Publications by authors named "Simone Sala"

71 Publications

Characterization of cardiac electrogram signals in atrial arrhythmias.

Minerva Cardiol Angiol 2021 Feb;69(1):70-80

Department of Arrhythmology, IRCCS San Raffaele Hospital, Milan, Italy.

Despite significant advancements in 3D cardiac mapping systems utilized in daily electrophysiology practices, the characterization of atrial substrate remains crucial for the comprehension of supraventricular arrhythmias. During mapping, intracardiac electrograms (EGM) provide specific information that the cardiac electrophysiologist is required to rapidly interpret during the course of a procedure in order to perform an effective ablation. In this review, EGM characteristics collected during sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (pAF) are analyzed, focusing on amplitude, duration and fractionation. Additionally, EGMs recorded during atrial fibrillation (AF), including complex fractionated atrial EGMs (CFAE), may also provide precious information. A complete understanding of their significance remains lacking, and as such, we aimed to further explore the role of CFAE in strategies for ablation of persistent AF. Considering focal atrial tachycardias (AT), current cardiac mapping systems provide excellent tools that can guide the operator to the site of earliest activation. However, only careful analysis of the EGM, distinguishing low amplitude high frequency signals, can reliably identify the absolute best site for RF. Evaluating macro-reentrant atrial tachycardia circuits, specific EGM signatures correspond to particular electrophysiological phenomena: the careful recognition of these EGM patterns may in fact reveal the best site of ablation. In the near future, mathematical models, integrating patient-specific data, such as cardiac geometry and electrical conduction properties, may further characterize the substrate and predict future (potential) reentrant circuits.
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http://dx.doi.org/10.23736/S2724-5683.20.05431-6DOI Listing
February 2021

Etiology is a predictor of recurrence after catheter ablation of ventricular arrhythmias in pediatric patients.

J Cardiovasc Electrophysiol 2021 Mar 8. Epub 2021 Mar 8.

Arrhythmia Unit and Electrophisiology Laboratories, San Raffaele Scientific Institute, Milano, Italy.

Background: Ventricular arrhythmias (VAs) are rare in pediatric patients, especially in absence of structural heart disease (SHD). Few data are available regarding the invasive VAs treatment with catheter ablation (CA) in pediatric patients and predictors of outcomes have not been fully investigated.

Objective: To describe the clinical presentation, procedural characteristics, and outcomes in pediatric patients undergoing CA for VAs.

Methods: Eighty-one consecutive pediatric patients (58 male [72%], 15.5 ± 2.2 years) treated by CA for ventricular tachycardia (VT) or premature ventricular beats (PVBs) were retrospectively evaluated. Study endpoints were VAs recurrence and mortality for any cause.

Results: Ninety-five procedures were performed in 81 patients, 52 (55%) PVBs and 43 (45%) VT ablations. During a follow-up of 35.0 months (interquartile range = 13.0-71.0), 14 patients (14.7%) had a VA recurrence: 11 (33.3%) patients treated with CA for VT and 3 (6.2%) patients treated for PVBs (p < .001). One patient (1%) died 26 months after the procedure during an electrical storm. Patients with SHD had higher VAs recurrence rate, as compared with idiopathic VAs (pairwise log-rank p < .001). Patients treated with CA for VT had higher VA recurrence rate, as compared with PVB patients (pairwise log-rank p = .002). At Cox multivariate analysis only SHD was an independent predictor of VAs recurrence (hazard ratio = 5.56, 95% confidence interval = 2.68-11.54, p < .001).

Conclusion: CA of VAs is effective and safe in a pediatric population. CA of idiopathic and fascicular VAs are associated with lower recurrence rate, than VAs in the setting of SHD.
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http://dx.doi.org/10.1111/jce.14984DOI Listing
March 2021

Immunosuppressive therapy in childhood-onset arrhythmogenic inflammatory cardiomyopathy.

Pacing Clin Electrophysiol 2021 Mar 18;44(3):552-556. Epub 2021 Jan 18.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

We present, to our knowledge, the first case of immunosuppressive therapy (IST) application in a 12-year-old child with arrhythmogenic inflammatory cardiomyopathy resulting from the overlap between autoimmune myocarditis and primary arrhythmogenic cardiomyopathy. Indication to off-lable IST was compelling, because of recurrent drug-refractory ventricular arrhythmias (VAs). We show that IST was feasible, safe, and effective on multiple clinical endpoints, including symptoms, VA recurrences, and T-troponin release. Remarkably, all diagnostic and therapeutic strategies were worked out by a dedicated multidisciplinary team, including specialized pediatric immunologists.
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http://dx.doi.org/10.1111/pace.14153DOI Listing
March 2021

First ptychographic X-ray computed tomography experiment on the NanoMAX beamline.

J Appl Crystallogr 2020 Dec 13;53(Pt 6):1444-1451. Epub 2020 Oct 13.

MAX IV Laboratory, Lund University, Lund, Sweden.

