Baroni Dott. Matteo
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Magnetic resonance-conditional cardiac implantable electronic devices: an Italian perspective on the prevalence of mixed-brand systems over time.
Sci Rep2024 Nov;14(1):27006. doi: 27006.
Saporito Davide, Celentano Eduardo, Amellone Claudia, Zanotto Gabriele, Baroni Matteo, Miracapillo Gennaro, Biffi Mauro, Calvi Valeria, Spighi Lorenzo, Curnis Antonio, Pisanò Ennio Carmine Luigi, Rovaris Giovanni, Senatore Gaetano, Caravati Fabrizio, Notarangelo Francesca, Marini Massimiliano, Solimene Francesco, Piacenti Marcello, Tomasi Luca, Bontempi Luca, Nigro Gerardo, Poggio Luca, Pedretti Stefano, Giaccardi Marzia, Pastori Paolo, Talini Enrica, Maglia Giampiero, Baldassarre Irene, Giacopelli Daniele, Gargaro Alessio, Giammaria Massimo
Abstract
The historical restriction of magnetic resonance imaging (MRI) for patients with cardiac implantable electronic devices (CIEDs) has been lifted by certified MRI-conditional systems in recent years. Mixed-brand CIED systems consisting of a generator from one manufacturer and at least one lead from another manufacturer are not certified for MRI. We evaluated the temporal trend in the prevalence of mixed-brand systems in the era of MRI-conditional systems. Data were analyzed on 5853 CIEDs implanted de novo between 2012 and 2022 in 81 Italian centers linked to the nationwide Home Monitoring Expert Alliance network. The percentage of mixed-brand implants was calculated by device type (pacemaker, implantable cardioverter-defibrillator [ICD], cardiac resynchronization therapy [CRT] device) and over time. A mixed-brand system was implanted in 4.1% (95% CI, 3.6-4.6%) of analyzed patients or, by device type, in 4.5% (3.5-5.7%) of pacemaker patients, 1.1% (0.7-1.7%) of ICD patients, and 6.8% (5.7-7.9%) of CRT pacemaker/defibrillator patients (p?0.001). Prevalence of mixed-brand implants exhibited significant temporal fluctuations, first declining from 6.6% (2012-2014) to 1.3% (2019), and then increasing to 5.1% (2022). Temporal changes were statistically significant for pacemakers (p?0.001) and CRT devices (p?=?0.001), but not for ICDs (p?=?0.438). In the decade between 2012 and 2022, mixed-brand CIED systems were more prevalent in patients treated with pacemakers and CRT devices than in ICD recipients. A decline in the prevalence of mixed-brand systems was observed after the introduction of MRI-conditional systems, reaching a minimum in 2019, followed by a progressive increase in the subsequent years.
© 2024. The Author(s).
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[Proposal of a Hub & Spoke model for the centralization of patients at high risk of lead extraction].
G Ital Cardiol (Rome)2024 Aug;25(8):541-544. doi: 10.1714/4309.42922.
Garofani Ilaria, Preda Alberto, Baroni Matteo, Vargiu Sara, Varrenti Marisa, Colombo Giulia, Carbonaro Marco, Gigli Lorenzo, Paolucci Marco, Mazzone Patrizio
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Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature.
J Cardiovasc Dev Dis2024 Jul;11(7):. doi: 222.
Bonvicini Eleonora, Preda Alberto, Tognola Chiara, Falco Raffaele, Gidiucci Roberto, Leo Giulio, Vargiu Sara, Varrenti Marisa, Gigli Lorenzo, Baroni Matteo, Carbonaro Marco, Colombo Giulia, Maloberti Alessandro, Giannattasio Cristina, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.
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Exploring suitability to electrical storm ablation in patients in waiting list for heart transplantation: A single center experience.
Pacing Clin Electrophysiol2024 Oct;47(10):1418-1422. doi: 10.1111/pace.15036.
Gigli Lorenzo, Preda Alberto, Varrenti Marisa, Baroni Matteo, Vargiu Sara, Guarracini Fabrizio, Ammirati Enrico, Mazzone Patrizio
Abstract
Electrical storm (ES) is among the most fearsome events in patients in waiting list for heart transplantation (HT) and catheter ablation (CA) demonstrated to be effective in reduce the arrhythmic burden. However, selection criteria for CA suitability in this specific population have never been addressed before. We retrospectively enrolled 36 patients (mean age 51 ± 8 years; 83% men) waiting HT referred to our department for ES resistant to antiarrhythmic drugs and percutaneous stellate ganglion blockade. Twenty patients were judged suitable for VT ablation according to specific criteria including absence of increased arrhythmic burden secondary to volume overload and hemodynamic decompensation; expected CA outcome favorable due to etiology of the cardiomyopathy, no need for coronary revascularization and technical feasibility of the procedure. The pre-emptive use of mechanical circulatory supports (MCS) were discussed integrating the PAINESD score with additional clinical and hemodynamic parameters. Acute procedural success was accounted in 85% of cases with only two major complications. The CA group reported lower length of in-hospital stay after CA suitability evaluation (56 ± 17 vs. 131 ± 64 days, p = .004). Furthermore, at a mean follow-up of 703 ± 145 days, this group showed reduction of ventricular arrhythmia (VA) recurrence leading to implantable cardioverter defibrillator shock (4 vs. 8, p = .051) and underwent HT with a lower level of urgency (0 vs. 6 patients needed for UNOS1 status upgrade). Respectively, one patient of the CA group and two patients of the conservative group died (p = .839). At the end of follow-up, eight patients underwent heart transplantation (p = .964) while four patients underwent Left Ventricular Assist device (LVAD) implantation (p = .440). This pilot study should be a proof for further studies exploring CA of VAs as a possible bridge therapy to HT.
© 2024 Wiley Periodicals LLC.
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Contemporary Advances in Cardiac Remote Monitoring: A Comprehensive, Updated Mini-Review.
Medicina (Kaunas)2024 May;60(5):. doi: 819.
Preda Alberto, Falco Raffaele, Tognola Chiara, Carbonaro Marco, Vargiu Sara, Gallazzi Michela, Baroni Matteo, Gigli Lorenzo, Varrenti Marisa, Colombo Giulia, Zanotto Gabriele, Giannattasio Cristina, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Over the past decade, remote monitoring (RM) has become an increasingly popular way to improve healthcare and health outcomes. Modern cardiac implantable electronic devices (CIEDs) are capable of recording an increasing amount of data related to CIED function, arrhythmias, physiological status and hemodynamic parameters, providing in-depth and updated information on patient cardiovascular function. The extensive use of RM for patients with CIED allows for early diagnosis and rapid assessment of relevant issues, both clinical and technical, as well as replacing outpatient follow-up improving overall management without compromise safety. This approach is recommended by current guidelines for all eligible patients affected by different chronic cardiac conditions including either brady- and tachy-arrhythmias and heart failure. Beyond to clinical advantages, RM has demonstrated cost-effectiveness and is associated with elevated levels of patient satisfaction. Future perspectives include improving security, interoperability and diagnostic power as well as to engage patients with digital health technology. This review aims to update existing data concerning clinical outcomes in patients managed with RM in the wide spectrum of cardiac arrhythmias and Hear Failure (HF), disclosing also about safety, effectiveness, patient satisfaction and cost-saving.
