bluuebunny/crossref_metadata_2025 huggingface dataset:
144 LONG-TERM PROGNOSTIC IMPACT OF SUBCLINICAL MYOCARDIAL DYSFUNCTION IN PATIENTS RECOVERED FROM COVID-19
Authors: Cannata Francesco , Pinto Giuseppe , Chiarito Mauro , Maurina Matteo , Condello Francesco , Bombace Sara , Villaschi Alessandro , Novelli Laura , Stankowski Kamil , Liccardo Gaetano , Gasparini Gaia , Donia Dario , Celata Anastasia , My Ilaria , Kallikourdis Marinos , Figliozzi Stefano , Mantovani Riccardo , Fazzari Fabio , Bragato Renato Maria , Condorelli Gianluigi , Stefanini Giulio Giuseppe
Published: December 2022

Aims

Cardiovascular sequelae may occur in patients recovered from COVID-19. Recent studies have detected a considerable incidence of subclinical myocardial dysfunction – assessed with speckle-tracking echocardiography – and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia.

Methods and Results

We prospectively followed-up 110 patients hospitalized at our Institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 6-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization and all-cause mortality. A subclinical myocardial dysfunction – defined as an impairment of left ventricular global longitudinal strain (≥ -18%) - was identified at 6-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (AUC: 0.73) and resulted a strong independent predictor of extended MACE in a multivariate regression analysis (OR 9.29, 95%CI 2.20–39.3, p=0.002). Long-COVID condition was not associated with a worse long-term prognosis, instead.

Conclusion

In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one third of the whole population at 6-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimise the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has not prognostic relevance.
614 PREDICTIVE ROLE OF ECHOCARDIOGRAPHIC PULMONARY TO LEFT ATRIAL RATIO FOR IN-HOSPITAL DEATH IN PATIENTS WITH COVID-19
Authors: Pizzoferrato Giovanni , Esposto Daniele , Alberani Angela , Falasca Katia , Vecchiet Jacopo , Mennuni Marco , Patti Giuseppe , Gallina Sabina , Renda Giulia
Published: December 2022

Background and aims

Echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') represents an accurate and sensitive non-invasive tool to estimate trans-pulmonary pressure gradient, showing a sensitivity for pre-capillary pulmonary obstruction higher than traditional echocardiographic measures. The prognostic value of ePLAR in patients with coronavirus disease-2019 (COVID-19) remains unknown.

We aimed to investigate the predictive role of ePLAR on mortality in COVID-19 patients.

Methods

One hundred consecutive patients admitted in two Italian institutions for COVID-19 undergoing early echocardiographic examination were included. ePLAR was determined from the maximum tricuspid regurgitation velocity at continuous wave Doppler (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e′-wave ratio (TRVmax/E:e′). Main outcome measure was in-hospital death.

Results

Patients who died during hospitalization had a higher prevalence of tricuspid regurgitation, higher ePLAR and right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR >0.28 m/s showed increased in-hospital mortality compared to those having ePLAR ≤0.28 m/s (27% vs 10.8%, p=0.05, Figure). A Cox model of multivariate analysis demonstrated that an ePLAR >0.28 m/s was independently associated with increased risk of death (HR 5.07, 95% CI 1.04-24.50, p=0.043), particularly among patients with increased pulmonary arterial pressure.

Conclusions

A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially to guide strategies of diagnosis and treatment.
829 IMPACT OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS ON CARDIAC REMODELLING IN LOW RISK PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Del Giudice Carmen , Fabiani Dario , D´aquino Malvezzi Marco Caracciolo , Scognamiglio Gabriella , Pezzullo Enrica , Caso Valentina , Castagnola Patrizia , Volpe Alessandra , Liccardo Biagio , Nigro Gerardo , Golino Paolo , Russo Vincenzo
Published: December 2022

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated to a reduced risk of major adverse cardiovascular events in type 2 diabetes mellitus (T2DM) patients. Subclinical left ventricular (LV) systolic disfunction has been observed in DM patients, even if ejection fraction is preserved. The impact of SGLT2i on cardiac structure and function is still unclear. Our aim was to evaluate the effects of SGLT2i on LV remodelling and global longitudinal strain (GLS) in patients with well compensated TIIDM.

Methods

Between November 2021 to April 2022, we prospectively evaluated 35 consecutives subjects with TIIDM in need of SGLT2i according to their referring physician. Main inclusion criteria were preserved ejection fraction (EF>50%), no history of heart failure and coronary artery disease, and the lack of moderate to severe valvular heart disease and chronic kidney disease (EGFR <50%). Conventional and speckle tracking echocardiography were performed at baseline and after 6 months of treatment.

Results

17 patients have been evaluated for statistical analysis (6% F, mean age 65± 9 years). GLS (p=0,007) and EF (p=0.01) reached statistically significance after 6 months therapy. Moreover on ECG analysis, we found significant reduction in P-wave dispersion (p =0.019). However no statistically significant changes in diastolic function parameters and Myocardial Work indices have been found.

Conclusions

Our study showed that SGLT2i treatment in people with T2DM may display a positive effect on LV remodelling and improve GLS, even in patients with low-risk DM.

