Publications by authors named "Ardan M Saguner"

110 Publications

Left femoral venous access for leadless pacemaker implantation: patient characteristics and outcomes.

Europace 2021 Apr 5. Epub 2021 Apr 5.

Electrophysiology Division, Department of Cardiology, University Heart Center Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Aims: Leadless pacing has become an alternative approach for patients requiring a single-chamber pacemaker. Conventionally, leadless Micra Transcatheter Pacing System (TPS) pacemakers are implanted via a right femoral venous access. However, due to various reasons, a left-sided femoral venous approach may be necessary. We hypothesized that a left-sided femoral venous approach is as safe and effective when compared with a right-sided approach. We assessed indications, procedural characteristics, safety and mid-term outcomes of Micra TPS implantation via a left femoral venous approach when compared with the conventional right-sided approach.

Methods And Results: In this retrospective single-centre analysis, 143 consecutive patients undergoing Micra TPS implantation were included. 87% (125/143) underwent Micra TPS implantation via a right, and 13% (18/143) via a left femoral venous access. The mean age at implantation was 79.8 ± 7.5 years. Acute procedural success, mean procedure and fluoroscopy times as well as device parameters at implantation and follow-up (mean 15 ± 11.5 months) were similar between the two groups. Five major complications (3.5%) were encountered, all using a right-sided approach. After a transfemoral TAVI procedure, left femoral venous access was used in 42% of cases when compared with 8% in the remaining population (P = 0.003).

Conclusions: A left femoral venous access for Micra TPS implantation is safe and effective with an excellent implantation success rate similar to a conventional right femoral venous access without longer implantation and fluoroscopy times. The most frequent reason for choosing left vs. right femoral venous access was a previous transfemoral TAVI procedure.
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http://dx.doi.org/10.1093/europace/euab083DOI Listing
April 2021

[CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders].

Praxis (Bern 1994) 2021 ;110(4):189-191

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich.

CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.
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http://dx.doi.org/10.1024/1661-8157/a003657DOI Listing
March 2021

The Link Between Sex Hormones and Susceptibility to Cardiac Arrhythmias: From Molecular Basis to Clinical Implications.

Front Cardiovasc Med 2021 17;8:644279. Epub 2021 Feb 17.

Arrhythmia and Electrophysiology, Department of Cardiology, University Heart Center, Zurich, Switzerland.

It is well-known that gender is an independent risk factor for some types of cardiac arrhythmias. For example, males have a greater prevalence of atrial fibrillation and the Brugada Syndrome. In contrast, females are at increased risk for the Long QT Syndrome. However, the underlying mechanisms of these gender differences have not been fully identified. Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. In this review, we describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to arrhythmias.
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http://dx.doi.org/10.3389/fcvm.2021.644279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925388PMC
February 2021

[CME ECG 68: Gender Specificities in Heart Rhythm Disorders].

Praxis (Bern 1994) 2021 ;110(3):131-139

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich.

CME ECG 68: Gender Specificities in Heart Rhythm Disorders Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.
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http://dx.doi.org/10.1024/1661-8157/a003656DOI Listing
March 2021

Exercise intolerance - from spiroergometry to transdiaphragmatic myocardial punch biopsy: a case report of isolated cardiac sarcoidosis.

Eur Heart J Case Rep 2021 Jan 4;5(1):ytaa121. Epub 2021 Jan 4.

Department of Cardiology, University Heart Centre, University Hospital Zurich, Zurich, Switzerland.

Background: Several aetiologies account for exercise intolerance, with cardiac sarcoidosis (CS) constituting a rare cause thereof. The pathogenesis of CS is still unresolved and its diagnosis still difficult to establish, in the absence of any extracardiac manifestations in particular.

