bluuebunny/crossref_metadata_2025_split huggingface dataset:
879 STUDY OF ATRIOVENTRICULAR CONDUCTION DEFECTS AND ARRHYTHMIAS IN PATIENTS WITH DILATATIVE CARDIOMIOPATHY CLINICAL PROGNOSTIC VALUE OF THE GENETIC ANALYSIS USING NEXT GENERATION SEQUENCING AT THREE YEARS
Authors: Campisi Mariapaola , Di Bella Gianluca , De Gregorio Cesare , De Sarro Rosalba , Luongo Alfredo , Greco Vittoria , Vacirca Veronica , Luigi Alioto , La Rosa Maria Angela , Magliozzi Monia , Antonio Novelli , Silvana Briguglia 
Published: December 2022

Abstract

Background
Dilated cardiomyopathy is one of the most common cardiomyopathies that at the onset shows a with dysfunction, commonly expressed by the reduced ejection fraction (EF) and which can lead to heart transplantation. Cardiac "laminopathies" are part of the complex set of CMD.
In many cases they show a defect in myocardial electrical conduction. Mutations in the Lamina A / C genes have been associated with high arrhythmic risk and sudden cardiac death. In addition to these, there are others concerning the MYH7, TTN, MYBPC3 genes, related to the CMD phenotype and whose meaning is being defined.

Objectives
The project has the goal of evaluating the association of arrhythmic disorders with possible CMD phenotypes and the genetic mutations described above.

Materials and Methods
We studied 33 out of 100 patients screened for CMD on voluntary availability, suffering from different forms without significant coronary lesions. All of them underwent diagnostic-instrumental checks (ECG, Holter Ecg, echocardiogram and enzymatic profile) and followed for a minimum period of 18 months. At the same time at the ordinary check -up, genetic analyses were carried out through the NGS study of a panel of genes related to CMD in collaboration between the AOU
G. Martino di Messina and the Bambino Gesu’ Hospital in Rome.

Results
On 33 patients undergoing a genetic study, variants of uncertain significance (VUS) were identified: variant c.2359 C&gt; T (p.Arg787Cys) in the MYH7 gene reported in VarSome as probably pathogenetic in a symptomatic patient with endomyocardial biopsy CMD +; the variant c.54016G&gt; T in heterozygosity in the TTN gene, in another case, which at the protein level determines the introduction of the premature stop codon not described in scientific literature and classified according to the ACMG guidelines as a probably pathogenic variant; finally pathogenic variant c.949G&gt; A in heterozygosity in the LMNA gene, in a family with a history of sudden cardiac death with manifest CMD in some members with arrhythmias at follow up (ICD). and the presence of a second mutation; c.836G&gt; C in heterozygosity in the MYBPC3 gene, in other members of the same family with better clinical course.

Conclusions
Our study shows that there are VUS associated with cases of CMD. Within these, the presence of mutations in the lamina gene seem to be more closely related to the incidence of arrhythmias. Therefore, further studies are necessary for a better definition of all possible VUS also to carry out a differential diagnosis in the broad spectrum of cardiomyopathies.
263 GENETIC CAUSES OF CARDIOMYOPATHIES IN CHILDREN
Authors: Girolami Francesca , Gozzini Alessia , Passantino Silvia , Calabri Giovanni Battista , Spaziani Gaia , Porcedda Giulio , Bennati Elena , Favilli Silvia , Olivotto Iacopo 
Published: December 2022

Abstract

Background
The genetic background of paediatric cardiomyopathies is only partially resolved, because of their rarity and heterogeneity. However, the assessment of aetiology is of paramount importance in order to define prognosis and therapeutic choices. Moreover, the recognition of genetic causes is the basis for cascade screening in the family.

Aims
This study aimed to identify the genetic causes of cardiomyopathies in children evaluated and followed at our paediatric hospital.

Methods
A validated Next Generation Sequencing (NGS) target panel was performed in a cohort of 76 paediatric patients: 36 Hypertrophic Cardiomyopathy, (HCM), 24 Dilated Cardiomyopathy (DCM), 3 Restrictive Cardiomyopathy (RCM), 2 Left Ventricular Non Compaction (LVNC), 10 Arrhythmogenic Cardiomyopathy (AC) and one with a cardiac arrest. Genetic counselling was offered to parents. Furthermore, 9 patients with negative genes panel were selected for Whole Exome Sequencing (WES).

