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Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63-0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53-0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2-0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57-0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12-0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25-3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.Trial registration: CRD42021257977.

The remarkable scientific progress in the treatment of patients with heart failure (HF) and reduced ejection fraction (HFrEF) has more than halved the risk of sudden cardiac death (SCD) in this setting. However, SCD remains one of the major causes of death in this patient population. Beyond the acknowledged role of beta blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS), a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNI), proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. The mechanism by which ARNI may reduce the mortality connected with harmful ventricular arrhythmias is not utterly clear. A variety of direct and indirect mechanisms have been suggested, but a favorable left ventricular reverse remodeling seems to play a key role in this setting. Furthermore, the well-known protective effect of implantable cardioverter-defibrillator (ICD) has been debated in HFrEF patients with non-ischemic cardiomyopathy (NICM) arguing against the role of primary prevention ICD in this setting, particularly when ARNI therapy is considered. The purpose of this review was to provide insights into the SCD mechanisms involved in HFrEF patients together with the current role of electrical therapies and new drug agents in this setting. [Figure not available: see fulltext.].

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. Objectives: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. Methods: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients’ outcomes. Results: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm2, p ​< ​0.001); Volume (487.79 ​± ​565.34 vs 207.77 ​± ​406.81, p ​< ​0.001)], aortic valve [Volume (322.45 ​± ​390.90 vs 98.27 ​± ​250.74 mm2, p ​< ​0.001; Agatston 337.38 ​± ​414.97 vs 111.70 ​± ​282.15, p ​< ​0.001)] and thoracic aorta [Volume (3786.71 ​± ​4225.57 vs 1487.63 ​± ​2973.19 mm2, p ​< ​0.001); Agatston (4688.82 ​± ​5363.72 vs 1834.90 ​± ​3761.25, p ​< ​0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046–1.637, p ​= ​0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200–3.251, p ​= ​0.007) resulted to be independent predictors of in-hospital mortality. Conclusion: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

The COVID-19 global pandemic has had striking effects on clinical practice and medical assistance and the progressive evolution of telemedicine and telehealth systems has allowed healthcare professionals to connect with patients yet respecting the striking need for social distancing. This article aims to review the possible ways to use telehealth and teleconsulting systems to guarantee an adequate level of clinical assistance starting from screening procedures up to support the management of patients admitted to intensive care units area, thus balancing the need to ensure continuity of care and at the same time limiting the possible sources of contagion expansion. Telemedicine may be a useful tool to improve clinical assistance and reduce the financial burden on the health system in a long-term view. Although it cannot completely replace patient-physician interactions, it would be desirable to implement this field and made it accessible to the largest part of the population.

Selective cardiac myosin activators constitute a new class of drugs capable of increasing cardiac contractility independently of intracellular calcium concentrations. In the GALACTIC-HF study, the first of this class of molecules, omecamtiv mercabil, was compared with the standard of care according to current guidelines, showing a significant reduction in the composite endpoint of first episode of heart failure or mortality due to cardiovascular causes in patients exposed to treatment compared with placebo. In particular, the effect was more pronounced for decreasing ejection fraction values, suggesting a potential further benefit of selective cardiac myosin activators in this category of patients.

Objectives: The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy. Background: The worldwide severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has created unprecedented challenges for public health, demanding exceptional efforts for the successful management and treatment of affected patients. Heart transplant patients represent a unique cohort of chronically immunosuppressed subjects in which SARS-CoV-2 may stimulate an unpredictable clinical course of infection. Methods: Since February 2020, we enrolled all 47 cases (79% male) in a first cohort of patients, with a mean age of 61.8 ± 14.5 years, who tested positive for SARS-CoV-2, out of 2,676 heart transplant recipients alive before the onset of the COVID-19 pandemic at 7 heart transplant centers in Northern Italy. Results: To date, 38 patients required hospitalization while 9 remained self-home quarantined and 14 died. Compared to the general population, prevalence (18 vs. 7 cases per 1,000) and related case fatality rate (29.7% vs. 15.4%) in heart transplant recipients were doubled. Univariable analysis showed older age (p = 0.002), diabetes mellitus (p = 0.040), extracardiac arteriopathy (p = 0.040), previous PCI (p = 0.040), CAV score (p = 0.039), lower GFR (p = 0.004), and higher NYHA functional classes (p = 0.023) were all significantly associated with in-hospital mortality. During the follow-up two patients died and a third patient has prolonged viral-shedding alternating positive and negative swabs. Since July 1st, 2020, we had 6 new patients who tested positive for SARS-CoV-2, 5 patients asymptomatic were self-quarantined, while 1 is still hospitalized for pneumonia. A standard therapy was maintained for all, except for the hospitalized patient. Conclusions: The prevalence and mortality of SARS-CoV-2 should spur cl

