Publications by authors named "Antonio Dello Russo"

195 Publications

Sports Activity and Arrhythmic Risk in Cardiomyopathies and Channelopathies: A Critical Review of European Guidelines on Sports Cardiology in Patients with Cardiovascular Diseases.

Medicina (Kaunas) 2021 Mar 25;57(4). Epub 2021 Mar 25.

Department of Biomedical Science and Public Health, Cardiology and Arrhythmology Clinic, University Hospital "Ospedali Riuniti Umberto I-Lancisi-Salesi", Marche Polytechnic University, 60100 Ancona, Italy.

The prediction and prevention of sudden cardiac death is the philosopher's stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.
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http://dx.doi.org/10.3390/medicina57040308DOI Listing
March 2021

Myocardial Inflammation, Sports Practice, and Sudden Cardiac Death: 2021 Update.

Medicina (Kaunas) 2021 Mar 17;57(3). Epub 2021 Mar 17.

Cardiology and Arrhythmology Clinic, University Hospital "Ospedali Riuniti Umberto I-Lancisi-Salesi", 60126 Ancona, Italy.

Myocardial inflammation is an important cause of cardiovascular morbidity and sudden cardiac death in athletes. The relationship between sports practice and myocardial inflammation is complex, and recent data from studies concerning cardiac magnetic resonance imaging and endomyocardial biopsy have substantially added to our understanding of the challenges encountered in the comprehensive care of athletes with myocarditis or inflammatory cardiomyopathy (ICM). In this review, we provide an overview of the current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of myocarditis, ICM, and myopericarditis/perimyocarditis in athletes, with a special emphasis on arrhythmias, patient-tailored therapies, and sports eligibility issues.
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http://dx.doi.org/10.3390/medicina57030277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002711PMC
March 2021

Prevalence and outcome of silent hypoxemia in COVID-19.

Minerva Anestesiol 2021 03;87(3):325-333

Department of Anesthesiology, Intensive Care and Emergency Medicine, Medical University of Göttingen, Göttingen, Germany.

Background: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission.

Methods: In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO2/FiO2 ratio <300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded.

Results: Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaO2/FiO2 ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO2/FiO2 from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO2 (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients.

Conclusions: Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.
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http://dx.doi.org/10.23736/S0375-9393.21.15245-9DOI Listing
March 2021

Worldwide Survey of COVID-19-Associated Arrhythmias.

Circ Arrhythm Electrophysiol 2021 03 7;14(3):e009458. Epub 2021 Feb 7.

Department of Medicine, Division of Cardiology, Columbia University Vagelos College of Physicians & Surgeons (E.J.C., S. Kochav, I.G., A.B., H.G., E.Y.W.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCEP.120.009458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982128PMC
March 2021

Assessment of patients presenting with life-threatening ventricular arrhythmias and suspected myocarditis: The key role of endomyocardial biopsy.

Heart Rhythm 2021 Jan 29. Epub 2021 Jan 29.

Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Life-threatening ventricular tachyarrhythmias (VAs) represent a significant cause of death in myocarditis.

Objective: The purpose of this study was to identify predictors of sustained VAs in patients with myocarditis and ventricular phenotype diagnosed by workflow including endomyocardial biopsy (EMB) guided by 3D electroanatomic mapping (3D-EAM).

Methods: We prospectively enrolled patients with suspected myocarditis and VAs, undergoing cardiac magnetic resonance, coronary angiography, 3D-EAM, and EMB guided by 3D-EAM. At follow-up, sustained VAs were detected by device interrogation and 24-hour electrocardiographic Holter monitoring.

Results: We enrolled 54 consecutive patients (mean age 41 ± 14 years; 32 men) with normal ventricular function; left ventricular and right ventricular (RV) late gadolinium enhancement was present, respectively, in 21 (46%) and 6 (13%) of the 46 patients who underwent cardiac magnetic resonance. In 31 patients, the histological diagnosis was myocarditis, while in 14 patients, focal replacement myocardial fibrosis (FRMF); in 9 patients, specimens were inadequate (diagnostic yield of EMB 83%). 3D-EAM showed a larger endocardial scar area for both ventricles in myocarditis than in FRMF (RV bipolar mean scar area 22 ± 16 cm vs 3 ± 2 cm; P = .02; left ventricular bipolar mean scar area 13 ± 5 cm vs 4 ± 2 cm; P = .02, respectively). At a follow-up of 21 months, freedom from sustained VAs was 58% in myocarditis and 92% in FRMF (log-rank, P = .008). Histological diagnosis of myocarditis and RV endocardial scar were independent predictors of sustained VAs (P = .02 for both).

Conclusion: Our data highlight the need for 3D-EAM-guided EMB in apparently healthy young patients with suspected myocarditis and VAs.
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http://dx.doi.org/10.1016/j.hrthm.2021.01.025DOI Listing
January 2021

Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: Findings from the SYNCOPACED registry.

Heart Rhythm 2021 Jan 16. Epub 2021 Jan 16.

Cardiology Unit, "Card. G. Panico" Hospital, Tricase, Italy.

Background: Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope.

Objective: The purpose of this study was to assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population.

Methods: The SYNCOpal recurrences in patients treated with permanent PACing for bradyarrhythmic syncope (SYNCOPACED) registry was a prospective multicenter observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic workup aimed at establishing the mechanism of syncope/collapse.

Results: During a median follow-up of 50 months, 213 patients (15.6%) reported at least 1 syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (P = .017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker or lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7% and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained.

Conclusion: In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases, and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in >25% of patients.
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http://dx.doi.org/10.1016/j.hrthm.2021.01.010DOI Listing
January 2021

Cryoablation for pulmonary veins isolation in obese patients with atrial fibrillation compared to nonobese patients.

Pacing Clin Electrophysiol 2021 Feb 12;44(2):306-317. Epub 2021 Jan 12.

Department of Cardiology, Ospedale San Luca, Istituto Auxologico, Milano, Italy.

