Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort.

Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with Arrhythmogenic Cardiomyopathy (ACM), or Dilated Cardiomyopathy (DCM) inherited in an autosomal dominant manner. A cohort of 18 probands, characterized as heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging features were retrospectively collected. A total of 16 DSP heterozygous pathogenic or likely pathogenic variants were identified, 75% (n = 12) truncating variants, n = 2 missense variants, n = 1 splicing variant, and n = 1 duplication variant. The mean age at diagnosis was 40.61 years (IQR 31-47.25), 61% of patients being asymptomatic (n = 11, New York Heart Association (NYHA) class I) and 39% mildly symptomatic (n = 7, NYHA class II). Notably, 39% of patients (n = 7) presented with a clinical history of presumed myocarditis episodes, characterized by chest pain, myocardial enzyme release, 12-lead electrocardiogram abnormalities with normal coronary arteries, which were recurrent in 57% of cases (n = 4). About half of the patients (55%, n = 10) presented with a varied degree of left ventricular enlargement (LVE), four showing biventricular involvement. Eleven patients (61%) underwent implantable cardioverter defibrillator (ICD) implantation, with a mean age of 46.81 years (IQR 36.00-64.00). Cardiac magnetic resonance imaging (CMRI) identified in all 18 patients a delayed enhancement (DE) area consistent with left ventricular (LV) myocardial fibrosis, with a larger localization and extent in patients presenting with recurrent episodes of myocardial injury. These clinical and genetic data confirm that DSP-related cardiomyopathy may represent a distinct clinical entity characterized by a high arrhythmic burden, variable degrees of LVE, Late Gadolinium Enhancement (LGE) with subepicardial distribution and episodes of myocarditis-like picture.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

An unexpected case of recurrence of pulmonary embolism in a patient recovered from COVID19 in full regimen dose of direct oral anticoagulant drug.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.

Pathophysiology and clinical presentation of paediatric heart failure related to congenital heart disease.

Congenital heart disease (CHD) and cardiomyopathies represent the two most important causes of paediatric heart failure (HF) in developed countries. We made a review of the literature on pathophysiology and clinical presentation of paediatric HF in children with CHD. Two main pathophysiologic models can be identified: the 'over-circulation failure', characterised by signs and symptoms of congestion or hypoperfusion, due respectively to volume or pressure overload, and the 'pump failure'. CONCLUSIONS: The comprehension of the HF pathophysiology in paediatric patients with CHD is of paramount importance for the optimal management and for addressing the best therapeutic choices.

Left ventricular thrombectomy in myocarditis: the epicardial scan & video-assisted transaortic approach.

In a 23-year-old man having myocarditis in the context of eosinophilic granulomatosis with polyangiitis, a mobile left ventricular apical thrombus was found with transthoracic echocardiography. Its surgical removal was established because there were no signs of resizing after effective intravascular anticoagulation therapy. Surgery was carried out via a median sternotomy with cardiopulmonary bypass. The site of endocardial implantation of the thrombus was identified with epicardial ultrasonography scan. The trans-aortic approach was adopted to avoid complications such as ventricular dysfunction and arrhythmias secondary to ventricular incision. Real-time imaging of the complete removal was obtained with optical instruments.

Addressing the Heterogeneity of Heart Failure in Future Randomized Trials.

PURPOSE OF THE REVIEW: The aim of review is to describe the essential role of study designs beyond RCTs in contemporary contest of HF patients giving perspectives on its evolving. The article concludes with concern about the support of observational studies for future randomized clinical trials. RECENT FINDINGS: With the aging population and spectacular advance in cardiovascular therapy, the clinical syndrome comprising heart failure (HF) is increasingly in complexity of heterogeneity. It remains among the most challenging of clinical syndromes with a magnitude of proposed pathophysiological mechanisms involving the heart and the interplay with cardiac and non-cardiac comorbidities. In this epidemiological scenario, randomized clinical trials are suffering from growing failed treatment, so that a deeper understanding of heterogeneity represents a major unmet need. This field also is greatly in a more nuanced comprehension about the applicability in clinical practice of trials' results derived from well-selected HF population. Thus, we need to reflect on trials failures and the translation of previous trials in clinical practice in order to redirect the future trial intervention.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

[Focus on heart failure with preserved ejection fraction: from trials to the real world of the Friuli-Venezia Giulia Cardiovascular Observatory]. / Uno sguardo allo scompenso cardiaco con frazione di eiezione preservata: dai trial al mondo reale dell'Osservatorio Cardiovascolare del Friuli-Venezia Giulia.

