-mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2. METHODS: Heart rate-corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD90) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening ≥40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model. RESULTS: After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate-corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD90 by 113 ms, indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and ΔQTc during the test (r= -0.8; P<0.001). The oral drug test correctly predicted long-term effect in 93% of the patients. Mexiletine reduced the mean yearly event rate from 0.10 (95% CI, 0.07-0.14) to 0.04 (95% CI, 0.02-0.08), with an incidence rate ratio of 0.40 (95% CI, 0.16-0.84), reflecting a 60% reduction in the event rate (P=0.01). CONCLUSIONS: Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy. Mexiletine should therefore be considered a valid therapeutic option to be added to conventional therapies in higher-risk patients with LQT2. [ABSTRACT FROM AUTHOR]

Background: Bone scintigraphy is emerging as a confirmatory diagnostic tool for transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to investigate the frequency and clinical characteristics of patients with incidental cardiac uptake and incidental ATTR-CA on bone scintigraphy. Methods: All bone scintigraphic studies performed at a tertiary teaching hospital between 2011 and 2022 were reviewed retrospectively. Patients who underwent bone scintigraphy to confirm ATTR-CA were excluded. Patients with cardiac uptake of grade 2 or 3 were included and divided into two groups: possible ATTR-CA group and noncardiac amyloidosis (non-CA) group. Results: Of the 61,432 bone scintigraphic studies performed on 32,245 patients, 23 (0.07%) had grade 2 or 3 cardiac uptake. Nine of 23 patients (39.1%) were assigned to the non-CA group because they showed cardiac uptake from definite other causes or focal uptake that did not match CA. The remaining 14 patients (60.9%) were classified as the possible ATTR-CA group, and five patients were referred to cardiologists and finally diagnosed with ATTR-CA. Two patients were treated with tafamidis. Patients in the ATTR-CA group were significantly older and had a less frequent history of end-stage renal disease than those in the non-CA group. Other characteristics were comparable in both groups. Conclusions: Although incidental ATTR-CA in patients undergoing bone scintigraphy for noncardiac reasons is uncommon, if cardiac uptake is observed in elderly patients without metastatic calcification associated with end-stage renal disease, further diagnostic work-up for ATTR-CA as a cause of undiagnosed heart failure should be considered. [ABSTRACT FROM AUTHOR]

The lifetime risk of heart failure (HF) is comparable in men and women; nevertheless, disparities exist in our understanding of how HF differs between sexes. Several differences in cardiac physiology exist between men and women including the propensity to develop specific HF phenotypes. Men are more likely to be diagnosed with HF failure with reduced ejection fraction, while women have a greater propensity to develop HF with preserved ejection fraction. The mechanisms responsible for these differences remain unclear. Post-translational modifications (PTMs) of myofilament proteins likely contribute to these sex-specific propensities. The role of PTMs in heart disease is an expanding field with immense potential therapeutic targets. However, numerous PTMs remain underexplored, particularly in the context of the female heart. Estrogen, a key gonadal hormone, cardioprotective in pre-menopausal women and its loss with menopause likely contributes to disease in aging women. However, how estrogen regulates PTMs to contribute to HF development is not fully clear. This review outlines key sex differences in HF along with characterizing the contributions of novel myocardial PTMs in cardiac physiology and their regulation by estrogen. Collectively, we highlight the necessity for further investigation into women's heart health and the distinctive mechanisms distinguishing women from men. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic devices (CIEDs), such as pacemakers and implantable cardiac defibrillators, are an increasing popular treatment for arrhythmias. Patients with CIEDs are likely to appear in many clinical areas, with pacemakers being the most common type. As healthcare support workers are likely to find these patients in their care, it is vital that they understand the reasons why CIEDs are implanted and how to prepare/care for them. This article will cover the conduction system of the heart and introduce the most common types of CIED. The article also explores how the healthcare assistant and assistant practitioner can support senior staff in preparation, post procedural and community care. [ABSTRACT FROM AUTHOR]

