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Abstract Arterial Vascular smooth muscle cells (VSMCs) play a central role in the onset and progression of atherosclerosis. Upon exposure to pathological stimuli, they can take on alternative phenotypes that, among others, have been described as macrophage like, or foam cells. VSMC foam cells make up >50% of all arterial foam cells and have been suggested to retain an even higher proportion of the cell stored lipid droplets, further leading to apoptosis, secondary necrosis, and an inflammatory response. However, the mechanism of VSMC foam cell formation is still unclear. Here, it is identified that mechanical stimulation through hypertensive pressure alone is sufficient for the phenotypic switch. Hyperspectral stimulated Raman scattering imaging demonstrates rapid lipid droplet formation and changes to lipid metabolism and changes are confirmed in ABCA1, KLF4, LDLR, and CD68 expression, cell proliferation, and migration. Further, a mechanosignaling route is identified involving Piezo1, phospholipid, and arachidonic acid signaling, as well as epigenetic regulation, whereby CUT&Tag epigenomic analysis confirms changes in the cells (lipid) metabolism and atherosclerotic pathways. Overall, the results show for the first time that VSMC foam cell formation can be triggered by mechanical stimulation alone, suggesting modulation of mechanosignaling can be harnessed as potential therapeutic strategy.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent determinant of cardiovascular mortality. Recently, CHIP has been found to occur frequently in patients with calcific aortic valve disease (CAVD) and it is associated with a poor prognosis after valve replacement. We assessed the frequency of CHIP by DNA sequencing in the blood cells of 168 CAVD patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation and investigated the effect of CHIP on 12 months survival. To investigate the pathological process of CAVD in CHIP carriers, we compared by RNA-Seq the aortic valve transcriptome of patients with or without CHIP and non-calcific controls. Transcriptomics data were validated by immunohistochemistry on formalin-embedded aortic valve samples. We confirm that CHIP is common in CAVD patients and that its presence is associated with higher mortality following valve replacement. Additionally, we show, for the first time, that CHIP is often accompanied by a broad cellular and humoral immune response in the explanted aortic valve. Our results suggest that an excessive inflammatory response in CHIP patients may be related to the onset and/or progression of CAVD and point to B cells as possible new effectors of CHIP-induced inflammation.

Dysregulation of the Notch pathway is implicated in the pathophysiology of cardiovascular diseases (CVDs), but, as of today, therapies based on the re-establishing the physiological levels of Notch in the heart and vessels are not available. A possible reason is the context-dependent role of Notch in the cardiovascular system, which would require a finely tuned, cell-specific approach. MicroRNAs (miRNAs) are short functional endogenous, non-coding RNA sequences able to regulate gene expression at post-transcriptional levels influencing most, if not all, biological processes. Dysregulation of miRNAs expression is implicated in the molecular mechanisms underlying many CVDs. Notch is regulated and regulates a large number of miRNAs expressed in the cardiovascular system and, thus, targeting these miRNAs could represent an avenue to be explored to target Notch for CVDs. In this Review, we provide an overview of both established and potential, based on evidence in other pathologies, crosstalks between miRNAs and Notch in cellular processes underlying atherosclerosis, myocardial ischemia, heart failure, calcification of aortic valve, and arrhythmias. We also discuss the potential advantages, as well as the challenges, of using miRNAs for a Notch-based approach for the diagnosis and treatment of the most common CVDs.

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as Lactiplantibacillus plantarum, enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with Lactiplantibacillus plantarum on the antioxidant and immunomodulatory effects of Pushgay berries (Vaccinium floribundum, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.7. Polyphenol content was assayed by Folin–Ciocalteu and HPLC-MS/MS analysis. The effects of berries solutions on cell viability or proliferation were assessed by WST8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and Lactate dehydrogenase (LDH) release, Trypan blue exclusion test, and Alamar blue assay. Antioxidant activity was evaluated by a cell-based chemiluminescent probe for the detection of intracellular H2O2 production in HUVECs. Heme oxygenase-1 (HO-1) expression levels were investigated by RT-qPCR. Glutathione reductase (GR), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) activities, as markers of intracellular antioxidant defense, were evaluated by spectrophotometric analysis. The immunomodulatory activity was examined in RAW 264.7 by quantification of inducible nitric oxide synthase (iNOS) and Tumor Necrosis Factor—alpha (TNFα) by RT-qPCR. Data showed that fermentation of Pushgay berries (i) enhances the content of quercetin aglycone, and (ii) increases their intracellular antioxidant activity, as indicated by the reduction in H2O2-induced cell death and the decrease in H2O2-induced HO-1 gene expression in HUVECs treated for 24 h with fermented berries solution (10 µg/mL). Moreover, treatment with Pushgay berries for 72 h (10 µg/mL) promotes cells growth in RAW 264.7, and only fermented Pushgay berries increase the expression of iNOS in the same cell line. Taken together, our results show that LAB fermentation of Pushgay berries enhances their antioxidant and immunomodulatory properties.