Case Summary: A 49-year-old amateur athlete presented with exercise intolerance during running over a 3-week period. Coronary artery and structural lung disease were excluded by coronary angiography and computer tomography. The symptoms could be reproduced during spiroergometry during which an exercise-induced high-degree atrioventricular (AV) block was documented. During electrocardiographic monitoring, a 2:1 AV block was observed. Different imaging modalities showed inferobasal septal inflammation and fibrosis. Transthoracic and transoesophageal echocardiography-guided endomyocardial biopsies were inconclusive and only subsequent epicardial biopsy performed by transdiaphragmatic minimally invasive surgery lead to the histological diagnosis of non-caseating granuloma, confirming CS. The patient was treated with high-dose steroids 1 week after implantation of a primary prevention dual-chamber implantable cardioverter-defibrillator (ICD). While tapering steroids, recurrence of myocardial inflammation occurred. However, no tachytherapies and <0.1% right ventricular pacing were needed after 2 years of follow-up.

Discussion: Differential diagnoses were either an infiltrative disease, a tumour, or an infectious disease. Due to the different treatment options, we had to establish definite diagnosis by myocardial biopsy. Retrospectively, the implantation of the ICD can be discussed. However, cardiac magnetic resonance imaging showed fibrosis which is usually irreversible and substrate for potentially lethal ventricular arrhythmia. Confirming the diagnosis of isolated CS is challenging. Long-term management should be guided individually based on clinical and imaging findings.
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http://dx.doi.org/10.1093/ehjcr/ytaa121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850611PMC
January 2021

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

Int J Radiat Oncol Biol Phys 2021 Jan 27. Epub 2021 Jan 27.

I. Medizinische Klinik, Universitätsklinikum Mannheim and German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany.

Purpose: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial.

Methods And Materials: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined.

Results: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm, 5.9 to 79.9 cm, and 9.4 to 34.3 cm; surface area varied from 1087 to 3285 mm, 1077 to 9500 mm, and 1620 to 4179 mm, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference.

Conclusions: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.028DOI Listing
January 2021

Atrial fibrillation and dementia: an unresolved 'Folie à Deux'.

Open Heart 2020 12;7(2)

Department of Cardiology, University Hospital of Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1136/openhrt-2019-001087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768951PMC
December 2020

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

Circ Arrhythm Electrophysiol 2021 Jan 9;14(1):e008509. Epub 2020 Dec 9.

Department of Medicine, Division of Cardiology (J.C.-T., W.W., A.B., C.T., B.M., S.C., J.E.C., D.P.J., H.T., H.C., C.A.J.), Johns Hopkins Hospital, Baltimore, MD.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD.

Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping.

Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism.

Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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http://dx.doi.org/10.1161/CIRCEP.120.008509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834666PMC
January 2021

Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports.

J Clin Med 2020 Nov 23;9(11). Epub 2020 Nov 23.

University Heart Center Zurich, Division of Cardiology, 8091 Zurich, Switzerland.

Arrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype-phenotype relationships have improved our understanding of the molecular mechanisms leading to the expression of the full-blown disease, the underlying genetic substrate and the clinical course of asymptomatic or oligo-symptomatic mutation carriers are still poorly understood. We aimed to analyze different phenotypic expression profiles of ACM in the context of the same familial genetic mutation by studying nine adult cases from four different families with four different familial variants (two plakophilin-2 and two desmoglein-2) from the Swiss Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Registry. The affected individuals with the same genetic variants presented with highly variable phenotypes ranging from no disease or a classical, right-sided disease, to ACM with biventricular presentation. Moreover, some patients developed early-onset, electrically unstable disease whereas others with the same genetic variants presented with late-onset electrically stable disease. Despite differences in age, gender, underlying genotype, and other clinical characteristics, physical exercise has been observed as the common denominator in provoking an arrhythmic phenotype in these families.
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http://dx.doi.org/10.3390/jcm9113781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700696PMC
November 2020

Impact of Genetic Variant Reassessment on the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy Based on the 2010 Task Force Criteria.

Circ Genom Precis Med 2021 Feb 24;14(1):e003047. Epub 2020 Nov 24.

Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Switzerland (S.C., A.G., D.A., F.R., C.B.B., F.D., A.M.S.).

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis.

Methods: This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria was reclassified after genetic readjudication.

Results: In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 () were shown to reclassify less frequently as compared with other genes (, n=1, 8.3%; desmosomal non-, n=20, 66.7%; nondesmosomal, n=26, 68.4%; =0.001for overall comparison; versus desmosomal non-=0.001; versus nondesmosomal, <0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) variants.

