Electrical impedance tomography (EIT) can monitor the real-time hemodynamic state of a conscious and spontaneously breathing patient noninvasively. However, cardiac volume signal (CVS) extracted from EIT images has a small amplitude and is sensitive to motion artifacts (MAs). This study aimed to develop a new algorithm to reduce MAs from the CVS for more accurate heart rate (HR) and cardiac output (CO) monitoring in patients undergoing hemodialysis based on the source consistency between the electrocardiogram (ECG) and the CVS of heartbeats. Two signals were measured at different locations on the body through independent instruments and electrodes, but the frequency and phase were matched when no MAs. As the number of motions per hour (MI) increased over 30, the proposed algorithm had a correlation of 0.83 and a precision of 1.65 beats per minute (BPM) compared to the conventional statical algorithm of a correlation of 0.56 and a precision of 4.04 BPM. For CO monitoring, the precision and upper limit of the mean ∆CO were 3.41 and 2.82 liters per minute (LPM), respectively, compared to 4.05 and 3.82 LPM of the statistical algorithm. The developed algorithm could reduce MAs and improve HR/CO monitoring accuracy and reliability, particularly in high-motion environments.

Maximal heart rate (HRmax) is a widely used measure of cardiorespiratory fitness. Prediction of HRmax is an alternative to cardiopulmonary exercise testing (CPET), but its accuracy among endurance athletes (EA) requires evaluation. This study aimed to externally validate HRmax prediction models in the EA independently for running and cycling CPET. 4043 runners (age=33.58 (8.12) years; 83.53% males; BMI=23.66 (2.54) kg·m−2) and 1026 cyclists (age=36.88 (9.03) years; 89.67% males; BMI=24.04 (2.65) kg·m−2) underwent maximum CPET. Student t-test, mean absolute percentage error (MAPE), mean absolute error (MAE), and root mean square error (RMSE) were applied to externally validate 8 running and 5 cycling HRmax equations. HRmax was 184.60 (9.79) beats·min−1 and 182.66 (10.28) beats·min−1 respectively for running and cycling, p=0.001. Measured and predicted HRmax differed significantly (p=0.001) for 9 of 13 (69.23%) models. HRmax was overestimated by 8 (61.54%) and underestimated by 5 (38.46%) formulae. Overestimated HRmax ranged 0.08-4.94 beats·min−1 and underestimated HRmax ranged 0.03-4.90 beats·min−1. MAE and RMSE were 0.18-4.94 beats·min−1 and 9.13-10.47, respectively. MAPE ranged 3.95-4.69%. Prediction models do not allow for accurate estimation of HRmax. HRmax was more often underestimated than overestimated. Predicted HRmax can be implemented for EA as a supplemental method but CPET is the preferable approach.

Patients often need the use of their arms to assist with functional activities, but after bone disruption, pushing is frequently limited to less than 4.5 kg. No method exists to measure arm weight bearing objectively in clinical settings. This project aimed to design, construct, and test a walker for patients who need to limit arm force to prevent excessive bone stress during post-fracture (iatrogenic or traumatic) ossification. First, a qualitative study was conducted to obtain critiques of a Clinical Force Measuring (CFM) walker prototype from rehabilitation professionals. Key statements and phrases were coded that allowed “themes” to emerge from transcribed interviews, which guided device revisions. Next, a second CFM Walker prototype was designed based on the qualitative data and device criteria/constraints and finally tested. The result was fabrication of a new lightweight, streamlined, and cost-effective prototype walker with a simple visual display and auditory cue with upper limit alarms. Key features included attachments for medical equipment and thin film force-sensing resistors integrated into the walker handles that progressively activated 3 LEDs and a buzzer when arm force exceeded programmed thresholds. The innovative CFM Walker will help patients with restricted arm weight bearing, especially elderly adults, recover safer and faster in the future.

Heart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the Left Ventricle (RV) is utilised to build the computa-tional model of the whole heart with little importance given to the unique mechanical properties of Right Ventricle (RV) and Mid-wall (MDW). Most of those studies focussed on the LV of the heart, and then apply the obtained characteristics with a few modifications to the right side of the heart. However, that view has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper is aimed at reporting and evaluating the passive mechanical property dif-ferences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5 % halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta and valves are all dissected out. Then 5 x 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid over-prestraining the specimens. The specimens were subjected tensile test. The elastic moduli, peak stresses in the toe region and stresses at 40 % strain, anisotropy indices as well as the stored strain energy in the toe and linear region up to 40 % strain are used for statistical significance tests. The following are the main findings of this study: (1) LV and MDW tissues have relatively shorter toe regions of 10 - 15 % strain as compared to RV tissue whose toe region extends up to twice as much as that (2) LV tissues have higher strain energy storage in the linear region despite being lower in stiffness than the RV (3) the MDW has the highest strain energy storage along both directions which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasize the importance of application of wall specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.

Wearable cardiac sensors pave the way to advanced cardiac monitoring applications based on heart rate variability (HRV). In real-life settings, heart rate (HR) measurements are subject to mo-tion artifacts that can be timely removed from the recordings. This leads to frequent data loss in the HR signal, especially for commercial devices based on photoplethysmography (PPG). The cur-rent study had two main goals: (i) to provide a white-box quality index that estimates the amount of missing samples in any piece of HR signal; and (ii) to quantify the impact of data loss on feature extraction in a PPG-based HR signal. This was done by comparing real-life recordings from com-mercial sensors featuring both PPG (Empatica E4) and ECG (Zephyr BioHarness 3). After an out-lier rejection process, our quality index was used to isolate portions of ECG-based HR signal that could be used as benchmark, to validate the output of Empatica E4 at the signal level and at the feature level. Our results showed high accuracy for estimating the mean HR, poor accuracy for short-term HRV features and moderate accuracy for longer-term HRV features. Levels of error could be substantially reduced by using our quality index to identify time windows with few or no missing data.