Ptychographic X-ray computed tomography is a quantitative three-dimensional imaging technique offered to users of multiple synchrotron radiation sources. Its dependence on the coherent fraction of the available X-ray beam makes it perfectly suited to diffraction-limited storage rings. Although MAX IV is the first, and so far only, operating fourth-generation synchrotron light source, none of its experimental stations is currently set up to offer this technique to its users. The first ptychographic X-ray computed tomography experiment has therefore been performed on the NanoMAX beamline. From the results, information was gained about the current limitations of the experimental setup and where attention should be focused for improvement. The extracted parameters in terms of scanning speed, size of the imaged volume and achieved resolutions should provide a baseline for future users designing nano-tomography experiments on the NanoMAX beamline.
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http://dx.doi.org/10.1107/S160057672001211XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710494PMC
December 2020

Immunosuppressive Therapy and Risk Stratification of Patients With Myocarditis Presenting With Ventricular Arrhythmias.

JACC Clin Electrophysiol 2020 10 24;6(10):1221-1234. Epub 2020 Jun 24.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy; San Raffaele Vita-Salute University, Milan, Italy.

Objectives: This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis.

Background: The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable.

Methods: We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade ≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti-intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST) were chosen after 1:1 matching to IST patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment.

Results: A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1 months. By the 24-month prospective follow-up, major VA occurred in 6 IST versus 10 IST patients (p = 0.42), with no episodes following IST termination. As compared to IST patients, IST patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p < 0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95% CI: 2.6 to 25.2, respectively; both p < 0.001). Furthermore, in the whole study population (N = 255), IST was independently associated with protection from major VA (HR: 0.3; 95% CI: 0.2 to 0.7; p = 0.01) at 38 ± 21 months of follow-up.

Conclusions: In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA.
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http://dx.doi.org/10.1016/j.jacep.2020.05.013DOI Listing
October 2020

Inflammation as a Predictor of Recurrent Ventricular Tachycardia After Ablation in Patients With Myocarditis.

J Am Coll Cardiol 2020 10;76(14):1644-1656

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy; San Raffaele Vita-Salute University, Milan, Italy.

Background: Little is known about the risk stratification of patients with myocarditis undergoing ventricular tachycardia (VT) ablation.

Objectives: This study sought to describe VT ablation results and identify factors associated with arrhythmia recurrences in a cohort of patients with myocarditis.

Methods: The authors enrolled 125 consecutive patients with myocarditis, undergoing VT ablation. Before ablation, disease stage was evaluated, to identify active (AM) versus previous myocarditis (PM). The primary study endpoint was assessment of VT recurrences by 12-month follow-up. Predictors of VT recurrences were retrospectively identified.

Results: All patients (age 51 ± 14 years, 91% men, left ventricular ejection fraction 52% ± 9%) had history of myocarditis diagnosed by endomyocardial biopsy (59%) and/or cardiac magnetic resonance (90%). Furthermore, all had multiple episodes of drug-refractory VTs. Multimodal pre-procedural staging identified 47 patients with AM (38%) and 78 patients with PM (62%). All patients showed low-voltage areas (LVA) at electroanatomical map (97% epicardial or endoepicardial); of them, 25 (20%) had wide borderzone (WBZ, constituting >50% of the whole LVA). VT recurrences were documented in 25 patients (20%) by 12 months, and in 43 (34%) by last follow-up (median 63 months; interquartile range: 39 to 87). At multivariable analysis, AM stage was the only predictor of VT recurrences by 12 months (hazard ratio: 9.5; 95% confidence interval: 2.6 to 35.3; p < 0.001), whereas both AM stage and WBZ were associated with arrhythmia recurrences anytime during follow-up. No VT episodes were found after redo ablation was performed in 23 patients during PM stage.

Conclusion: Our findings suggest that VT ablation should be avoided during AM, but is often of benefit for recurrent VT after the acute phase of myocarditis.
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http://dx.doi.org/10.1016/j.jacc.2020.08.012DOI Listing
October 2020

Late gadolinium enhancement role in arrhythmic risk stratification of patients with LMNA cardiomyopathy: results from a long-term follow-up multicentre study.

Europace 2020 12;22(12):1864-1872

Department of Arrhythmology and Cardiac Electrophysiology, IRCCS San Raffaele Hospital, Milan, Italy.

Aims: We aimed at addressing the role of late gadolinium enhancement (LGE) in arrhythmic risk stratification of LMNA-associated cardiomyopathy (CMP).