Results
By target genes panel analysis we identified a pathogenic or likely pathogenic variant in 32/76 patients (42%). Most genotyped patients had a sarcomeric aetiology and MYH7 (11/32, 34%), MYBPC3 (7/32, 22%) and thin-filaments genes (9/32, 28%) resulted the most mutated genes. 11/32 (34%) patients had a complex genotype. In one patient we found the rare coexistence of two independent monogenic diseases (Osteogenesis Imperfecta and HCM) due respectively to COL1A1 and MYH7 variants. Moreover, we identified five syndromic cases (5/32, 16%): three patients with Noonan Syndrome (one with SOS1 variant and two with PTPN11 variants), one boy with Danon Disease (with LAMP2 variant) and a newborn with Alström Syndrome (due to ALMS1 variants). By WES we identified a de novo variant in FLNC gene in a 7 years old child RCM, a Noonan Syndrome due to biallelic LZTR1 variants in a 9 years old child, two PLEC1 variants in a newborn with DCM and Epidermolysis bullosa, and a de novo NKX2-5 variant in a child with RCM.

Conclusions
A definitive molecular diagnosis could be obtained in a substantial proportion of children (42%). The genetic test results had direct implications for clinical management, to suggest therapeutic interventions. Moreover, predictive genetic testing in family members resulted very important for clinical follow-up and to establish the recurrence risk for subsequent pregnancies.
965 PROGNOSTIC VALUE OF CARDIOPULMONARY EXERCISE TESTING IN PATIENTS WITH TRANSTHYRETIN CARDIAC AMYLOIDOSIS
Authors: Silverii Maria Vittoria , Argiro Alessia , Baldasseroni Samuele , Zampieri Mattia , Fumagalli Carlo , Mazzoni Carlotta , Di Mario Carlo , Perfetto Federico , Fattirolli Francesco , Olivotto Iacopo , Cappelli Francesco 
Published: December 2022

Abstract

Background
ATTR-CA is associated with a progressive reduction in functional capacity. The prognostic role of CPET parameters and in particular of normalized peak VO2 (%ppVO2) remains to be thoroughly evaluated.

Methods
In this study 75 patients with ATTR-CA underwent cardiological evaluation and CPET in a National Referral Center for cardiac amyloidosis (Careggi University hospital, Florence).

Results
Fifty-seven patients (76%) had wild type ATTR. Median age was 80 (75-83) years, 68 patients (91%) were men. Peak oxygen consumption (14.1±4.1 ml/kg/min) and %ppVO2 (68.4±18.8%) were blunted. Twenty-seven (36%) patients had an abnormal pressure response to exercise. After a median follow-up of 25 (12-31) months the composite outcome of death or heart failure hospitalization was registered in 19 (25.3%) patients. At univariate analysis %ppVO2 was a stronger predictor for the composite outcome than peak VO2. %ppVO2 and NTproBNP remained associated with the composite outcome at multivariate analysis. The optimal predictive threshold for %ppVO2 was 62% (sensitivity: 71%; specificity: 68%; AUC:0.77, CI: 0.65-0.88). Patients with %ppVO2 ≤ 62%and NTproBNP &gt;3000pg had the worse prognosis with 1- and 2-year survival of 69±9% and 50±10%, respectively.