Conclusions: Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.
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http://dx.doi.org/10.1161/CIRCGEN.120.003047DOI Listing
February 2021

Redefining the Prognostic Value of High-Sensitivity Troponin in COVID-19 Patients: The Importance of Concomitant Coronary Artery Disease.

J Clin Med 2020 Oct 12;9(10). Epub 2020 Oct 12.

Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, 20157 Milan, Italy.

Background: Although studies assessing cardiovascular comorbidities and myocardial injury in Coronavirus disease 2019 (COVID-19) patients have been published, no reports focused on clinical outcomes of myocardial injury in patients with and without chronic coronary syndromes (CCS) are currently available.

Methods: In this study, consecutive COVID-19 patients admitted to four different institutions were screened for enrolment. Patients were divided into two groups (CCS vs. no-CCS). Association with in-hospital mortality and related predictors represented the main study outcome; myocardial injury and its predictors were deemed secondary outcomes.

Results: A total of 674 COVID-19 patients were enrolled, 112 (16.6%) with an established history of CCS. Myocardial injury occurred in 43.8% patients with CCS vs. 14.4% patients without CCS, as confirmed by high-sensitivity cardiac troponin (hs-cTn) elevation on admission or during hospitalization. The mortality rate in the CCS cohort was nearly three-fold higher. After adjusting for disease severity, myocardial injury resulted significantly associated with in-hospital mortality in the no-CCS group but not in CCS patients.

Conclusions: Patients with CCS and COVID-19 showed high mortality rate. Myocardial injury may be a bystander in CCS patients and COVID-19, while in patients without known history of CCS, myocardial injury has a significant role in predicting poor outcomes.
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http://dx.doi.org/10.3390/jcm9103263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601151PMC
October 2020

[CME ECG 66/Answers: Torsade de Pointes: The Danger of a Rotating Heart Axis].

Praxis (Bern 1994) 2020 ;109(13):1035-1038

Universitätsspital Zürich, Klinik für Kardiologie.

CME ECG 66/Answers: Torsade de Pointes: The Danger of a Rotating Heart Axis Torsade de pointes tachycardia is a potentially life-threatening heart rhythm disorder, caused by prolongation of the QT interval resulting in triggered activity. This QT prolongation can be congenital or acquired. If acquired, it is mainly caused by pharmacological therapy. The hallmark of torsade de pointes is an undulating QRS axis with a twist of the QRS complex around the ECG's baseline. Often, this polymorphic ventricular tachycardia is self-limiting, but degeneration into ventricular fibrillation is possible, which makes torsade de pointes tachycardia dangerous. This article aims to provide insights into etiology, diagnostics, prevention and management of this heart rhythm disorder.
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http://dx.doi.org/10.1024/1661-8157/a003584DOI Listing
October 2020

Use of the wearable cardioverter-defibrillator - the Swiss experience.

Swiss Med Wkly 2020 Sep 30;150:w20343. Epub 2020 Sep 30.

Division of Cardiology, University Heart Centre Zurich, Switzerland.

Introduction: Sudden cardiac death caused by malignant arrhythmia can be prevented by the use of defibrillators. Although the wearable cardioverter defibrillator (WCD) can prevent such an event, its role in clinical practice is ill defined. We investigated the use of the WCD in Switzerland with emphasis on prescription rate, therapy adherence and treatment rate.

Materials And Methods: The Swiss WCD Registry is a retrospective observational registry including patients using a WCD. Patients were included from the first WCD use in Switzerland until February 2018. Baseline characteristics and data on WCD usage were examined for the total study population, and separately for each hospital.

