Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.

Objectives: Evaluate hand-held echocardiography (HHE) performed and interpreted by trained Advanced Practice Providers (APPs) on hospitalized CHF patients for image quality and interpretation, by comparing against expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: a) Left ventricular (LV) size, b) LV ejection fraction (LVEF), and c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted HHE images and compared with APPs and SE findings. Kappa-statistics determined the degree of agreement between APPs and study echocardiographer interpretation of HHE images and SE. Results: 80 CHF patients [age 73±14 years, 58% males; LVEF (by SE) 45±19%; 36.3% body mass indexes ≥30 kg/m2] were enrolled. HHE interpretation by APPs had good agreement for LVEF (kappa 0.79) with study echocardiographer and SE (kappa 0.74), and good agreement for RAP (kappa 0.67) with study echocardiographer. Correlation between absolute LVEF interpretation by study echocardiographer on HHE and SE was r=0.88 (p<0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted LV function and RAP in CHF patients, with good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients leading to expedited and optimized treatment.

Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI predict molecular insights of this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicts 13 miRNAs and 3 of these miRNAs were validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicts 24 miRNAs among 1310 molecules and 6 of these miRNAs were selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

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

Background: The 6-minute walk test (6MWT) is a simple and low-cost method that allows assessment of functional capacity in patients with heart failure (HF). However, the prognostic role of 6MWT in HF remains uncertain. Objectives: We aimed to evaluate the 6MWT as a predictor of mid-term adverse outcomes in patients with HF with mid-range and reduced ejection fraction. Methods: Prospective single-center cohort study that included patients with HF with an ejection fraction under 50% at a specialized outpatient HF service. Patients underwent the 6MWT on admission and were compared according to the distance walked: Group I walked ≥350 meters and group II <350 meters. The primary outcome was a composite of death from any cause or hospitalization for HF decompensation in one-year follow-up. Secondary outcomes were the components of the primary outcome in an isolated analysis. Results: Sixty patients were included, 43.3% male, with a mean age of 61.1 ± 12.9 years and ejection fraction 34.3 ± 10.1%. 52 patients (86.7%) were on guideline-directed triple therapy for HF. The average distance walked in the 6MWT was 395.1 ± 98.8 meters, with 40 patients (66.7%) in group I and 20 (33.3%) in group II. The primary outcome in groups I and II were, respectively, 15,0% and 35,0% (p=0.05). One-year mortality was 5.0% vs 15.0% (p=0.18) and the hospitalization rate was 10.0% vs 20.0% (p=0.28). Conclusions: There was no association of distance <350 meters in the 6MWT with the primary outcome in patients with HF. Despite the higher occurrence of outcomes in group II, the difference was not statistically significant in this analysis. On a selective basis, the 6MWT may be a useful tool for prognostic stratification in HF, if combined with other methods.

(1) Objectives. Patients with heart failure (HF) who experience hospitalizations for worsening HF (HFH) are at high risk of subsequent events. We aimed to evaluate the impact of an outpatient care management program that includes a clinician-to-clinician e-consultation using an integrated electronic medical record in a healthcare area with a widely dispersed population on delay time in care, hospital admissions, and mortality in a high-risk group of patients with HF and previous episodes of HFH. (2) Methods. We selected 6,444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4,851 were attended in e-consult, and 2,008 in one-time in-person consultations. In 2,230 HF patients, there was documentation of a previous episode of HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the health care model in the group of patients with HFH and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). (3) Results. In the group of patients with previous HF hospitalizations, the introduction of e-consult substantially decreased waiting times to cardiology care. The time elapsed to care after e-consult implementation was significantly reduced compared with the previous in-person period (8.6 [8.7] vs 55.4 [79.9] days, p&lt;0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [CI95%]: 0,837 [0,840-0,833]), 0,900 [0,862-0,949] for CV and 0,699 [0,678-0,726] for all-cause hospitalizations. There was also lower mortality (iRR [CI95%]: 0.715 [0.657-0.798] due to HF, 0,737 [0.764-0.706] for CV and 0,687 [0.652-0,718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH and were independent of the patient’s clinical characteristics managed during the in-person or e-consultation periods. (4) Conclusions. In HF patients with previous HFH, an outpatient care program that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

Heart failure (HF) is a disease state which has been shown to affect 1-2% of the global population, being often associated with comorbidities such as diabetes, hypertension, obesity or hyperlipidaemia which increase the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non pharmacological approaches have led to significant improvements in clinical outcomes in patients affected by HF, residual unmet needs remain. Treatment of the disease remains unclear particularly related to poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to may contribute in the protection of the failing myocardium, though their place in the treatment of HF still needs to be better clarified. In this context, the ONUS-HF working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease in order to counteract selected pathways which are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring druing the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, cardiac stem cell mobilization and imbalanced regulation of metalloproteinases. Several candidates for nutraceutical supplementation in HF, such as CoQ10, grape seed extract, Olea Europea L- related antioxidants, SGLT2 inhibitors-rich apple extract and bergamot polyphenolic fraction have been assessed for their potential contribution to cardiomyocyte prottection. This approach should define the optimal approach for more targeted and successful strategies based on the use of nutraceuticals in HF to be confirmed by means of clinical trials exploring efficacy and safety of these compounds.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Heart failure (HF) diagnosis, phenotyping, prognosis, and treatment decisions are all based on the left ventricular ejection fraction (EF). Heart failure with mid-range EF (HFmrEF) is a third EF category for heart failure with an EF between 40 and 49 percent. Comparatively, heart failure with preserved EF or reduced EF has been largely unexplored. 10–25% of patients with HF have HFmrEF. Although HFmrEF has an intermediate clinical profile, it is more similar to HF with reduced EF, particularly because these patients have a high incidence of ischaemic heart disease. Heart failure with preserved EF has a lower risk of cardiovascular events than heart failure with reduced EF, which is milder. HFmrEF and HF with preserved EF patients have a similar or higher risk of non-cardiovascular adverse events than patients with HF with reduced EF. There is still a great deal of mystery surrounding HFmrEF. The purpose of this review is to describe the major pathophysiology of HFmrEF and its similarities and differences with the other two types of EF. It is the purpose of this paper to present a comprehensive overview of the currently available evidence in support of the pathophysiology of patients with HFmrEF. Further investigation of the pathophysiology, treatment, and prognosis of this condition will be needed in the future in order to better understand it.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assign-ment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many dark aspects related to different patients profile, various associated risk factors and wide aetiologies. It comprises several pathophysiological pathways related to endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and high inflammatory response. Up to now, it has been described only for clinical appearance and most common associated risk factors without an effective characterization of biological processes responsible for cardiovascular deteriorations. Recent advances in laboratory and metabolomic researches showed that HFpEF appears strictly related to specific cells and molecular mechanisms dysregulation. Some biomarkers are capable to early identify these processes adding new insights into diagnosis and risk stratification. Additionally recent advances on intermediate metabolites reflecting provide relevant information on intrinsic cellular and energetic substrate alterations. The systematic combination of clinical imaging and laboratory data may lead to a precision medicine approach providing prognostic and therapeutic advantages. Current review reports traditional and emerging biomarkers recently investigated in HFpEF setting, and it purpose a new diagnostic approach based on integrative information achieved from risk factors burden, hemodynamic dysfunction and biomarkers signature partnership.

Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.

Although renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF), it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated chronic congestive cardiopulmonary heart failure (CHF) by creating aorta-vena cava fistula (AVF) in C57BL/6J wild type (WT) mice. There are four ways to create experimental CHF: (1) myocardial infarction (MI) which is basically ligating coronary by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC), although it mimics systematic hypertension but TAC again constricts aorta on top of the heart and exposes the heart; (3) acquired CHF such as by dietary factors, diabetes/salt diets etc. but it is multifactorial, and finally (4) AVF, which is the only one wherein AVF is created ~1cm below the kidney where the aorta and vena cava share the common middle-wall. By creating fistula, the red blood enters vena cava without an injury to the heart. This model mimics CHF such as during aging where with age the preload keeps increasing than the aging heart can pump out due to the weakened cardiac myocytes. This also involves the right ventricle to lung to left ventricle flow, thus creating congestion. The heart in AVF goes to transition from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation but these are also injurious models. Our lab is one of the original labs in creating and studying the AVF phenotype. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers and renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO). Fibrosis was analyzed with trichrome staining. The results suggested that there was robust increase in exosomes’ level in AVF blood, suggesting compensatory systemic response during AVF-CHF. During AVF there was no change in cardiac eNOS, Wnt1 and β-catenin, however; during RDN there was robust increase in eNOS, Wnt1 and β-catenin compared to the sham group. As expected in HFpEF there was perivascular fibrosis, hypertrophy and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher that most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against renal stresses, and apoptosis. Our findings also suggest that RDN is cardioprotective during HFpEF via the preservation of eNOS and accompanied endocardial-endothelial function.

Background: the aim of this study was to assess acute changes on left atrial (LA) function a during a progressive exercise in patients with heart failure with mid-range ejection fraction (HFmrEF) in comparison to healthy controls (HS). Methods: twenty patients with established HFmrEF were compared with 10 HS, age-matched controls. All subiects performed a stepwise exercise test on cyclette. Echocardiography was performed at baseline, during submaximal effort, at peak of exercise, and after 5 minutes of recovery. Results: HS obtained an higher value of METs at peak exercise than HFmrEF (7.4 vs 5.6; between group p 0.002). Heart rate and systolic blood pressure presented a greater increase in the HS group than in HFmrEF (between-groups p 0.006 and p 0.003 respectively). In the HFmrEF group peak atrial longitudinal strain (PALS), and conduit strain were both increased at submaximal exercise (p<0.05 for both versus baseline) and remained constant at peak exercise. Peak atrial contraction strain (PACS) did not show significant changes during the exercise. In the control group PALS and PACS increased significantly at submaximal level (p<0.05 for both versus baseline) but PALS returned near baseline values at peak exercise; conduit strain decreased progressively during the exercise in HS. Stroke volume (SV) increased in both groups at submaximal exercise; at peak exercise SV remained constant in the HFmrEF while it decreased in controls (between-groups p 0.002). Conclusions: Patient with HFmrEF, show a proper increase of LA reservoir function during incremental exercise that contributes to maintain SV throughout the exercise.

Background: The 2021 “Universal Definition of Heart Failure (HF)” Proposed the following left ventricle ejection (LVEF) phenotype classification: ≤40%; HF with intermediate LVEF: between 41-49% and HF with preserved LVEF: ≥50%. LVEF represents the percentage of left ventricular ejected volume in each cardiac cycle and Cut-points considered statistically normal are: ≥52% in men and ≥54% in women. The prevalence HFpEF is of 35-60% among the HF phenotypes, with a facing to increase rates in relation to HFrEF and is associated with mortality rates similar to those of HFrEF. The pathophysiology of HFpEF is based on vascular and metabolic dysfunction, therefore, there is less neurohumoral stimulation compared to HFrEF. Methodology: A systematic review was performed to report of information related to Sacubitril-valsartan and the treatment of HFrEF. Terms related to “treatment” and “brazil” were used in the databases PubMed (MEDLINE) and Scientific Electronic Library Online (SCIELO). Results: Clinical trials testing drugs that modulate the neurohumoral system in patients with HFpEF failed to demonstrate benefit in the combined endpoint of reduced mortality/hospitalization due to HF compared to placebo to date. Sacubitril-valsartan is a drug with a mechanism of action surrogate the pathophysiological concept of HFpEF, it is safe and decreased endpoints of natriuretic peptides and left atrial structure in a phase II clinical study. Conclusions: The PARAGON-HF trial demonstrated that sacubitril-valsartan reduced the primary endpoint of the study when assessed the pre-specified subgroup of LVEF≤57% and improved the secondary endpoints of performance status and renal function in the population.

Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

Background: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalisation and often results in death. Patients hospitalised to the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological predictors for AHF. Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to determine AHF. Important risk variables for AHF diagnosis were identified using LASSO feature selection. To test the efficacy of the suggested prediction model (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP, were used to assess the importance and influence of the model's incorporated risk factors. Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p&lt;0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH) and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p &lt;0.05). When XGBoost was used in conjunction with LASSO to estimate AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF. Conclusions: The XGBoost model demonstrated exceptional performance in accurately estimating Acute Heart Failure, and the application of Explainable Artificial Intelligence effectively provided intuitive explanations for the model's estimations. The suggested interpretable model holds potential for the identification of patients at high risk, thereby facilitating the optimization of treatment and planning for follow-up in cases of AHF.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily triggers an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Aims: The objective of this study was to assess the cost-effectiveness of the CardioMEMS HF system in a HF Clinic in Spain by evaluating the real-time remote monitoring of pulmonary artery pressures, which has shown to reduce heart failure (HF) related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods: This single-centre study enrolled all consecutive HF patients who had been implanted with a pulmonary artery pressure sensor (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA). The number of HF hospitalizations in the year before and the year after the sensor implantation was compared and quality-adjusted life years (QALY) gained based on a literature review of previous studies was calculated. Results: The rate of HF hospitalisations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 versus 1.10 events/patient-years, HR 0.22, p=0.001). At the end of first year, the usual management outperformed the CardioMEMS HF system, resulting in a net monetary value difference of 2,540€ per patient and a benefit-cost ratio of 0.38. However, by the end of the second year, the CardioMEMS system is estimated to reduce costs compared to usual management. Conclusions: Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF system represents a long-term cost-effective strategy in a healthcare setting in Southern Europe.

Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a 12-weeks supervised concurrent, aerobic continuous plus resistance, exercise training (SCT) pro-gram on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three session/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12-weeks, all patients performed: ergometric test, 6-minute walk test and echocardiography. At 12-weeks, exercise duration at ergometric test and distance walked at 6-minute walk test presented a significant greater increase in the SCT compared to control (be-tween-groups p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34% respectively in the SCT and were unchanged in the CON (between-groups p 0.008 and p 0.001 respectively). Peak atrial contraction strain increased of 21% in the SCT with no changes in the CON (between-groups p 0.002). Left ventricular global longi-tudinal strain increased significantly SCT compared to control (between-groups p 0.03). In con-clusions SCT improved left atrial and left ventricular function in HFmrEF

Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare but associated with ad-verse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in myocardial wall thickness and contractility while waiting for cardiac magnetic resonance (CMR). Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the echocardiographic findings, biomarkers for myocardial injury N-terminal pro b-type natriuretic peptide (NT-proBNP) and hs-troponin I, biomarkers for systemic inflammation erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and biomarkers for SLE disease activity (Complement C)3, C4, and anti-dsDNA levels.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

Heart failure with reduced ejection fraction (HFrEF) is considered a major healthcare problem with frequent decompensations, high hospitalization and mortality rates. In severe heart failure (HF), the symptoms are refractory to medical treatment and require advanced therapeutic strategies. Early recognition of HF sub- and decompensation is the cornerstone of the timely treatment intensification and, therefore, improvement of the prognosis. Echocardiography is the gold standard for the assessment of systolic and diastolic functions. It allows to obtain accurate and non-invasive measurements of the ventricular function in HF. In severely compromised HF patients, advanced cardiovascular ultrasound modalities may provide a better assessment of intracardiac hemodynamic changes and subclinical congestion. Particularly, cardiovascular and lung ultrasound allow to make a more accurate diagnosis of subclinical congestion in HFrEF. The aim of this review is to summarize the advantages and limitations of currently available ultrasound modalities in the ambulatory monitoring of patients with HFrEF.

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.

Background and Objectives: Acute Heart Failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying the pulmonary hypertension (PH) in patients admitted due to AHF, predict the evolution of the disease during hospitalization and identify areas of improvement in the care of patients with AHF. Materials and Methods: Patients were evaluated with a standard exam of lung ultrasound, echocardiography, inferior vena cava (IVC) and femoral, renal, hepatic, portal venous Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation – SD 13,4). Seven patients (23.3%) had a renal function worsening. Regarding ultrasound findings, venous excess ultrasonography score (VExUS) score was calculated at admission and at discharge, surprisingly remaining unchanged or even worsened in most of them (21 patients, 70.0%). The area under the curve for the Lung Score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (p &lt;0.001), hepatic vein Doppler (p &lt;0.001), portal vein Doppler (p = 0.030), intra-renal vein Doppler (p = 0.025) and VExUS score (p = 0.023), remaining similar the femoral vein Doppler (p = 0.177) and IVC (p = 0.132). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VExUS score, should be further studied in different populations before expanding its use in AHF patients.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

Abstract Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: A PubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that “pace and ablate” strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding the implantation of pacemaker, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle brunch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and implantation of pacemaker is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

Background: Congestive heart failure is the inability to pump blood throughout the body which causes the walls to be unable to pump adequately. Purpose: This study aimed to ascertain the effect of a contrast bath with a 30 º elevation on the reduction of edema in congestive heart failure patients at Ulin General Hospital, Banjarmasin. Methods: The design of this study was quasi-experimental with an unequal control group design. The population is patients with congestive heart failure, and the sample used is successive sampling. 34 respondents were divided into two groups, 17 respondents in the intervention group and 17 in the control group. Results: The Mann-Whitney result value P = 0.027 (P < 0.05) represented a significant reduction in Bath contrast edema with 30º feet elevation in the intervention group and control group patients with congestive heart failure. Conclusion: Based on the results of this study, it is expected to be able to apply contrast showers with an elevation of 30 º in nursing services to reduce the degree of edema in congestive heart failure patients.

This review paper presents a flashback on the evolution of the disease throughout the centuries, describes in summary pathophysiologic mechanisms, discusses briefly the mechanism of action of the diuretics, presents their role in decongesting heart failure patients and unfolds the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of the loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories, without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer-leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively characterised cEVs by flow cytometry with special attention to the proportions of PS in chronic heart failure patients (cHF; n=119) and reference non-HF group (n=21). PS─-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS─-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in non-HF. We observed similar levels of PS+- and PS─-cEVs in non-HF subjects when analysing immune cell-derived EVs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+ and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+ and CD56+ were mainly PS─-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients as detected by a high shedding of cEVs. Despite PS+-cEVs and PS─-cEVs represent two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to PS content.

Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However the effect on cardiac performance remains unknown. We sought to evaluate the effects of sacubitril/valsartan on clinical, bioumoral and echocardiographic parameters in patients with HFrEF. Methods: Sacubitril/valsartan was administered to 205 HFrEF patients. Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow–up of 10.49 (2.93±18.44) months, the percentage of patients in NYHA class III changed from 40% to 17% (p<0.001). Median N–Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, (p=0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 (p=0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% (p<0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 (p=0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p=0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/sec to 2.64 ± 0.59 m/sec (p<0.014). CONCLUSIONS: Sacubitril/valsartan induce “hemodynamic reverse remodeling” and in association with Nt-proBNP concentrations lowering improve NYHA class despite a diuretic dose reduction.

Mortality and readmission rates for decompensated acute heart failure (AHF) is overall increasing and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultraso-nography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, a multiorgan ultrasound assessment (lung, inferior vena cava, Doppler of hepatic, portal, intrarenal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). An intrarenal monophasic pattern (AUC 0.923, Sn 90%, Sp 81%, PPV 43%, NPV 98%), a portal pulsatility >50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 (AUC 0.885, sensitivity 80%, specificity 75%, PPV 33%, NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intrarenal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF related readmission. Addi-tional scans during hospitalization or calculate a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to guide therapy or the predic-tion of complications, compared to the presence of an inferior vena cava greater than 2 cm, a venous mo-nophasic intrarenal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisci-plinary follow-up visit remains necessary to improve prognosis of this highly prevalent disease.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

Background: our purpose is to assess the effectiveness and safety of sacubitril/valsartan (SV) in “real-world” patients with heart failure and reduced ejection fraction (HFrEF), including a broader spectrum of patients than those in clinical trials and evaluating variables not previously described in the literature. Methods: real-world study in HFrEF patients (N:204), both in and out-patients, who started SV between October 2017 and December 2018. We performed a prospective analysis with a 12-month follow-up. The study outcomes were effectiveness and safety, measured by individual parameters and combined endpoints, comparing the pre and post practice periods. Results: at the end of follow-up, an improvement of left ventricle ejection fraction (LVEF): 29.8% vs 33.7; p<0.0001, a decrease in NT-proBNP levels (3928 pg/mL vs 2902 pg/mL; p=0.012), number of hospital admissions (141 vs 35; p<0.0001) and percentage of patients with implantable cardioverter defibrillator (ICD) indication (79.9% vs 49.5%; p<0.0001) were observed. Of our population, 81.3% met a combined efficacy endpoint (defined by increase of LVEF, reduction of hospital admission or improvement in functional class). No differences were observed in parameters regarding safety. Conclusions: Sacubitril/valsartan has brought about a revolution in the therapeutic management of HFrEF patients and its use may raise questions about what is considered "optimal medical therapy" prior to implantation of cardiac devices.

Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, that can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F / 53.70% M, age 63.95±12.82 years) presented CA at baseline. In 53 patients, there was associated with multiorgan involvement, while in one there was primary myocardial deposition. As control group, we enrolled 81 patients (49.30% F / 50.70% M, aged 58.33±15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA, 3/54 of patients with ATTR, in 1/54 AL was related to hemodialysis and 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/40) or IgD (2/40), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0±8.4 mmHg; DBP 73.8±4.9 mmHg), while those with nCA had increased proteinuria (p=0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p=0.047, respectively). In CA patients we found an increased LDH compared to nCA (p=0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p=0.002), a decreased Ejection Fraction % (p=0.0018) and Doppler velocity E/e’ ratio (p=0.0095). Moreover, CA patients were seen to have an enhanced right atrium area (p=0.0179), right ventricle basal diameter (p= 0.0112) and wall thickness (p=0.0471) as compared to nCA, as well as an increased inferior cava vein diameter (p=0.0495). TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p=0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r=0.47; p=0.031) as well as Gamma globulins (r=0.43, p=0.033), Monoclonal component (r=0.72; p=0.047) and IgG values (r=0.62, p=0.018). On the contrary, a significant negative correlation with LDH (r=-0.57, p=0.005), IVS (r=-0.51, p=0.008) and diastolic function evaluated as E/e’ (r=-0.60, p=0.003) were verified. CA patients had very poor survival compared to controls (30 vs. 66 months in CA vs nCA, respectively, P=0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs higher values than the median, respectively p=0.013). In much the same way, decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18mm, p=0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement and propose that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.

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

This study investigated modifications in the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. mRNA levels of USP18 (deubiquitinating enzyme), psmb8, and psmb9 (proteasome β-subunits) were downregulated in db/db mice while mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were downregulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. Reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

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

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

Chamois are mountain ungulates (Subfamily Caprinae) which inhabit several medium and high altitude mountain ranges from southern Europe to the Near East. The first findings of Sarcocystis cysts in the musculature of chamois were reported in the 1970s. However, only limited work on the epidemiology of sarcocystosis and identification of the species of Sarcocystis in chamois has been done in the past. The present work was part of a comprehensive study on the parasites of chamois in Germany aiming to provide, for the first time, data on the prevalence and intensity of Sarcocystis infection in native Alpine chamois using histology examination of heart and/or diaphragm tissue samples collected from 216 chamois (40 kids and 176 chamois ranging of one up to 18 years of age). Sarcocysts were detected in either heart or diaphragm of 167/216 chamois (77.3%) with 131 of 183 heart samples and 127 of 215 diaphragm samples testing sarcocyst positive. Of the 181 chamois with both heart and diaphragm available (34 kids and animals up to 18 years of age), sarcocysts were detected in heart and/or diaphragm of 142 animals translating in an overall 78.5% prevalence of Sarcocystis infection (95%CI 72.5% - 84.4%). Sarcocysts were more frequently recorded in heart vs. diaphragm (72.4% vs. 56.4%; p=0.0021), and diaphragm positivity was associated with heart positivity (p=0.0001). Sarcocyst positivity (heart and/or diaphragm) was significantly (p<0.001) lower in kids than in the older chamois (27.1% vs. 88.6%, respectively) but prevalence did not differ between the sexes, regardless of the chamois’ age (p>0.3). Intensity of infection was generally low (<10 sarcocysts per cm² muscle cut) in both heart positive and diaphragm positive animals (94.7% and 93.7%, respectively) with heart yielding higher sarcocyst counts than diaphragm (p<0.001). Both heart and diaphragm sarcocyst counts were significantly (p<0.001) lower in kids than in the older chamois. Sarcocystis infection was demonstrated to be prevalent in chamois in Germany but intensity is apparently low. Further studies are desired to identify the species of Sarcocystis parasitizing the chamois using both phenotypic and molecular characteristics.

