bluuebunny/crossref_metadata_2025 huggingface dataset:
1055 MALMÖ POTS SYMPTOM SCORE: ASSESSING SYMPTOM BURDEN IN POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME
Authors: Spahic Jasmina Medic , Hamrefors Viktor , Johansson Madeleine , Ricci Fabrizio , Melander Olle , Sutton Richard , Fedorowski Artur
Published: December 2022

Background

Postural orthostatic tachycardia syndrome (POTS) is a common cardiovascular autonomic disorder characterized by excessive heart rate increase on standing and symptoms of orthostatic intolerance, posing significant limitations on functional capacity. No objective tool exists to classify symptom burden in POTS.

Methods

We conducted a case-control study in 62 POTS patients and 50 healthy controls to compare symptom burden between groups using the newly developed, self-rating, 12-item, Malmö POTS Score (MAPS; 0-10 per item, total range 0-120) based on patients’ own perception of symptoms through visual analogue scale assessment. We have also explored correlations between symptom severity assessed by MAPS, basic clinical parameters and postural haemodynamic changes.

Results

POTS patients showed significantly higher total MAPS score (78±20 vs. 14±12, p<0.001), higher baseline systolic blood pressure (BP), diastolic BP and heart rate (HR)(p<0.001) compared with healthy controls. The most prominent symptoms in POTS were palpitations, fatigue, and concentration difficulties. Haemodynamic parameters on standing were significantly correlated with palpitations in POTS after adjustment for age and sex (lower systolic and diastolic BP, and higher HR) (p<0.001 for all). Orthostatic HR was significantly associated with concentration difficulties and total MAPS score. The optimal cut-point value of MAPS to differentiate POTS and healthy controls was ≥42 (sensitivity, 97%; specificity, 98%).

Conclusions

Symptom severity, as assessed by MAPS score, is 5-fold higher in POTS compared with healthy individuals. The new MAPS score can be useful as a semi-quantitative system to assess symptom burden, monitor disease progression and evaluate pre-test likelihood of disease.
336 TEMPORAL CONNECTION BETWEEN HOME MONITORING TRENDS OF THORACIC IMPEDANCE AND SUSTAINED VENTRICULAR ARRHYTHMIAS
Authors: Rodio Giovanna , Iacopino Saverio , Pisanò Ennio C , Calvi Valeria , Rovaris Giovanni , Marini Massimiliano , Giammaria Massimo , Caravati Fabrizio , Maglia Giampiero , Maines Massimiliano , Orsida Daniela , Santamaria Matteo , Bisignani Giovanni , Baroni Matteo , Lissoni Fabio , Duca Antonio , Luzzi Giovanni , Giacopelli Daniele , Gargaro Alessio , D´onofrio Antonio
Published: December 2022

Introduction

Implantable cardioverter defibrillators (ICDs) provide daily values of thoracic impedance (TI) that are inversely correlated with fluid accumulation in the lungs. Since sustained ventricular arrhythmias (SVA) are known to have a short-term relationship with heart failure exacerbations, our objective was to assess TI trends temporally related to SVA episodes.

Methods

This study analyzed data daily transmitted from patients with ICD or cardiac resynchronization therapy defibrillator (CRT-D) of the nationwide Home Monitoring Expert Alliance network. Device-detected SVAs were adjudicated for appropriateness. Patients were randomly split into a derivation and validation cohort. To identify the most significant TI trend (TI-index), several numerical TI transformations were tested in a cross-sectional analysis of the derivation cohort modelling the odds of first SVA with univariate logistic regressions. In the same cohort, the threshold of the selected transformation was identified to maximize the projected specificity. The relative risk of SVA for TI-index above threshold was estimated in the validation cohort by applying Cox proportional hazard models stratified by individual patients to 60-day duration windows. Analyses were performed separately in the ICD and CRT-D groups.

Results

The study cohort included 2,384 patients with 69 years of age (interquartile range: 60, 77); 19% were women, 42% had coronary artery disease, and 43% had a CRT-D. After a median follow-up of 2.0 (1.0, 3.4) years, there were 3,298 appropriate SVA episodes in 727 patients (30%).

The derived IT-index consisted of the percentage of 6-day intervals of the rolling average of TI values showing monotone decrease in the last 82 days. The increase in the risk of SVA was 3% (p<0.0001) per unit of percentage. The threshold of 60% of intervals with monotone decrease was associated with 99.9% projected specificity and 70.3% accuracy.

In the validation cohort, the TI-Index was associated with a 42% increased risk of SVA episodes in the ICD group (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.05-1.92, p=0.023). The TI-index exceeded the 60% threshold before the episode in 38% of the detected episodes. The association was not significant in the CRT-D group (HR 0.96, 95% CI 0.62-1.47, p=0.84).

Conclusions

In our analysis of remote monitoring data, a specific monotonic decreasing trend of TI was temporally associated with SVA in patients with ICD. Careful monitoring of TI can identify a period of susceptibility to ventricular arrhythmias that deserves more intensive attention.
161 ABLATION OF EPICARDIAL VENTRICULAR TACHYCARDIA ORIGINATING IN THE AREA OF PERICARDIAL ADHESIONS INDUCED BY STEREOTACTIC RADIOABLATION IN A PATIENT WITH ISCHEMIC CARDIOMYOPATHY
Authors: Ruzzarin Alessandro , Torri Federica , Agbariah Andrea , Manfrin Massimiliano , Bertagnolli Livio
Published: December 2022

