bluuebunny/crossref_metadata_2025_split huggingface dataset:
55 Brisk walking can be a maximal effort in heart failure patients. A comparison of cardiopulmonary exercise and 6-min walking test cardiorespiratory data
Authors: Salvioni Elisabetta , Mapelli Massimo , Paneroni Mara , Gugliandolo Paola , Bonomi Alice , Scalvini Simonetta , Raimondo Rosa , Sciomer Susanna , Mattavelli Irene , Rovere Maria Teresa La , Agostoni Piergiuseppe 
Published: December 2021

Abstract

Aims
Cardiopulmonary exercise test (CPET) and 6-min walking test (6MWT) are frequently used in heart failure (HF). CPET is a maximal exercise, whereas 6MWT is a self-selected constant load test usually considered a submaximal, and therefore safer, exercise but this has not been tested previously. The aim of this study was to compare the cardiorespiratory parameters collected during CPET and 6MWT in a large group of healthy subjects and patients with HF of different severity.

Methods and results
Subjects performed a standard maximal CPET and a 6MWT wearing a portable device allowing breath-by-breath measurement of cardiorespiratory parameters. HF Patients were grouped according to their CPET peak oxygen uptake (peakṼO2). One-hundred and fifty-five subjects were enrolled, of whom 40 were healthy (59 ± 8 years; male 67%) and 115 were HF patients (69 ± 10 years; male 80%; left ventricular ejection fraction 34.6 ± 12.0%). CPET peakṼO2 was 13.5 ± 3.5 ml/kg/min in HF patients and 28.1 ± 7.4 ml/kg/min in healthy (P &lt; 0.001). 6MWT-ṼO2 was 98 ± 20% of the CPET peakṼO2 values in HF patients, while 72 ± 20% in healthy subjects (P &lt; 0.001). 6MWT-ṼO2 was &gt;110% of CPET peakṼO2 in 42% of more severe HF patients (peakṼO2 &lt;12 ml/kg/min). Similar results have been found for ventilation and heart rate. Of note, the slope of the relationship between ṼO2 at 6MWT, reported as percentage of CPET peakṼO2 vs. 6MWT ṼO2 reported as absolute value, progressively increased as exercise limitation did.

Conclusions
6MWT must be perceived as a maximal or even supra-maximal exercise activity at least in patients with severe exercise limitation from HF. Our findings should influence the safety procedures needed for the 6MWT in HF.
164 Effect of cardiac contractility modulation therapy on myocardial work in patients with heart failure with reduced ejection fraction
Authors: Masarone Daniele , Vivo Stefano De , Errigo Vittoria , Onofrio Antonio D’ , D’Alterio Giuliano , Ammedola Ernesto , Nigro Gerardo , Pacileo Giuseppe 
Published: December 2021

Abstract

Aims
Cardiac contractility modulation therapy (CCMT) has been shown to reduce hospitalizations and to improve quality of life in heart failure patients with reduced ejection fraction (HFrEF) who remain symptomatic despite disease-modifying therapies. Strain imaging derived myocardial work (MW) is an emerging tool for evaluating left ventricular mechanics by incorporating systolic deformation and afterload burden in the analysis. To evaluate prospectively the impact of CCMT in HFrEF patients on MW derived parameters in relation to standard echocardiographic indices.

Methods and results
We recruited 12 HFrEF patients with indications to CCMT according to current clinical practice. A comprehensive echo-Doppler evaluation, including speckle tracking derived assessment of global longitudinal strain (GLS), was performed before and after three months from the CCM device implantation. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW), and global work efficiency (GWE) were calculated according to standardized procedures. Median values (interquartile range) were compared for all those parameters from baseline and 3-month follow-up with Wilcoxon Rank Sum test for continuous variables. At three months from CCM implant an improvement of LVEF [from 32% (27–34) to 36% (29–39), P &lt; 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P &lt; 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P &lt; 0.05], GCW [from 800 mmHg (620–930) to 970 mmHg (644–1009), P = 0.236], and GWE [from 73% (65–78) to 85% (78–87), P &lt; 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P &lt; 0.05]. We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.727, P = 0.011).

