bluuebunny/crossref_metadata_2025 huggingface dataset:
46 A clinical and echocardiographic score to differentiate pulmonary hypertension due to heart failure with preserved ejection fraction from idiopathic pulmonary hypertension: the PH-HFpEF score
Authors: Chietera Francesco , Dardi Fabio , Rotunno Mariangela , Palazzini Massimiliano , Guarino Daniele , Ballerini Alberto , Magnani Ilenia , Bertozzi Riccardo , Donato Federico , Rapparini Luca , Manes Alessandra , Galiè Nazzareno
Published: December 2021

Aims

One of the most challenging differential diagnoses in pulmonary hypertension clinical practice, is the discrimination between idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF).

We elaborate a score (considering patient clinical history, demographics, and echocardiographic characteristics) that can predict, noninvasively, PH-HFpEF vs. IPAH diagnosis.

Methods and results

Data were prospectively collected on 466 consecutive patients with a final diagnosis of IPAH or PH-HFpEF referred to a single tertiary pulmonary vascular disease centre. Data included clinical history, demographics, and parameters of an electrocardiogram and a transthoracic echocardiogram. A multivariate regression model was developed to predict a PH-HFpEF diagnosis, and an integer risk score was generated using adjusted regression coefficients of the multivariate logistic regression analysis. At the multivariate logistic regression a high ratio between left and right ventricular dimensions, a history of atrial fibrillation (AF), a high body mass index (BMI), a reduced mitral deceleration time and a high E-wave at trans-mitral Doppler, an advanced age and a high right ventricular fractional area change (FAC) were predictors of PH-HFpEF. The derived PH-HFPEF score (Figure), with a cut-point ≥11, yielded a specificity/sensitivity, respectively, for the diagnosis of PH-HFpEF, of 100%/49% with an AUC of 0.987.

ED, end-diastolic; LV, left ventricle; RV, right ventricle.

Conclusions

The PH-HFPEF score can predict PH-HFpEF vs. IPAH. The PH-HFPEF score may be used to potentially avoid an invasive diagnostic testing in almost half of PH-HFpEF patients.
388 Haemodynamic arterial changes in heart failure: a proposed new paradigm of heart and vessels failure. The Copernican revolution?
Authors: Galati Giuseppe , Germanova Olga , Iozzo Renato V. , Buraschi Simone , Germanov Andrey , Germanov Vladimir , Fedorina Marina , Senni Michele , Margonato Alberto
Published: December 2021

Aims

Although heart failure (HF) is one of the most common conditions affecting the heart, little attention has been placed on the role of arteries in contributing to the progression of this disease. We sought to determine the haemodynamic change of arteries in HF patients subdivided according to left ventricular ejection fraction. The major goal was to establish the active compensatory role of arteries in HF.

Methods and results

Using sphygmography, we systematically studied a cohort of 228 HF patients and 52 healthy controls. We focused on the common carotid as the main elastic artery and the posterior tibial as the main muscular artery (Figure 1). Moreover, we categorized the three HF groups, HFrEF, HFmrEF, HFpEF, into two subgroups (A and B) according to the presence or absence of HF signs at baseline. We discovered that all the parameters of measured arterial kinetics, i.e. work, power, acceleration, and speed, were significantly increased (P < 0.001 by one-way ANOVA) in the groups without HF signs. In contrast, all the arterial kinetics parameters were significantly reduced (P < 0.001) in the groups exhibiting HF signs. Similar results were obtained in both types of arteries and were consistently observed across all the three different types of HF, although with some differences in magnitude. Finally, we discovered that HFpEF patients exhibited more compromised arterial function vis-à-vis HFrEF patients [Figure 2: Patients disposition (Top) and quantification of arterial kinetics and haemodynamic parameters (Down) from the common carotid artery (A) and the posterior tibial artery (B)].