Background: Pulmonary veins isolation (PVI) by cryoballoon (CB) ablation is marginally represented in clinical studies in obese patients. The aim of this analysis was to evaluate the safety and efficacy of CB-PVI in a large cohort of overweight and obese patients from the 1STOP project.

Methods: From 2012 to 2018, 2048 patients with atrial fibrillation (AF) (70% male, 59 ± 11 years; 75% paroxysmal AF) underwent index CB-PVI. The patient data were separated into three cohorts for statistical evaluation, including: normal weight (body mass index [BMI] < 25 kg/m ), overweight (BMI = 25-30 kg/m ), and obese patients (BMI > 30 kg/m ).

Results: Out of 2048 patients, 693 (34%) patients had a BMI < 25 and were deemed as normal. There were 944 (46%) patients categorized as overweight (BMI = 25-30) and 411 (20%) as obese (BMI > 30). Overweight or obese patients were more often in persistent AF, had more frequently hypertension and diabetes, had higher CHA DS -VASc score, and had a number of failed antiarrhythmic drug (AAD). Periprocedural complication rates were similar among the three cohorts. The 12-month freedom from AF recurrence was 76.4% in the normal BMI group as compared to 79.2% in the overweight and 73.5% in the obese group (p = .35). However, 48% of overweight patients were on AAD treatment during the follow-up. By multivariate analysis, BMI was not a predictor for AF recurrence following the index CB-PVI.

Conclusion: CB-PVI in obese patients is a safe procedure. Increased BMI (either moderate or severe) does not seem to be associated with a worse outcome or to a different rate of AAD discontinuation at 12 months.
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http://dx.doi.org/10.1111/pace.14149DOI Listing
February 2021

Myocardial Infarction Without Obstructive Coronary Artery Disease (MINOCA): A Practical Guide for Clinicians.

Curr Probl Cardiol 2021 Mar 10;46(3):100761. Epub 2020 Dec 10.

Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital "Umberto I - Lancisi - Salesi," Ancona, Italy. Electronic address:

Myocardial infarction without obstructive coronary artery disease (MINOCA) is defined by the evidence of spontaneous acute myocardial infarction (MI) and angiographic exclusion of coronary stenoses ≥50% in any potential infarct related artery, after having ruled out other clinically overt causes for the acute presentation. The introduction of this new concept was meant to encourage discovery of putative pathophysiological mechanisms and development of specific therapeutic measures. In recent years, we have witnessed significant advances in the fields of epidemiology, pathophysiology, diagnosis, prognosis estimation and therapeutics of MINOCA. So far, however, the definition of MINOCA has been rather heterogeneous since specific cardiac conditions such as myocarditis and Takotsubo syndrome have often been included, generating conflicting results. In this review, we summarize the current state-of-the-art in the expanding MINOCA field and propose a comprehensive stepwise approach for the rational diagnostic assessment of these challenging patients. Our aim is to provide clinicians with an "Ariadne's thread" according to the recent fourth universal definition of MI in order to not get lost in MINOCA's labyrinth.
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http://dx.doi.org/10.1016/j.cpcardiol.2020.100761DOI Listing
March 2021

Prior myocarditis and ventricular arrhythmias: The importance of scar pattern.

Heart Rhythm 2021 Apr 24;18(4):589-596. Epub 2020 Dec 24.

Centro Cardiologico Monzino, IRCCS, Milano, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milano, Italy.

Background: Multiple studies have addressed the importance of anteroseptal scar in patients with nonischemic cardiomyopathy. However, this pattern has never been fully evaluated in patients with prior myocarditis.

Objective: The purpose of this study was to evaluate whether anteroseptal scar is associated with worse outcome in patients with prior myocarditis and how it affects the efficacy of catheter ablation (CA).

Methods: This was a retrospective study of consecutive patients with prior myocarditis and arrhythmic presentation. Cardiac magnetic resonance and electroanatomic voltage mapping were used to identify the scar pattern. Patients were referred for either CA or escalated antiarrhythmic drug (AAD) therapy. The main outcome was ventricular arrhythmia (VA)-free survival according to the presence of anteroseptal scar.

Results: A total of 144 consecutive patients with prior myocarditis were included. Mean age was 42.1 ± 14.9 years, and 58% were men. Ejection fraction was normal in 73% of patients. Anteroseptal scar was present in 44% of cases. Sixty-one patients (42%) underwent CA. Overall, at 2-year follow-up, VA-free survival was 77% in the CA group. After CA, the mean number of AADs taken by each patient decreased from 1.8 to 0.9 per day (p<0.001). The presence of anteroseptal scar was found to be an independent predictor of VA relapse both in patients treated with CA (hazard ratio [HR] 3.6; 95% confidence interval [CI] 1.1-11.4; P = .03) and in the overall population (HR 2.0; 95% CI 1.2-3.5; P = .02) .

Conclusion: In patients with prior myocarditis and VA, the presence of anteroseptal scar negatively predicts outcomes irrespective of treatment strategy.
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http://dx.doi.org/10.1016/j.hrthm.2020.12.016DOI Listing
April 2021

[Management of access site vascular complications in transcatheter aortic valve implantation].

G Ital Cardiol (Rome) 2020 Nov;21(11):4-12

SOSD Emodinamica Interventistica Strutturale e Pediatrica.

Since its advent, transcatheter aortic valve implantation (TAVI) has experienced a continuous expansion, thanks to extraordinary clinical results and to the dramatic increase of safety, enabled by improvements of prosthesis and delivery systems, refinement of implantation techniques, increasing operator experience, and use of computed tomography scan for procedural planning. However, complications rates are still not negligible. As vascular complications, and, particularly, access-related complications are among the most frequent adverse events, all TAVI operators should know how to prevent and how to manage those potentially catastrophic situations. Here we provide an overview of the most frequent access site vascular complications and the respective treatment options.
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http://dx.doi.org/10.1714/3487.34667DOI Listing
November 2020

Pharmacological therapy for the prevention of cardiovascular events in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA): Insights from a multicentre national registry.