Objective: Vasospasm is a severe complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and cannot be reliably predicted. Its pathophysiology remains elusive with the current body of evidence suggesting inflammation as one of the main driving forces. We here aimed to analyze circulating immune cell subsets over time in patients with aSAH with or without vasospasm.Methods: We performed a prospective observational study recruiting patients with spontaneous aSAH. Peripheral blood withdrawn at pre-specified time-points after aSAH, day 0, days 3–4, 6–8, 10–11, 13–15, and 18–21. Flow cytometry analysis, cell blood counts, and laboratory and diagnostic parameters were performed. Patients were monitored by transcranial Doppler for vasospasm as well as by advanced imaging and divided into a group with (VS) and without vasospasm VS (NVS).Results: We included 42 patients for study analysis, 21 VS and 21 NVS. An early significant increase at day 0 in platelet, leukocyte, neutrophil, lymphocyte, NK lymphocyte, monocyte, and CD 14++ CD16− DR+ monocyte counts was found in patients with later ensuing vasospasm. The early differences in platelets, leukocytes, lymphocytes, and NK lymphocytes remained significant on multivariate analysis.Conclusions: An early increase of immune cellular subsets in aSAH may contribute to predict VS.

Liquefaction-induced surface manifestations are the result of a complex geological–geotechnical phenomenon, driven by several controlling factors. We propose a multidisciplinary methodological approach, involving engineering geologists, geomorphologists, sedimentologists, and geotechnical engineers, to build a 3D engineering geological model for liquefaction assessment studies. The study area is Cavezzo (Po Plain, Italy), which is a municipality hit by superficial liquefaction manifestations during the Emilia seismic crisis of May–June 2012. The site is characterized by a Holocene alluvial sequence of the floodplain, fluvial channel, and crevasse splay deposits prone to liquefaction. The integration of different geotechnical investigations, such as boreholes, CPTm, CPTu, and laboratory tests, allowed us to recognize potentially liquefiable lithological units, crucial for hazard assessment studies. The resulting 3D engineering geological model reveals a strict correlation of co-seismic surface manifestations with buried silty sands and sandy silts within the shallow 10 m in fluvial channel setting, which is capped and laterally confined by clayey and silty deposits.

There is a growing interest in arterial and heart valve calcifications, as these contribute to cardiovascular outcome, and are leading predictors of cardiovascular and kidney diseases. Cardiovascular calcifications are often considered as one disease, but, in effect, they represent multifaced disorders, occurring in different milieus and biological phenotypes, following different pathways. Herein, we explore each different molecular process, its relative link with the specific clinical condition, and the current therapeutic approaches to counteract calcifications. Thus, first, we explore the peculiarities between vascular and valvular calcium deposition, as this occurs in different tissues, responds differently to shear stress, has specific etiology and time courses to calcification. Then, we differentiate the mechanisms and pathways leading to hyperphosphatemic calcification, typical of the media layer of the vessel and mainly related to chronic kidney diseases, to those of inflammation, typical of the intima vascular calcification, which predominantly occur in atherosclerotic vascular diseases. Finally, we examine calcifications secondary to rheumatic valve disease or other bacterial lesions and those occurring in autoimmune diseases. The underlying clinical conditions of each of the biological calcification phenotypes and the specific opportunities of therapeutic intervention are also considered and discussed.

After almost a decade of stagnation in clinical research for HF treatment, five large randomized trials recently published have supported the use of four new classes of drugs, namely: angiotensin receptor/neprilysin inhibitor, sodium–glucose co-transporters 2 inhibitors, soluble guanylate cyclase modulators, and myosin activators. Each treatment has proved to be beneficial for both long-term outcomes and quality of life. Beside their clinical relevance, all these novel treatments have a different mechanism of action beyond the usual neuro-hormonal blockage. These different pathways, together with the unquestionable clinical evidence, advocate a re-thinking of HF treatment and of the appropriate drug to integrate with the existing standard therapy, according to different characteristics of HFrEF patients. This study aimed to offer a synthetic overview of the mechanisms of action of the new drugs and to propose a more personalized approach, considering patients’ characteristics and safety profiles. To this end, we have identified seven profiles for patients with chronic heart failure with reduced ejection fraction and two for pre-discharge patients.