Conclusions
CPET is a safe and useful prognostic tool in patients with ATTR-CA. CPET may help to identify patients with advanced disease that may benefit of targeted therapy.
884 IMPLEMENTATION OF THERAPEUTIC STRATEGIES IN HFREF PATIENTS EQUIPPED WITH A DIGITAL APP
Authors: Augusto Florinda Maria , Curcio Antonio , Volpe Lorenzo , Romano Letizia Rosa , Cardia Giada , Fiore Davide , Malizia Biagio , Indolfi Ciro 
Published: December 2022

Abstract

Background
The comprehensive management of patients affected by heart failure with reduced ejection fraction (HFrEF) should pursue the goals of improving quality of life and reducing hospitalizations. Disease amelioration and cardiovascular mortality reduction are currently obtained by following guidelines-directed medical therapy (GDMT) that includes beta blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), diuretics and mineralocorticoid receptor antagonists (MRAs); recently, sodium-glucose cotransporter-2 inhibitors (SGLT2Is) have been added on top of previous drugs, but real-world data are yet missing. Whether clinical management of patients affected by HFrEF bearing either implantable cardioverter/defibrillators (ICD) or cardiac resynchronization therapy devices (CRT-D) with a digital application (App) might further reduce hospitalization for HF independently of GDMT yet needs to be addressed.

Materials and methods
From February 2021 to June 2022 a total of 28 patients with HFrEF in GDMT previously undergone ICD/CRT-D implants were remotely monitored at our institution. Patients were instructed to download a dedicated application (MYTRIAGEHF) on their smartphones/tablets. Clinical data were retrieved monthly, through the App, according to data sent from answering to the following questions: i) shortness of breath; ii) feet, legs or ankles swelling; iii) feeling tired; iv) fatigue, lack of energy; v) weight gain in the last 3 days; vi) inconstant intake of diuretic therapy. Medical therapy was optimized accordingly.

Results
Satisfaction and regular use of the app was reported by 18/28 patients; most data came from ICD-implanted subjects (n=12, 75% dual chamber; 25% single chamber), while remaining were CRT-D. Eleven percent of App-users received SGLT2 inhibitors on top of medical therapy. Remarkably, only one patient of the non-App group was treated with SGLT2 inhibitors on top of medical therapy. Remaining non-App users as well as patients not in therapy with SGLT2 inhibitors are lost at follow-up; they presented with ischemic etiology in most cases and significantly reduced ejection fraction compared to App-group.

Conclusion
Our cohort demonstrated that implementing therapy with SGLT2 inhibitors and/or digital applications that follow patients remotely are valuable tools for the optimization of HFrEF clinical condition. Although cause and effect cannot be decisive from this study, the utilization of remote monitoring for therapy adjustments requires further investigation. The use of digital technologies to ensure a more personalized decision-making process will lead better care assistance.
842 PREVALENCE AND MECHANISMS OF SEVERE MITRAL AND TRICUSPID RECURGITATION IN A HEART FAILURE OUTPATIENTS POPULATION
Authors: Biroli Matteo , Vanoni Francesca Pugno , Cannata Francesco , Pagliaro Beniamino Rosario , Pellegrino Marta , Villaschi Alessandro , Gasparini Gaia , Ardino Laura , Vrinceanu Elena Maricica , Pini Daniela 
Published: December 2022

Abstract

Introduction
Mitral regurgitation (MR) and tricuspid regurgitation (TR) are an established cause of morbidity and mortality in heart failure (HF) patients. The development of successful transcatheter therapies for mitral and tricuspid diseases have opened new therapeutic opportunities, in addition to guideline-directed medical therapy (GDMT) for HF. However, an accurate evaluation of the mechanisms of valve regurgitation is key to tailor the best treatment for each patient. This study aims at evaluating the prevalence and underlying mechanisms of at least moderate-to-severe (≥3+/4+) MR and/or TR in a cohort of HF outpatients.

Methods
We retrospectively analyzed the medical records of 1260 outpatients evaluated by our HF Unit between January 2020 and June 2021. All patients with echocardiographic evidence of at least moderate-to-severe MR and/or TR were included in the registry and a thorough review of echocardiographic images and collection of clinical data were also performed.

Results
Of the 1260 analyzed patients, 173 (13.7%) presented with at least moderate-to-severe MR and/or TR and were included in the registry. The mean age was 80±7 years and median ejection fraction was 45% (IQR 33; 55%) and 77 (45%) had HF of ischemic etiology. All patients were treated with maximal tolerated doses of GDMT and, when appropriate, with devices and myocardial revascularization.
At least moderate-to-severe MR and TR was observed in 7.3% (92/1260) and 9.3% (117/1260) patients, respectively. Patients with significant isolated MR were 56 (4.4%), with isolated TR were 81 (6.4%), while with both significant MR and TR were 36 (2.8%). Among patients with significant MR, 54% (50/92) had functional valvular defect, of whom 82% (41/50) had a ventricular etiology (18/41 with asymmetric tethering), while the 18%(9/50) an atrial one (3/9 with atriogenic tethering). Among patients with significant TR, 72.6% (85/117) had functional valvular defect, of whom 35.3% (30/85) had a ventricular etiology while 64.7% (55/85) presented with an atrial one.