Int J Cardiol 2021 Mar 23;327:9-14. Epub 2020 Nov 23.

Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital "Ospedali Riuniti", Ancona, Italy.

Aims: To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA.

Methods And Results: In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02).

Conclusion: The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.040DOI Listing
March 2021

Characteristics of Patients With Arrhythmogenic Left Ventricular Cardiomyopathy: Combining Genetic and Histopathologic Findings.

Circ Arrhythm Electrophysiol 2020 12 15;13(12):e009005. Epub 2020 Dec 15.

Heart Rhythm Center (M.C., A.G., R.S., V.C., M.B., G.V., C.T.), Centro Cardiologico Monzino IRCCS, Milano.

Background: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an under-characterized phenotype of arrhythmogenic cardiomyopathy involving the LV ab initio. ALVC was not included in the 2010 International Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy diagnosis and data regarding this phenotype are scarce.

Methods: Clinical characteristics were reported from all consecutive patients diagnosed with ALVC, defined as a LV isolated late gadolinium enhancement and fibro-fatty replacement at cardiac magnetic resonance plus genetic variants associated with arrhythmogenic right ventricular cardiomyopathy and of an endomyocardial biopsy showing fibro-fatty replacement complying with the 2010 International Task Force Criteria in the LV.

Results: Twenty-five patients ALVC (53 [48-59] years, 60% male) were enrolled. T wave inversion in infero-lateral and left precordial leads were the most common ECG abnormalities. Overall arrhythmic burden at study inclusion was 56%. Cardiac magnetic resonance showed LV late gadolinium enhancement in the LV lateral and posterior basal segments in all patients. In 72% of the patients an invasive evaluation was performed, in which electroanatomical voltage mapping and electroanatomical voltage mapping-guided endomyocardial biopsy showed low endocardial voltages and fibro-fatty replacement in areas of late gadolinium enhancement presence. Genetic variants in desmosomal genes (desmoplakin and desmoglein-2) were identified in 12/25 of the cohort presenting pathogenic/likely pathogenic variants. A definite/borderline 2010 International Task Force Criteria arrhythmogenic right ventricular cardiomyopathy diagnosis was reached only in 11/25 patients.

Conclusions: ALVC presents with a preferential involvement of the lateral and postero-lateral basal LV and is associated mostly with variants in desmoplakin and desmoglein-2 genes. An amendment to the current International Task Force Criteria is reasonable to better diagnose patients with ALVC.
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http://dx.doi.org/10.1161/CIRCEP.120.009005DOI Listing
December 2020

Implantation technique and optimal subcutaneous defibrillator chest position: a PRAETORIAN score-based study.

Europace 2020 12;22(12):1822-1829

Department of Experimental, Diagnostic and Specialty Medicine, Institute of Cardiology, University of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy.

Aims: The traditional technique for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation involves three incisions and a subcutaneous pocket. Recently, a two-incision and intermuscular (IM) technique has been adopted. The PRAETORIAN score is a chest radiograph-based tool that predicts S-ICD conversion testing. We assessed whether the S-ICD implantation technique affects optimal position of the defibrillation system according to the PRAETORIAN score.

Methods And Results: We analysed consecutive patients undergoing S-ICD implantation. The χ2 test and regression analysis were used to determine the association between the PRAETORIAN score and implantation technique. Two hundred and thirteen patients were enrolled. The S-ICD generator was positioned in an IM pocket in 174 patients (81.7%) and the two-incision approach was adopted in 199 (93.4%). According to the PRAETORIAN score, the risk of conversion failure was classified as low in 198 patients (93.0%), intermediate in 13 (6.1%), and high in 2 (0.9%). Patients undergoing the two-incision and IM technique were more likely to have a low (<90) PRAETORIAN score than those undergoing the three-incision and subcutaneous technique (two-incision: 94.0% vs. three-incision: 78.6%; P = 0.004 and IM: 96.0% vs. subcutaneous: 79.5%; P = 0.001). Intermuscular plus two-incision technique was associated with a low-risk PRAETORIAN score (hazard ratio 3.76; 95% confidence interval 1.01-14.02; P = 0.04). Shock impedance was lower in PRAETORIAN low-risk patients than in intermediate-/high-risk categories (66 vs. 96 Ohm; P = 0.001). The PRAETORIAN score did not predict shock failure at 65 J.

Conclusion: In this cohort of S-ICD recipients, combining the two-incision technique and IM generator implantation yielded the lowest PRAETORIAN score values, indicating optimal defibrillation system position.

Clinical Trial Registration: http://clinicaltrials.gov/ Identifier: NCT02275637.
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http://dx.doi.org/10.1093/europace/euaa231DOI Listing
December 2020

Prospective use of ablation index for the ablation of right ventricle outflow tract premature ventricular contractions: a proof of concept study.

Europace 2021 Jan;23(1):91-98

Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, IT, Italy.

Aims: Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premature ventricular contractions (PVCs) treatment. Ablation Index (AI) is a novel ablation marker incorporating RF power, contact force, and time of delivery into a single weighted formula. Data regarding AI-guided PVCs RFCA are currently lacking. Aim of the study was to compare AI-guided and standard RFCA outcomes in patients with PVCs originating from the right ventricle outflow tract (RVOT).