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Coronary venous lead reimplantation vs. left bundle branch area pacing crossover following cardiac resynchronization therapy defibrillator extraction: a single-centre experience.
Europace2024 May;26(5):. doi: euae101.
Baroni Matteo, Preda Alberto, Carbonaro Marco, Fortuna Matteo, Guarracini Fabrizio, Gigli Lorenzo, Mazzone Patrizio
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Atrial tachycardia ablation through the sub-pulmonary ventricle in a patient with multiple malformations associated with congenitally corrected transposition of the great arteries and double-sided slow-pathway.
Clin Case Rep2024 Apr;12(4):e8745. doi: e8745.
Preda Alberto, Testoni Alessio, Baroni Matteo, Mazzone Patrizio, Gigli Lorenzo
Abstract
A 46-year-old woman with congenitally corrected transposition of the great arteries (ccTGA) associated with dextrocardia, situs viscerus inversus, and left superior vena cava persistence presented with an incessant supraventricular tachycardia. Electrophysiological study was not conclusive in differential diagnosis of atrial tachycardia versus atypical atrioventricular (AV) nodal reentrant tachycardia, also due to the unconventional anatomy of the coronary sinus. By a comprehensive mapping of cardiac chambers, a double side slow-pathway was localized in both atrial chambers and subsequently ablated by radiofrequency delivery without tachycardia changes. Aortic root and cusps were devoid of electrical activity. The muscular part of the sub-pulmonary ventricle at the level of interatrial septum showed an earliest activation signal of -90?ms and ablation of this site was effective in abolish the tachycardia. This is the first case to report technical concerns of septal atrial tachycardia ablation in ccTGA associated with multiple anatomical malformations. Moreover, some peculiarities have been reported for the first time including the presence of double-side AV nodal slow-pathway and atypical localization of the tachycardia origin into the muscular part of the sub-pulmonary ventricle instead of posterior pulmonary cusp.
© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.
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Left bundle branch area versus conventional pacing after transcatheter valve implant for aortic stenosis: the LATVIA study.
J Cardiovasc Med (Hagerstown)2024 Jun;25(6):450-456. doi: 10.2459/JCM.0000000000001619.
Dell'Era Gabriele, Baroni Matteo, Frontera Antonio, Ghiglieno Chiara, Carbonaro Marco, Penela Diego, Romano Carmine, Giordano Federica, Del Monaco Guido, Galimberti Paola, Mazzone Patrizio, Patti Giuseppe
Abstract
BACKGROUND:
Atrioventricular block (AVB) is a frequent complication in patients undergoing transcatheter aortic valve implantation (TAVI). Right apex ventricular pacing (RVP) represents the standard treatment but may induce cardiomyopathy over the long term. Left bundle branch area pacing (LBBAP) is a promising alternative, minimizing the risk of desynchrony. However, available evidence with LBBAP after TAVI is still low.
OBJECTIVE:
To assess the feasibility and safety of LBBAP for AVB post-TAVI compared with RVP.
METHODS:
Consecutive patients developing AVB early after TAVI were enrolled between 1 January 2022 and 31 December 2022 at three high-volume hospitals and received LBBAP or RVP. Data on procedure and at short-term follow-up (at least 3?months) were collected.
RESULTS:
A total of 38 patients (61% men, mean age 83?±?6?years) were included; 20 patients (53%) received LBBAP. Procedural success was obtained in all patients according to chosen pacing strategy. Electrical pacing performance at implant and after a mean follow-up of 4.2?±?2.8?months was clinically equivalent for both pacing modalities. In the LBBAP group, procedural time was longer (70?±?17 versus 58?±?15?min in the RVP group, P ?=?0.02) and paced QRS was shorter (120?±?19 versus 155?±?12?ms at implant, P ?0.001; 119?±?18 versus 157?±?9?ms at follow-up, P ?0.001). Complication rates did not differ between the two groups.
CONCLUSION:
In patients with AVB after TAVI, LBBAP is feasible and safe, resulting in a narrow QRS duration, either acutely and during the follow-up, compared with RVP. Further studies are needed to evaluate if LBBAP reduces pacing-induced cardiomyopathy in this clinical setting.
Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.
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Device-detected atrial sensing amplitudes as a marker of increased risk for new onset and progression of atrial high-rate episodes.
Heart Rhythm2024 Sep;21(9):1630-1639. doi: 10.1016/j.hrthm.2024.03.034.
Biffi Mauro, Celentano Eduardo, Giammaria Massimo, Curnis Antonio, Rovaris Giovanni, Ziacchi Matteo, Miracapillo Gennaro, Saporito Davide, Baroni Matteo, Quartieri Fabio, Marini Massimiliano, Pepi Patrizia, Senatore Gaetano, Caravati Fabrizio, Calvi Valeria, Tomasi Luca, Nigro Gerardo, Bontempi Luca, Notarangelo Francesca, Santobuono Vincenzo Ezio, Boggian Giulio, Arena Giuseppe, Solimene Francesco, Giaccardi Marzia, Maglia Giampiero, Perini Alessandro Paoletti, Volpicelli Mario, Giacopelli Daniele, Gargaro Alessio, Iacopino Saverio
Abstract
BACKGROUND:
Atrial high-rate episodes (AHREs) are frequent in patients with cardiac implantable electronic devices. A decrease in device-detected P-wave amplitude may be an indicator of periods of increased risk of AHRE.
OBJECTIVE:
The objective of this study was to assess the association between P-wave amplitude and AHRE incidence.
METHODS:
Remote monitoring data from 2579 patients with no history of atrial fibrillation (23% pacemakers and 77% implantable cardioverter-defibrillators, of which 40% provided cardiac resynchronization therapy) were used to calculate the mean P-wave amplitude during 1 month after implantation. The association with AHRE incidence according to 4 strata of daily burden duration (?15 minutes, ?6 hours, ?24 hours, ?7 days) was investigated by adjusting the hazard ratio with the CHADS-VASc score.
RESULTS:
The adjusted hazard ratio for 1-mV lower mean P-wave amplitude during the first month increased from 1.10 (95% confidence interval [CI], 1.05-1.15; P
CONCLUSION:
Device-detected P-wave amplitudes
Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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Arrhythmogenic Cardiomyopathy: Definition, Classification and Arrhythmic Risk Stratification.
J Clin Med2024 Jan;13(2):. doi: 456.
