Seattle proportional risk model in GISSI-HF: Estimated benefit of ICD in patients with EF less than 50.

BACKGROUND: The Seattle Proportional Risk Model (SPRM) estimates the proportion of sudden cardiac death (SCD) in heart failure (HF) patients, identifying those most likely to benefit from implantable cardioverter-defibrillator (ICD) therapy (those with ≥50% estimated proportion of SCD). The GISSI-HF trial tested fish oil and rosuvastatin in HF patients. We used the SPRM to evaluate its accuracy in this cohort in predicting potential ICD benefit in patients with EF ≤50% and an SPRM-predicted proportion of SCD either ≥50% or <50%. METHODS: The SPRM was estimated in patients with EF ≤50% and in a logistic regression model comparing SCD with non-SCD. RESULTS: We evaluated 6,750 patients with EF ≤50%. There were 1,892 all-cause deaths, including 610 SCDs. Fifty percent of EF ≤35% patients and 43% with EF 36% to 50% had an SPRM of ≥50%. The SPRM (OR: 1.92, P < 0.0001) accurately predicted the risk of SCD vs non-SCD with an estimated proportion of SCD of 44% vs the observed proportion of 41% at 1 year. By traditional criteria for ICD implantation (EF ≤35%, NYHA class II or III), 64.5% of GISSI-HF patients would be eligible, with an estimated ICD benefit of 0.81. By SPRM >50%, 47.8% may be eligible, including 30.2% with EF >35%. GISSI-HF participants with EF ≤35% with SPRM ≥50% had an estimated ICD HR of 0.64, comparable to patients with EF 36% to 50% with SPRM ≥50% (HR: 0.65). CONCLUSIONS: The SPRM discriminated SCD vs non-SCD in GISSI-HF, both in patients with EF ≤35% and with EF 36% to 50%. The comparable estimated ICD benefit in patients with EF ≤35% and EF 36% to 50% supports the use of a proportional risk model for shared decision making with patients being considered for primary prevention ICD therapy.

Incidence, Characteristics, and Management of Patients with Recurrent Myocardial Infarctions: Insights from the EYESHOT POST-MI.

Background: It is unknown whether patients who survived two or multiple episodes of myocardial infarction (MI) present different clinical characteristics and management than patients at their first MI. Methods: The EYESHOT post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. In 3 months of enrolment, 165 Italian cardiology centers included 1633 consecutive post-MI patients. In the present analysis, we stratified the study cohort according to the number of prior MI episodes (i.e., 1, 2 or ≥3). Results: Among the 1618 patients enrolled with complete data on MI history, 1335 (82.5%) were at their first MI episode, 209 (12.9%) had a history of 2 MIs, and the remaining 74 (4.6%) had ≥ 3 prior MIs. Patients with a history of multiple MIs were increasingly older and presented a significantly higher rate of risk factors compared to those at their first MI. During the year prior to enrolment, patients with 2 or ≥3 MI episodes more frequently underwent coronary angiography compared to the other group (p < 0.0001). In addition, several lifesaving and antianginal drugs were more frequently prescribed in patients presenting with a history of multiple MIs compared to those at their first MI. Conclusions: Our data suggest that patients with multiple MIs managed by cardiologists in routine clinical practice present an incremental clinical risk, more frequently undergo coronary angiography, and are more intensively managed with pharmacological therapies compared to patients at their first MI episode.

Could the PARIS Risk Scores Be Useful for the Choice of Triple versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

INTRODUCTION: Current guidelines recommend dual antithrombotic therapy (DAT) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT) for those at very high thrombotic risk (TR) but low bleeding risk (BR). METHODS: We analyze if the PARIS ischemic-hemorrhagic scale could be useful for the choice of antithrombotic strategy in patients with acute coronary syndromes and AF treated with coronary stenting enrolled in the prospective, observational, nationwide MATADOR-PCI study. RESULTS: Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients. According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate, and 292 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized in the low, 260 (44.2%) in the intermediate, and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n = 130, 22%), followed by those at intermediate risk according to both scores (n = 122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at intermediate to high TR but low BR, according to the PARIS score. CONCLUSION: Our data suggest that some variables associated with increased TR or BR are poorly considered in the daily practice, while the use of PARIS scales could help in the implementation of guidelines' recommendations.

Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation.