Methods And Results: Consecutive patients undergoing AI-guided RFCA of RVOT idiopathic PVCs were prospectively enrolled. Radiofrequency catheter ablation was performed following per-protocol target cut-offs of AI, depending on targeted area (RVOT free wall AI cut-off: 590; RVOT septum AI cut-off: 610). A multi-centre cohort of propensity-matched (age, sex, ejection fraction, and PVC site) patients undergoing standard PVCs RFCA was used as a comparator. Sixty AI-guided patients (44.2 ± 18.0 years old, 58% male, left ventricular ejection fraction 56.2 ± 3.8%) were enrolled; 34 (57%) were ablated in RVOT septum and 26 (43%) patients in the RVOT free wall area. Propensity match with 60 non-AI-guided patients was performed. Acute outcomes and complications resulted comparable. At 6 months, arrhythmic recurrence was more common in non-AI-guided patients whether in general (28% vs. 7% P = 0.003) or by ablated area (RVOT free wall: 27% vs. 4%, P = 0.06; RVOT septum 29% vs. 9% P = 0.05). Ablation Index guidance was associated with improved survival from arrhythmic recurrence [overall odds ratio 6.61 (1.95-22.35), P = 0.001; RVOT septum 5.99 (1.21-29.65), P = 0.028; RVOT free wall 11.86 (1.12-124.78), P = 0.039].

Conclusion: Ablation Index-guidance in idiopathic PVCs ablation was associated with better arrhythmic outcomes at 6 months of follow-up.
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http://dx.doi.org/10.1093/europace/euaa228DOI Listing
January 2021

Risk of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: role of correlation between symptoms and electrocardiogram findings.

Europace 2020 11;22(11):1729-1736

Division of Cardiology, Azienda Ospedaliera Universitaria "Maggiore della Carità", Novara, Italy.

Aims: To evaluate the risk of syncopal recurrences after pacemaker implantation in a population of patients with syncope of suspected bradyarrhythmic aetiology.

Methods And Results: Prospective, multicentre, observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for syncope of bradyarrhythmic aetiology (proven or presumed). Before pacemaker implantation, all patients underwent a cardiac work-up in order to establish the bradyarrhythmic aetiology of syncope. According to the results of the diagnostic work-up, patients were divided into three groups: Group A, patients in whom a syncope-electrocardiogram (ECG) correlation was established (n = 329, 24.1%); Group B, those in whom clinically significant bradyarrhythmias were detected without a documented syncope-ECG correlation (n = 877, 64.3%); and Group C, those in whom bradyarrhythmias were not detected and the bradyarrhythmic origin of syncope remained presumptive (n = 158, 11.6%). During a median follow-up of 50 months, 213 patients (15.6%) reported at least one syncopal recurrence. Patients in Groups B and C showed a significantly higher risk of syncopal recurrences than those in Group A [hazard ratios (HRs): 1.60 and 2.66, respectively, P < 0.05]. Failure to establish a syncope-ECG correlation during diagnostic work-up before pacemaker implantation was an independent predictor of syncopal recurrence on multivariate analysis (HR: 1.90; P = 0.002).

Conclusion: In selecting patients with syncope of suspected bradyarrhythmic aetiology for pacemaker implantation, establishing a correlation between syncope and bradyarrhythmias maximizes the efficacy of pacing and reduces the risk of syncopal recurrences.
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http://dx.doi.org/10.1093/europace/euaa188DOI Listing
November 2020

Differentiating hereditary arrhythmogenic right ventricular cardiomyopathy from cardiac sarcoidosis fulfilling 2010 ARVC Task Force Criteria.

Heart Rhythm 2021 Feb 22;18(2):231-238. Epub 2020 Sep 22.

University Heart Center, University Hospital Zurich, Switzerland. Electronic address:

Background: The clinical presentation of cardiac sarcoidosis (CS) may resemble that of arrhythmogenic right ventricular cardiomyopathy (ARVC).

Objective: The purpose of this study was to identify clinical variables to better discriminate between patients with genetically determined ARVC and those with CS fulfilling definite 2010 ARVC Task Force Criteria (TFC).

Methods: In this multicenter study, 10 patients with CS fulfilling definite 2010 ARVC TFC were age and gender matched with 10 genetically proven ARVC patients. A cardiac F-fluorodeoxyglucose positron emission tomographic (F-FDG PET) scan was required for patients to be included in the study.

Results: The 2010 ARVC TFC did not reliably differentiate between the 2 diseases. CS patients presented with longer PR intervals, advanced atrioventricular block (AVB), and longer QRS duration (P <.001 and P = .009, respectively), whereas T-wave inversions (TWIs) in the peripheral leads were more common in ARVC patients (P = .009). CS patients presented with more extensive left ventricular involvement and lower left ventricular ejection fraction (LVEF), whereas ARVC patients had a larger right ventricular outflow tract (RVOT) (P = .044). PET scan positivity was only present in CS patients (90% vs 0%).

Conclusion: The 2010 ARVC TFC do not reliably differentiate between CS patients fulfilling 2010 ARVC TFC and those with hereditary ARVC. Prolonged PR interval, advanced AVB, longer QRS duration, right ventricular apical involvement, reduced LVEF, and positive F-FDG PET scan should raise the suspicion of CS, whereas larger RVOT dimensions, subtricuspid involvement and peripheral TWI favor a diagnosis of hereditary ARVC.
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http://dx.doi.org/10.1016/j.hrthm.2020.09.015DOI Listing
February 2021

Procedural sedation for direct current cardioversion: a feasibility study between two management strategies in the emergency department.

BMC Cardiovasc Disord 2020 08 25;20(1):388. Epub 2020 Aug 25.

Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital "Ospedali Riuniti Umberto I - Lancisi - Salesi", Via Conca 71, Ancona, Italy.

Background: A cardiologist-only approach to procedural sedation with midazolam in the setting of elective cardioversion (DCC) for AF has already been proven as safe as sedation with propofol and anaesthesiologist assistance. No data exist regarding the safety of such a strategy during emergency procedures. The aim of this study is to compare the feasibility of sedation with midazolam, administered by a cardiologist, to an anaesthesiologist-assisted protocol with propofol in emergency DCC.

Methods: Single centre, prospective, open blinded, randomized study including all consecutive patients admitted to the Emergency Department requiring urgent or emergency DCC. Patients were randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the midazolam group were managed by the cardiologist only, while patients treated with propofol group underwent DCC with anaesthesiologist assistance.