This is the case of a 64-year-old male patient with prior inferior wall myocardial infarction, wearing a cardiac resynchronization therapy defibrillator and suffering from recurrent ventricular tachycardia (VT). The patient had undergone a transitory successful endocardial radiofrequency catheter ablation (RFCA) in 2013 and a stereotactic ablative body radiotherapy (SABR) in 2021, targeting the VT originating in the inferior wall myocardial scar. The patient was referred to our institution due to recurrent highly symptomatic slow-VT. A coronary angiography ruled out coronary artery disease (CAD) progression and a RFCA was rescheduled. Given the suspected epicardial origin of VT based on a 12-lead ECG, the decision was made to perform a combined epi-endocardial ablation. SABR-induced pericardial adhesions prevented posterior pericardial access, thus requiring an anterior access approach (Figure 1, Panel A, yellow star). Following epicardial and endocardial electroanatomic mapping (EAM), VT ablation relied on a substrate-based approach. Local abnormal ventricular activities (LAVAs), detected both in the accessible epicardial inferior wall of the left ventricle and at the opposite endocardial site, were eliminated by radiofrequency (RF) current. Upon completion of endocardial ablation, ventricular pacing induced hemodynamically unstable VT, exiting from the epicardial region corresponding to the SABR-induced pericardial adhesions. Mechanical adhesiolysis, using the elbow of the open-irrigated ablation catheter, was performed to disrupt SABR-induced pericardial adhesions in the inferior wall. The epicardial EAM performed with the open-irrigated catheter recorded LAVAs in the infero-posterior wall of the left ventricle, corresponding to the SABR-disrupted pericardial adhesions. A RF current was delivered, targeting LAVAs at this site (Figure 1, Panel B: the central green dot corresponds to the area of disrupted pericardial adhesions). At the end of the procedure, no sustained VT was induced by programmed ventricular stimulation.

Conclusion

SABR constitutes a novel and promising non-invasive radioablative treatment of VT, potentially associated with cardiac toxicity. To our knowledge, this is the first reported case of combined epicardial and endocardial RFCA of recurrent VT after SABR. Based on the first RFCA report and exclusion of CAD progression, we hypothesized that SABR might have favoured progression of the inferior low voltage area. With this case report, we would like to demonstrate that even if pericardial adhesions could be a consequence of SABR, gentle catheter-driven manoeuvres can be enough to disrupt the adhesions and to achieve full EAM. Further research is mandatory to shed light on SABR's long-term arrhythmogenic role.
55 ARE TWO PACEMAKERS BETTER THAN ONE? SYNCOPE WITHOUT PRODROMES IN A YOUNG PM-DEPENDENT SUBJECT: A CASE STUDY
Authors: Sabatini Antonella , Baessato Francesca , Tomaino Marco
Published: December 2022

Patient presentation and follow-up

A 33-year-old woman was admitted to the ER of our hospital because of syncope without prodromes during her routine cycling training.

The patient's clinical history is characterized by congenital heart disease, interventional and cardiac surgical procedures in 1992-2021: percutaneous aortic valve (AoV) reconstruction for severe aortic stenosis in bicuspid AoV; conservative surgical Ao valvuloplasty and mitral valve (MV) commissuroplasty; MV substitution surgery; surgical AoV and MV replacement; surgical iatrogenic IVD closure. Atrial fibrillation became chronic and, following repeated interventions, an iatrogenic AV block developed requiring pacemaker implantation. In Dec. 2019, a submuscular PM (epicardial leads) was implanted (Medtronic Adapta DDDRR programmed in VVIRR for permanent atrial fibrillation). 2 years later, a transvenous-lead PM was implanted (Biotronik Evity 8 SR-T VVI-RR MRI conditional) without extracting the Medtronic PM (re-programmed in “back-up” VVI 30 bpm).

Patient management and treatment

A conservative strategy was adopted by programming the Biotronik/endocardial device in VOO-R mode stimulation only, while waiting for the total discharge of the old (Medtronic/epicardial) device. An alternative strategy could have been the removal of the epicardial PM. PM follow-up was performed via “remote” control and clinical checks in our Congenital Heart Disease Center.

The complex clinical history and the choice of up-grading to an endocardial device without removing the epicardial device, has caused a predictable condition that was overlooked.

The entry into operation of the ERI VOO 65 bpm mode of the epicardial device, in addition to causing a physiological increase in the pacing threshold of the epicardial catheter itself, produced the inhibition of the endocardial device whenever there was a pacing capture failure of the epicardial system. This situation set asystole off and consequent patient's loss of consciousness.

Conclusions
812 FOLATES-RELATED ERYTHROCYTE DIVERSION LEAD TO ATRIAL CARDIOMYOPATHY/FIBRILLATION THROUGH EPCS DYSFUNCTION
Authors: Sgarra Luca , Desantis Vanessa , Potenza Maria Assunta , Montagnani Monica , Grimaldi Massimo
Published: December 2022

Background

Recent advances support the concept that pre-persistent Atrial Fibrillation (AF) and paradoxical embolism do not explain the wholeness of embolic strokes, thus suggesting a broad Atrial Cardiomyopathy (AC). Pathogenic mechanisms underlying AC are still largely unknown. Folate cycle disorders are a yet underrated dysmetabolism. MTHFR-inherited defects could hinder both endothelial and circulating endothelial progenitor cell (EPCs) functioning, therefore providing one-shot explanation to both atrial stasis (increasing atrial fibrosis and generating atrial hypocontractility even in sinus rhythm) and endothelial dysfunction (ED).

Purpose

This study aims to enquire for the hypothesis that: 1) atrial fibrosis (AFib – intended as a relative percentage of low voltage area in the context of left atrial endocavitary voltage mapping) would relate to folate cycle disorders (intended as both: a)MTHFR C677T inherited mutations and b)bone-marrow function disorders, here referring to erythropoiesis diversions) and 2) AF patients would show dysfunctional EPCs.