Background: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis which contributes to heart failure, arrhythmias, and sudden cardiac death (SCD). Objective: To identify the factors implicated in heart failure symptoms and functional capacity of patients with HCM. Methods: In this cohort study, 43 patients with HCM were recruited. According to functional capacity and symptoms presentation, patients were categorized according to NYHA classification, and echocardiographic measurements of left ventricle systolic and diastolic function have been conducted. The echocardiographic assessment of right vetriculo-arterial coupling (RVAC) has been made by calculating the tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP) ratio. Results: Almost half, 22 (51%) of our study population present symptoms of heart failure and were categorized as the symptomatic group - NYHA 2 or higher. Maximum LVOT gradient, RVSP, and the ratio of E/e’ were higher in the “symptomatic” compared to the “asymptomatic” group. TASV was lower in the “symptomatic” compared to the asymptomatic group (11±1cm/sex vs. 13±2cm/sec, p=0.04). However, there was no difference in other potentially influential factors, such as heart rate or systemic blood pressure. The SCD risk score does not differ between the two studied groups. The RVAC (estimated with the TASV/RVSP ratio) was lower in the “symptomatic” compared with the “asymptomatic” group (0.32±0.09 vs. 0.46±0.11, p<0.001). Conclusion: A low RVAC (as TASV/RVSP ratio) value could represent an echocardiographic marker of right ventricular-arterial uncoupling in patients with HCM and may impaired functional status.

Heart rate variability (HRV) is commonly intended as the variation in the heart rate (HR) and it is evaluated in the time and frequency domains with various well known methods. In the present paper, we first consider an abstract model in which the HR is the instantaneous frequency of an otherwise periodic signal such as the electrocardiogram (ECG). Thus the ECG is assumed as a frequency modulated signal, or carrier signal, where HRV or HRVt is a supposed time-domain signal which is frequency modulating the carrier ECG signal around its average frequency. Hence we describe an algorithm able to frequency demodulate the ECG signal to extract a continuous signal HRVt with possibly enough time resolution to analyse fast time-domain variations in the instantaneous HR. After exhaustive testing of the method on simulated frequency modulated sinusoidal signals, we have applied the procedure on actual ECG tracings. The purpose of the work is to eventually use the heart as a kind of biological sensor of the fast activity of the autonomic nervous system (ANS) to study the ANS ultra-short-term event-evoked responses. A few preliminary, not clinical, real examples are also given.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising from diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include the prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function, and calcium regulation. The present review summarizes the recent findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.

A 36-year-old professional marathon runner reported sudden heart palpitations occurring during competitions, with heart rates (HR) of 230 bpm recorded on sports HR monitor (HRM) over 4 years. These episodes subsided upon the cessation of exercise. Electrocardiograms, echocardiography, and cardiac magnetic resonance imaging results were borderline for athlete's heart. Because an electrophysiology study and standard exercise tests provoked no arrhythmia, doctors suspected Munchhausen syndrome. Ultimately, an exercise test that simulated the physical effort during a competition provoked tachyarrhythmia consistent with the HRM readings. This case demonstrates the diagnostic difficulties related to exercise-induced arrhythmia and the diagnostic usefulness of sports HRMs.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging infectious disease with currently a pandemic state. Cardiac function can be involved, affecting prognosis, in addition with lung feature severity, particularly in patients with comorbidities. Since the renin angiotensin aldosterone (RAA) system may interact with SARS-Cov-2, researches are still ongoing to assess the prognostic value of RAA blockers in cardiology.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.

Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.

Background: Infective endocarditis(IE) is a serious disease and in many cases surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement(AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival, recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. Methods: This was an analysis of the INFECT-REGISTRY. Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549 aged between 40 and 65 years underwent AVR. 268(48.8%) received mechanical prostheses, and 281(51.2%) biological ones. Confounders were adjusted using optimal full matching propensity score. Results: A significant trend in reduction of implantation of mechanical vs biological prostheses was observed during the study period(p&lt;0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546,95%CI: 0.322-0.926, p=0.025). Mechanical prostheses were significantly associated with less recurrent endocarditis after AVR (HR 0.268,95%CI:0.077-0.933,p=0.039).Conclusions: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after mechanical aortic valve prosthesis implant for IE in middle-aged patients.

Abstract: Background: Coronary angiography CT scans play a pivotal role in diagnosing cardiovascular diseases, providing crucial information for treatment planning. However, concerns regarding radiation exposure have prompted the need for establishing region-specific diagnostic reference levels (DRLs) to ensure patient safety. This study aims to assess radiation exposure during coronary angiography CT scans in the Northeast Assam population and establish DRLs tailored to this demographic. Methods: A total of 380 patients were referred to the Primus Diagnostic Centre and Heath City Hospital, Guwahati Assam, during the study with coronary artery disturbances. Data on the technical parameters used in CT procedures were taken in 2021-2022. The aim and study's objective was Organ and surface dose to specific radiosensitive organs (Chest) estimation using software imPACT 1.0.4 from National Radiological Protection Board (NRPB) SR250 Monte Carlo dataset. Results: The study population (n = 380) comprised 190 men and 190 women with an average age of 29 to 75 years. The Mean ± SD of BMI and ED are 22.42±1.06 and 21.57±4.27 respectively. The mean DLP is 854.67, and the mean ED is 21.57. The effective doses for males (13- 27) mSv were in females (13-29) mSv. The DRL for Male population was found to be 24.26mSv.cm2 whereas for female population it was 24.69mSv.cm2. Conclusions: This study highlights the necessity of establishing tailored diagnostic reference levels for coronary angiography CT scans in the Northeast Assam population. By doing so, healthcare providers can ensure optimal image quality while minimizing radiation exposure, ultimately enhancing patient safety and quality of care. These findings have implications for radiological practice in the region and contribute to the ongoing efforts to standardize radiation doses in medical imaging procedures.

