(1) Background: Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodelling. We aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor-beta-1 (TGF-β1 ), on cardiac remodelling in an in vivo model. (2) Methods: Six-week-old male wild-type (WT) and TGF-β1 -overexpressing transgenic (TGF-β1 -TG) mice were infused with subhypertensive doses of Ald for 2 weeks, and/or treated orally with eplerenone from postnatal day 21. Heart’s ventricles were examined: by morphometry, immunoblotting to assess intracellular signalling pathways, RT qPCR to determine hypertrophy and fibrosis marker genes. (3) Results: TGF-β1 -TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis, exhibited higher baseline phosphorylation of p44/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in ventricular heart weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but less pronounced increase in interstitial fibrosis in transgenic compared to WT mice (23.6% vs 80.9%, p<0.005). Ald increased phosphorylation of p44/42 and p38 in WT but not TGF-β1 -TG mice. While eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in WT controls, it completely protected from additional fibrosis in transgenic mice. (4) Conclusions: Ald appears to induce cardiac hypertrophy independently of TGF-β1 , while in case of fibrosis downstream signalling pathways of these two factors probably converge

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and &lt;100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p&lt;0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p&lt;0.01); vs LT=2.74±0.84; (p&lt;0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p&lt;0.001), and LAVi (r=0.70; p&lt;0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

Background: Recently, minimally invasive access via right-anterolateral mini-thoracotomy (RAMT) has been gaining popularity in cardiac surgery. This approach is also an option for sur-geons performing aortic surgery. Aim of the study is to present our surgical method highlighting the total endoscopic minimally invasive approach via RAMT for replacement of the ascending aorta (AAR) with or without involvement of the aortic root and the aortic valve. Methods: Clini-cal data of 44 patients from three participating institutions with AAR with or without involving the aortic valve or aortic root via RAMT between April 2017 and February 2024 were retrospec-tively analyzed. According to surgical procedure patients were divided in group A with only AAR and group B with concomitant valve or root replacement. Operative time, length of ventila-tion, perioperative outcome, length of intensive care unit (ICU) as well as postoperative hospital stay, and mid- and long-term results were retrospectively analyzed. Results: Mean age was 61.4 ± 10.7 years old with a frequency of male gender (63.6%). Mean cardiopulmonary bypass (CBP) time and aortic cross-clamping time was 94.9 ± 32.5 min. and 63.8 ± 25.9 min., respectively. CPB and aortic clamp time were significantly lower in group A. In the first 24 hours the mean drain-age volume was 790.3 ± 423.6 ml. Re-thoracotomy due to bleeding was zero. Sternotomy could be avoided in all patients. Patients stayed 35.9 ± 23.5 hrs at ICU and were discharged 7.8 ± 3.0 days following surgery from hospital. Mean ventilation time was 5.8 ± 7.6 hrs. All patients survived and 30-day mortality was 0.0%. At a median follow-up time of 18.2 months, all patients were alive. The results were similar in both groups. Conclusions: The full endoscopic RAMT approach with 3D visualization is a safe and feasible technique which can be transferred in the field of aor-tic surgery without compromising surgical quality, postoperative outcomes, or patient safety when performed by an experienced team in a high-volume center.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

The purpose of the study was to identify factors characterizing a decrease in LV global systolic function in patients with ST-segment elevation myocardial infarction (STEMI) after revascularization using cardiac magnetic resonance imaging (MRI)-based ischemic injury pattern and laboratory parameters sensu left ventricular global systolic function. A total of 109 STEMI patients were examined. The patients underwent contrast-enhanced cardiac MRI with a 1.5 Tesla GE SIGNA Voyager (GE HealthCare, USA) on the 7th-10th days from the onset of the disease. According to cardiac MRI analysis, the patients were divided into the following groups with regard to left ventricular ejection fraction (LVEF) values: group 1 – patients with LVEF ≥50%; group 2 – patients with mildly reduced LVEF 40-49%; group 3 – patients with low LVEF <40%. A predominance of most parameters of the ischemic injury pattern was noted in patients with mildly reduced and low LVEF versus patient group with LVEF ≥50%. Some risk factors for a decrease in LVEF <50% systolic function in STEMI patients after revascularization were revealed: male gender; time from the onset of the anginal attack to revascularization; coronary artery status; several LV parameters; ischemic injury characteristics; natriuretic peptide and troponin I levels.

Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (T_max) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged T_max in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in T_max at high preload. The [Ca²⁺]_i transient decay time constant was consistent with the greater preload dependency in T_max of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to the different cellular responses to stretch, which may provide a decrease in transmural dispersion of cellular shortening in the intact heart.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Aim: To analysis the relationship between healthy adults right ventricular diameter (RVD) and geographical factors. Location: China’s 22 provinces, municipalities and autonomous regions. Methods: Using correlation analysis the relationship between RVD and nine geographic factors, build predictive models by factor analysis. Results: There is significant correlation between RVD and geographical factors, and the annual average temperature is most relevant geographical factors, a predictive model was built by factor analysis: Ŷ = 19.46 + 0.0007072X1 + 0.001034X2 -0.05412X3 -0.001405X4 -0.0006351X5 + 0.02903X6 + 0.01243X7 -0.01033X8 + 0.03816X9 ± 0.63. Then using Kriging interpolation interpolate the geographical distribution of Chinese healthy adult right ventricular diameter reference value in ArcGIS software. Main Conclusion: If geographic factors can be derived in anywhere of China, RVD can be calculated by the model, you can also get RVD from geographical distribution.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤4µm) and intercapillary meshes (diameter >4µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose by a combination of sprouting, lumen expansion, and/or by creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one third of them disappeared between 28-48 hours post fertilisation (hpf) and of the remaining ones only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and establishment of hierarchy was dominated by the dynamics of intercapillary meshes, which formed mainly by sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.

In this paper, we aim to assess the electric current parameters and report the analysis of the associated degree of ventricular recovery during left ventricular assist device (LVAD) support. An assumption was made there is a linear relationship between ventricular recovery degree and the pump electric current pulsatility index (PI). The experimental study was carried out using the ViVitro Pulse Duplicator System with Sputnik 1 LVAD connected. Cardiac output (CO) and cardiac power output (CPO) were used as a measure of ventricular recovery degree. Different heart rates (HR) (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) were investigated. Ventricular stroke volumes in the range of 30–80 ml for each heart rate at certain pump speed were used. The obtained relationships of CO and CPO vs. PI was linear as the coefficients of determination for each regression curve were more than 0.8. CO vs. PI: R2=0.9218; 0.9271; 0.9172 and CPO vs. PI: R2=0.8517; 0.841; 0.8244 for HR=59 bpm; 73 bpm; 86 bpm, respectively. Study findings suggest that adequate interpretation of parameters could potentially serve as a valuable clinical tool to assess ventricular recovery based on LVAD infrastructure without requiring any special hemodynamic assessment.

Percutaneous vertebroplasty procedure is of major importance, given the significant increasing aging population and higher number of orthopedic procedures related to vertebral compression fractures. Vertebroplasty is a complex technique involving injection of polymethylmethacrylate (PMMA) into the compressed vertebral body for mechanical stabilization of the fracture. Our understanding and ability to modify these mechanisms through alterations in cement material is rapidly evolving. However, the rate of cardiac complications secondary to PMMA injection and subsequent cement leakage has increased with time. The following review considers the main features of PMMA bone cement on the heart, and the extent of influence of materials on cardiac embolism. Clinically, cement leakage results in life-threatening cardiac injury. The convolution of this outcome through an appropriate balance of complex material properties is highlighted via clinical case report.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

Specialized classes of proteins, working together in a tightly orchestrated manner, induce and maintain highly curved cellular and organelles membrane morphology. Due to the various ex- perimental constraints, including the resolution limits of imaging techniques, it is non-trivial to accurately elucidate interactions among the various components involved in membrane deformation. The spatial and temporal scales of the systems also make it formidable to investigate them using simulations with molecular details. Interestingly, mechanics-based mesoscopic models have been used with great success in recapitulating the membrane defor- mations observed in experiments. In this review, we collate together and discuss the various mechanics based mesoscopic models for protein-mediated membrane deformation studies. In particular, we provide an elaborate description of a mesoscopic model where the membrane is modeled as a triangulated sheet and proteins are represented as either nematics or fila- ments. This representation allows us to explore the various aspects of protein-protein and protein-membrane interactions as well as examine the underlying mechanistic pathways for emergent behavior such as curvature-mediated protein localization and membrane deforma- tion. We also put forward current efforts in the field towards back-mapping these mesoscopic models to finer-grained particle based models - a framework that could be used to explore how molecular interactions propagate to physical scales and vice-versa. We end the review with an integrative-modeling based road map where experimental imaging micrograph and biochemical data are combined with mesoscopic and molecular simulations methods in a theoretically consistent manner to faithfully recapitulate the multiple length and time scales in the membrane remodeling processes.