Methods

We studied 59 consecutive patients admitted to the cardiology Unit of the General Hospital “F.Miulli”, with preserved EF, subjected to AF ablation. AFib was quantified by bipolar peak-to-peak voltage areas (<0,5 mV) with respect to the wholeness of the picked voltage points. Blood count cell was evaluated by a commercial laboratory test. EPCs isolation and characterization were performed by Ficoll-Hypaque gradient and following flow cytometry analysis for cell surface antigens: CD45, CD34, CD133, VEGFR2 and KDR. EPCs functional wound healing assay was performed to determine the number of EPCs migrated to the “wound”, measuring the percentage of relative wound closure compared with matched-controls.

Results

Baseline characteristics did not differ between Sample and Control groups. % of Afib significantly differs between C677T MTHFR homozigosis patients (n=15) with respect to non-C&//T MTHFR homozygosis patients (n=44 p < 0,02). Once univariate analysis was performed, subsequent multivariate analysis highlights highest fit once merged RBC, RDW-SD and folates values were inputed: Goodness of fit was proper, modelling good (Low figure - R2=0,39; p=0,0001). Either RBC, RDW-SD and folates coefficient reached significance (p < 0,0001; p < 0,01; p < 0,05 respectively). Number of EPCs significantly differs between AF patients and matched controls (p < 0,001).

Conclusions

Our findings support the hypothesis that genetically determined folates dysmetabolism (MTHFR dysfunction) promotes AFib via a complex cardiac-bone marrow networking involving circulating EPCs and unraveled by erythropoiesis diversions. Such results suggest a pathogenic role of folate cycle disorders in the AC development
23 IMPLANTABLE CARDIOVERTER DEFIBRILLATOR (ICD) EXPLOSION AFTER GUNSHOT: WHEN DEVICE PROTECTS TWICE
Authors: Sorvillo Graziano , Giano Angelo , Manzo Michele , Ciccarelli Michele , Galasso Gennaro , Vecchione Carmine , Esposito Cristina
Published: December 2022

A 70 years old man presented to the emergency department with “accidental” gunshot wound at left hemithorax and left shoulder/arm. Initial clinical assessment showed stable vital signs and implantable cardioverter defibrillator(ICD) protruding outside from large wound in the infraclavicular region. The ICD, previously implanted for secondary prevention of ventricular tachycardia, appeared burned and the battery was exploded. Urgent chest computed tomography scan was performed with evidence of left omeral displaced fracture, large hematoma without arterial injury and many shotgun pellets in left shoulder/arm. The ICD generator was disconnected from passive fixation leads and removed. Patient was stabilized and omeral fracture was fixed. Following leads extraction was successfully performed in hybrid operating room with cardiac surgery standby considering the difficulty of the procedure, the type of leads (double coil, passive fixation) and the risk of complications. The patient was discharged home in good clinical conditions after re-implantation of novel ICD in right infraclavicular region.

Emerging technologies are promising in making lead extractions safer and more accessible for patients worldwide. This clinicl case report will provide the most up-to-date indications and procedural approaches for lead extractions and insight on the future trends in this field.
432 SACUBITRIL/VALSARTAN AND RISK OF SUPRAVENTRICULAR ARRHYTHMIAS AS DETECTED BY REMOTE MONITORING IN HEART FAILURE PATIENTS
Authors: Stronati Giulia , Marchese Procolo , Pimpini Lorenzo , Flori Marco , Scarano Michele , Gennaro Francesca , Antonicelli Roberto , Busacca Paolo , Parato Vito Maurizio , Grossi Pierfrancesco , Dello Russo Antonio , Guerra Federico
Published: December 2022

Introduction

Sacubitril/valsartan (ARNI) has demonstrated a significant benefit compared to angiotensin inhibitor (enalapril) in decreasing both morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). While. recent studies demonstrated that in HFrEF patients, ARNI decreased ventricular arrhythmias no data is available with regards to the supraventricular arrhythmic burden in HFrEF patients with an implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy-defibrillator (CRT-D) and remote monitoring. The aim of out study was to assess if ARNI therapy was able to significantly reduce supraventricular arrhythmias. More specifically the primary endpoint was the incidence of AT/AF episodes, as detected by the device. Secondary endpoints included the total burden of AT/AF, the mean number of premature ventricular contractions (PVC) per hour and the percentage of biventricular pacing per day (in patients with CRT-D).

Methods

We conducted a multicentre, observational, prospective registry : the SAVE THE RHYTHM (SAacubitril Valsartan rEal-world registry evaluating THE arRHYTHMia burden in HFrEF patients with implantable cardioverter defibrillator). We enrolled all patients with HFrEF, ICD or CRT-D actively followed through remote monitoring and starting treatment with sacubitril/valsartan. All patients were followed-up for at least one year.

Results

At the end of enrollment, 265 patients from 5 centres had at least one sacubitril/valsartan prescription (88% males, age 68±10 years). The annual incidence of AT/AF episodes decreased from 16.6% before sacubitril/valsartan to 12.8%, 6.7% and 0.7% according to the maximum tolerated dose (24/26 mg, 49/51 mg and 97/103 mg, respectively; p=0.026). After treatment with sacubitril/valsartan, patients with at least one episode of AT/AF decreased from 32.6% to 26.5% (24/26 mg), 24.3% (49/51 mg) and 6.9% (97/103 mg); p=.041. A significant decrease in the number of PVC (-28 per hour) and in the rate of appropriate shock (-0.8% per year) were seen in patients with a previous diagnosis of paroxysmal or persistent AF. Patients with permanent AF (n=7) experienced no benefits from sacubitril/valsartan therapy in terms of arrhythmic burden reduction. Patients with a CRT device (41%) experienced a significant increase in biventricular pacing time (+3% per day).

