bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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 < 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

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<0.0001) and 2.73% ± 0.27 (p<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.
1113 EFFICACY OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION ACROSS DIFFERENT DEFINITIONS: A META-ANALYSIS OF PHASE 3 RANDOMIZED CONTROLLED TRIALS
Authors: De Marzo Vincenzo , Savarese Gianluigi , Porto Italo , Metra Marco , Ameri Pietro
Published: December 2022

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Aim

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

Methods

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

Results

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

Conclusion

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

Background

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

Aim of the study

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Case Summary

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

Discussion

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

Background

In clinical practice, anaerobic threshold (AT), is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). VO2AT has been reported as absolute value (VO2ATabs), as percentage of predicted peak VO2 (VO2AT%peak_pred) or as percentage of observed peak VO2 value (VO2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing.

In this work, we aim to compare the risk-identifying ability of the AT value when expressed in these three different ways in a large population of heart failure patients. This will help identify which is more correct to use in assessing patient prognosis, especially when peakVO2 is not reached appropriately.

Methods

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

Results

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

Conclusions

In HF, VO2AT%peak_pred is the best way to report VO2 at AT in relation to prognosis, with a prognostic power comparable to that of peak VO2 and, remarkably, in severe HF patients.

Fig. 1

Fig 2

Fig. 2B
848 SACUBITRIL/VALSARTAN IMPROVES EXERCISE PERFORMANCE IN PATIENTS WITH REDUCED EJECTION FRACTION: A DOSE AND TIME DEPENDENT EFFECT
Authors: Mattavelli Irene , Mapelli Massimo , Salvioni Elisabetta , Paolillo Stefania , De Martino Fabiana , Vignati Carlo , Magrì Damiano , Mantegazza Valentina , Tamborini Gloria , Capovilla Teresa , Agostoni Piergiuseppe
Published: December 2022

Background

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

Aim of the study

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

Methods

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

Results

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

Conclusions

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

Background and purpose

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

Methods

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

Results

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

Conclusion

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

Aims

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

Methods and results

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

ED was measured by means of International Index of Erectile Function-5 questionnaire and its score was correlated with exercise cardiopulmonary test parameters, HF severity, treatment and HF comorbidities.

Results

ED prevalence was 69.94%, 74.46%, and 64.08% in total population and in patients with and without coronary artery lesions, respectively. ED was absent in 98 while it scored mild, mild to moderate, moderate and severe in 65, 57, 32, 73 individuals, respectively. Depression was found in 33.96%, mild urological symptoms in 54,23% and signs of low testosterone in 74.23%.

All the individuals with peakVO2 < 10 mL/min/kg had at least a slightly impaired sexual function. We have found no correlation between ED and ejection fraction, use of beta-blockers and ischemic etiology of HF. The only independent predictor of ED presence and severity is the symptomatology related to low testosterone.

Conclusions

ED is frequent in HF. A normal or only slightly impaired sexual activity is possible with peakVO2 > 10 mL/min/kg. The symptomatology related to low testosterone should be investigated during cardiological examinations.
334 AMYLOID-BETA 1-40 AND DAPT IN ACUTE MYOCARDIAL INFARCTION
Authors: Aleksova Aneta , Janjusevic Milijana , Gagno Giulia , Fluca Alessandra Lucia , Derin Agnese , Santon Daniela , Oriana Zhou Xin Ning , Chiaradia Vincenzo , Pierri Alessandro , Restivo Luca , Hiche Cristina , D’errico Stefano , Fabris Enrico , Perkan Andrea , Sinagra Gianfranco
Published: December 2022

Background

Atherosclerotic plaque destabilization and platelet activation is a prompt and progressive process that is the basis of acute coronary syndromes (ACS). Amyloid-β 1-40 (Aβ (1-40)), is highly expressed in atherosclerotic plaques and is released in plasma by activated platelets. Some animal studies suggested that an increase in amyloid precursor protein (sAPP770) levels upon atherosclerotic plaque activation, anticipates myocardial injury. Platelets inhibition is the keystone in the management of patients with ACS, but the data regarding the benefits of Dual Antiplatelet Therapy (DAPT) before coronary angiography is still disputed.