Methods And Results: We present data from a multicentre national cohort of patients with LMNA mutations. Of 164 screened cases, we finally enrolled patients with baseline cardiac magnetic resonance (CMR) including LGE sequences [n = 41, age 35 ± 17 years, 51% males, mean left ventricular ejection fraction (LVEF) by echocardiogram 56%]. The primary endpoint of the study was follow-up (FU) occurrence of malignant ventricular arrhythmias [MVA, including sustained ventricular tachycardia (VT), ventricular fibrillation, and appropriate implantable cardioverter-defibrillator (ICD) therapy]. At baseline CMR, 25 subjects (61%) had LGE, with non-ischaemic pattern in all of the cases. Overall, 23 patients (56%) underwent ICD implant. By 10 ± 3 years FU, eight patients (20%) experienced MVA, consisting of appropriate ICD shocks in all of the cases. In particular, the occurrence of MVA in LGE+ vs. LGE- groups was 8/25 vs. 0/16 (P = 0.014). Of note, no significant differences between LGE+ and LGE- patients were found in currently recognized risk factors for sudden cardiac death (male gender, non-missense mutations, baseline LVEF <45% and non-sustained VT), all P-value >0.05.

Conclusions: In LMNA-CMP patients, LGE at baseline CMR is significantly associated with MVA. In particular, as suggested by this preliminary experience, the absence of LGE allowed to rule-out MVA at 10 years mean FU.
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http://dx.doi.org/10.1093/europace/euaa171DOI Listing
December 2020

Telemedicine in myocarditis: Evolution of a mutidisciplinary "disease unit" at the time of COVID-19 pandemic.

Am Heart J 2020 11 12;229:121-126. Epub 2020 Aug 12.

Myocarditis Disease Unit, IRCCS San Raffaele Hospital, Milan, Italy; Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Myocarditis Disease Unit (MDU) is a functional multidisciplinary network designed to offer multidisciplinary assistance to patients with myocarditis. More than 300 patients coming from the whole Country are currently followed up at a specialized multidisciplinary outpatient clinic. Following the pandemic outbreak of the SARS-CoV-2 infection in Italy, we present how the MDU rapidly evolved to a "tele-MDU", via a dedicated multitasking digital health platform.
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http://dx.doi.org/10.1016/j.ahj.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419248PMC
November 2020

Atrial fibrillation, anticoagulation management and risk of stroke in the Cardiomyopathy/Myocarditis registry of the EURObservational Research Programme of the European Society of Cardiology.

ESC Heart Fail 2020 Sep 17. Epub 2020 Sep 17.

Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.

Aims: Cardiomyopathies are a heterogeneous group of disorders that increase the risk for atrial fibrillation (AF). The aim of the study is to assess the prevalence of AF, anticoagulation management, and risk of stroke/transient ischaemic attack (TIA) in patients with cardiomyopathy.

Methods And Results: Three thousand two hundred eight consecutive adult patients with cardiomyopathy (34.9% female; median age: 55.0 years) were prospectively enrolled as part of the EURObservational Research Programme Cardiomyopathy/Myocarditis Registry. At baseline, 903 (28.2%) patients had AF (29.4% dilated, 27.5% hypertrophic, 51.5% restrictive, and 14.7% arrhythmogenic right ventricular cardiomyopathy, P < 0.001). AF was associated with more advanced New York Heart Association class (P < 0.001), increased prevalence of cardiovascular risk factors and co-morbidities, and a history of stroke/TIA (P < 0.001). Oral anticoagulation was administered in 71.7% of patients with AF (vitamin K antagonist: 51.6%; direct oral anticoagulant: 20.1%). At 1 year follow-up, the incidence of cardiovascular endpoints was as follows: stroke/TIA 1.85% (AF vs. non-AF: 3.17% vs. 1.19%, P < 0.001), death from any cause 3.43% (AF vs. non-AF: 5.39% vs. 2.50%, P < 0.001), and death from heart failure 1.67% (AF vs. non-AF: 2.44% vs. 1.31%, P = 0.033). The independent predictors for stroke/TIA were as follows: AF [odds ratio (OR) 2.812, P = 0.005], history of stroke (OR 7.311, P = 0.010), and anaemia (OR 3.119, P = 0.006).

Conclusions: The study reveals a high prevalence and diverse distribution of AF in patients with cardiomyopathies, inadequate anticoagulation regimen, and high risk of stroke/TIA in this population.
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http://dx.doi.org/10.1002/ehf2.12854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754739PMC
September 2020

Pulse-to-pulse wavefront sensing at free-electron lasers using ptychography.

J Appl Crystallogr 2020 Aug 8;53(Pt 4):949-956. Epub 2020 Jul 8.

Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.

The pressing need for knowledge of the detailed wavefront properties of ultra-bright and ultra-short pulses produced by free-electron lasers has spurred the development of several complementary characterization approaches. Here a method based on ptychography is presented that can retrieve high-resolution complex-valued wavefunctions of individual pulses without strong constraints on the illumination or sample object used. The technique is demonstrated within experimental conditions suited for diffraction experiments and exploiting Kirkpatrick-Baez focusing optics. This lensless technique, applicable to many other short-pulse instruments, can achieve diffraction-limited resolution.
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http://dx.doi.org/10.1107/S1600576720006913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401787PMC
August 2020

High-Density Characterization of the Ventricular Electrical Substrate During Sinus Rhythm in Post-Myocardial Infarction Patients.