BACKGROUND: Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. OBJECTIVES: To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. METHODS: A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. RESULTS: Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04-1.36], p = 0.026; NT-proBNP: HR:1.19[1.06-1.35], p = 0.016; Ang2: HR:1.07[0.95-1.20], p = 0.283; BMP10: HR:1.09[0.96-1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29-1.90], p < 0.001 1.63], p = 0.097). CONCLUSIONS: The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

Modes of death and prognostic outliers in chronic heart failure.

BACKGROUND: The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. METHODS AND RESULTS: The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. CONCLUSIONS: The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.

Management of atrial fibrillation in the emergency room and in the cardiology ward: the BLITZ AF study.

AIMS: To assess the number of admissions to the emergency room (ER) of patients with atrial fibrillation (AF) or atrial flutter (af) and their subsequent management. To evaluate the clinical profile and the use of antithrombotics and antiarrhythmic therapy in patients with AF admitted to cardiology wards. METHODS AND RESULTS: BLITZ-AF is a multicentre, observational study conducted in 154 centres on patients with AF/af. In each centre, data were collected, retrospectively for 4 weeks in ER and prospectively for 12 weeks in cardiology wards. In ER, there were 6275 admissions. Atrial fibrillation was the main diagnosis in 52.9% of the cases, af in 5.9%. Atrial fibrillation represented 1.0% of all ER admissions and 1.7% of all hospital admissions. A cardioversion has been performed in nearly 25% of the cases. Out of 4126 patients, 52.2% were admitted in cardiology ward; mean age was 74 ± 11 years, 41% were females. Patients with non-valvular AF were 3848 (93.3%); CHA2DS2-VASc score was ≥2 in 87.4%. Cardioversion was attempted in 38.8% of the patients. In-hospital mortality was 1.2%. At discharge, 42.6% of the patients were treated with vitamin K antagonists, 39.5% with direct oral anticoagulants, 13.6% with other antithrombotic drugs, and 4.2% did not take any antithrombotic agent. Rate control strategy was pursued in 47.2%, rhythm control in 44.0%, 45.6% were discharged in sinus rhythm. CONCLUSION: Atrial fibrillation still represents a significant burden on health care system. Oral anticoagulant use increased over time even if compliance with guidelines, with respect to prevention of the risk of stroke, remains suboptimal.

Effects of Dipeptidyl Peptidase-4 Inhibitor Linagliptin on Left Ventricular Dysfunction in Patients with Type 2 Diabetes and Concentric Left Ventricular Geometry (the DYDA 2™ Trial). Rationale, Design, and Baseline Characteristics of the Study Population.

PURPOSE: A multicentre, randomized, double-blind, placebo-controlled, parallel-group study aimed to define the potential positive effect of dipeptidyl peptidase-4 inhibition on left ventricular systolic function (LVSF) beyond glycemic control in type 2 diabetes mellitus (T2DM) (DYDA 2™ trial). METHODS: Individuals with fairly controlled T2DM and asymptomatic impaired LVSF were randomized in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their stable diabetes therapy. Eligibility criteria were age ≥ 40 years, history of T2DM with a duration of at least 6 months, HbA1c ≤ 8.0% (≤ 64 mmol/mol), no history or clinical signs/symptoms of cardiac disease, evidence at baseline echocardiography of concentric LV geometry (relative wall thickness ≥ 0.42), and impaired LVSF defined as midwall fractional shortening (MFS) ≤ 15%. The primary end-point was the modification from baseline to 48 weeks of MFS. As an exploratory analysis, significant changes in LV global longitudinal strain and global circumferential strain, measured by speckle tracking echocardiography, were also considered. Secondary objectives were changes in diastolic and/or in systolic longitudinal function as measured by tissue Doppler. RESULTS: A total of 188 patients were enrolled. They were predominantly males, mildly obese, with typical insulin-resistance co-morbidities such as hypertension and dyslipidemia. Mean relative wall thickness was 0.51 ± 0.09 and mean MFS 13.3% ± 2.5. CONCLUSIONS: DYDA 2 is the first randomized, double-blind, placebo-controlled trial to explore the effect of a dipeptidyl peptidase-4 inhibitor on LVSF in T2DM patients in primary prevention regardless of glycemic control. The main characteristics of the enrolled population are reported. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT02851745.

Progression of Renal Impairment and Chronic Kidney Disease in Chronic Heart Failure: An Analysis From GISSI-HF.

