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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 The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy‐three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow‐up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51–0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49–0.90]) along with all‐cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56–0.97] and HR, 0.56 [95% CI, 0.38–0.84], respectively). The results were consistent in the propensity‐score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39–0.89] for ST‐segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50–0.99] for non‐ST‐elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37–0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37–1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST‐segment elevation myocardial infarction and non‐ST‐elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT 04895176.

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.

ABSTRACT Introduction and objectives: Coronary artery aneurysms are a complex situation. Our main objective is to describe the frequency of use of covered stents (grafts) for their management, as well as to characterize their long-term results compared to drug-eluting stents. Methods: Ambispective observational study with data from the International Coronary Artery Aneurysm Registry (CAAR) (NCT-02563626). Only patients who received a stent-graft or a drug-eluting stent where the aneurysm occurred were selected. Results: A total of 17 patients received, at least, 1 stent-graft while 196 received 1 drug-eluting in the aneurysmal vessel. Male predominance, a higher rate of dyslipidemia, a past medical history of coronary artery disease, previously revascularized coronary artery disease, and giant aneurysms were reported in the stent-graft cohort. The independent predictive variables of the composite endpoint of all-cause mortality, heart failure, unstable angina, reinfarction, stroke, systemic embolism, bleeding or any aneurysmal complications at the median follow-up of 38 months were suggestive of the existence of connective tissue diseases (HR, 5.94; 95%CI, 1.82-19.37), left ventricular dysfunction ≤ 55% (HR, 1.84; 95%CI, 1.09-3.1), and an acute indication for heart catheterization (HR, 2.98; 95%CI, 1.39-6.3). The use of stent-grafts was not associated with the occurrence of more composite endpoints (23.5% vs 29.6%; P = .598). Conclusions: The use of stent-grafts to treat coronary aneurysms is feasible and safe in the long-term. Randomized clinical trials are needed to decide what the best treatment is for these complex lesions. Keywords: Coronary aneurysm. Registry. Stent. Stent graft. Angioplasty.

RESUMEN Introducción y objetivos: Los aneurismas coronarios son una situación compleja. Planteamos como objetivo principal describir la frecuencia de utilización de stents recubiertos (grafts) para su tratamiento y caracterizar sus resultados a largo plazo en comparación con stents farmacoactivos. Métodos: Estudio observacional ambispectivo, con información procedente del Registro Internacional de Aneurismas Coronarios (CAAR) (NCT-02563626). Se seleccionaron los pacientes que recibieron un stent-graft o un stent farmacoactivo en la zona del aneurisma. Resultados: Un total de 17 pacientes recibieron al menos un stent-graft y 196 un stent farmacoactivo en la zona aneurismática. Se observa un predominio del sexo masculino y una mayor frecuencia de dislipemia, antecedentes de coronariopatía, enfermedad coronaria revascularizada previamente y aneurismas gigantes en la cohorte de stent-graft. Como variables independientes predictoras del desarrollo del evento combinado (muerte por cualquier causa, insuficiencia cardiaca, angina inestable, reinfarto, ictus, embolia sistémica, sangrado o cualquier complicación en el aneurisma), tras una mediana de seguimiento de 38 meses, destacaron la existencia de conectivopatías (hazard ratio [HR] = 5,94; intervalo de confianza del 95% [IC95%], 1,82-19,37), la disfunción del ventrículo izquierdo ≤ 55% (HR = 1,84; IC95%, 1,09-3,1) y la indicación aguda del cateterismo índice (HR = 2,98; IC95%, 1,39-6,3). El uso de stent-grafts comparado con el de stents farmacoactivos no se asoció al desarrollo de más eventos combinados (23,5 frente a 29,6%; p = 0,598). Conclusiones: El uso de stents recubiertos en aneurismas coronarios es factible y seguro a largo plazo. Se necesitan estudios clínicos aleatorizados para decidir el mejor tratamiento de este tipo de lesiones complejas.

Sodium–glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known glucose reduction power. The cardioprotective effects of gliflozins seem to be linked to the maintenance of cellular homeostasis and to an action on the main metabolic pathways. They improve the oxygen supply for cardiomyocytes with a considerable impact on both functional and morphological myocardial aspects. Moreover, multiple molecular actions of SGLT2i are being discovered, such as the reduction of both inflammation, oxidative stress and cellular apoptosis, all responsible for myocardial damage. Various studies showed controversial results concerning the role of SGLT2i in reverse cardiac remodeling and the lowering of natriuretic peptides, suggesting that their overall effect has yet to be fully understood. In addition to this, advanced imaging studies evaluating the effect on all four cardiac chambers are lacking. Further studies will be needed to better understand the real impact of their administration, their use in daily practice and how they can contribute to benefits in terms of reverse cardiac remodeling.