Methods

In a large prospective cohort of 1038 patients hospitalized for AMI (both STEMI 702 /NSTEMI 333 patients), we evaluated the impact of DAPT on Aβ (1-40) levels, the correlation with inflammatory biomarkers, and Aβ (1-40) prognostic value on long-term mortality.

Results

The median concentration of Aβ (1-40) in plasma at admission was 90.47 (54.49-130.47) pg/ml. At hospital admission patients on DAPT had significantly lower levels of Aβ (1-40) compared to patients receiving only aspirin (67.56 (42.7-120.23) pg/ml vs. 92.25 (56.16-131.17) pg/ml, p=0.004), independently of patients’ gender or diagnosis STEMI/NSTEMI. Aβ (1-40) positively correlated with older age and higher levels of CRP and TNFα.

There was no significant difference among patients who received DAPT therapy and those who did not towards age, presence of chronic renal failure, hypertension, nor in the rate of revascularization procedures (both percutaneous coronary intervention and bypass).

Kaplan-Meier analysis showed that higher Aβ ​​(1-40) levels during the 49-month follow-up were associated with higher mortality risk (p<0.0001). Also, at multivariate Cox regression analysis Aβ ​​(1-40) level (HR =1.003 (95% CI, 1.001-1.005), p=0.017 was predictive for mortality, together with older age, higher interleukin (Il)-1β, worse left ventricular systolic function, and GFR ≤ 60 mL/min.

Conclusions

STEMI/NSTEMI patients receiving DAPT at hospital admission, have a significantly lower plasma concentration of Aβ (1-40), which is an independent predictor of long-term mortality.
342 TMAO PLASMA LEVELS PREDICT RECURRENT ISCHEMIC EVENTS IN SURVIVORS OF MYOCARDIAL INFARCTION
Authors: Aleksova Aneta , Janjusevic Milijana , Stornaiolo Mariano , Gagno Giulia , Pierri Alessandro , Fluca Alessandra Lucia , Derin Agnese , Oriana Zhou Xin Ning , Hiche Cristina , D’errico Stefano , Novellino Ettore , Sinagra Gianfranco
Published: December 2022

Background

Recent studies have highlighted a direct link between dietary nutrients, microbiota and cardiovascular disease (CVD). In this context, trimethylamine-N-oxide (TMAO), a metabolite derived from the intestinal microbiota, stands out, paving its way as one of the important biomarkers associated with atherosclerosis, increased risk of CVD, recurrent events and adverse outcomes.

Methods

81 patients who survived acute myocardial infarction (AMI), (both STEMI 50 / NSTEMI 31) were enrolled in this study together with 10 healthy individuals. Further, we evaluated the relationship between plasma TMAO levels and cardiovascular events during the follow-up. The measurement of plasma levels of TMAO was performed using liquid chromatography-tandem mass spectrometry (LC-MS).

Results

The median plasma concentration of TMAO were significantly higher in patients with AMI compared with healthy control (1.62 (1.37–2.25) µM. vs 0.55 (0.35–0.74) µM, p < 0.0001). During a median follow-up of 61.74 (59.34–64.24) months, 10 out of 81 patients (12.3%) had a re-infarction. Patients who had another ischemic event had higher TMAO values compared with individuals who did not (2.29 (1.60–6.49) µM vs 1.60 (1.34–2.09) µM, p = 0.026). Further, TMAO values positively correlate with CRP, a pro-inflammatory marker. However, at multivariate Cox regression analysis, plasma TMAO values were not predictive of re-infarction.

Conclusions

The data of our pilot study show that higher TMAO values are associated with the risk of recurrent ischemic event. A future prospective study, including larger cohort is necessary to analyze this issue.
56 ANALYSIS OF A 23,270-PATIENT STUDY: UNSUPERVISED MACHINE LEARNING WITH CLUSTER ANALYSIS IN PATIENTS DISCHARGED AFTER AN ACUTE CORONARY SYNDROME
Authors: Bernardi Marco , Mohammadi Tanya , D´ascenzo Fabrizio , Spadafora Luigi , Testa Alberto , De Filippo Ovidio , De Ferrari Gaetano Maria , Biondi-zoccai Giuseppe
Published: December 2022

Background

Characterization and management of patients with acute coronary syndromes (ACS) remain challenging, and it is unclear whether currently available clinical and procedural features can suffice to inform adequate decision making.

Methods

Details on patients discharged after an ACS were obtained by querying an extensive multicenter registry, detailing patient features as well as management details. Clinical outcomes included fatal and non-fatal cardiovascular events at 1-year follow-up. After missing data imputation, two unsupervised machine learning approaches (k-means and Clustering Large Applications [CLARA]) were used to generate separate clusters with different features. Bivariate and multivariable-adjusted analyses were performed to compare different clusters for clinical outcomes.

Findings: 23,270 patients discharged after ACS were included. Two clusters were identified by k-mean algorithm (k1 and k2), and two clusters by CLARA algorithm (C1 and C2). Differences in 2-years outcomes between k1 and k2 and between C1 and C2 were substantial. K2 cluster (N=21,988) in comparison with k1 cluster (N=1,282) had significantly higher occurrence of death (9.5% vs 3.8%, p<0.001), reinfarction (7.2% vs 3.7%, p<0.001), and major bleeding (6.0% vs 3.0%, p<0.001). Similarly, C1 cluster (N=11,268) showed a worse prognosis than C2 cluster (N=12,002): death (4.8% vs 3.5%, p<0.001), reinfarction (4.5% vs 3.4%, p<0.001), and major bleeding (3.6% vs 2.8%, p=0.001). Most associations did not hold at multivariable analysis based on supervised learning techniques, with the exception of major bleeding (odds ratio=1.37 [95% confidence interval 1.02-1.83] for the k1/C1 subcluster vs k1/C2 subcluster, p=0.039.

Conclusions

A machine-learning based clustering approach is effective at face value to inform on the prognosis of patients with ACS managed invasively. These findings can be leveraged to inform decision-making in this setting, but also highlight the potential role of cluster analysis in first-in-man, and preapproval studies of medical devices.
194 THROMBOEMBOLIC ACUTE ST ELEVATION MYOCARDIAL INFARCTION AFTER TRANSCATHETER VALVE IMPLANTATION
Authors: Caggiari Ludovica , Angius Simone , Corda Marco , Contini Francesca Valeria , Fazzini Luca , Dessalvi Christian Cadeddu
Published: December 2022

Transcatheter aortic valve implantation (TAVI) is an established treatment of severe symptomatic aortic valve stenosis and is an effective and less invasive treatment option compared with conventional surgical aortic valve replacement (SAVR) for patients considered inoperable or at high surgical risk. Thromboembolic and bleeding complications negatively impact recovery and survival after TAVI. This case describes one of the few reported TAVI-associated myocardial infarction due to thrombosis of the prosthetic aortic valve.

A 82-years-old woman, suffering from severe symptomatic aortic stenosis, underwent TAVI. Before the procedure, coronary artery disease was excluded by invasive coronary angiography.