Results: From 1 December 2011 to 18 February 2018, a total of 456 patients (67.1% of all WCDs prescribed in Switzerland and 81.1% of all prescribed in the participating hospitals) were included in the registry. Up to 2017 there was a yearly increase in the number of prescribed WCDs to a maximum of 271 prescriptions per year. The mean age of patients was 57 years (± 14), 81 (17.8%) were female and mean left ventricular ejection fraction (EF) was 32% (± 13). The most common indications for WCD use were new-onset ischaemic cardiomyopathy (ICM) with EF ≤35% (206 patients, 45.2%), new-onset nonischaemic cardiomyopathy (NICM) with EF ≤35% (115 patients, 25.2%), unknown arrhythmic risk (83 patients, 18.2%), bridging to implantable cardioverter-defibrillator implantation or heart transplant (37 patients, 8.1%) and congenital/inherited heart disease (15 patients, 3.3%). Median wear duration was 58 days (interquartile range [IQR] 31–94) with a median average daily wear time of 22.6 hours (IQR 20–23.2). Seventeen appropriate therapies from the WCD were delivered in the whole population (treatment rate: 3.7%) to a total of 12 patients (2.6% of all patients). The most common underlying heart disease in patients with a treatment was ICM (13/17, 76.5%). There were no inappropriate treatments.

Conclusion: The use of WCDs has increased in Switzerland over the years for a variety of indications. There is high therapy adherence to the WCD, and a treatment rate comparable to previously published registry data.  .
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http://dx.doi.org/10.4414/smw.2020.20343DOI Listing
September 2020

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

Neurology 2020 12 7;95(24):e3355-e3363. Epub 2020 Oct 7.

From the Stroke Centre and Department of Neurology (J.-q.A., Y.-w.C., Y.-c.G., M.W., M.-j.G., Y.-l.T., X.-y.Y., W.-f. S., C.-y.M., G.-g.L.) and Atrial Fibrillation Centre and Department of Cardiovascular Medicine (J.-q.A., G.-l L.), First Affiliated Hospital of Xi'an Jiaotong University, China; Renal Division (A.-f.Z.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Cardiology (A.M.S.), University Heart Center Zurich, Switzerland.

Objective: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT).

Methods: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated.

Results: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score ( = 0.364) or occur-to-treatment time ( = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; = 0.016). We further found significantly lower plasma S100-β ( = 0.007) and higher vascular endothelial growth factor ( = 0.003) levels in the RIPC group than in the control group.

Conclusions: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS.

Clinicaltrialsgov Identifier: NCT03218293.

Classification Of Evidence: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.
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http://dx.doi.org/10.1212/WNL.0000000000010884DOI Listing
December 2020

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

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

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

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

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

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

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

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

[CME ECC 66: Torsade de Pointes: The Danger of a Rotating Heart Axis].

Praxis (Bern 1994) 2020 Sep;109(12):944-951

Universitätsspital Zürich, Klinik für Kardiologie.

CME ECC 66: Torsade de Pointes: The Danger of a Rotating Heart Axis Torsade de pointes tachycardia is a potentially life-threatening heart rhythm disorder, caused by prolongation of the QT-interval resulting in triggered activity. This QT-prolongation can be congenital or acquired. If acquired, it is mainly caused by pharmacological therapy. The hallmark of torsade de pointes is an undulating QRS axis with a twist of the QRS complex around the ECG's baseline. Often, this polymorphic ventricular tachycardia is self-limiting, but degeneration into ventricular fibrillation is possible, which makes torsade de pointes tachycardia dangerous. This article aims to provide insights into etiology, diagnostics, prevention and management of this heart rhythm disorder.
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http://dx.doi.org/10.1024/1661-8157/a003583DOI Listing
September 2020

Biomarkers in inherited arrhythmias: opportunities for validation and collaboration.

Eur Heart J 2020 12;41(47):4521-4522

Department of Cardiology, University Heart Center Zurich, Rämistrasse 100, 8091 Zürich, Switzerland.

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http://dx.doi.org/10.1093/eurheartj/ehaa672DOI Listing
December 2020

Assessment of injury current during leadless pacemaker implantation.

Int J Cardiol 2021 Jan 9;323:113-117. Epub 2020 Sep 9.

Electrophysiology, Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.

Background: Leadless pacemakers are an established treatment option for bradyarrhythmias. Similar to conventional transvenous pacemakers, satisfying pacing values during implantation are targeted for optimal long-term device function. The objective is to investigate the role of a local injury current (IC) in leadless pacemaker implantations.