Depression is a multifactorial disease with unknown etiology affecting globally. It's the second most significant reason for infirmity in 2020, affecting about 50 million people worldwide, with 80% living in developing nations. Recently, a surge in depression research has been witnessed, resulting in a multitude of emerging techniques developed for prediction, evaluation, detection, classification, localization, and treatment. The main purpose of this study is to determine the volume of depression research conducted on different aspects such as genetics, proteins, hormones, oxidative stress, inflammation, mitochondrial dysfunction, and associations with other mental disorders like anxiety and stress using traditional and medical intelligence (medical with AI). In addition, it also designs a comprehensive survey on detection, treatment planning, and genetic predisposition, along with future recommendations. This work is designed through different methods, including a systematic mapping process, literature review, and network visualization. In addition, we also used VOSviewer software and some authentic databases such as Google Scholar, Scopus, PubMed, and Web of Science for data collection, analysis, and designing comprehensive picture of the study. We analyzed 60 articles related to medical intelligence, including 47 from machine learning with 513,767 subjects (mean ± SD = 10,931.212 ± 35,624.372) and 13 from deep learning with 37,917 subjects (mean ± SD = 3159.75 ± 6285.57). Additionally, we also found that stressors impact the brain's cognitive and autonomic functioning, resulting in increased production of catecholamine, decreased cholinergic and glucocorticoid activity, with increased cortisol. These factors lead to chronic inflammation and hinder the brain's normal functioning, leading to depression, anxiety, and cardiovascular disorders. In the brain, reactive oxygen species (ROS) production is increased by IL-6 stimulation and mitochondrial cytochrome c oxidase is inhibited by nitric oxide, a potent inhibitor. Proteins, lipids, oxidative phosphorylation enzymes, and mtDNA are further disposed to oxidative impairment in the mitochondria. Consequently, mitochondrial dysfunction exacerbates oxidative stress, impairs mitochondrial DNA (mtDNA) or deletions of mtDNA, increases intracellular Ca2+ levels, changes in fission/fusion and mitochondrial morphology, and lastly leads to neuronal death. This study highlights the multidisciplinary approaches to depression with different aspects using traditional and medical intelligence. It will open a new way for depression research through new emerging technologies. [ABSTRACT FROM AUTHOR]

Introduction: Myasthenia gravis (MG), a rare autoimmune disorder, poses diagnostic and management challenges, with increasing incidence in Europe and significant impact on patient quality of life. Despite prevalent autonomic symptoms, comprehensive assessments integrating subjective and objective measures are lacking. We aimed to investigate the prevalence and severity of autonomic dysfunction in patients with MG and healthy controls (HCs). Materials and methods: We used beat-to-beat hemodynamic responses during standardized autonomic function tests (AFTs) and the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire. Study participants including, 53 patients with MG and 30 age- and sex matched HCs underwent standardized cardiovascular AFTs and completed the COMPASS-31 questionnaire. Patients were categorized into Non-CAN and CAN groups based on their Cardiovascular Autonomic Neuropathy (CAN) status, as evaluated using the Composite Autonomic Scoring Scale (CASS). During the AFTs, cardiovascular parameters including heart rate, systolic blood pressure (BP), diastolic BP, mean BP, stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured. Results: Twenty patients with MG (38%) exhibited mild CAN (CASS =2) with a median total CASS score of 1.00 and CASS 0.00 in HCs. Adrenergic impairment was observed in 27 patients (52%), with 13 patients (24.5%) exhibiting longer pressure recovery time after Valsalva maneuver (VM). Cardiovagal impairment was evident in 71% of patients, with abnormal results observed in 39.6% for the deep breathing test and 56.6% for the VM. CAN MG showed worse scores than HCs for the total COMPASS-31 (p < 0.001), orthostatic (OI) (p < 0.001), secretomotor (p = 0.004), and pupillomotor domains (p = 0.004). Total COMPASS-31 and OI scores were correlated with worse disease outcomes (disease duration, severity), hemodynamic parameter changes (SV, CO, TPR) during phase II late of VM, and with changes (tilt-supine) in systolic BP, diastolic BP, mean BP, TPR during head-up-tilt test, but not with CASS score. Conclusion: Our findings demonstrate mild cardiovascular autonomic impairment in adrenergic and cardiovagal domains in patients with MG. Additionally, patient-reported autonomic symptoms correlated with hemodynamic changes during AFTs and worse disease outcomes and not with the grade of autonomic abnormalities. Incorporating beat-to-beat hemodynamics during AFTs may offer further insights for characterizing orthostatic intolerance symptoms in MG group. [ABSTRACT FROM AUTHOR]