Except for a few species, the outer shape of vertebrates normally is characterized by bilateral symmetry. The inner organs, on the other hand, normally are arranged in bilaterally asymmetric patterns, which are of special importance for the normal function of the cardiovascular system of lung-breathing vertebrates. Deviations from the normal organ asymmetry can occur in the form of mirror imagery of the normal arrangement (situs inversus), or in the form of arrangements that have the tendency for development of bilateral symmetry, either in a pattern of bilateral left-sideness (left isomerism) or bilateral right-sidedness (right isomerism). The latter two forms of visceral situs anomalies are called “heterotaxy syndromes”. During the past 30 years, remarkable progress has been made in uncovering of the genetic etiology of heterotaxy syndromes. However, the pathogenetic mechanisms causing the spectrum of cardiovascular defects found in these syndromes remain poorly understood. In the present report, a spontaneous case of left cardiac isomerism found in a HH-stage 23 chick embryo is described. The observations made in this case suggest that hearts with left cardiac isomerism may have the tendency for development of a non-compaction cardiomyopathy caused by defective development of the proepicardium.

Fibroblasts are differentiated to myofibroblasts and produce collagen and other extracellular matrix when the heart is exposed to stresses. Myocardial infarction and pressure overload-induced hypertrophy are major stresses to induce differentiation of fibroblasts. Since collagen can compensate the missing tissue due to injury, appropriate production of collagen is beneficial for the injured heart against rupture. However, excessive deposition of collagen is called fibrosis and causes cardiac dysfunction. After fibroblasts are differentiated to myofibroblasts, myofibroblasts can further change their phenotypes. In addition, myofibroblasts are found to have a new function other than collagen production. Myofibroblasts have macrophage-like functions that engulf dead cells and secrete anti-inflammatory cytokines. So far, research on fibroblasts has been delayed due to the lack of available markers for selective isolation of fibroblasts. In recent years, it has become possible to genetically label fibroblasts, sequence the cells at single cell levels, and manipulate function or the number of cells. Based on new technologies, the origin of fibroblasts and myofibroblasts, time-dependent changes of fibroblast states after injury, and heterogeneity have been demonstrated. Here, I will introduce recent advances in fibroblasts and myofibroblasts.

Mesenchymal stem cells (MSCs), whose main function is tissue repair, use collagen to restore the structural integrity of damaged tissue, maintaining its organization through concomitant remodelling. The non-enzymatic glycation of collagen is likely to compromise its communication with MSC, which indeed underlies various pathological conditions such as late complications of diabetes and aging. However, data on the effect of more early stages of collagen glycation on the MSC interaction are lacking. This study focused on the fate of in vitro glycated rat tail collagen (RTC) in contact with MSCs after its pre-exposure to glucose for 1 or 5 days. Using human adipose tissue-derived MSCs (ADMSCs), we showed that their interaction with glycated collagen is significantly altered, manifested morphologically by reduced cell spreading, less formation of focal adhesions, and weaker development of the actin cytoskeleton, further confirmed by ImageJ morphometric analysis. This suggests a poorer recognition of early glycated collagen by integrin receptors, possibly due to steric hindrance of their binding sites. These morphological events were also accompanied by greatly reduced fibril-like reorganization of adsorbed FITC-collagen (a sign of impaired remodeling), complemented by reduced sensitivity to proteases. The latter was confirmed in two ways: measuring directly FITC-collagen degradation by the attached cells and quantifying the proteolysis reduction upon exogenous addition of collagenase in a cell-free system. The mechanism of the observed effects is unclear, although differential scanning calorimetry confirmed the presence of weak structural changes in glycated collagen. All this led us to conclude that the reason for the morphological changes of ADMSCs is the impaired interaction with early-glycated collagen due to the hindrance of complementary sequences for integrins, which certainly also affects the mechanical remodeling of collagen. However, the impaired collagenolytic activity, together with the observed small changes in the thermal transition profile, undoubtedly indicate some internal changes in the structural organization of the collagen molecule occurring even at this early stage of glycation, which in turn contributes further to the impaired MSC remodeling activity.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

COVID-19 affects many organs in our body, including the heart and lungs. COVID-19 cases that require hospitalization often exhibit pulmonary hypertension (PH) due to changes in the lung microvasculature in which the blood vessels become stiff, damaged, or narrow, causing increased pulmonary arterial pressure. This review examines the hypothesis that PH can lead to right ventricular hypertrophy (RVH) as a long-lasting aftereffect of COVID-19. Recent studies have shown that significant percentages of hospitalized patients develop right ventricular hypertension and right ventricular dilatation (RVD), which may lead to right ventricular failure and death. Despite recommendations for echocardiogram reports to include right ventricular wall thickness to assess RVH, few published reports have reported this parameter. Relevant studies on animal models of PH in which the timing of PH can be precisely controlled suggest that one to three weeks of PH can cause RVH. Thus, according to the hypothesis proposed here COVID-19 patients who have long-lasting severe disease (e.g., needed to be on a ventilator for one or more weeks) accompanied by PH and RVD may develop RVH as a long-lasting sequela outlasting the infection itself. Echocardiogram studies of recovered COVID-19 patients may determine whether oft-reported cardiovascular sequelae include RVH.

Premature ventricular complexes (PVCs) are frequently encountered in clinical practice. The association of PVCs with adverse cardiovascular outcomes in the context of structural heart disease is well established, yet the association between PVCs and cardiovascular outcomes in the absence of structural heart disease is not fully elucidated. Cardiac magnetic resonance (CMR) seems to contribute prognostically in the latter subgroup. PVC- induced myocardial dysfunction refers to the impairment of ventricular function due to the PVCs and is mainly associated with a PVC burden greater than 10%. The surface 12- lead ECG is used to localize the anatomic site of origin and multiple algorithms have been developed to differentiate right ventricular and left ventricular outflow tract (RVOT and LVOT, respectively) origin. Novel algorithms include alternative ECG configurations and lately, sophisticated artificial intelligence methods have been utilized to distinguish the origins of outflow tract arrhythmias. The decision to therapeutically address PVCs should be taken upon the presence of symptoms or the development of PVC- induced myocardial dysfunction. The therapeutic modalities include pharmacological therapy, namely I-C antiarrhythmic drugs and beta blockers, as well as catheter ablation, which demonstrates superior efficacy and safety.

The prevalence and incidence of cardiac pro-arrhythmic disorders are often influenced by sex due to specific effects on the QT interval. Androgens shorten QT, which may be protective against acquired long QT syndromes and their related arrhythmias in men such as torsade de pointes (TdP). On the other hand, androgens can potentiate Brugada and early repolarization syndromes, which are most prevalent in men. In this case series, we highlight four male patients with aborted SCD in the setting of abnormal testosterone status; two patients with TdP in a setting of testosterone deprivation (of which one drug-induced) and 2 patients with ventricular fibrillation associated with exogenous androgenic booster (Tribulus terrestris) intake. From this case series, we review the current available literature of the effects of androgen as a double-edged sword on the QTc interval and emphasize the importance of QTc monitoring in this subset of patients.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Cardiac surgery is a modern science in the history of medicine. The impact in cardiac disease, in term of treatment and prognosis, has made this discipline indispensable in the global health. In recent decades, the greatest investment has been dispensed in technological and material improvement, for increase the life expectancy. This surgery must address different epidemiological aspects dictated by the geography and economic-social conditions of the global populations. For this reason, it is progressively important to address the cardiac surgery accessibility disparity. Many scientific paper and international meetings have studied how cardiac surgery can increase accessibility in various countries around the world. In this review we analyze all the challenges, solutions and suggestions to make this surgery accessible to the entire global population, with the purpose to reducing the disparity across the all seven continents. For a long time, high-income countries have invested in technological capabilities and experimental advancement, not caring about unequal access in the rest of the world. We believe that it is time to reverse the growth trajectory, placing – as a priority – the accessibility and distribution of a surgical science, too significant for the right to health of all the people of the world. This is the real new challenge in cardiosurgery.