Conclusions
At 3 months, CCMT significantly improves standard and advanced left ventricular systolic function indices. This improvement is due to the increase of constructive work and a reduction of wasted work. In addition, the increase of left ventricular ejection fraction can be predicted by the global constructive work levels at baseline.
266 Deformation imaging by strain in chronic heart failure over sacubitril–valsartan: a multicentre echocardiographic registry (discover)—ARNI
Authors: Mandoli Giulia Elena , Pastore Maria Concetta , Giannoni Alberto , Benfari Giovanni , Dini Frank Lloyd , Rosa Gianmarco , Pugliese Nicola Riccardo , Taddei Claudia , Correale Michele , Brunetti Natale Daniele , Mazzeo Pietro , Carluccio Erberto , Mengoni Anna , Guaricci Andrea Igoren , Piscitelli Laura , Citro Rodolfo , Ciccarelli Michele , Novo Giuseppina , Corrado Egle , Pasquini Annalisa , Loria Valentina , Carli Giuseppe De , Degiovanni Anna , Patti Giuseppe , Santoro Ciro , Moderato Luca , Cicoira Mariantonietta , Canepa Marco , Malagoli Alessandro , Emdin Michele , Cameli Matteo 
Published: December 2021

Abstract

Aims
Sacubitril/valsartan have changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects morbidity and mortality partly mediated by left ventricular reverse remodelling (LVRR). The aim of this multicentre study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration.

Methods and results
Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic indexes including speckle tracking echocardiography (STE) indexes were used to predict LVRR [defined as LV end-systolic volume reduction and ejection fraction (LVEF) improvement &gt; 10% at follow-up] at 6 months follow-up as the primary endpoint. Changes in symptoms (NYHA class) and neurohormonal activations [N-terminal-pro-brain natriuretic peptide (NTproBNP)] were also evaluated as secondary endpoints. The final population (excluding patients with poor acoustic windows and missing data) consists of 341 patients [mean age: 65 ± 10 years; 18% female, median LVEF 30% (interquartile range: 25–34)]. At 6 months follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥35%), 55 (16%) early incomplete response (LVRR and LVEF &lt;35%), 204 (60%) no response (no LVRR and LVEF &lt;35%). Non-ischaemic etiology, a lower left atrial volume index and a higher global longitudinal strain were all independent predictors of LVRR at multivariable logistic analysis (all P &lt; 0.01). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P &lt; 0.05) (Figure 1).

Conclusions
STE parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan, and thus could be used as a guide for treatment in patients with HFrEF.
570 Prevalence and prognosis of cardiac cachexia in acute heart failure patients
Authors: Ruocco Gaetano , Pastorini Guido , Testa Marzia , Rossi Arianna , Feola Mauro 
Published: December 2021

Abstract

Aims
Cachexia is characterized by a pathological shift of metabolism towards a catabolic state. The prevalence of cardiac cachexia in heart failure (HF) patients is around 10% and it recognizes a negative prognostic impact. In this study we would like to evaluate prevalence and prognosis of cardiac cachexia in acute heart failure (AHF) patients.

Methods and results
This is an observational retrospective study enrolling patients with diagnosis of acute heart failure (AHF) de novo or not, admitted to our department from January 2015 to September 2018 within 12 h from emergency department admission. Patients underwent to clinical examination, laboratory analysis and echocardiography. Cardiac cachexia was defined as unintentional weight loss, with or without skeletal muscle wasting, of at least 5% of baseline weight during the previous year. For the diagnosis, three of the following factors are also required: anorexia, fatigue, reduced muscle strength, reduced fat-free mass index, and abnormalities in blood biomarkers (haemoglobin ≤12 g/dl, serum albumin &lt;3.2 g/dl, elevated IL-6, or increased C-reactive protein).1 Patients were followed for 1 year after hospital discharge for the composite outcome of HF re-hospitalization and cardiovascular death through 1 year. A total of 415 AHF patients were included in this analysis. 111 patients met the criteria for the diagnosis of cardiac cachexia. Median age was 78(70–83) years. Patients with cardiac cachexia showed higher age [79 (73–84) vs. 77 (68–82) years; P = 0.005], length of hospital stay [12 (8–15) vs. 9 (6–13) days; P = 0.004], and RDW [14.9 (13.9–16.3) vs. 15.3 (14.3–16.9); P = 0.02] with respect to patients without cachexia. Moreover, patients with cachexia demonstrated reduced eGFR [53 (38–68) vs. 48 (31–60) ml/min/m2; P = 0.03] and TAPSE [18 (15–20) vs. 15 (14–19) mm; P = 0.002] compared to patients without cachexia. No differences were found among groups in terms of NTproBNP. In-hospital mortality was higher in patients with cachexia compared to other patients (6.3% vs. 1.3%; P = 0.005). Univariate Cox regression analysis confirmed the poor prognosis of patients with cachexia at one month [HR: 2.53 (1.24–5.19); P = 0.01], six months [HR: 2.47 (1.61–3.77); P &lt; 0.001] and 1 year [HR: 2.04 (1.40–2.98); P &lt; 0.001].