Keywords: Diabetes mellitus; SGLT2 inhibitors; Speckle tracking echocardiography; Left ventricular systolic function; Cardiac remodelling.
769 EFFECT OF GLUCOSE LOWERING AGENTS ON CARDIAC AUTONOMIC FUNCTION AND STRUCTURE IN TYPE 2 DIABETES MELLITUS
Authors: Veneziano Francesco Antonio , Cavallari Ilaria , Grigioni Francesco , Tuccinardi Dario , Maddaloni Ernesto , Indennidate Carla , Pieralice Silvia , Napoli Nicola , Buzzetti Raffaella
Published: December 2022

Effects of novel glucose-lowering agents on cardiac autonomic function and structure in type 2 diabetes

Ilaria Cavallari, Ernesto Maddaloni, Francesco Veneziano, Carla Indennidate, Maria Valeria Giaccari, Dario Tuccinardi, Silvia Pieralice, Nicola Napoli, Raffaella Buzzetti, Francesco Grigioni

Background

Novel glucose-lowering agents, such as sodium glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, have the potential to reduce major adverse cardiovascular events among people with type 2 diabetes. However, mechanisms behind their cardiovascular protection and the implications of positive chronotropic effects of GLP-1 receptor agonists are not fully understood.

Purpose

To elucidate and compare the effects of novel glucose-lowering agents on cardiac autonomic function and structure.

Methods

This prospective observational study included subjects with type 2 diabetes and either a history of established cardiovascular disease or multiple risk factors and early initiation (within 2 weeks) of a SGLT-2 inhibitor or a GLP-1 receptor agonist on top of standard of care. Patients were followed for a median of 2 months. As per study protocol, background medical therapy should have remained stable for the entire duration of the study. Cardiac autonomic reflex tests (heart rate response to a deep breathing and to standing) and echocardiography were performed in all patients at baseline and at the end of follow-up. Endpoints were changes from baseline of E/I ratio, 30:15 ratio and indices of cardiac structure and function.

Results

A total of 37 patients completed follow-up, of whom 20 were on SGLT-2 inhibitors and 17 on GLP-1 receptor agonists. Mean age was 69 years, mean disease duration was 14 years and mean HbA1c value was 7.5%. Cardiac autonomic dysfunction, defined as at least an abnormal test, was found in 19% of patients (n=7). At a median follow-up of 2 months, there were no differences from baseline in heart rate response to a deep breathing test (p=0.92) and to standing (p=0.86). No differences were found when patients were stratified according to drug class. Among echocardiographic parameters, significant reductions of left ventricular mass (300.5±73.3 vs 280.4±68.3 g/m2, p=0.048) and left atrial volume (61.3±29.4 vs 54.7±18.0 ml, p=0.034) were found with no interaction by drug class. Left ventricular end-diastolic and systolic volumes, ejection fraction, filling pressures and pulmonary artery pressure did not substantially change.

Conclusions

In a population of patients with type 2 diabetes, short-term treatment with novel glucose-lowering agents significantly reduced left ventricular mass and left atrial volume but did not affect cardiac autonomic function.
820 VARIABLE EXPRESSIVITY OF SCN5A MUTATION IN A FAMILY WITH CARDIAC DYSFUNCTION AND SUSPECTED BRUGADA SYNDROME
Authors: Malizia Biagio , Curcio Antonio , Rodolfo Iuliano , Colao Emma , Pingitore Elisabetta , Cardia Giada , Romano Letizia Rosa , Pasceri Eugenia , Aquila Iolanda , Indolfi Ciro
Published: December 2022

Background

Inherited arrhythmogenic diseases (IADs) represent a group of life-threatening genetic cardiomyopathies that predispose young individuals to sudden cardiac death (SCD), often in the absence of structural cardiac alterations. Some IADs share mutations in genes encoding for surface membrane ion channels, and the gene for the alpha subunit of the voltage-dependent channel Nav1.5 (SCN5A) is among the ones mostly involved. Brugada syndrome represents one of the possible spectrum deriving from SCN5A gene mutations, and it is characterized by “loss-of-function” genetic alterations. Interestingly, both loss-of and gain-of-function mutations have been associated with familial dilated cardiomyopathy (DCM).

Materials and Methods

In the context of an Italian Ministry of Health-funded research project devoted to identify genetic isolates of IADs in the Calabria region, we found a family affected by different cardiovascular manifestations including cardiac dysfunction, ventricular tachyarrhythmias, atrioventricular block and suspected Brugada syndrome pattern in first-degree relatives in association with a newly identified SCN5A mutation.

Results

The proband came to our attention with a diagnosis of DCM, echocardiographic assessment of reduced left ventricular ejection fraction (EF) to 38%, high occurrence of premature ventricular complexes (PVCs) and first-degree atrioventricular block (PR = 240ms) at electrocardiogram. In spite of negative electrophysiologic study, he underwent implantable cardioverter defibrillator implantation (ICD), hypothesizing lamin A/C mutation; genetic analysis turned out negative for lamin A/C and CACNA1C, while a SCN5A gene mutation (c.4554 G<T p.Gln1518His) was detected. Proband's sons and his brother underwent clinical evaluations as well as genetic testing: the second son's ECG showed first-degree AV block (PR = 220ms), QTc interval 426ms, and coved type ST-segment elevation of 1.5mm, in the context of normal cardiac function; the remaining male (see Figure 1) was asymptomatic, while the daughter had a hypokinetic non-dilated cardiomyopathy. The proband's brother had first-degree AV block and very frequent monomorphic ventricular couplets.

Conclusions

These phenotypic differences in first degree-relatives, can be explained by the concept of variable expressivity of genes, according to which individuals carrying the same mutation can have different clinical features. Therefore, the search for genetic mutations assumes a preponderant role for stratifying the risk of SCN5A-related diseases and to adopt appropriate diagnostic and therapeutic strategies.
514 ATAXIA TELANGIECTASIA MUTATED PROTEIN MODULATES GLUCOSE AND LIPID METABOLISM IN THE HEART
Authors: Paolillo Roberta , D´apice Stefania , Caterino Marianna , Pezone Antonio , Iole Danila , Polese Pina , Pentella Tommaso , Ruoppolo Margherita , Enrico Avvedimento Vittorio , Esposito Giovanni , Perrino Cinzia
Published: December 2022

Background

Ataxia Telangiectasia Mutated (ATM) protein kinase is the major sensor of DNA damage response (DDR) and oxidative stress, variously implicated in cellular metabolism. Previous studies on ATM functions in the heart have produced conflicting results. Here we hypothesized that ATM might regulate cardiomyocyte metabolic homeostasis and function.