In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving the natural tissue architecture. SD and SDS are detergent derivatives frequently used in decellularization studies. The aim of our study is to decellularize the pulmonary heart valves of young Merino sheep by using low-density SDS and SD detergents together, and then to perform their detailed characterization to determine whether they are suitable for clinical studies. Pulmonary heart valves of 4-6 month old sheep were decellularized in detergent solution for 24 hours. The amount of residual DNA was measured to determine the efficiency of decellularization. Then, the effect of decellularization on the ECM by histological staining was examined. In addition, the samples were visualized by SEM to determine the surface morphologies of the scaffolds. Uniaxial tensile test was performed to examine the effect of decellularization on biomechanical properties. The results showed DNA removal of 94% and 98% from the decellularized leaflet and artery portions after decellularization relative to the control group. No cell nuclei were found in histological staining and it was observed that the 3-layer leaflet structure was preserved. As a result of the tensile test, it was determined that there was no statistically significant difference between the control and decellularized groups in the UTS and elasticity modulus, and the biomechanical properties did not change. In conclusion, we suggest that the pulmonary valves of decellularized young Merino sheep can be used as a initial matrix in heart valve tissue engineering studies.

This study aimed to evaluate the role of chest radiographs and electrocardiograms in predicting the hemodynamics of congenital heart disease (CHD). This retrospective study included 50 patients with a diagnosis of CHD who had undergone any form of cardiac intervention, either surgical or nonsurgical between September 2019 and September 2020. Chest radiographs and electrocardiograms were evaluated and compared with the diagnostic gold standard echocardiography. Chest radiographs had the highest sensitivity, specificity, and accuracy, with all being 100%, in detecting situs and cardiac position. There was a very good agreement between chest radiographs and echocardiography in the detection of both situs and cardiac position (κ = 1.00, p &lt; 0.001), while moderate agreement was observed for the detection of cardiomegaly, position of aortic knuckle, main pulmonary artery dilation, and right pulmonary artery dilation. Electrocardiograms had a high sensitivity (100.00%), but modest specificity and accuracy for the detection of left ventricle pressure overload. For the detection of left atrial enlargement and left ventricle volume overload, electrocardiograms had high specificity (94.12% and 94.29%, respectively) but low sensitivity and modest accuracy. There was a moderate agreement between electrocardiograms and echocardiography in the detection of right ventricle pressure overload (κ = 0.43, p = 0.002) and left ventricle volume overload (κ = 0.46, p &lt; 0.001). The study findings indicate that chest radiographs and electrocardiograms alone are not adequate for the assessment of hemodynamics of CHD and reinstates the recommendation that in addition to routine chest radiographs and electrocardiograms, echocardiography should be performed.

Introduction: The effect of halogenated drugs as cardioprotectors in cardiac surgery has been evaluated in several studies. However, the possibility that there is a protective role at renal level, triggered by their use, is currently under study. Aortic valve replacement and coronary revascularization are the most frequent surgeries in cardiac surgery. Our research evaluates the effect of desflurane compared to propofol in aortic valve replacement surgery at renal level; including its administration during extracorporeal circulation. Method: Quasi-experimental prospective study performed on 60 patients, divided into 2 groups according to the drug used in intraoperative aortic valve replacement surgery. In group 1 propofol was used as a hypnotic during surgery, in group 2 desflurane was used. Differences in kidney damage measured through the urinary NGAL marker were evaluated. Other markers of renal function and myocardial damage and the need for inotropic support during the first 48 hours were also measured. Results: There were significant variations in the values ​​of urinary NGAL and creatinine regarding to basal values ​​in the propofol group, but not in the desflurane group, in which there were no differences in the hemodynamic parameters and myocardial damage. Conclusion: the use of desflurane during aortic valve replacement surgery produced better renal preservation than propofol.

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.

Studies have demonstrated the positive effects of acupuncture on athletic performance. The aim of this study was to determine the acute effects of acupuncture on heart rate, the perceived exertion scale and lactate levels in recreational athletes. Fifteen competitive males engaged in HIIT. The characteristic was 29.86±2.51 years old, heart rate reserve 59.00±3.33, lactate 3.17±0.50 mM/DL. The subjects were submitted to two exercise sessions. Both training sessions consisted of 10 burpees, 12 thrusters and 14 box jumps (75 cm high) for 12 minutes. Activity intensity was between 85 and 95% of maximum heart rate. Acupuncture points: ST36, L3, LI11. The student’s t-test was adopted, Shapiro-Wilk test was applied for normality, and Pearson correlation. There was a positive correlation of r = 0.69 between lactate levels and heart rate. Lactate: Lac1 15.00±1.18 – Lac2 19.59± 1.46 p= 0.0001*; Heart 1rate: HRF 163.71±7.27 – HRF2 177.60±6.99 p=0.0001*; Blood pressure: SBP1 174.86±1.57 – SBP2 180.86±1.77 p= 0.0001*; PES1: 19.4±1.14; PES2 16.8±0.84 p= 0.0001*; weight1 – 182,57±12,05; weight 2 206,43±11,39 p=0.0325*. Acupuncture increased lactate accumulation, heart rate and blood pressure, suggesting that the exertion reached after acupuncture is higher than without acupuncture. The acupuncture technics improved the athlete performance.