Varrenti Marisa, Preda Alberto, Frontera Antonio, Baroni Matteo, Gigli Lorenzo, Vargiu Sara, Colombo Giulia, Carbonaro Marco, Paolucci Marco, Giordano Federica, Guarracini Fabrizio, Mazzone Patrizio
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a heart disease characterized by a fibrotic replacement of myocardial tissue and a consequent predisposition to ventricular arrhythmic events, especially in the young. Post-mortem studies and the subsequent diffusion of cardiac MRI have shown that left ventricular involvement in arrhythmogenic cardiomyopathy is common and often develops early. Regarding the arrhythmic risk stratification, the current scores underestimate the arrhythmic risk of patients with arrhythmogenic cardiomyopathy with left involvement. Indeed, the data on arrhythmic risk stratification in this group of patients are contradictory and not exhaustive, with the consequence of not correctly identifying patients at a high arrhythmic risk who deserve protection from arrhythmic death. We propose a literature review on arrhythmic risk stratification in patients with ACM and left involvement to identify the main features associated with an increased arrhythmic risk in this group of patients.
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The Fluoroless Future in Electrophysiology: A State-of-the-Art Review.
Diagnostics (Basel)2024 Jan;14(2):. doi: 182.
Preda Alberto, Bonvicini Eleonora, Coradello Elena, Testoni Alessio, Gigli Lorenzo, Baroni Matteo, Carbonaro Marco, Vargiu Sara, Varrenti Marisa, Colombo Giulia, Paolucci Marco, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Fluoroscopy has always been the cornerstone imaging method of interventional cardiology procedures. However, radiation exposure is linked to an increased risk of malignancies and multiorgan diseases. The medical team is even more exposed to X-rays, and a higher incidence of malignancies was reported in this professional group. In the last years, X-ray exposure has increased rapidly, involving, above all, the medical team and young patients and forcing alternative fluoroless imaging methods. In cardiac electrophysiology (EP) and pacing, the advent of 3D electroanatomic mapping systems with dedicated catheters has allowed real-time, high-density reconstruction of both heart anatomy and electrical activity, significantly reducing the use of fluoroscopy. In addition, the diffusion of intracardiac echocardiography has provided high anatomical resolution of moving cardiac structures, providing intraprocedural guidance for more complex catheter ablation procedures. These methods have largely demonstrated safety and effectiveness, allowing for a dramatic reduction in X-ray delivery in most arrhythmias' ablations. However, some technical concerns, as well as higher costs, currently do not allow their spread out in EP labs and limit their use to only procedures that are considered highly complex and time-consuming and in young patients. In this review, we aim to update the current employment of fluoroless imaging in different EP procedures, focusing on its strengths and weaknesses.
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Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.
Artif Organs2024 May;48(5):525-535. doi: 10.1111/aor.14708.
Rordorf Roberto, Pignalosa Leonardo, Casula Matteo, Perna Enrico, Baroni Matteo, Garascia Andrea, Guida Stefania, Gazzoli Fabrizio, Pini Daniela, Cannata Francesco, Pellegrino Marta, Vittori Claudia, De Filippo Paolo, Malanchini Giovanni, Vergara Pasquale, Della Bella Paolo, Gulletta Simone,
Abstract
BACKGROUND:
Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD.
METHODS:
We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy.
RESULTS:
A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21?months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively.
CONCLUSIONS:
Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.
© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
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Fighting Cardiac Thromboembolism during Transcatheter Procedures: An Update on the Use of Cerebral Protection Devices in Cath Labs and EP Labs.
Life (Basel)2023 Aug;13(9):. doi: 1819.
Preda Alberto, Montalto Claudio, Galasso Michele, Munafò Andrea, Garofani Ilaria, Baroni Matteo, Gigli Lorenzo, Vargiu Sara, Varrenti Marisa, Colombo Giulia, Carbonaro Marco, Della Rocca Domenico Giovanni, Oreglia Jacopo, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.
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Subcutaneous Implantable Cardioverter Defibrillator: A Contemporary Overview.
Life (Basel)2023 Jul;13(8):. doi: 1652.
Guarracini Fabrizio, Preda Alberto, Bonvicini Eleonora, Coser Alessio, Martin Marta, Quintarelli Silvia, Gigli Lorenzo, Baroni Matteo, Vargiu Sara, Varrenti Marisa, Forleo Giovanni Battista, Mazzone Patrizio, Bonmassari Roberto, Marini Massimiliano, Droghetti Andrea
Abstract
The difference between subcutaneous implantable cardioverter defibrillators (S-ICDs) and transvenous ICDs (TV-ICDs) concerns a whole extra thoracic implantation, including a defibrillator coil and pulse generator, without endovascular components. The improved safety profile has allowed the S-ICD to be rapidly taken up, especially among younger patients. Reports of its role in different cardiac diseases at high risk of SCD such as hypertrophic and arrhythmic cardiomyopathies, as well as channelopathies, is increasing. S-ICDs show comparable efficacy, reliability, and safety outcomes compared to TV-ICD. However, some technical issues (i.e., the inability to perform anti-bradycardia pacing) strongly limit the employment of S-ICDs. Therefore, it still remains only an alternative to the traditional ICD thus far. This review aims to provide a contemporary overview of the role of S-ICDs compared to TV-ICDs in clinical practice, including technical aspects regarding device manufacture and implantation techniques. Newer outlooks and future perspectives of S-ICDs are also brought up to date.
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Electrocardiogram Changes in the Postictal Phase of Epileptic Seizure: Results from a Prospective Study.
J Clin Med2023 Jun;12(12):. doi: 4098.
Gigli Lorenzo, Sala Simone, Preda Alberto, Okubo Kenji, Peretto Giovanni, Frontera Antonio, Varrenti Marisa, Baroni Matteo, Carbonaro Marco, Vargiu Sara, Di Resta Chiara, Striano Pasquale, Mazzone Patrizio, Della Bella Paolo
Abstract
BACKGROUND:
The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure.
MATERIALS AND METHODS:
From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed.
RESULTS:
One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure ( = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4).
CONCLUSION:
The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure.
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Left Atrial Appendage Occlusion in Patients with Failure of Antithrombotic Therapy: Good Vibes from Early Studies.
J Clin Med2023 Jun;12(11):. doi: 3859.
Preda Alberto, Baroni Matteo, Varrenti Marisa, Vargiu Sara, Carbonaro Marco, Giordano Federica, Gigli Lorenzo, Mazzone Patrizio
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and predisposes patients to an increased risk of cardioembolic events (CE), such as ischemic stroke, TIA, or systemic embolism [...].
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Prognostic significance of remotely monitored nocturnal heart rate in heart failure patients with reduced ejection fraction.
Heart Rhythm2023 Feb;20(2):233-240. doi: 10.1016/j.hrthm.2022.10.018.