Conclusions
Patients with cardiac cachexia were characterized by renal dysfunction and right ventricle dysfunction. These alterations should act as worsening factors in terms of abdominal venous congestion and subsequent malabsorption. Finally, in our population, cardiac cachexia was related to poor short term and long term outcome as confirmed by recent studies.
81 Safety of sacubitril/valsartan in the elderly population with heart failure and reduced ejection fraction: a real-life observational study
Authors: Vincenzi Antonella , Casati Matteo , Cirò Antonio , Annaloro Alessandra , Rea Federico , Arace Francesco , Lettino Maddalena 
Published: December 2021

Abstract

Aims
Prevalence of heart failure (HF) increases with age, but the elderly population is underrepresented in trials and the only data on the efficacy and safety of sacubitril/valsartan (S/V) in this group provided by the subanalysis of the PARADIGM trial, which confirms a favourable benefit-risk profile in all age groups. Information in a real-world setting is still lacking. Our study aims to evaluate the safety profile of S/V, in terms of risk of symptomatic hypotension, renal failure, and hyperkalaemia, in a group of real-life patients (pts) &gt; 75 years old (yo) presenting with HF and reduced Ejection Fraction (HFrEF).

Methods and results
59 patients on S/V therapy older than 75 years (average age 78.9 ± 2.6) were identified out of a total number of 148 patients with HFrEF (39.8%), followed at our Heart Failure Clinic from December 2016 to April 2019. They were included in our retrospective observational cohort study. We compared their baseline characteristics (cardiovascular risk factors, mean serum creatinine, atrial fibrillation, EF) with the PARADIGM subgroup (1563pts, 18.6%) (average age: 79.1 ± 3.5) At time 0 (T0), and at 6 (T1), 12 (T2), and 18 (T3) months we assessed their serum creatinine, potassium and Nt-proBNP levels, blood pressure (BP), heart rate, NYHA class, eGFR (with MDRD), and the occurrence of death, hospital admissions for HF, symptomatic hypotension and angioedema. For the statistical analysis we used a marginal model with an unstructured covariance structure. Compared to the PARADIGM subgroup our study population showed a higher prevalence of AF (64.4% vs. 50.7%, P 0.039), a worse baseline creatinine (1.46 mg/dl vs. 1.22 mg/dl, P &lt; 0.001) and eGFR (51.5 vs. 57.5 ml/min/1.73 m2, P 0.005) (Figure 1). During the 18 months follow-up there was no significant increase in serum creatinine (P 0.092) and potassium (P 0.799). There was however a significant decrease in eGFR (from 51.46 to 45.36; P 0.015) and systolic BP (from 123.6 to 116.4 mmHg; P 0.021) and a higher rate of treatment discountination for symptomatic hypotension (5.1% vs. 1.8%, P 0.082) (Figure 2).

Conclusions
The present study confirmed the safety of S/V already shown in the PARADIGM trial, despite the worse baseline clinical characteristics of our elderly population. Our population had no significance increase in serum creatinine and potassium, similarly to the trial subgroup. Nevertheless there was a trend towards a higher rate of symptomatic hypotension leading more frequently to treatment discontinuation. Whether a more personalized implementation of S/V therapy in the ageing HF population (minimum starting dose, slower uptitration) would determine a higher tolerability of the drug should be specifically addressed by focused, prospective clinical trials.
695 Upregulated monocyte expression of PLIN2 is associated with plaque instability in coronary artery disease
Authors: Canonico Francesco , Severino Anna , Camilli Massimiliano , Migliaro Stefano , Vinci Ramona , Pidone Chiara , Galli Mattia , Pisano Eugenia , Arcudi Alessandra , Bonanni Alice , Di Sario Marianna , De Ciutiis Astrid , Russo Sara , Angelini Giulia , Pedicino Daniela , Montone Rocco , Niccoli Giampaolo , Liuzzo Giovanna , Crea Filippo , D’Amario Domenico 
Published: December 2021

Abstract

Aims
Perilipin 2 (PLIN2), a protein associated with intracellular lipid droplets (LDs), is involved in lipid metabolism of macrophages resident in atherosclerotic plaques and its up-regulation leads to LDs accumulation. LDs enlargement results in the macrophage transformation into foam cells, a key step for the onset of atherosclerosis. In the present study, we investigated the role of PLIN2 and its regulation mechanisms in atherosclerosis and plaque instability in patients with a diagnosis of ST-elevation myocardial infarction (STEMI) and stable chronic angina (SA).