Methods

Atm-mutated mice (Atm-/-) and their wild-type littermates (Atm+/+) were used to assess the effects of ATM inactivation on cardiomyocyte hypertrophy, cardiac structure, function, DDR and metabolism under sham conditions or after pressure overload by transverse aortic constriction (TAC).

Results

ATM inactivation induced cardiomyocyte hypertrophy (FIG.1 A), fetal gene expression re-activation and a specific metabolomic signature in the heart, characterized by significant accumulation of pyruvate, branched chain amino-acids, short-medium acyl-carnitines and metabolites of tricarboxylic acid cycle (FIG.1 C, D),. Importantly, pyruvate was trapped in the cytosol because mitochondrial carriers were suppressed and the enzymes that process pyruvate were dysregulated. As a consequence of pyruvate metabolic block, fatty acids oxidation was inefficient and resulted in the accumulation of acyl-carnitines and insulin resistance. Although these metabolic changes were present constitutively in Atm-/- mice, they were amplified by TAC, which rapidly induced heart failure (FIG.1 B) in Atm-/- mice. ATM inactivation also increased basal and TAC-induced genomic stress in cardiomyocytes, as shown by the levels of p-γ-H2AX, 8-oxodG glycosylase (OGG1/2) and apurinic site nuclease (APE1). Cardiac metabolic changes induced by ATM loss (rise of pyruvate, lactate and succinate levels) were also present in Atm-/- brains, although the basal conditions were different.

Conclusions

ATM rewires the metabolism of cardiac cells by inducing glycolysis and fatty acids oxidation. Combining metabolomic, DNA damage and cardiac phenotypes, we deduce that ATM stimulates glycolysis to repair DNA lesions and protect the heart against stress-induced dysfunction.
527 CIRCULATING SMALL NUCLEOLAR RNA SNORD3A AS A NOVEL PREDICTIVE BIOMARKERS OF HEART FAILURE
Authors: Paolillo Roberta , D´apice Stefania , Schiattarella Giacomo Gabriele , Holley Christopher , Della Corte Alessandro , Bancone Ciro , Esposito Giovanni , Perrino Cinzia
Published: December 2022

Background

Despite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of myocardial human tissues, identification of circulating biomarkers mirroring myocardial pathological signaling pathways, especially in peripheral blood mononuclear cells (PBMC) is expected to be extremely relevant. Small Nucleolar RNAs (snoRNAs) have been shown to play important roles in various cellular physiological processes. However, the connection between snoRNAs and pathological dysfunction in the heart or peripheral blood mononuclear cells (PBMC) is still poorly understood.

Purpose

To identify novel circulating PBMC biomarkers linked to myocardial dysfunction and HF.

Methods

: Myocardial left ventricle (LV) samples and PBMC were obtained from patients affected by ischemic HF (HF, n =13) undergoing heart transplantation and control donors (CD, n=7) and analyzed by RNA sequencing analysis (RNASeq). SNORD3A expression levels in the different groups were evaluated by quantitative real-time PCR. HF was induced in 8-week-old wild type C57BL/6 mice by transverse aortic constriction (TAC). Sham-operated mice (sham) were used as controls. After twelve-week-TAC (12w) or sham operation, mice were anesthetized, cardiac function was analyzed by echocardiography, and cardiac/PBMC samples were collected after sacrifice. In order to test the role of SNORD3A in cardiomyocyte hypoxia, H9C2 cardiomyoblasts were transfected with SNORD3A-targeted antisense oligonucleotides (ASO) and cell survival was analyzed.

Results

RnaSeq analysis identified a small set of genes differentially expressed in the heart and PBMC from HF patients. Among these, SNORD3A was up-regulated in cardiac and PBMC samples from HF patients compared to CD (Figure 1A). Similarly, in murine HF induced by 12w TAC, SNORD3A levels were increased by rtPCR, both in the heart and PBMC (Figure 1B). SNORD3A expression levels were also significantly increased in H9C2 cells exposed to in vitro hypoxia (Figure 1C). Interestingly, H9C2 transfection with SNORD3A-specific ASO significantly reduced hypoxia-induced SNORD3A upregulation and reduced hypoxia-induced cell death (Figure 1D).

Conclusions

In this study, we identify SNORD3A as a novel possible biomarker in human HF, similarly up-regulated in the heart and PBMC, induced by hypoxia in vitro and modulating cell survival.
953 KEY ROLE OF GENETIC ANALYSIS IN A FAMILIAR CASE OF HYPERTROPHIC CARDIAC PHENOTYPE AND VENTRICULAR PREEXCITATION RELATED TO PRKAG2 GENE MUTATION
Authors: Scimé Irene , Rubino Claudia , Micciché Serena , Lo Nigro Maria Claudia , Crea Pasquale , Dattilo Giuseppe , Carerj Scipione , Luzza Francesco , Micari Antonio , Di Bella Gianluca
Published: December 2022

A 38-year-old male patient (A2) was referred to our ambulatory for paroxysmal atrial fibrillation in young age and ventricular preexcitation.