To analyze the predictive ability and incremental value of left ventricular longitudinal axis strain (LAS) and late gadolinium enhancement (LGE) using standard cardiovascular magnetic resonance (CMR) imaging for the diagnosis and prognosis of severe aortic stenosis (AS) in patients with an indication for aortic valve replacement. We conducted a prospective study on 128 patients with severe AS and 52 volunteers. The evaluation protocol included standard biochemistry tests, novel biomarkers of myocardial fibrosis, 12-lead electrocardiograms and 24-hour Holter, the 6-minute walk test and extensive echocardiographic and CMR imaging studies. Outcomes were defined as the composite of major cardiovascular events (MACEs). Among AS patients, most (n = 17, 77.2%) of those who exhibited LGE at CMR imaging had MACEs during follow-up. Kaplan-Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE (p < 0.01) and decreased LAS (p < 0.001). In Cox regression analysis, only reduced LAS [hazard ratio 1.33, 95%CI (1.01 to 1.74), p < 0.01] and the presence of LGE [hazard ratio 11.3, 95%CI (1.82 to 70.0), p < 0.01] were independent predictors for MACEs. The predictive value increased if both LGE and reduced LAS were added to LVEF. None of the biomarkers of increased collagen turnover exhibited any predictive value for MACEs. LAS by CMR is an independent predictor of outcomes in patients with AS and provides incremental value beyond the assessment of LVEF and the presence of LGE.

Diabetic cardiac autonomic neuropathy (DCAN) is a severe complication of type 1 diabetes mellitus (T1DM) characterized by autonomic nerve fiber dysfunction in the heart and blood vessels. This study aimed to elucidate the histopathological mechanisms underlying DCAN and evaluate the therapeutic potential of MCC950, an NLRP3 inflammasome inhibitor, in a Wistar rat model. Male Wistar rats were divided into control and T1DM groups, with diabetes induced by streptozotocin (STZ) injection. Following confirmation of DCAN through elevated serum noradrenaline levels, diabetic rats were subdivided into positive control (insulin-treated), treatment (MCC950), and untreated groups. The stellate ganglia, thoracic aorta, and left ventricle were dissected for histological examination using Haematoxylin and Eosin (H&E) and Masson Trichrome staining. STZ-induced hyperglycemia was evident by Week 2 and sustained throughout the study. Serum noradrenaline levels significantly increased by Week 14 in diabetic rats, indicating DCAN onset. Histological analysis revealed atrophy in stellate ganglia, endothelial damage in the thoracic aorta, and myocardial fibrosis in untreated diabetic rats. MCC950 treatment preserved ganglionic structure, mitigated vascular damage, and reduced myocardial fibrosis, demonstrating its potential in attenuating DCAN progression. These findings highlight MCC950 as a promising therapeutic agent for DCAN by targeting inflammation and preserving autonomic and cardiovascular function. Further investigations are warranted to validate MCC950’s efficacy in human trials, with the potential to improve clinical outcomes for T1DM patients at risk of DCAN.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Background and Objectives: Pulmonary Hypertension (PH) is a clinical condition with high mortality rates, particularly in patients over 65. Current guidelines recommend assessing the Probability of Pulmonary Hypertension (PHP) using advanced echocardiography, before pro-ceeding to right heart catheterization. This study proposes using the common femoral vein (CFV), an accessible vein that reflects right atrial pressure, as an alternative method to assess the like-lihood of severe PHP. Materials and Methods: This prospective observational study included 175 emergency patients from three hospitals. Ultrasound assessed the Pulsed Wave Doppler (PW-Doppler) morphology of the CFV. This diagnostic yield for high PHP was evaluated along-side traditional ultrasound parameters (right-to-left ventricular basal diameter ratio greater than 1 (RV>LV), septal flattening, right ventricular outflow acceleration time of less than 105 ms and/or mesosystolic notching, pulmonary artery diameter greater than the aortic root diameter or over 25 mm, early pulmonary regurgitation maximum velocity >2.2 m/s, TAPSE/PASP less than 0.55, in-ferior vena cava (IVC) diameter over 21 mm with decreased inspiratory collapse, and right atrial (RA) area over 18 cm²). Results: The CFV's PW-Doppler cardiac pattern correlated strongly with high PHP, showing a sensitivity (Sn) of 72% and a specificity (Sp) of 96%. RA dilation and TAPSE/PASP < 0.55 also played significant diagnostic roles. Conclusions: The CFV's PW-Doppler cardiac pattern is an effective indicator of high PHP, allowing reliable exclusion of this condition when absent. This approach could simplify initial PHP evaluation in emergency settings or where echocardiographic resources are limited.

Right heart masses are usually suspected during a routine examination by transthoracic echocardiography or due to cardiac symptoms. Although very important, sometimes it may be a challenge to differentiate between normal structures (variants) and aberrant or pathologic masses regarding the right heart cardiac tumors. In the last entity, the majority of primary cardiac tumors in adults and children are benign; however, they may have a malignant counterpart. Right heart tumors might involve not only the walls (myocardium, endocardium and pericardium), but also valves and cardiac chambers. Cardiac tumors exhibit altered signal intensity and enhancement characteristics, requiring the use of several imaging methods following a multimodality-imaging algorithm that culminates in the excision or biopsy of the tumor formation. Therefore, various imaging modalities, including echocardiography, computer tomography, positron emission tomography, cardiac magnetic resonance imaging, scintigraphy or, even, invasive angiography, can be useful during their diagnosis. Echocardiography is the first-line non-invasive imaging modality used in the evaluation of the right heart tumors. Before the other diagnosis imaging modalities it is essential for defining morphology, assessing size, observing dynamic appearance, and evaluating functional abnormalities and hemodynamic consequences,. However, all imaging methods have frequently a complementary role; therefore, an integrated imaging approach is recommended.

Background and Objectives: The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is two times higher compared to the general population. The objective of this retrospective study was to determine the type of cardiovascular complications that can appear in men vs. women with rheumatoid arth-ritis. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. Materials and Methods: We included a number of 200 pa-tients, divided in 2 groups according to gender (124 women and 76 men) with rheumatoid arthritis, presenting various stages of disease concomitant with cardiovascular complications. We assessed traditional and non-traditional risk factors, electrocardio-graphic and echocardiographic findings in both groups. Results: All patients presented an atherogenic coefficient over two, indicating a significant risk of atherogenesis. Men had elevated levels of total cholesterol compared with women (≥ 200 mg/dL; 77.6% - men vs. 25.8% - women, p<0.001). The participants presented cardiac arrhythmias, especially in the active stage of RA. Women had an increased risk of atrial fibrillation by 2.308 times compared with men (p=0.020). One of the most important complications in young women was pulmonary arterial hypertension (p=0.007). Conclusion: However, in daily clinical practice, the screening for RA is poorly done. Thus, patients are often undiagnosed, while the risk factors are not assessed and RA patients continue to present an increased risk of developing CVD.