BACKGROUND: Data on the natural change in renal function in patients with chronic heart failure (HF) are limited. METHODS AND RESULTS: Estimated glomerular filtration rate (eGFR) was assessed over 36 months in 6934 patients included in the GISSI-HF study. Associations from baseline, changes in renal function, and occurrence of cardiovascular death or HF hospitalization were assessed. Mean age was 67 years, mainly men (78%), and mean eGFR was 68 mL • min-1 • 1.73 m-2. Change in eGFR in the 1st year was -1.5 ± 16 mL • min-1 • 1.73 m-2, and over 36 months it was -3.7 ± 18 mL • min-1 • 1.73 m-2. Over the latter period, only 25% deteriorated ≥1 Kidney Disease Outcomes Quality Initiatives (KDOQI) class of chronic kidney disease (CKD). Fifteen percent of patients had >15 mL • min-1 • 1.73 m-2 decrease in eGFR in the 1st 12 months. Lower eGFR was associated with outcome: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.08-1.10 (P < .001) per 10 mL • min-1 • 1.73 m-2 decrease, as well as every 10 mL • min-1 • 1.73 m-2 decrease over the 1st year (HR 1.10, 95% CI 1.04-1.17; P < .001). A deterioration in eGFR >15 mL • min-1 • 1.73 m-2 in the 1st year showed the highest risk of events (HR 1.22, 95% CI 1.10-1.36; P < .001). CONCLUSIONS: Mean decrease in renal function over time in patients with chronic HF was modest. Only 25% deteriorated ≥1 KDOQI class of CKD after 3 years. Any decrease in eGFR over time was associated with strongly increased event rates.

Prognostic effects of rosuvastatin in patients with co-existing chronic obstructive pulmonary disease and chronic heart failure: A sub-analysis of GISSI-HF trial.

OBJECTIVES: Rising evidences showed a possible protective role of statins in chronic obstructive pulmonary disease (COPD). We aimed to evaluate in a post-hoc analysis of the GISSI-HF trial the prognostic effect of the use of rosuvastatin in patients with co-existing COPD and HF, assuming that the anti-inflammatory properties of these drugs may imply a potential beneficial effect in these associated chronic inflammatory conditions. METHODS: We analyzed patients with chronic HF and history of COPD deriving from the GISSI-HF study. Of all 4574 patients eligible to statin, 1060 ambulatory patients with HF and concomitant COPD were enrolled and randomly assigned to rosuvastatin 10 mg daily (538 patients) or placebo (522 patients). The primary end-point was to compare all cause death rate in patients randomized to rosuvastatin or placebo. Further, we assessed the effects of rosuvastatin (10 mg daily) on cardiovascular (CV) death, non-CV death and hospital admissions. Median follow-up was 3.9 years with an interquartile range (IQR) of 3.0-4.4. RESULTS: During the follow-up 438 (41.3%) patients died, 304 (28.6%) for CV death and 687 (64.8%) had at least one hospitalization. The two patient groups had similar outcome, irrespective of randomization, in terms of all-cause mortality (log-rank test p = 0.30) CV, non CV-death (p = 0.88 and 0.09 respectively) and all-cause hospitalization (p = 0.82). Cox regression analysis did not show a favorable association between the use of statin and the examined end-points both on unadjusted and adjusted models. CONCLUSIONS: Statin use is not associated with a beneficial effects on all cause, CV, non CV mortality and hospitalization in patients with coexistent chronic HF and history of COPD. ClinicalTrials.gov Identifier: NCT00336336.

Galectin-3 and the Mineralocorticoid Receptor Antagonist Canrenone in Mild Heart Failure.

BACKGROUND: Galectin-3 (Gal-3) is involved in collagen deposition and inflammation and is a prognostic biomarker in heart failure (HF).Methods and Results:Gal-3 and other markers of fibrosis or cardiac stress were measured serially in 413 patients with mild HF randomized to the mineralocorticoid receptor antagonist canrenone or placebo to evaluate treatment effect and association with clinical outcome. Gal-3 increased slightly over 6 months in both arms of the study and was associated with clinical endpoints. CONCLUSIONS: Although Gal-3 showed prognostic value, the effect of canrenone on clinical outcomes was unaffected by baseline concentrations of biomarkers of fibrosis or cardiac stress.

Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry.