D'Onofrio Antonio, Marini Massimiliano, Rovaris Giovanni, Zanotto Gabriele, Calvi Valeria, Iacopino Saverio, Biffi Mauro, Solimene Francesco, Della Bella Paolo, Caravati Fabrizio, Pisanò Ennio C, Amellone Claudia, D'Alterio Giuliano, Pedretti Stefano, Santobuono Vincenzo E, Russo Antonio Dello, Nicolis Daniele, De Salvia Alberto, Baroni Matteo, Quartieri Fabio, Manzo Michele, Rapacciuolo Antonio, Saporito Davide, Maines Massimiliano, Marras Elena, Bontempi Luca, Morani Giovanni, Giacopelli Daniele, Gargaro Alessio, Giammaria Massimo
Abstract
BACKGROUND:
Elevated resting heart rate is a risk factor for cardiovascular events.
OBJECTIVE:
The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices.
METHODS:
We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on ?-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF).
RESULTS:
The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (?57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P 75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P
CONCLUSION:
In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on ?-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity.
Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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Uric acid significantly correlates with the presence of low-voltage areas at the endocardial mapping in patients with non-valvular atrial fibrillation.
Nutr Metab Cardiovasc Dis2023 Jul;33(7):1323-1329. doi: 10.1016/j.numecd.2023.05.002.
Baroni Matteo, Fortuna Matteo, Maloberti Alessandro, Leidi Filippo, Ciampi Claudio Mario, Carbonaro Marco, Testoni Alessio, Vargiu Sara, Varrenti Marisa, Paolucci Marco, Gigli Lorenzo, Giannattasio Cristina, Mazzone Patrizio
Abstract
BACKGROUND AND AIMS:
Interest in the role of atrial substrate in maintaining Atrial Fibrillation (AF) is growing. Fibrosis is the culprit in the electrical derangement of the myocytes. Many cardiovascular risk factors are known to be linked to atrial scarring; among them Uric Acid (UA) is emerging. The purpose of our study is to find whether UA is associated with Left Atrium (LA) with pathological substrate.
METHODS AND RESULTS:
81 patients who underwent radiofrequency transcatheter ablation for nonvalvular AF at the cardiological department of the Niguarda Hospital were enrolled in an observational, cross-sectional, single-center study. UA levels were analysed before the procedure. High density electroanatomic mapping of the LA was performed and patients were divided according to the presence or not of areas of pathological substrate (bipolar voltage
CONCLUSIONS:
In a population of patients who underwent AF ablation, higher UA levels were significantly associated with pathological LA substrate at electro-anatomical mapping.
Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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Left Bundle Branch Area Pacing over His Bundle Pacing: How Far Have We Come?
J Clin Med2023 May;12(9):. doi: 3251.
Baroni Matteo, Preda Alberto, Varrenti Marisa, Vargiu Sara, Carbonaro Marco, Giordano Federica, Gigli Lorenzo, Mazzone Patrizio
Abstract
Implantable cardiac pacemakers have greatly evolved during the few past years, focusing on newer modalities of physiologic cardiac pacing [...].
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Temporal association between drops in thoracic impedance and malignant ventricular arrhythmia: A longitudinal analysis of remote monitoring trends.
J Cardiovasc Electrophysiol2023 Apr;34(4):947-956. doi: 10.1111/jce.15834.
Rodio Giovanna, Iacopino Saverio, Pisanò Ennio C, Calvi Valeria, Rovaris Giovanni, Marini Massimiliano, Giammaria Massimo, Caravati Fabrizio, Maglia Giampiero, Zanotto Gabriele, Della Bella Paolo, Biffi Mauro, Curnis Antonio, Maines Massimiliano, Orsida Daniela, Santamaria Matteo, Bisignani Giovanni, Baroni Matteo, Lissoni Fabio, Duca Antonio, Forleo Giovanni B, Piemontese Carlo, De Salvia Alberto, Miracapillo Gennaro, Celentano Eduardo, Zecchin Massimo, Luzzi Giovanni, Giacopelli Daniele, Gargaro Alessio, D'Onofrio Antonio
Abstract
INTRODUCTION:
Thoracic impedance (TI) drops measured by implantable cardioverter-defibrillators (ICDs) have been reported to correlate with ventricular tachycardia/fibrillation (VT/VF). The aim of our study was to assess the temporal association of decreasing TI trends with VT/VF episodes through a longitudinal analysis of daily remote monitoring data from ICDs and cardiac resynchronization therapy defibrillators (CRT-Ds).
METHODS AND RESULTS:
Retrospective data from 2384 patients were randomized 1:1 into a derivation or validation cohort. The TI decrease rate was defined as the percentage of rolling weeks with a continuously decreasing TI trend. The derivation cohort was used to determine a TI decrease rate threshold for a ?99% specificity of arrhythmia prediction. The associated risk of VT/VF episodes was estimated in the validation cohort by dividing the available follow-up into 60-day assessment intervals. Analyses were performed separately for 1354 ICD and 1030 CRT-D patients. During a median follow-up of 2.0 years, 727 patients (30.4%) experienced 3298 confirmed VT/VF episodes. In the ICD group, a TI decrease rate of >60% was associated with a higher risk of VT/VF episode in a 60-day assessment interval (stratified hazard ratio, 1.42; 95% confidence interval (CI), 1.05-1.92; p?=?.023). The TI decrease preceded (40.8%) or followed (59.2%) the VT/VF episodes. In the CRT-D group, no association between TI decrease and VT/VF episodes was observed (p?=?.84).
CONCLUSION:
In our longitudinal analysis, TI decrease was associated with VT/VF episodes only in ICD patients. Preventive interventions may be difficult since episodes can occur before or after TI decrease.
© 2023 Wiley Periodicals LLC.
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Ventricular Arrhythmias and Implantable Cardioverter-Defibrillator Therapy in Women: A Propensity Score-Matched Analysis.
JACC Clin Electrophysiol2022 Dec;8(12):1553-1562. doi: 10.1016/j.jacep.2022.08.002.
Maglia Giampiero, Giammaria Massimo, Zanotto Gabriele, D'Onofrio Antonio, Della Bella Paolo, Marini Massimiliano, Rovaris Giovanni, Iacopino Saverio, Calvi Valeria, Pisanò Ennio C, Ziacchi Matteo, Curnis Antonio, Senatore Gaetano, Caravati Fabrizio, Saporito Davide, Forleo Giovanni B, Pedretti Stefano, Santobuono Vincenzo Ezio, Pepi Patrizia, De Salvia Alberto, Balestri Giulia, Maines Massimiliano, Orsida Daniela, Bisignani Giovanni, Baroni Matteo, Lissoni Fabio, Bertini Matteo, Giacopelli Daniele, Gargaro Alessio, Biffi Mauro
Abstract
BACKGROUND:
Causes of sex differences in incidence of sustained ventricular arrhythmias (SVAs) are poorly understood.