Methods and results
We enrolled 120 patients with a diagnosis of STEMI and 42 SA patients with symptoms of stable effort angina lasting more than 12 months. Peripheral blood mononuclear cells (PBMCs) were isolated from EDTA whole blood samples through standard gradient centrifugation over Ficoll-Hypaque. Monocytes were purified through indirect magnetic labelling of PBMCs. PLIN2 mRNA expression was investigated by Real Time-PCR and PLIN2 protein level was analysed in CD14+ monocytes by flow cytometry. Proteasome activity was assayed using AMC-tagged peptide substrate (Succ-LLVY-AMC), which releases free highly fluorescent AMC (Ex/Em 350/440 nm) in the presence of proteolytic activity. In CD14+ monocyte, PLIN2 protein expression was significantly increased in STEMI as compared to SA patients (P &lt; 0.001), while PLIN2 mRNA level was not different in the two groups (P = n.s.). Despite proteasome activity was higher in STEMI as compared to SA patients (P &lt; 0.001), significant inverse correlations were evident between PLIN2 levels and proteasome activity in the two groups (P = 0.05).

Conclusions
CD14+ monocyte PLIN2 protein expression was higher in STEMI as compared to SA patients suggesting an involvement in plaque instability. Despite proteasome activity was higher in STEMI patients, probably due to the elevated inflammatory burden, PLIN2 could escape proteasome degradation in a more efficient manner in STEMI as compared to SA patients.
760 Prevalence of eligibility criteria for prolonged dual antithrombotic therapy in patients with PEGASUS and COMPASS phenotypes: insights from the start-antiplatelet registry
Authors: Cesaro Arturo , Gragnano Felice , Calabrò Paolo , Moscarella Elisabetta , Santelli Francesco , Fimiani Fabio , Patti Giuseppe , Cavallari Ilaria , Antonucci Emilia , Cirillo Plinio , Pignatelli Pasquale , Palareti Gualtiero , Pelliccia Francesco , Bossone Eduardo , Pengo Vittorio , Gresele Paolo , Marcucci Rossella 
Published: December 2021

Abstract

Aims
After 1 year of dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS), clinicians face the dilemma of choosing between prolonged DAPT with aspirin and ticagrelor 60 mg twice daily (PEGASUS strategy) or aspirin and rivaroxaban 2.5 mg twice daily (COMPASS strategy). In recent years, there has been a widespread discussion about the optimal duration of DAPT and the best combination of drugs. To analyse the prevalence and clinical implications of the eligibility criteria for prolonged dual antithrombotic therapy with ticagrelor 60 mg twice daily and/or rivaroxaban 2.5 mg twice daily in a contemporary real-world ACS registry.

Methods and results
Patients from the START-ANTIPLATELET registry (NCT02219984) were stratified according to the eligibility criteria of the PEGASUS and COMPASS studies to investigate the proportion of patients eligible for prolonged dual antithrombotic therapy at discharge and after 1-year of DAPT. Net adverse clinical events (NACE), defined as all-cause death, myocardial infarction, stroke, and major bleeding, at 1 year were also evaluated and compared among groups. 1844 were considered for the analysis at baseline. Out of 849 event-free patients continually receiving dual antiplatelet therapy for at least 1 year, 577 (68%) and 583 (68.7%) met at least one eligibility criterion for ticagrelor and rivaroxaban, respectively. In the PEGASUS-like patients, age was the most common criterion (71% of cases). The presence ≥2 cardiovascular risk factors was the most common eligibility criterion in the COMPASS-like patients (80.8%). At 1-year follow-up, 211 (11.4%) and 119 (6.5%) patients experienced NACE and MACE, respectively. The incidence of NACEs was higher in the PEGASUS-only group (15.4% vs. 8.4%; P = 0.008) and numerically higher in the COMPASS-only group (10.9% vs. 8.4%; P = 0.299).