Method: The IC, sensing value, capture threshold and impedance were collected in 30 consecutive patients receiving a leadless pacemaker.

Results: 39 EGMs were recorded from 30 patients (including 9 device repositions). An IC was detected in 15 cases (38%). At implantation, the presence of an IC was associated with a significantly lower sensing (7.1 ± 3.7 mV vs 12.0 ± 4.0 mV; P = 0.004) and a higher capture threshold (median threshold 1.13 V at 0.24 ms [0.50-2.00] vs 0.50 V at 0.24 ms [0.25-0.75]; P = 0.002) and with a 26 fold higher likelihood of device repositioning compared to the absence of an IC (OR 26.3 [2.79-248], P < 0.001). Patients with an IC in their final implant position had a lower sensing (9.3 ± 4.4 mV vs 13.6 ± 4.7 mV at implantation, P = 0.04), while the initially similar capture threshold was lower after 24 h in the IC group. After 2 weeks, all parameters were similar between the two groups.

Conclusions: Our study shows that an IC can readily be observed during leadless pacemaker implantation associated with a lower sensing and a higher capture threshold at implantation but with similar to even better values during follow-up.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.098DOI Listing
January 2021

Cardiovascular disease during the COVID-19 pandemic: Think ahead, protect hearts, reduce mortality.

Cardiol J 2020 13;27(5):616-624. Epub 2020 Aug 13.

Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Coronavirus disease 2019 (COVID-19) is rapidly spreading globally. As of October 3, 2020, the number of confirmed cases has been nearly 34 million with more than 1 million fatalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for COVID-19. Newly diagnosed and worsening cardiovascular disease are common complications in COVID-19 patients, including acute cardiac injury, hypertension, arrhythmia, myocardial infarction, heart failure and sudden cardiac arrest. The mechanisms contributing to cardiac disease burden include hypoxemia, inflammatory factor storm, dysfunctional angiotensin converting enzyme 2 (ACE2), and drug-induced cardiac toxicity. Notably, the macrophages expressing ACE2 as direct host cells of SARS-CoV-2 secrete chemokine and inflammatory cytokines, as well as a decrease in cellular immune responses to SARS-CoV-2 infection due to elevated exhaustion levels and dysfunctional diversity of T cells, that may be accountable for the "hyperinflammation and cytokine storm syndrome" and subsequently acute cardiac injury and deteriorating cardiovascular disease in COVID-19 patients. However, no targeted medication or vaccines for COVID-19 are yet available. The management of cardiovascular disease in patients with COVID-19 include general supportive treatment, circulatory support, other symptomatic treatment, psychological assistance as well as online consultation. Further work should be concentrated on better understanding the pathogenesis of COVID-19 and accelerating the development of drugs and vaccines to reduce the cardiac disease burden and promote the management of COVID-19 patients, especially those with a severe disease course and cardiovascular complications.
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http://dx.doi.org/10.5603/CJ.a2020.0101DOI Listing
November 2020

Arrhythmogenic cardiomyopathy: An in-depth look at molecular mechanisms and clinical correlates.

Trends Cardiovasc Med 2020 Jul 29. Epub 2020 Jul 29.

Division of Cardiology, University Heart Center Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address:

Arrhythmogenic cardiomyopathy (ACM) is a familial disease, with approximately 60% of patients displaying a pathogenic variant. The majority of genes linked to ACM code for components of the desmosome: plakophilin-2 (PKP2), desmoglein-2 (DSG2) and desmocollin-2 (DSC2), plakoglobin (JUP) and desmoplakin (DSP). Genetic variants involving the desmosomes are known to cause dysfunction of cell-to-cell adhesions and intercellular gap junctions. In turn, this may result in failure to mechanically hold together the cardiomyocytes, fibrofatty myocardial replacement, cardiac conduction delay and ventricular arrhythmias. It is becoming clearer that pathogenic variants in desmosomal genes such as PKP2 are not only responsible for a mechanical dysfunction of the intercalated disc (ID), but are also the cause of various pro-arrhythmic mechanisms. In this review, we discuss in detail the different molecular interactions associated with desmosomal pathogenic variants, and their contribution to various ACM phenotypes.
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http://dx.doi.org/10.1016/j.tcm.2020.07.006DOI Listing
July 2020

Stereotactic Radiotherapy for the Management of Refractory Ventricular Tachycardia: Promise and Future Directions.