JACC Clin Electrophysiol 2020 07 24;6(7):799-811. Epub 2020 Jun 24.

Department of Arrhythmology, IRCCS San Raffaele Hospital, Milan, Italy.

Objectives: The aim of this study was to characterize, during sinus rhythm, the electric activation abnormalities in post-myocardial infarction patients undergoing ablation of ventricular tachycardia (VT) in order to identify specific signatures of those abnormal electrograms (EGMs).

Background: In the setting of VT ablation, substrate characterization hinges on the identification of local abnormal ventricular activity (LAVA) and late potentials (LPs) that are considered to be related to the VT circuit.

Methods: Patients scheduled for VT ablation underwent high-density ventricular substrate mapping. The substrate map during sinus rhythm was then compared with the activation maps of the clinical VT. Abnormal EGMs (LAVA and LPs) during sinus rhythm were characterized according to their configuration, duration, and amplitude and distinguished as belonging to bystander region or to the re-entrant circuit. Underlying electrophysiological mechanisms (wave-front collision, slow conduction) were identified on the activation maps and assigned to corresponding EGMs.

Results: Ten patients satisfied the criteria to be enrolled in the study. A mean of 5 ± 1 slow-conduction areas and 4 ± 2 wave-front collisions were identified. LAVA was due to slow conduction in 60.5%, followed by wave-front collision (17.5%). LPs were caused by slow conduction in 52% of cases and by wave-front collision in 43% of cases. During sinus rhythm, entrance and exit sites were characterized by LAVA, while at the VT isthmus, only LPs were identified. Cutoff values of duration <24.5 ms (95% sensitivity and 99% specificity) and amplitude <0.14 mV (90% sensitivity and 48.1% specificity) discriminated those LPs belonging to the circuit from those playing a bystander role.

Conclusions: In the setting of post-myocardial infarction cardiomyopathy, specific EGM signatures are expressions of distinct electrophysiological phenomena. LAVA and LPs may play a bystander or an active role in the VT circuit, but only LPs with low amplitude and short duration predicted the VT isthmus.
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http://dx.doi.org/10.1016/j.jacep.2020.04.008DOI Listing
July 2020

Bipolar radiofrequency ablation for ventricular tachycardias originating from the interventricular septum: Safety and efficacy in a pilot cohort study.

Heart Rhythm 2020 12 26;17(12):2111-2118. Epub 2020 Jun 26.

Department of Arrhythmology and Cardiac Electrophysiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Interest has grown in recent years in bipolar radiofrequency ablation (B-RFA). However, indications and outcome in patients with ventricular tachycardia (VT) are still to be defined.

Objective: The purpose of this study was to describe patient selection, safety and effectiveness of B-RFA, in a pilot cohort study of patients with nonischemic dilated cardiomyopathy (NIDCM) and drug-refractory VT.

Methods: We enrolled 21 patients with NIDCM (mean age 66±10 years; 18/21 (86%) men; left ventricular ejection fraction 35%±14%; 100% redo procedures) scheduled for a B-RFA procedure because of drug-refractory VT of suspected septal (interventricular septum [IVS]) origin. After electroanatomic mapping by using the CARTO®3 system, B-RFA was performed in all patients. Short- and long-term outcomes, including procedural success, major complications, and occurrence of major ventricular arrhythmias (MVAs), were evaluated at 25±8 months of follow-up (FU).

Results: Endocardial mapping showed IVS scar in all patients and extra-IVS in 7 patients (33%). B-RFA was performed at an average power of 33 W, for 60-90 seconds, over a 4.1 cm area, with 13±3 mm distance between catheters tips. The impedance drop was 27±4 Ω. The primary end point of noninducibility of the target clinical VT was obtained in 20 patients (95%). During FU, MVAs were documented in 7 patients (33%). FU MVAs occurred in all (100%) patients with extra-IVS localizations (7 of 7) or inflammatory nonischemic cardiomyopathy etiology (2 of 2). IVS thinning (tip-to-tip catheter distance < 5 mm) represented the only anatomical limitation to B-RFA.

Conclusion: B-RFA is feasible in patients with NIDCM and drug-refractory VT of septal origin. Extra-IVS substrate and inflammatory NIDCM etiology were associated with an adverse outcome.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.025DOI Listing
December 2020

Compressive Sensing for Dynamic XRF Scanning.

Sci Rep 2020 06 19;10(1):9990. Epub 2020 Jun 19.

Elettra - Sincrotrone Trieste S.C.p.A, 34149 Basovizza, Trieste, Italy.