Abstract Background Early detection of myocardial involvement can be relevant in coronavirus disease 2019 (COVID-19) patients to timely target symptomatic treatment and decrease the occurrence of the cardiac sequelae of the infection. The aim of the present study was to assess the clinical value of cardiovascular magnetic resonance (CMR) in characterizing myocardial damage in active COVID-19 patients, through the correlation between qualitative and quantitative imaging biomarkers with clinical and laboratory evidence of myocardial injury. Methods In this retrospective observational cohort study, we enrolled 27 patients with diagnosis of active COVID-19 and suspected cardiac involvement, referred to our institution for CMR between March 2020 and January 2021. Clinical and laboratory characteristics, including high sensitivity troponin T (hs-cTnT), and CMR imaging data were obtained. Relationships between CMR parameters, clinical and laboratory findings were explored. Comparisons were made with age-, sex- and risk factor–matched control group of 27 individuals, including healthy controls and patients without other signs or history of myocardial disease, who underwent CMR examination between January 2020 and January 2021. Results The median (IQR) time interval between COVID-19 diagnosis and CMR examination was 20 (13.5–31.5) days. Hs-cTnT values were collected within 24 h prior to CMR and resulted abnormally increased in 18 patients (66.6%). A total of 20 cases (74%) presented tissue signal abnormalities, including increased myocardial native T1 (n = 11), myocardial T2 (n = 14) and extracellular volume fraction (ECV) (n = 10), late gadolinium enhancement (LGE) (n = 12) or pericardial enhancement (n = 2). A CMR diagnosis of myocarditis was established in 9 (33.3%), pericarditis in 2 (7.4%) and myocardial infarction with non-obstructive coronary arteries in 3 (11.11%) patients. T2 mapping values showed a moderate positive linear correlation with Hs-cTnT (r = 0.58; p = 0.002). A high degree positive linear correlation between ECV and Hs-cTnT was also found (r 0.77; p

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (KATP) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the KATP channel that provides a potential protective effect against IHD.

Abstract Aims The recent coronavirus disease 19 (COVID‐19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID‐19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. Methods and results We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter‐year period (21 February to 31 March 2019) and an intra‐year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra‐year period, and 192 during inter‐year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra‐year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56–0.89; P = 0.0037), or with inter‐year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45–0.72; P

Abstract Background Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. Methods From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. Results Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p

The research experience "Narrating the museum to promote empathy and critical thinking in medical science students and doctors through online activities", carried out within the "Inclusive Memory" project, co-funded by University Roma Tre, aims at promoting empathy and critical thinking skills in medical science students and doctors through heritage education activities. The innovative features of the research experience lie in the use of online activities, combining different learning methodologies: Visual Thinking Strategies, Reflective Questioning, Storytelling, and Object-Based Learning. The paper presents the results of the pilot activity carried out by the Centre for Museum Studies research group, based at the Department of Education – Roma Tre, in collaboration with the Sapienza University of Rome. It also describes the teaching activities, learning and evaluation tools used during the pilot experience, which involved 35 participants. The trial results highlight a statistically significant improvement in the Critical Thinking use of language indicators and an improvement of Sensitivity to the context empathy dimension; participants state that their levels of communication and critical thinking skills improved at the end of the activities and that the exercises foreseen stimulated reflection, observation, and interpretation.

Objective Approximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR.Methods Participants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR.Results Of 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; p

Micronutrients are ions and vitamins humbly required by the human body. They play a main role in several physiological mechanisms and their imbalance is strongly associated with potentially-fatal complications. Micronutrient imbalance is associated with many cardiovascular diseases, such as arrythmias, heart failure, and ischemic heart disease. It has been also observed in coronavirus disease 2019 (COVID-19), particularly in most severe patients. The relationship between cardiovascular diseases and COVID-19 is mutual: the latter triggers cardiovascular disease onset and worsening while patients with previous cardiovascular disease may develop a more severe form of COVID-19. In addition to the well-known pathophysiological mechanisms binding COVID-19 and cardiovascular diseases together, increasing importance is being given to the impact of micronutrient alterations, often present during COVID-19 and able to affect the balance responsible for a good functioning of the cardiovascular system. In particular, hypokalemia, hypomagnesemia, hyponatremia, and hypocalcemia are strongly associated with worse outcome, while vitamin A and D deficiency are associated with thromboembolic events in COVID-19. Thus, considering how frequent the cardiovascular involvement is in patients with COVID-19, and how it majorly affects their prognosis, this manuscript provides a comprehensive review on the role of micronutrient imbalance in the interconnection between COVID-19 and cardiovascular diseases.