Conclusions
In a contemporary real-world ACS cohort, approximately two-thirds of patients that complete 1-year DAPT met the eligibility criteria for ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily, showing a higher risk of NACEs.
291 Ticagrelor monotherapy after percutaneous coronary intervention in high-risk patients with prior myocardial infarction: a prespecified twilight substudy
Authors: Chiarito Mauro , Cao Davide , Baber Usman , Pivato Carlo , Briguori Carlo , Sardella Gennaro , Stefanini Giulio , Dangas George , Pocock Stuart , Mehran Roxana 
Published: December 2021

Abstract

Aims
Patients with history of myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) remain at risk of recurrent ischaemic events. The optimal antithrombotic strategy for this cohort remains debated.

Methods and results
In this prespecified analysis of the TWILIGHT trial, we evaluated the impact of prior MI on treatment effect of ticagrelor monotherapy vs. ticagrelor plus aspirin in patients undergoing PCI with at least one clinical and one angiographic high-risk feature and free from adverse events at 3 months after the index PCI. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5, the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. 1937 (29.7%) patients with and 4595 (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. Patients with prior MI had increased rates of death, MI or stroke (5.7 vs. 3.2%, P &lt; 0.001) but similar BARC 2–5 bleeding (5.0 vs. 5.5%, P = 0.677). Ticagrelor monotherapy reduced the risk of BARC 2–5 bleeding in patients with [3.4% vs. 6.7%; hazard ratio (HR): 0.50; 95% confidence interval (CI): 0.33–0.76] and without prior MI [4.2% vs. 7.0%; HR: 0.58; 95% CI: 0.45–0.76; pinteraction = 0.54). Rates of the key secondary ischaemic outcome were similar between treatment groups irrespective of history of MI (prior MI: 6.0% vs. 5.5%; HR: 1.09; 95% CI: 0.75–1.58; no prior MI: 3.1% vs. 3.3%; HR: 0.92; 95% CI: 0.67–1.28; pinteraction = 0.52).

Conclusions
Ticagrelor monotherapy is associated with significantly lower risk of bleeding events as compared to ticagrelor plus aspirin without any compromise in ischaemic prevention among high-risk patients with history of MI undergoing PCI.
472 Coronary disease in ADPKD patient: a giant coronary aneurysm
Authors: Mora Francesco Della , Fezzi Simone , Porto Marta Dal , Pighi Michele , Ribichini Flavio 
Published: December 2021

Abstract

Aims
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder driven by mutation of one of two genes: PKD1, which codifies polycystin-1, and PKD2, which codifies polycystin-2. The mutated proteins determine the formation of multiple renal cysts with a consequent decline in kidney function eventually leading to end-stage renal disease (ESRD). In the last decades the cardiovascular complications of ADPKD are emerging as the leading cause of death, but coronary artery disease (CAD) remains to be an uncommon complication.

Methods and results
A 60-year-old male patient affected by ADPKD, in dialysis treatment for ESRD, was admitted in 2020 to our hospital for invasive coronary angiography (ICA), checking eligibility for kidney transplantation. He had a previous history of hypertension and chronic ischaemic cardiomyopathy. ICA performed in 2017 for unstable angina assessed ectasiant coronary arteries with diffuse atherosclerotic disease (Figure 1), determining significant stenosis of the proximal left anterior descending artery and proximal circumflex artery, treated with percutaneous coronary intervention (PCI). In 2020 was so repeated ICA, that evidenced a good result of the previous PCI, but pointed out a severe progression of ectasiant disease, which led to formation of giant aneurysm of the proximal tract of the right coronary artery, assessed at 3.8 cm × 2.5 cm (Figure 2), fistulizing to the right atrium and determining significant flow limitation in the following part of the right coronary artery. The absence of any symptoms and the lack of evidence of ongoing heart dysfunction, led our team to indicate conservative management and angiography follow-up.

Conclusions
Cardiovascular disease is a major cause of morbidity and death in ADPKD, underlying a tendency towards accelerated atherosclerosis, but wide data about coronary involvement are still lacking. ADPKD patients seem to have an increased risk of developing coronary aneurisms, but either due to the expression of mutated proteins in arterial smooth cells, to the accelerated atherosclerotic disease or to the combination of both, is still controversial. Consequently, it is difficult to differentiate the underlying pathophysiology of aneurysm formation in an individual patient and to speculate whether ADPKD patients have an increased risk of developing coronary aneurysms independent of their accelerated atherosclerotic process.