X-Ray Fluorescence (XRF) scanning is a widespread technique of high importance and impact since it provides chemical composition maps crucial for several scientific investigations. There are continuous requirements for larger, faster and highly resolved acquisitions in order to study complex structures. Among the scientific applications that benefit from it, some of them, such as wide scale brain imaging, are prohibitively difficult due to time constraints. However, typically the overall XRF imaging performance is improving through technological progress on XRF detectors and X-ray sources. This paper suggests an additional approach where XRF scanning is performed in a sparse way by skipping specific points or by varying dynamically acquisition time or other scan settings in a conditional manner. This paves the way for Compressive Sensing in XRF scans where data are acquired in a reduced manner allowing for challenging experiments, currently not feasible with the traditional scanning strategies. A series of different compressive sensing strategies for dynamic scans are presented here. A proof of principle experiment was performed at the TwinMic beamline of Elettra synchrotron. The outcome demonstrates the potential of Compressive Sensing for dynamic scans, suggesting its use in challenging scientific experiments while proposing a technical solution for beamline acquisition software.
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http://dx.doi.org/10.1038/s41598-020-66435-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305138PMC
June 2020

Low prevalence of arrhythmias in clinically stable COVID-19 patients.

Pacing Clin Electrophysiol 2020 08 3;43(8):891-893. Epub 2020 Jul 3.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: No studies investigated the prevalence of arrhythmias among clinically-stable patients affected by COVID-19 infection.

Methods: We assessed prevalence, type, and burden of arrhythmias, by a single-day snapshot in seven non-intensive COVID Units at a third-level center.

Results: We enrolled 132 inhospital patients (mean age 65±14y; 66% males) newly diagnosed with COVID-19 infection. Arrhythmic episodes were detected in 12 patients (9%). In detail, 8 had atrial fibrillation, and 4 self-limiting supraventricular tachyarrhythmias. There were no cases of ventricular arrhythmias or new-onset atrioventricular blocks. In addition, we report no patients with QTc interval >450 ms.

Conclusions: Our single-day snapshot survey suggests that the prevalence of arrhythmias among clinically stable COVID-19 patients is low. In particular, no life-threatening arrhythmic events occurred.
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http://dx.doi.org/10.1111/pace.13987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323294PMC
August 2020

The COVID-19 challenge to cardiac electrophysiologists: optimizing resources at a referral center.

J Interv Card Electrophysiol 2020 May 18:1-7. Epub 2020 May 18.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Vita-Salute University and San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy.

Purpose: To describe how a referral center for cardiac electrophysiology (EP) rapidly changed to comply with the ongoing COVID-19 healthcare emergency.

Methods: We present retrospective data about the modification of daily activities at our EP unit, following the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Italy. In particular, in the context of a pre-existing "hub-and-spoke" network, we describe how procedure types and volumes have changed in the last 3 months.

Results: Since our institution was selected as a COVID-19 referral center, the entire in-hospital activity was reorganized to assist more than 1000 COVID-positive cases. Only urgent EP procedures, including ventricular tachycardia ablation and extraction of infected devices, were both maintained and optimized to meet the needs of external hospitals. In addition, most of the non-urgent EP procedures were postponed. Finally, following prompt internal reorganization, both outpatient clinics and on-call services underwent significant modification, by integrating telemedicine support whenever applicable.

Conclusion: We presented the fast reorganization of an EP referral center during the ongoing COVID-19 healthcare emergency. Our hub-and-spoke model may be useful for other centers, aiming at a cost-effective management of resources in the context of a global crisis.
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http://dx.doi.org/10.1007/s10840-020-00761-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232930PMC
May 2020

Acute myocardial injury, MINOCA, or myocarditis? Improving characterization of coronavirus-associated myocardial involvement.

Eur Heart J 2020 06;41(22):2124-2125

Department of Cardiac Thoracic Vascular Sciences and Public Health, Cardiology, Padua University, Padua, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehaa396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197551PMC
June 2020

Hybrid FDG-PET/MR or FDG-PET/CT to Detect Disease Activity in Patients With Persisting Arrhythmias After Myocarditis.

JACC Cardiovasc Imaging 2021 Jan 15;14(1):288-292. Epub 2020 Apr 15.

Experimental Imaging Center, Radiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jcmg.2020.03.009DOI Listing
January 2021

Septal Late Gadolinium Enhancement and Arrhythmic Risk in Genetic and Acquired Non-Ischaemic Cardiomyopathies.

Heart Lung Circ 2020 Sep 15;29(9):1356-1365. Epub 2019 Nov 15.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital and Vita-Salute University, Milan, Italy.

Background: In many genetic and acquired non-ischaemic cardiomyopathies (NICM) there have been frequent reports of involvement of the interventricular septum (IVS) by late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). However, no studies have investigated the relationship between septal LGE and arrhythmias in different NICM subtypes.

Methods: This study enrolled 103 patients with septal LGE at baseline CMR and different NICM: hypertrophic (n=29) or lamin A/C gene (LMNA)-associated (n=23) cardiomyopathy, and acute (n=30) or previous (n=21) myocarditis. During follow-up, the occurrences of malignant ventricular arrhythmias (MVA) and major bradyarrhythmias (BA) were evaluated.