Conclusions

We provide the first documentation of an active compensatory role of arteries during HF. Mechanistically, we explain these findings by a dual activity of large arteries accomplished via an active propulsive work and a concurrent haemodynamic suction. These underestimated arterial functions partially compensate for the heart dysfunction in HF, underlining a key interplay between the heart and the vessels. We propose a new paradigm that we define as ‘heart and vessels failure’ that explicitly focuses on both heart and vessels’ interaction during the progression of HF.
157 Efficacy and tolerability of sacubitril/valsartan in patients with chronic heart failure and reduced ejection fraction
Authors: Cerciello Antonio , Lamaida Norman
Published: December 2021

Aims

The PARADIGM-HF study has shown, as is well known, that the association of sacubitril/valsartan (SV) was superior in terms of efficacy compared to enalapril in patients suffering from heart failure chronic cardiac (SC) and reduced systolic function (HFrEF). We have analysed the use of SV in patients with symptomatic HF and HFrEF, andits effect on humoural and functional parameters of easy evaluation.

Methods and results

From March 2018 to December 2019 we have introduced the SV in 158 patients 135 M and 23 F mean age 40–80 years with fraction of ejection <35% with idiopathic dilated cardiomyopathy (six patients) or post-ischaemic (150 patients), in NYHA III class. Patients were declared eligible according to the ESC 2016 criteria (EF 40%, NT-proBNP> 400 ng/l, target dose of ACE inhibitors/receptor antagonists angiotensin, GFR> 30 ml/min/1.73 m2, serum S-potassium <5.2 mmol/l, treatment with beta-blockers and antialdosteronics). Initially the administration of SV was a cp of 49/51 mg bid up to maximum tolerated dose (one tablet of 97/103 mg bid). All the patients had stopped taking ACE-I or sartans 48 h before and were evaluated at 4-week intervals for two years. In all patients we evaluated: ejection fraction (FE), filtered glomerular, systolic blood pressure, body weight, side effects, hospitalization and mortality. Of the 156 patients, 17 achieved the optimal dose of SV (97/103 mg), 113 achieved SV 49/51 mg bid. In all patients did not experience side effects or alterations of the electrolyte picture and renal function. The SV has determined an improvement NYHA class of at least 1; the echocardiogram showed a significant increase in FE: at follow-up 89 patients reached FE 45%, 44 patients FE 40–44%, and 6 patients about 50%; besides it is an improvement in indexed end-diastolic volume in moles was noted above patients (from 118.4 ± 38.4 to 110.9 ± 30 ml/m2). No case of re-hospitalization.

Conclusions

Our experience shows that the use of SV is well tolerated, improves functional capacity and ventricular remodelling and that does not modify the parameters of renal function and electrolytic of the patients.
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

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 < 0.001). 6MWT-ṼO2 was 98 ± 20% of the CPET peakṼO2 values in HF patients, while 72 ± 20% in healthy subjects (P < 0.001). 6MWT-ṼO2 was >110% of CPET peakṼO2 in 42% of more severe HF patients (peakṼO2 <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

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 < 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P < 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P < 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 < 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P < 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

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 > 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 <35%), 204 (60%) no response (no LVRR and LVEF <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 < 0.01). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 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

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 <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 < 0.001] and 1 year [HR: 2.04 (1.40–2.98); P < 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

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) > 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 < 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

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 < 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 < 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

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

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 < 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

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.
452 Saline-induced coronary hyperaemia is mediated by intravascular haemolysis
Authors: Gallinoro Emanuele , Candreva Alessandro , Paolisso Pasquale , Fernandez-peregrina Estefania , Sonck Jeroen , Bermpeis Kostantinos , Bertolone Dario Tino , Esposito Giuseppe , Collet Carlos , Barbato Emanuele , De Bruyne Bernard
Published: December 2021

Aims

Absolute coronary blood flow can be measured by intracoronary continuous thermodilution of saline through the lateral side holes of a dedicated infusion catheter placed in the proximal segment of the coronary artery. A room-temperature saline infusion rate at 15–20 ml/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear. The aim of the present study is to test whether local haemolysis is a potential mechanism of coronary hyperaemia.