Results: Sixty-nine patients were enrolled and split into two groups. Eighteen patients (26.1%) experienced peri-procedural adverse events (bradycardia, severe hypotension and severe hypoxia), which were similar between the two groups and all successfully managed by the cardiologist. No deaths, stroke or need for invasive ventilation were registered. Patients treated with propofol experienced a greater decrease in systolic and diastolic blood pressure when compared with those treated with midazolam. As the procedure was shorter when midazolam was used, the median cost of urgent/emergency DCC with midazolam was estimated to be 129.0 € (1st-3rd quartiles 114.6-151.6) and 195.6 € (1st-3rd quartiles 147.3-726.7) with propofol (p < .001).

Conclusions: Procedural sedation with midazolam given by the cardiologist alone was feasible, well-tolerated and cost-effective in emergency DCC.
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http://dx.doi.org/10.1186/s12872-020-01664-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449000PMC
August 2020

Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design.

J Interv Card Electrophysiol 2020 Aug 24. Epub 2020 Aug 24.

Heart Rhythm Center, Centro Cardiologico Monzino IRCCS, Milan, Italy.

Purpose: Catheter ablation (CA) procedures are characterized by exposure to ionizing radiations (IR). IR can cause DNA damage and may lead to carcinogenesis if not efficiently repaired. The primary endpoint of this study is to investigate whether intravenous administration of N-acetylcysteine prior to CA procedure may prevent systemic oxidative stress and genomic DNA damage induced by exposure to IR.

Methods: The "Cardiac Arrhythmia catheter ablation procedures guided by x-Ray imaging: N-Acetylcysteine Protection Against radiation induced Cellular damagE" (CARAPACE) study is a prospective, randomized, single-blinded, parallel-arm monocenter study enrolling 550 consecutive patients undergoing CA at the Arrhythmology Unit of Centro Cardiologico Monzino (CCM). Inclusion criteria are age ≥ 18, indication for CA procedure guided by IR imaging, and written informed consent. IR levels will be measured via fluoroscopy time, effective dose, and dose area product. Glutathione and glutathione disulfide concentrations will be measured, and urinary levels of 8-iso-prostaglandin-F and 8-hydroxy-2-deoxyguanosine will be quantified. The enrolled patients will be randomized 1:1 to the N-acetylcysteine group or to the control group.

Results: We expect that pre-operative administration of N-acetylcysteine will prevent IR-induced systemic oxidative stress. The study will provide data on oxidative DNA damage assessed by urinary 8-hydroxy-2-deoxyguanosine levels and direct evidence of genomic DNA damage in blood cells by comet assay.

Conclusion: Catheter ablation procedures can lead to IR exposure and subsequent DNA damage. N-acetylcysteine administration prior to the procedure may prevent them and therefore lead to less possible complications.

Trial Registration: www.clinicaltrials.gov (NCT04154982).
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http://dx.doi.org/10.1007/s10840-020-00853-4DOI Listing
August 2020

Diagnostic Yield of Electroanatomic Voltage Mapping in Guiding Endomyocardial Biopsies.

Circulation 2020 Sep 14;142(13):1249-1260. Epub 2020 Aug 14.

Department of Clinical Electrophysiology and Pacing(M.C., V.C., A.G., G.V., F.T., R.S., C.T.), Centro Cardiologico Monzino IRCCS, Milano, Italy.

Background: Electroanatomic voltage mapping (EVM) is a promising modality for guiding endomyocardial biopsies (EMBs). However, few data support its feasibility and safety. We now report the largest cohort of patients undergoing EVM-guided EMBs to show its diagnostic yield and to compare it with a cardiac magnetic resonance (CMR)-guided approach.

Methods: We included 162 consecutive patients undergoing EMB at our institution from 2010 to 2019. EMB was performed in pathological areas identified at EVM and CMR. CMR and EVM sensitivity and specificity regarding the identification of pathological substrates of myocardium were evaluated according to EMB results.

Results: Preoperative CMR showed late gadolinium enhancement in 70% of the patients, whereas EVM identified areas of low voltage in 61%. Right (73%), left (19%), or both ventricles (8%) underwent sampling. EVM proved to have sensitivity similar to CMR (74% versus 77%), with specificity being 70% and 47%, respectively. In 12 patients with EMB-proven cardiomyopathy, EVM identified pathological areas that had been undetected at CMR evaluation. Sensitivity of pooled EVM and CMR was as high as 95%. EMB analysis allowed us to reach a new diagnosis, different from the suspected clinical diagnosis, in 39% of patients. The complications rate was low, mostly related to vascular access, with no patients requiring urgent management.

Conclusions: EVM proved to be a promising tool for targeted EMB because of its sensitivity and specificity for identification of myocardial pathological substrates. EVM was demonstrated to have accuracy similar to CMR. EVM and CMR together conferred a positive predictive value of 89% on EMB.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046900DOI Listing
September 2020

Electrocardiogram for the Diagnosis of Acute Myocardial Infarction in Patients with Right Ventricular Paced Rhythm: Old but Gold.

J Electrocardiol 2020 Sep - Oct;62:1-4. Epub 2020 Jul 21.

Division of Cardiology, S. Maria della Misericordia Hospital, Perugia, Italy.

Ventricular pacing may interfere with the interpretation of ECG among patients with suspected acute myocardial infarction (AMI), with possible delay of reperfusion therapy. Since left bundle branch block has a similar ECG morphology to right ventricular paced rhythm, Sgarbossa and modified Sgarbossa criteria could be useful in this setting. We present four clinical cases in which a recently proposed clinical-instrumental algorithm has been adopted to manage patients with right ventricular paced rhythm and suspected AMI.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.07.006DOI Listing
July 2020

Impact of the COVID-19 Pandemic on a Tertiary-Level Electrophysiology Laboratory in Italy.

Circ Arrhythm Electrophysiol 2020 09 23;13(9):e008774. Epub 2020 Jul 23.