Results: At 4.9±0.7 years of follow-up, the occurrence of MVA and major BA in genetic vs acquired NICM were 10 of 52 vs 12 of 51, and 10 of 52 vs 4 of 51, respectively (both p=n.s.). However, MVA occurred more frequently in LMNA-NICM (eight of 23 vs two of 29 hypertrophic, p=0.015) and in previous myocarditis (nine of 21 vs three of 30 acute, p=0.016), while major BAs were particularly common in LMNA-NICM patients only (nine of 23 vs one of 29 hypertrophic, p=0.003). Different patterns of septal LGE were consistently retrospectively identified at baseline CMR: junctional and limited to the base in 79.3% of uneventful hypertrophic NICM; extended and focally transmural in LMNA-NICM with follow-up arrhythmias (both p<0.05); transitory in patients with acute myocarditis, who, differently from the post-myocarditis ones, showed follow-up arrhythmias only in the presence of unmodified LGE at follow-up CMR (five of 13, p=0.009).

Conclusion: Septal LGE was significantly associated with MVA at the 5-year follow-up in LMNA-NICM or previous myocarditis, and with major BA in LMNA-NICM only. These differences correlated with heterogeneous patterns of IVS LGE in different NICM.
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http://dx.doi.org/10.1016/j.hlc.2019.08.018DOI Listing
September 2020

Early T1 Myocardial MRI Mapping: Value in Detecting Myocardial Hyperemia in Acute Myocarditis.

Radiology 2020 05 10;295(2):316-325. Epub 2020 Mar 10.

From the Experimental Imaging Centre, Radiology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy (A.P., G.B., E.B., A.D.M., F.D.C., A.E.); School of Medicine, Vita-Salute San Raffaele University, Milan, Italy (A.P., A.D.M., F.D.C., A.E.); Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, London, England (G.B.); Department of Surgical Sciences, Radiology Unit, University of Turin, Turin, Italy (R.F., M.G.); University Centre for Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy (P.M.V.R.); Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy (G.P., S.S.); Department of Radiological, Oncological and Pathological Sciences, "La Sapienza" University of Rome, Rome, Italy (M.F., N.G.); and Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy (C.B.).

Background Hyperemia is a key component of acute myocarditis (AM). Early gadolinium uptake because of myocardial hyperemia may be quantified by using T1 mapping. Purpose To evaluate the value of early enhanced T1 shortening for the diagnosis of acute myocarditis. Materials and Methods Study participants suspected of having AM and healthy control (HC) participants were prospectively enrolled from September 2016 to May 2019. Participants underwent 1.5-T cardiac MRI including Lake Louise criteria, T2 mapping, native T1, and extracellular volume, with the addition of early enhanced T1 mapping (2 minutes after intravenous administration of 0.15 mmol/kg gadobutrol). Color-coded maps of the percentage of T1 shortening from precontrast to early postcontrast were generated. Optimal early T1 shortening cut-off value and its diagnostic performance in the identification of acute myocarditis were calculated. Results Forty-five study participants with AM (median age, 40 years; interquartile range [IQR], 20-46 years; 22 women) diagnosed according to multidisciplinary clinical evaluation, electrocardiography, laboratory test, echocardiography, cardiac MRI, and coronary CT and/or invasive angiography. Findings were confirmed by endomyocardial biopsy in 64% (29 of 45) of participants. MRI parameters were compared with 19 HC participants (median age, 39 years; IQR, 28-46 years; seven women). Median early T1 shortening was 75% (IQR, 72%-78%) in participants with AM versus 65% (IQR, 61%-66%) in HC participants ( < .001). Early T1 shortening showed high diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.97; 95% confidence interval [CI]: 0.94, 1.00) and excellent interobserver reproducibility (intraclass correlation coefficient: 0.98; 95% CI: 0.96, 1.00). Early T1 shortening of 70% or greater identified acute myocarditis with 93% sensitivity, 100% specificity, and 95% diagnostic accuracy. Early T1 shortening had better diagnostic performance than late percentage T1 shortening (AUC, 0.97 vs 0.90, respectively; = .03) and extracellular volume (AUC, 0.97 vs 0.88, respectively; = .046), and similar to native T1 (AUC, 0.97 vs 0.93, respectively; = .63) and T2 mapping (AUC, 0.97 vs 0.97, respectively; > .99). Conclusion In this proof-of-concept study, percentage of T1 shortening at early enhanced T1 mapping showed high accuracy for the diagnosis of acute myocarditis. © RSNA, 2020 See also the editorial by De Cecco and Monti in this issue.
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http://dx.doi.org/10.1148/radiol.2020191623DOI Listing
May 2020

Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation.

J Am Coll Cardiol 2020 03;75(9):1046-1057

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital and Vita-Salute University, Milan, Italy.

Background: Ventricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages.

Objectives: The purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM).

Methods: A total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown's grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation.