Discussion

Therapy with sacubitril/valsartan could decrease arrhythmic burden in patients with non-permanent AF and HFrEF and reduce subclinical supraventricular arrhythmias in patients with no history of AF.
1123 DIAGNOSTIC ACCURACY OF SMART GADGETS/WEREABLE DEVICES IN ATRIAL FIBRILLATION DETECTION: A METANALYSIS
Authors: Vetta Giampaolo , Parlavecchio Antonio , Gianni Carola , Cipolletta Laura , Polselli Marco , Vuono Francesco De , Pannone Luigi , Mohanty Sanghamitra , Cauti Fillippo Maria , Caminiti Rodolfo , Miraglia Vincenzo , Monaco Cinzia , Chierchia Gian Battista , Rossi Pietro , Biase Luigi Di , Bianchi Stefano , De Asmundis Carlo , Natale Andrea , Della Rocca Domenico Giovanni
Published: December 2022

Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia and an important risk factor for stroke and heart. Recent technology advances have allowed for heart rhythm monitoring using smart gadgets/wearable devices which can be used for early AF diagnosis.

Hypothesis

We performed a systemic review and meta-analysis to assess the accuracy of AF diagnosis by smart gadgets/wearable devices.

Methods

We systematically searched Medline, Embase and Cochrane electronic databases up to April 15th, 2022 for observational studies of the diagnostic accuracy of smartphone application, wrist-worn wearables and external devices in detecting AF. We calculated the area under the curve (AUC) of the summary receiver operating characteristic curves (SROC) and pooled sensitivities and specificities.

Results

A total of 79 studies were included enrolling 36903 patients, 66.3% male with average age of 68.3±8 years. In the overall analysis of all devices, the AUC was 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(95% CI: 94–96%), the specificity 96%(95% CI: 96–97%). Wrist-worn wearables had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(9% CI: 92–97%), the specificity 97%(95% CI: 96–98%)(Figure 1A). Smartphone applications had AUC of 0.98 (95% CI: 0.96-0.99), the sensitivity 96%(9% CI: 94–97%), the specificity 96%(95% CI: 93–98%)(Figure 1B). External devices had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(9% CI: 93–97%), the specificity 96%(95% CI: 95–97%)(Figure 1C). Single-lead ECG had AUC of 0.99 (95% CI: 0.98- 1.00), the sensitivity 95%(9% CI: 92–96%), the specificity 96%(95% CI: 95–97%). PPG had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 96%(9% CI: 95–97%), the specificity 97%(95% CI: 95–98%).

Conclusions

Smartphone application, wrist-worn devices and external devices with PPG and single-lead ECG have excellent diagnostic accuracy in atrial fibrillation diagnosis.

Figure 1. Summary Receiver Operating Characteristic curves and Areas Under The Curve of Wrist-worn wearables (A), Smartphone applications (B) and External devices (C).
284 EFFECTS OF TWO DIFFERENT COMBINATIONS OF POLICOSANOLS IN LIPID LOWERING AND ENDOTHELIAL FUNCTION
Authors: Cersosimo Angelica , Amore Ludovica , Cimino Giuliana , Calvi Emiliano , Arabia Gianmarco , Raddino Riccardo
Published: December 2022

Aims

Current guidelines recommend the use of lipid lowering agents based on the patient's cardiovascular risk. In the last years, a great interest was driven towards the cathegory of "very low risk" patients, in which a single cardiovascular risk factor is sufficient to make them been considered at "relatively higher" risk.

For the last category of patients nutraceutical acquired importance in the last years.

The present study aims to evaluate the efficacy and safety of a combination of monacolin K 2.9 mg, (fermented yest rice), coenzyme Q10 30 mg (Formulation A) versus monacolin K 10 mg, and coenzyme Q10 10 mg (Formulation B) on lipidic profile and on the vascular function evaluated as endothelial function and arterial stiffness.

Methods

The present is a single-center, open-label randomized controlled parallel group study to compare efficacy and safety of two different type of nutraceutical compounds (Formulation A or Formulation B).

Patients enrolled were with low cardiovascular risk, in primary prevention, in order to evaluate the evolution of the lipidic profile of these patients and the impact of a nutraceutical-based treatment strategy.

Patients eligible for the study were randomized 1:1 to receive either a pill day of Formulation A or B.

Results

Both treatments with Formulation A or B were tolerated; no patients reported side effects or withdrew from the study. The two groups were balanced with respect clinical and biochemical variables. After 24 weeks of treatment we demonstrated a statistically significant reduction in total cholesterol (p 0.010) and LDL (p 0.002).

We observed also an improvement in endothelial function (p 0.292) and a reduction of arterial stiffness (p 0.209) evaluated through the non-invasive methods of EndoPAT and SphygmoCOR. Data obtained suggest monacolin K 2.9 mg, coenzyme Q10 30 mg and rice policosanols 20 mg (Formulation A), was non inferiority to monacolin K 10 mg, coenzyme Q10 10 mg (Formulation B) in endothelial function improvement and serum lipids lowering.