Echocardiographic evaluation showed left ventricle hypertrophy (localized particularly at inter-ventricular septum (SIV) and normal LV ejection fraction. He also had a positive family history of hypertrophic cardiomyopathy since the latter was already diagnosed with the maternal grandmother (M0), the mother (M1) and the two brothers (A1 and A3). His father was apparently healthy (P1- consanguineous third degree of the mother M1). Specifically, the mother (M1) was suffering from non-obstructive hypertrophic cardiomyopathy, and tachy-brady (paroxysmal atrial flutter, sinus arrest) syndrome requiring pacemaker implantation. The firstborn (A1) was affected by paroxysmal atrial fibrillation, ventricular prexcitation and mild hypertrophy of the interventricular septum (SIV). The third child (A3) had a diagnosis of hypertrophic cardiomyopathy and a history of successfully ablation of a left postero-septal accessory pathway. A3 suffered also by paroxysmal typical atrial common flutter.

Genetic analysis of the proband A2 confirmed a heterozygous pathological mutation of the PRKAG2 gene. Thus, genetic analysis was extended to the other two brothers A1 and A3 and the mother. We proposed to the all three brothers electrophysiological study in order to assess arrhythmic substrate and appropriate therapy (strict FUP, PM or ICD implantation).

Mutation of the PRKAG2 gene is a rare disease, classified as non-lysosomal cardiac glycogenosis with clinical onset in late adolescence or in the third decade of life and presents an autosomal dominant inheritance with complete penetrance. It is associated with cardiac arrhythmias, such as ventricular preexcitation (Wolff-Parkinson-White syndrome), sinus node disease, atrioventricular block, atrial fibrillation.

Genetic analysis has a crucial role especially in the evaluation of inheritance with autosomal dominant transmission and regarding the prognostic impact, since PRKAG2 gene mutation involved a greater arrhythmic risk comparing with other subtypes of hypertrophic cardiomyopathy. Affected patients should be closely monitored to facilitate early detection of arrhythmia and conduction problems.

PRKAG2 mutation should be considered in patients with LVH who develop AF or require permanent pacemakers at a young age. Early recognition is important to allow prompt identification and appropriate management of genetic carriers.
1021 VASODILATOR CHALLENGE TEST WITH ISOSORBIDE DINITRATE DURING RIGHT HEART CATHETERIZATION: ANY ROLE IN POST-CAPILLARY PULMONARY HYPERTENSION PHENOTYPING?
Authors: Giudice Francesco Lo , Baccelli Andrea
Published: December 2022

Background and aims

Despite recent advances in the diagnosis and treatment of pulmonary arterial hypertension (PAH), pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF-PH) still represents a diagnostic and therapeutic dilemma. Among HFpEF-PH patients, discriminating between isolated post-capillary (IpcPH) from combined post-/pre-capillary (CpcPH) PH, and especially a better understanding of the latter, is still challenging. Such a distinction can have an important therapeutic impact, as new evidence suggests that therapy with PDE5i might be beneficial in specific CpcPH patients [Humbert M, Kovacs G, Hoeper M et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022]. Our study sought to comprehensively assess and explore the role of Isosorbide Dinitrate (ISDN) testing in HFpEF-PH phenotyping.

Methods

From November 2019, all patients referred to our service to investigate PH and elevated pulmonary artery wedge pressures (PAWP) at rest or after fluid challenge at the time of the right heart catheterization, had a vasodilator test with a slow IV bolus of ISDN (with a specific protocol). Clinical, echocardiographic and hemodynamic data were collected.

Results

38 patients (25 CpcPH, 13 IpcPH) were included in the analysis. Baseline characteristics are shown in table 1. Based on ISDN response, patients were stratified into three groups (Table 2). Group 1 showed a lack of significant pressures reduction after ISDN (“vasodilator negative Cpc-PH”). Group 2 displayed a significant reduction of PAWP < 15 mmHg, but persistent PH and high Pulmonary Vascular Resistance (PVR) (“vasodilator positive Cpc-PH”). Group 3 were patients whose pulmonary pressures normalized after ISDN (Ipc-PH).

Conclusions

albeit on a small group of patients, our preliminary results warrant further studies on the potential role of ISDN in better phenotyping HFpEF-PH and identify subgroups of patients who might benefit from PH specific therapies (“vasodilator positive Cpc-PH”) after treatment of the underling left heart disease.
488 NOVEL POTASSIUM BINDERS IMPROVES RAASI THERAPY OPTIMIZATION IN HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Esposito Immacolata , Dell´aversana Simona , Basile Christian , Chirico Alfonsina , Colella Angela , Ambrosio Antonio , Esposito Gennaro , Marzano Federica , Amato Chiara , Gargiulo Paola , Perrone-filardi Pasquale , Paolillo Stefania
Published: December 2022

Background

Hyperkalemia (HK) often occurs among patients with heart failure (HF), particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest variations from normal potassium levels raise the risk of mortality and prompt patients to limit or cease disease-modifying treatment. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are approved for treatment of HK, but whether this results in a real optimization of HF treatment remains to be seen.

Objectives

To assess the efficacy of NPB on the persistence of therapy with RAASi in HF patients.

Methods

PubMed and Web of Science were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified main outcome was the proportion of HF patients achieving target dose of RAASi. Secondary outcomes were the reduction in potassium levels, hyperkalemia events and persistence of therapy with RAASi in the overall population.

Results

Eight studies, with a total of 2247 patients were included. NPB improved optimization of RAASi therapy in HF compared to placebo by 21% (95% CI: 5% – 39%), decreased potassium levels by 0.48 mEq/L (95% CI: 0.28–0.67) and decreased hyperkalemia events by 53% (95% CI: 34% – 64%) and improved the proportion of the overall study population on RAASi therapy by 28% (95% CI: 7% – 52%).