Background: Patients with infectious complications related to the presence of cardiac implantable electronic devices (CIED) constitute a heterogeneous group, including local pocket infection (PI) and lead related infectious endocarditis (LRIE). The diagnosis of CIED-related infection is often difficult and requires complex imaging and microbiological tests. The aim of the current study was to evaluate the usefulness of new simple hematological parameters in detecting infectious complications in patients with CIED and assessing their extent. Methods: The retrospective analysis of clinical data of 2909 patients (36.37% with CIED-related infections), undergoing transvenous lead extraction (TLE) procedures in three high-volume centres in the years 2006-2020, was conducted. The sensitivity and specificity of new hematological markers were evaluated: the neutrophil to lymphocyte ratio (NLR), neutrophil to platelet ratio (NPR), and lymphocyte to platelet ratio (LPR) in the diagnosis of infectious complications, assessment of the spread of the infectious process and differentiation of additional structures related to the presence of leads. Results: In patients with CIED infections, compared to the non-infectious group, high inflammatory parameters were confirmed, and the highest specificity of the new markers in detecting the infectious process was demonstrated. (79.47% for NPR and 72.82% for NLR). Analysis of laboratory parameters in infectious and non-infectious patients with the presence of additional lead-related masses showed the highest specificity of NPR (82,78%) in predicting the diagnosis of vegetation. Comparison of laboratory parameters in patients with LRIE and PI showed higher NLR % (4.24 vs 2.56; p<0.001, area under curve (AUC) in a receiver operating characteristic (ROC) curve: 0.67 and 0.78 respectively) and higher NPR (0.03 vs 0.02; p<0.001; AUC: 0,51 and 0,55) in patients with LRIE. The highest sensitivity in the detection of coexistence LRIE with PI has been demonstrated for NLR (87.33%). Conclusions: Novel hematological markers may be helpful in the recognition of the inflammatory process in patients with CIED, differentiation of vegetation and vegetation-like masses, and the extent of infection in patients with PI.

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.

Myocardial infarction (MI) is a serious cardiovascular disease that can lead to death. Cardiac troponin I (cTnI) is a biomarker of MI in the circulation system. For detection cTnI protein, many method suffer the same problem, time-consuming. Main drawbacks are time consuming, have tedious operation, require an expensive reader for translating signals, and require non-accessible reagents. Our goal is to create a kit for cTnI protein testing, that the result can easily be read by color difference. The main breakthrough is, the resolution between different concentration can be told by eyes. The result will be future used to create a commercial, potable, convenient, daily-used rapid-test kit. In this study, a cTnI biosensor is proposed that can be read by the naked eye, performs diagnosis based on the pattern color, does not require a reader machine, is easy to operate, and is portable. Our work proposed a device that shortens the diagnosis time, has a quantitative analysis range of 0.32 –200 ng/mL in the human serum matrix, has a 0.32 ng/mL limit of detection (LOD), and shows many advantages comparing to traditional cTnI ELISA plate.

(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&lt;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

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haemato-chemical parameters as a POAF onset biomarker in subjected to cardiac surgery. Materials and Methods: We enrolled 90 patients (mean age= 66.9±2.8 years; 40 men and 20 females) with diverse heart pathologies and subjected to cardiothoracic surgery. Their blood samples were collected and used to determine haemato-chemical parameters. The tree test approach was used to detect the best data-driven ferritin cuff-off value (=141 ng/ml) to predict POAF risk. Results: The data obtained demonstrated significant higher concentrations, absolute values, and percentages, of ferritin, RDW, PLTs, in POAF patients. However, the ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥ 141 ng/ml identifies the subjects at the highest POAF risk. Conclusions: Ferritin values≥ 141 ng/ml might be used as predictive POAF biomarker.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; two weeks later, the labeled cells were transplanted into ISO-induced heart-injury rats through the tail vein or ASD device for five days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson’s trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after three days of transplantation, there were many BMSCs on the epicardial surface, and after five days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD+BMSCs-three days treated group and ASD+BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P<0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. Can HTK also protect neurons from severe hypoxia (SH) following CA? We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and NADPH oxidase-4 (NOX4) expression were evaluated at different time points till 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluating NOX4 and H2O2 level in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persisted HIF-1α expression, reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity and NOX4 gene expression were all decreased in the brain specimen of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution.

While the importance of continuous monitoring of electrocardiographic (ECG) or photoplethysmographic (PPG) signals to detect cardiac anomalies is generally accepted in preventative medicine, there remain major barriers to its actual widespread adoption. Most notably, current approaches tend to lack real-time capability, exhibit high computational cost, and be based on restrictive modeling assumptions or require large amounts of training data. We propose a lightweight and model-free approach for the online detection of cardiac anomalies such as ectopic beats in ECG or PPG signals based on the change detection capabilities of Singular Spectrum Analysis (SSA) and nonparametric rank-based cumulative sum (CUSUM) control charts. The procedure is able to quickly detect anomalies without requiring the identification of fiducial points such as R-peaks and is computationally significantly less demanding than previously proposed SSA-based approaches. Therefore, the proposed procedure is equally well suited for standalone use and as an add-on to complement existing (e.g. heart rate (HR) estimation) procedures.