Cardiology and Arrhythmology Clinic (P.C., G.V., R.P., U.F., A.M., S.M., G.S., L. Cipolletta, M.C., G.G., A.C., M.C., F.G., A.D.R.), University Hospital "Ospedali Riuniti", Ancona, Italy.

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http://dx.doi.org/10.1161/CIRCEP.120.008774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482615PMC
September 2020

Recent advances in three-dimensional electroanatomical mapping guidance for the ablation of complex atrial and ventricular arrhythmias.

J Interv Card Electrophysiol 2020 May 26. Epub 2020 May 26.

Cardiology and Arrhythmology Clinic, University Hospital "Ospedali Riuniti Umberto I - Lancisi - Salesi", Ancona, Italy.

Purpose: To provide a brief overview of some relevant technological advances in the field of three-dimensional electroanatomical mapping (3D-EAM) that have recently entered the clinical arena and their role in guiding catheter ablation (CA) of complex atrial and ventricular arrhythmias.

Methods: In this technical report, we describe the general features of three novel algorithms featured in the updated CARTO PRIME™ mapping module for CARTO®3 version 7 3D-EAM system (Biosense Webster Inc., Diamond Bar, CA, USA): local activation time (LAT) hybrid, coherent mapping and map replay modules. We also report three challenging arrhythmia cases in which CA was successfully guided by these softwares.

Results: The LAT hybrid module was used in a case of premature ventricular complex originating from the right coronary cusp. This algorithm facilitated safe positioning of the ablation catheter away from the right coronary ostium, avoiding potential harm to this vital structure. The coherent mapping module helped to identify the critical as well as a bystander isthmus of an atrial macro-re-entrant tachycardia in a grown-up patient with congenital heart disease. The map replay module allowed rapid retrospective activation mapping of two unstable ventricular tachycardias in a case of nonischemic cocaine-associated cardiomyopathy.

Conclusion: 3D-EAM systems offer significant advantages in the management of challenging arrhythmias, and the introduction of novel algorithms underpins improvements in patients' outcomes. Given the increasing sophistication of these systems, however, a close collaboration among cardiac electrophysiologists, engineers and technicians is highly needed in order to get the best from the available technology.
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http://dx.doi.org/10.1007/s10840-020-00781-3DOI Listing
May 2020

Clinical and Molecular Data Define a Diagnosis of Arrhythmogenic Cardiomyopathy in a Carrier of a Brugada-Syndrome-Associated Mutation.

Genes (Basel) 2020 05 20;11(5). Epub 2020 May 20.

Cardiac Arrhythmia Research Centre, Centro Cardiologico Monzino IRCCS, 20141 Milan, Italy.

Plakophilin-2 () is the most frequently mutated desmosomal gene in arrhythmogenic cardiomyopathy (ACM), a disease characterized by structural and electrical alterations predominantly affecting the right ventricular myocardium. Notably, ACM cases without overt structural alterations are frequently reported, mainly in the early phases of the disease. Recently, the p.S183N mutation was found in a patient affected by Brugada syndrome (BS), an inherited arrhythmic channelopathy most commonly caused by sodium channel gene mutations. We here describe a case of a patient carrier of the same BS-related p.S183N mutation but with a clear diagnosis of ACM. Specifically, we report how clinical and molecular investigations can be integrated for diagnostic purposes, distinguishing between ACM and BS, which are increasingly recognized as syndromes with clinical and genetic overlaps. This observation is fundamentally relevant in redefining the role of genetics in the approach to the arrhythmic patient, progressing beyond the concept of "one mutation, one disease", and raising concerns about the most appropriate approach to patients affected by structural/electrical cardiomyopathy. The merging of genetics, electroanatomical mapping, and tissue and cell characterization summarized in our patient seems to be the most complete diagnostic algorithm, favoring a reliable diagnosis.
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http://dx.doi.org/10.3390/genes11050571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288341PMC
May 2020

Long-Term Arrhythmic Risk Assessment in Biopsy-Proven Myocarditis.

JACC Clin Electrophysiol 2020 05 26;6(5):574-582. Epub 2020 Feb 26.

Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy.

Objectives: This study sought to assess long-term arrhythmic risk in patients with myocarditis who received an implantable cardioverter-defibrillator (ICD).

Background: The arrhythmic risk of patients with myocarditis overtime remains poorly known.

Methods: The study enrolled 56 patients with biopsy-proven myocarditis who received an ICD for either primary (57%) or secondary prevention (43%) according to current guidelines. Clinical characteristics, biopsy findings, electrophysiological data from endocardial 3-dimensional electroanatomic voltage mapping, and device interrogation data were analyzed to detect arrhythmic events overtime. Coronary angiography excluded significant coronary artery disease in all patients.

Results: At a mean follow-up of 74 ± 60 months (median 65 months), 25 (45%) patients had major ventricular arrhythmias treated by ICD intervention (76% being terminated by ICD shock and 24% by antitachyarrhythmia burst pacing). At multivariable analysis, the presence of sustained ventricular tachycardia on admission (hazard ratio: 13.0; 95% confidence interval: 2.0 to 35.0; p = 0.032) and the extension of the areas of low potentials at the bipolar endocardial mapping (hazard ratio: 1.19; 95% confidence interval: 1.04 to 1.37; p = 0.013) were the only independent predictors of appropriate ICD interventions. A cutoff value of 10% of abnormal bipolar area at electroanatomical ventricular mapping discriminated patients with appropriate ICD interventions with a sensitivity of 89% and a specificity of 85%.

Conclusions: The study demonstrates that the prevalence of life-threatening ventricular arrhythmias in patients with myocarditis receiving an ICD according to current guidelines is high and the arrhythmic risk persists late overtime. Electroanatomical ventricular mapping may be a useful tool to identify patients at greater arrhythmic risk.
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http://dx.doi.org/10.1016/j.jacep.2019.12.010DOI Listing
May 2020

Subclinical progression of systemic sclerosis-related cardiomyopathy.

