Right ventricular dysfunction in chronic heart failure: clinical laboratory and echocardiographic characteristics. (the RIVED-CHF registry).

BACKGROUND: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated. METHODS: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study. RESULTS: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact. CONCLUSIONS: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321).

The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

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.

Current Approaches to Worsening Heart Failure: Pathophysiological and Molecular Insights.

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.

Spontaneous Coronary Artery Dissection in Clinical Practice: Pathophysiology and Therapeutic Approaches.

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.

Heart failure 'the cancer of the heart': the prognostic role of the HLM score.

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.

Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

A Meta-Analysis of Short-Term Outcomes of TAVR versus SAVR in Bicuspid Aortic Valve Stenosis and TAVR Results in Different Bicuspid Valve Anatomies.

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 <0.001). Mildly lower post-procedural transprothesic gradients were found in patients with type 1 morphology. CONCLUSIONS: In BAS patients, TAVR has comparable short-term outcomes rates with SAVR, but higher PPI rates and lower incidence of bleeding events. In patients undergoing TAVR, type 1 BAS is associated with lower postoperative transvalvular gradients but higher PPI rates and conduction abnormalities.

Risk Factors and Cellular Differences in Heart Failure: The Key Role of Sex Hormones.

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.

New Challenges in Heart Failure with Reduced Ejection Fraction: Managing Worsening Events.

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).

[Anticoagulant therapy in left ventricular non-compaction: when, how and why]. / Terapia anticoagulante nel ventricolo sinistro non compatto: quando, come e perché.

Left ventricular non compaction (LVNC) comprises a heterogeneous group of diseases that can cause heart failure, arrhythmias, and thromboembolic events. In particular, the prevalence of thromboembolism in patients with LVNC is relevant compared to the general population. Atrial fibrillation and left ventricular thrombosis are strong predictors and require anticoagulant treatment in primary or secondary prevention, with a significant reduction in the risk of events. Long-term oral anticoagulation can be considered in patients with LVNC associated with left ventricular systolic dysfunction and sinus rhythm. On the contrary, it is not entirely clear whether the presence of deep intertrabecular recesses that cause blood flow stagnation can itself represent a thrombogenic substrate even in the absence of ventricular dysfunction and in sinus rhythm, thus indicating the use of anticoagulation.This article addresses the open question of the indication for anticoagulant therapy in LVNC, through a review of the current evidence on thromboembolic risk stratification and the initiation of anticoagulant therapy and by proposing a flow-chart as a guide to decision-making according to the clinical picture of the patient.

Telemedicine: an Effective and Low-Cost Lesson From the COVID-19 Pandemic for the Management of Heart Failure Patients.

PURPOSE: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain.

Sizing SGLT2 Inhibitors Up: From a Molecular to a Morpho-Functional Point of View.

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.

Medical Management of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

PURPOSE OF REVIEW: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH). RECENT FINDINGS: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH.

The Role of MicroRNA in the Myocarditis: a Small Actor for a Great Role.

PURPOSE OF REVIEW: Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management. RECENT FINDINGS: Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis.

Protection against Ischemic Heart Disease: A Joint Role for eNOS and the KATP Channel.

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.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA): Focus on Coronary Microvascular Dysfunction and Genetic Susceptibility.

Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it.

Biobanks: The unmet need in heart failure management.

Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies. The institution of biobanks may represent the game changer in HF scenario, providing a collection of human biological materials with the related medical and epidemiological data fueling the development of personalized therapeutic approach and fostering current and/or future research projects.

Heart Failure Pharmacological Management: Gaps and Current Perspectives.

Proper therapeutic management of patients with heart failure (HF) is a major challenge for cardiologists. Current guidelines indicate to start therapy with angiotensin converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors (ACEi/ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRAs) and sodium glucose cotransporter 2 inhibitors (SGLT2i) to reduce the risk of death and hospitalization due to HF. However, certain aspects still need to be defined. Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations. However, these last do not always reflect the precise hemodynamic status of patients and pathophysiological mechanisms involved, particularly in the acute setting. Even in the field of chronic management there are still some critical points to discuss. The guidelines do not specify which of the four pillar drugs to start first, nor at what dosage. Some authors suggest starting with SGLT2i and BB, others with ACEi or ARNI, while one of the most recent approach proposes to start with all four drugs together at low doses. The aim of this review is to revise current gaps and perspectives regarding pharmacological therapy management in HF patients, in both the acute and chronic phase.

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

Dual pathway inhibition in atherothrombosis prevention: yes, now we can!

Despite ongoing developments, prevention and treatment of atherothrombotic cardiovascular disease remains a common challenge. Antithrombotic options for cardiocerebrovascular disease prevention involves a choice between dual antiplatelet therapy (DAPT) and dual pathway inhibition (DPI), which includes an antiplatelet agent and a reduced dose anticoagulant agent. In selected patients at high risk of event and low risk of bleeding, especially those undergoing recent and complex coronary revascularization using drug-eluting stents (DES) ("revascularization-driven effect"), DAPT is superior to single antiplatelet therapy with aspirin. DPI involves a wider potential range of treatment and is superior to single antiplatelet therapy with aspirin, particularly in patients with atherothrombotic involvement in different vascular beds both previously revascularized and not ("no revascularization-driven effect"). After nearly thirty years of randomized trials and observational registries, we have sufficient data to customize antithrombotic therapy in patients at high cardiovascular risk. Therefore, "atherothrombosis stakeholders" must identify the right patient for the right therapy to ensure high levels of efficacy and safety with the best of current therapeutic opportunities.