The therapeutic applicability of mesenchymal stem cells (MSC) for a range of conditions has garnered increasing interest. This study aimed to evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period in a population of 2,504 patients (age, 54.09 ± 11.65 years) receiving MSC therapy (mean dose, 1.49 ± 0.75 billion cells) for various indications (over two-thirds [n=1,700, 67.89%] received MSC therapy as an anti-ageing therapy) and evaluate for potential risk factors for MACCE development in this cohort. In multivariate Cox proportional hazards regression analysis, age, but not sex and MSC dose, was significantly associated with MACCE risk (hazard ratio=1.127; 95% confidence interval=1.0418, 1.219; p=0.0029). The adverse event rate was 0.8%, and none of the reported adverse events were severe. In conclusion, our study showed that stem cell therapy was safe in a large cohort of individuals and was associated with a low rate of MACCE.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p&lt;0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Background: Since the onset of widespread COVID-19 vaccination campaigns, there have been concerns about serious cardiovascular adverse events, including myocarditis, myocardial infarction, and venous thromboembolisms, all of which can lead to cardiopulmonary arrest. This study aimed to estimate excess cardiopulmonary arrest mortality in King County, WA, and investigate any association with COVID-19 vaccination rates. Methods: Data was obtained from the annual King County, WA, EMS reports, the U.S. Census Bureau, and The Tennessean COVID-19 Vaccine Tracker. An exploratory data analysis was performed. Excess deaths were calculated using the 2015-2020 cardiopulmonary arrest mortality trend line. The relationship between excess cardiopulmonary arrest mortality and vaccination rates was analyzed using polynomial regression analysis. A quadratic regression model was used to generate expected population growth trends. The excess mortality model for King County was used to calculate yearly estimates for excess cardiopulmonary arrest fatalities in the USA. Results: Approximately 98% of the King County population received at least one dose of a COVID-19 vaccine by 2023. Our analysis revealed a 25.7% increase in total cardiopulmonary arrests and a 25.4% increase in cardiopulmonary arrest mortality from 2020 to 2023 in King County, WA. Excess cardiopulmonary arrest deaths were estimated to have increased by 1,236% from 2020 to 2023, rising from 11 excess deaths (95% CI: -12, 34) in 2020 to 147 excess deaths (95% CI: 123, 170) in 2023. A quadratic increase in excess cardiopulmonary arrest mortality was observed with higher COVID-19 vaccination rates. The general population of King County sharply declined by 0.94% (21,300) in 2021, deviating from the expected population size. Applying our model from these data to the entire United States yielded 49,240 excess fatal cardiopulmonary arrests from 2021-2023. Conclusions: We identified a very strong ecological and temporal association between excess cardiopulmonary arrest mortality and the COVID-19 vaccination campaign, which resulted in high vaccination rates. The biological plausibility of death from acute cardiac and pulmonary causes after COVID-19 vaccination has been previously demonstrated and is concerning given these real-world observations. Urgent further research is needed to determine if similar trends are observed in other regions with attention to risk mitigation for incident events and improved survival with resuscitation.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

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.

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.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed for a median of 28 months. Digitalis use was assessed at the time of CRT implantation. Multivariate Cox-regression model and propensity score matching was used to determine all-cause mortality as primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%), and ICD shocks were assessed as secondary endpoints. Results: The study comprised 552 CRT recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR=1.14; 95% CI 0.88-1.5; p=0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR=1.04; 95% CI 0.75-1.45; p=0.82). Also, in comparison to 286 propensity score matched patients, mortality was not affected by digitalis intake (propensity adjusted HR=1.11; 95% CI 0.72-1.70; p=0.64). CRT response was predominant in digitalis non-users concerning both improvement of HF symptoms and LVEF (NYHA p<0.01; LVEF p<0.01) while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p=0.01). Conclusions: Digitalis therapy had no effect on mortality but did negatively affect CRT response and susceptibility to ventricular arrhythmias requiring ICD shock treatment.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via the whole-genome genotyping with genetic markers and linkage assay in a family suffering AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89-cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. Exome-wide sequencing assay unveiled that at the defined locus, solely the mutation in the TBX20 gene, NM_001077653.2: c.695A&gt;G; p.(His232Arg), co-segregated with AF in the family. Additionally, Sanger sequencing assay of TBX20 in another family suffering AF uncovered a novel mutation, NM_001077653.2: c.862G&gt;C; p.(Asp288His). Neither of the two mutations was observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while without effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-causative gene, shedding light on the mechanism underlying AF and suggesting clinical significance for allele-specific treatment of AF patients.

Background Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular the potential to prolong cardiac repolarisation by using this combination has been discussed. Materials and methods We report a pragmatic and simple safety approach which we implemented in the first patients treated for COVID-19 in our center early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) >500 ms, hypokalaemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 hours of the initial prescription. Results Among 424 consecutive adults (mean age 46.3 ± 16.1 years; 216 women). Patients were followed in conventional wards (21.5%) or in a day-care unit (78.5%). A total of 11 patients (2.6%) had contraindications to HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after two days (p=0.003). Ten patients (2.4%) developed QTc prolongation >60 ms, and none had QTc >500 ms. Conclusions This report do not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, a simple initial assessment of patient medical history, ECG and kalaemia identifies contraindicated patients and enables the safe treatment by HCQ-AZ of COVID-19 patients. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are followed.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Our brain continuously interacts with the body as we engage with the world. Although we are mostly unaware of internal bodily processes, such as our heartbeats, they may be influenced by and in turn influence our perception and emotional feelings. While there is a recent focus on understanding cardiac interoceptive activity and interaction with brain activity during emotion processing, the investigation of cardiac-brain interactions with more ecologically valid naturalistic emotional stimuli is still very limited. We also do not understand how an essential aspect of emotions like context familiarity influences affective feelings and is linked to cardiac-brain interactions. Hence to answer these questions, we designed an exploratory study by recording ECG and EEG signals for the emotional events while participants were watching emotional movie clips. Participants also rated their familiarity with the stimulus on the familiarity scale. Linear mixed effect modelling was performed in which the ECG power and familiarity were considered as predictors of EEG power. We focused on three brain regions, including prefrontal (PF), frontocentral (FC) and parietooccipital (PO). The analyses showed that cardiac-brain interaction is dependent on familiarity such that the interaction is stronger with high familiarity. In addition, the results indicate that arousal is predicted by cardiac-brain interaction, which also depends on familiarity. The results support emotional theories that emphasize context dependency and interoception. Multimodal studies with more realistic stimuli would further enable us to understand and predict different aspects of emotional experience.

This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene coding for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research on PITX2-dependent AF is not sufficient for understanding atrial functional proprieties. Linking PITX2 to ion channels, cells, tissues, atria and the whole heart, computational models are necessary for achieving a quantitative understanding of atrial structure and function in PITX2-dependent AF. Computational approaches are used to capture all that we know about PITX2-dependent AF and to develop improved therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives.