: Inflammation may mediate the association of mitral valve prolapse (MVP) with ventricular scarring and arrhythmia. The purpose of this study is to investigate the association of neutrophil- and platelet-to-lymphocyte ratios (NLR, PLR) with ventricular arrhythmia in MVP. Clinical and demographic data were extracted from electronic medical records for all patients aged 18-90 years with MVP on echocardiography between 2016-19 at our institution. We studied 65 patients who had a differential blood count within six months prior to ambulatory ECG (A- ECG) (medi-an age [IQR] 70 [61-77] years; 62% female; 12% African American). Patients with surgery or in-fection within six months prior to CBC were excluded. Complex or frequent ventricular ectopy (cfVE) was defined as the presence of two or more premature ventricular contractions (PVCs) on a 10-second ECG tracing or greater than 1% PVC burden or NSVT on ambulatory ECG monitoring. Logistic and bivariate regression was used to analyze clinical, electrocardiographic and echo-cardiographic factors associated with NLR and PLR. Factors associated with higher NLR were congestive heart failure (p=0.005), male sex (p=0.01), age (p=0.003), and bileaflet MVP (p=0.04). NLR was associated with higher absolute PVC burden (rs=0.28, p=0.03) and cfVE (median NLR [IQR] 3.0 [1.6 – 6.3]) with cfVE versus (2.4 [1.4-3.4], p=0.04) without cfVE. An NLR of 5.6 yielded 50% sensitivity and 90% specificity for PVC burden >1% (AUC 0.69). No significant association was found between PLR and PVC burden or cfVE. NLR is associated with PVC burden and com-plex ventricular ectopy in MVP, suggesting that inflammation is a significant factor in the patho-genesis of ventricular arrhythmia in this condition.

In this presented case, a 77 years old woman suffering from ongoing knee pain underwent a bone scan using 99mTc-hydroxydiphosphonate (HDP) in suspicious for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient’s medical records, she had received 1000mg of ferric carboxymaltose for iron-deficient anemia, the day before the 99mTc-HDP bone scan. Therefore, it is assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share this bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.

The present article seeks to study whether there is any relationship between the equation of the rhythmic figures (Lugos Abarca, 2023) and cardiac auscultation using Field's method, which consists of representing cardiac sounds by means of musical notation (Field, 2010). A new meaning is given to the equation, concluding a mathematical equality between the equation of the rhythmic figures and the formula for calculating the RR Interval.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Background Acute right heart failure (RHF) is associated with high morbidity and mortality. Temporary mechanical circulatory support (tMCS) is now part of the advanced management strategy for refractory cardiogenic shock (CS). Among such support systems, VA-ECMO remains the fastest MCS system to set up. The ProtekDuo cannula can be used as a temporary and percutaneous right ventricular assist device (RVAD) in relay with VA-ECMO in the context of prolonged weaning. Case Summary This case report describes the clinical course of a 69-year-old patient who underwent elective aortic valve replacement surgery complicated by acute RHF due to iatrogenic ligation of the right coronary artery. VA-ECMO was initiated in the context of refractory cardiogenic shock. Faced with prolonged MCS weaning, due to lack of recovery of the right ventricle associated with the absence of any other therapeutic option, a percutaneous RVAD via a ProtekDuo cannula was implanted as a bridge to recovery. The ProtekDuo was gradually weaned while the patient began rehabilitation. The patient was transferred to the medical ward after 5 weeks in the ICU, stayed 5 months in an acute medical setting, went to a rehabilitation center afterward and returned home 6 months after the initial surgery without any neurological sequalae or organ failures. In total, she remained on MCS for 39 days (21 on VA-ECMO and 18 on ProtekDuo). Discussion In cases of refractory RHF, after stabilization and organ perfusion restoration under VA-ECMO, it is feasible to switch to a percutaneous RVAD, allowing early mobilization of patients during prolonged MCS weaning until the right ventricle adapts to new loading conditions.

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. Rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted irrespective of CHA2DS2Vasc score in patients with favorable bleeding profile; data on left appendage closure devices is 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.

Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first level examination for LVH diagnosis. Cardiac magnetic resonance (CMR) defines accurately LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), undetermined LVH in 50(16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p<0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed a diagnosis in 41 out of 50 (82%) with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echo but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change of survival risk of patients: after CMR reclassification no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patient with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.

The beating heart is subject to intrinsic mechanical factors, exerted by contraction of the myocardium (stretch and strain) and fluid forces of the enclosed blood (wall shear stress). The earliest contractions of the heart occur already in the 10-somite stage in the tubular as yet unsegmented heart. With development the looping heart becomes asymmetric providing varying diameters and curvatures resulting in unequal flow profiles. These flow profiles exert various wall shear stresses and as a consequence different expression patterns of shear responsive genes. In this paper we investigate the morphological changes of the heart after changes the blood flow by ligation of the right vitelline vein in a model chicken embryo and analyze the extended expression in the endocardial cushions of the shear responsive gene Tgfbeta receptor III. A major phenomenon is the diminished endocardial-mesenchymal transition resulting in hypoplastic (even absence of) atrioventricular and outflow tract endocardial cushions, that might be lethal in early phases. The surviving embryos exhibit several cardiac malformations including ventricular septal defects and malformed semilunar valves related to a malposition of the aortopulmonary septum and the enclosed neural crest cells. We discuss the results in the light of the interactions between several shear stress responsive signaling pathways including Vegf, Notch, Pdgf, Klf2, eNos, Endothelin and Tgfβ/Bmp/Smad.

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Background: Heart failure is a major cause of morbidity and mortality worldwide; left ventricular diastolic dysfunction plays a leading role in this clinical context. Diastolic dysfunction may be predisposed by increased abdominal fat and, consequently, increased pericardial and epicardial adiposity. This study aimed to determine whether pericardial and epicardial fat are associated with left ventricular diastolic function. Methods: 82 patients had their abdominal circumference measured and underwent transthoracic echocardiography to measure the thickness of pericardial and epicardial fat and assess the left ventricular diastolic function. Two groups were created based on mean pericardial fat thickness (4.644 mm) and were related to abdominal circumference and echocardiographic parameters. Results: Subjects in the PF High group showed a significant decrease in septal e' (p&lt;0.0001), lateral e' (p&lt;0.0001) and E/A ratio (p=0.003) and a significant increase in E/e' ratio (p&lt;0. 0001), E wave deceleration time (p=0. 013), left atrial volume (p&lt;0.0001), LV mass (p=0.003), tricuspid regurgitant jet velocity (p&lt;0.0001) and LV diameter (p=0.014) compared to the PF Low group. Conclusions: Measurement of abdominal circumference, pericardial and epicardial fat is an early indicator of diastolic changes with transthoracic echocardiography being the gold standard exam.