Eur J Prev Cardiol 2020 11 19;27(17):1876-1886. Epub 2020 Apr 19.

Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital 'Ospedali Riuniti', Italy.

Aims: Cardiac involvement in patients with systemic sclerosis (SSc) is frequent and represents a negative prognostic factor. Recent studies have described subclinical heart involvement of both the right ventricle (RV) and left ventricle (LV) via speckle-tracking-derived global longitudinal strain (GLS). It is currently unknown if SSc-related cardiomyopathy progresses through time. Our aim was to assess the progression of subclinical cardiac involvement in patients with SSc via speckle-tracking-derived GLS.

Methods: This was a prospective longitudinal study enrolling 72 consecutive patients with a diagnosis of SSc and no structural heart disease nor pulmonary hypertension. A standard echocardiographic exam and GLS calculations were performed at baseline and at follow-up.

Results: Traditional echocardiographic parameters did not differ from baseline to 20-month follow-up. LV GLS, despite being already impaired at baseline, worsened significantly during follow-up (from -19.8 ± 3.5% to -18.7 ± 3.5%,  = .034). RV GLS impairment progressed through the follow-up period (from -20.9 ± 6.1% to -18.7 ± 5.4%,  = .013). The impairment was more pronounced for the endocardial layers of both LV (from -22.5 ± 3.9% to -21.4 ± 3.9%,  = .041) and RV (-24.2 ± 6.2% to -20.6 ± 5.9%,  = .001). A 1% worsening in RV GLS was associated with an 18% increased risk of all-cause death or major cardiovascular event ( = .03) and with a 55% increased risk of pulmonary hypertension ( = .043).

Conclusion: SSC-related cardiomyopathy progresses over time and can be detected by speckle-tracking GLS. The highest progression towards reduced deformation was registered for the endocardial layers, which supports the hypothesis that microvascular dysfunction is the main determinant of heart involvement in SSc patients and starts well before overt pulmonary hypertension.
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http://dx.doi.org/10.1177/2047487320916591DOI Listing
November 2020

Prospective evaluation of the multisensor HeartLogic algorithm for heart failure monitoring.

Clin Cardiol 2020 Jul 18;43(7):691-697. Epub 2020 Apr 18.

Cardiology Division, Università Politecnica delle Marche, Ancona, Italy.

Background: The HeartLogic algorithm measures data from multiple implantable cardioverter-defibrillator-based sensors and combines them into a single index. The associated alert has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation.

Hypothesis: We describe a multicenter experience of remote HF management by means of HeartLogic and appraise the value of an alert-based follow-up strategy.

Methods: The alert was activated in 104 patients. All patients were followed up according to a standardized protocol that included remote data reviews and patient phone contacts every month and at the time of alerts. In-office examinations were performed every 6 months or when deemed necessary.

Results: During a median follow-up of 13 (10-16) months, the overall number of HF hospitalizations was 16 (rate 0.15 hospitalizations/patient-year) and 100 alerts were reported in 53 patients. Sixty alerts were judged clinically meaningful, and were associated with multiple HF-related conditions. In 48 of the 60 alerts, the clinician was not previously aware of the condition. Of these 48 alerts, 43 triggered clinical actions. The rate of alerts judged nonclinically meaningful was 0.37/patient-year, and the rate of hospitalizations not associated with an alert was 0.05/patient-year. Centers performed remote follow-up assessments of 1113 scheduled monthly transmissions (10.3/patient-year) and 100 alerts (0.93/patient-year). Monthly remote data review allowed to detect 11 (1%) HF events requiring clinical actions (vs 43% actionable alerts, P < .001).

Conclusions: HeartLogic allowed relevant HF-related clinical conditions to be identified remotely and enabled effective clinical actions to be taken; the rates of unexplained alerts and undetected HF events were low. An alert-based management strategy seemed more efficient than a scheduled monthly remote follow-up scheme.
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http://dx.doi.org/10.1002/clc.23366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368302PMC
July 2020

Novel risk calculator performance in athletes with arrhythmogenic right ventricular cardiomyopathy.

Heart Rhythm 2020 08 19;17(8):1251-1259. Epub 2020 Mar 19.

Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.

Background: Disease progression and ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are correlated with physical exercise, and clinical detraining and avoidance of competitive sport practice are suggested for ARVC patients. An algorithm assessing primary arrhythmic risk in ARVC patients was recently developed by Cadrin-Tourigny et al. Data regarding its transferability to athletes are lacking.

Objective: The purpose of this study was to assess the reliability of the Cadrin-Tourigny risk prediction algorithm in a cohort of athletes with ARVC and to describe the impact of clinical detraining on disease progression.

Methods: All athletes undergoing clinical detraining after ARVC diagnosis at our institution were enrolled. Baseline and follow-up clinical characteristics and data on VA events occurring during follow-up were collected. The Cadrin-Tourigny algorithm was used to calculate the a priori predicted VA risk, which was compared with the observed outcomes.

Results: Twenty-five athletes (age 36.1 ± 14.0 years; 80% male) with definite ARVC who were undergoing clinical detraining were enrolled. Over median (interquartile range) follow-up of 5.3 (3.2-6.6) years, a reduction in premature ventricular complex (PVC) burden (P = .001) was assessed, and 10 VA events (40%) were recorded. The a priori algorithm-predicted risk seemed to fit with the observed cohort arrhythmic risk [mean observed-predicted risk difference over 5 years -0.85% (interquartile range -4.8% to +3.1%); P = .85]. At 1-year follow-up, 11 patients (44%) had an improved stress ECG response, and no significant changes in right ventricular ejection fraction were observed.

Conclusion: Clinical detraining is associated with PVC burden reduction in athletes with ARVC. The novel risk prediction algorithm does not seem to require any correction for its application to ARVC athletes.
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http://dx.doi.org/10.1016/j.hrthm.2020.03.007DOI Listing
August 2020

Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis.