Conclusions

The new combination of natural nutraceuticals, have a protective cardiovascular effect, not also through reduction of plasma lipids but also in endothelial function and arterial stiffness, despite the reduction of monacolin K.
101 LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 IN STEMI VS NSTE-ACS PATIENTS: A MARKER OF CARDIOVASCULAR ATHEROSCLEROTIC RISK RATHER THAN THROMBOSIS
Authors: Verdoia Monica , Gioscia Rocco , Rognoni Andrea , Luca Giuseppe De
Published: December 2022

Background

The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation.

Methods

A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed on blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay.

Results

We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p=0.05), displayed a lower rate of hypertension (p=0.002), previous MI (p=0.001) and PCI (p=0.01) and used less frequently statins (p=0.01) and clopidogrel (p=0.02). White blood cells and admission glycemia were increased in STEMI (p=0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p<0.001) and lower TIMI flow (p=0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132±41.1 vs 154.6 ±40.9 nmol/min/mL, p=0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs 57%, p=0.02, adjusted OR[95% CI]=0.20[0.06-0.68], p=0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r=0.47, p<0.001), but not with inflammatory biomarkers.

Conclusion

The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, and with recurrent cardiovascular events, therefore potentially representing a marker of a more aggressive atherosclerotic disease and higher cardiovascular burden and risk.
697 SGLT2-INHIBITORS PREVENT LEFT VENTRICULAR DISFUNCTION INDUCED BY ANTHRACYCLINE CHEMOTERAPY IN MOUSE MODEL: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Faggiano Andrea , Gherbesi Elisa , Carugo Stefano
Published: December 2022

Background

No human studies evaluating the efficacy of sodium glucose cotransporter 2 inhibitors (SGLT2-i) in preventing left ventricular dysfunction induced by anthracycline chemotherapy are available. Current evidence on this topic is based on few studies conducted on mouse models.

Objective

We investigated this issue through a meta-analysis of echocardiography studies that reported data on difference in left ventricular function between animals assuming SGLT2-i and controls in mouse models of anthracycline-induced cardiomyopathy.

Methods

The PubMed, OVID-MEDLINE and Cochrane library databases were systematically analysed to search English-language articles published from inception to 31 July 2022. Studies were identified by using Me-SH terms and crossing the following terms: “ sodium glucose cotransporter 2 inhibitors”, “gliflozin”, “anthracycline”, “cardiotoxicity”, “systolic dysfunction” and “echocardiography”.

Results

The meta-analysis included a total of 106 mice (Sprague Dawley and C57Bl/6 species) with anthracycline-induced cardiomyopathy from 7 studies, 60 mice assuming a SGLT2-i (Empagliflozin:4 studies, Dapagliflozin:2, Canagliflozin:1) and 46 controls. Compared with controls, left ventricle systolic function was significantly better in the pooled SGLT2-i group. Precisely, both fractional shortening (FS: 44,7±3,7 vs 32,6±3,3) and left ventricle ejection fraction (LVEF: 78,2±3,4 vs 64,2±4,9) were higher in the pooled SGLT2-i group than in the controls group, with standard mean difference (SMD) respectively being 2,42±0,56 for FS (CI: 1,326-3,510, p value <0.001) and 2,46±0,61 for LVEF (CI: 1,267-3,656, p value <0.001). Figure 1.

Conclusions

Our study shows a favourable effect of SGLT2-i in the prevention of left ventricular dysfunction induced by anthracycline chemotherapy in mouse models, suggesting that this pharmacological strategy should also be tested in clinical studies involving human subjects.
367 LEFT VENTRICULAR MALIGNANT PERIPHERAL NERVE SHEATH TUMOR, A RARE PRIMARY CARDIAC NEOPLASM
Authors: Lapolla Davide , Fileti Luca , Campo Gianluca Calogero , Guardigli Gabriele , Tonet Elisabetta
Published: December 2022

This is a case of a 71 year-old man, symptomatic for heart failure (NYHA II class), with recent weight loss and occurrence of arthralgia. In the last month episodes of non sustained ventricular tachycardia were observed.

Transthoracic echocardiography showed a dilated left ventricle with reduced ejection fraction (30%) and the presence of an apical left ventricular cyst (dimensions 33×36 mm), with no doppler signal inside. No relevant valvular diseases were found. The first hypothesis was a cystic echinococcosis with left ventricle localization, but the serological testing resulted negative.

In order to obtain a better characterization of the apical lesion a Cardiac Magnetic Resonance (CMR) was performed: it confirmed the apical mass with thin wall, high T2 and T1 signal and no contrast enhancement. CMR findings raised the suspicion of cardiac tumor.

The case was discussed in the local heart team, and the patient was scheduled for cardiac surgery with mass removal. The histological examination showed a malignant mesenchymal neoplasm related to a primary cardiac schwannoma.

Follow up outpatient visit showed a decrease of the arrhythmic burden and a progressive improvement in patient's symptoms. Echocardiography reported little improvement in EF (38%) and no suspicious lesions.