OBJECTIVES:
This study aims to investigate sex-specific risk of SVAs and device therapies by balancing sex groups in relation to several baseline characteristics with the propensity score (PS).
METHODS:
We used a large remote monitoring dataset from implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds). Study endpoints were time to the first appropriate SVA, time to the first device therapy for SVA, and time to the first ICD shock. Results were compared between females and a PS-matched male subgroup.
RESULTS:
In a cohort of 2,532 patients with an ICD or CRT-D (median age, 70 years), 488 patients (19.3%) were women. After selecting 488 men PS-matched for 19 variables relative to baseline demographics, implant indications, principal comorbidities, and concomitant therapy, yet the SVA rate at the 2.1-year median follow-up was significantly lower in women than in man (adjusted HR: 0.65; 95% CI: 0.51-0.81; P
CONCLUSIONS:
After matching demographics, indications, principal comorbidities, and concomitant therapy, women still exhibited a lower SVA risk profile than men, except in the subgroups of CRT-D or/and ejection fraction
Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Direct anchoring technique for pacing and defibrillation leads inserted through cephalic vein: insight for a single high-volume center.
Minerva Cardiol Angiol2023 Jun;71(3):342-348. doi: 10.23736/S2724-5683.22.06147-6.
Baroni Matteo, Gigli Lorenzo, Posca Francesco, Carbonaro Marco, Leidi Filippo, Fortuna Matteo, Ciampi Claudio M, Proietti Riccardo
Abstract
BACKGROUND:
Direct anchoring of PM and ICD leads over cephalic vein body is officially discouraged by manufactures due to a supposed risk of conductor fracture or insulation failure, however careful tightening of anchoring knots can probably prevent lead damage. Direct anchoring (DA) technique is routinely used in our center for all leads inserted by cephalic vein while standard anchoring sleeves are used to secure subclavian leads only. Aim of the study is to assess short- and long-term safety of cephalic direct anchoring technique.
METHODS:
All patients undergoing PM and ICD implantation in our center from November 2014 to March 2016 were consecutively enrolled. Primary endpoints were acute lead fracture, lead dislodgement and chronic lead failure. Secondary endpoint was a composite of short-term surgical complications (pocket hematoma, pneumothorax, and pericardial effusion) plus device infections. Subclavian leads secured with sleeve anchoring (SA) were used as control.
RESULTS:
A total of 550 leads were implanted in 310 consecutive patients. DA involved 323 leads (59%) while SA was used for 227 (41%). Median follow-up was 50 months (IQR 24-62 months). 17 lead malfunctions (3.1%) were observed during follow-up. No difference was observed between groups (10 DA vs. 7 SP, P=ns). Survival analysis found no difference between groups. Secondary endpoints were not statistically different between groups (5 vs. 1, P=0.08).
CONCLUSIONS:
Direct anchoring technique of PM and ICD leads is a safe technique and does not increase lead malfunction risk.
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Clinical Performance of Oral Anticoagulants in Elderly with Atrial Fibrillation and Low Body Weight: Insight into Italian Cohort of PREFER-AF and PREFER-AF Prolongation Registries.
J Clin Med2022 Jun;11(13):. doi: 3751.
Russo Vincenzo, Attena Emilio, Baroni Matteo, Trotta Roberta, Manu Marius Constantin, Kirchhof Paulus, De Caterina Raffaele
Abstract
Background: Elderly patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus well-controlled vitamin-K antagonists (VKA) therapy among AF patients aged >75 years and with a body weight
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A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL.
Mol Ther2022 Feb;30(2):550-563. doi: 10.1016/j.ymthe.2021.08.033.
Zanetti Samanta Romina, Velasco-Hernandez Talia, Gutierrez-Agüera Francisco, Díaz Víctor M, Romecín Paola Alejandra, Roca-Ho Heleia, Sánchez-Martínez Diego, Tirado Néstor, Baroni Matteo Libero, Petazzi Paolo, Torres-Ruiz Raúl, Molina Oscar, Bataller Alex, Fuster José Luis, Ballerini Paola, Juan Manel, Jeremias Irmela, Bueno Clara, Menéndez Pablo
Abstract
CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR T cell persistence or resistance of either CD19 or CD19 B-ALL clones. CD22 is a pan-B marker whose expression is maintained in both CD19 and CD19 relapses. CD22-CAR T cells have been clinically used in B-ALL patients, although relapse also occurs. T cells engineered with a tandem CAR (Tan-CAR) containing in a single construct both CD19 and CD22 scFvs may be advantageous in achieving higher remission rates and/or preventing antigen loss. We have generated and functionally validated using cutting-edge assays a 4-1BB-based CD22/CD19 Tan-CAR using in-house-developed novel CD19 and CD22 scFvs. Tan-CAR-expressing T cells showed similar in vitro expansion to CD19-CAR T cells with no increase in tonic signaling. CRISPR-Cas9-edited B-ALL cells confirmed the bispecificity of the Tan-CAR. Tan-CAR was as efficient as CD19-CAR in vitro and in vivo using B-ALL cell lines, patient samples, and patient-derived xenografts (PDXs). Strikingly, the robust antileukemic activity of the Tan-CAR was slightly more effective in controlling the disease in long-term follow-up PDX models. This Tan-CAR construct warrants a clinical appraisal to test whether simultaneous targeting of CD19 and CD22 enhances leukemia eradication and reduces/delays relapse rates and antigen loss.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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Circadian periodicity affects the type of ventricular arrhythmias and efficacy of implantable defibrillator therapies.
J Cardiovasc Electrophysiol2021 Sep;32(9):2528-2535. doi: 10.1111/jce.15154.
Vergara Pasquale, Pignalberi Carlo, Pisanò Ennio C, Maglia Giampiero, Della Bella Paolo, Zanotto Gabriele, Iacopino Saverio, Solimene Francesco, Calvi Valeria, Marini Massimiliano, Giammaria Massimo, Biffi Mauro, Rovaris Giovanni, Caravati Fabrizio, Quartieri Fabio, Curnis Antonio, Rapacciuolo Antonio, Senatore Gaetano, Pedretti Stefano, Saporito Davide, Dello Russo Antonio, Santobuono Vincenzo E, Pepi Patrizia, Duca Antonio, Baroni Matteo, Falasconi Giulio, Giacopelli Daniele, Gargaro Alessio, D'Onofrio Antonio
Abstract
INTRODUCTION:
Factors influencing malignant arrhythmia onset are not fully understood. We explored the circadian periodicity of ventricular arrhythmias (VAs) in patients with implantable cardioverter and cardiac resynchronization defibrillators (ICD/CRT-D).