While the pathophysiology of pre‐eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre‐eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre‐eclampsia.   Common pathways of inflammatory and anti‐angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre‐eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders. [ABSTRACT FROM AUTHOR]

Objective: To appraise the dietary perception and knowledge of cardiac patients visiting Outpatient department of a tertiary care hospital. Methods: A cross sectional study of 466 patients attending cardiac outdoor clinic at a tertiary care cardiac hospital in Rawalpindi, Pakistan were selected through convenient sampling from January to April 2021. Patients included in the study were above 18 years of age and had a cardiac disease. A structured questionnaire in English and Urdu was drafted with questions related to patient demographics, dietary perception and knowledge. Results: Among 466 patients, 60% (n=280) were males and 40% (n=186) were females whereas 14% (n=66) of the patients were uneducated and 15% (n=68) had completed postgraduate education. In this study 23% (n=106) of the participants used internet to search nutrition related information and 72 % (n=339) of the patients consider their lifestyle to be healthy. Majority (n=261, 56%) of the patients had no idea regarding sodium consumption. 46% (n=215) of the patients had no knowledge regarding the effects of bakery items on cardiac health. Conclusion: Dietary Knowledge plays a predominant role in the management of cardiac disease. The study concluded that cardiac patients had inadequate knowledge regarding dietary intake in cardiac disease and has high prevalence of dietary myths and misconceptions. Strategic plan including nutritional awareness program and intensive counseling sessions should be designed to increase dietary knowledge of cardiac patients. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To investigate the association between postpartum haemorrhage (PPH) and subsequent cardiovascular disease.Population‐based retrospective cohort study, using record linkage between Aberdeen Maternity and Neonatal Databank (AMND) and Scottish healthcare data sets.Grampian region, Scotland.A cohort of 70 904 women who gave birth after 24 weeks of gestation in the period 1986–2016.We used extended Cox regression models to investigate the association between having had one or more occurrences of PPH in any (first or subsequent) births (exposure) and subsequent cardiovascular disease, adjusted for sociodemographic, medical, and pregnancy and birth‐related factors.Cardiovascular disease identified from the prescription of selected cardiovascular medications, hospital discharge records or death from cardiovascular disease.In our cohort of 70 904 women (with 124 795 birth records), 25 177 women (36%) had at least one PPH. Compared with not having a PPH, having at least one PPH was associated with an increased risk of developing cardiovascular disease, as defined above, in the first year after birth (adjusted hazard ratio, aHR 1.96; 95% confidence interval, 95% CI 1.51–2.53; p < 0.001). The association was attenuated over time, but strong evidence of increased risk remained at 2–5 years (aHR 1.19, 95% CI 1.11–1.30, P < 0.001) and at 6–15 years after giving birth (aHR 1.17, 95% CI 1.05–1.30, p = 0.005).Compared with women who have never had a PPH, women who have had at least one episode of PPH are twice as likely to develop cardiovascular disease in the first year after birth, and some increased risk persists for up to 15 years. [ABSTRACT FROM AUTHOR]

Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at a molecular level. Proteomics provides biologists with a snapshot of context-dependent protein and proteoform expression, structural conformations, dynamic turnover, and protein-protein interactions. Cardiac proteomics can offer a broader and deeper understanding of the molecular mechanisms that underscore cardiovascular disease, and it is foundational to the development of future therapeutic interventions. This review encapsulates the evolution, current technologies, and future perspectives of proteomic-based mass spectrometry as it applies to the study of the heart. Key technological advancements have allowed researchers to study proteomes at a single-cell level and employ robot-assisted automation systems for enhanced sample preparation techniques, and the increase in fidelity of the mass spectrometers has allowed for the unambiguous identification of numerous dynamic posttranslational modifications. Animal models of cardiovascular disease, ranging from early animal experiments to current sophisticated models of heart failure with preserved ejection fraction, have provided the tools to study a challenging organ in the laboratory. Further technological development will pave the way for the implementation of proteomics even closer within the clinical setting, allowing not only scientists but also patients to benefit from an understanding of protein interplay as it relates to cardiac disease physiology. [ABSTRACT FROM AUTHOR]

Little is known about how plasma and whole blood taurine and plasma carnitine correlate to concentrations in skeletal and cardiac muscle and the effects of diet in dogs. The purpose of this study was to evaluate the correlation among plasma, skeletal and cardiac muscle carnitine and taurine and whole blood taurine and determine the effect of diet. The study protocol was approved by the Pet Food Solutions Institutional Animal Care and Use Committee. Thirty‐three mixed‐breed hounds and 32 beagles were evaluated at Day 0 then removed from their baseline diet and randomized to a test diet: high animal protein, grain‐inclusive (HA‐GI), low animal protein, grain‐free (LA‐GF), low animal protein, grain‐inclusive (LA‐GI), or high animal protein, grain‐free (HA‐GF). Blood was drawn every 30 days and endomyocardial (mixed breeds only) and skeletal muscle biopsies were collected at Days 0 and 180. The correlations between plasma and whole blood taurine, or plasma carnitine and skeletal and cardiac muscle concentrations were weak (p < 0.01–0.05). Mixed‐breed hounds had increased (p = 0.029) whole blood taurine compared to beagles. Plasma taurine was lower with diet HA‐GF, (p = 0.009) however, all diets had increased taurine from Day 0 and were, on average within the laboratory reference range. Dogs fed the HA‐GI diet had increased cardiac muscle carnitine esters (p = 0.014). Increased carnitine esters were also appreciated in cardiac muscle in all diets from Day 0 to 180 (p = 0.0001). On Day 180 mixed‐breed hounds had increased skeletal total carnitine (p < 0.001) compared to all time points and breeds. This study observed no correlation between plasma, whole blood, skeletal and cardiac muscle taurine concentrations but noted some effects between time, breed and diet. [ABSTRACT FROM AUTHOR]

Patients admitted with principal cardiac diagnosis (PCD) can encounter difficult inpatient stays that are often marked by malnutrition. In this setting, enteral feeding may improve nutritional status. This study examined the association of PCD with perioperative outcomes after elective enteral access procedures. Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care institution were reviewed retrospectively. Differences in baseline characteristics between patients with and without PCD were adjusted using entropy balancing. Multivariable logistic and linear regressions were subsequently developed to evaluate the association between PCD and nutritional outcomes, perioperative morbidity and mortality, length of stay, and nonelective readmission after enteral access. 912 patients with enteral access met inclusion criteria, of whom 84 (9.2%) had a diagnosis code indicating PCD. Compared to non-PCD, patients with PCD more commonly received percutaneous endoscopic gastrostomy by general surgery and had a higher burden of comorbidities as measured by the Charlson comorbidity index. Multivariable risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups (standardized differences ranged from −2.45 × 10−8 to 3.18 × 108). After adjustment, despite no significant association with in-hospital mortality, percentage change prealbumin, length of stay, or readmission, PCD was associated with an approximately 2.25-day reduction in time to meet goal feeds (95% CI -3.76 to −0.74, P = 0.004) as well as decreased odds of reoperation (adjusted odds ratio 0.28, 95% CI 0.09-0.86, P = 0.026) and acute kidney injury (adjusted odds ratio 0.24, 95% CI 0.06-0.91, P = 0.035). Despite having more comorbidities than non-PCD, adult enteral access patients with PCD experienced favorable nutritional and perioperative outcomes. • Heart failure (10.7%) was the most common indication for enteral access among PCD. • PCD was linked to an approximately 2.25-day reduction in time to reach goal feeds. • No association between PCD and in-hospital mortality despite greater comorbidities. [ABSTRACT FROM AUTHOR]