OBJECTIVES In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (3 months). RESULTS In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER(3 months): 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. CONCLUSIONS In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent. As a registry of the European Association for Cardio-Thoracic Surgery, the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) offers a robust repository of clinica

OBJECTIVES: In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS: Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (<3 vs >3 months). RESULTS: In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER<3 months: 1.44 vs AER>3 months: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. CONCLUSIONS: In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent.

Left ventricular hypertrophy is a common complication of different diseases. Among these, cardiac involvement of amyloidosis or Anderson-Fabry disease are often unrecognized. Early diagnosis is therefore crucial because new therapies can impact the progression of these diseases. Different specific signs unmasked by clinical, laboratory, and non-invasive diagnostic tests such as echocardiography or cardiac magnetic resonance could guide clinicians towards an appropriate diagnosis. The aim of this review is to underline the major diagnostic clues of different forms of left ventricular hypertrophy in adult patients, guiding clinicians towards a more appropriate diagnosis.

Clinical guidelines, while representing an objective reference to perform appropriate treatment choices, contain grey zones, where recommendations are not supported by solid evidence. In a conference held in Bergamo in October 2018, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding new oral anticoagulants (NOACs) and atrial fibrillation (AF). The manuscript represents the organization of the meeting, with an initial review of current guidelines on this topic, followed by an expert presentation of pros (white) and cons (black) related to the identified "gaps of evidence". For every issue is then reported the response derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical "take home messages" to be used in everyday clinical practice. The first topic concerns the indication for anticoagulant therapy in patients with subclinical AF revealed by implanted devices. The second issue examines the opportunity to use NOACs in oncological patients with AF. The third gap evaluates the necessity of anticoagulating patients with AF and CHA2DS2-VASc 1 or CHA2DS2-VASc 2 if women. The last "gap in evidence" concerns the preference of triple or double therapy in patients with AF and acute coronary syndrome/coronary stenting. The work has also been implemented with evidences deriving from important randomized studies published after the date of the Conference.

Since the beginning of the SARS-CoV-2 outbreak, few cases of COVID-19 pneumonia in patients with pulmonary arterial hypertension have been reported. We present four patients with known history of PAH admitted to our hospital with SARS-CoV-2 pneumonia to analyze the impact of this disease on their clinical outcome.

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest 'unmet medical need', because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ~50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve 'surrogate' outcomes, such as quality of life.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes – with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

Heart failure (HF) is a pandemic syndrome characterised by raised morbidity and mortality. An acute HF event requiring hospitalisation is associated with a poor prognosis, in both the short and the long term. Moreover, early rehospitalisation after discharge negatively affects HF management and survival rates. Cardiovascular and non-cardiovascular conditions combine to increase rates of HF hospital readmission at 30 days. A tailored approach for HF pharmacotherapy while the patient is in hospital and immediately after discharge could be useful in reducing early adverse events that cause rehospitalisation and, consequently, prevent worsening HF and readmission during the vulnerable phase after discharge.

Background: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. Methods: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute–right ventricular failure (N = 8, 11%) or chronic–right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an “all-subsets” approach. Results: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular–free wall were the most significant predictors of acute–right ventricular failure (maximum receiver operating characteristic–area under the curve = 0.95, 95% confidence interval = 0.91–1.00, by the naïve Bayes), while the right ventricular–free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic–area under the curve = 0.97, 95% confidence interval = 0.91–1.00, according to naïve Bayes). Conclusion: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute–right ventricular failure and chronic–right ventricular failure, respectively.

Heart failure with preserved ejection fraction represents an emerging pandemic and one of the most relevant causes of admission in the elderly population. The hemodynamic and prognostic role of the right ventricular function in this population has been recently investigated and a position statement on behalf of the Heart Failure Association of the European Society of Cardiology has been published to guide physicians to perform a multiparametric evaluation of right ventricular morphology and function. In this brief review we summarize the role of the right ventricle and pulmonary pressure in heart failure with preserved ejection fraction, focusing on hemodynamic and clinical characteristics that identify high-risk patients with poor prognosis.

Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. Methods Among 4047 subjects aged >_55/<_80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg and results study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/functional ones, associated with higher risk of HF/death [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.84–0.95, Padjusted < 0.001]. The risk of HF/death related to clinical data and NT-proBNP (baseline model) was reclassified by echocardiography only when MWFS was included into the model (baseline C-statistics 0.761; adding conventional structural/functional echocardiographic data 0.776, P = 0.09; adding MWFS 0.791, P = 0.007). Compared to subjects with normal LVEF and MWFS, only subjects with combined systolic dysfunction (11% of the population) were at higher risk (P = 0.001 for both abnormal; P > 0.24 for either LVEF or MWFS abnormal). Conclusion DAVID-Berg data suggest to include MWFS assessment in clinical practice, a simple and reliable echocardiographic parameter able to improve risk stratification in subjects at high risk for HF.

Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may be associated with incident heart failure (HF). However, this gray zone group needs incremental risk refinement. We hypothesized that diastolic dysfunction (DD) may refine HF and death risk prediction in mild ALVSD., Background: Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may be associated with incident heart failure (HF). However, this gray zone group needs incremental risk refinement. We hypothesized that diastolic dysfunction (DD) may refine HF and death risk prediction in mild ALVSD. Methods and results: Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, N-terminal pro B-type natriuretic peptide, and echocardiogram. Based on left ventricular ejection fraction (LVEF) and DD, subjects were classified as: control group (normal LVEF, n = 459, 76%), mild ALVSD (LVEF ≥40%/<53%) without DD (n = 89, 15%) and with DD (n = 54, 9%). Subjects with LVEF <40% or without full echocardiographic data were excluded from the analysis (n = 21). Mean age of the population was 69 ±7 years, 56% were men, mostly hypertensive, mean LVEF was 61%. During a median follow-up of 5.7 years, 88 subjects (15%) experienced HF/death events (59 HF events and 29 deaths). Compared to the control group, mild ALVSD was associated with a higher risk of incident HF/death (hazard ratio 1.80, 95% confidence interval 1.10–2.93, adjusted P = 0.019) according to the Cox proportional hazards model. However, this higher risk was present only in subjects with combined DD (P = 0.005) and not in those without it (P = 0.30). Results were consistent even considering the individual components of the primary outcome. Conclusion: In a high-risk population, an echocardiographic exam is normally performed to assess systolic dysfunction. Our data underline the importance of also relying on DD to risk stratify mild ALVSD. Mild ALVSD might be a predictor of adverse events mainly in subjects with combined DD, though further studies are needed to confirm these results.

BACKGROUND: In patients with ischemic mitral regurgitation requiring mitral valve replacement (MVR), the choice of the prosthesis type is crucial. The exercise hemodynamic and functional capacity performance in patients with contemporary prostheses have never been investigated. To compare exercise hemodynamic and functional capacity between biological (MVRb) and mechanical (MVRm) prostheses. METHODS AND RESULTS: We analyzed 86 consecutive patients with ischemic mitral regurgitation who underwent MVRb (n=41) or MVRm (n=45) and coronary artery bypass grafting. All patients underwent preoperative resting echocardiography and 6-minute walking test. At follow-up, exercise stress echocardiography was performed, and the 6-minute walking test was repeated. Resting and exercise indexed effective orifice areas of MVRm were larger when compared with MVRb (resting: 1.30±0.2 versus 1.19±0.3 cm 2 /m 2 ; P=0.03; exercise: 1.57±0.2 versus 1.18±0.3 cm 2 /m 2 ; P=0.0001). The MVRm had lower exercise systolic pulmonary arterial pressure at follow-up compared with MVRb (41±5 versus 59±7 mm Hg; P=0.0001). Six-minute walking test distance was improved in the MVRm (pre-operative: 242±43, post-operative: 290±50 m; P=0.001), whereas it remained similar in the MVRb (pre-operative: 250±40, post-operative: 220±44 m; P=0.13). In multivariable analysis, type of prosthesis, exercise indexed effective orifice area, and systolic pulmonary arterial pressure were joint predictors of change in 6-minute walking test (ie, difference between baseline and follow-up). CONCLUSIONS: In patients with ischemic mitral regurgitation, bioprostheses are associated with worse hemodynamic performance and reduced functional capacity, when compared with MVRm. Randomized studies with longer follow-up including quality of life and survival data are required to confirm these results.