Methods and results

Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured using the continuous intracoronary thermodilution of saline through a dedicated infusion catheter (RayFlow®). Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 ml/min); hyperaemia (Hyperaemia, saline infusion at 20 ml/min); post-hyperaemia [Post-Hyperaemia, 2 min after the cessation of saline infusion; and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min). Haemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperaemia phase. As compared to Rest, during Hyperaemia both LDH [131.50 ± 21.89 U/dL (Rest) and 258.33 ± 57.40 U/dl (Hyperaemia), P < 0.001] and plasma-free haemoglobin [PFHb, 4.92 ± 3.82 mg/dl (Rest) and 108.42 ± 46.58 mg/dl (Hyperaemia), P < 0.001] significantly increased in the coronary sinus. The percentage of haemolysis was significantly higher during the hyperaemia phase [0.04 ± 0.02% (Rest) vs. 0.89 ± 0.34% (Hyperaemia), P < 0.001].

Conclusions

Saline-induced hyperaemia through a dedicated intracoronary infusion catheter is associated with haemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation. The role of other substances released by erythrocytes in inducing hyperaemia cannot be excluded and requires further investigations.
222 Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery
Authors: Nanni Samuele , Corsini Anna , Garofalo Mattia , Schinzari Matteo , Nardi Elena , Semprini Franco , Baiocchi Massimo , Castelli Andrea , Pacini Davide , Galie Nazzareno
Published: December 2021

Aims

The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and/or instrumental findings. However, there is not a clear cut-off value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease.

Methods and results

We retrospectively enrolled all consecutive adult patients undergoing CABG at our Institution over 1 year. Hs-cTnI concentrations (Access assay, Beckman-Coulter) were serially measured in the post-operative period and correlated with post-operative outcomes. 300 patients were enrolled; 71.3% of them underwent CABG alone, mainly on-pump (96.7%), 33.7% in the setting of an acute coronary syndrome. Most patients showed hs-cTnI values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, and 10.6% showed a LVEF decrease ≥10%. Hs-cTnI concentrations did not correlate with death or PMI whereas they did correlate with LVEF decrease ≥ 10% (P-value < 0.05 at any time interval). Indeed, higher hs-cTnI values at 9–12 h post-operatively, along with previous cardiac surgery, number of surgical procedures, longer cardiopulmonary bypass time, and PMI diagnosis were predictors of LVEF decrease.

Conclusions

After CABG surgery, hs-cTnI at 9–12 h post-operatively may be a useful method to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.
609 Prognostic role of renal function in patients with previous myocardial infarction. A study with cardiac magnetic resonance
Authors: Restelli Davide , Licordari Roberto , Piaggi Paolo , Carerj Scipione , Santoro Domenico , Arcadi Vittoria , Aquaro Giovanni Donato , Pingitore Alessandro , Di Bella Gianluca
Published: December 2021

Aims

There is not strong evidence in literature about the impact of renal function on the prognosis of patients with ischaemic cardiomyopathy. Thus, the aim of the study was to investigate mild renal impairment [estimated glomerular filtration rate (eGFR): 60–89 ml/min] as an independent prognostic factor in patients with history of myocardial infarction (MI).