Cardiac ischemia-reperfusion injury (IRI) occurs when blood flow is restored to the myocardium after a period of ischemia, leading to oxidative stress and subsequent myocardial cell damage, primarily due to the accumulation of reactive oxygen species (ROS). In our previous research, we identified that miR-25 is significantly overexpressed in pressure overload-induced heart failure, and its inhibition improves cardiac function by restoring the expression of SERCA2a, a key protein involved in calcium regulation. In this study, we aimed to investigate the role of miR-25 in the context of ischemia-reperfusion injury. We found that miR-25 was markedly upregulated under hypoxic conditions in both in vitro and in vivo models. Through in silico analysis, we identified Sestrin3 (SESN3), an antioxidant protein known for its protective effects against oxidative stress, as a novel target of miR-25. Based on these findings, we hypothesized that inhibiting miR-25 would restore Sestrin3 expression, thereby reducing ROS-induced myocardial cell damage and improving cardiac function. To test this hypothesis, we employed two model systems: a hypoxia/reoxygenation (H/R) stress model using H9c2 myoblasts and a surgically induced ischemia-reperfusion injury mouse model. Our results demonstrated that the use of miR-25 inhibitors significantly improved cardiac function and reduced myocardial damage in both models through the restoration of SESN3 expression. In conclusion, our findings suggest that targeting miR-25 may serve as a novel therapeutic modality to alleviate oxidative damage in the heart.

Introduction: The Fontan procedure, a palliative surgery for univentricular heart physiology, of-ten reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Methods: Fontan patients aged 8-30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions, with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results: The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and per cent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min, but did not reach statistical significance (p = 0.05). Most haemodynamic and ventila-tory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains (p < 0.001). High adherence (85-93%), no adverse events, and reduced NT-proBNP levels supported the program's safety. Conclusion: This study's findings have im-portant implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ven-tricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained ben-efits.

Background: pathophysiological changes like low cardiac output (LCO) impact pharmacokinetics, but its extent may be different throughout pediatrics compared to adults. Physiologically based pharmacokinetic (PBPK) modelling enables further exploration. Methods: A validated propofol model was used to simulate the impact of LCO on propofol clearance across age groups using the PBPK platform, Simcyp® (version 19). The hepatic and renal extraction ratio of propofol was then determined in all age groups. Subsequently, dose explorations were conducted under LCO conditions, targeting a 3 µg/mL (80-125%) propofol concentration range. Results: Both hepatic and renal extraction ratios increased from neonates, infants, children to adolescents and adults. The relative change in clearance following CO reductions increased with age, with the least impact of LCO in neonates. The predicted concentration remained within the 3 µg/mL (80-125%) range under normal CO and LCO (up to 30%) conditions in all age groups. When CO was reduced by 40-50%, a dose reduction of 15% is warranted in neonates, infants and children, 25% in adolescents and adults. Conclusions: PBPK driven, the impact of reduced CO on propofol clearance is predicted to be age-dependent, proportionally greater in adults. Consequently, age group specific dose reductions for propofol are required in LCO conditions.

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.

Microvascular complications are one of the key causes of mortality among type-2 diabetic patients. This study was sought to investigate the use of a novel machine learning approach for predicting these complications from patient demographic, clinical, and laboratory profiles only. A total of 96 Bangladeshi participants having type-2 diabetes were recruited during their routine hospital visits. All patient profiles were assessed by using a Chi-squared (2) test to statistically determine the most important markers in predicting four microvascular complications; namely cardiac autonomic neuropathy (CAN), diabetic peripheral neuropathy (DPN), diabetic nephropathy (NEP), and diabetic retinopathy (RET). A machine learning approach based on random forest (RF) and support vector machine (SVM) was then developed to ensure automated clinical testing for microvascular complication in diabetic patients. The highest prediction accuracies were obtained by RF using diastolic blood pressure, Albumin-Creatinine ratio, and gender for CAN testing (98.67%), Microalbuminuria, smoking history, and hemoglobin A1C for DPN testing (67.78%), Albumin-Creatinine ratio for NEP testing (100%), and hemoglobin A1C, Microalbuminuria, and smoking history for RET testing (84.38%). This study suggests machine learning as a promising automated tool for predicting microvascular complications in diabetic patients using their profiles, which could help prvent those patients from further microvascular complications leading to early death.

Motorcycles can be considered a new form of smart vehicle when taking into account their small and modern structure and due to the fact that nowadays they are used in the new role of ambu-lance to rapidly reach emergency patients in large cities with traffic congestion. However, there is no study regarding the measuring of access time for motorcycle ambulances in large cities of Thailand. Therefore, this study aims to compare access times to patients between motorcycle ambulances and conventional ambulances, including analysis of the use of AED installed on motorcycle ambulances to contribute to the sustainable development of public health policies. In two hundred and seventy-one operations, it was found that the times from dispatch to vehicle (ambulance and motorlance) being en route and times from the 1669 center (center for com-mand-and-control EMS in Thailand) call receipt to arrival on scene (response time) of motorcycle ambulances was shorter than that of a conventional ambulance and the use of AED on a motor-cycle ambulance can increase the chances of survival for patients with cardiac arrest outside the hospital in public places where AEDs are not available and in all cases where access to an AED was less than eight minutes.

The pleiotropic biochemical and antioxidant functions of Vitamin C (Vit C) have recently sparked interest in its application in intensive care. Vit C protects important organ systems such as the cardiovascular, neurologic and renal system during inflammation and oxidative stress. Vit C also influences the systems of coagulation and inflammation and its application might prevent the development of organ damage. The current evidence of Vit C’s effect on the pathophysiological reactions during various acute stress events, such as sepsis, shock, trauma, burn and ischemia-reperfusion injury imposes the question, if the application of Vit C might be especially beneficial for cardiac surgery patients, who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of Vit C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between Vit C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence regarding the administration of Vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage and most the appropriate application strategy.

There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model, where in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus were accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich “transition zone” at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with “perforations” lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations, created by localized MMP activity serve as a site for the initiation of a “split” of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and it’s signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements.