Background and Objectives Depression in childhood often co-occurs with anxiety disorders and a range of somatic symptoms. Recent studies have identified physical activity as a target for preventing the onset of depression. Idiopathic ventricular extrasystoles (VE) in children are sometimes associated with somatic symptoms and limitations in physical activity. The problem of arrhythmia existence can also be distressing for children and their parents. The study was conducted to determine the relationship between symptoms of depression, physical activity and somatic symptoms in children with idiopathic VE. Materials and Methods The study of children with structurally normal hearts and VE was approved by the Ethics Committee No. 2021/10-1383˗859(1). The authors developed Questionnaire to assess symptoms, physical activity, and general well-being. Symptoms of depression evaluated with modified pediatric PHQ-9 (MP-PHQ-9) questionnaire with the interpretation of 0-4 scores for none; 5-9 mild; 10-14 moderate; >15 severe depression. Children aged ≥12 years and parents who assessed their children's condition completed Questionnaires. All children underwent 24-hour electrocardiography and echocardiography to evaluate arrhythmia frequency and cardiac condition. Results Questionnaires were completed by 60 children’s parents and 39 children (≥12 years old). Median children’s age was 13 (5-17) years. Palpitations experienced 26 (43.3%), chest pain 13 (21.7%), exercise intolerance 15 (25%) children. All patients had normal ventricular function and hemodynamically normal hearts. The median score of the MP-PHQ-9 completed by parents was 2 (0-16); by children - 4 (0-18). The median VE frequency was 4,77 (0,1-32,77) % per 24 hours. Extra-sports participation had 31 (51.7%) children with a median time of 3.75 (0.75-25) hours/ week. Eleven-patients were suspended from sports. There was no significant difference between VE frequency, and MP-PHQ-9 scores. Higher MP-PHQ-9 scores showed <5 hours/week active symptomatic children. Conclusions Idiopathic VE, limitations in physical activity and depression remain the actual theme for clinicians and need further research. Higher depression scores showed patients with somatic symptoms.

A 52-y/o asymptomatic male with history of hypertension, was referred to our Heart Failure Clinic due to report of hypertrophic cardiomyopathy, TTE with an increased end-diastolic thick-ness (basal inferoseptal of 23 mm, and basal anteroseptal of 21 mm). CMR demonstrated late gadolinium enhancement at the septum, anterior, inferolateral, and inferior walls with a mid-myocardial distribution, T1 mapping which reported an average T1 of 929 ms. A next-generation sequencing panel was requested. Results demonstrated hemizygosis, in the ga-lactosidase alpha gene, consistent with Fabry Disease. The replacement of the enzyme was start-ed. Extended familial genetic counseling and testing were done.

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

Many clinical research datasets have a large percentage of missing values that directly impacts their usefulness in yielding high accuracy classifiers when used for training in supervised machine learning. While missing value imputation methods have been shown to work well with smaller percentages of missing values, their ability to impute sparse clinical research data can be problem specific. We previously attempted to learn quantitative guidelines for ordering cardiac magnetic resonance imaging during the evaluation for pediatric cardiomyopathy, but missing data significantly reduced our usable sample size. In this work, we sought to determine if increasing the usable sample size through imputation would allow us to learn better guidelines. We first review several machine learning methods for estimating missing data. Then, we apply four popular methods (mean imputation, decision tree, k-nearest neighbors, and self-organizing maps) to a clinical research dataset of pediatric patients undergoing evaluation for cardiomyopathy. Using Bayesian Rule Learning (BRL) to learn ruleset models, we compared the performance of imputation-augmented models versus unaugmented models. We found that all four imputation-augmented models performed similarly to unaugmented models. While imputation did not improve performance, it did provide evidence for the robustness of our learned models.

Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.

In Holter monitoring, the precise detection of standard heartbeats and Ventricular Premature Contractions (PVCs) is paramount for accurate cardiac rhythm assessment. This study introduces a novel application of the 1D U-Net neural network architecture aimed at enhancing PVC detection in Holter recordings. Training data comprised the Icentia11k, INCART DB, and our custom dataset. The model’s efficacy was subsequently validated against traditional Holter analysis methodologies across multiple databases, including AHA DB, MIT 11 DB, NST, and another custom dataset encompassing challenging real-world examples. The results underscored the 1D U-Net model’s prowess in QRS complex detection, achieving near-perfect balanced accuracy scores across all databases. PVC detection exhibited variability, with balanced accuracy scores ranging from 0.909 to 0.986. Despite some databases, like the AHA DB, showcasing lower sensitivity metrics, their robust balanced accuracy accentuates the model’s equitable performance in discerning both false positives and negatives. In conclusion, while the 1D U-Net architecture is a formidable tool for QRS detection, there’s a clear avenue for further refinement in its PVC detection capability, given the inherent complexities and noise challenges in real-world PVC occurrences.

Cardiomyopathy is the leading cause of morbidity and mortality among all complications of type 2 diabetes (T2D) and obese patients. Diabetic cardiomyopathy (DC) is characterized by changes in cardiac morphology with declines in both systolic and diastolic functions. No rodent models fully captured phenotypes of DC. The ZDSD rat, a new generation of T2D rat model with intact leptin signaling features with slow onset of diabetes and obesity, which closely mimics the development of the disease in patients. Age-matched male ZDSD and SD rats were monitored for blood pressure, glucose and cardiac function using echocardiography. Animals were also challenged with 1 mg/kg dobutamine for the assessment of cardiac reserve. ZDSD rats developed hypertension from age of 18 weeks with blood pressure significantly higher than controls. At resting state, ZDSD rats showed biphasic changes in left ventricular posterior wall thickness and cavity volume. Concomitantly, both ejection fraction (EF) and transmitral E/A ratio of LV declined at 34 weeks old. Upon treatment with dobutamine, ZDSD lost cardiac contractility. Therefore, ZDSD rats may serve as a suitable preclinical model to study potential therapeutic approaches to treat cardiomyopathy with presence of metabolic syndromes.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVD), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC) and high-sensitivity cardiac troponin (hsTn), in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTn between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTn within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS and hsTn levels, while VAC was significantly reduced (p&lt;0.001). Further, SLE patients with active disease (SELENA-SLEDAI≥4) exhibited higher levels of CAVI and troponin than those with inactive disease (p&lt;0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTn in SLE cohort. Conclusion: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

Left ventricular (LV) remodeling is a dynamic process which is characterized by abnormal LV wall thickness and altered myocardial geometry, and it is considered as a negative prognostic factor in both heart failure with reduced eject fraction (HFrEF) and heart failure with preserved eject fraction (HFpEF). Hypertension, type 2 diabetes (T2D) and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies highlight that exercise training enhances functional capacity, muscle strength and endurance, cardiac function and cardiac-related biomarkers, among patients with established coronary artery disease (CAD) or HF, thus improving substantially their cardiovascular prognosis, survival rates and needs for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.

Introduction: Intraventricular Hemorrhage (IVH) is a devastating condition mostly in preterm infants at < 30 weeks GA with large morbidities and mortality usually in the first 72 hours after birth. Prevention seems to be the only way to completely deal with this problem. The IVH prevention in this age group has been studied and includes some strategies such as prenatal corticosteroids, cesarean delivery, careful extraction among others, but still, it has an unacceptably high incidence in this population. A protocol with the name Drive to Zero IVH Prevention Project that was presented in one of EpicLatino conferences some years ago. As with any quality improvement in practices, we adapted this project to our unit. Objective: To compare the IVH incidence in our unit after the protocol implementation with and historic cohort from the same unit and with all other units un the epilactino network. Material and method: In October 2017 we begun to implement a neuro protection protocol. For this analysis we include every patient born <30 weeks of GA, inborn or outborn but less than 2 days old, that survived at least three days and had a neuroimaging preformed. We include cases until July 2022, and we use the EpicLatino, a Latin-American database, from 2018 to 2020 excluding our own unit for comparison as well as an historical cohort from our unit from 2010-2017. The protocol consists of: Minimal manipulation, low volume ventilation, one routine fiscal exam a day, neutral head position, one blood pressure measured per shift, no keel stick measurements, continuous dim light and low noise level, minimal touch, no vasoactive therapy except in extreme cases, temperature and humidity at 80%, catheters, when possible, fluid restriction followed with diuresis, no PDA therapy or Echo if possible and routine therapy with hydrocortisone, erythropoietin, caffeine, parenteral nutrition, and trophic feeding. e performed a univariate analysis for IVH and groups and a logistic regression model with variables that had statistical significance in the univariate analysis. Results: The study group included 64 cases, the historic cohort 123 and the EpicLatino 1029. Demographic characteristics were similar with few statistically significant differences. We found four grade 1-2 and six grade 3-4 IVH in the study group (some caused by very traumatic delivery with multiples hematomas in head, body, and extremities), all significantly lower that the other two groups. The logistic regression model confirmed the independent statistically significant result in the study group. Conclusion: The hemorrhage during delivery must be prevented by the obstetric team. Afterwards, a set of interventions like very gentle handling with minimal manipulation and unnecessary strict lab managing seams to decrease the incidence of IVH.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disorder which is characterized by fibrofatty degeneration of cardiac muscles mainly in the right ventricular myocardium. It may cause tachyarrhythmias or right-heart failure or may cause sudden death, especially in young athletes. In our case report, we present a case of young age male patient who presented at a local community hospital with the complaint of atypical chest pain, palpitations, and vomiting and sustained ventricular tachycardia (VT) on electrocardiograph (ECG) showing sustained ventricular tachycardia, left bundle branch morphology with the superior axis. The normal sinus rhythm was achieved after multiple DC cardioversion attempts and he was referred to our tertiary care hospital. Later ECG demonstrated epsilon waves and T wave inversion in v1 to v4 and RBBB morphology. The echocardiography showed a severely dilated right ventricle with dysfunction and right ventricle ventricular apical aneurysm. The definitive diagnosis of ARVC was made as per Revised Task Force Criteria 2010 and the electrophysiology review suggested implantable cardiac defibrillator (ICD) device placement. The patient successfully received a dual-chamber ICD device and he remained asymptomatic.