Methods and results

We studied 339 consecutive patients (65 ± 13 years old, female 13%) from 2001 and 2012 with previous MI. Patients with eGFR <60 ml/min were excluded. We performed cardiac magnetic resonance (CMR) in all patients to quantify left ventricular ejection fraction (LVEF), volumes, and wall motion score index (WMSI), and to measure the infarction extent by late gadolinium enhancement (LGE). Renal function was estimated by creatinine value with Cockcroft–Gault formula and patients were divided according to normal (≥90 ml/min) and reduced (60–89 ml/min) eGFR. Patients with normal eGFR were 106 (31%, 56.9 ± 10.5 years old), 233 (69%, 66.1 ± 9.9 years old) had renal impairment. During follow-up (median 3.5 years), cardiac events (cardiac death or appropriate intra-cardiac defibrillator shock) occurred in 28/233 (12%) of patients with eGFR <90 ml/min and in 4/106 (4%) of patients with eGFR ≥90 ml/min (P < 0.05). Furthermore, survival curve showed a significantly worst prognosis in patients with renal impairment (P < 0.03). In the group of patients with ejection fraction (EF) < 35% (121 patients), cardiac events were observed only in patients with eGFR <90 ml/min (23/99, 23%, P < 0.05). At multivariate stepwise analysis, age >65 years old, eGFR <90 ml/min and WMSI >1.7 turned out to be independent predictor of cardiac events (P < 0.05).

Conclusions

In patients with previous MI, a mild renal impairment (eGFR between 60 and 89 ml/min) was an independent predictor of prognosis, especially if combined with left ventricular disfunction.
16 Impaired glucose tolerance and cardiovascular outcomes after an acute coronary syndrome—the important role of 1-h plasma glucose at the oral glucose tolerance test
Authors: Zywicki Viola , Capozza Paola , Caravelli Paolo , De Caterina Raffaele
Published: December 2021

Aims

2-h plasma glucose (PG) ≥140 mg/dl but <200 mg/dl at the oral glucose tolerance test (OGT), defined as impaired glucose tolerance (IGT), has been reported as related to adverse cardiovascular outcomes in non-diabetic patients. The added value of 1-h plasma glucose (PG) ≥155 mg/dl at the OGTT is unknown. We investigated the value of 1-h PG in IGT patients admitted for an acute coronary syndrome (ACS) in relation to in hospital outcome.

Methods and results

Among 109 patients admitted to Coronary Care Unit for an ACS, with both no previous diagnosis of diabetes and first-line in-hospital screening with glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) negative for either diabetes and prediabetes, OGTT was performed. On the basis of the OGTT results, 21 patients (19.3%) were newly diagnosed diabetes. The remaining 88 patients were divided into: Group A: ‘fully glucose tolerant’, with 1 h PG-OGTT <155 mg/dl and 2 h PG-OGTT <140 mg/dl; Group B: ‘early-impaired IGT’ with 1 h-PG at OGTT ≥155 mg/dl and 2 h-PG <140 mg/dl; Group C: ‘late impaired-IGT’, with 1 h-PG at OGTT <155 mg/dl and 2 h PG-OGTT ≥140 mg/dl; and Group D: ‘fully impaired IGT’, with 1 h-PG at OGTT ≥155 mg/dl and 2 h PG-OGTT ≥140 mg/dl. In this analysis we compared the four groups as to cardiac markers and days of hospitalization by the Kruskal–Wallis test and correcting multiple comparisons with the Bonferroni’s adjustment. On the basis of the OGTT results, 12 patients (13.5%) belonged to Group A, 32 (39%) to Group B, 8 (9%) to Group C, and 35 (39%) patients to Group D. Group D patients had significant higher Hs-TnT at admission compared to Group A (P = 0.013), Group B (P = 0.023), and Group C (P = 0.005). Group D patients featured significant higher Hs-TnT peak compared to Group A (P = 0.016) and Group B (P = 0.005). Patients in Group D had a longer hospitalization compared to Group A (P = 0.005).

Conclusions

In the setting of ACS, compared to non-diabetic patients with a normal OGTT, only IGT patients characterized by both 1 h-PG ≥155 mg/dl and 2 h PG ≥ 140 mg/dl had more severe myocardial injury and longer hospitalization. These results suggest that, within currently defined IGT patients, 1 h-PG importantly contributes to assessing cardiac risk.
515 Exertional syncope and ventricular arrhythmia in a patient with cardiac amyloidosis
Authors: Fede Giuseppe , Abate Giuseppe , Belluardo Paolo , Guccione Nicoletta , Tasca Giovanni , Guarrella Maria Luisa , Di Tommasi Carmelo , Piccione Guglielmo , Sulsenti Giuseppe , Ficili Sabina
Published: December 2021

Aims

Systemic amyloidosis is a multisystem disorder caused by the misfolding, aggregation, and deposition of certain proteins in various organs and tissues. Cardiac involvement is common and worsens the prognosis. Atrial fibrillation is the most frequent arrhythmia in cardiac amiloidosis (CA), but many cases of ventricular arrhythmias (VA) and sudden cardiac death (SCD) have been described.