Front Cardiovasc Med 2020 25;7:108. Epub 2020 Jun 25.

Heart and Vessel Department, Service of Cardiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Ventricular tachycardia (VT) caused by myocardial scaring bears a significant risk of mortality and morbidity. Antiarrhythmic drug therapy (AAD) and catheter ablation remain the cornerstone of VT management, but both treatments have limited efficacy and potential adverse effects. Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated for the treatment of VT. This review presents the basic underlying principles, proof of concept, and main results of trials and case series that used SBRT for the treatment of VT refractory to AAD and catheter ablation.
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http://dx.doi.org/10.3389/fcvm.2020.00108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329991PMC
June 2020

Differential effect of cardiac resynchronization therapy in patients with diabetes mellitus: a long-term retrospective cohort study.

ESC Heart Fail 2020 10 11;7(5):2773-2783. Epub 2020 Jul 11.

Department of Cardiology, University Heart Center Zurich, Raemistr. 100, Zurich, 8091, Switzerland.

Aims: Cardiac resynchronization therapy (CRT) has become an important therapy in patients with heart failure with reduced left ventricular ejection fraction (LVEF). The effect of diabetes on long-term outcome in these patients is controversial. We assessed the effect of diabetes on long-term outcome in CRT patients and investigated the role of diabetes in ischaemic and non-ischaemic cardiomyopathy.

Methods And Results: All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were enrolled. The study endpoints were (i) a composite of ventricular assist device (VAD) implantation, heart transplantation, or all-cause mortality; and (ii) reverse remodelling (improvement of LVEF ≥ 10% or reduction of left ventricular end-systolic volume ≥ 15%). Median follow-up of the 418 patients (age 64.6 ± 11.6 years, 22.5% female, 25.1% diabetes) was 4.8 years [inter-quartile range: 2.8;7.4]. Diabetic patients had an increased risk to reach the composite endpoint [adjusted hazard ratio (aHR) 1.48 [95% CI 1.12-2.16], P = 0.041]. Other factors associated with an increased risk to reach the composite endpoint were a lower body mass index or baseline LVEF (aHR 0.95 [0.91; 0.98] and 0.97 [0.95; 0.99], P < 0.01 each), and a higher New York Heart Association functional class or creatinine level (aHR 2.14 [1.38; 3.30] and 1.04 [1.01; 1.05], P < 0.05 each). Early response to CRT, defined as LVEF improvement ≥ 10%, was associated with a lower risk to reach the composite endpoint (aHR 0.60 [0.40; 0.89], P = 0.011). Reverse remodelling did not differ between diabetic and non-diabetic patients with respect to LVEF improvement ≥ 10% (aHR 0.60 [0.32; 1.14], P = 0.118). However, diabetes was associated with decreased reverse remodelling with respect to a reduction of left ventricular end-systolic volume ≥ 15% (aHR 0.45 [0.21; 0.97], P = 0.043). In patients with ischaemic cardiomyopathy, survival rates were not significantly different between diabetic and non-diabetic patients (HR 1.28 [0.83-1.97], P = 0.101), whereas in patients with non-ischaemic cardiomyopathy, diabetic patients had a higher risk of reaching the composite endpoint (HR 1.65 [1.06-2.58], P = 0.027). The latter effect was dependent on other risk factors (aHR 1.47 [0.83-2.61], P = 0.451). The risk of insulin-dependent patients was not significantly higher than in patients under oral antidiabetic drugs (HR 1.55 [95% CI 0.92-2.61], P = 0.102).