Background: Newer generation viscoelastic tests, TEG6s, offer point‐of‐care hemostatic therapy in adult patients. However, their efficacy in estimating fibrinogen levels in pediatric patients undergoing cardiac surgery is not well established. Aims: This study evaluates TEG6s for estimating fibrinogen levels in pediatric cardiac surgery patients and its predictive capability for post‐bypass hypofibrinogenemia. Methods: A single‐center, retrospective study on pediatric patients (under 18 years) who underwent cardiac surgery with cardiopulmonary bypass from August 2020 and November 2022. Blood samples for estimated whole blood functional fibrinogen level via TEG6s (Haemonetics Inc.) and concurrent laboratory‐measured plasma fibrinogen via von Clauss assay were collected at pre‐ and post‐cardiopulmonary bypass. Results: Paired data for TEG6s estimated functional fibrinogen levels and plasma fibrinogen were analyzed for 432 pediatric patients pre‐bypass. It was observed that functional fibrinogen consistently overestimated plasma fibrinogen across all age groups with a mean difference of 138 mg/dL (95% confidence interval [CI]: 128–149 mg/dL). This positive bias in the pre‐bypass data was confirmed by Bland–Altman analysis. Post‐bypass, functional fibrinogen estimates were comparable to plasma fibrinogen in all patient groups with a mean difference of −6 mg/dL (95% CI: −20–8 mg/dL) except for neonates, where functional fibrinogen levels underestimated plasma fibrinogen with a mean difference of −38 mg/dL (95% CI: −64 to −12 mg/dL). The predictive accuracy of functional fibrinogen for detecting post‐bypass hypofibrinogenemia (plasma fibrinogen ≤250 mg/dL) demonstrated overall fair accuracy in all patients, indicated by an area under the curve of 0.73 (95% CI: 0.65–0.80) and good accuracy among infants, with an area under the curve of 0.80 (95% CI: 0.70–0.90). Similar performance was observed in predicting critical post‐bypass hypofibrinogenemia (plasma fibrinogen ≤200 mg/dL). Based on these analyses, optimal cutoffs for predicting post‐bypass hypofibrinogenemia were established as a functional fibrinogen level ≤270 mg/dL and MAFF ≤15 mm. Conclusion: This study demonstrates that whole blood functional fibrinogen, as estimated by TEG6s, tends to overestimate baseline plasma fibrinogen levels in pediatric age groups but aligns more accurately post‐cardiopulmonary bypass, particularly in neonates and infants, suggesting its potential as a point‐of‐care tool in pediatric cardiac surgery. However, the variability in TEG6s performance before and after bypass highlights the need for careful interpretation of its results in clinical decision‐making. Despite its contributions to understanding TEG6s in pediatric cardiac surgery, the study's design and inherent biases warrant cautious application of these findings in clinical settings. [ABSTRACT FROM AUTHOR]