Endothelial dysfunction characterizes every aspect of the so-called cardiovascular continuum, a series of events ranging from hypertension to the development of atherosclerosis and, finally, to coronary heart disease, thrombus formation, myocardial infarction, and heart failure. Endothelial dysfunction is the main prognostic factor for the progression of vascular disorders, which responds to drug intervention and lifestyle changes. Virtually all of the drugs used to prevent cardiovascular disorders, such as long-used and new antilipidemic agents and inhibitors of angiotensin enzyme (ACEi), exert an important effect on the endothelium. Endothelial dysfunction is a central feature of coronavirus disease -19 (COVID-19), and it is now clear that life-risk complications of the disease are prompted by alterations of the endothelium induced by viral infection. As a consequence, the progression of COVID-19 is worse in the subjects in whom endothelial dysfunction is already present, such as elderly, diabetic, obese, and hypertensive patients. Importantly, circulating biomarkers of endothelial activation and injury predict the severity and mortality of the disease and can be used to evaluate the efficacy of treatments. The purpose of this review is to provide updates on endothelial function by discussing its clinical relevance in the cardiovascular continuum, the latest insights from molecular and cellular biology, and their implications for clinical practice, with a focus on new actors, such as the Notch signaling and emerging therapies for cardiovascular disease.

In recent years, there has been a continuously growing interest in antioxidants by both customers and food industry. The beneficial health effects of antioxidants led to their widespread use in fortified functional foods, as dietary supplements and as preservatives. A variety of analytical methods are available to evaluate the total antioxidant capacity (TAC) of food extracts and beverages. However, most of them are expensive, time-consuming, and require laboratory instrumentation. Therefore, simple, cheap, and fast portable sensors for point-of-need measurement of antioxidants in food samples are needed. Here, we describe a smartphone-based chemosensor for on-site assessment of TAC of aqueous matrices, relying on the antioxidant-induced formation of gold nanoparticles. The reaction takes place in ready-to-use analytical cartridges containing an hydrogel reaction medium preloaded with Au(III) and is monitored by using the smartphone’s CMOS camera. An analytical device including an LED-based lighting system was developed to ensure uniform and reproducible illumination of the analytical cartridge. The chemosensor permitted rapid TAC measurements of aqueous samples, including teas, herbal infusions, beverages, and extra virgin olive oil extracts, providing results that correlated with those of the reference methods for TAC assessment, e.g., oxygen radical absorbance capacity (ORAC).

Abstract The diagnostic and prognostic implication of exaggerated blood pressure response to exercise has been controversial, with opinions ranging from a benign process to a harbinger of potential cardiovascular morbidity. Nonetheless, lowering of blood pressure and prevention of hypertension is in first instance preferable by lifestyle changes, and many studies have shown the inverse association between physical activity level and the incidence of cardiovascular diseases suggesting low aerobic fitness as a strong predictor for future cardiovascular disease and all-cause mortality in both healthy and cardiovascular disease patients, including those with hypertension. Endothelial function, large artery stiffness and neurohormonal response are surely implicated both in the development of exaggerated blood pressure response to exercise and in the positive effect of physical exercise in the prevention and management of hypertension and cardiovascular disease in general. In their interesting and well documented review published in this issue Kim and Ha broadly described the possible pathophysiologic mechanisms of exaggerated blood pressure response to exercise and its clinical implications: in this regard, a very interesting issue could be represented by the role of exercise training. In fact, there is an the ample evidence in the literature that physical activity could positively affect endothelial function, arterial stiffness, neurohormonal response and finally blood pressure levels both in healthy men and in hypertensive patients and so should be considered a very important element in the prevention and management of cardiovascular disease.