Conclusion

The present meta-analysis suggests that NPB are favorable in improving the proportion of patients on RAASi therapy, whether they have HF or not, in reducing potassium levels and hyperkalemia events.
782 RATIONALE AND DESIGN OF EFI-CHF (ENDOTHELIAL FUNCTION IN PATIENTS WITH CHRONIC HEART FAILURE TREATED BY SGLT2I)STUDY
Authors: Di Nunno Nicola , D´alessandro Damiano , Granatiero Michele , Tricarico Lucia , Mazzeo Pietro , Ceci Vincenzo , Amatruda Marco , Pugliese Rosanna , Alfieri Simona , Croella Francesca , Mallardi Adriana , Leopizzi Alessandra , Correale Michele , Iacoviello Massimo , Di Biase Matteo , Stabile Eugenio , Brunetti Natale D
Published: December 2022

Background

Chronic heart failure (CHF) is characterized by endothelial dysfunction (ED). Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycemic agents for type 2 diabetes mellitus (T2DM) that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. Nevertheless, it is unclear whether the benefits of SGLT-2i therapy also rely on the endothelial function in patients with CHF.

Aim of the study

To evaluate the effect of SGLT-2i on endothelial function through flow-mediated dilatation (FMD) in patients with CHF at baseline and after 3 months.

Design and Methods

EFI-CHF is a multi-center, prospective study that will evaluate the effect of SGLT-2i on endothelial function in patients with chronic stable heart failure across the left ventricular ejection fraction (LVEF) spectrum. Patients with NYHA class II/III symptoms, eGFR> 25 mL/min/1.73 m2, age >18 years will be enroll. Exclusion criteria are type 1 diabetes mellitus (T1DM), previous amputation surgery, recurrent urinary tract infections. For each patient medical history, clinical and biochemistry data will be collected. Starting treatment with SGLT2 inhibitors will be included. All patients will undergo FMD in an ambulatory setting, at time of enrolment and after 3 months of begin of study.

Results

The primary endpoint will be the improvement of endothelial function as assessed by FMD. An univariate and multivariate analysis will be performed to search for predictors of improvement of endothelian function.

Conclusions

The EFI-CHF will determine whether SGLT2i therapy improves endothelian function in patients with CHF starting SGLT2i therapy.
974 SACUBITRIL-VALSARTAN AMELIORATES MITOCHONDRIAL FUNCTION IN A MURINE MODEL OF ISOPROTERENOL-INDUCED LEFT VENTRICULAR DYSFUNCTION
Authors: Del Franco AnnaMaria , Carecci Alessandro , Ferrari Chen Yu Fu , Forini Francesca , Nicolini Giuseppina , Castiglione Vincenzo , Gentile Francesco , Kusmic Claudia , Emdin Michele , Vergaro Giuseppe
Published: December 2022

Background

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, has proven to promote left ventricular (LV) reverse remodelling in patients with heart failure (HF) with reduced ejection fraction. However, its molecular and tissue effects have not been fully elucidated yet, due to the paucity of preclinical studies, mostly based on ischaemic models.

Aim

To evaluate the effects of sacubitril/valsartan on LV remodelling and cardiac mitochondrial function in a murine model of non-ischaemic LV dysfunction.

Methods

Adult male transgenic mice with cardiac-specific hyperaldosteronism (AS mice) received subcutaneous isoproterenol injection (300 mg/kg BID over two days), to induce LV systolic dysfunction. Mice were then randomized to a 2-week treatment with saline (0,2 mL BID) (ISO-AS n=15), valsartan (26 mg/kg in 0,2 mL of saline) (ISO+V n=12) or sacubitril/valsartan (57 mg/kg in 0,2 mL of saline) (ISO+S/V n=12). Echocardiography was performed at baseline, day 7, 15 and 21 of treatment. Mice were sacrificed at day 21, and histological and immunochemical assays were performed. A control group (Ctrl-AS n=8), not receiving isoproterenol nor pharmacological treatment, was obtained.

Results

Treatment with sacubitril/valsartan, but not with valsartan, induced a significant improvement of LV ejection fraction (p=0.009 vs ISO-AS) and fractional shortening (p= 0.032 vs ISO-AS) after 2-week treatment. In both ISO+V and ISO+S/V groups, a trend toward reduction of the extent of myocardial fibrosis was detected at histological analysis, confirmed by the lower cardiac collagen 1/3 expression ratio (p= 0.074). ISO+V and ISO+S/V groups showed a significant recovery of mitochondrial morphology and inner membrane function meant for oxidative phosphorylation. Additionally, both treatments reverted the alterations of the expression of genes involved in mitochondrial distribution, transport of organic/inorganic compounds, myocardial cell death, and response to the superoxide.

Conclusion

In a murine model of non-ischaemic HF, sacubitril/valsartan proved to have beneficial effects on LV remodelling and on cardiac energetics by improving mitochondrial activity.
1153 SODIUM GLUCOSE COTRANSPORTER-2 INHIBITORS ELIGIBILITY IN PATIENTS WITH HEART FAILURE ACROSS THE SPECTRUM OF EJECTION FRACTION
Authors: Ferrari Ilaria , Monzo Luca
Published: December 2022

Background

Large randomized clinical trials demonstrated that sodium–glucose co-transporter-2 (SGLT2) inhibitors reduced adverse cardiovascular outcomes in patients with heart failure (HF) with both reduced (HFrEF) and preserved (HFpEF) ejection fraction. Despite the high potential to change clinical practice, the strict trial selection criteria might reduce external validity of these findings.

Purpose

The aim of the study was to evaluate the proportion of outpatients with HF that would be eligible for SGLT2 inhibitors across the spectrum of left ventricular ejection fraction (LVEF) in a contemporary real-world population.