Purpose: Adaptive servo-ventilation (ASV) is a ventilator algorithm able to correct breathing through anticyclic support of breathing in patients with central sleep apnea (CSA). So far, very few data exist regarding the role of ASV on acute heart failure with preserved ejection fraction (HFpEF). Methods: We performed a single-center prospective, randomized, case-control study in consecutive acute HFpEF (left ventricle ejection fraction, LVEF ≥ 45%) patients with sleep-disordered breathing (SDB, apnea–hypopnea index, AHI > 15/h) and prevalence of CSA. Results: We included ten consecutive patients randomized for ASV on top of standard therapy for acute heart failure (group 1) versus standard care alone (group 2). ASV therapy significantly reduced AHI and CSA. An improvement in cardiac diastolic function was seen in group 1 compared to group 2 (E/E’ 17.5 to 9.6, p < 0.02 vs 18.5 to 14.5, p = 0.4). Brain natriuretic peptide (BNP) markedly decreased in cases, but not in controls (298 to 84 pg/ml, p < 0.02 vs 280 to 120 pg/ml, p = 0.06). Right ventricle (RV) function significantly improved in group 1, differently from group 2. Conclusions: An acute use of ASV seems effective in reducing BNP and improving diastolic and RV function in acute HFpEF patients with SDB and CSA, compared to standard treatment.

The autonomic nervous system, the renin–angiotensin–aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II. We review the multiple, potentially competing, substrates for neprilysin inhibition, and the resultant composite clinical effects of ARNi therapy. A mechanistic understanding of this novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.

Aims The aim is to investigate autonomic nervous system imbalance in hypertrophic cardiomyopathy (HCM) by combining echocardiographic morphological and functional parameters with the analysis of the autonomic responses to orthostatic stress. Methods A 10-min tilting test and a transthoracic echocardiogram focused on ventricular septal systolic (S wave) and diastolic function (isovolumic relaxation time) were performed. Low frequency on high frequency ratio (LF/HF) and RR variation (variation of beat to beat intervals) in response to passive orthostatism were used as measures of sympathetic reflex activation [delta LF/HF (D-LF/HF) and delta RR (DRR), respectively]. Brain natriuretic peptide was measured. Results A total of 50 HCM patients were categorized in two groups: D-LF/HF more than 0 (group 1, sympathetic response) and D-LF/HF 0 or less (group 2, parasympathetic response). Patients in group 2 had higher New York Heart Association class, a more frequent history of atrial fibrillation (38 versus 9% P = 0.04) or syncope (46 versus 12% P = 0.01) and an increased septal isovolumic relaxation time (122 versus 82 ms P = 0.02). The same categorization was made according to lowest quartile DRR (DRR at least 23 ms, group 1: sympathetic response; DRR less than 23 ms, group 2: parasympathetic response). In group 2, patients were older, with advanced New York Heart Association class and higher history of atrial fibrillation. Conclusions Autonomic response to passive orthostatism in HCM appears correlated with specific functional features of the hypertrophic heart. Altered neural afferent traffic from the localized area of segmental hypertrophy resulted in autonomic changes with a blunted sympathetic response, and an inappropriate vagal activation, especially in patients with history of atrial fibrillation or syncope.

This study sought to develop a novel echocardiogram outflow ramp test to detect device malfunctions in centrifugal-flow left ventricular assist devices (LVADs). This new ramp pump test is based on the direct analyses of systolic and diastolic ratio (S/D) Doppler velocity in the outflow cannula in the HeartWare LVAD during progressive increases in speed. The results showed that in patients with normal pump function, the Doppler velocity S/D ratio gradually decreased during LVAD speed increases. This test is easily performed and seems promising to detect normal pump function in patients assisted by a centrifugal flow LVAD.