Conclusions: Long-term follow-up revealed diabetes mellitus as independent risk factor for all-cause mortality, heart transplantation, or VAD in heart failure patients undergoing CRT. The detrimental effect of diabetes appeared to weigh heavier in patients with non-ischaemic compared with ischaemic cardiomyopathy.
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http://dx.doi.org/10.1002/ehf2.12876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524059PMC
October 2020

An autoantibody profile detects Brugada syndrome and identifies abnormally expressed myocardial proteins.

Eur Heart J 2020 08;41(30):2878-2890

Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute and the University of Toronto, Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada.

Aims: Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients.

Methods And Results: For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates.

Conclusion: A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.
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http://dx.doi.org/10.1093/eurheartj/ehaa383DOI Listing
August 2020

Dysfunctional Coagulation in COVID-19: From Cell to Bedside.

Adv Ther 2020 07 5;37(7):3033-3039. Epub 2020 Jun 5.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which can induce multisystem disease. Human angiotensin-converting enzyme 2 (ACE2) widely expressing in arterial and venous endothelial cells and arterial smooth muscle cells has been identified as a functional receptor for SARS-CoV-2. Dysfunction of ACE2 leads to abnormal activation of the renin-angiotensin system and a systemic endotheliitis that may relate to abnormal coagulation and sepsis. Meanwhile, innate immune response and inflammation activation participate in dysfunctional coagulation. Previous research indicated that dysfunctional coagulation was one of the important risk factors accountable for a high risk of severe disease and death in patients with COVID-19. Understanding the possible mechanisms of dysfunctional coagulation and appropriate anticoagulation therapeutic strategies are important to prevent disease deterioration and reduce fatality rates during the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1007/s12325-020-01399-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274265PMC
July 2020

Clinical predictors of left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Am Heart J 2020 05 7;223:34-43. Epub 2020 Feb 7.

Department of Cardiology, University Heart Center Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address:

Aim: The impact of clinical characteristics for predicting patterns of ventricular involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC) are not well defined. The aims of this study were to characterize different patterns of ventricular involvement in patients with ARVC and to stratify them based on clinical characteristics exercise and underlying genetic mutations.

Methods: Sixty-four patients with definite ARVC from the Swiss ARVC Registry were enrolled. Right and left ventricular functions were assessed at baseline and most recent follow-up. All patients received genetic testing. Serum high-sensitivity cardiac Troponin T (hs-cTNT) and N-terminal of pro-brain natriuretic peptide (NT-proBNP) were determined at baseline.

Results: Thirty-five patients (55%) had isolated right ventricular (RV) involvement, 12 patients (19%) had biventricular (BiV) involvement at baseline and 17 patients (26%) had no left ventricular (LV) involvement at baseline, but revealed new onset LV involvement at mean follow-up of 7.5 years. Patients with BiV involvement at baseline harbored significantly more desmoplakin and multiple mutations and patients with new-onset LV involvement at follow-up frequently showed non-desmosomal mutations. Patients engaging in competitive sports more often showed LV involvement during follow-up. Baseline hs-cTNT and NT-proBNP levels were higher in patients developing BiV involvement.

Conclusion: Multiple mutations are more common in ARVC patients with BiV involvement. Competitive exercise is associated with disease progression resulting in BiV involvement. Hs-cTNT and NT-proBNP are elevated in patients with BiV involvement and may help to identify ARVC patients at risk for developing BiV disease.
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http://dx.doi.org/10.1016/j.ahj.2020.01.019DOI Listing
May 2020

First magnetic resonance imaging-guided cardiac radioablation of sustained ventricular tachycardia.

Radiother Oncol 2020 11 14;152:203-207. Epub 2020 Feb 14.

Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Switzerland.

Purpose: To report the feasibility of magnetic resonance imaging-guided cardiac single fraction radioablation (MRgRA) in a patient with dilated cardiomyopathy and recurrent sustained ventricular tachycardia (VT) leading to electrical storms (ES).