Among the actions designed to manage the water crisis that have taken place in the summers of recent years in the southeastern part of the Emilia-Romagna Region, it has recently launched a trial of managed aquifer recharge in the alluvial fan of the Marecchia river (Rimini), where annually are withdrawn about 28 million m3 of water, 19 of witch for drinking water use. This test consists in conveying into quarry lake, located in the recharge area of the alluvial fan, an additional volume of water through a channel. The increase in the volume of water in the lake, should result in a rapid increase in the availability of water in the aquifers. To verify the recharge efficacy a special monitoring network consisting of 20 measuring points, 5 of which are specially drilled, it has been implemented. In 9 of these points a data logger for the continuous measure of level, temperature and electric conductivity at 20°C, it has been installed. A data logger has also been positioned in the channel from which the water flows into the lake. For about a month groundwater level was monitored prior to the recharge experiment. On 25 February 2014 managed aquifer recharge began and the volume of water flowing through the canal to lake until April 30, 2014, was approximately 600,000 m3. In this period it was possible to observe that the intervention produces the expected effects, thus inducing an increase in the groundwater level which is maximum near the lake and decreases away from it. The rise in the water level of the lake has been rapid and substantial. Within the area of the lake have settled some protected bird species in need of a precise environmental balance for nesting; an excessive increase of the lake level could put at risk of flooding some nests present. The objective of the following phases of the study will be to calibrate an adequate water level of the lake, to the purposes of managed aquifer recharge and to maintain the existing ecosystem. At the moment, it was decided to stop the flow of water into the lake and then to re-set it at a lower flow rate. In the test area also falls a well field that is not currently used. It will be interesting to check in the future, in the event of a major withdrawal, the influence on the progress of the flow lines in conjunction with the managed aquifer recharge.

IntroductionSupraventricular tachyarrhythmias (ST) are the most common cardiac arrhythmias. Little is known about the potential impact of demoralization, which is considered as partially distinct from depression, on the course of ST. A correct assessment of both depressive symptoms and demoralization appears relevant for the treatment of these cardiac diseases, potentially influencing their course.MethodsThe sample consisted of 110 subjects affected by different ST, such as atrial fibrillation (AF), atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). They all underwent a psychiatric evaluation; the Italian version of 9-item Patient Health Questionnaire (PHQ-9) and the Italian version of Demoralization Scale (DS) were administered. Descriptive statistics, pairwise comparisons, and correlational analysis have been implemented.Results26 individuals (23.6%) presented high levels of demoralization. Of these, 20 (76.9%) had a diagnosis of AF and six patients (23.1%) received a diagnosis of other ST. No differences in demoralization levels resulted in regard of sex, cardiac diagnoses and anticoagulant therapies. Amongst people with high levels of demoralization, 13 (50%) received no formal psychiatric diagnosis, and 12 (46.2%) showed moderate/severe depressive symptoms. Demoralization levels and PHQ-9 scores showed a significant positive correlation in the whole sample (r=0.550, p

Abstract Aims The multi‐systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients. Methods and results We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow‐up period was 12 months. The primary endpoint was a composite of all‐cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12 month follow‐up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all‐cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5 ± 12.9. The mean LVEF at admission was 42.5 ± 13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM‐1, 507 (29.5%) in the HLM‐2, 587 (34.1%) in the HLM‐3, and 253 (14.7%) in the HLM‐4. HLM was the most accurate score to predict the primary endpoint at 12 months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM = 0.645; NYHA = 0.580; ACC/AHA = 0.589; LVEF = 0.572). The AUC of the HLM score was significantly better compared with the LVEF (P = 0.002), ACC/AHA (P = 0.029), and NYHA (P = 0.009) AUC. Conclusions The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all‐cause death and rehospitalization due to HF at 12 months of follow‐up.

Background: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial condition with a variety of pathophysiological causes and morphological manifestations. The inclusion criteria and patient classification have become overly simplistic due to the customary differentiation regarding the ejection fraction (EF) cutoff. EF is considered a measure of systolic function; nevertheless, it only represents a portion of the true contractile state and has been shown to have certain limits due to methodological and hemodynamic irregularities. Methods: As a result, broader randomized clinical trials have yet to incorporate the most recent criteria for HFpEF diagnosis, leading to a lack of data consistency and confusion in interpreting the results. The primary variations between the bigger clinical trials published in this context concerning patient selection and echocardiographic characteristics were analyzed. For all these reasons, we aim to clarify the main features and clinical impact of HFpEF in a study combining imaging, bio-humoral analysis, and clinical history to identify the specific subgroups that respond better to tailored treatment. Results: Disparate clinical characteristics and a lack of uniform diagnostic standards may cause suboptimal therapeutic feedback. To optimize treatment, we suggest shifting the paradigm from the straightforward EF measurement to a more comprehensive model that considers additional information, such as structural traits, related disorders, and biological and environmental data. Therefore, by evaluating certain echocardiographic and clinical factors, a stepwise diagnostic procedure may be useful in identifying patients at high risk, subjects with early HFpEF, and those with evident HFpEF. Conclusions: The present assessment underscores the significance of the precision medicine approach in guaranteeing optimal patient outcomes by providing the best care according to each distinct profile.