OBJECTIVE The purpose of the study reported herein was to determine the dose of oleander extract and oleandrin (the key pharmacologically active constituent) that could be safely administered PO to dogs. ANIMALS 42 purebred Beagle dogs were used to study an extract of Nerium oleander. METHODS 3 studies were performed in 42 purebred young adult (ages 12 months or older) Beagle dogs using a supercritical fluid extract of N oleander leaves. The first study was an 8-day initial dose-ranging study in 2 dogs, a second 7-day repeat-dosing study was performed in 4 dogs, and the final study was performed in 32 dogs where test subjects were given extract or placebo once daily for 28 consecutive days via oral (gavage) administration followed by a 14day recovery period. RESULTS At 2.3 µg/kg of oleandrin, there were no observable adverse effects during the duration of the study. Adverse effects were not seen until doses exceeded 6.9 µg/kg of oleandrin, at which time mild, reversible clinical signs were noted. However, a dose > 460 µg of oleandrin/kg was fatal in 1 of 2 dogs in this study. CLINICAL RELEVANCE The studies reported here, taken in totality, suggest that doses exceeding 6.9 µg/kg of oleandrin may be associated with cardiac abnormalities. An estimated no treatment effective adverse event oral dose of oleandrin appears to be 4.6 µg of oleandrin/kg. Higher doses may be tolerable but should be used with appropriate monitoring. [ABSTRACT FROM AUTHOR]

Although the unfolded protein response (UPR) contributes to survival by removing misfolded proteins, endoplasmic reticulum (ER) stress also activates proapoptotic pathways. Changed sensitivity to normal developmental stimuli may underlie observed cardiomyocyte apoptosis in the healthy perinatal heart. We determined in vitro sensitivity to thapsigargin in sheep cardiomyocytes from four perinatal ages. In utero cardiac activation of ER stress and apoptotic pathways was determined at these same ages. Thapsigargin-induced phosphorylation of eukaryotic initiation factor 2 (EIF2A) was decreased by 72% between 135 and 143 dGA (P = 0.0096) and remained low at 1 dPN (P = 0.0080). Conversely, thapsigargin-induced caspase cleavage was highest around the time of birth: cleaved caspase 3 was highest at 1 dPN (3.8-fold vs. 135 dGA, P = 0.0380; 7.8-fold vs. 5 dPN, P = 0.0118), cleaved caspase 7 and cleaved caspase 12 both increased between 135 and 143 dGA (25-fold and 6.9-fold respectively, both P < 0.0001) and remained elevated at 1 dPN. Induced apoptosis, measured by TdT-mediated dUTP nick-end labeling (TUNEL) assay, was highest around the time of birth (P < 0.0001). There were changes in myocardial ER stress pathway components in utero. Glucose (78 kDa)-regulated protein (GRP78) protein levels were high in the fetus and declined after birth (P < 0.0001). EIF2A phosphorylation was profoundly depressed at 1 dPN (vs. 143 dGA, P = 0.0113). In conclusion, there is dynamic regulation of ER proteostasis, ER stress, and apoptosis cascade in the perinatal heart. Apoptotic signaling is more readily activated in fetal cardiomyocytes near birth, leading to widespread caspase cleavage in the newborn heart. These pathways are important for the regulation of normal maturation in the healthy perinatal heart. NEW & NOTEWORTHY: Cardiomyocyte apoptosis occurs even in the healthy, normally developing perinatal myocardium. As cardiomyocyte number is a critical contributor to heart health, the sensitivity of cardiomyocytes to endoplasmic reticulum stress leading to apoptosis is an important consideration. This study suggests that the heart has less robust protective mechanisms in response to endoplasmic reticulum stress immediately before and after birth, and that more cardiomyocyte death can be induced by stress in this period. [ABSTRACT FROM AUTHOR]

The heart is the most metabolically active organ in the human body, and cardiac metabolism has been studied for decades. However, the bulk of studies have focused on animal models. The objective of this review is to summarize specifically what is known about cardiac metabolism in humans. Techniques available to study human cardiac metabolism are first discussed, followed by a review of human cardiac metabolism in health and in heart failure. Mechanistic insights, where available, are reviewed, and the evidence for the contribution of metabolic insufficiency to heart failure, as well as past and current attempts at metabolism-based therapies, is also discussed. Most knowledge of cardiac metabolism derives from studying model organisms. Here, Bornstein et al. review cardiac metabolism specifically in humans, including discussions of available experimental approaches, quantitative determinations of fuel use, alterations in heart failure, pharmaceutical interventions, and future directions. [ABSTRACT FROM AUTHOR]