The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and identify decelerations and accelerations. These steps can potentially be automated and made more objective by data processing analysis, but training and evaluation datasets are required. Here, we describe a dataset of 155 FHR recordings in which a reference baseline, accelerations and decelerations have been annotated by expert consensus. 66 FHR recordings with a shared expert analysis have been included in a training dataset, and 90 other FHR recordings with a non-shared expert analysis have been included in an evaluation dataset. Researchers wishing to evaluate their automatic analysis method should submit their results for comparison with the expert consensus. The dataset also contains the results produced by 11 re-coded automatic analysis methods from the literature. All the data are available at http://utsb.univ-catholille.fr/fhr-review.

The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and then identify decelerations and accelerations. These steps can potentially be automated and made more objective by signal processing analysis. Various methods have been described in the literature but there are no open-source programs for performing these steps. The MATLAB toolbox presented here comprises a standard signal pre-processing function, 11 re-coded literature methods for fetal heart rate analysis, a signal viewer (enabling annotation by an expert) and an evaluation procedure with various criteria measuring intrarater agreement.

Background and objectives: Smoking leads to autonomic dysfunction. However, the clinical methods for diagnosing this dysfunction are not sufficient. Since exogenous hypoxia leads to changes in the autonomic cardiac control, the aim of our study was to compare the activity of the autonomic nervous system via heart rate variability (HRV) in young “healthy” smokers and non-smokers before, during and after a short-term exogenous hypoxic exposure. Methods: Twenty-one healthy non-smoking males aged 28.0±7.4 (mean±SD) and fourteen healthy smoking males aged 28.1±4.3 with 9.2±5.6 pack-years were subjected to one-hour hypoxic exposure (FiО2=12.3±1.5%) via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada) with simultaneous recording of electrocardiography and pulse oximetry. HRV data was derived via specific software (Kubios HRV, Finland) by analyzing the pre-hypoxic, hypoxic and post-hypoxic periods. Results: Standard deviation of the intervals between normal beats (SDNN) was higher in non-smokers in the pre-hypoxic period (62.0±32.1 vs 40.3±16.2, p=0.013) but not in hypoxia (75.7±34.8 vs 57.9±18.3, p=0.167). When comparing intragroup HRV changes of shifting from hypoxic to post-hypoxic (normoxic) conditions we found that there is a significant increase in the root mean square of successive RR interval differences (RMSSD) (65.9±40.2 vs 75.1±45.9, p=0.011) and in the high frequency (lnHF) (6.8±1.4 vs 7.2±1.3, p=0.014) and a decrease in LF/HF (3.0±2.3 vs 1.9±1.5, p<0.001), but these changes were observed only in the group of non-smokers. Conclusions: Smoking likely impairs autonomic regulation in young healthy males and may lead to a decreased HRV even before subjective clinical signs and symptoms. Hypoxic exposure test could be applied in clinical practice for early detection of autonomic dysfunction in smokers, because their parasympathetic reactivation is blunted when shifting from hypoxic to normoxic ambient conditions measured by HRV.

The sensitivity of exercise ECG is marginally sufficient for detection of mild reduction of coronary blood flow in patients with early coronary atherosclerosis. Here we describe the application of new technique of ECG registration/analysis – ultrahigh resolution ECG (UHR ECG) – for early detection of myocardial ischemia (MIS). The utility of UHR ECG vs. conventional ECG (C ECG) was tested in anesthetized rats and pigs. Transmural MIS was induced in rats by the ligation of the left coronary artery (CA). In pigs, subendocardial ischemia of variable extent was produced by stepwise inflation of balloon within the right CA causing 25-100% reduction of its lumen. In rats, a reduction in power spectral density (PSD) in high-frequency (HF) channel of UHR ECG was registered at 60 s after ischemia (power 0.81±0.14 vs. 1.25±0.12 mW at baseline, p<0.01). This was not accompanied by any ST segment elevation on C ECG. In pigs, PSD in HF channel of UHR ECG was significantly decreased at 25% reduction of CA lumen, while ST segment on C ECG remained unchanged. In conclusion, UHR ECG enabled earlier detection of transmural MIS compared to C ECG. PSD in HF-channel of UHR ECG demonstrated greater sensitivity in the settings of subendocardial ischemia.

Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.

We describe real-world use of mavacamten in 50 patients with oHCM. Consistent with EXPLORER-HCM and VALOR-HCM, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and NYHA class. Moreover, in our center’s experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: We note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

Personalized surgery is not just a new trend but rather a patient-specific approach to therapy that makes it possible to adopt a targeted approach for a specific patient and closely mirrors the approach of personalized medicine. However, the application of tailored surgery in the context of cardiovascular replacement surgery was not systematically reviewed. The ability to customize a device is highly dependent on the collection of radiological image data for precise prosthesis modelling. These facts are essential to "tailor-made" device design for precise prosthesis implantation. According to this study, computed tomography (CT) was the most prominent imaging modality; however, transoesophageal echocardiography and echocardiography were also found to be helpful. Additionally, a dynamic finite element simulation is also an attractive alternative to the finite element analysis for an in-silico experiment. Nonetheless, there is a paucity of relevant publications and sporadic evidence. More clinical studies have been warranted, notwithstanding that the derived data and results from the insight into the use of therapeutic interventions may be of multiple directives in clinical practices and beyond. This study may help the integration of personalized devices for better comprehending predicted clinical outcomes, thus leading towards enhanced performance gains.

Background: There is limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. Our aim was to examine gender-related differences in medical attention in emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010-2015, with a minimum FU of one year. Data on medical attention received, mortality and other adverse outcomes were collected and analyzed. Results: Among the 2 013 patients selected, 1232 (60%) was female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p=0.001) and were less likely to be admitted (5.9% vs. 9.5%, p<0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p=0.001) and during FU (15.9% vs. 10.6%, p<0.001), in spite of a lower AF recurrence rate in women (9.9% vs 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p<0.001). Conclusions: In patients with AF, although no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists and showed a higher probability of hospitalization for heart failure. Being alert to these iniquities should facilitate to adopt measures to correct them.