Materials/methods: A workflow to perform Stereotactic Arrhythmia Radioablation (STAR) on a hybrid MR-Linac with real-time tracking and beam-gating was established. Challenges of the MRgRA approach included: (a) the safety of a non-MR compatible cardiac implantable electronic device (CIED) in the MR-Linac field, (b) artefacts caused by the CIED and (c) respiratory motion management with cine-tracking of the moving heart. The specific absorption rate and slew rate of the MR-Linac were within the specifications of a MR-conditional CIED. Phantom measurements showed CIED distortion artefacts of less than 1.5 mm. During MR simulation, tracking could be established on the upper liver to avoid interference with the moving heart and CIED extinction artefacts. Areas of anatomical scarring and critical substrate were identified using invasive three-dimensional electroanatomical mapping of the clinical VT during electrophysiological studies and cardiac MR imaging/computed tomography to build a volumetric target.

Results: A 71-year-old male patient with non-ischemic dilated cardiomyopathy and recurrent therapy-refractory sustained VT with repetitive implantable cardioverter-defibrillator (ICD) shocks was treated with a single fraction of 25 Gy @85% isodose, cine-tracking time was 46 min, beam-on time 24 min. 24 h post intervention the patient developed an aggravation of the clinical VT and prolonged ES. VT ceased following high-dose dexamethasone administration after 48 h. After this point, the patient remained without any episodes of sustained ventricular tachyarrhythmia requiring ICD interventions until the last follow-up at three months.

Conclusion: Real-time tracking and beam-gating were successfully applied in this first MRgRA to treat sustained VT.
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http://dx.doi.org/10.1016/j.radonc.2020.01.008DOI Listing
November 2020

Outcomes during and after the use of the wearable cardioverter-defibrillator in a tertiary-care and a regional hospital in Switzerland.

Swiss Med Wkly 2019 11 10;149:w20136. Epub 2019 Nov 10.

Department of Cardiology, University Hospital of Zurich, Switzerland/ Centre for Integrative Human Physiology, University of Zurich, Switzerland.

Introduction: The wearable cardioverter-defibrillator (WCD) has established itself in treatment of potentially life-threatening ventricular arrhythmias, when implantation of an implantable cardioverter-defibrillator (ICD) is not warranted. Careful patient selection for this therapy is crucial, but unfortunately very little information from randomised controlled trials is available to guide clinical decision-making. Consequently, data from real-world patient registries play a more important role in this context.

Materials And Methods: A retrospective observational study was conducted at the University Hospital of Zurich and the GZO Regional Healthcare Centre in Wetzikon. Clinical databases were screened for patients with a history of WCD use from the time of its approval in Switzerland in July 2014 until February 2018. Baseline characteristics, WCD data and outcome data, with an emphasis on ICD implantation and ICD therapies, were collected and analysed.

Results: Two-hundred and seven patients were included in the primary analysis. Eighty-six percent were male and the mean age was 58 ± 13 years. The underlying heart disease was ischaemic cardiomyopathy (ICM), non-ischaemic cardiomyopathy (NICM) and congenital/inherited heart diseases in 60, 35 and 5%, respectively. The most common indication for WCD use was heart failure with an ejection fraction (EF) <35% due to ICM or NICM (43 and 27%, respectively). Three of the 207 patients received an appropriate shock over a median WCD wear-time of 62 days (interquartile range [IQR] 35–95). No inappropriate shocks were registered. Median average daily wear-time was 22.6 hours (IQR 19.9–23.2) and was significantly shorter for patients for whom WCD discontinuation was due to comfort issues (17 patients, p = 0.003). After the end of WCD therapy, 48% were implanted with an ICD. In those receiving an ICD, the rate of appropriate ICD therapies (either shock or antitachycardia pacing) was 8% during a median follow-up of 110 days (IQR 23–421).

Conclusion: The WCD is safe and effective in terminating malignant ventricular arrhythmias. A substantial subgroup of patients, however, discontinued WCD use prematurely because of comfort issues. This subset of patients deserves further attention in clinical practice to ensure therapy adherence.  .
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http://dx.doi.org/10.4414/smw.2019.20136DOI Listing
November 2019

Extraction of a leadless pacemaker 23 months after implantation.

Eur Heart J 2020 06;41(21):2038

Electrophysiology Division, University Heart Centre, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland.

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http://dx.doi.org/10.1093/eurheartj/ehz671DOI Listing
June 2020