MPNST (malignant peripheral nerve sheath tumor) is a type of cancer extremely rare and not fully considered in literature with a poor prognosis. CMR and echocardiography could help to early diagnose this neoplasms when dimension and localization are not prohibitive for operating.
411 AN UNEXPECTED (AND UNDESIRED) ECHOCARDIOGRAPHIC FINDING IN A PATIENT WITH RIGHT-SIDED CHEST PAIN
Authors: Radesich Cinzia , Pezzato Andrea , Saro Riccardo , Luca Antonio De , Ferro Matteo Dal , Dore Franca , Sinagra Gianfranco
Published: December 2022

A 71-year-old man, former smoker, without other cardiovascular risk factors nor previously known cardiological history, was admitted to our emergency department for nonproductive cough and right-sided chest pain, worsened by inspiration. ECG documented reduced peripheral QRS voltages. Echocardiography was performed, revealing the presence of an inhomogeneous, hyperechoic neoformation involving the lateral wall of the right ventricle (RV), dislocating the right coronary artery, protruding into the cavity towards the intraventricular septum and reaching the sub-valvular apparatus of the tricuspid valve, without any hemodynamic interference. Pericardial effusion was also documented (maximum 20 mm around the atrioventricular groove), without signs of cardiac tamponade. For better mass characterization, a computed tomography (CT) scan and a cardiac magnetic resonance (CMR) were performed, confirming the presence of a solid neoformation involving the RV and pericardial effusion, also showing right pleural effusion. Furthermore, right hilar and subcarinal lymphadenomegaly with compression of the bronchi was observed. A positron emission tomography (PET) scan showed areas of increased 18-fluorodeoxyglucose (18FDG) uptake in supra- and infra diaphragmatic lymph nodes, adrenal glands, bones, and lungs. Due to the clinical suspicion of a lymphoproliferative neoplasm, corticosteroid therapy was started.

Before a diagnostic lymph node biopsy could be performed, the patient had a syncopal episode due to cardiac tamponade, requiring pericardiocentesis. During hospitalization, continuous heart monitoring revealed intermittent third-degree atrioventricular block, so a permanent pacemaker was implanted. Finally, an excisional lymph node biopsy was obtained, and a diagnosis of diffuse large B-cell lymphoma was established. Treatment with Prednisone, Cyclophosphamide, Vincristine, nonpegylated liposomal Doxorubicin, and Rituximab (R-COMP) was promptly started. Seven months later, after five cycles of chemotherapy, complete remission was documented by PET scan, and the cardiac mass was no longer evident at echocardiography.

Metastatic involvement of the heart is a relatively frequent event in oncologic patients, with an estimated prevalence of 8% at autopsy. Lymphoproliferive neoplasms have a not negligible rate of heart mestastatization (9,4%). Neoplastic invasion secondary to lymphoma tends to infiltrate the myocardium, typically causing arrhythmias and conduction disturbances.

Diagnostic evaluation relies upon echocardiography, CT and CMR. PET/TC is of paramount importance to assess the malignant nature of the mass, to stage the disease and to evaluate the response to chemotherapy. Metastatic cardiac involvement typically occurs as a late manifestation of disseminated lymphoma and the prognosis is usually poor; however, survival is increasing thanks to new chemo-immunotherapy strategies.
608 PEAK ATRIAL SYSTOLIC LONGITUDINAL STRAIN (PALS) AS AN EARLY PARAMETER OF CANCER THERAPY-RELATED CARDIAC DYSFUNCTION
Authors: Minnucci Ilaria , Bergamini Corinna , Niro Lorenzo , Springhetti Paolo , Trento Laura , Benfari Giovanni , Rossi Andrea , Tafciu Elvin , Maffeis Caterina , Fiorio Elena , Luciano Ribichini Flavio
Published: December 2022

Background

Trastuzumab (TZ) is widely used for his key role in HER2 positive breast cancer. However, the most concerning cardiovascular complication is cardiotoxicity. Many studies have highlighted the importance of screening for subclinical myocardial dysfunction using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, there are only few studies investigating a possible atrial damage.

Purpose

Aim of this study was to analyze the modification peak atrial systolic longitudinal strain (PALS) in patients undergoing therapy with TZ in a follow-up period of 12 months. The fluctuation of left atrial function parameters under chemotherapy was evaluated focusing the attention on those patients who developed cancer therapy–related cardiac dysfunction (CTRCD).

Methods

116 women affected by breast cancer treated with TZ were enrolled. Each patient underwent a complete echocardiography at baseline and every 3 months.

Exclusion criteria were poor quality imaging and lack of a complete follow up with consequent missing data.

CTRCD was defined as a decrease in the left ventricular ejection fraction of >10 percentage points to a value <53% at any time of follow-up. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software to analyze both atrial and left ventricular function. Trends of GLS, and PALS during 12 months-follow up periods were analyzed. Additionally, we explored if diabetes and renal impairment were associated with more prevalent atrial subclinical disfunction as demonstrated in previous studies.

Results

A total of 10 patients (9%) developed cancer therapy–related cardiac dysfunction. A significant reduction in GLS compared to the baseline was observed during the whole follow-up (p=0.05), starting in the first six months of treatment (-21 ± 2% vs -17 ± 2%, p= 0.021). Interestingly, PALS showed a similar trend with a significant decrease during the whole 12 months-follow up (p=0.012), starting in the first 3 months (45 ± 9% vs 35 ± 8%, p=0.001).

6 patients presented a diagnosis of diabetes at baseline, and presented lower PALS compared to the non-diabetic counterpart (38± 10% vs 49 ± 12% p=0.03).

2 patients presented a significant renal impairment (eGFR ≤30 ml/min). Similarly, these patients presented a lower PALS at baseline (32 ± 7% and 48 ± 7%; p=0.055).

Conclusions

In patients treated with Trastuzumab the development of left atrial impairment is frequent and PALS modifications seem to precede GLS variations in patients with CTRCD, suggesting a possible cardiotoxic effect of such therapy on both atrial and left ventricular myocardium and physiology.
847 CONCENTRATIONS OF GROWTH DIFFERENTIATION FACTOR 15 AND LEFT VENTRICULAR FUNCTION IN SURVIVORS FROM HODGKIN LYMPHOMA TREATED WITH ANTHRACYCLINE-CONTAINING CHEMOTHERAPY
Authors: Perna Valentina , Bertero Edoardo , Sirello Davide , Sarocchi Matteo , Porto Italo , Spallarossa Paolo , Ameri Pietro
Published: December 2022

Background

Recent studies have shown that the concentrations of growth differentiation factor 15 (GDF-15) increase after anthracycline administration and may be associated with cardiotoxicity during or shortly after treatment. The relation of GDF-15 with late-onset cardiotoxicity has far less been studied.