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

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

The impact of a non-anticholinergic spasmolytic drug (drotaverine hydrochloride) on 23 heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) motility in the normal, resting 24 horses was determined. Ten adult riding horses had ECG recordings for 180 minutes after treat-25 ment with drotaverine (180 mg) or saline. Horses from the drotaverine group presented a de-26 creased of GIT contraction for two hours after treatment, but also showed drowsiness. Drotaverine 27 caused a reduction in cardiac vagal modulation of HR at T30 (P=0.050) and T60 (P=0.008) compared 28 to those receiving saline. RMSSD and high frequency (HF) recorded significantly low values after 29 drotaverine treatment by the end of the study, suggesting a decrease in parasympathetic activity. 30 HRV analysis indicated that drotaverine decreased both the low frequency (LF) and Lf/HF ratio 31 reflecting a decrease in sympathetic system. Non linear parameters registered low values after 32 drotaverine administration pointing a diminished in parasympathetic (for SD1) and sympathetic 33 (for SD2) activity. Decreased HRV was suggestive for a pervasive state of sympathetic hypervigi-34 lance of horses. The marked effect of drotaverine on HRV and GIT function in horses should be 35 taken into consideration when evaluating a clinical response to this drug in diseases associated 36 with smooth muscle spasm.

Non-invasive heart rate (HR) monitoring is important in clinical settings as it plays a critical role in diagnosing a range of health conditions and assessing well-being. Presently, the gold standards for HR measurement are all based on sensors which require skin contact. Apart from inconvenience, contact sensors have proven problematic in certain scenarios – they cannot be used when mechanical isolation of the patient is imperative (burn victims, patients with shaky hands and feet), cause skin damage to premature babies in the ICU and increase the risk of spreading infections. Non-contact HR monitoring using a camera has been recently shown to be a viable alternative. It is now possible to record cardiac-synchronous blood volume variations from facial videos of human subjects under ambient lighting. These variations produce corresponding changes in skin reflectance which can be extracted as a raw reflectance photoplethysmography (rPPG) signal and processed to reveal HR. In this project, an algorithmic framework for webcam-based HR detection was successfully implemented in MATLAB. The investigation was based on 100 self-captured videos (dark-skinned subject) and 48 videos (from 12 subjects, all but one fair-skinned) obtained from COHFACE – an online database of facial videos and corresponding physiological signals. While the performance metrics (mean error, SNR) of the rPPG signals obtained from the self-captured videos were poor (best case mean error of 22%), they were good enough to demonstrate the success of the implementation. The poor results were primarily imputed to skin tone as rPPG SNR is known to be particularly low for dark tones. The results of the COHFACE videos were far superior, with mean error ranging from 3% to 15% (among 8 different rPPG signals) and 0% to 9% under ambient and dedicated lighting, respectively. This investigation sets the foundation for future research directed at optimizing rPPG performance metrics for dark-skinned subjects.

Background/Objectives: The purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.Methods: The stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).Results: The degree of correlation of functional indicators (M, HR_M, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers. Conclusions: CANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate that has a stiffness much higher than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting sex-disaggregated analysis of changes in cellular morphology and relative concentrations of profibrotic signaling proteins in CFs cultured on 8kPa stiffness plates with and without 17-β estradiol (E2). Cyclic immunofluorescent analysis indicated that there is a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs are occurring at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein-protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored, sex-informed prevention and treatment interventions of cardiac fibrosis.

Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extra-mitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP-synthase (E55A mutation), indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca2+ handling, which resulted in sarcoplasmic reticulum Ca2+ overloading. The effects of IF1 on Ca2+ handling were associated with the cytosolic activation of CaMKII and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF-1 induced pathological hypertrophy. Conclusions IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase independent, role for IF1 in mitochondrial Ca2+ handling and mitochondrial- to nuclear crosstalk involving CaMKII.

One of the oldest and common methods of diagnosing heart abnormalities is auscultation. Even for experienced medical doctors, it is not an easy task to detect abnormal patterns in the heart sounds. Most of the digital stethoscopes are now capable of recording and transferring the heart sounds. Moreover, it is proven that auscultation records can be classified as healthy or unhealthy via artificial intelligence techniques. In this work, an artificial intelligence-powered mobile application that works in a connectionless fashion is presented. According to the clinical experiments, the mobile application can detect heart abnormalities with approximately 92% accuracy which is comparable if not better than humans since only a small number of well-trained cardiologists can analyze auscultation records better than artificial intelligence. Using the diagnostic ability of artificial intelligence in a mobile application would change the classical way of auscultation for heart disease diagnosis.

This study aimed at evaluating changes in the clinical and echocardiographic parameters of pregnant sheep, as well as the HRV indexes due to the physiological alterations that happen at this stage implicating in high maternal metabolic demands. For this purpose, the study evaluated 10 Dorper sheep through their pregnancy, starting from the second month until the day before birth, conducting clinical, echocardiographic and electrocardiographic examinations focused on the HRV. The echocardiogram was conducted in a doppler ultrasound device with a multifrequency sectorial transducer in bidimensional mode. The HRV indexes were obtained through the Televet 100® system. There were increases in the thickness of the interventricular septum during diastole starting from the third month, and in the internal diameter of the left ventricle during systole and diastole at the second and third months, while the ejection fraction increased as the pregnancy progressed. The size of the left atrium increased starting at the second month. The SDNN, RMSSD and PNN50 HRV indexes were higher at the fifth month of pregnancy and after delivery. There were no significant differences in the frequency-domain HRV indexes during pregnancy. The gestation leads to alterations in the clinical parameters and the activity of the autonomic nervous system.

The mere co-presence of another person synchronizes physiological signals, but no study has systematically investigated effects of type of emotional context and type of relationship in eliciting dyadic physiological synchrony. In this study, we investigated the synchrony of pairs of strangers, companions, and romantic partners while watching a series of video clips designed to elicit different emotions. Maximal cross-correlation of heart rate variability (HRV) was used to quantify dyadic synchrony. The findings suggest that an existing social relationship might reduce the predisposition to conform one's autonomic responses to a friend or romantic partner during social situations that do not require direct interaction.

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.