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) utilizes the angiotensin‐converting enzyme‐2 (ACE‐2) receptor to enter human cells. Angiotensin‐converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE‐2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID‐19). Methods and Results We used the Coracle registry, which contains data of patients hospitalized with COVID‐19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in‐hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (PTrend

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients’ survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients’ outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease’s natural course.

An amendment to this paper has been published and can be accessed via the original article.

Background Many patients with severe aortic stenosis are referred late with advanced symptoms or inappropriately denied intervention. The objective was to investigate whether a structured communication to referring physicians (facilitated data relay) might improve the rate and timeliness of intervention. Methods and Results A prospective registry of consecutive patients with severe aortic stenosis at 23 centers in 9 European countries with transcatheter as well as surgical aortic valve replacement being available was performed. The study included a 3‐month documentation of the status quo (phase A), a 6‐month intervention phase (implementing facilitated data relay), and a 3‐month documentation of a legacy effect (phase‐B). Two thousand one hundred seventy‐one patients with severe aortic stenoses were enrolled (phase A: 759; intervention: 905; phase‐B: 507). Mean age was 77.9±10.0 years, and 80% were symptomatic, including 52% with severe symptoms. During phase A, intervention was planned in 464/696 (67%), 138 (20%) were assigned to watchful waiting, 8 (1%) to balloon aortic valvuloplasty, 60 (9%) were listed as not for active treatment, and in 26 (4%), no decision was made. Three hundred sixty‐three of 464 (78%) patients received the planned intervention within 3 months. Timeliness of the intervention improved as shown by the higher number of aortic valve replacements performed within 3 months (59% versus 51%, P=0.002) and a significant decrease in the time to intervention (36±38 versus 30±33 days, P=0.002). Conclusions A simple, low‐cost, facilitated data relay improves timeliness of treatment for patients diagnosed with severe aortic stenosis, resulting in a shorter time to transcatheter aortic valve replacement. This effect was mainly driven by a significant improvement in timeliness of intervention in transcatheter aortic valve replacement but not surgical aortic valve replacement. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02241447.

Ischemic heart disease (IHD) has several risk factors, among which diabetes mellitus represents one of the most important. In diabetic patients, the pathophysiology of myocardial ischemia remains unclear yet: some have atherosclerotic plaque which obstructs coronary blood flow, others show myocardial ischemia due to coronary microvascular dysfunction in the absence of plaques in epicardial vessels. In the cross-talk between myocardial metabolism and coronary blood flow (CBF), ion channels have a main role, and, in diabetic patients, they are involved in the pathophysiology of IHD. The exposition to the different cardiovascular risk factors and the ischemic condition determine an imbalance of the redox state, defined as oxidative stress, which shows itself with oxidant accumulation and antioxidant deficiency. In particular, several products of myocardial metabolism, belonging to oxidative stress, may influence ion channel function, altering their capacity to modulate CBF, in response to myocardial metabolism, and predisposing to myocardial ischemia. For this reason, considering the role of oxidative and ion channels in the pathophysiology of myocardial ischemia, it is allowed to consider new therapeutic perspectives in the treatment of IHD.

Magnesium is an essential mineral naturally present in the human body, where it acts as cofactor in several enzymatic reactions. Magnesium is a key cardiovascular regulator, which maintains electrical, metabolic, and vascular homeostasis. Moreover, magnesium participates in inflammation and oxidative processes. In fact, magnesium deficiency is involved in the pathophysiology of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, endothelial dysfunction, coronary artery disease, cardiac arrhythmias, and sudden cardiac death. In consideration of the great public-health impact of cardiovascular disease, the recognition of the negative effects of magnesium deficiency suggests the possible role of hypomagnesaemia as cardiovascular risk factor and the use of serum magnesium level for the screening and prevention of cardiovascular risk factors and cardiovascular diseases. Moreover, it might help with the identification of new therapeutical strategies for the management of cardiovascular disease through magnesium supplementation.

Atrial fibrillation (AF) is the most widely recognized arrhythmia. Systemic arterial hypertension, diabetes, obesity, heart failure, and valvular heart diseases are major risk factors for the onset and progression of AF. Various studies have emphasized the augmented anxiety rate among AF patients due to the poor quality of life; however, little information is known about the possibility of triggering atrial fibrillation by anxiety. The present review sought to underline the possible pathophysiological association between AF and anxiety disorders and suggests that anxiety can be an independent risk factor for AF, acting as a trigger, creating an arrhythmogenic substrate, and modulating the autonomic nervous system. The awareness of the role of anxiety disorders as a risk factor for AF may lead to the development of new clinical strategies for the management of AF.