METHODS:
Time, morphology (monomorphic/polymorphic), and mode of termination (anti-tachycardia pacing [ATP] or shock) of VAs stored in a database of remote monitoring data were adjudicated. Episodes were grouped in six 4-h timeslots from 00:00 to 24:00. Circadian distributions and adjusted marginal odds ratios (ORs), with 95% confidence interval (CI), were analyzed using mixed-effect models and logit generalized estimating equations, respectively, to account for within-subject correlation of multiple episodes.
RESULTS:
Among 1303 VA episodes from 446 patients (63% ICD and 37% CRT-D), 120 (9%) self-extinguished, and 842 (65%) were terminated by ATP, 343 (26%) by shock. VAs clustered from 08:00 to 16:00 with 44% of episodes, as compared with 22% from 00:00 to 08:00 (p?.001) and 34% from 16:00 to 24:00 (p?=?.005). Episodes were more likely to be polymorphic at night with an adjusted marginal OR of 1.66 (CI, 1.15-2.40; p?=?.007) at 00:00-04:00 versus other timeslots. Episodes were less likely to be terminated by ATP in the 00:00-04:00 (success-to-failure ratio, 0.67; CI, 0.46-0.98; p?=?.039) and 08:00-12:00 (0.70; CI, 0.51-0.96; p?=?.02) timeslots, and most likely to be terminated by ATP between 12:00 and 16:00 (success-to-failure ratio 1.42; CI, 1.06-1.91; p?=?.02).
CONCLUSION:
VAs did not distribute uniformly over the 24?h, with a majority of episodes occurring from 08:00 to 16:00. Nocturnal episodes were more likely to be polymorphic. The efficacy of ATP depended on the time of delivery.
© 2021 Wiley Periodicals LLC.
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Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope.
J Immunother Cancer2020 Aug;8(2):. doi: e000896.
Velasco-Hernandez Talia, Zanetti Samanta Romina, Roca-Ho Heleia, Gutierrez-Aguera Francisco, Petazzi Paolo, Sánchez-Martínez Diego, Molina Oscar, Baroni Matteo Libero, Fuster Jose Luis, Ballerini Paola, Bueno Clara, Fernandez-Fuentes Narcis, Engel Pablo, Menendez Pablo
Abstract
BACKGROUND:
There are few therapeutic options available for patients with B-cell acute lymphoblastic leukemia (B-ALL) relapsing as CD19 either after chemotherapy or CD19-targeted immunotherapies. CD22-chimeric antigen receptor (CAR) T cells represent an attractive addition to CD19-CAR T cell therapy because they will target both CD22CD19 B-ALL relapses and CD19 preleukemic cells. However, the immune escape mechanisms from CD22-CAR T cells, and the potential contribution of the epitope binding of the anti-CD22 single-chain variable fragment (scFv) remain understudied.
METHODS:
Here, we have developed and comprehensively characterized a novel CD22-CAR (clone hCD22.7) targeting a membrane-distal CD22 epitope and tested its cytotoxic effects against B-ALL cells both in in vitro and in vivo assays.
RESULTS:
Conformational epitope mapping, cross-blocking, and molecular docking assays revealed that the hCD22.7 scFv is a high-affinity binding antibody which specifically binds to the ESTKDGKVP sequence, located in the Ig-like V-type domain, the most distal domain of CD22. We observed efficient killing of B-ALL cells in vitro, although the kinetics were dependent on the level of CD22 expression. Importantly, we show an efficient in vivo control of patients with B-ALL derived xenografts with diverse aggressiveness, coupled to long-term hCD22.7-CAR T cell persistence. Remaining leukemic cells at sacrifice maintained full expression of CD22, ruling out CAR pressure-mediated antigen loss. Finally, the immunogenicity capacity of this hCD22.7-scFv was very similar to that of other CD22 scFv previously used in adoptive T cell therapy.
CONCLUSIONS:
We report a novel, high-affinity hCD22.7 scFv which targets a membrane-distal epitope of CD22. 4-1BB-based hCD22.7-CAR T cells efficiently eliminate clinically relevant B- CD22 and CD22 ALL primary samples in vitro and in vivo. Our study supports the clinical translation of this hCD22.7-CAR as either single or tandem CD22-CD19-CAR for both naive and anti-CD19-resistant patients with B-ALL.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo.
J Immunother Cancer2020 Jun;8(1):. doi: e000845.
Baroni Matteo Libero, Sanchez Martinez Diego, Gutierrez Aguera Francisco, Roca Ho Heleia, Castella Maria, Zanetti Samanta Romina, Velasco Hernandez Talia, Diaz de la Guardia Rafael, Castaño Julio, Anguita Eduardo, Vives Susana, Nomdedeu Josep, Lapillone Helene, Bras Anne E, van der Velden Vincent H J, Junca Jordi, Marin Pedro, Bataller Alex, Esteve Jordi, Vick Binje, Jeremias Irmela, Lopez Angel, Sorigue Marc, Bueno Clara, Menendez Pablo
Abstract
BACKGROUND:
Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative.
METHODS:
We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs.
RESULTS:
Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs.
CONCLUSIONS:
This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Bone Marrow Clonogenic Myeloid Progenitors from -Mutated AML Patients Do Not Harbor the Mutation: Implication for the Cell-Of-Origin of AML.
Genes (Basel)2020 Jan;11(1):. doi: 73.
Guardia Rafael Diaz de la, González-Silva Laura, López-Millán Belén, Rodríguez-Sevilla Juan José, Baroni Matteo L, Bueno Clara, Anguita Eduardo, Vives Susana, Palomo Laura, Lapillonne Helene, Varela Ignacio, Menendez Pablo
Abstract
The cell-of-origin of - and -mutated acute myeloid leukemia (AML) is still a matter of debate. Here, we combined in vitro clonogenic assays with targeted sequencing to gain further insights into the cell-of-origin of NPM1 and FLT3-ITD-mutated AML in diagnostic bone marrow (BM) from nine NPM1+/FLT3-ITD (+/-) AMLs. We reasoned that individually plucked colony forming units (CFUs) are clonal and reflect the progeny of a single stem/progenitor cell. NPM1 and FLT3-ITD mutations seen in the diagnostic blasts were found in only 2/95 and 1/57 individually plucked CFUs, suggesting that BM clonogenic myeloid progenitors in NPM1-mutated and NPM1/FLT3-ITD-mutated AML patients do not harbor such molecular lesions. This supports previous studies on NPM1 mutations as secondary mutations in AML, likely acquired in an expanded pool of committed myeloid progenitors, perhaps CD34-, in line with the CD34 phenotype of NPM1-mutated AMLs. This study has important implications on the cell-of-origin of NPM1+ AML, and reinforces that therapeutic targeting of either or mutations might only have a transient clinical benefit in debulking the leukemia, but is unlikely to be curative since will not target the AML-initiating/preleukemic cells. The absence of NPM1 and FLT3-ITD mutations in normal clonogenic myeloid progenitors is in line with their absence in clonal hematopoiesis of indeterminate potential.