Methods and results

We present a case of a 64-year-old man admitted following exertional syncope occurred after climbing a flight of stairs. In the previous 2 weeks he had experienced fatigue and poor tolerance to exertion; moreover, 2 days before he had another episode of transient loss of consciousness after exertion. His medical history included left gonarthrosis and surgery for right carpal tunnel syndrome one year before. Physical examination did not revealed signs of heart failure. A 12-lead electrocardiogram (ECG) showed a pseudoinfarction pattern with QS waves in V2 and V3 leads and low voltage in all limb leads (Figure 1). Routine blood tests revealed N-terminal pro-bran natriuretic peptide (NT-ProBNP) of 3436 pg/ml (n.v. 0–125) and high-sensitive troponin T of 67 pg/ml (n.v. < 58). A trans-thoracic echocardiogram showed left ventricle (LV) concentric thickening wall with granular and sparkling pattern, mild reduced ejection fraction, reduced global longitudinal strain with apical sparing, grade 3 diastolic disfunction, biatrial enlargement, mild mitral regurgitation, right ventricle free wall thickening (8 mm), mild reduced TAPSE, and mild pericardial effusion. Cardiac magnetic resonance (CMR) confirmed ventricular wall thickening with evidence at T1 mapping of interstitial infiltration more evident in the septum and inferior-lateral wall with apical savings (Figure 2). A total body 99mTc-HDP scintigraphy showed cardiac uptake with intensity similar to bone signal (Perugini Score 2) suggesting ATTR cardiac amyloidosis (Figure 3). Both kappa and lambda concentrations were normal. The genetic testing did not reveled mutations in the TTR gene. We concluded for a diagnosis of ATTR wild-type CA. The Holter ECG monitoring registered numerous ventricular ectopic beats and an episode of non-sustained ventricular tachycardia. A coronary angiography ruled out coronary artery disease. In consideration of the clinical-instrumental picture an ICD was implanted.

Conclusions

In conclusion, CA is still underdiagnosed. VA and SCD may further complicate the prognosis. Early diagnosis and adequate stratification of the arrhythmic risk are essential to ensure patients the best therapeutic strategies.
790 Pacemaker lead and atrial thrombosis, a rare event but of high clinical importance
Authors: Pistelli Lorenzo , Dattilo Giuseppe , Parisi Francesca , Crea Pasquale , Gurioli Lorenzo , Marra Walter Grosso
Published: December 2021

Aims

Trans-venous lead-related thrombosis is an undervalued issue. Since the lack of guidelines or evidences regarding the best therapeutic option, treatment of endocavitary clots on pacemaker wire is left to individual decision between surgical catheter extraction, thrombolysis, or anticoagulation therapy. In some patients, the labile equilibrium between hemorrhagic and thrombotic events may further complicate management.