A diagnosis of congenital heart disease increases perioperative risk for children having surgical procedures. Some will require anaesthesia at a specialist cardiac centre, while for others it is safe and appropriate to have their procedure in a local district general hospital. Children with complex congenital heart disease and poor physiological status carry the highest risk of cardiac arrest and mortality. Clinical features of cardiomyopathy, cyanosis, pulmonary hypertension, arrhythmia and cardiac failure are most likely to require specialist input and tertiary referral, whereas those with a preoperative stay of less than 10 days undergoing elective, minor surgery, who are older than 2 years of age and physiologically well may be safely anaesthetized in a district general hospital. In order to maximize safety, the anaesthetist must carry out a thorough preoperative assessment, have an understanding of the patient's individual physiology and be prepared for the potential effects of general anaesthesia. Systemic vascular resistance is reduced by most induction agents and volatile anaesthetics; pulmonary vascular resistance is affected by changes in ventilation and gas exchange. The anaesthetist should also be alert to particular potential complications, such as arrhythmias, hypoxia, bleeding and cardiac arrest. [ABSTRACT FROM AUTHOR]

Wolff-Parkinson-White (WPW) syndrome is a rare cardiac condition arising from abnormal embryologic development of the annulus fibrosus in combination with the cardiac conduction system. The abnormality results in the development of accessory pathways and preexcitation changes which can provoke episodes of tachyarrhythmias. The most common presentation of WPW syndrome is supraventricular tachycardia. Beyond customary abortive therapy, chronic management strategies vary based upon timing and clinical severity of the initial disease presentation. Prompt diagnosis and rate control have a dramatic impact on the outcomes of morbidity and mortality. The purpose of this article is to present a case study of a preterm infant who manifested with WPW syndrome. Additionally, the article will explore the pathophysiology of WPW syndrome and the timing and presentation of common clinical manifestations of the disease, along with current diagnostic and treatment strategies to achieve optimal patient outcomes in the neonatal population. [ABSTRACT FROM AUTHOR]

Objective: We evaluated ductal closure rates in preterm neonates with hemodynamically significant patent ductus arteriosus (hsPDA) who received paracetamol (PCM) as first-line therapy. Methods: In this retrospective chart review, we included inborn preterm (< 37 weeks) neonates (January 2017–December 2021) with hsPDA (ductal diameter > 1.5 mm and left atrium-to-aortic root ratio (La/Ao > 1.4) who were treated with oral or intravenous PCM. Primary outcome was hsPDA closure (defined as small or no PDA) following 3-day treatment. Secondary outcomes were need for retreatment and surgical ligation, pulmonary hypertension (PH), and in-hospital morbidities. Results: Out of 2784 preterm births, 117 neonates were diagnosed with hsPDA. Out of 96 neonates who received PCM in the first course, 20 died before the completing the first course. The median (IQR) gestation and birth weight of neonates who received PCM were 28 (26, 29) weeks and 841 (714, 1039) g, respectively. Out of 76 neonates who completed treatment with first course of PCM (57 intravenous, 19 oral), 43 (56.6%) achieved successful closure and five (6.6%) developed PH. 14 neonates received a second course of PCM; 10 achieved closure of hsPDA while one expired. Conclusion: Paracetamol is associated with successful closure of hsPDA in 56.6% of preterm neonates after one course and 70% of preemies after two courses [ABSTRACT FROM AUTHOR]