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Combined leadless pacemaker and subcutaneous implantable cardioverter-defibrillator to manage recurrent transvenous system failures.
J Electrocardiol2019 ;54():43-46. doi: 10.1016/j.jelectrocard.2019.03.002.
Baroni Matteo, Colombo Giulia, Testoni Alessio, Arupi Michele, Lunati Maurizio, Cattafi Giuseppe
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Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia.
Blood2019 May;133(21):2291-2304. doi: 10.1182/blood-2018-10-882944.
Sánchez-Martínez Diego, Baroni Matteo L, Gutierrez-Agüera Francisco, Roca-Ho Heleia, Blanch-Lombarte Oscar, González-García Sara, Torrebadell Montserrat, Junca Jordi, Ramírez-Orellana Manuel, Velasco-Hernández Talía, Bueno Clara, Fuster José Luís, Prado Julia G, Calvo Julien, Uzan Benjamin, Cools Jan, Camos Mireia, Pflumio Françoise, Toribio María Luisa, Menéndez Pablo
Abstract
Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse. This article reports that the expression of CD1a is mainly restricted to developing cortical thymocytes, and neither CD34 progenitors nor T cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. We thus developed and preclinically validated a CD1a-specific CAR with robust and specific cytotoxicity in vitro and antileukemic activity in vivo in xenograft models of coT-ALL, using both cell lines and coT-ALL patient-derived primary blasts. CD1a-CARTs are fratricide resistant, persist long term in vivo (retaining antileukemic activity in re-challenge experiments), and respond to viral antigens. Our data support the therapeutic and safe use of fratricide-resistant CD1a-CARTs for relapsed/refractory coT-ALL.
© 2019 by The American Society of Hematology.
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CD133-directed CAR T-cells for MLL leukemia: on-target, off-tumor myeloablative toxicity.
Leukemia2019 Aug;33(8):2090-2125. doi: 10.1038/s41375-019-0418-8.
Bueno Clara, Velasco-Hernandez Talia, Gutiérrez-Agüera Francisco, Zanetti Samanta Romina, Baroni Matteo L, Sánchez-Martínez Diego, Molina Oscar, Closa Adria, Agraz-Doblás Antonio, Marín Pedro, Eyras Eduardo, Varela Ignacio, Menéndez Pablo
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Subcutaneous ICD implantation in a patient with hypertrophic cardiomyopathy after transvenous ICD failure: A case report.
J Arrhythm2018 Feb;34(1):81-83. doi: 10.1002/joa3.12011.
Baroni Matteo, Cattafi Giuseppe, Arupi Michele, Paolucci Marco, Pelenghi Stefano, Lunati Maurizio
Abstract
We describe the case of a patient with hypertrophic cardiomyopathy who experienced the failure of a transvenous implantable cardioverter defibrillator (T-ICD) lead and the following inability of a second T-ICD to convert a ventricular fibrillation. A subcutaneous ICD (S-ICD) was finally implanted and was effective at defibrillation test.
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Complexity of scar and ventricular arrhythmias in dilated cardiomyopathy of any etiology: Long-term data from the SCARFEAR (Cardiovascular Magnetic Resonance Predictors of Appropriate Implantable Cardioverter-Defibrillator Therapy Delivery) Registry.
Clin Cardiol2018 Apr;41(4):494-501. doi: 10.1002/clc.22911.
Pedretti Stefano, Vargiu Sara, Baroni Matteo, Dellegrottaglie Santo, Lanzarin Barbara, Roghi Alberto, Milazzo Angela, Quattrocchi Giuseppina, Lunati Maurizio, Pedrotti Patrizia
Abstract
BACKGROUND:
Late gadolinium enhancement (LGE) assessed with cardiovascular magnetic resonance (CMR) correlates with ventricular arrhythmias and survival in patients with structural heart disease. Whether some LGE characteristics may specifically improve prediction of arrhythmic outcomes is unknown.
HYPOTHESIS:
We sought to evaluate scar characteristics assessed with CMR to predict implantable cardioverter-defibrillator (ICD) interventions in dilated cardiomyopathy of different etiology.
METHODS:
96 consecutive patients evaluated with CMR received an ICD. Biventricular volumes, ejection fraction, and myocardial LGE were evaluated. LGE was defined as "complex" (Cx-LGE) in presence of ?1 of the following: ischemic pattern, involving ?2 different coronary territories; epicardial pattern; global endocardial pattern; and presence of ?2 different patterns. The primary endpoint was occurrence of any appropriate ICD intervention. A composite secondary endpoint of cardiovascular death, cardiac transplantation, or ventricular assist device implantation was also considered.
RESULTS:
During a median follow-up of 75 months, 30 and 25 patients reached the primary and secondary endpoints, respectively. Cx-LGE was correlated with a worse primary endpoint survival (log-rank P
CONCLUSIONS:
Cx-LGE identified at CMR imaging seems promising as an independent and specific prognostic factor of ventricular arrhythmias requiring ICD therapy in dilated cardiomyopathy of different etiologies.
© 2018 Wiley Periodicals, Inc.
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[Catecholamine-induced myocarditis in pheochromocytoma].
G Ital Cardiol (Rome)2017 Feb;18(2):164-168. doi: 10.1714/2663.27302.
Muratori Davide, Pedrotti Patrizia, Baroni Matteo, Belloni Armando, Quattrocchi Giuseppina, Milazzo Angela, Giannattasio Cristina, Roghi Alberto
Abstract
Pheochromocytoma is a rare tumor, usually benign, potentially lethal in case of crisis with acute release of catecholamines. The heart is a target and the clinical presentation can mimic various cardiac conditions, thus rendering diagnosis elusive. Cardiac magnetic resonance is a valuable non-invasive diagnostic tool for the evaluation of cardiomyopathies; it allows the identification of catecholamine-induced myocarditis pattern and, in some cases, it can detect the primary tumor. The definitive treatment of pheochromocytoma is surgical, while the acute crisis may require mechanical support to circulation. We here report a case of pheochromocytoma in a 25-year-old man complicated by catecholamine-induced myocarditis and heart failure.
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Erratum to: Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
High Blood Press Cardiovasc Prev2015 Dec;22(4):451. doi: 10.1007/s40292-015-0124-1.
Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
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Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
High Blood Press Cardiovasc Prev2015 Dec;22(4):411-6. doi: 10.1007/s40292-015-0121-4.
Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
Abstract
Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p
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[Primary prevention of sudden cardiac death through a wearable cardioverter-defibrillator].
G Ital Cardiol (Rome)2015 ;16(7-8):418-25. doi: 10.1714/1954.21242.