Methods

We retrospectively evaluated patients with chronic stable HF followed-up at the outpatient clinic of our institution. HFrEF (LVEF <40%) patients’ eligibility was assessed according to the entry criteria of DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials and to US Food and Drug Administration (FDA) label criteria (only dapagliflozin). In HFpEF group (LVEF>40%), Eligibility to SGLT2 inhibitors was based both strict and pragmatic (most likely influencing treatment decisions in clinical practice)

EMPEROR- Preserved inclusion/exclusion criteria (empagliflozin).

Results

A total of 642 HF patients (441 HFrEF; 201 HFpEF) was studied. Among HFrEF patients, according to the major inclusion and exclusion criteria from DAPA-HF and EMPEROR-Reduced trials, 198 (45%) patients would be candidates for initiation of both dapagliflozin and empagliflozin, 61 (14%) would be eligible only to dapagliflozin and 23 (5%) only to empagliflozin, On the other hand, in HFpEF patients, 125 (62%) patients would be candidates for initiation of empagliflozin based on the EMPEROR-Preserved trial selection criteria. No significant differences were found between diabetic and non-diabetic patients in both HFrEF (p=0.23) and HFpEF (p=0.37). In patients not suitable for gliflozins treatment the major determinant of ineligibility was the failure to achieve the predefined NTproBNP inclusion threshold. Excluding NTproBNP as per FDA label criteria, dapagliflozin eligibility increased to 86%. Similarly, applying EMPEROR-Preserved criteria most likely influencing treatment decisions in clinical practice (symptomatic HF; eGFR <20 mL/min/1.73 m2; symptomatic hypotension; history of ketoacidosis) the proportion of HFpEF patients potentially eligible to empagliflozin rose to 85%.

Conclusions

In our real-world analysis the proportion of HF patients potentially candidate for initiation of SGLT2 inhibitors is consistent across the entire spectrum of LVEF. Our findings might herald an extensive use of gliflozins in HF treatment, with a consequent strong beneficial impact on cardiovascular outcomes in eligible patients.
427 MUTUAL INTERDEPENDENCE OF BNP, PLASMA VOLUME, RENAL FUNCTION AND LVEF IN HEALTHY SUBJECTS
Authors: Fumarulo Isabella , Aspromonte Nadia , Valle Roberto
Published: December 2022

Background

Natriuretic peptides play an important role in cardiovascular control, stimulating diuresis and vasodilatation and suppressing the renin-angiotensin-aldosterone system. They are also pivotal markers in diagnosis, prognosis and therapy of heart failure (HF), specially BNP and its precursor pro-hormone Nt-proBNP. .Many factors can affect BNP levels in HF patients, potentially reducing its diagnostic accuracy. The main important ones include left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR) and plasma volume (PV). Though the mutual relationship between BNP levels and these drivers is well studied in HF patients, paradoxically little is known about this relationship in physiological conditions in healthy subjects. We tried to elucidate mutual interdependence of BNP, PV, renal function and LVEF in healthy subjects.

Methods

A total of 200 healthy adult males underwent clinical assessment, measurement of serum levels of BNP, creatinine, uricemia, hemochrome and echocardiography for LVEF assessment. GFR was calculated according to EPI-CKD formula. PV was estimated with both the Hakim formula and the Kaplan formula. The ideal PV (iPV) i.e. the normal PV was calculated using body weight and sex: iPV (in ml) = c × body weight (in kg), where c = 39 in males and 40 in females.

Results

Mean levels of BP, LVEF, BNP, serum creatinine, GFR, uricemia and PV were all within the normal range. PV1 and PV2 were significantly different from each other and both differed from iPV (Friedman ANOVA; | = 28.4; df = 2; P <0.01 for all the comparisons). Nevertheless, the three estimates of PV were all significantly and strictly correlated to each other (Spearman correlation coefficient, Rho >0.82 and P<0.001 for all the correlations). BNP levels were positively correlated with age and inversely with both uricemia and iPV. The latter ones were positively correlated to each other. GFR was inversely correlated with both age and uricemia (but not with PV nor with BNP levels). No correlation was found between LVEF and BNP levels or PV.

Conclusions

In homeostatic conditions, BNP and PV are inversely correlated in healthy adult males (contrary to the positive correlation existing in HF patients due to the predominant effects of angiotensin II and aldosterone), whereas opposite correlations between uricemia and both PV (positive) and GFR (negative) exist. The positive correlation between uricemia and PV could be explained by the strict dependence of tubular reabsorption of uric acid on serum levels of sodium, which is in turn strictly related to the extracellular fluid volume. The negative correlation between uricemia and GFR can be explained by the mutual influence of these two factors, since hyperuricemia seems to be both a cause and a consequence of chronic kidney disease (CKD).
539 GOING BEYOND CRT NON-RESPONSE: ECHO-GUIDED LEFT BUNDLE-BRANCH PACING
Authors: Latini Alessia Chiara , Poggio Luca , Riccardo Mantovani , Bragato Renato Maria , Frontera Antonio
Published: December 2022

We present the case of a 56-year-old man affected by heart failure (HF) with reduced ejection fraction (HFrEF) and permanent atrial fibrillation, who previously underwent a CRT-D implant with left ventricular stimulation delivered by an epicardial pacing lead due to an unfavourable CS anatomy. We upgraded this system to left bundle branch pacing. The LBB lead was connected to the atrial plug in of the device in order to deliver multisite left ventricular pacing. The device was programmed in DDDR mode and the delay between the two LV pacing sites was chosen (modifying atrioventricular delay) after multimodality assessment (both electrocardiographic and echocardiographic) to obtain the best resynchronization and systolic performance.
139 INTRAVENOUS CONTINUOUS HOME INOTROPIC THERAPY IN ADVANCED HEART FAILURE - RESULTS AND PRACTICAL GUIDELINES
Authors: Gentile Piero , Palazzini Matteo , Tedeschi Andrea , Ammirati Enrico , Perna Enrico , Verde Alessandro , D´angelo Luciana , Masciocco Gabriella , Garascia Andrea
Published: December 2022

Background

no firm data exist regarding continuous intravenous inotropic infusion in outpatients with advanced heart failure (AHF).