The rhythmical nature of the cardiovascular system constantly generates dynamic mechanical forces. At the center of this system is the heart which must detect these changes and adjust its performance accordingly. Mechano-electric feedback provides a rapid mechanism for detecting even subtle changes in the mechanical environment and transducing these signals into electrical responses which can adjust a variety of cardiac parameters such as heart rate and contractility. However, pathological conditions can disrupt this intricate mechanosensory system and manifest as potentially life-threatening cardiac arrhythmias. Mechanosensitive ion channels are thought to be the main proponents of mechano-electric feedback as they provide a rapid response to mechanical stimulation and can directly affect cardiac electrical activity. Here we demonstrate that the mechanosensitive ion channel Piezo1 is expressed in zebrafish cardiomyocytes. Furthermore, chemically prolonging Piezo1 activation in zebrafish results in cardiac arrhythmias indicating that this ion channel plays an important role in mechano-electric feedback. This also raises the possibility that Piezo1 gain of function mutations could be linked to heritable cardiac arrhythmias such as atrial fibrillation in humans.

Cardiovascular diseases are the leading cause of death worldwide. Cardiovascular diseases complication can give rise to myocardial infarction which produces cell death by blockage of blood flow, leading to loss of heart function. Current treatments directed at heart repair have several disadvantages such as the lack of donors for heart transplantation or the use of non-bioactive inert materials for replacement of the damage tissue. New treatment strategies involve stimulation of heart tissue regeneration with the use of bioactive materials like chitosan, in combination with cells and biochemical factors. Chitosan scaffolds have the necessary proprieties of biocompatibility, porosity, and biodegradation, that imitates the heart extracellular matrix. Chitosan scaffolds physical proprieties, such as electrical conductivity and mechanical proprieties, can be improved by different preparation techniques and by the functionalization with other materials.

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. This study examined the clinical characteristics, genetic basis, and arrhythmic outcomes of CPVT patients from China. Methods: PubMed and EMBASE were systematically searched for case reports or series reporting on CPVT patients from China until February 19th, 2022 using the keyword “Catecholaminergic Polymorphic Ventricular Tachycardia” OR “CPVT”, with the location limited to “China” OR “Hong Kong” or “Macau” in EMBASE, with no language or publication type restriction. Clinical characteristics, genetic findings, and primary outcome of spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) were analyzed. Results: A systematic search of the PubMed and Embase databases yielded 1049 and 47 articles, respectively. After the exclusion of overlapping cohorts, a total of 58 unique cases from 15 studies (median presentation age: 8 [5.0-11.8] years old) were included. All patients except for one presented at or before 19 years of age. 56 patients (96.6%) were initially symptomatic. Premature ventricular complexes (PVCs) were present in 44 of 51 patients (86.3%) and VT in 52 of 58 patients (89.7%). Genetic tests were performed on 54 patients (93.1%) with a yield of 87%. RyR2, CASQ2, TERCL, and SCN10A mutations were found in 35 (71.4%), 12 (24.5%), one (0.02%) patient, and one patient (0.02%) respectively. 54 patients were treated with beta-blockers, eight received flecainide, five received amiodarone, two received verapamil and one received propafenone. Sympathectomy (n=10) and implantable-cardioverter defibrillator implantation (n=8) were performed. On follow-up, 13 patients developed VT/VF. Conclusion: This is the first systematic review of CPVT patients from China. Most patients had symptoms on initial presentation, with syncope as the presenting complaint. RyR2 mutation accounts for more than half of the CPVT cases, followed by CASQ2, TERCL and SCN10A mutations.

Background: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous cardiomyopathy characterized by a two-layered myocardium consisting of compacted and noncompacted segments, prominent ventricular trabeculations, and intertrabecular recesses. Patients with LVNC are at increased risk to develop heart failure, atrial and ventricular arrhythmias, and/or systemic thromboembolic events. Familial forms of primary sinus bradycardia have been attributed to mutations in HCN4. There are very few reports about the association between HCN4 mutations and LVNC. The aim of our study was to characterize the clinical phenotype of families with LVNC and sinus bradycardia caused by mutation of the HCN4 gene. Methods: From March 2008 to July 2021 we prospectively enrolled 6 patients from 4 families with diagnosed isolated LVNC based on the clinical presentation, family history and echocardiographic and cardiovascular magnetic resonance (CMR) evidence of LVNC. Next generation sequencing (NGS) analysis was undertaken for evaluation of the molecular basis of the disease in each family. Results: A total of 6 children (median age 11 years) were enrolled and followed prospectively for the median of 12 years. All 6 patients were diagnosed with LVNC by echocardiography and 5 participants additionally by CMR. The presence of LGE was found in 3 children. Sinus bradycardia and dilation of the ascending aorta occurred in 5 studied patients. In 4 patients from 3 families the molecular studies demonstrated the presence of rare heterozygous HCN4 mutations. Conclusion: (1) The HCN4 mutation influences the presence of a complex LVNC phenotype, sinus bradycardia and dilation of the ascending aorta. (2) HCN4 mutation may be associated with the early presentation of clinical symptoms and the severe course of the disease. (3) It is particularly important to assess myocardial fibrosis not only within the ventricles, but also in the atria in patients with LVNC and sinus bradycardia.

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. The aim of this study is to examine the genetic basis and identify predictive factors for arrhythmic outcomes of CPVT patients from China. Methods: PubMed and MedRxiv were systematically searched for case reports or case series reporting on CPVT patients from China. Clinical characteristics, genetic findings and primary outcome of spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) were analyzed. Results: A total of 56 (median presentation age=9 [6-13] years old) patients were included. All patients except for one presented at or before 19 years of age. Fifty-three patients (94.6%) were initially symptomatic. PVCs were present in 40 out of 45 patients (88.9%) and VT in 51 out of 56 patients (91.1%). Genetic tests were performed in 50 patients (89.3%). RyR2, CASQ2 and TERCL mutations were found in 32 (57.1%), 11 (19.6%) and one (0.02%) patients, respectively. Fifty patients were treated with beta-blockers, eight patients received flecainide, four patients received amiodarone, two received verapamil and one received propafenone. Sympathectomy (n=10) and implantable-cardioverter defibrillator implantation (n=7) were performed. On follow-up, 17 patients developed incident VT/VF. Conclusion: This is the first systemic review and meta-analysis of CPVT patients from China. Most patients had symptoms on initial presentation, and around a third had VT as the presenting complaint. RyR2 mutation accounts for more than half of the CPVT cases, followed by CASQ2 and TERCL mutations. Some of these mutations have not been hitherto reported outside of China. Most patients received β-blocker therapy. Around 18% had sympathectomy and 13% had ICDs implanted.