Heart failure with preserved ejection fraction (HFpEF) has been for decades a nosological entity lacking specific therapy, with some even questioning its existence. Recently, targeted therapies have been introduced for specific, albeit rare, phenotypes such as Fabry disease, hypertrophic cardiomyopathy and amyloidosis. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally developed as anti-diabetic drugs, have fortuitously emerged as effective molecules in improving the prognosis for both patients with heart failure with reduced ejection fraction (HFrEF) and those with HFpEF, reducing heart failure exacerbations by almost a third. Although there are some epidemiological differences, depending on the country and the context analyzed, it is generally agreed that HFpEF is the most represented phenotype of heart failure, and its prevalence has been increasing in recent years due to the increase in life expectancy, improved diagnostic sensitivity and accuracy, and an exponential increase in risk factors such as diabetes, hypertension, renal failure, chronic obstructive pulmonary disease and obesity. These are often associated, turning out to be an epiphenomenon of a more complex cardio-nephro-metabolic disease. However, data and characteristics from major trials are not always aligned with the features and needs of these patients in real-world settings.The Cardiovascular Observatory of Friuli-Venezia Giulia is a powerful clinical governance tool that allows us to specifically characterize these patients, identifying and directing them towards the most appropriate diagnostic and therapeutic pathways, contributing significantly to improved prognosis and reduced expenditure paid by the National Health System.The use of SGLT2i in HFrEF patients is poised to match that of historic neurohormonal treatments, while, being the only class of drugs currently recommended by the international guidelines, they should even surpass them in HFpEF patients. However, given the high prevalence of HFpEF, it is unlikely for its treatment to be a prerogative of cardiologists alone. In this regard, it will be crucial in the near future to implement shared and integrated pathways with other medical specialists (internists, diabetologists, and nephrologists), and especially with general practitioners, who most frequently encounter these patients, to select the cases with greater complexity and potential for effective therapeutic intervention.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

The chronic heart failure evolutions: Different fates and routes.

AIMS: Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. METHODS AND RESULTS: From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53-71], male gender n = 3973 (81.5%), NYHA class I-II n = 3576 (73.3%), III-IV n = 1300 (26.7%), LVEF = 33 [25.5-39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). CONCLUSIONS: Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Spontaneous coronary artery dissection: Overview of pathophysiology.

The growing use of imaging examinations has led to increased detection of spontaneous coronary artery dissection (SCAD) as a non-atherosclerotic cause of acute coronary syndrome (ACS). Since a greater awareness of pathophysiologic mechanisms has relevant implications in clinical practice, we aim to provide an update to current knowledge of SCAD pathophysiology. We discuss the most common conditions associated with SCAD, including predisposing factors and triggers, and focus on potential mechanisms leading to SCAD development. Furthermore, we report the main genetic research findings that have shed further light on SCAD pathophysiology. Finally, we summarize practical considerations in SCAD management based on pathophysiologic insights.

Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study.

INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

Sex-related differences in chronic heart failure: a community-based study.

AIMS: To evaluate sex-related differences among real-life outpatients with chronic heart failure across the ejection fraction spectrum and to evaluate whether these differences might impact therapy and outcomes. METHODS: A total of 2528 heart failure patients were examined between 2009 and 2015 [mean age 76, 42% females; 59% with heart failure with preserved ejection fraction (HFpEF), 17% with heart failure with mid-range ejection fraction (HFmrEF) and 24% with heart failure with reduced ejection fraction (HFrEF)]. Females showed a higher prevalence of HFpEF than males. RESULTS: Females were older, less obese and with less ischaemic heart disease. They have renal failure and anaemia more frequently than males. There were no differences in terms of heart failure therapy in the HFrEF group, but a lower prescription rate of angiotensin-converting enzyme-I/AT1 blockers in HFmrEF and HFpEF and a higher prescription of mineralocorticoid receptor antagonists in the female group with HFpEF were observed. Crude rate mortality and composite outcome (death/heart failure progression) run similarly across sexes regardless of the ejection fraction categories. After adjustment, risk of mortality was significantly lower in females than males in the HFmrEF and HFpEF groups, whereas similar risk was confirmed across sexes in the HFrEF group. Considering prognostic risk factors, noncardiac comorbidities emerged in the HFpEF group. CONCLUSION: In a community-based heart failure cohort, females were differently distributed within heart failure phenotypes and they presented some different characteristics across ejection fraction categories. Although in an unadjusted model there was no significant difference for adverse outcomes, in an adjusted model females showed a lower risk of mortality in HFpEF and HFmrEF. Concerning sex-related prognostic risk factors, noncardiac comorbidities significantly affected adverse prognosis in females with HFpEF.

Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account.

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

Pathophysiology and management of recreational drug-related acute coronary syndrome: ANMCO position statement.

Recreational drug use may cause coronary artery disease through several mechanisms. An increasing number of young patients with drug-related acute coronary syndrome have been reported over recent years. The present position statement reports the most recent epidemiological data on acute coronary syndrome in the setting of drug abuse, describes the main pathophysiological mechanisms underlying coronary artery disease and acute events in these patients, and provides practical recommendations on management and an overview of prognosis.