Methods

We reviewed medical records of all inotrope dependent patients discharged from our institution on continuous home inotropes infusion for AHF after a hospitalization between 2014 and 2021. Indications for inotropic agents included bridge to transplant (BTT) or to candidacy (BTC) strategies or palliative care. We compared the number of hospitalizations the year before and the year after beginning the inotrope continuous infusion, assessing the main hospital diagnosis and the duration of hospital recovery in days, through hospital charts revision. Moreover, we used a linkert 7 item scale to assess quality of life (QoL) and, using peripheral blood sample, we esteemed the end organ damage trend evaluating NTproBNP, creatinine, blood urea nitrogen (BUN) and bilirubin.

Results

From 2014 to 2021, 27 patients (Median age 56 years (Q1-Q3 50-63 years), 74% male and 26% female) were dismissed with continuous inotrope infusion from our institution. The total number of days of hospital stay was 1591 the year before beginning inotropic support (average 58.93 ± 38.70 for patient), significantly different if compared with the post inotropes period (average 22,19 ± 36,84 days for patients, IC 95% 17,488-55,994 p < 0,001). Moreover, the number of hospitalizations per patient fell from 1.93 ± 0.997 to 0,93 ± 0,958 (IC 95% 0,522- 1,478, p < 0,001). After 6 months, 53% of the patients experienced an improvement in quality of life. Regarding end organ damage, while creatinine and BUN showed a significant reduction in the first month, with a trend to stability in the following period, bilirubin and NTproBNP significantly trended to reduction during the 6 month of monitoring.

Conclusions

In a real world population of contemporary AHF, continuous inotropes home infusion documented an improvement in hospitalization, QoL and end organ damage. We offer a practical guideline on initiation, selection and maintenance of chronic inotrope therapy in a population of challenging patients.
353 B-BLOCKERS EFFECTS ACCORDING TO SEX: DO SELECTIVITY AND DOSE EQUALLY MATTER?
Authors: Salvioni Elisabetta , Paolillo Stfania , Galotta Arianna , Mapelli Massimo , Mattavelli Irene , Basile Christian , Vignati Carlo , Moscucci Federica , Piepoli Massimo , Agostoni Piergiuseppe
Published: December 2022

Background

β-blockers are one of the four recommended disease-modifying classes of drugs for the treatment of heart failure with reduced ejection fraction (HFrEF). Although their efficacy and prognostic role is unquestionable in the general population of HFrEF patients, the differences in their effect in relation to sex have not been yet investigated in detail. The present study analyzed a large, real-world, Italian population of HFrEF patients aiming to highlight any prognostic difference between males and females in relation to dose and β-selectivity of the ongoing β-blocker treatment.

Methods

Out of the 7900 HFrEF patients included in the MECKI score registry, we retrospectively analyzed those treated with β-blockers. We investigated the prognostic role of β-selectivity, dividing the population in assuming β1/β2-receptor blockers (carvedilol) vs. β1-selective blockers (bisoprolol, nebivolol or metoprolol), according to sex, and the prognostic role of daily carvedilol-equivalent β-blocker dose in relation to sex. The primary outcome of the study was the composite of all cause mortality, urgent heart transplant and LVAD implant analyzed at 5 years, both as raw data and after correction of potential confounders.

Results

6784 HFrEF patients treated with β-blockers were analyzed (1215 females, 5569 males). Patients median follow-up was 4.05 years [1.72-7.47]: 4.37 [1.6-8.13] for females and 3.99 [1.75-7.3] for males (p=ns). According to β-selectivity no prognostic differences were found in the general population, as in female or males (Fig. 1 right panel). Stratification of patients according to β-blockers equivalent dose showed significant difference among groups: mortality decreases with increasing β-blockers dose in both males and females (Fig. 1, left panel), both at baseline and after adjustment for the main confounders (LVEF, age, peakVO2, systolic pressure, hemoglobin, rest heart rate; VE/VCO2 slope, etiology. ICD, MDRD).

Conclusions

In a large, real-life population of chronic HFrEF patients analyzed according to sex, no prognostic differences were found between stratifying for β-selectivity. A better outcome was observed in subjects receiving a high daily dose, independently from sex.
235 COMPARISON OF THE PROGNOSTIC RELEVANCE OF DIFFERENT ECHOCARDIOGRAPHIC PARAMETERS OF RIGHT VENTRICULAR SYSTOLIC FUNCTION IN CHRONIC HEART FAILURE
Authors: Sforna Stefano , Colucci Eliana , Viti Caterina , Mengoni Anna , Biagioli Paolo , Zuchi Cinzia , Lauciello Rosanna , Bardelli Giuliana , Carluccio Erberto , Ambrosio Giuseppe
Published: December 2022

Background

Right ventricular (RV) systolic function is an important predictor of prognosis in heart failure (HF). Several RV echocardiographic functional parameters have been described as sensitive prognostic markers.

Aim

To compare the predictive value of different RV systolic echocardiographic parameters in patients with HF.