Conclusion
Despite optimized GDMT, the prevalence of patients presenting with significant MR and TR was considerably high in our ambulatory HF population. This registry is the first study to comprehensively detail the mechanisms of atrioventricular valve regurgitations in a wide cohort of HF outpatients.
Further studies are needed to assess the reasons for a potential undertreatment and to identify the patients who would benefit the most from the percutaneous correction of their valvular defects.
677 PREDICTION OF RIGHT VENTRICULAR FAILURE AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: ROLE OF VASODILATOR CHALLENGE
Authors: Cacioli Giulio , Polizzi Vincenzo , Ciabatti Michele , Cristiano Ernesto , Pergolini Amedeo , Distefano Giada , Della Monica Paola Lilla , Comisso Marina , Piazza Vito , Sbaraglia Fabio , Musumeci Francesco 
Published: December 2022

Abstract
Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve.
Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP)(OR: 0.856, CI: 0.761–0.964; P=0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033).
Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.
39 ECHOCARDIOGRAPHIC FINDING BETWEEN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION IN TREATMENT WITH ARNI AND SGLT2I
Authors: Ceci Vincenzo , Mazzeo Pietro , Ferrara Salvatore , Nardella Luigi , Tricarico Lucia , Alfieri Simona , Croella Francesca , Amatruda Marco , Granatiero Michele , D´alessandro Damiano , Di Nunno Nicola , Pugliese Rosanna , Noviello Giulia , Correale Michele , Stabile Egenio , Stabile Eugenio , Iacoviello Massimo , Di Biase Matteo , Brunetti Natale D 
Published: December 2022

Abstract

Background
Cardiac remodelling is an adverse phenomenon linked to heart failure progression. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and β-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling were demonstrated. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described.

Aim of study
to evaluate possible echocardiographic differences between patients with HFrEF in treatment with ARNI or SGLT2I and patients with HFrEF in therapy with ARNI plus SGLT2i.

Materials
Between June 2021 and April 2022, consecutive patients with HFrEF underwent to conventional and advanced echocardography (TDI, 2DSTE). After 3 month, these patients underwent to echocardiographic follow-up.

Results
76 patients (68 male, 66,51±9,68 years old) with HFrEF were enrolled in the study. After 3 month of therapy, there was an inverse relation between number of HFrEF drugs (0, 1 or 2) and echocardiographic parameters [E/E’ (r: -0,28; p: 0,036) and E/A (r: -0,37; p: 0,012)].

Conclusions
About cardiac remodelling, there are not significant echocardiographic differeces but a better trend for the diastolic dysfunction in patients with HFrEF in treatment with ARNI plus SGLT2i vs HFrEF patients in therapy with ARNI or SGLT2i was showed.
268 IMPACT OF AORTIC REGURGITATION ON LONG TERM OUTCOME IN HEART FAILURE AND PRESERVED EJECTION FRACTION
Authors: De Colle Cristina , Paolisso Pasquale , Gallinoro Emanuele , Bertolone Dario , Mileva Niya , Fabbricatore Davide , Valeriano Chiara , Mancusi Costantino , Collet Carlos , Vanderheyden Marc , De Luca Nicola , Van Camp Guy , Barbato Emanuele , Bartunek Jozef , Penicka Martin 
Published: December 2022

Abstract

Background
Aortic Regurgitation (AR) may aggravate the clinical course in patients with heart failure and preserved ejection fraction (HFpEF) by increasing filling pressures and triggering LV remodelling.

Objective
To assess AR's prevalence and long-term prognostic implications in patients with HFpEF.