Since the time of the discharge the patient didn't assume any therapy with aspirin or other antithrombotic drugs. A month after TAVI she complained persistent epigastric pain and was admitted to our department for anterior ST elevation myocardial infarction. Coronary angiography highlighted a monovascular coronary artery disease with thrombotic occlusion of the first diagonal and of the distal left anterior descending coronary artery. In consideration of the thrombotic load thyrofiban was started and it was performed a chest contrast CT which confirmed the diagnostic suspicion of bioprosthetic valve thrombosis. She was first treated with unfractionated heparin (UFH) and then oral anticoagulant therapy with warfarin was started. Echocardiograms (echo) showed a severely reduced systolic function (EF 25%) and high trans-prosthetic gradients (mean transprosthetic pressure gradient of 30 mmHg). On the 8th day after hospitalization she complained chest pain with evidence of moderate pericardial effusion. Epistenocardica pericarditis was therefore diagnosed and the patient started acetylsalicylic acid therapy with progressive clinical, instrumental and laboratory improvement. After 10 days of anticoagulation therapy, she underwent a transesophageal echocardiogram which turned out negative for bioprosthetic valve thrombosis. The predischarge transthoracic echocardiography showed severely reduced systolic function (EF 30%) with a mean transprothesic gradient of 12 mmHg; the circumferential pericardial effusion was mild-moderate but not haemodynamically significative. Therapy at discharged included warfarin and aspirin. Ten days after an echo showed a reduction of the pericardial effusion, an improved systolic function (EF 42%) and mean transprothesic gradient not changed significantly since discharge.

Prosthetic valve thrombosis has been reported in up to 40% of patients after TAVI and this case hightlights the importance of antithrombotic therapy after this procedure. Therapeutic anticoagulation appears to be the only non-invasive treatment for resolving valve thrombosis but it is not clear how long this therapy should last for the prevention of prosthetic valve thrombosis.
57 ISCHEMIC HEART SCOMBROID SYNDROME: FURTHER EVIDENCE FROM ALL OVER THE WORLD
Authors: Perfetti Silvia , Ferrazzo Giuseppe , Andò Giuseppe , Costa Francesco , Pistelli Lorenzo , Restelli Davide , Campanella Francesca , Borgi Marco , Koniari Ioanna , Kounis Nicholas G , De Gregorio Cesare
Published: December 2022

Objective

Scombroid syndrome (SS) is a long-standing poisoning illness caused by ingestion of improperly stored fish food (usually tuna fish) contaminated by Gram-negative bacteria. The main pathogenetic feature is toxicity by the high histamine (and/or other toxin) levels within the fish muscle. Scombroid syndrome accounts for approximately 5% of food toxicities at emergency department in the USA. It consists of gastrointestinal symptoms, sickness, at times (head) rash or flushing, peppery taste, hypotension, and other symptoms. Cardiovascular complications are infrequent, but acute coronary syndromes (ACSs) have been described in some patients on admission to hospital. We identified those cases as with ischemic heart scombroid syndrome (IHSS).

Methods

An accurate literature search for IHSS in case series and single reports, published as by the end of July 2022, was performed. Herein main clinical features are summarized.

Results

From 1997 to 2022, 18 studies were found describing 25 patients aged 42±15 years, 14 women (56%), likely to have IHSS. Countries of origin are depicted in the Figure nearby. Apart from typical clinical presentation of SS, chest pain, oppression and hypotension were complained by almost all patents. Symptoms and signs of ACS started 10 to 180 minutes from the meal. Four patients (mostly before 2015) required advanced life support or mechanical ventilation. Widespread ST-depression (first in the inferior leads) was the most frequently reported ECG feature (approximately in 90% of cases). Hospitalization was required for unstable patients or those admitted for coronary angiography. However, this latter was performed only in 10 cases (40%), and only in 3 (12%) a culprit lesion was identified and treated. Therapy consisted with antihistamine drugs, fluids and circulatory support, symptomatic drugs, and steroids in some cases. All patients were discharged from hospital with uneventful follow-up.

Conclusions

To date, 25 published cases of IHSS have been recognized, mostly from Italy, but reports are from all over the world. As in typical SS, myocardial ischemia begins shortly after raw or cocked (tuna) fish ingestion. However, due to unfamiliarity with the syndrome, diagnostic misinterpretation is possible. IHSS can be classified as a transient (usually benign) ACS, caused by coronary vasospasm in response to a nitroxide-mediated histamine-induced tissue hypoperfusion, in a similar way to type-I Kounis syndrome. Based on current knowledge, coronary angiography is mandatory in patients with a history of coronary artery disease and/or allergic diathesis, persistent symptoms or unresponsive to emergency treatment.