The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

Assessment of cardiac function is the leading parameter when evaluating the state of the cardiovascular system of patients undergoing chronic hemodialysis. The aim of the paper: to assess the state of the cardiovascular system of these patients using new sensitive echocardiography and Doppler techniques and thus advance the prevention of cardiovascular disease.Method: Twenty children with end-stage renal insufficiency on chronic hemodialysis and twenty healthy controls underwent echocardiographic monitoring using standard Doppler and tissue Doppler imaging. Structural and functional changes in the left ventricle were evaluated.Results: Patients on hemodialysis had significantly greater left ventricular mass indices compared to the controls (p<0.001). The patients on hemodialysis had preserved systolic function – their fractional shortening, ejection fraction and Sm (systolic myocardial velocity) did not differ significantly compared to the controls (p>0.05). Early diastolic function in children on hemodialysis was also preserved: the E/A and Em/Am ratio did not differ significantly from the control group (p>0.05). Children on hemodialysis exhibited impaired late diastolic function (compliance index), that is, considerably higher E/Em compared to controls (p<0.00). Myocardial Performance Index values showed statistically significant elevation in children on hemodialysis compared to the control group (p<0.001).Conclusion: Tissue Doppler in tandem with conventional Pulsed Doppler can provide additional information on left ventricular filling pressures (E/Em) in children on hemodialysis. It is therefore recommended to perform routine measuring of Em waves and the E/Em ratio, not only in order to evaluate myocardial relaxation and ventricular filling pressures, but primarily to stratify risk and provide a prognosis.

This paper reports the novel design of a touch mode capacitive pressure sensor (TMCPS) system with a wireless approach for a full-range continuous monitoring of ventricular pressure. The system consists of two modules: an implantable set and an external reading device. The implantable set, restricted to a 2x2 cm² area, consists of a TMCPS array connected with a dual-layer coil, for making a reliable resonant circuit for communication with the external device. The capacitive array is modelled considering the small deflection regime for achieving a dynamic and full 5-300 mmHg pressure range. In this design, the two inductive-coupled modules are calculated considering proper electromagnetic alignment, based on two planar coils and considering the following: 13.56 MHz frequency to avoid tissue damage and three types of biological tissue as core (skin, fat and muscle). The system was validated with the Comsol Multiphysics and CoventorWare softwares; showing a 90% power transmission efficiency at a 3.5 cm distance between coils. The implantable module includes aluminum- and polyimide-based devices, which allows ergonomic, robust, reproducible, and technologically feasible integrated sensors. In addition, the module shows a simplified and low cost design approach based on PolyMEMS INAOE® technology, featured by low-temperature processing.

There are no investigations about the outcomes of idiopathic PVCs catheter ablation (CA) in athletes compared to sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were premature ventricular contractions (PVCs) post-ablation reduction in athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in non-athletes group was 96 (IQR 68 – 98) and 98 in athletes group (IQR 92 – 99) (p=0,08). Considering the athletes, the median percentage of decrease in PVCs number was 98 (IQR 93-99) and 98 (IQR 87-99) respectively in leisure-time and agonistic athletes (p=0,42). Sixteen (70%) leisure time and 17 (90%) agonist athletes (p=0,24) have resumed physical activity 3 months after PVCs CA; among agonistic athletes, 59% have resumed competitive physical activity. Much of leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Cardiovascular diseases are one of the most common causes of death in the United States of America and the sudden rise of patients having cancer are suffering from cardiovascular side effects of Chemotherapeutics drugs. Trastuzumab is a potent targeted agent for HER2-positive cancers though despite its excellent efficacy, the cardiotoxic effects of Trastuzumab restrict its usage globally. The most severe adverse effect is cardiotoxicity presents as contractile dysfunction that is reduction in left ventricular systolic function but the electrophysiological side effects are still not known. Due to these severe life-threatening side effects, it routinely results in the cessation of Trastuzumab. This review aims to provide a comprehensive overview of Trastuzumab-induced cardiomyopathy, offering insights into the mechanisms through which Trastuzumab exerts its cardiotoxic effects, clinical manifestations, diagnostic strategies, and potential cardioprotective interventions. By shedding light on the multifaceted aspects of this condition, we hope to emphasize the importance of early detection and effective management, while highlighting the urgent need for continued research to optimize the balance between oncological success and cardiovascular well-being. Cardiologists, oncologists, and researchers stand at the forefront of this critical intersection between oncology and cardiology, collectively striving to improve patient outcomes in the era of Trastuzumab therapy.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP-CRT) is considered a mainstay treatment for symptomatic heart failure patients with reduced ejection fraction and wide QRS. However, up to one third of patients receiving BiVP-CRT are considered non-responders to the therapy. Multiples strategies have been proposed to maximize the percentage of CRT responders including two new physiological pacing modalities that have emerged during the lasts years: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Both pacing techniques aim at restoring the normal electrical activation of the ventricles through the native conduction system in opposition to the cell-to-cell activation of conventional right ventricular myocardial pacing. Conduction system pacing (CSP), including both HBP and LBBAP appears to be a promising pacing modality for delivering CRT and has proven to be safe and feasible in this particular setting. This article will review the current state of the art of CSP-based CRT, its limitations and future directions.

We simulate elementary calcium release events (sparks) in a single calcium release unit in ventricular myocyte. Previously developed and tested electron-conformational model of the stochastic dynamics of RyR-channels is integrated to the calcium dynamics model in the cardiac cell. This approach allows to observe RyRs opening/closing in details on the macromolecular level during the calcium dynamics course. We simulate calcium diffusion in the dyadic space and “domino-like” RyR’s activation during the so-called “calcium induced-calcium release process”. Ca²⁺ sparks initiation, spread and termination are investigated in the computer experiments. Sparks’ initiation and termination rate dependence on the Ca²⁺ diffusion velocity is observed. We show that sarcoplasmic reticulum lumen local depletion and RyR’s stochastic attrition could be the reasons of Ca²⁺ spark termination.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

This report elucidates the first surgical correction of an infundibular muscular ventricular septal defect (VSD) in a one-year-old Ragdoll cat via cardiac arrest using cardiopulmonary bypass, a method that is rarely used in feline cardiac surgery. VSDs can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. This case involved a VSD that was atypically located and classified under the Soto classification instead of the standard Kirklin classification. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it has led to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.

This article explores the intricate journey of neural progenitor cells from the ventricular zones of the embryonic brain, focusing on their pivotal role in the formation of rich club networks, which are integral to the brain's functional architecture. Initially, the ventricular zones, particularly the cerebral ventricular zone, serve as the primary sites for the proliferation and differentiation of neural progenitors, giving rise to various types of neurons and glial cells. We delve into the sequential migration patterns of these cells, emphasizing how early-migrating neurons, destined to form deeper cortical layers, establish extensive and robust connections, potentially evolving into rich club nodes. These nodes are characterized by their high-degree connectivity and serve as crucial hubs for integrating and disseminating information across disparate brain regions.The article further discusses the implications of this developmental pathway in the context of brain network efficiency, resilience, and cognitive function. We highlight how disruptions in early cell migration can lead to anomalies in rich club formation, drawing connections to various neurodevelopmental disorders such as autism, ADHD and schizophrenia. Additionally, the significance of rich club nodes in maintaining efficient information transfer and network resilience is elucidated, underscoring their role in supporting complex cognitive processes and overall brain dynamics.In summary, this article offers a comprehensive overview of the developmental trajectory from the ventricular zones to the establishment of rich club networks, providing insights into the fundamental processes that shape the brain's intricate connectivity and functional capabilities. Ric

Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous study has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation;(2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish cardiac fibrosis animal model. Here, results showed that BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by BTK、STAT3、NF-κB and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Athlete’s heart is characterised by structural, functional, and electrical remodelling. During an exercise session, the heart increases the use of oxygen, which is associated with decreased vascular resistance in the lungs’ circulation. Left ventricular hypertrophy is an echocardiographic modification especially met in endurance athlete’s heart. Moreover, left atrial dilatation represents another important characteristic of endurance athletes. Electrical modulation in the athletic heart induces neurological modifications leading to sinus arrhythmia, bradycardia, early repolarisation, and first-grade atrioventricular (AV) blocks. Athletes' nutritional status involves the assimilation of macronutrients such as proteins, carbohydrates, and fats. Depending on the duration of physical exercise, ATP can be obtained in aerobic or anaerobic conditions. This systematic review aims to find correlations between different evaluative methods of cardiac adaptation and present the metabolism in performance athletes.