Methods
The study population consisted of 458 consecutive patients (age 77.5 ± 9.2 y, 57.9% females) hospitalized with de novo or worsened HFpEF. Patients with more than moderate aortic and/or mitral valve disease were excluded. Data on cardiovascular death, HF re-hospitalization and their composite (MACE) were collected.

Results
Out of 309 (67.5%) patients with any AR, 156 (34.0%) and 153 (33.5%) had mild-AR and moderate-AR, respectively. The remaining 149 (32.5%) individuals had no-AR. Patients with versus without AR were significantly older with larger LV and LA volumes and a higher prevalence of diastolic dysfunction (all p &lt; 0.05). During a median follow-up of 33 ± 25 months, a total of 114 patients (24.9%) died from cardiovascular causes, 126 patients (27.5%) were re-hospitalized for HF, while 272 (59.4%) had the composite endpoint (MACE). In multivariable Cox regression analysis, any AR emerged as an only independent predictor of MACE (HR=1.90, 95%CI 1.26–2.87, p=0.002). Mild-AR and Moderate AR increased the risk of MACE by 77% and 92%, respectively, compared to the No-AR.

Conclusions
In patients with HFpEF, mild-to-moderate AR is highly prevalent, and it seems to identify individuals with worse long-term outcomes. This suggests that even mild AR should be considered a high-risk prognostic marker in patients with HFpEF.
393 PERIODIC BREATHING: WHAT HAPPENS IN THE MUSCLE?
Authors: De Martino Fabiana , Mattavelli Irene , Vignati Carlo , Salvioni Elisabetta , Campodonico Jeness , Mapelli Massimo , Gugliandolo Paola , Agostoni Piergiuseppe 
Published: December 2022

Abstract
Periodic breathing (PB) is a recognized sign of poor prognosis in heart failure (HF). It is defined as a cyclic fluctuation of minute ventilation, and oxygen uptake (V̇O2) and carbon dioxide elimination (V̇CO2) at the lungs. It is unknow whether PB influences O2 availability in the cardiac, respiratory and locomotor muscles. To evaluate whether O2 availability at the muscles was affected by PB, we measured at rest, continuously and simultaneously, ventilation, ventilatory gas exchange, arterial hemoglobin O2 saturation and oxygenated/deoxygenated haemoglobin (O2Hb/HHb) content over the quadriceps by near infra-red spectroscopy (NIRS) in a patient with severe HF due to a dilated cardiomyopathy with severe biventricular dysfunction with PB at rest. NIRS application in clinical medicine started after the observation that biological tissues are quite transparent to light in the near infrared spectrum (i.e.700-1,300 nm), the second critical element that enables the use of NIRS is the oxygenation-dependent light absorbing characteristics of haemoglobin (Hb): by applying different light impulse wavelengths, the relative changes in O2Hb and HHb concentration in skeletal muscle can be monitored.
The left panel shows cyclic fluctuation of ventilation, V̇O2, V̇CO2, PetO2 and PetCO2 patterns, which are partially out of phase between each other and respiratory exchange ratio pattern, and haemoglobin O2 saturation shows a cyclic pattern (95-90%). The cycle length of ventilation was 110 ± 6 s with an amplitude of 28.9 ± 5.1 l/min. NIRS (upper right panel) shows a directionally opposite fluctuation of O2Hb and HHb with a cycle length similar to that observed with ventilation. The average fluctuation on 6 consecutive cycles was 2.95% ± 0.27 (p&lt;0.0001) and 2.73% ± 0.27 (p&lt;0.0001) for O2Hb and HHb respectively. Total Hb was not significantly affected by PB in the muscle, 0.22%±0.38 (p=ns). The present study is the first recording of periodic oscillations of O2 saturated and desaturated Hb concentration at the muscular level at rest in a patient with severe HF and PB: we speculate that the cyclic ventilatory pattern is responsible for a cycling of ventilation and perfusion coupling in the lung. This so-called ventilation/perfusion mismatch induces cyclic fluctuation of blood flow to perfused but unventilated or poorly ventilated (shunt and low V̇A/Q) lung zones and to unperfused or poorly perfused (high V̇A/Q and dead space) ventilated lung zones.