Results: At presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p < 0.001) and polymorphic VA (NSVT and VT: 19% vs. 2%; p = 0.002; premature ventricular complexes: 63% vs. 16%; p < 0.001). Only in PM patients with NSVT or VT, the dominant morphology (right-bundle branch block with superior axis) was 100% predictive of abnormal LV inferoposterior substrate at both cardiac magnetic resonance and electroanatomic mapping. At 27 ± 7 months prospective follow-up, 55 patients (30%) experienced malignant VA (AM vs. PM, p = 0.385). Although a prevalence of polymorphic and irregular VA was confirmed in AM patients with persistent inflammation in follow-up (58%), a predominance of monomorphic and regular VA was found in AM patients after myocarditis healing (42%), as well as in PM patients (all p < 0.001).

Conclusions: In myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis.
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http://dx.doi.org/10.1016/j.jacc.2020.01.036DOI Listing
March 2020

Ptychographic characterization of a coherent nanofocused X-ray beam.

Opt Express 2020 Feb;28(4):5069-5076

The NanoMAX hard X-ray nanoprobe is the first beamline to take full advantage of the diffraction-limited storage ring at the MAX IV synchrotron and delivers a high coherent photon flux for applications in diffraction and imaging. Here, we characterize its coherent and focused beam using ptychographic analysis. We derive beam profiles in the energy range 6-22 keV and estimate the coherent flux based on a probe mode decomposition approach.
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http://dx.doi.org/10.1364/OE.386068DOI Listing
February 2020

[Diagnostic and therapeutic approach to myocarditis patients presenting with arrhythmias].

G Ital Cardiol (Rome) 2020 Mar;21(3):187-194

U.O. Elettrofisiologia Cardiaca ed Aritmologia Clinica, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milano.

Myocarditis is a complex inflammatory disease of the myocardium, occurring secondary to viral infections or autoimmune mechanisms in most cases. Among its multiple clinical manifestations, arrhythmias are often underdiagnosed, in spite of their important prognostic value. In particular, ventricular arrhythmias complicating either active or previous myocarditis, are a significant cause of sudden cardiac death, especially in young people. Because of the absence of clinical trials specifically addressing this topic, nowadays updated international guidelines report extremely generic recommendations about optimal clinical management of patients with arrhythmic myocarditis. This review aims at both (i) showing the state of the art about patients with myocarditis and arrhythmias (ventricular arrhythmias in particular); and (ii) suggesting optimal diagnostic and therapeutic strategies for these patients, based on the experience of a high-volume referral center for arrhythmic myocarditis and ventricular arrhythmia management.
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http://dx.doi.org/10.1714/3306.32767DOI Listing
March 2020

Programmed ventricular stimulation in patients with active vs previous arrhythmic myocarditis.

J Cardiovasc Electrophysiol 2020 03 3;31(3):692-701. Epub 2020 Feb 3.

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital and Vita-Salute University, Milan, Italy.

Introduction: No studies so far addressed the role of invasive programmed ventricular stimulation (PVS) in myocarditis patient's arrhythmic risk stratification.

Methods And Results: We present a single-center prospective study on 96 consecutive adult patients (44 ± 13 years, 70.1% males) with myocarditis and ventricular arrhythmias (VA) at index hospitalization. Depending on baseline endomyocardial biopsy (EMB) and cardiac magnetic resonance, patients were divided into two groups: active (A) vs nonactive (NA) myocarditis. All of the patients underwent PVS at index hospitalization. Medical treatment and implantable cardioverter-defibrillator (ICD) implantation were clinically-driven. Malignant VA episodes (MVA = ventricular tachycardias [VT], ventricular fibrillation [VF], appropriate ICD therapy) were evaluated at 54 ± 18 months follow-up (FU). Patients who underwent VT ablation or with myocarditis recurrence (n = 9) were excluded. Of 87 patients, 41 (47.2%) were in group A. PVS was positive in 32 cases (36.8%), 16 A vs 16 NA (P = NS), with no associations with VA type at presentation. Before discharge, 55 patients (63.2%) underwent ICD implant. In FU, MVA occurred in 27 patients (31.0%), 13 A vs 14 NA (P = NS), 18 PVS+ vs 9 PVS- (P < .001). The association between PVS result and FU MVA was maximal in group NA (high rule-out performance with negative predictive value = 90.0%, P < .001) and minimal in group A (low rule-in performance with PPV = 43.8%, P = .302). In the whole population, three independent factors for major VA were identified: major arrhythmic onset by sustained VT or VF (HR 2.8, 95% CI, 1.0-7.4, P = .042), presence of fibrosis at EMB (HR 5.8, 95% CI, 1.1-30.0, P = .038), and PVS positivity (HR 4.2, 95% CI, 1.7-10.7, P = .003).

Conclusion: In myocarditis patients presenting with VA, PVS is associated with FU MVA in NA patients, but not in A ones. Overall, risk stratification of arrhythmic myocardits is still complex and multifactorial.
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http://dx.doi.org/10.1111/jce.14374DOI Listing
March 2020

Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a comparative histological analysis.