Cardiac amyloidosis (CA) results mainly from infiltration of myocardium by either immunoglobulin light chain fibrils (AL) or transthyretin fibrils (ATTR), causing restrictive cardiomyopathy and eventually death if untreated (3). AL derives from monoclonal immunoglobulin light chain produced by plasma cell clone in the bone marrow, while ATTR is the misfolded form of hepatically-derived transthyretin (TTR) protein, and could be hereditary (hATTR) or wild-type (wtATTR). Over the last decade, improvement in diagnostic imaging and better clinical awareness has unleashed a notable presence of CA in the community, especially ATTR in the elderly population. These multimodality imaging modalities include echocardiography, cardiac magnetic resonance and radionuclide scintigraphy with bone-avid tracers. There has been remarkable progress in the therapeutic landscape as well, and there are disease-modifying therapies available now that can alter the course of the disease and improve survival if initiated at an early stage in the disease. There remains an unmet need for detecting this disease accurately and early, so that these patients could benefit the most from newly-emerging therapies.

Right atrial isomerism (RAI) is a complex entity whose treatment and outcome are heterogeneous. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted; it included patients diagnosed with RAI who underwent cardiac surgery; their follow-up was from January 1, 2010 to March 31, 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients with RAI were included, the median age was 4 years (IQR 2-9.2), and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock‐Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). The use of inhaled nitric oxide was a marker of postoperative mortality in critically ill patients (OR: 10.33; 95% CI: 1.04 - 102.08; p = 0.02). The overall survival was 86.8%, with a better outcome in those who did not require reintubation (Log Rank, p < 0.01). The survival of RAI was similar to other centers of reference. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Biomarkers play key roles in diagnosis, risk assessment, treatment and supervision of car-diovascular diseases (CVD). Optical biosensors and assays are valuable analytical tools answering the need for fast and reliable measurements of biomarkers levels. This review presents a survey of recent literature with a focus on the past 5 years. The data indicates continuing trends towards multiplexed, simpler, cheaper, faster and innovative sensing while newer tendencies concern minimizing the sample volume or using alternative sam-pling matrices such as saliva, for less invasive assays. The use of enzyme mimicking activity of nanomaterials gained ground in comparison to their more traditional roles as signaling probe, immobilization support for biomolecules or for signal amplification. The growing use of aptamers as replacements for antibodies prompted emerging applications of DNA am-plification and editing techniques. Optical biosensors and assays were tested with larger sets of clinical samples and compared with the current standard methods. The ambitious goals on the horizon for CVD testing include the discovery and determination of relevant biomarkers with the help of artificial intelligence, more stable specific recognition elements for biomarkers and fast, cheap readers and disposable tests to facilitate rapid testing at home. As the field is progressing at an impressive pace the opportunities for biosensors in the optical sensing of CVD biomarkers remain significant.

ABSTRACT: Iodixanol is an iso-osmolar nonionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)approved isoosmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. In the field of cardiology, iodixanol among other intravenous contrast media is used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability and efficacy of iodixanol in the field of cardiology are reviewed, specifically evaluating the use for CCTA and coronary angiography, including outcome studies, randomized trials and comparisons to other contrast agents.

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD) induced Ventricular arrhythmias, that exhibit heightened proinflammatory-like pathology which is also observed in human obesity VT, as well as immunofluorescence, and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling exhibit enhanced Ventricular arrhythmias /SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat (LFD) diet fed controls, HFD promotes phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4) leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 more than LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval that resulted in greater susceptibility to VT/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective VT therapy in the vulnerable obese patient population.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between stiff AA and reduced longitudinal strain and subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). A proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in-silico utilizing Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with A) Elastic AA; B) Stiff AA; and C) Stiff AA with free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that can abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of LV longitudinal strain are common in patients HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and RV structure and function in PAB animals. PH models and PAB frequently exhibited similar results (73.1% concordance) with drugs other than endothelin receptor antagonists and phosphodiesterase inhibitors. RV systolic pressure accounted for most differences between PH models and PAB. On the other side, all results on RV fibrosis agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Dapagliflozin was the only drug that improved no parameters. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.

The technology of left ventricular assist devices (LVADs) requires developing and implementing an intelligent control systems to optimize pump speed to achieve a physiological metabolic demands for heart failure (HF) patients. This work aimed to present an advanced control algorithm to drive an LVAD under different physiological conditions. Pole placement method in conjunction with of sliding mode control approach (PP-SMC) was utilized to design and construct the proposed control method. In this design, the method was adopted to use neural networks to eliminate system uncertainties of disturbances. An elastance function was also developed and used as an input signal to mimic the physiological perfusion of HF patients. Two scenarios ranging from rest to exercise were introduced to evaluate the proposed technique. In this technique, a lumped parameter model of cardiovascular system (CVS) was used for this evaluation. The results demonstrated that the designed controller was robustly tracking the input signal in the presence of the system parameter variations of CVS. In both scenarios, the proposed method shows that the controller automatically drive the LVAD with a minimum flow of 1.7 L/min to prevent suction and 5.7 L/min to prevent over-perfusion.

Objective: One of the major causes of cerebral ventricular shunt failure is proximal catheter occlusion. We describe a novel ventricular cerebrospinal fluid (CSF) flow replicating system that assesses pressure and flow responses to varied degrees of catheter occlusion. Methods: Ventricular catheter performance was assessed during conditions of partial and complete occlusion. The catheters were placed into a three-dimensionally printed phantom ventricular replicating system. Artificial CSF was pumped through the ventricular system at a constant rate of 1 ml/min to mimic CSF flow, with the proximal end of the catheter in the phantom ventricle. Pressure transducer and flow rate sensors were used to measure intra-phantom pressure, outflow pressure and CSF flow rates. The catheters were also inserted into silicone tubing and pressure was measured in the same manner for comparison with the phantom. Results: Pressure measured in the phantom ventricle did not change when the outflow of the ventricular catheter was partially occluded. However, the intraventricular phantom pressure significantly increased when the outflow catheter was 100% occluded. Flow through the catheter showed no significant difference in rate with any degree of partial occlusion of the catheter. At the distal end of the partially occluded catheters, there was less pressure compared with the nonoccluded catheters. This difference in pressure in partially occluded catheters correlated with the percentage of catheter hole occlusion. Conclusions: Our model mimics physiological dynamics of the CSF flow in partially and completely obstructed ventricular catheters. We found that partial occlusion of the catheter had no effect on CSF flow rate, but did reduce outflow pressure of the catheter.

Background and objectives: The fact that the results of troponin and Nt-proBNP interfere from biotin caused some commercial firms to update their measurement methods. In particular, the clinical incompatibility of cardiac test results may affect the risk of morbidity and mortality. The aim of this study is to investigate the interference effects of 7 different contrast agents on cardiac markers (Troponin-I, Nt-proBNP, Mass CK-MB, CK, AST, LDH) and coagulation tests (PT, APTT). Materials and Methods: Seven different contrast medias were added into control materials by using interference protocol. Concentration of PT, APTT, CK, AST, LDH, Mass CK-MB, Troponin-I, Nt-proBNP were measured by Sysmex CS-2100, Abbott c16000, Siemens Centaur XP and AFİAS-6 analyzer. The amount of deviations from target values were calculated. Results: 7 different contrast medias caused negative interference in troponin levels between 57.43% and 62.87%. It was found that different contrast medias produced false negativity in the Nt-proBNP test ranging from 6.11% to 96.01%. Enzymes and coagulation tests have been less affected. Conclusions: Different contrast medias may cause false negative cTnI and Nt-proBNP. Therefore, the contrast medias which causes the least interference should be preferred. The results of samples taken in the first hour of contrast imaging should be interpreted with care.