Clin Chem Lab Med 2020 Sep;58(10):1725-1730

CEINGE Advanced Biotechnologies s.c.a.r.l., Naples, Italy.

Background Patients with cystic fibrosis (CF) have a reduced intestinal absorption of cholesterol and in a preliminary study we observed differences in plasma sterol profile between patients with pancreatic sufficiency (PS) and those with pancreatic insufficiency (PI). Therefore, we hypothesized that the sterol analysis may contribute to study the digestion and absorption state of lipids in patients with CF. To this aim we evaluated plasma sterols in a significant number of adult patients with CF in relation to the pancreatic status. Methods Beside cholesterol, we measured phytosterols and lathosterol as markers of intestinal absorption and hepatic biosynthesis, respectively, by gas-chromatography in plasma of adult CF patients with pancreatic sufficiency (PS-CF, n = 57), insufficiency (PI-CF, n = 97) and healthy subjects (control group, CT, n = 71). Results PI-CF patients had cholesterol and phytosterols levels significantly lower than PS-CF and CT (p < 5 × 10-10) suggesting a reduced intestinal absorption of sterols related to PI. Instead, lathosterol was significantly higher in PI-CF patients than PS-CF and CT (p < 0.0003) indicating an enhanced cholesterol biosynthesis. In PI-CF patients, phytosterols positively correlate with vitamin E (p = 0.004). Both the classes of molecules need cholesterol esterase for the intestinal digestion, thus the reduced levels of such lipids in serum from PI-CF patients may depend on a reduced enzyme activity, despite the pancreatic enzyme supplementation in all PI-CF patients. Conclusions A plasma sterols profile may be useful to evaluate the metabolic status of lipids in adult patients with CF and could help to manage the pancreatic enzyme supplementation therapy.
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http://dx.doi.org/10.1515/cclm-2019-1112DOI Listing
September 2020

Long-term follow-up analysis of a highly characterized arrhythmogenic cardiomyopathy cohort with classical and non-classical phenotypes-a real-world assessment of a novel prediction model: does the subtype really matter.

Europace 2020 05;22(5):797-805

Cardiology and Arrhythmology Clinic, Marche Polytechic University, University Hospital "Ospedali Riuniti", Ancona (AN), Italy.

Aims: To provide long-term outcome data on arrhythmogenic cardiomyopathy (ACM) patients with non-classical forms [left dominant ACM (LD-ACM) and biventricular ACM (Bi-ACM)] and an external validation of a recently proposed algorithm for ventricular arrhythmia (VA) prediction in ACM patients.

Methods And Results: Demographic, clinical, and outcome data were retrieved from all ACM patients encountered at our institution. Patients were classified according to disease phenotype (R-ACM; Bi-ACM; LD-ACM). Overall and by phenotype long-term survival were calculated; the novel Cadrin-Tourigny et al. algorithm was used to calculate the a priori predicted VA risk, and it was compared with the observed outcome to test its reliability. One hundred and one patients were enrolled; three subgroups were defined (R-ACM, n = 68; Bi-ACM, n = 14; LD-ACM, n = 19). Over a median of 5.41 (2.59-8.37) years, the non-classical form cohort experienced higher rates of VAs than the classical form [5-year freedom from VAs: 0.58 (0.43-0.78) vs. 0.76 (0.66-0.89), P = 0.04]. The Cadrin-Tourigny et al. predictive model adequately described the overall cohort risk [mean observed-predicted risk difference (O-PRD): +6.7 (-4.3, +17.7) %, P = 0.19]; strafing by subgroup, excellent goodness-of-fit was demonstrated for the R-ACM subgroup (mean O-PRD, P = 0.99), while in the Bi-ACM and LD-ACM ones the real observed risk appeared to be underestimated [mean O-PRD: -20.0 (-1.1, -38.9) %, P < 0.0001; -22.6 (-7.8, -37.5) %, P < 0.0001, respectively].

Conclusion: Non-classical ACM forms appear more prone to VAs than classical forms. The novel prediction model effectively predicted arrhythmic risk in the classical R-ACM cohort, but seemed to underestimate it in non-classical forms.
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http://dx.doi.org/10.1093/europace/euz352DOI Listing
May 2020

Age-related changes of cholestanol and lathosterol plasma concentrations: an explorative study.

Lipids Health Dis 2019 Dec 30;18(1):235. Epub 2019 Dec 30.

Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.

Background: Cerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and lathosterol, respectively. The age of the patients suspected of having these disorders is highly variable due to the very different phenotypes. The early diagnosis of these disorders is important because specific therapeutic treatment could prevent the disease progression. The biochemical diagnosis of these defects is generally performed analyzing the sterol profile. Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and lathosterol among Italian unaffected newborns, children and healthy adults.

Methods: The sterols were extracted from 130 plasma samples (24 newborns, 33 children and 73 adults) by a liquid-liquid separation method and quantified by gas chromatography coupled with a flame ionization detector.

Results: Cholesterol, cholestanol and lathosterol levels together with the cholestanol/cholesterol and lathosterol/cholesterol ratios are statistically different among the three groups. Cholesterol levels progressively increased from newborns to children and to adults, whereas cholestanol/cholesterol and cholestanol/lathosterol ratios progressively decreased from newborns to children and to adults. Lathosterol levels were higher in adults than in both newborns and children. In the total population a positive correlation was observed between cholesterol levels and both cholestanol (correlation coefficient = 0.290, p = 0.001) and lathosterol levels (correlation coefficient = 0.353, p <  0.0001).

Conclusions: Although this study can only be considered an explorative experience due to the low number of analyzed samples, we revealed several differences of plasma cholestanol and lathosterol levels and their ratios to cholesterol levels among newborns, children and adults. These evidences indicate the need of age-related reference values of cholestanol and lathosterol concentrations, including also newborns and children.
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http://dx.doi.org/10.1186/s12944-019-1176-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937658PMC
December 2019