BACKGROUND: Available data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias. METHODS: From 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD). RESULTS: Patients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ≥50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p < .0001). During one-year follow-up, 819 patients (14.2%) died or were hospitalized for HF [187 (9.9%) DCM, 632 (16.2%) IHD]; DCM was associated with lower risk of the combined end-point (adjusted HR 0.745, 95% CI 0.625- 0.888, p = .0011). Among the 1954 patients with 1-year echocardiograms available, 1483 had LVEF≤40% at baseline; of these,166 (30.6%) DCM and 165 (17.5%) IHD improved their LVEF to >40% (p < .0001). DCM aetiology was associated with higher likelihood of LVEF improvement (adjusted OR 1.722, 95% CI 1.328 -2.233, p < .0001). CONCLUSIONS: DCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM.

[BLITZ-AF Cancer study: an international observational research project on patients with atrial fibrillation and cancer]. / Studio BLITZ-AF Cancer: un progetto di ricerca osservazionale internazionale sui pazienti con fibrillazione atriale e cancro.

BACKGROUND: Cancer is an important condition associated with the development of atrial fibrillation (AF). The objectives of the BLITZ-AF Cancer study were to collect real-life information on the clinical profile and use of antithrombotic drugs in patients with AF and cancer to improve clinical management, as well as the evaluation of the association between different antithrombotic treatments (or their absence) and the main clinical events. METHODS: European multinational, multicenter, prospective, non-interventional study conducted in patients with AF (electrocardiographically confirmed) and cancer occurring within 3 years. The CHA2DS2-VASc and the HAS-BLED scores were calculated in all enrolled patients. RESULTS: From June 2019 to July 2021, 1514 patients were enrolled, 36.5% women, from 112 cardiology departments in 6 European countries (Italy, Belgium, the Netherlands, Spain, Portugal and Ireland). Italy enrolled 971 patients in 77 centers. Average age of patients was 74 ± 9 years, of which 20.9% affected by heart failure, 18.1% by ischemic heart disease, 9.8% by peripheral arterial disease and 38.5% by valvular diseases; 41.5% of patients had a CHA2DS2-VASc score ≥4. The most represented cancer sites were lung (14.9%), colorectal tract (14.1%), prostate (8.8%), or non-Hodgkin's lymphoma (8.1%). Before enrollment, 16.6% of patients were not taking antithrombotic therapy, while 22.7% were on therapy with antiplatelet agents and/or low molecular weight heparin. After enrollment these percentages decreased to 7.7% and 16.6%, respectively and, at the same time, the percentage of patients on direct oral anticoagulant (DOAC) therapy increased from 48.4% to 68.4%, also to the detriment of those on vitamin K antagonist therapy. CONCLUSIONS: The BLITZ-AF Cancer study, which enrolled patients diagnosed with AF and cancer, highlights that the use of DOACs by cardiologists in this clinical context has increased, even though the guidelines on AF do not give accurate indications about oral anticoagulant therapy in patients with cancer.

[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

Is there a reduced confidence towards direct oral anticoagulants compared to vitamin K antagonists in patients scheduled for an elective electrical cardioversion? The results of the BLITZ-AF study.

OBJECTIVE: To study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE). METHODS: Data about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV. RESULTS: Overall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33-0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59-9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69-6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23-2.82). CONCLUSION: our study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.

Contemporary Management and Clinical Course of Acute Pulmonary Embolism: The COPE Study.

BACKGROUND: New diagnosis, risk stratification, and treatment strategies became recently available for patients with acute pulmonary embolism (PE) leading to changes in clinical practice and potentially influencing short-term patients' outcomes. RESEARCH QUESTION: The COntemporary management of PE (COPE) study is aimed at assessing the contemporary clinical management and outcomes in patients with acute symptomatic PE. STUDY DESIGN AND METHODS: Prospective, noninterventional, multicenter study. The co-primary study outcomes, in-hospital and 30-day death, were reported overall and by risk categories according to the European Society of Cardiology (ESC) and American Heart Association guidelines. RESULTS: Among 5,213 study patients, PE was confirmed by computed tomography in 96.3%. In-hospital, 289 patients underwent reperfusion (5.5%), 92.1% received parenteral anticoagulants; at discharge, 75.6% received direct oral anticoagulants and 6.7% vitamin K antagonists. In-hospital and 30-day mortalities were 3.4 and 4.8%, respectively. In-hospital death occurred in 20.3% high-risk patients (n = 177), in 4.0% intermediate-risk patients (n = 3,281), and in 0.5% low-risk patients (n = 1,702) according to ESC guidelines. Further stratification in intermediate-high and intermediate-low risk patients did not reach statistical significance, but intermediate-risk patients with sPESI > 0 alone had lower mortality compared to those with one or both among right ventricular dilation at echocardiography or increased troponin. Death or clinical deterioration occurred in 1.5, 5.0, and 9.4% of patients at low, intermediate-low, and intermediate-high risk for death according to ESC guidelines. CONCLUSION: For the majority of patients with PE, contemporary initial management includes risk stratification and treatment with direct oral anticoagulants. In-hospital mortality remains high in intermediate and high-risk patients calling for and informing research focused on its reduction. TRIAL REGISTRATION NUMBER: NCT03631810.