Understanding how cannabis affects our heart is like navigating through a maze of conflicting findings. While it's known for its diverse uses, from medicinal to industrial, cannabis also raises red flags regarding its impact on heart health. This review dives into the intricate relationship between cannabis use and cardiovascular well-being, particularly focusing on changes seen in electrocardiogram (ECG) readings, which serve as vital indicators of heart function and rhythm. When someone tokes up, their heart might race temporarily, but chronic cannabis use paints a darker picture, with potential risks of heart attacks and strokes looming on the horizon. The ECG alterations observed in cannabis users, such as irregular heartbeats and unusual wave patterns, hint at disruptions in the heart's normal workings. Furthermore, cannabis has been linked to prolonging the QT interval in the heart's electrical cycle, potentially setting the stage for dangerous arrhythmias. Amidst this mixed bag of effects, some studies even suggest that tiny amounts of THC, the main psychoactive component of cannabis, might lend a helping hand to the heart. However, caution flags are raised, especially for vulnerable groups. While researchers strive to unravel the mysteries of cannabis and the heart, limitations in current studies remind us that we're still far from having all the answers. Moving forward, future investigations should delve deeper into understanding how cannabis tinkers with our heart's inner workings, especially across different demographics. Armed with this knowledge, we can better tailor interventions to safeguard the heart health of cannabis users.

Approximately 300 million non-cardiac surgeries are performed each year. Perioperative mortality after non-cardiac surgery is estimated at 2% in patients over 45 years of age . Half of these deaths are attributable to cardiovascular complications, and most to perioperative myocardial infarction (MINS). Before introduction of cardiac biomarkers the diagnosis of postoperative myocardial infarction was based on symptoms and electrocardiographic changes and its incidence was largely underestimated. The incidence of MINS when standard troponin assay is used ranges between 8 and 19% but increases to 20-30% whit high sensitivity troponin assays. Higher troponin values sugegsting myocardial injury , both with or without definite diagnosis of myocardial infarction, are associated with increased 30 day and 1-year mortality . Diagnostic and therapeutic strategies are reported .

Cardiac amyloidosis (CA) is a restrictive cardiomyopathy characterized by deposition of amyloid in the myocardium and recent studies revealed it is more frequently seen than we thought. Advances have been made over the last years, but a delayed diagnosis is frequently seen. An online survey was conducted among cardiologists from Romania representing the first assessment of the knowledge of CA among them with 195 cardiologists answering the questionnaire. There was a wide variation in their knowledge regarding CA. Our participants had few experience with CA and reported a significant delay between first cardiac symptom and diagnosis. Around one half of them did not seem familiar with the noninvasive diagnostic algorithm and with the wild-type transthyretin amyloidosis (ATTRwt). Even the participants who are aware of this condition and the available treatment options stated this is a rare disease and there is no disease modifying treatment available for ATTRwt. Awareness among cardiologists is the most important challenge in diagnosing CA. Romanian cardiologists are partially aware of this topic, but there are still gaps in their knowledge. Educational programs can improve screening of patients with a high suspicion for this progressive condition whose evolution has been dramatically changed by the new treatment options.

The operating room in a cardiothoracic surgical case is a complex environment, with multiple handoffs often required by staffing changes, and can be variable from program to program. This study was done to characterize what types of practitioners provide anesthesia during cardiac operations to determine the variability in this aspect of care. A survey was sent out via a list serve of members of the cardiac surgical team. Responses from 40 programs from a variety of countries showed variability across every dimension requested of the cardiac anesthesia team. Given that anesthesia is proven to have influence on the outcome of cardiac procedures, this study indicates the opportunity to further study how this variability influences outcomes, and to identify best practices.

The aim of this paper is to develop an intelligent event-driven Electrocardiogram (ECG) processing module in order to achieve an efficient solution for diagnosis of the cardiac diseases. The suggested method acquires the signal with an event-driven A/D converter (EDADC). The output of EDADC is passed through the activity selection and interpolation blocks. It allows focusing only on the important signal parts and resampling it uniformly. Later on, the signal is de-noised. The autoregressive (AR) method is used to extract the classifiable features of the de-noised signal. Afterwards, the output is classified by employing different robust classification techniques such as support vector machines (SVMs), K- Nearest Neighbor (KNN) and Artificial Neural Network (ANN). The event-driven feature enables to adapt the system processing load according to the signal temporal variations. This interesting feature of the devised system aptitudes a drastic reduction in its processing activity and therefore in the power consumption as compared to the traditional ones. A comparison of the performance of different classifiers is also made in terms of accuracy. Results show that the proposed system is a potential candidate for an automatic diagnosis of the cardiac diseases.

Nutrition support is increasingly recognized as a clinically relevant aspect of the intensive care treatment of cardiac surgery patients. However, evidence from adequate large-scale studies evaluating its clinical significance for patients’ mid- to long-term outcome remains sparse. Considering nutrition support as a key component in the perioperative treatment of these critically ill patients, led us to review and discuss our understanding of the metabolic response to the inflammatory burst induced by cardiac surgery. In addition, we discuss how to identify patients who may benefit from nutrition therapy, when to start nutritional interventions, present evidence about the use of enteral and parenteral nutrition and the potential role of pharmaconutrition in cardiac surgery patients. Although the clinical setting of cardiac surgery provides advantages due to its scheduled insult and predictable inflammatory response, researchers and clinicians face lack of evidence and several limitations in the clinical routine, which are critically considered and discussed in this paper.

Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of ranolazine, registered as an antianginal agent while also establishing its safety profile. This review compiles clinical evidence investigating the antiarrhythmic properties of ranolazine, focusing primarily on ventricular tachycardia (VT) and atrial fibrillation (AF), as common rhythm abnormalities with serious complications. Data from RCTs indicate that ranolazine reduces VT incidence, although this effect is not universal. Therefore, we attempt to better describe the patient population that gains the most benefit from ranolazine by VT suppression. Additionally, ranolazine is known to enhance the conversion rate of AF to sinus rhythm when combined with other antiarrhythmic drugs such as amiodarone, highlighting its synergistic effect in the atrium without provoking ventricular dysrhythmias. Despite the heterogeneity in currently available data, ranolazine appears to be an effective and safe option for the management of various arrhythmias.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted July 1, 2019, comprising an initial 10-minute OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 hours after extubation. Severe postoperative respiratory complications (primary outcome measure) included need for antibiotics, increased supplemental oxygen use, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcomes data were compared for patients before (usual care with postextubation hyperinflation) and after protocol implementation (OPE). Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs 62%; P=.19) and were older (median, 70 vs 67 years; P=.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs 7.4 days; P=.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs 1.1 days with usual care; P=.06) and shorter LOS in the intensive care unit (mean, 2.7 vs 3.4 days; P=.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, 0.85 days; 95% CI, 1.65 to 0.06; P=.04). The OPE group had a lower percentage of postoperative complications (10% vs 20%). Conclusion: OPE therapy after cardiac surgery is associated with decreased ICU and hospital LOS.

Cardiac hypertrophy is an adaptive response to various pathological insults including hypertension. However, sustained hypertrophy can cause impaired calcium regulation, cardiac dysfunction, and remodeling, accompanied by cardiac fibrosis. Our previous study identified miR-25 as a regulator of SERCA2a, and that inhibition of miR-25 improved cardiac function and reduced fibrosis by restoring SERCA2a expression in a murine heart failure model. However, the precise mechanism underlying the reduction of fibrosis by miR-25 inhibition remains unclear. Therefore, we postulate that miR-25 may have additional targets that contribute to regulating cardiac fibrosis. Using in silico analysis, Krüppel-like factor 4 (KLF4) was identified as an additional target of miR-25. Further experiments confirmed that KLF4 was directly targeted by miR-25 and that its expression was reduced by long-term treatment with Angiotensin II, a major hypertrophic inducer. Subsequently, treatment with a miR-25 inhibitor alleviated the cardiac dysfunction, fibrosis, and inflammation induced by Angiotensin II. These findings indicate that inhibiting miR-25 not only enhances calcium cycling and cardiac function via SERCA2a restoration but also reduces fibrosis by restoring KLF4 expression. Therefore, targeting miR-25 may be a promising therapeutic strategy for treating hypertensive heart diseases.

Parkinson’s-disease (PD) is an incurable age-related neurodegenerative disease and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD, however its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine, are the metabolites that significantly discriminate Parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, glucose-alanine cycle, the glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and Parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.