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02–0.078) and 0.031 ng/mL (IQR 0.02–0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02–4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006–3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54–6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43–4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH.

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician’s experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio–renal interactions, and HF phenotypes.

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction without obstructive coronary artery disease (MINOCA). It is determined by a coronary artery wall layers separation, which occurs regardless of traumatic or iatrogenic injuries. Even if it is often a missed diagnosis, its incidence is growing along with the improvement of intracoronary imaging techniques that allow for better detection. The main angiographical classification distinguishes three different forms, with slightly different prognoses at long-term follow up. SCAD is a recurrent condition, severely hampering the life quality of affected patients. The predominantly young age of patients with SCAD and the high prevalence of females among them have made the topic increasingly important, especially regarding therapeutic strategies. According to the data, the most recommended treatment is conservative, based on the use of antiplatelet agents and supportive anti-ischemic therapy. However, there are conflicting opinions concerning the need for dual antiplatelet therapy and its duration. In the case of invasive treatment, the choice between percutaneous coronary intervention and coronary artery bypass graft depends on the patient’s clinical stability and the interested vessel. The purpose of the current review is to revise the pathophysiological mechanisms underlying SCAD and the current knowledge of its treatment.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.

Background: To provide a comprehensive analysis of the current literature comparing the outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS), with particular attention to BAV morphology in patients undergoing TAVR. Methods: Following PRISMA guidelines, all relevant articles with no design restrictions from PubMed, CCTR (Cochrane Controlled Trials Register), and Google Scholar were screened for inclusion. Studies were included if they reported clinical endpoints for SAVR and TAVR or, in BAS treated with TAVR, for type 1 and non-type 1 morphology. Odds ratio and Cohen’s D were considered as effect size measurements for qualitative and quantitative variables, respectively. Results: A total of eight studies comparing short-term outcomes between SAVR and TAVR and nine studies with outcomes data between type 1 and non-type 1 BAS treated with TAVR were considered for the final analysis. No statistically significant difference was found for what concerns the rates of death, stroke, and acute kidney injury between SAVR and TAVR. In comparison to patients undergoing SAVR, the incidence of PPI (permanent pacemaker implantation) was greater in the TAVR group (OR 0.35, 95% CI 0.15–0.79, p = 0.01), and the frequency of bleeding events was found to be higher among patients undergoing SAVR (OR 4.3, 95% CI 2.9–6.4, p < 0.001). The probabilities of 30-day mortality, stroke, and any bleeding were not significantly affected by bicuspid valve morphology in TAVR patients. PPI or development of new conduction anomalies was found to be more frequent in type 1 anatomies (OR 0.46, 95% CI 0.30–0.70, p

Patients with heart failure are conventionally stratified into phenotypic groups based on their ejection fraction. The aim of this stratification is to improve disease management with a more targeted therapeutic approach. A further subdivision based on patient gender is justified. It is recognized that women are underrepresented in randomized controlled clinical trials, resulting in limited clinical and molecular differentiation between males and females. However, many observational studies show that the onset, development, and clinical course of the disease may substantially differ between the two sexes. According to the emerging concept of precision medicine, investigators should further explore the mechanisms responsible for the onset of heart failure due to sex differences. Indeed, the synergistic or opposing effects of sex hormones on the cardiovascular system and underlying heart failure mechanisms have not yet been clarified. Sex hormones, risk factors impact, and cardiovascular adaptations may be relevant for a better understanding of the intrinsic pathophysiological mechanisms in the two sexes. Despite the differences, treatment for HF is similar across the whole population, regardless of sex and gender. In our review, we describe the main differences in terms of cardiovascular dysfunction, risk factors, and cellular signaling modifications related to the hormonal pattern.

Patients with an established diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed “worsening heart failure” (WHF). Despite guideline-directed medical therapy, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF, and patients experiencing WHF carry a substantially higher risk of death and hospitalization than patients with “stable” HF. New drugs are emerging as arrows in the quiver for clinicians to address the residual risk of HF hospitalization and cardiovascular deaths in patients with WHF. This question-and-answer-based review will discuss the emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC), the new therapeutic approaches to treat WHF and then move on to their timing and safety concerns (i.e., renal profile).