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.

fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Join us on a journey that unravels the mysteries of molecular intricacies, delves into advanced imaging techniques, and sheds light on therapeutic pathways. Unveiling the role of cardiac amyloidosis, particularly sub-clinical isolated cardiac amyloidosis (ICA), the narrative unfolds the heightened risk of AF in the elderly. State-of-the-art imaging techniques like cardiac magnetic resonance (CMR) and molecular imaging step into the spotlight, unraveling diagnostic and prognostic nuances of AF and HFpEF. Embarking on the molecular voyage, the article navigates through next-generation sequencing and comprehensive genomic profiling, shedding light on genetic alterations shaping the AF-HFpEF landscape. This molecular compass lays the groundwork for personalized medicine, illuminating pathways to identify therapeutic bullseyes and biomarkers. In the realm of medical strategies, the discussion homes in on the promising notes struck by SGLT2 inhibitors, particularly dapagliflozin, orchestrating a reduction in AF burden. Characters like spironolactone and dronedarone make appearances, each weaving a distinct tale, revealing their potential roles in steering the ship for AF- HFpEF patients. The subplot involving obesity in HFpEF unfolds, with the LEGACY study portraying the benefits of weight reduction. The pivotal intervention of catheter ablation emerges as the hero, boasting positive outcomes in reducing hospitalization rates and overall mortality for AF-HFpEF patients. However, cautionary tales echo about its impact on left atrial function, adding layers of complexity that beckon careful consideration and monitoring. Amidst the narrative, critical discussions unfold about the limitations of current research, echoing the need to define acute heart failure, refine imaging techniques, and tailor management strategies. The narrative passionately advocates for a personalized touch in addressing AF-HFpEF, recognizing the unique blend of clinical and molecular personas. In essence, this review paints a vivid mural of AF-HFpEF, skillfully bridging the realms of molecular intricacies and the artistry of clinical management.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Keywords: Hypertensive emergency; diagnosis; lactate dehydrogenase; high sensitivity cardiac troponin T; brain natriuretic peptide; area under the curve.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

Decades of research identified numerous gene biomarkers of cardiac diseases whose restored sequence or/and expression level was hoped to recover the normal cardiac function. However, each human has unique and dynamic pathophysiological characteristics resulting from the unrepeatable combination of favoring factors such are: race, sex, age, medical history, diet, stress, exposure to toxins, habits etc. As such, no treatment fits everybody and finding personalized solutions is a top priority for medicine of 21st century. The Genomic Fabric Paradigm (GFP) provides the most theoretically possible comprehensive characterization of the transcriptome, its alterations in disease and recovery following a treatment. By attaching to each gene the independent average expression level, expression variation and expression coordination with each other gene, GFP delivers thousands times more information than the traditional analysis. This report presents the theoretical bases of the GFP and some applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failure. The GFP analyses revealed novel transcriptomic aspects of the gene expression control and networking under ischemic conditions. Through all-inclusive characterization of the transcriptome and the unrepeatable gene hierarchy in each condition, GFP is an essential avenue towards development of a truly personalized cardiogenomic therapy.

In the recent years, tissue engineering researchers have exploited a variety of biomaterials that can potentially mimic extracellular matrix (ECM) for tissue regeneration. Natural cellulose, mainly obtained from bacterial (BC) and plant-based (PC) sources, can serve as a high potential scaffold material for different regenerative purposes. Natural cellulose has drawn the attention of researchers due to its advantage over synthetic cellulose in terms of availability, cost-effectiveness, perfusablility, biocompatibility, negligible toxicity, mild immune response and due to imitating native tissues. In this article, we will review the recent in vivo and in vitro studies aimed to assess the potentials of natural cellulose for the purpose of soft (skin, heart, veins, nerve, among others) and hard (bone and tooth) tissue engineering.

The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we performed docking calculations and high-throughput electrophysiology experiments. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the “mouth” of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.

(1) Background: In patients suffering from heart failure, the main causes of death are either he-modynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extend of these devices. (2) Methods: The primary outcome of this single center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fi-brillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients – symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death – were included retrospectively: 59% is-chemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP). Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not signif-icantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 pa-tients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95%confidence interval [CI] 0.45 to 2.28; p =0.97). All-cause mortality occurred in 14 of 166 pa-tients (8.4%) in NICMP group and 18 of 237 patients (7.6%) in ICMP group. Sudden cardiac death occurred in 2 patients (1.2%) in the NICMP group and in 4 patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; P=0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusion: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovas-cular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

In cardiac surgery, post-sternotomy pain is a significant issue, peaking within 48 hours and requiring proper analgesia for both acute relief and to avoid chronicization. Opioids are commonly used for pain management post-surgery but pose risks like adverse effects and dependency. Post-cardiac surgery pain can stem from various sources - somatic, visceral, and neuropathic, making opioid reliance a concern. Multimodal analgesia, combining different medications and regional anesthesia techniques, is increasingly recommended to decrease opioid use and its related problems. Strategies include acetaminophen, gabapentinoids, NMDA antagonists, alpha-2 agonists, intravenous lidocaine, anti-inflammatory drugs, and regional anesthesia. Implementing these approaches can enhance pain control, lessen opioid reliance, and improve cardiac surgery outcomes. The ERAS® Cardiac Society strongly advocates for an opioid-sparing multimodal approach to benefit patient recovery by reducing complications and enhancing satisfaction. This review aims to consolidate current evidence to assist healthcare providers in customizing pain management for patients post-cardiac surgery, emphasizing reduced opioid use and optimizing the recovery process.

Sudden unexpected death (SUD) is a fatal event that occurs in an apparently healthy subject so that such an abrupt outcome could have not been predicted. SUD - including sudden intrauterine unexplained death (SIUD), sudden neonatal unexpected death (SNUD), sudden infant death syndrome (SIDS), sudden unexpected death of the young (SUDY), sudden unexpected death in the adult (SUDA) - occurs as the first manifestation of an unknown underlying disease or within a few hours of presentation of a disease. SUD is a major unsolved, shocking form of death that occurs frequently and can happen at any time without warning. For each case of SUD, a review of clinical history data and performance of a complete autopsy, particularly focused on the study of the cardiac conduction system were carried out according to the necropsy protocol devised by the Lino Rossi Research Center, Università degli Studi di Milano, Italy. Research cases are represented by 75 SUD victims, subdivided into 15 SIUD, 15 SNUD, 15 SUDY, and 15 SUDA victims, collected and selected for this study. After the routine autopsy and clinical history analysis, the death remained unexplained and hence a diagnosis of SUD was assigned to the 75. subjects, which included45 females (60%) and 30 (40%) males, ranging in age from 27 gestational weeks to 76 years. Serial sections of the cardiac conduction system disclosed frequent congenital alterations, of the cardiac conduction system in fetuses and infants. An age-related significant difference in distribution among the 5 age-related groups was detected for the following anomalies of the conduction system: central fibrous body (CFB) islands of conduction tissue, fetal dispersion, resorptive degeneration, Mahaim fiber, CFB cartilaginous meta-hyperplasia, His bundle septation, sino-atrial node (SAN) artery fibromuscular thickening, atrio-ventricular junction hypoplasia, intramural right bundle branch, and SAN hypoplasia. The results data are useful to understand the cause of death for all SUD cases that were unexpected and would have otherwise remained unexplained, so to motivate medical examiners and pathologists to perform more in-depth studies.