Genetic cardiomyopathies are complex diseases with heterogeneous clinical presentation and phenotypes. Early descriptions of cardiomyopathies originated from case studies involving individuals with severe, paradigmatic presentation, which provided insight into the worst-case scenarios of these conditions. With time, improved diagnostic sensitivity and awareness of cardiomyopathies has uncovered a more heterogeneous disease spectrum, including mild phenotypes overlapping with physiological variation. This diagnostic 'grey area' poses important dilemmas, particularly in athletes. Current screening policies have the potential to identify affected individuals at very early stages, leading to effective prevention of cardiomyopathy-related complications such as sudden cardiac death. Conversely, however, some physicians actively impose diagnoses on individuals who perceive themselves to be disease-free. In addition, the high sensitivity of contemporary diagnostic techniques carries a serious risk of misinterpreting physiological variation as disease. In this Review, three of the most common and controversial areas are discussed, including left ventricular hypertrophy; left ventricular dilatation, noncompaction, and fibrosis; and arrhythmias originating from the right ventricle. A systematic and cautious approach is necessary in patients with mild phenotypes suggestive of, but not definitely diagnostic for, cardiomyopathies. Preventing the mislabelling of healthy individuals and overdiagnosis should be a priority, with the aim to combine adequate counselling and optimal protection.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality, but the identification of LVAD candidates at risk for RVF remains challenging. We undertook a systematic review and meta-analysis of observational studies of risk factors associated with RVF after LVAD implant. Thirty-six studies published between 1 January 1995 and 30 April 2015, comprising 995 RVF patients out of a pooled final population of 4428 patients, were identified. Meta-analysed prevalence of post-LVAD RVF was 35%. A need for mechanical ventilation [odds ratio (OR) 2.99], or continuous renal replacement therapy (CRRT; OR 4.61, area under the curve 0.78, specificity 0.91) were the clinical variables with the highest effect size (ES) in predicting RVF. International normalized ratio [INR; standardized mean difference (SMD) 0.49] and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD 0.52) were the biochemical markers that best discriminated between RVF and No-RVF populations, though NT-proBNP was highly heterogeneous. Right ventricular stroke work index (RVSWI) and central venous pressure (CVP) (SMD −0.58 and 0.47, respectively) were the haemodynamic measures with the highest ES in identifying patients at risk of post-LVAD RVF; CVP was particularly useful in risk stratifying patients undergoing continuous-flow LVAD implant (SMD 0.59, P < 0.001, I2 = 20.9%). Finally, pre-implant moderate to severe right ventricular (RV) dysfunction, as assessed qualitatively (OR 2.82), or a greater RV/LV diameter ratio (SMD 0.51) were the standard echocardiographic measurements with the highest ES in comparing RVF with No-RVF patients. Longitudinal systolic strain of the RV free wall had the highest ES (SMD 0.73) but also the greatest heterogeneity (I2 = 74%) and was thus only marginally significant (P = 0.05). Patients on ventilatory support or CRRT are at high risk for post-LVAD RVF, similarly to patients with slightly incr

Despite the burden of heart failure (HF) with preserved ejection fraction (HFpEF), its pathophysiological mechanisms remain controversial and are likely to be multifactorial. Indeed, it has been suggested that HFpEF may represent “a forest of a variety of trees”, because of heterogeneity in pathophysiological mechanisms involved and phenotypic expression of the disease. A better understanding of HFpEF is crucial for the development of appropriate therapeutic targets. Recent studies on HFpEF have highlighted its particular haemodynamic features, and haemodynamic derangements are critical to both early and advanced stages of the disease. By definition, haemodynamic properties are determined by the result of the dynamic interchange between the heart, vasculature, and autonomic nervous system, which regulate the circulation of blood. Importantly, it has been shown that both intrinsic and extrinsic factors are implicated in the haemodynamic impairments typical of HFpEF patients. Thus, understanding of HFpEF haemodynamics requires consideration of the interplay between both cardiac and non-cardiac factors.

Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal hypertrophy, mitral valve (MV) abnormalities may play an important role in MV displacement into the left ventricular (LV) outflow tract. Therefore, isolated myectomy may not relieve outflow obstruction and symptoms, and MV replacement is often the surgical alternative. Objectives This study sought to assess the clinical and hemodynamic results of cutting thickened secondary MV chordae combined with a shallow septal muscular resection in severely symptomatic patients with obstructive HCM and mild septal hypertrophy. Methods Clinical features were compared before surgery and at most recent clinical evaluation in 39 consecutive patients with obstructive HCM. Results Over a 23 ± 2 months follow-up, New York Heart Association functional class decreased from 2.9 ± 0.5 pre-operatively to 1.1 ± 1.1 post-operatively (p < 0.001), with no patient in class III at most recent evaluation. The resting outflow gradient decreased from 82 ± 43 mm Hg to 9 ± 5 mm Hg (p < 0.001) and septal thickness decreased from 17 ± 1 mm to 14 ± 2 mm (p < 0.001). No patient had MV prolapse or flail and 1 had residual moderate-to-severe MV regurgitation at most recent evaluation. MV geometry before and after surgery was compared with that of 25 consecutive patients with similar clinical profile and septal thickness that underwent isolated myectomy. After adjustment for differences in pre-operative values between the groups, the post-operative anterior MV leaflet-annulus ratio was 17% greater and tenting area 24% smaller in patients with chordal cutting, indicating that MV apparatus had moved to a more normal posterior position within the LV cavity, preventing MV systolic displacement into the outflow tract and outflow obstruction. Conclusions This procedure relieves heart failure symptoms, abolishes LV outflow gradient, and avoids MV replacement in patients with obstructive HCM and m

Objective To identify the exercise echocardiographic determinants of long-term functional capacity, in patients with chronic ischemic mitral regurgitation, after restrictive mitral valve annuloplasty (RMA) or mitral valve replacement (MVR). Methods We retrospectively analyzed 121 patients with significant chronic ischemic mitral regurgitation, who underwent RMA (n = 62) or MVR (n = 59), between 2005 and 2011. Preoperatively, all patients underwent a resting echocardiographic examination, and a 6-minute walking test (6-MWT) to measure distance. Resting and exercise stress echocardiography, and the 6-MWT were repeated at 41 ± 16.5 months. Results After surgery, the 6-MWT distance significantly improved in the MVR group, and decreased in the RMA group (+37 ± 39 m vs -24 ± 49 m, respectively; P <.0001). Exercise indexed effective orifice area was significantly higher in the MVR, versus the RMA, group (MVR: change from 1.3 ± 0.2 cm2/m2 to 1.5 ± 0.3 cm2/m2; RMA: change from 1.1 ± 0.3 cm2/m2 to 1.2 ± 0.3 cm2/m2; P =.001). The mean mitral gradients significantly increased from rest to exercise, in both groups, but to a greater extent in the RMA group (change from 4.4 ± 1.4 to 11 ± 3.6 mm Hg; MVR: change from 4.3 ± 1.8 to 9 ± 3.5 mm Hg; P =.006). On multivariate analysis, MVR and exercise indexed effective orifice area were the main independent determinants of postoperative 6-MWT. In the RMA group, 25 patients experienced late mitral regurgitation recurrence, severe in 9 (14%) of them. The rate of postoperative cardiovascular events was significantly higher in the RMA group (21% vs MVR: 8%; P =.03). Follow-up survival was 83% in the RMA group and 88% in the MVR group (P =.54). Conclusions For chronic ischemic mitral regurgitation, MVR versus RMA was associated with better postoperative exercise hemodynamic performance and long-term functional capacity.

Survival in patients with heart failure in the last two decades has significantly improved, owing to availability of new drugs, devices, and technologies. However, these new therapeutic tools are often costly and not without attendant risks. Thus, accurate and reproducible risk stratification is required to assess appropriateness of therapy. Although a growing body of evidence has characterized various predictors of poor outcomes, the application of comprehensive prognostic models in clinical practice remains limited. Herein, we critically evaluate the utility of prognostic scores in heart failure, discussing the strategies to select the most efficient and appropriate risk estimator in the individual patient.

Background: Left ventricular assist device (LVAD) implantation improves survival and quality of life in patients with advanced heart failure (HF). Despite these advantages, LVADs are not free from risks. Among all adverse events (AE), pump thrombosis and bleeding, especially of the gastrointestinal (GI) tract, have been reported to occur with increasing frequency in some CF-LVADs. The INCOR LVAD system is a third-generation, continuous flow, axial pump with active magnetic levitation, avoiding the potential downsides of mechanical bearings. Methods: The aim of this retrospective study was to review the Italian clinical experience with the INCOR LVAD and to determine the prevalence of GI bleeding and pump thrombosis. All patients implanted between January 2006 and May 2012 were considered eligible. Results: The total population consisted of 42 patients. LVAD indication was BTT in 36 (86%) and DT in 6 (14%) patients; 31 patients (74%) were INTERMACS class 1 or 2. Mean support time was 525 ± 570 days. The 1-year and 2-year survival rates were 74% and 60%, respectively. The most frequent AE was driveline infection (0.33 events PPY) followed by stroke with consequence (0.17 events PPY), sepsis (0.07 events PPY), and right HF (0.05 events PPY). No episodes of pump thrombosis or GI bleeding were observed. Conclusions: In this cohort of high-risk, advanced HF patients, the INCOR LVAD provided effective support with improved survival. Moreover, the absence of GI bleeding and pump thrombosis demonstrates a favorable characteristic of this device. Further prospective studies are needed to confirm these data.