Background. Residual angina after PCI is a frequently occurring disease. Ivabradine improves symptoms but its role in patients without left ventricular systolic dysfunction is still unclear. The aim was to quantify the effects of ivabradine in terms of MVO2 indicators and diastolic function. Methods. Twenty-eight consecutive patients with residual angina after PCI were randomized to ivabradine 5 mg twice/day (IG) or standard therapy (CG). All patients performed a stress echocardiography at the enrollment and after 30 days. MVO2 was estimated from double product (DP) and triple product (TP) integrating DP with ejection time (ET). Diastolic function was evaluated determining E and A waves, E′ measurements, and E/E′ ratio both at rest and at the peak of exercise. Results. The exercise time was longer in IG 9′49″ ± 48″ vs 8′09″ ± 59″ in CG (p=0.0001), reaching a greater workload (IG 139.3 ± 13.4 vs CG 118.7 ± 19.6 Watts; p=0.003). MVO2 expressed with DP and TP was significantly higher in IG (DP: IG 24194 ± 2697 vs CG 20358 ± 4671.8, p=0.01; TP: IG 17239 ± 4710 vs CG 12206 ± 4413, p=0.007). At peak exercise, the ET was diminished in IG than CG. The analysis of diastolic function after the exercise revealed an increase of E and A waves, without difference in the E/A ratio. The E′ wave was higher in IG than CG, and in the same group, the differences between baseline and peak exercise were greater (∆E′3.14 ± 0.7 vs 2.4 ± 1.13, p=0.047). The E/E′ ratio was reduced in patients treated with ivabradine (IG 10.2 ± 2.0 vs CG 7.9 ± 1.6, p=0.002). Conclusions. Ivabradine seems to produce a significant improvement of ischemic threshold, chronotropic reserve, and diastolic function.

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large–medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction.

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.

Heart failure is a complex syndrome responsible for high rates of death and hospitalization. Ischemic heart disease is one of the most frequent causes of heart failure and it is normally attributed to coronary artery disease, defined by the presence of one or more obstructive plaques, which determine a reduced coronary blood flow, causing myocardial ischemia and consequent heart failure. However, coronary obstruction is only an element of a complex pathophysiological process that leads to myocardial ischemia. In the literature, attention paid to the role of microcirculation, in the pathophysiology of ischemic heart disease and heart failure, is growing. Coronary microvascular dysfunction determines an inability of coronary circulation to satisfy myocardial metabolic demands, due to the imbalance of coronary blood flow regulatory mechanisms, including ion channels, leading to the development of hypoxia, fibrosis and tissue death, which may determine a loss of myocardial function, even beyond the presence of atherosclerotic epicardial plaques. For this reason, ion channels may represent the link among coronary microvascular dysfunction, ischemic heart disease and consequent heart failure.

Advanced heart failure (AdHF) represents a challenging aspect of heart failure patients. Because of worsening clinical symptoms, high rates of re-hospitalization and mortality, AdHF represents an unstable condition where standard treatments are inadequate and additional interventions must be applied. A heart transplant is considered the optimal therapy for AdHF, but the great problem linked to the scarcity of organs and long waiting lists have led to the use of mechanical circulatory support with ventricular-assist device (VAD) as a destination therapy. VAD placement improves the prognosis, functional status, and quality of life of AdHF patients, with high rates of survival at 1 year, similar to transplant. However, the key element is to select the right patient at the right moment. The complete assessment must include a careful clinical evaluation, but also take into account psychosocial factors that are of crucial importance in the out-of-hospital management. It is important to distinguish between AdHF and end-stage HF, for which advanced therapy interventions would be unreasonable due to severe and irreversible organ damage and, instead, palliative care should be preferred to improve quality of life and relief of suffering. The correct selection of patients represents a great issue to solve, both ethically and economically.

Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IHD.

Heart Failure (HF) is an acute or chronic syndrome, that causes a lot of damaging effects to every system. The involvement of different systems is variably related to age and others comorbidities. The severity of organ damage is often proportional to the duration of heart failure. The typology of HF and the duration determine which organs will be affected and vice versa the severity of organ damage supplies precious information about prognosis and outcome of patients with heart failure. Moreover, a classification based not only on symptomatic and syndromic typical features of heart failure, but also on functional data of each system, could allow us to apply the most appropriate therapies, to obtain a more accurate prognosis, and to employ necessary and not redundant human and financial resources. With an eye on the TNM staging used in oncology, we drawn up a classification that will consider the different involvement of organs such as lungs, kidneys, and liver in addition to psychological pattern and quality of life in HF patients. For all these reasons, it is our intention to propose a valid and more specific classification available for the clinical staging of HF that takes into account pathophysiological and structural changes that can remark prognosis and management of HF.