Patients recovering from bone disruption due to trauma or surgery need to limit movement to minimize shear force, thereby protecting callus formation and osteogenesis. Patients often use their arms to assist with functional activities, but pushing is frequently limited to <10 lb (4.5 kg). With only verbal instructions, patients’ ability to accurately limit weight-bearing (WB) force is poor. A therapeutic intervention to improve patient adherence with upper extremity (UE) WB guidelines during functional mobility using an instrumented walker could be beneficial. Therefore, the purpose of this article is to describe a feedback training protocol to improve the ability to modulate weight-bearing force in older adults and then provide an overview of the efficacy of this protocol and subsequent development of a Clinical Force Measuring Walker. An instrumented walker was used to measure UE WB during functional mobility in older healthy subjects (n = 30) before, during, and after (immediately and 2 hours) a visual and auditory concurrent feedback training session. During feedback training, force was significantly reduced with all 3 sessions as compared to baseline. When using the front wheeled walker, UE WB force during the second and third feedback training trials went down compared to the first trial. During the third feedback training trial, force was greater than the two previous trials while transferring sit-to-stand and stand-to-sit. After completion of practice with feedback, UE WB force was significantly reduced and remained so 2 hours later. These findings suggest that feedback training is effective for helping patients to modulate UE WB. Use of an instrumented walker and feedback training would be beneficial in clinical practice, especially with older patients. A more intensive feedback training with additional trials and or simultaneous visual and auditory cues during whole-practice may be needed to get UE WB below a 10 lb threshold.

The peril of a 3-dimensional, robust and sustained myocardial restoration by means of Tissue Engineering is that it still remains a largely experimental approach. Prolific protocols have been developed and tested in small and large animals, but as clinical cardiac surgeons, we have not come to the privilege of utilizing any of them in our clinical practice. The question arises: why? The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support its viability and function. Currently available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed and a heart transplantation is an ultima ratio treatment option. Owing to equivocal results of cell-based therapies, several strategies have been pursued to overcome limitations of the current treatment options. Preclinical data as well as first-in-human studies conducted to date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In the light of the available data, injectable biomaterials suitable for transcatheteter delivery appear to have the highest translational potential,. This article presents a current state-of-the-art in the field of hydrogel-based myocardial restoration therapy.

Background: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoid malignancy. The majority of patients are asymptomatic and HCL is usually diagnosed incidentally during a routine blood cell counts. In symptomatic patients, typical symptoms are related to pancytope-nia and splenomegaly. In this review we present, rare clinical symptoms in patients with HCL. Methods: A literature search was conducted of PubMed, Web of Science, and Google Scholar for articles concerning hairy cell leukemia, leukemia cutis, bone lesions, neurological manifesta-tions, pulmonary symptoms, ocular manifestations, cardiac manifestation, rare symptoms. Publications from January 1980 to August 2024 were scrutinized. Additional relevant publica-ions were obtained by reviewing the references from the chosen articles. Results: Extra medul-lary and extra nodal manifestations of classic HCL are rare. However, leukemic involvement in the skin, bone, central nervous system, gastrointestinal tract, heart, kidney, liver, lung, ocular and other organs have been reported.

Background: Substance use continues to be on the rise in the United States and has been linked to new onset cardiovascular (CVDs) and cerebrovascular disorders (CeVDs) leading to hospitalizations. We aimed to study the association of different subtypes of substance use disorders (SUDs) among hospitalized patients, with the different subtypes of CVDs and CeVDs, using the National Inpatient Sample (NIS) Database. Additionally, we aimed to assess the odds of hospitalizations with new onset CVDs and CeVDs among patients with different types of SUDs. Methods: A retrospective study of the NIS database (2016-2017) using the ICD-10-CM codes was performed. The hospitalizations with a secondary diagnosis of SUDs were identified. Weighted univariate analysis using the chi-square test and multivariate survey logistic regression analysis was performed to evaluate for the incidence, prevalence, and odds of association between vascular events and SUDs. Results: There were a total of 58,259,589 hospitalizations, out of which 21.42% had SUDs. Out of all the hospitalized patients between the age 18-50, more patients had SUDs than not (31.83%, p< 0.0001). This difference existed for all the different subtypes of SUDs including alcohol related disorder (42.61%), amphetamine dependence (76.17% vs 31.83%), cannabis related disorder (75.17%), cocaine related disorders (57.87%), hallucinogen related disorder (82.91%), inhalant related disorders (67.25%), opioid related disorders (52.86%), and nicotine dependence (35.72%). We found a significant association of acute ischemic stroke with amphetamine dependence (OR 1.23, 95%CI 1.14-1.33), cocaine related disorders (1.17, 1.12-1.23) and nicotine dependence (1.42, 1.40-1.43). Similarly, the association of intracerebral hemorrhage was higher with amphetamine dependence (2.58, 2.26-2.93), and cocaine related disorders (1.62, 1.46-1.79). The association of subarachnoid hemorrhage was noted to be higher with amphetamine dependence (1.82, 1.48-2.24) and nicotine dependence (1.47, 1.39-1.55). In terms of association of cardiovascular disorders with SUDs,the patients with myocardial infarction had higher odds of nicotine dependence (1.85, 1.83-1.87) than not, Similarly, the patients with angina pectoris were noted to have a higher association with cocaine related disorders (2.21, 1.86-2.62), and those with atrial fibrillation had a higher association alcohol related disorders (1.14, 1.11-1.17). Conclusion: Our study demonstrates the variability of CVD and CeVD in patients hospitalized for SUD. Findings from our study may help promote increased awareness and early management of these events. Further studies are needed to evaluate specific effects of frequency and dose on the incidence and prevalence of CVD and CeVD in patients with SUD.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines’ storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, rather than thrombolysis performed, to avoid potential adverse events of the latter in the setting of SCAD.