Rheumatology (Oxford) 2020 Sep;59(9):2523-2533

Rheumathology Division, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome.

Objective: To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM).

Methods: We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0-3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used.

Results: We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P < 0.001].

Conclusion: SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis.
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http://dx.doi.org/10.1093/rheumatology/kez658DOI Listing
September 2020

Tocilizumab for the Treatment of Myocardial Inflammation Shown by Cardiac Magnetic Resonance: Report of Two Cases and Rationale for Its Therapeutic Use.

J Clin Rheumatol 2019 Nov 19. Epub 2019 Nov 19.

Unit of Immunology Rheumatology Allergy and Rare Disease IRCCS San Raffaele Hospital Milan, Italy Vita-Salute San Raffaele University Milan, Italy Unit of Arrhythmology IRCCS San Raffaele Hospital Milan, Italy. Cardiac Magnetic Resonance Unit Department of Radiology and Cardiovascular Imaging IRCCS San Raffaele Hospital Milan, Italy. Unit of Immunology Rheumatology Allergy and Rare Disease IRCCS San Raffaele Hospital Milan, Italy Vita-Salute San Raffaele University Milan, Italy.

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http://dx.doi.org/10.1097/RHU.0000000000001194DOI Listing
November 2019

Thyroid dysfunction in adult patients with biopsy-proved myocarditis: Screening and characterization.

Eur J Intern Med 2020 01 14;71:98-100. Epub 2019 Nov 14.

Department of Cardiovascular Pathology, Padua University Hospital, Padua, Italy.

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http://dx.doi.org/10.1016/j.ejim.2019.11.008DOI Listing
January 2020

Efficacy and safety of mycophenolate mofetil in patients with virus-negative lymphocytic myocarditis: A prospective cohort study.

J Autoimmun 2020 01 3;106:102330. Epub 2019 Sep 3.

Unit of Immunology, Rheumatology, Allergy and Rare Diseases IRCCS San Raffaele Hospital Vita-Salute San Raffaele University Milan, Italy. Electronic address:

Background: virus-negative lymphocytic myocarditis (VNLM) is a severe inflammatory heart disease with elusive therapies. We aimed to assess the efficacy of mycophenolate-mofetil (MMF) in patients with VNLM.

Methods: patients were enrolled in this prospective cohort study and were treated with MMF, as the initial treatment in case of concomitant systemic immune diseases (SIDs), or as rescue therapy in isolated myocarditis intolerant/resistant to azathioprine. All were initially evaluated for endomyocardial biopsy; ECG, 24-h Holter, echocardiography, troponin T and NT-proBNP were obtained in all patients at baseline and after 6 months. The primary end-point was the change in left-ventricular ejection-fraction (LVEF) on echocardiogram after 6 months.

Secondary Outcomes: decrease in serum NT-proBNP and troponin-T levels, reduction of LV end-diastolic-volume (LVEDV), amelioration of regional wall motion abnormalities (RWMA), and modification of clinical status.

Results: 20 patients (10 females, median age at diagnosis 32 [41-59] years) were enrolled. Baseline echocardiography revealed a reduced LVEF (<55%) in 11 patients (55%) and a median LV-EF of 53.5 [44-60.5]%. Baseline median troponin T and NT-proBNP were 50.5 (14.4-288.5)ng/L and 257.0 (90.5-912.0)pg/ml, respectively. After 6 months, the median LVEF significantly improved (57 [50-61]%,p = 0.016), irrespective of concomitant steroid dose. Consistently, after 6 months LVEDV decreased from 135 ± 50 ml to 114 ± 38 ml (p < 0.001), and only 6 patients had RWMA, compared to 14 at baseline (p = 0.016). The amelioration of cardiac function was paralleled by a reduction of median troponin T (12.0 [10.0-24.0],p = 0.02) and NT-proBNP(79.5 [74.5-223-2],p = 0.007) and by a reduction in the number of patients with dyspnea NYHA class II-III(p = 0.02). None of the patients required drug discontinuation.

Conclusions: MMF migh be a safe and effective therapeutic option in VNLM, both as first-line agent and as a rescue therapy.
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http://dx.doi.org/10.1016/j.jaut.2019.102330DOI Listing
January 2020

Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy.

Ann Intern Med 2019 10 3;171(7):458-463. Epub 2019 Sep 3.

Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy (C.D., S.C.P., L.G., A.A., M.F., P.D.B., S.B., S.S.).

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood.

Objective: To learn more about the natural history of LMNA-related disease.

Design: Observational study.

Setting: 13 clinical centers in Italy from 2000 through 2018.

Patients: 164 carriers of an LMNA mutation.

Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up.

Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only.

Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies.

Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions.

Primary Funding Source: None.
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http://dx.doi.org/10.7326/M18-2768DOI Listing
October 2019