Contemporary anticoagulant treatment strategies in patients with acute pulmonary embolism at different risk for death.

INTRODUCTION: Availability of new treatment strategies for patients with acute pulmonary embolism (PE) have changed clinical practice with potential influence in short-term patients' outcomes. We aimed at assessing contemporary anticoagulation strategies and mortality in patients with acute PE included in the prospective, non-interventional, multicentre, COntemporary management of PE study. MATERIALS AND METHODS: Anticoagulant treatment at admission, during hospital-stay, at discharge and at 30-day are described in the overall population and by clinical severity. RESULTS: Overall, 5158 patients received anticoagulant treatment (99%); during the hospital-stay, 2298 received completely parenteral, 926 completely oral and 1934 parenteral followed by oral anticoagulation (1670 DOACs, 264 VKAs). Comorbidities and PE severity influenced the choice of in-hospital anticoagulation. The use of completely parenteral and completely oral anticoagulation varied based on PE severity. In patients treated with thrombolysis, DOACs were used in 46.4% and 80.1% during the hospital stay and at discharge, respectively. Death at 30 days occurred in 34.6% of patients not receiving anticoagulant treatment and in 1.5, 1.3, 3.4 and 8.1% of patients receiving completely oral, sequential with DOACs, sequential with VKAs and completely parenteral regimens, respectively. Increased mortality in patients receiving completely parenteral anticoagulation persisted after adjustment for PE severity. Completely oral anticoagulation was effective and safe also in patients at intermediate-high risk of death. CONCLUSIONS: Contemporary anticoagulation for acute PE includes parenteral agents in over 90% of patients; DOACs are used in the large majority of PE patients at discharge and their early use seems effective and safe also in selected intermediate-risk patients. TRIAL REGISTRATION NUMBER: NCT03631810.

Valsartan for prevention of recurrent atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, and no current therapy is ideal for control of this condition. Experimental studies suggest that angiotensin II-receptor blockers (ARBs) can influence atrial remodeling, and some clinical studies suggest that they may prevent atrial fibrillation. METHODS: We conducted a large, randomized, prospective, placebo-controlled, multicenter trial to test whether the ARB valsartan could reduce the recurrence of atrial fibrillation. We enrolled patients who were in sinus rhythm but had had either two or more documented episodes of atrial fibrillation in the previous 6 months or successful cardioversion for atrial fibrillation in the previous 2 weeks. To be eligible, patients also had to have underlying cardiovascular disease, diabetes, or left atrial enlargement. Patients were randomly assigned to receive valsartan or placebo. The two primary end points were the time to a first recurrence of atrial fibrillation and the proportion of patients who had more than one recurrence of atrial fibrillation over the course of 1 year. RESULTS: A total of 1442 patients were enrolled in the study. Atrial fibrillation recurred in 371 of the 722 patients (51.4%) in the valsartan group, as compared with 375 of 720 (52.1%) in the placebo group (adjusted hazard ratio, 0.97; 96% confidence interval [CI], 0.83 to 1.14; P=0.73). More than one episode of atrial fibrillation occurred in 194 of 722 patients (26.9%) in the valsartan group and in 201 of 720 (27.9%) in the placebo group (adjusted odds ratio, 0.89; 99% CI, 0.64 to 1.23; P=0.34). The results were similar in all predefined subgroups of patients, including those who were not receiving angiotensin-converting-enzyme inhibitors. CONCLUSIONS: Treatment with valsartan was not associated with a reduction in the incidence of recurrent atrial fibrillation. (ClinicalTrials.gov number, NCT00376272.)

Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure.

PURPOSE: Heart failure (HF) is characterized by activation of neurohormonal systems such as aldosterone and natriuretic peptides. In the absence of published data, CandHeart trial was designed to assess the effects on left ventricular (LV) function, aldosterone and brain natriuretic peptide (BNP) of candesartan in patients with HF and preserved (LVEF ≥ 40%) or depressed (LVEF <40%) LV systolic function. METHODS: A total of 514 patients with stable symptomatic NYHA II-IV HF and any left ventricular ejection fraction (LVEF)were randomized to candesartan (target dose 32 mg once daily) as add-on therapy or standard medical therapy alone. Standardized echocardiographic exams were performed locally under central quality control, whereas biomarkers were assayed in a core laboratory. RESULTS: The majority of patients (73.3%) were NYHA II and on ACE inhibitors (91.8%) and beta-blockers (85.4%). Mean age was 66 ± 11 years. Mean LVEF was 36.2 ± 9.7% and 24.9% of patients had LVEF ≥ 40%. LVEF increased significantly more in the candesartan group (p = 0.09 at 12 weeks and p = 0.01 at 48 weeks) and left ventricular end-diastolic diameter decreased in candesartan group (p = 0.05 at 12 weeks). Candesartan significantly reduced aldosterone at 48 weeks (p = 0.009). BNP was reduced similarly over time in both study groups (p = 0.35 and p = 0.98 at 12 and 48 weeks, respectively). There were 6.6% of discontinuations of candesartan for adverse events. CONCLUSIONS: In CandHeart, the addition of candesartan to standard medical treatment did not reduce circulating BNP more than standard therapy (primary endpoint), but it significantly improved LV function and produced a marked decrease in aldosterone levels at study end.

Type of hospitalisations and in-hospital outcomes in the Italian coronary care unit network at the time of COVID-19 pandemic: the BLITZ-COVID19 Registry.

OBJECTIVE: The aim of the study was to describe the epidemiology and outcome of patients hospitalised during the COVID-19 pandemic in intensive cardiac care units (ICCs). DESIGN: Non-interventional, retrospective and prospective, nationwide study. SETTING: 109 private or public ICCs in Italy. PARTICIPANTS: 6054 consecutive patients admitted to Italian ICCs during COVID-19 pandemic. PRIMARY AND SECONDARY OUTCOME MEASURES: To obtain accurate and up-to-date information on epidemiology and outcome of patients admitted to ICCs during the COVID-19 pandemic, the impact that the COVID-19 infection may have determined on the organisational pathways and in-hospital management of the various clinical conditions being admitted to ICCs. RESULTS: Acute coronary syndromes were the most frequent ICC discharge diagnoses followed by heart failure and hypokinetic arrhythmias. The prevalence of COVID-19 positivity was approximately 3%. Most patients with a COVID-19 diagnosis at discharge (52%) arrived to ICC from other wards, in particular 22% from non-cardiology ICCs. The overall mortality was 4.2% during ICC and 5.8% during hospital stay. The cause of in-hospital death was cardiac in 74.4% of the cases, non-cardiovascular in 13.5%, vascular in 5.8% and related to COVID-19 in 6.3% of the patients. CONCLUSIONS: This study provides a unique nationwide picture of current ICC care during COVID-19 pandemic. TRIAL REGISTRATION NUMBER: NCT04744415.

BLITZ-HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines.

AIMS: To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure (HF) and to evaluate if an ad-hoc educational intervention can improve their performance on several pharmacological and non-pharmacological indicators. METHODS AND RESULTS: BLITZ-HF was a cross-sectional study based on a web-based recording system with pop-up reminders on guideline recommendations used during two 3-month enrolment periods carried out 3 months apart (Phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (Phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included, respectively, 84% with chronic HF and 16% with acute HF in Phase 1, and 74% with chronic HF and 26% with acute HF in Phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among acute HF patients, an improvement was obtained in three out of eight indicators, with a significant rise in echocardiographic evaluation. Among chronic HF patients with HF and preserved or mid-range ejection fraction, performance increased in two out of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six out of nine indicators in ambulatory HF with reduced ejection fraction patients with a significant increase in angiotensin receptor-neprilysin inhibitor prescription rates. CONCLUSIONS: Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered.