bluuebunny/crossref_metadata_2025_split huggingface dataset:
1113 EFFICACY OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION ACROSS DIFFERENT DEFINITIONS: A META-ANALYSIS OF PHASE 3 RANDOMIZED CONTROLLED TRIALS
Authors: De Marzo Vincenzo , Savarese Gianluigi , Porto Italo , Metra Marco , Ameri Pietro 
Published: December 2022

Abstract

Background
Sodium glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) in phase 3 randomized controlled trials (RCTs). However, a granular definition of HF was adopted only in the most recent RCTs (hereafter, HF RCTs). In earlier studies, which assessed cardiovascular (CV) outcomes in patients with type 2 diabetes (CV outcomes trials, CVOTs), HF status was assigned based on medical history.

Methods
We searched for RCTs evaluating SGLT2i vs placebo in HFpEF and published from inception to Aug. 31st 2022, irrespective of whether additional criteria were used to define HFpEF besides left ventricular ejection fraction ≥50%. Heterogeneity between studies was examined by the Cochran's Q test and Higgins and Thompsons’ I2 statistics. Risk ratios (RRs) with 95% confidence intervals (95%CI) and number needed to treat (NNT) were calculated with a random-effects model (moderate-to-high heterogeneity) or a Mantel-Haenszel fixed-effect model (low heterogeneity) using R 4.2.1.

Results
Seven RCTs were included in the meta-analysis: 3 HF RCTs (EMPEROR-Preserved, DELIVER, and SOLOIST-WHF) and 4 CVOTs (EMPA-REG OUTCOME, DECLARE-TIMI58, VERTIS-CV, and SCORED). The overall population included 14,644 patients, and the mean follow-up was 29.8±14.5 months (range: 9.0-50.4 months). The risk of the composite outcome of CV death or HF hospitalization (HFH) was significantly reduced by SLGT2i as compared with placebo (RR 0.75, 95%CI 0.63-0.89, I2=59.7%, NNT 19). The benefit was confirmed in HF RCTs (RR and 95%CI displayed in the Figure; I2=75.7%, NNT 13) and CVOTs (Figure; I2=56.9%, NNT 26). Based on the available data (i.e., only some of the selected studies), SGLT2i also had a positive effect on HFH (RR 0.81, 95%CI 0.73-0.90, I2=18.1%, NNT 45), which was maintained in both HF RCTs (Figure; I2=18.1%, NNT 37) and CVOTs (Figure; I2=0.0% and NNT 46, respectively). The effect on CV or all-cause death was neutral in all RCTs (RR 0.94, 95%CI 0.85-1.04, I2=36.0%; and RR 1.00, 95%CI 0.92-1.08, I2=0.0%, respectively), and in HF RCTs or CVOTs considered separately (Figure).

Conclusions
The efficacy of SGLT2i was consistent across RCTs with a stricter or simpler definition of HFpEF, supporting an extensive clinical use.
1045 COMPARISON OF CEPHALIC VEIN VERSUS SUBCLAVIAN APPROACH FOR LEFT BUNDLE BRANCH PACING: A SINGLE CENTRE EXPERIENCE
Authors: Fabbricatore Davide , Valeriano Chiara , Gallinoro Emanuele , Paolisso Pasquale , De Schouwer Koen , De Potter Tom 
Published: December 2022

Abstract

Background
left bundle branch area pacing (LBBAP) is a recently introduced pacing method and has been described suggesting the subclavian venous puncture as the preferred approach.

Aim
This is the first study comparing the cephalic access to the “classical” subclavian approach for the implantation of LBBAP.

Methods
Retrospective study evaluating all consecutive patients undergoing LBBAP at the cardiovascular research Centre of Aalst in Belgium from October 2020 to February 2022. LBBAP was performed either using cephalic or subclavian approach at the operator's discretion and for one of lead or both in case of multiple leads. In both cases, dedicated delivery sheaths were used for the implantation of the ventricular lead in the left bundle branch area. Implant success, complications, procedural and pacing characteristics were analyzed at implant.

Results
81 patients were enrolled (age 78.20±11.47), 44 (54%) of which in the cephalic groups. LBBAP was successful at first attempt in 97% of the population, without significant differences between groups (P=0.886); dislocation of leads after the slitting occurred in 5 (11,4%) and 3 (8,1%) patients (P=0,625). Procedural and X-ray times were not significantly different in the two groups. Pacing parameters were normal at the end of the procedure in both groups.

Conclusion
This is the first study comparing safety and feasibility of LBBAP of a cephalic versus the subclavian one. Procedural success and times were not affected from the choice of cephalic instead than subclavian access. Periprocedural dislocation rates did not differ between groups.
141 DIFFERENT KINETICS OF NT-PROBNP AND S-ST2 HIGHLIGHT DIFFERENT THERAPEUTIC THERAPEUTIC PATHWAYS OF SACUBITRIL/VALSARTAN
Authors: Mapelli Massimo , Mattavelli Irene , Salvioni Elisabetta , Bonomi Alice , Palermo Pietro , Banfi Cristina , Paolillo Stefania , Biondi Maria Luisa , Agostoni Piergiuseppe 
Published: December 2022

Abstract

Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. The first is associated with the patient's hemodynamic status, while the second is indicative of the inflammatory component and of myocardial fibrosis and both are potential targets of HFrEF treatment.

Aim of the study
The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF.

Methods
We analyzed blood samples of HFrEF patients at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26–49/51–97/103mg doses), and 6 months after the maximum tolerated dose was reached (end-study).

Results
We obtained samples from 34 HFrEF patients (age 65.9±9.0, 74% males). NT-proBNP and sST2 values progressively and significantly reduced up to 21%±33 and 9%±16, respectively, with a greater reduction for NT-proBNP (p&lt;0.05). Specifically, NT-proBNP reduced from 1286 [609-3205] to 877 [437-1866] pg/mL and sST2 from 29.3 [19.5-34.1] to 20.4 [15.6-28.9] ng/mL, p&lt;0.05 in both cases). The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP. No significant changes in renal function and potassium levels were recorded.

Conclusions
These findings suggest that, in HF patients, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic, delayed pathway. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.
356 DAPAGLIFLOZIN USE IN HEART FAILURE WITH REDUCED EJECTION FRACTION PATIENTS: A SINGLE CENTRE COMPARISON BETWEEN REAL-LIFE AND DAPA-HF DATA
Authors: Capovilla Teresa Maria , Mapelli Massimo , Mattavelli Irene , Salvioni Elisabetta , Marongiu Alessandro , Maranzano Gaspare , Vignati Carlo , Palermo Pietro , Sinagra Gianfranco , Agostoni Piergiuseppe 
Published: December 2022

Abstract

Background
Practice guidelines recommend Sodium-glucose co-transporter-2 inhibitors (SGLT2-i) for patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to describe our population of patients with indications for Dapagliflozin, to compare it with the DAPA-HF trial population and assess the possible prognostic evolution.

Methods
We retrospectively analysed clinical data of the first 100 HFrEF patients treated with Dapagliflozin at our heart failure clinic (Centro Cardiologico Monzino) from September 2021.

Results
Table 1 shows patient characteristics in our study (n = 100) and in the DAPA-HF trial (n = 2373). Our patients had a mean age of 69±11 years, mean left ventricular ejection fraction of 31,1±8,0%, New York Heart Association class II (78%), class III (21%) and class IV (1%). 64% of our patients performed cardiopulmonary exercise test (CPET), with mean peak VO2/kg of 14,3±4,5 ml/min/kg and mean VE/VCO2 slope of 39,1±10,5. In our study, compared to the DAPA-HF trial population, there were fewer diabetic patients (14,1% vs 41,8%, p &lt; 0,001), a larger number of patients with implanted cardioverter defibrillator (ICD) (59,6% vs 26,2%, p &lt; 0,001) and cardiac resynchronization therapy (CRT) (22,2% vs 8,0%, p &lt; 0,001). Furthermore, our population had a higher percentage of patients already on optimised therapy with Sacubitril/Valsartan (86,9% vs 10,5%, p &lt; 0,001) and mineralocorticoid receptor antagonists (82,8% vs 71,5%, p &lt; 0,001), along with beta-blockers (97,9% vs 96%, p = 0,434).

Conclusions
Our patients were slightly older and frailer than those in the pivotal DAPA-HF trial and probably at a more advanced stage of the disease as suggested by the higher prevalence of ICD/CRT and Sacubitril/Valsartan. Based on these results, it may be that the expected prognostic benefit of adding Dapagliflozin to their therapy, in terms of absolute risk, will be lower than in the DAPA-HF trial. Future studies and a longer follow-up are needed to compare death and hospitalisation rates.
252 SHORT-TERM ANTI-REMODELING EFFECTS OF GLIFLOZINS IN DIABETIC PATIENTS WITH REDUCED EJECTION FRACTION: AN EXPLAINABLE ARTIFICIAL INTELLIGENCE APPROACH.
Authors: Mele Marco , Ragnatela Ilaria , Mele Antonietta , Imbrici Paola , Nicolotti Orazio , Togo Maria Vittoria , De Luca AnnaMaria , Altomare Cosimo Damiano , Brunetti Natale Daniele , Correale Michele , Liantonio Antonella , Amoroso Nicola 
Published: December 2022

Abstract

Background
Sodium glucose cotransporter type 2 inhibitors (SGLT2i), also called gliflozins, are playing an emerging role for the treatment of heart failure with reduced left ventricle ejection fraction (HFrEF). However, the direct effects of SGLT2i on left and right ventricular remodeling and function have not been completely clarified. We therefore aimed to assess clinical response to gliflozins focusing on echocardiographic evaluation and identify any predictive factors with a machine learning approach.

Methods
Based on Random Forest, a robust and consolidated machine learning approach, we carried out a single subject analysis to evaluate to which extent patients treated with gliflozins can effectively be distinguished from patients undergoing non-gliflozins treatments. Besides, we carried out an eXplainability analysis using Shapley values to outline the clinical parameters which mostly took advantage by gliflozins. Finally, machine learning experiments were designed to highlight the presence of specific clinical patterns undermining the gliflozins effectiveness.

Results
5-fold cross-validation analyses showed that gliflozin treatment was identified with a 0.70 ± 0.03% accuracy; the most important parameters supporting such accuracy were Right Ventricle S’ Velocity (RV S’), Left Ventricle End Systolic Diameter (LVESD) and E/e’ ratio. Low Tricuspid Annular Plane Systolic Excursion (TAPSE) values along with high LVESD and End Diastolic Volume (EDV) values are likely to impair the gliflozin effectiveness.

Conclusions
Treatment with gliflozins resulted in an improvement of several echocardiographic parameters related to biventricular function and left ventricle remodeling. Several clinical parameters, as simple echocardiographic parameters, may accurately predict the cardiovascular response to gliflozins treatment.
116 A CASE REPORT OF ISOLATED CARDIAC LIGHT CHAIN AMYLOIDOSIS WITHOUT HEART FAILURE: AN UNDER-RECOGNISED PRESENTATION
Authors: Nuzzi Vincenzo , Porcari Aldostefano , Gigli Marta , Pezzato Andrea , Zaja Francesco , Dore Franca , Bussani Rossana , Sinagra Gianfranco , Merlo Marco 
Published: December 2022

Abstract

Background
Cardiac involvement in light-chain amyloidosis (AL) usually represents a brick in the wall of a multi-system disease. The presence of cardiac deposition of free light chains (FLCs) is the main determinant of survival. Isolated cardiac AL is un uncommon scenario characterised by a challenging diagnostic and therapeutic work-up.

Case Summary
A 57-year-old asymptomatic man presented for an incidental finding of myocardial necrosis at the ECG performed for newly-diagnosed arterial hypertension. Alongside signs of previous myocardial infarction, transthoracic echocardiography showed a severely increased left ventricular (LV) wall thickness not consistent with ECG voltages, segmental akinesia with normal LV systolic function with ‘apical sparing’ pattern. Laboratory assessment showed an unexpectedly high level of natriuretic peptide and persistently abnormal troponin in the absence of symptoms or signs of heart failure or ongoing ischemia. Coronary angiogram confirmed the coronary artery disease. Before revascularization, a complete diagnostic work-up was carried. Serum electrophoresis detected a monoclonal gammopathy that was further investigated by serum immunofixation, revealing high lambda FLCs concentration. Fat pad, bone marrow and salivary glands biopsies resulted negative for amyloid deposition. Finally, endomyocardial biopsy was consistent with AL amyloidosis. Urgent percutaneous revascularization was performed and the patients was timely started on chemotherapy.

Discussion
The diagnosis of isolated cardiac AL amyloidosis is challenging and carries important therapeutic implications. As the short-term prognosis might be severely compromised, an accurate diagnostic flow-chart have to be systematically pursued to obtain a precise diagnosis and address the optimal, tailored management.
14 PICK YOUR THRESHOLD: A COMPARISON AMONG DIFFERENT METHODS OF ANAEROBIC THRESHOLD EVALUATION IN HEART FAILURE PROGNOSTIC ASSESSMENT
Authors: Salvioni Elisabetta , Mapelli Massimo , Bonomi Alice , Mattavelli Irene , De Martino Fabiana , Vignati Carlo , Gugliandolo Paola , Agostoni Piergiuseppe 
Published: December 2022

Abstract

Background
In clinical practice, anaerobic threshold (AT), is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). VO2AT has been reported as absolute value (VO2ATabs), as percentage of predicted peak VO2 (VO2AT%peak_pred) or as percentage of observed peak VO2 value (VO2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing.
In this work, we aim to compare the risk-identifying ability of the AT value when expressed in these three different ways in a large population of heart failure patients. This will help identify which is more correct to use in assessing patient prognosis, especially when peakVO2 is not reached appropriately.

Methods
The population analyzed counts 7746 patients with heart failure with history of reduced ejection fraction (&lt;40%), recruited between 1998 and 2020 during the MECKI score project. All patients underwent a maximal cardiopulmonary exercise test (CPET), executed in using a ramp protocol on an electronically braked cycle ergometer.

Results
In this study we considered 6157HF patients with identified AT (table 1). Follow up was 4.2 years (1.9-5.0). Both VO2ATabs population as regards prognosis (composite endpoint: cardiovascular death, urgent heart transplant or left ventricular assist device), Figure 1. Comparing AUC values, VO2ATabs (0.680) and VO2AT%peak_pred (0.688) performed similarly, while VO2AT%peak_obs (0.538) was significantly weaker (P&lt;0.001), Figure 2 A. Moreover, VO2AT%peak_pred AUC value was the only performing as well as AUC based on peakVO2 (0.710), with even a higher AUC (0.637 vs. 0.618 respectively) in the group with severe HF (peakVO2&lt;12mL/min/kg). Finally, the combination of VO2AT%peak_pred with Peak VO2 and VE/VCO2 shows the highest prognostic power Figure 2B.

Conclusions
In HF, VO2AT%peak_pred is the best way to report VO2 at AT in relation to prognosis, with a prognostic power comparable to that of peak VO2 and, remarkably, in severe HF patients.
Fig. 1
Fig 2
Fig. 2B
848 SACUBITRIL/VALSARTAN IMPROVES EXERCISE PERFORMANCE IN PATIENTS WITH REDUCED EJECTION FRACTION: A DOSE AND TIME DEPENDENT EFFECT
Authors: Mattavelli Irene , Mapelli Massimo , Salvioni Elisabetta , Paolillo Stefania , De Martino Fabiana , Vignati Carlo , Magrì Damiano , Mantegazza Valentina , Tamborini Gloria , Capovilla Teresa , Agostoni Piergiuseppe 
Published: December 2022

Abstract

Background
Sacubitril/Valsartan therapy has become a cornerstone of heart failure with reduced ejection fraction (HFrEF) pharmacological therapy due to its positive prognostic impact. However, conflicting results have emerged on the effects of sacubitril/valsartan on exercise performance assessed by cardiopulmonary exercise test (CPET).

Aim of the study
The aim of this study was to prospectively evaluate the effects of sacubitril/valsartan on prognostically significant CPET parameters in a larger population of HFrEF patients at different drug doses.

Methods
We prospectively enrolled HFrEF outpatients eligible to start sacubitril/valsartan according to 2016 ESC Guidelines in 3 Heart Failure Units. Patients underwent CPET at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26–49/51–97/103mg doses), and 6 months after the maximum tolerated dose was reached (end-study). The subjective impression of disease-related limitation was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ).

Results
113 patients were enrolled (age 64.5±9.7, 81% males). Peak oxygen intake (peakVO2) improved at each step from 15.0±4.5 mL/min/kg at baseline to 16.5±4.9 mL/min/kg at end study visit, corresponding to 61.5±16.0 and 67.9±17.4% of predicted, respectively (p&lt;0.05). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) reduced from 39.6±5.5 to 35.9±7.1 (p = 0.005) in the 39 patients (42%) with pathological VE/VCO2≥34 at baseline. KCCQ improved significantly since the first visit with an overall summary score increase from 47.9±11.1 to 52.6±9.8 (p&lt;0.001).

Conclusions
These findings suggest that sacubitril/valsartan benefits on exercise capacity are immediately evident at the lowest dose and progressively improve as the dose increases.
1143 IMPACT OF NON-CARDIAC COMORBIDITIES ON DIASTOLIC PROPERTIES IN HFREF AND HFMREF PATIENTS
Authors: Serino Giorgia , Caputo Annalisa , Filomena Domenico , Manzi Giovanna , Neccia Matteo , Boromei Michela , Rubino Giovanni , Papa Silvia , Vizza Carmine Dario , Badagliacca Roberto 
Published: December 2022

Abstract

Background and purpose
The impact of non-cardiac comorbidities on left ventricular (LV) diastolic properties in HFrEF and HFmrEF patients is still uncertain. Aim of the study was to determine how comorbidities affect LV relaxation and diastolic compliance in patients with HFrEF and HFmrEF.

Methods
Consecutive patients diagnosed with HFrEF or HFmrEF were enrolled. Non-cardiac comorbidity were recorded: diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea syndrome (OSAS), dyslipidemia and active or previous cancer. Patients underwent laboratory tests, including NT-pro-BNP. The following diastolic properties were evaluated non-invasively by echocardiography using previously validated methods: the time constant of isovolumetric relaxation (τ) and the diastolic stiffness index (β). Left atrial volume index (LAVi) was also recorded. Patients were divided in two groups: a) ≥2 comorbidities and b) &lt;2 comorbidities.

Results
Seventy-five patients were enrolled of whom 73% reported dyslipidaemia, 26% diabetes, 20% CKD, 18% COPD, 8% cancer, 4% OSAS. Thirty-five patients (47%) presented with ≥2 comorbidities showing higher values of τ (62±15ms vs 48±15ms, p&lt;0.001). Non- significant differences were found in β (6.12±0.3 vs 6.17±0.2; p= 0.582), left atrial volume index (47±34 vs 40±19, p= 0.386) and log-transformed NT-pro-BNP (6.2±1.4 vs 5.6±1.3; p= 0.323).

Conclusion
Among patients with HFrEF e HFmrEF the presence of multiple non-cardiac comorbidities was associated with more impaired proto-diastolic relaxation reflected by higher τ values. No significant differences were found in diastolic stiffness (β) and imaging and laboratory characteristics suggestive of increased end-diastolic LV filling pressure.
50 ERECTILE DYSFUNCTION IN HEART FAILURE PATIENTS: CORRELATION WITH SEVERITY, COMORBIDITIES, EXERCISE CAPACITY AND TREATMENT
Authors: Manfredini Lucia , Vignati Carlo , Salvioni Elisabetta , Mattavelli Irene , Mapelli Massimo , Agostoni Piergiuseppe 
Published: December 2022

Abstract

Aims
Erectile dysfunction (ED) is frequent in males with chronic heart failure (HF) with a severe impact on quality of life for many individuals. We evaluated the correlation between ED and HF severity, exercise capacity, treatment and psychological framework.

Methods and results
We enrolled 328 HF patients aged ≤70 years, with left ventricular ejection fraction ≤40%, and stable clinical condition. We measured: (i) hemoglobin, glycemia, glicated hemoglobin, creatinine, cholesterol, thyroid-stimulating-hormone, C-reactive-protein, total/free testosterone, brain natriuretic peptide, N-terminal prohormone of brain natriuretic peptide; (ii) ED, depression, urological symptoms and signs of low testosterone by means of questionnaires; (iii) HF severity by means of echo and cardiopulmonary exercise test.
ED was measured by means of International Index of Erectile Function-5 questionnaire and its score was correlated with exercise cardiopulmonary test parameters, HF severity, treatment and HF comorbidities.

Results
ED prevalence was 69.94%, 74.46%, and 64.08% in total population and in patients with and without coronary artery lesions, respectively. ED was absent in 98 while it scored mild, mild to moderate, moderate and severe in 65, 57, 32, 73 individuals, respectively. Depression was found in 33.96%, mild urological symptoms in 54,23% and signs of low testosterone in 74.23%.
All the individuals with peakVO2 &lt; 10 mL/min/kg had at least a slightly impaired sexual function. We have found no correlation between ED and ejection fraction, use of beta-blockers and ischemic etiology of HF. The only independent predictor of ED presence and severity is the symptomatology related to low testosterone.

Conclusions
ED is frequent in HF. A normal or only slightly impaired sexual activity is possible with peakVO2 &gt; 10 mL/min/kg. The symptomatology related to low testosterone should be investigated during cardiological examinations.