Methods

We examined GDF-15 levels across the spectrum of left ventricular (LV) function in a single-center cohort of adult patients who had received curative chemotherapy for Hodgkin lymphoma and underwent comprehensive cardiologic assessment including transthoracic echocardiography (TTE) as part of long-term follow-up. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay, and the concentrations between TTE phenotypes were compared by unpaired Student's t test. The correlation between GDF-15 values and echocardiographic parameters was investigated by linear regression.

Results

35 (18 males, 51%) patients were evaluated a median of 47 months (IQR 24-67) after doxorubicin-containing chemotherapy. The median age at the end of treatment and at the time of TTE was 35 years (IQR 28-50) and 40 years (IQR 32-56), respectively. All subjects had received ABVD with or without rituximab as a first-line treatment; 2 (6%) had also received mediastinal irradiation, 6 (17.4%) a second-line therapy, 2 (8.7%) a third-line treatment, and 8 (17.4%) had ultimately undergone bone marrow transplantation. None had a history of heart disease or atrial fibrillation, nor NYHA class ≥II. Body mass index was 24 ± 5 Kg/m2. Seven (20%) patients had hypertension, 9 dyslipidemia (26%), and 2 (6%) diabetes; 28 (80%) were prior or current smoker. Mean GDF-15 was 1132,9 ± 485,0 pg/mL. LV ejection fraction (LVEF) was always >50%; 3 (9%) subjects had global longitudinal strain (GLS) < -18%. Moreover, 7 (20%) had mild or moderate diastolic dysfunction, as defined by E/A ratio <1 or a pseudonormal mitral inflow pattern, respectively. There was no significant relation between GDF-15 and LVEF or GLS values. By contrast, GDF-15 levels were higher in patients with diastolic dysfunction than in those without. Moreover, GDF-15 concentrations correlated with E/A and E/e’ ratios, estimated pulmonary capillary wedge pressure, and estimated systolic pulmonary artery pressure (Figure).

Conclusions

Our results suggest that GDF-15 tracks with LV diastolic, rather than systolic, dysfunction years after anthracycline chemotherapy.
545 INVESTIGATING THE RISK OF CARDIAC FIBROSIS IN RESPONSE TO HEAT-NOT-BURN CIGARETTES THROUGH HUMAN CARDIAC STROMAL CELLS
Authors: Picchio Vittorio , Pagano Francesca , Carnevale Roberto , D´amico Alessandra , Cozzolino Claudia , Floris Erica , Bordin Antonella , Schirone Leonardo , Saade Wael , Miraldi Fabio , De Falco Elena , Sciarretta Sebastiano , Peruzzi Mariangela , Biondi-zoccai Giuseppe , Frati Giacomo , Chimenti Isotta
Published: December 2022

Background

The use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain.

Objective

To investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs).

Methods

Resident CSCs were isolated from the atrial tissue of non-smokers patients with cardiovascular diseases, and exposed to the serum pools derived from 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference.

Results

CSCs treated with TCC serum versus NS displayed impaired 3D growth (NS 568±24 vs. TCC 442±27 spheroids/well, p≤0,01) and reduced migration after 6h (NS 0,62±0,04 vs. TCC 0,80±0,03 normalized scratch area versus t0, p≤0,01) and 10h (NS 0,49±0,03 vs. TCC 0,36±0,03 normalized scratch area versus t0, p≤0,05), as well as significantly increased expression (IL-6, IL-8) and/or release of pro-inflammatory (e.g CRP, PAI-1, CD40L, CXCL4) and pro-fibrotic cytokines (PDGFA, MMP1). CSCs cultured with HNBC serum showed significantly increased mRNA levels of pro-fibrotic genes (PDGFA, THY1, COL1A1, p<0,01), and significantly reduced expression of the gap junction protein CX43 (p<0,05). Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors (e.g. VEGF, Adiponectin, CHI3L1) from CSCs, as assessed by protein arrays and ELISA. In fact, their paracrine support to tube-formation by endothelial cells (NS 63,29±4,72 vs. TCC 41,43±6,64 vs. HNBC 37,29±5,67 mesh number per well, p≤0,05) and to preserved cell viability of neonatal rat cardiomyocytes (NS 0,60±0,04 vs. TCC 0,40±0,01 vs. HNBC 0,47±0,01 OD490 normalized OD versus t0, p≤0,001) were significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2 (NS 1,76±0,09 vs. TCC 3,84±0,25 vs. HNBC 2,90±0,35 µM, p≤0,05) and significantly reduced the release of NO (NS 6,98±0,43 vs. TCC 4,65±0,07 vs. HNBC 5,06±0,13 µM, p≤0,01) by CSCs.