Methods

One hundred and sixty patients with stable HF and left ventricular ejection fraction (LV EF) <45% were assessed for the following: (1) tricuspid annular plane systolic excursion (TAPSE), (2) RV fractional area (RVFA), (3) tissue Doppler-derived RV peak systolic velocity (PSVtdi), (4) RV free wall longitudinal 2D-strain (RVFWS); and (5) 3D-RVEF. The primary endpoint was death and/or HF-hospitalization.

Results

During a mean follow-up of 16.9±10 months, 35 patients reached the primary endpoint. Each of the RV echocardiographic parameters was significantly associated with outcome at univariable analysis. After adjusting for age, eGFR, logNTproBNP, LVEF, restrictive filling pattern, pulmonary artery systolic pressure, and RV end-diastolic volume, by Lasso Cox multivariable analysis, RVFWS (HR 1.09, 95%CI: 1.02-1.18, P=0.0093) and 3D-RVEF (HR 0.95, 95%CI: 0.91-0.99, P=0.0076) remained the only parameters independently associated with outcome with a cut-off of -18.6% and 43.6% respectively, without any difference in C-statistic between the two models (0.826 versus 0.812, p=0.3255).

Conclusions

RVFWS and 3D-RVEF are strong independent predictors of outcome in HF and appear to be superior to other standard RV systolic echocardiographic parameters.
162 HFREF WITH IMPROVED EJECTION FRACTION AFTER CORONARY ARTERY BYPASS GRAFT (CABG) AND REVERSE REMODELING PREDICTOR FACTORS
Authors: Geatti Veronica , Varrà Giuseppe Guerino , Stolfo Davide , Enrico Fabris , Franzese Ilaria , Mazzaro Enzo , Sinagra Gianfranco
Published: December 2022

Background

The purpose of this study is [1] to evaluate the incidence of heart failure with improved ejection fraction (HFimpEF) in patients with reduced ejection fraction (HFrEF, EF<40%) undergoing surgical myocardial revascularization via coronary artery bypass graft (CABG), [2] to identify predictor factors for improved ejection fraction and [3] to study overall survival between the two populations, i.e. patients with improved EF (i.e. impEF) versus patients with non-improved EF (i.e. non-impEF).

Methods

N=699 patients, admitted between January 2000 and December 2020, were selected from the Cardiac Surgery database of our facility and analyzed retrospectively. The selection criteria for this study were [1] having EF<40% at the time of surgery and [2] undergoing coronary artery bypass surgery. Patients were evaluated at preoperative baseline, immediate post-operative, 3-months follow up, 1-year follow-up and the last available follow-up. ImpEF was defined as EF>40% and at least 10% EF points improvement at 1-3 months follow-up.

We assessed the incidence of improved Ejection Fraction (impEF) after surgical revascularization at 3-months follow-up, defined as the improvement of Ejection Fraction from a baseline LVEF of ≤40% to a new LVEF >40%, within a measurable improvement of ≥10 points of percentage from baseline EF; predictors of impEF were investigated and the association between impEF and mortality risk was finally explored.

Results

At 3-months follow-up, 221 patients were evaluated and the 42.5% (n=94) of these showed impEF. BMI, LVESVi and LVEF were predictors of impEF at multivariable analysis. ImpEF was significantly associated with better long-term survival in our cohort.

Conclusions

In patients with reduced EF undergoing surgical myocardial revascularization, impEF occurs in 42.5% of cases within 3 months and is associated with better overall survival. The predictors of impEF identified in this study might be helpful in the definition of patients at higher probability of impEF before surgery.
8 DIFFERENCES BETWEEN PATIENTS HOSPITALIZED FOR PAROXYSMAL ATRIAL FIBRILLATION AND HEART FAILURE WITH PRESERVED, MIDLY-REDUCED, AND SEVERELY-REDUCED EJECTION FRACTION
Authors: Tufano Nicola
Published: December 2022

Introduction

Paroxysmal atrial fibrillation (PAF), is a very common cardiac arrhythmya in patients with heart failure (HF). In the last five years we observed many patients with AF. Aim of this observation was to evaluate differences on clinical outcomes of a paroxysmal AF episode on patients with preserved (HFpEF), mildly reduced (HFmrEF), or severely-reduced (HFrEF) ejection fraction.

Methods

439 patients consecutively hospitalized in our Cardiology Unit from January 2017 to January 2022 for paroxysmal AF were retrospectively evaluated. Of them, 201 presented without heart failure, 59 with a previously known HFpEF, 49 patients with HFmrEF, and 130 patients with HFrEF. For each patient, demographic and clinical characteristics, comorbidities, instrumental data and clinical outcomes (percentage of cardioverted arrhythmia, length of hospitalization) were collected. To examinate the correlations between characteristics of patients and clinical outcomes, chi-square or Pearson test were performed.

Results

patients with AF and HF were significantly older rather than AF patients without HF. No significantly differences we found between the three HF groups. The three groups of AF patients with HF presented more comorbidities rather than AF patients without HF. The duration of hospitalization were significantly longer for AF patients with HF rather than AF no-HF patient, without differences between the three goups . Percentage of cardioverted AF were significantly higher in no-HF patients rather than in HFrEF, but not in HFpEF and HFmrEF patients . In no-HF and in HF groups, age and length of hospitalizations were significantly correlated, but no differences we found between the groups. In the three HF groups, number of comorbidity were inversely correlated with percentage of cardioversion, but not in no-HF group. Age was significantly correlated with failure in attemps of cardioversion, without differences between HF and no-HF patients.

Conclusions

our hospitalized patients for a newly onset AF and HF presented worse clinical outcomes rather AF patients without HF. This worsening clinical outcome, seem at least in part due to differences on age and comorbidities between the three groups, whereas cardiac systolic function seems not been significantly related with worse clinical outcomes.