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.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

The objective of this study was to identify the key elements used by prehospital emergency physicians (EP) to decide whether or not to attempt advanced life support (ALS) in asystolic out-of-hospital cardiac arrest (OHCA). From 01.01.2009 to 01.01.2017, all adult victims of asystolic OHCA in Geneva, Switzerland, were retrospectively included. Patients with signs of "obvious death" or with a Do-Not-Attempt-Resuscitation order were excluded. Patients were categorized as having received ALS if this was mentioned in the medical record, or, failing that, if at least one dose of adrenaline had been administered during cardio-pulmonary resuscitation (CPR). Prognostic factors known at the time of EP's decision were included in a multivariable logistic regression model. 784 patients were included. Factors favourably influencing the decision to provide ALS were witnessed OHCA (OR=2.14, 95%CI1.43–3.20) and bystander CPR (OR=4.10, 95%CI2.28–7.39). Traumatic aetiology (OR=0.04, 95%CI0.02–0.08), age >80 years (OR=0.14, 95%CI0.09–0.24) and a Charlson comorbidity index greater than 5 (OR=0.12, 95%CI0.06–0.27) were the factors most strongly associated with the decision not to attempt ALS. Factors influencing the EP’s decision to attempt ALS in asystolic OHCA are the relatively young age of the patients, few comorbidities, presumed medical aetiology, witnessed OHCA and bystander CPR.

The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.

Introduction: The aim of our study was to assess the role of ECG-gated Coronary CT Angiography (CCTA) in the diagnosis, imaging follow-up, and treatment guidance in post-procedural/surgical interventions of the heart and thoracic aorta (PTCA, TAVI, PMK/ICD placement, CABGs).

Cardiac vascular diseases, especially acute myocardial infarction (AMI), are one of the leading causes of death worldwide. Therefore cardio-specific biomarkers such as cardiac Troponin I (cTnI) play an essential role in diagnostics. In order to enable rapid and accurate measurement of cTnI with the potential of online measurements, a proof of concept of a chemiluminescence-based biosensor is presented. A flow cell was designed and combined with a sensitive CMOS camera allowing an optical readout. In addition, a microfluidic setup was established, and cTnI was determined selectively. The biomarker cTnI was expressed in E. coli, and its characterization and correct folding were investigated by different analytical methods. This recombinant cTnI was used for enzyme-linked immunosorbent assays (ELISA), calibrated against commercially available recombinant cTnI, and applied for the biosensor measurements. Based on chemiluminescence detection, the biosensor was successfully tested, and the cTnI biomarker could be reproducibly determined in buffer, spiked blood serum, and plasma.

Background: In the heart, aldosterone (Aldo) binds the mineralocorticoid receptor (MR) to exert damaging, adverse remodeling-promoting effects. We recently showed that G protein-coupled receptor (GPCR)-kinase (GRK)-5 blocks the cardiac MR by directly phosphorylating it, thereby repressing its transcriptional activity. MR antagonist (MRA) drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure. Non-steroidal MRAs, such as finerenone, may provide better cardio-protection against Aldo than classic, steroidal MRAs, like spironolactone and eplerenone. Herein, we sought to investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade. Methods: We used the cardiomyocyte cell line H9c2 and neonatal rat ventricular myocytes (NRVMs). Results: GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone. Unlike eplerenone, finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity, thus displaying inverse agonism. GRK5 is necessary for finerenone`s inverse agonism, since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity. Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels. Finally in NRVMs, GRK5 is necessary for the anti-apoptotic and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis and fibrosis. Conclusions: Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart. GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

The aim of study was to investigate epidemiology aspects of magnetic resonance imaging (MRI) during COVID-19 pandemic. The study comprised depersonalized residents of Tomsk and Tomsk Region (n = 1714). Invitations to take online survey were sent to 50,000 residents by target SMS with response rate of 1.2% (n = 727, Cohort 1). Cohort 2 comprised retrospective patients (n = 987) who underwent contrast-enhanced cardiac MRI (CMR) in 2019-2022. Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. 29% of respondents in cohort 1 received MRI examination within past two years; 26% of respondents considered MRI the most informative imaging modality for detecting COVID-19 pneumonia; 12% of respondents reported MRI unavailable. Proportion of CMR among MRI studies increased during COVID-19 pandemic, and maximum incidence of cardiac diseases detected by MRI was in 2021. Incidence of myocardial fibrosis increased from ~67% in 2019 to ~84% in 2022. The rate of outpatient MRI studies significantly increased in 2020, but returned to pre-pandemic level in 2021. COVID-19 pandemic increased the need for MRI and CMR. Patients with history of COVID-19 had persistent and newly occurring symptoms of myocardial damage suggesting chronic cardiac involvement requiring continuous follow-up.

Heart failure with preserved ejection fraction (HFpEF) is a multifariousness syndrome, account-ing for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF, or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dys-function seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from an-imal models and human myocardial tissues from failed hearts shows that mitochondrial aberra-tions cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angioten-sin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodelling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and associ-ated signal molecules.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Also, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

Objective: The primary objective of this study was to develop a logistic regression model to predict post-operative in-hospital mortality rates for patients undergoing emergency cardiac surgeries, with the aim of improving predictive accuracy over traditional risk assessment tools and enhancing patient outcomes and clinical decision-making. Methods: Data were collected from 4,855 patients who underwent emergency cardiac surgeries at a tertiary hospital between 2008 and 2017. The analysis incorporated demographic, anthropomet- ric, and clinical factors, including the ASA classification, emergency status, and various preoperative laboratory values. A logistic regression model was developed, and the Elixhauser Comorbidity Index was calculated using standard ICD-10 codes for its comprehensive assessment of comorbidities. Model performance was evaluated using metrics such as AUROC, AUPRC, accuracy, precision, recall, and F1 score. Results: The logistic regression model demonstrated strong predictive performance, with an AUROC of 0.939 and an AUPRC of 0.350. Key pre-operative factors identified included emergency operation status, ASA classification, and preoperative prothrombin time. The model significantly outperformed the traditional ASA classification system, which showed an AUROC of 0.524 and an AUPRC of 0.010. These findings suggest a substantial improvement in predicting post-operative mortality. Conclusion: The logistic regression model significantly improves the prediction of post-operative mortality in emergency cardiac surgeries compared to the ASA classification system. These findings highlight the potential of incorporating comprehensive pre-operative factors into predictive models to enhance clinical decision-making and patient outcomes. Implementing such models in routine clinical practice could lead to more accurate risk assessments, better resource allocation, and improved patient care.