Cardiotoxicity induced by doxorubicin (Dox) is a major complication in cancer patients. Exosomes (Ex) derived from mesenchymal cells could be a promising therapeutic for various heart diseases. This study investigated the role of Ex in Dox‐induced cardiotoxicity and its mechanistic insights, using Sacubitril/valsartan (S/V) as a reference drug widely recommended in heart failure management. The study involved 24 Wistar rats, divided into a control, Dox, Dox + S/V, and Dox + Ex groups. The rats were assessed for cardiac enzymes, inflammatory and oxidative stress markers. Immunohistochemical expression of caspase‐1, nuclear factor erythroid 2‐related factor 2 (NrF2), E‐Cadherin, CD117/c‐kit, and Platelet‐derived growth factor‐α (PDGFα) was evaluated. P53 and Annexin V were assessed by PCR. Histological examination was performed using hematoxylin and eosin and Sirius red stains. Ex ameliorated the adverse cardiac pathological changes and significantly decreased the cardiac enzymes and inflammatory and oxidative stress markers. Ex also exerted antifibrotic and antiapoptotic effect in heart tissue. Ex treatment also improved NrF2 immunohistochemistry, up‐regulated E‐Cadherin immune expression, and restored the telocyte markers CD117/c‐kit and PDGFα. Ex can mitigate Dox‐induced cardiotoxicity by acting as an anti‐inflammatory, antioxidant, antiapoptotic, and antifibrotic agents, restoring telocytes and modulating epithelial mesenchymal transition. Research Highlights: Exosomes exhibit positive expression for CD90 and CD105 whereas showing −ve expression for CD 34 by flow cytometry.Exosomes restore the immunohistochemical expression of the telocytes markers CD117/c‐kit and PDGFα.Exosomes alleviate myocardial apoptosis, oxidative stress and fibrosis. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) integration in cardiac magnetic resonance imaging presents new and exciting avenues for advancing patient care, automating post-processing tasks, and enhancing diagnostic precision and outcomes. The use of AI significantly streamlines the examination workflow through the reduction of acquisition and postprocessing durations, coupled with the automation of scan planning and acquisition parameters selection. This has led to a notable improvement in examination workflow efficiency, a reduction in operator variability, and an enhancement in overall image quality. Importantly, AI unlocks new possibilities to achieve spatial resolutions that were previously unattainable in patients. Furthermore, the potential for low-dose and contrast-agent-free imaging represents a stride toward safer and more patient-friendly diagnostic procedures. Beyond these benefits, AI facilitates precise risk stratification and prognosis evaluation by adeptly analysing extensive datasets. This comprehensive review article explores recent applications of AI in the realm of cardiac magnetic resonance imaging, offering insights into its transformative potential in the field. [ABSTRACT FROM AUTHOR]

Both Neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are RASopathies. Characteristic cardiac phenotypes of NS, including specific electrocardiographic changes, pulmonary valve stenosis and hypertrophic cardiomyopathy have not been completely studied in NF1. Purpose: The aims of this study were to assess: (1) similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS in asymptomatic patients with NF1, and (2) the presence of discrete myocardial dysfunction in NF1 patients using myocardial strain imaging. Methods: Fifty-eight patients with NF1 (ages 0–18 years), and thirty-one age-matched healthy controls underwent cardiac assessment including blood pressure measurements, a 12-lead ECG, and detailed echocardiography. Quantification of cardiac chamber size, mass and function were measured using conventional echocardiography. Myocardial strain parameters were assessed using 2-Dimensional (2D) Speckle tracking echocardiography. Results: Asymptomatic patients with NF1 had normal electrocardiograms, none with the typical ECG patterns described in NS. However, patients with NF1 showed significantly decreased calculated Z scores of the left ventricular internal diameter in diastole and systole, reduced left ventricular mass index and a higher incidence of cardiac abnormal findings, mainly of the mitral valve, in contrast to the frequently described types of cardiac abnormalities in NS. Peak and end systolic global circumferential strain were the only significantly reduced speckle tracking derived myocardial strain parameter. Conclusions: Children with NF1 demonstrated more dissimilarities than similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS. The role of the abnormal myocardial strain parameter needs to be explored. [ABSTRACT FROM AUTHOR]

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P