Methods and results

We report the case of a 86-years-old man with heart failure (HF) severely reduced ejection fraction due to chronic ischaemic cardiomyopathy and several co-morbidities. He had a reacution of HF requiring hospitalization secondary to new-onset atrial flutter. During hospital stay, in light of episodes of severe bradycardia, he underwent single-lead PM implantation. Few days after discharge he developed deep vein thrombosis in situ of PM electro catheter insertion (poor compliance to anticoagulation therapy was reported) which improved after few days of regular therapy assumption. After few months anticoagulation therapy was dismitted due to etiology unknown-anemization requiring transfusion, but 20 days later he was once again admitted, this time because of pulmonary embolism. Trans thoracic echocardiography (TTE) enlightened a severely dysfunctioning right ventricle and a mass in right atrium hanging the wire. Trans oesophageal echocardiography was then performed showing hyper-reflective and highly mobile material with numerous ‘arborizations’. Intravenous heparin was started as pulmonary embolism therapy. Once infective etiology was excluded, total body computer tomography was performed to investigate a possible paraneoplastic origin. Presence of a meningioma was enlightened. Heart-team evaluation excluded catheter extraction in light of patient’s frailty, while thrombolysis was controindicated. Vitamin K antagonists was then started. At 1 month follow up no further embolic neither haemorrhagic events were reported. TTE showed a reduction in mass dimension and an improvement in right ventricle function.

Conclusions

In a guidelines-lacking field, VKA can be an effective option in cases of lead-related thrombosis when surgery or thrombolysis is not suitable. Further studies are needed to establish their real effectiveness in management of E-C-related endocavitary thrombi.
305 Usefulness of CHA2DS2-VASc scoring system for predicting risk of embolism in patients with cardiac tumours: a single-centre study
Authors: Magnani Ilenia , Paolisso Pasquale , Chiti Chiara , Angeli Francesco , Foa Alberto , Rinaldi Andrea , Bergamaschi Luca , Fabrizio Michele , Sansonetti Angelo , Stefanizzi Andrea , Armillotta Matteo , Galiè Nazzareno , Pizzi Carmine
Published: December 2021

Aims

The link between pro-protein convertase subtilisin/kexin 9 (PCSK9) and inflammatory-related disease has been supported in several experimental and human studies, which show how the protein could acts independent its canonical mechanism, by activation of inflammatory, apoptotic and immune pathways. Among these, TLR4/NFKB signalling pathway has been found to be one of the main pathways mediating the PCSK9-induced increase of pro-inflammatory and pro-thrombotic molecules, such as TNF-alpha, IL-6, IL-1, MCP-1, and TF. To investigate the direct involvement of hTLR4 in recognition of exogenous human recombinant (hr) PCSK9.

Methods and results

Experiments were carried out in three cell line: (i) HEK293-hTLR4-GFP cell lines obtained by stable co-transfection of HEK293 cells with the pUNO1-hTLR4-GFP, a plasmid expressing the hTLR4 gene fused to a GFP gene; (ii) HEK293-hTLR4+ cells obtained by co-transfection of hTLR4 receptor and its accessory proteins MD-2 and CD14, and an inducible secreted embryonic alkaline phosphatase (SEAP) reporter gene; (iii) HEK293-Null2 cells, a cell line lacking TLR4 expression, used as negative control. NFkB activity were measured by the SEAP reporter gene assay using a fluorescence detection method, while localization of hTLR4 and exogenous hrPCSK9 by confocal microscopy. hrPCSK9 (1 µg/mL) activates NFkB in HEK293-hTLR4+ cells [SEAP activity-OD 620 nm: from a baseline of 0.18 ± 0.06 to 0.68 ± 0.05 (N = 8), P < 0.001] to an extent comparable to lipopolysaccharide, the specific agonist of TLR4. Co-localization of hrPCSK9 and TLR4s was clearly documented by quantitative confocal microscopy in HEK293-hTLR4-GFP cell line, that comprises the analysis of more than 80 fields in ∼2.105 cells/well and showing a percentage of co-localization of ∼4% in membrane spots (P < 0.01).

Conclusions

Our data support the results reported in previous studies that attribute to PCSK9 a pathophysiological role in development of chronic inflammation and related-diseases such as atherothrombosis. A behavior that extends far beyond LDLR degradation, via a mechanism that might be mediated at least in part by recognition of PCSK9 by the TLRs and later activation of NFkB intracellular pathway. Future studies will be important to better investigate the specific binding site engaged in the PCSK9-TLR interaction and to discriminate the intracellular transduction pathways involved in this response, in order to provide a theoretical basis for the development of innovative therapeutic strategies.