Conclusion

The circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.
1075 USE OF LIPID-LOWERING COMBINATION THERAPIES IN SANTORINI STUDY: EVIDENCE FROM ITALIAN COHORT
Authors: Cesaro Arturo , Calabrò Paolo , Arca Marcello , Solini Anna , Gambacurta Rosanna , Soronen Jarkko , Diamand Francoise , Catapano Alberico L
Published: December 2022

The SANTORINI registry is an observational study that aims to evaluate the management of patients with high and very high cardiovascular (CV) risk in clinical practice, collecting data at enrolment and after 12 months. Italy participated in this study with 1531 patients at very high risk and 446 at high risk. The scope of the present analysis was to investigate low-density lipoprotein cholesterol (LDL-C) goal attainment in patients who do not qualify for PCSK9 inhibitors (PCSK9i) (according to Italian reimbursement regulations) in Italian cohort, with focus on patients in secondary prevention. The current indications for PCKS9i charged to the National Health System in Italy in secondary prevention, are for patients aged ≤ 80 years with LDL-c levels ≥ 70 mg/dl in at least three detections despite therapy for at least 6 months with high intensity statin at the highest tolerated dose and ezetimibe or after a single LDL-C detection for recent myocardial infarction or multiple cardiovascular events or with demonstrated intolerance to statins and/or ezetimibe. At enrolment, a total of 509 (33.2%) of 1531 patients at very-high risk had an LDL-C level of less than 70 mg/dl. Of them, about half do not reach the LDL-C target. In particular, 34.4% takes statin monotherapy, and 50.3% of them do not reach the target. Even patients taking high-intensity statins as monotherapy reach the target in only 47.9% of cases, leaving more than half of patients with LDL-C levels between 55 and 70 mg/dl. Regarding combination therapy, statin and ezetimibe, patients taking this combination account for 26.9%, of these those taking the combination of moderate-intensity statin and ezetimibe reach the target in 56.7% of cases while those taking high-intensity statins and ezetimibe reach the target in 51.4% of cases. Our findings show that there is a proportion of patients with LDL-C below 70 mg/dl who do not qualify for PCSK9i who are not at target for LDL-C levels despite maximal therapy with statins and ezetimibe.
761 PRASUGREL OR CLOPIDOGREL IN PATIENTS WITH ACUTE CORONARY SYNDROMES AT DIFFERENT THROMBOTIC RISK: RESULTS FROM THE PROMETHEUS STUDY
Authors: Chiarito Mauro , Cao Davide , Sartori Samantha , Zhang Zhongjie , Vogel Birgit , Nicholas Johny , Pivato Carlo Andrea , Spirito Alessandro , Tavenier Annerieke , Effron Mark , Stefanini Giulio G , Baber Usman , Kapadia Samir , Rao Sunil , Henry Timothy D , Pocock Stuart , Dangas George , Kini Annapoorna , Mehran Roxana
Published: December 2022

Background

Potent P2Y12 inhibitors are recommended in patients with acute coronary syndrome (ACS), although the optimal antithrombotic strategy should be tailored based on patients thrombotic and hemorrhagic risk profile. We evaluated if the benefits associated with prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) are similar in patients with different thrombotic risk profiles.

Methods

PROMETHEUS was a multicenter observational study comparing prasugrel vs. clopidogrel in ACS patients undergoing PCI. Patients were defined at high thrombotic risk if presenting with a clinical and a procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated using propensity-stratified analysis and with multivariable Cox regression.

Results

Among 16,065 patients, 4,293 were defined at high and 11,772 at low-to-moderate thrombotic risk. Patients receiving prasugrel had less comorbidities and risk factors than those treated with clopidogrel, both in the high and low-to-moderate thrombotic risk strata. High thrombotic risk patients had increased rates of ischemic and bleeding events at 90-day and 1-year follow-up. Patients treated with prasugrel had a lower adjusted 1-year risk of MACE (HR 0.86, 95% CI 0.77-0.96), irrespective of their thrombotic risk (pinteraction =0.32). Stratifying the study population by number of risk factors there was a significant interaction (pinteraction =0.026) for a greater reduction in MACE with prasugrel among patients with ≤1 thrombotic risk factor. The risk of clinically significant bleeding was similar in patients treated with prasugrel and clopidogrel.

Conclusions

Patients with ACS at high thrombotic risk who undergo PCI are at increased risk of adverse events at 1 year. Prasugrel, mainly reserved to patients with less comorbidities, reduced the risk of ischemic events both in patients at high and low-to-moderate thrombotic risk as compared with clopidogrel.
290 A UNIQUE CASE OF AORTIC VALVE LEAFLET'S ANEURYSM DETECTED BY CARDIAC COMPUTED TOMOGRAPHIC ANGIOGRAPHY-CCTA
Authors: Pergola Valeria , Cabrelle Giulio , Mele Donato , Motta Raffaella , Amato Filippo , Cozza Elena
Published: December 2022

Heart valve leaflet's aneurysm is a rare finding and literature about this topic is sparse. Early recognition is important because their rupture can lead to catastrophic valve regurgitation.

An 84 years old male with chronic ischemic cardiomyopathy was admitted to coronary-intensive-care-unit for non-ST-elevation-myocardial-infarction. Baseline transthoracic-echocardiography showed normal biventricular function with inhomogeneous thickening of aortic leaflets with moderate aortic regurgitation. Because acoustic window was limited, a trans-esophageal echocardiography was performed detecting a small mass in the right aortic coronary cusp with moderate regurgitation (orifice regurgitation area: 0,54 cm2; med/max gradient: 16/32 mmHg). Endocarditis was ruled out. Because of the rapid worsening of patient's conditions, requiring mechanical ventilation and hemofiltration, and the potential hazard of an urgent coronary angiography, a cardiac computed tomographic angiography (CCTA) was performed. Detailed spatial reconstructions highlighted a bilobed cavitation in the commissure between right-left aortic coronary cusps. Diagnosis of aortic leaflets’ aneurysm was made. A “wait and see” strategy was chosen and patient's general conditions gradually improved and now he is stable and uneventful. To date no aortic leaflet's aneurysm were described in literature.