The almost universal availability of electronic connectivity, web software, and portable devices is bringing about a major revolution: information of all kinds is rapidly becoming accessible to everyone, transforming social, economic and cultural life practically everywhere in the world. Internet technologies represent an unprecedented and extraordinary two-way channel of communication between producers and users of data. For this reason the web is widely recognized as an asset capable of achieving the fundamental goal of transparency of information and of data products, in line with the growing demand for transparency of all goods that are produced with public money. This paper describes "Open Universe" an initiative proposed to the United Nations Committee on the Peaceful Uses of Outer Space (COPUOS) with the objective of stimulating a dramatic increase in the availability and usability of space science data, extending the potential of scientific discovery to new participants in all parts of the world., Comment: 10 pages, to appear in the proceedings of the ESPI-UNISPACE+50 conference "Space 2030 and Space 4.0: synergies for capacity building in the XXI century"

The almost universal availability of electronic connectivity, web software, and portable devices is bringing about a major revolution: information of all kinds is rapidly becoming accessible to everyone, transforming social, economic and cultural life practically everywhere in the world. Internet technologies represent an unprecedented and extraordinary two-way channel of communication between producers and users of data. For this reason the web is widely recognized as an asset capable of achieving the fundamental goal of transparency of information and of data products, in line with the growing demand for transparency of all goods that are produced with public money. This paper describes "Open Universe" an initiative proposed to the United Nations Committee on the Peaceful Uses of Outer Space (COPUOS) with the objective of stimulating a dramatic increase in the availability and usability of space science data, extending the potential of scientific discovery to new participants in all parts of the world., Comment: 10 pages, to appear in the proceedings of the ESPI-UNISPACE+50 conference "Space 2030 and Space 4.0: synergies for capacity building in the XXI century"

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity.

Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT). Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity.

Objective Mitral valve annuloplasty and mitral valve replacement are common strategies for the management of functional ischemic mitral regurgitation with ischemic cardiomyopathy. However, mitral valve annuloplasty may create some degree of functional mitral stenosis. The purpose of this study was to compare the mitral valve hemodynamics in patients with functional ischemic mitral regurgitation undergoing mitral valve annuloplasty or mitral valve replacement, using exercise echocardiography. Methods We performed resting and exercise echocardiography in 70 patients matched for indexed effective orifice area, systolic pulmonary arterial pressure, and left ventricular ejection fraction after mitral valve annuloplasty or mitral valve replacement with coronary artery bypass grafting. Results There was no significant difference between the 2 groups regarding baseline demographic and clinical data. Exercise systolic pulmonary arterial pressure was higher in the mitral valve annuloplasty group compared with the mitral valve replacement group (from 36.3 ± 8.1 mm Hg to 55 ± 12 mm Hg, vs mitral valve replacement: 33 ± 6 mm Hg to 42 ± 6.2 mm Hg, P =.0001). Exercise-induced improvement in effective orifice area and indexed effective orifice area was better in the mitral valve replacement group (mitral valve replacement: +0.23 ± 0.04 vs mitral valve annuloplasty: -0.1 ± 0.09 cm, P =.001, for effective orifice area; mitral valve replacement: +0.14 ± 0.03 vs mitral valve annuloplasty: -0.04 ± 0.07 cm/m, P =.03, for indexed effective orifice area). Exercise indexed effective orifice area was correlated with exercise systolic pulmonary arterial pressure (r = -0.45; P =.01). In a multivariable analysis mitral valve annuloplasty, postoperative indexed effective orifice area and resting mitral peak gradients were independent predictors of elevated systolic pulmonary arterial pressure during exercise. Conclusions In patients with functional ischemic mitral regurgitation, mitral valve ann