Gabrielli Domenico, Benvenuto Manuela, Baroni Matteo, Oliva Fabrizio, Capucci Alessandro
Abstract
Nowadays, the implantable cardioverter-defibrillator is the gold standard for the prevention of sudden cardiac death due to tachyarrhythmias. However, its use is not free from short and long-term risks. In the last years, the wearable cardioverter-defibrillator (WCD) has become a widespread option for patients who need a safe and reversible protection against ventricular tachyarrhythmias. Notwithstanding this, its everyday application is restricted by several limitations, including the risk of inappropriate shocks, the device size and the need for strict compliance of both patients and caregivers. In this review, we report the most relevant literature data on WCD usage along with the main fields of applications and future perspectives.
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[A matter of perspective: multimodality imaging of a giant cardiac mass].
G Ital Cardiol (Rome)2015 Mar;16(3):186-7. doi: 10.1714/1820.19830.
Baroni Matteo, Nava Stefano, Vignati Gabriele, Marianeschi Stefano Maria, Giannattasio Cristina, Pedrotti Patrizia
Abstract
A newborn was suspected of having situs inversus with levocardia based on chest X-ray. Echocardiography ruled out this hypothesis but revealed a giant cardiac mass that was confirmed by magnetic resonance imaging. Coronary angiography showed that the right coronary artery ran on the surface of the mass, and only partial debulking surgery was performed to relieve right heart compression. Histological examination classified the mass as cardiac fibroma. Complex diagnostic work-up allowed correct anatomic definition of the mass as well as its relationship with adjacent structures, and helped guide surgical planning.
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Cardiac magnetic resonance imaging of left ventricular apical hypoplasia in two complex congenital clinical syndromes.
Circ J2014 ;78(6):1507-9.
Baroni Matteo, Pedrotti Patrizia, Nava Stefano, Giannattasio Cristina, Roghi Alberto
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Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus.
Blood Press2013 Dec;22(6):355-61. doi: 10.3109/08037051.2013.791413.
Cesana Francesca, Giannattasio Cristina, Nava Stefano, Soriano Francesco, Brambilla Gianmaria, Baroni Matteo, Meani Paolo, Varrenti Marisa, Paleari Felice, Gamba Pierluigi, Facchetti Rita, Alloni Marta, Grassi Guido, Mancia Giuseppe
Abstract
AIMS:
Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness.
MAJOR FINDINGS:
The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability.
PRINCIPAL CONCLUSION:
Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control.
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Oral antiplatelet therapy after drug-eluting stent implantation: adherence and side-effects.
J Cardiovasc Med (Hagerstown)2013 Feb;14(2):81-90. doi: 10.2459/JCM.0b013e328356a545.
Rossini Roberta, Baroni Matteo, Musumeci Giuseppe, Gavazzi Antonello
Abstract
Prolonged dual antiplatelet therapy is the cornerstone of the therapy after drug-eluting stent implantation. However, it is associated with risks and side-effects, such as bleeding events, which can negatively affect overall prognosis. Moreover, premature antiplatelet therapy discontinuation is not uncommon both in clinical trials and in clinical practice. It can lead to serious short-term and long-term complications, such as stent thrombosis, acute myocardial infarction and death. Although lack of patient's motivation can be regarded as an important cause of drug withdrawal, recent studies showed that medical decisions can be an even more frequent cause of premature discontinuation. The management of a patient with a coronary stent, undergoing surgery, is challenging and might lead to antiplatelet therapy withdrawal. In the present article, adherence and side-effects of antiplatelet therapy will be reviewed, also focusing on new antiplatelet drugs, such as prasugrel and ticagrelor. Furthermore, pharmacological interactions (e.g. proton pump inhibitors) as well as other causes of drug discontinuation will be addressed, particularly focusing on their prognostic and practical implications.
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GP IIb/IIIa inhibitors for STEMI: still the gold standard or an old survivor?
Curr Vasc Pharmacol2012 Jul;10(4):443-7.
Musumeci Giuseppe, Baroni Matteo, Rossini Roberta
Abstract
Glycoprotein (GP) IIb\IIIa receptor plays a central role on platelets activation and its blockage has been a matter of interest since the beginning of percutaneous revascularization. After first promising trials, GP IIb\IIIa inhibitors (GPI) have been widely used in cath labs for about a decade, significantly improving prognosis for patients with STSegment Elevation Myocardial Infarction (STEMI). However, their utilization isn't exempt from risks, mainly in form of bleeding disorders, which can negatively affect patients' outcome. Moreover, routinary administration of thyenopiridines like clopidogrel and the introduction of new anticoagulants like bivalirudin significantly reduced indications for GPI. In this review, a risk/benefit evaluation GP IIb\IIIa inhibitors is presented and their indications for STEMI patients addressed to revascularization are discussed according to recent advances reported in literature.
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Quinidine for Pharmacological Cardioversion of Long-lasting Atrial Fibrillation.
J Atr Fibrillation2011 ;4(2):350. doi: 350.
Baroni Matteo, Kheir Antoine, Manfredi Margherita, Pattarino Francesco, Doni Flavio
Abstract
In the daily clinical practice, patients with atrial fibrillation (AF) lasting more than 48h (or not datable at all) are not uncommon. In long-lasting AF changes in electrophysiological features (electrical remodeling) can occur, resulting in a loss of sensibility to most antiarrhythmic drugs. There is strong evidence that the main mechanism involved in electrical remodeling is a global shortening in refractory period. To assess safety and efficacy of quinidine in pharmacological cardioversion of long-lasting AF, compared with propafenone and amiodarone. Ninety consecutive patients with AF lasting more than 6 weeks were randomized to amiodarone (5mg\kg bolus, then 15mg\kg in 24h) , propafenone (2 mg\kg bolus then 0.007mg\kg for 2h), and quinidine (275mg of quinidine arabogalattan sulphate per os every 2h for 8h maximum) for pharmacologic cardioversion. All patients had been previously treated with adequate oral anticoagulation and had been submitted to transthoracic echocardiogram. The 3 groups of patients did not differ for baseline and echocardiographic characteristics. Sinus rhythm was restored in 16 patients treated with quinidine (53%), compared with 6 patients (20%) in the amiodarone and propafenone groups (p
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Carboplatin-induced Kounis syndrome.
J Cardiol Cases2011 Aug;4(1):e58-e61. doi: 10.1016/j.jccase.2011.04.004.
Baroni Matteo, Todd Sarah, Pattarino Francesco, Doni Flavio
Abstract
A 50-year-old man in chemotherapy for an advanced lung adenocarcinoma presented with chest pain and cutaneous rash during carboplatin infusion with electrocardiographic (ECG) evidence of an inferior lesion wave. The administration of steroids and nitrates promptly resulted in clinical and ECG normalization, without enzymatic dismission. This reaction was considered compatible with allergic coronary vasospasm (also known as Kounis syndrome), a rare but possible complication of chemotherapy. In these cases prompt diagnosis and a correct approach can avoid useless invasive interventions.
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